Sample records for g2 chromatid radiosensitivity

  1. Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gantt, R.; Sanford, K.K.; Parshad, R.

    1987-03-01

    A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containingmore » the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.« less

  2. Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Takai, N.; Wu, H.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

    2001-01-01

    PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.

  3. A comparison of G2 phase radiation-induced chromatid break kinetics using calyculin-PCC with those obtained using colcemid block.

    PubMed

    Bryant, Peter E; Mozdarani, Hossein

    2007-09-01

    To study the possible influence of cell-cycle delay on cells reaching mitosis during conventional radiation-induced chromatid break experiments using colcemid as a blocking agent, we have compared the chromatid break kinetics following a single dose of gamma rays (0.75 Gy) in metaphase CHO cells using calyculin-induced premature chromosome condensation (PCC), with those using colcemid block. Calyculin-induced PCC causes very rapid condensation of G2 cell chromosomes without the need for a cell to progress to mitosis, hence eliminating any effect of cell-cycle checkpoint on chromatid break frequency. We found that the kinetics of the exponential first-order decrease in chromatid breaks with time after irradiation was similar (not significantly different) between the two methods of chromosome condensation. However, use of the calyculin-PCC technique resulted in a slightly increased rate of disappearance of chromatid breaks and thus higher frequencies of breaks at 1.5 and 2.5 h following irradiation. We also report on the effect of the nucleoside analogue ara A on chromatid break kinetics using the two chromosome condensation techniques. Ara A treatment of cells abrogated the decrease in chromatid breaks with time, both using the calyculin-PCC and colcemid methods. We conclude that cell-cycle delay may be a factor determining the absolute frequency of chromatid breaks at various times following irradiation of cells in G2 phase but that the first-order disappearance of chromatid breaks with time and its abrogation by ara A are not significantly influenced by the G2 checkpoint.

  4. Kinetics of chromatid break repair in G2-human fibroblasts exposed to low- and high-LET radiations

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Durante, M.; George, K.; Furusawa, Y.; Gotoh, E.; Takai, N.; Wu, H.; Cucinotta, F. A.

    2001-01-01

    The purpose of this study is to determine the kinetics of chromatid break rejoining following exposure to radiations of different quality. Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290 MeV/u), silicon (490 MeV/u) and iron (200 MeV/u, 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Prematurely condensed chromosomes were collected after several post-irradiation incubation times, ranging from 5 to 600 minutes, and the number of chromatid breaks and exchanges in G2 cells were scored. The relative biological effectiveness (RBE) for initial chromatid breaks per unit dose showed LET dependency having a peak at 55 keV/micrometers silicon (2.4) or 80 keV/micrometers carbon particles (2.4) and then decreased with increasing LET. The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components. Chromatid breaks decreased rapidly after exposure, and then continued to decrease at a slower rate. The rejoining kinetics was similar for exposure to each type of radiation, although the rate of unrejoined breaks was higher for high-LET radiation. Chromatid exchanges were also formed quickly.

  5. Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

    PubMed Central

    De Ruyck, K; de Gelder, V; Van Eijkeren, M; Boterberg, T; De Neve, W; Vral, A; Thierens, H

    2008-01-01

    The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (⩽50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (⩽10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients. PMID:18414410

  6. Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

    PubMed

    De Ruyck, K; de Gelder, V; Van Eijkeren, M; Boterberg, T; De Neve, W; Vral, A; Thierens, H

    2008-05-20

    The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G(2) scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients.

  7. Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low-LET gamma-rays and high-LET fast neutrons.

    PubMed

    Vral, A; Thierens, H; Baeyens, A; De Ridder, L

    2002-04-01

    To determine by means of the G2 assay the number of chromatid breaks induced by low-LET gamma-rays and high-LET neutrons, and to compare the kinetics of chromatid break rejoining for radiations of different quality. The G2 assay was performed on blood samples of four healthy donors who were irradiated with low-LET gamma-rays and high-LET neutrons. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for gamma-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments, the kinetics of chromatid break formation and disappearance were investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 and 3.5 h. For the highest dose of 0.5 Gy, the number of isochromatid breaks was also scored. No significant differences in the number of chromatid breaks were observed between low-LET gamma-rays and high-LET neutrons for the four donors at any of the doses given. The dose-response curves for the formation of chromatid breaks are linear for both radiation qualities and RBEs = 1 were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high-LET neutrons were, however, more effective at inducing isochromatid breaks (RBE = 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low-LET gamma-rays or high-LET neutrons were not significantly different. Half-times of 0.92 h for gamma-rays and 0.84 h for neutrons were obtained. Applying the G2 assay, the results demonstrate that at low doses of irradiation, the induction as well as the disappearance of chromatid breaks is independent of the LET of the radiation qualities used (0.24 keV x microm(-1) 60Co gamma-rays and 20 keV x microm(-1) fast neutrons). As these radiation qualities produce the same initial number of double-strand breaks, the results support the signal model that proposes that chromatid breaks are the result

  8. G2 Chromatid Damage and Repair Kinetics in Normal Human Fibroblast Cells Exposed to Low-or High-LET Radiation

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Ito, H.; Uno, T.; Saito, M.; Yamamoto, S.; Furusawa, Y.; Durante, M.; George, K.; Wu, H.; Cucinotta, F. A.

    2004-01-01

    Radiation-induced chromosome damage can be measured in interphase using the Premature Chromosome Condensation (PCC) technique. With the introduction of a new PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can be condensed within five minutes, and it is now possible to examine the early damage induced by radiation. Using this method, it has been shown that high-LET radiation induces a higher frequency of chromatid breaks and a much higher frequency of isochromatid breaks than low-LET radiation. The kinetics of chromatid break rejoining consists of two exponential components representing a rapid and a slow time constant, which appears to be similar for low- and high- LET radiations. However, after high-LET radiation exposures, the rejoining process for isochromatid breaks influences the repair kinetics of chromatid-type breaks, and this plays an important role in the assessment of chromatid break rejoining in the G2 phase of the cell cycle.

  9. Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G1 phase

    PubMed Central

    Furuya, Kanji; Takahashi, Kohta; Yanagida, Mitsuhiro

    1998-01-01

    The loss of sister chromatid cohesion triggers anaphase spindle movement. The budding yeast Mcd1/Scc1 protein, called cohesin, is required for associating chromatids, and proteins homologous to it exist in a variety of eukaryotes. Mcd1/Scc1 is removed from chromosomes in anaphase and degrades in G1. We show that the fission yeast protein, Mis4, which is required for equal sister chromatid separation in anaphase is a different chromatid cohesion molecule that behaves independent of cohesin and is conserved from yeast to human. Its inactivation in G1 results in cell lethality in S phase and subsequent premature sister chromatid separation. Inactivation in G2 leads to cell death in subsequent metaphase–anaphase progression but missegregation occurs only in the next round of mitosis. Mis4 is not essential for condensation, nor does it degrade in G1. Rather, it associates with chromosomes in a punctate fashion throughout the cell cycle. mis4 mutants are hypersensitive to hydroxyurea (HU) and UV irradiation but retain the ability to restrain cell cycle progression when damaged or sustaining a block to replication. The mis4 mutation results in synthetic lethality with a DNA ligase mutant. Mis4 may form a stable link between chromatids in S phase that is split rather than removed in anaphase. PMID:9808627

  10. Replication-Dependent Sister Chromatid Recombination in Rad1 Mutants of Saccharomyces Cerevisiae

    PubMed Central

    Kadyk, L. C.; Hartwell, L. H.

    1993-01-01

    Homolog recombination and unequal sister chromatid recombination were monitored in rad1-1/rad1-1 diploid yeast cells deficient for excision repair, and in control cells, RAD1/rad1-1, after exposure to UV irradiation. In a rad1-1/rad1-1 diploid, UV irradiation stimulated much more sister chromatid recombination relative to homolog recombination when cells were irradiated in the G(1) or the G(2) phases of the cell cycle than was observed in RAD1/rad1-1 cells. Since sister chromatids are not present during G(1), this result suggested that unexcised lesions can stimulate sister chromatid recombination events during or subsequent to DNA replication. The results of mating rescue experiments suggest that unexcised UV dimers do not stimulate sister chromatid recombination during the G(2) phase, but only when they are present during DNA replication. We propose that there are two types of sister chromatid recombination in yeast. In the first type, unexcised UV dimers and other bulky lesions induce sister chromatid recombination during DNA replication as a mechanism to bypass lesions obstructing the passage of DNA polymerase, and this type is analogous to the type of sister chromatid exchange commonly observed cytologically in mammalian cells. In the second type, strand scissions created by X-irradiation or the excision of damaged bases create recombinogenic sites that result in sister chromatid recombination directly in G(2). Further support for the existence of two types of sister chromatid recombination is the fact that events induced in rad1-1/rad1-1 were due almost entirely to gene conversion, whereas those in RAD1/rad1-1 cells were due to a mixture of gene conversion and reciprocal recombination. PMID:8454200

  11. Late G1 accumulation after 2 Gy of gamma-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells.

    PubMed Central

    Warenius, H. M.; Jones, M.; Jones, M. D.; Browning, P. G.; Seabra, L. A.; Thompson, C. C.

    1998-01-01

    We have previously reported a correlation between high endogenous expression of the protein product of the RAF-1 proto-oncogene, intrinsic cellular radiosensitivity and rapid exit from a G2/M delay induced by 2 Gy of gamma-irradiation. Raf1 is a positive serine/threonine kinase signal transduction factor that relays signals from the cell membrane to the MAP kinase system further downstream and is believed to be involved in an ionizing radiation signal transduction pathway modulating the G1/S checkpoint. We therefore extended our flow cytometric studies to investigate relationships between radiosensitivity, endogenous expression of the Raf1 protein and perturbation of cell cycle checkpoints, leading to alterations in the G1, S and G2/M populations after 2 Gy of gamma-irradiation. Differences in intrinsic radiosensitivity after modulation of the G1/S checkpoint have generally been understood to involve p53 function up to the present time. A role for dominant oncogenes in control of G1/S transit in radiation-treated cells has not been identified previously. Here, we show in 12 human in vitro cancer cell lines that late G1 accumulation after 2 Gy of radiation is related to both Raf1 expression (r = 0.91, P = 0.0001) and the radiosensitivity parameter SF2 (r = -0.71, P = 0.009). PMID:9579826

  12. Cut2 proteolysis required for sister-chromatid seperation in fission yeast.

    PubMed

    Funabiki, H; Yamano, H; Kumada, K; Nagao, K; Hunt, T; Yanagida, M

    1996-05-30

    Although mitotic cyclins are well-known substrates for ubiquitin-mediated proteolysis at the metaphase-anaphase transition, their degradation is not essential for separation of sister chromatids; several lines of evidence suggest that proteolysis of other protein(s) is required, however. Here we report the anaphase-specific proteolysis of the Schizosaccharomyces pombe Cut2 protein, which is essential for sister-chromatid separation. Cut2 is located in the nucleus, where it is concentrated along the short metaphase spindle. The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction. Expression of non-degradable Cut2 blocks sister-chromatid separation but not cell-cycle progression. This defect can be overcome by grafting the N terminus of cyclin B onto the truncated Cut2, demonstrating that the regulated proteolysis of Cut2 is essential for sister-chromatid separation.

  13. The Rejoining Time of Chromatid Breaks Induced by Gamma Radiation in Vicia faba Root Tips at 3 °C

    PubMed Central

    Savage, J. R. K.; Neary, G. J.; Evans, H. J.

    1960-01-01

    The observation was made previously that the reduction in radiosensitivity in Vicia faba (as measured by postirradiation root growth) by prolonging the exposure time from about 10 minutes to 24 hours is much less marked at 3°C. than at 19°C. If chromosome damage is mainly responsible for the reduced root growth, this observation might be explained by a smaller drop in the "two-hit" aberration component, resulting from an increased time for which breaks are available for rejoining at 3°C. This hypothesis was tested by comparing chromatid aberration frequencies in root meristem cells produced by 105 rads of 60Co γ rays, given at dose rates of 19.4 and 0.073 rads per minute. Beans were maintained in aerated water at 2°C. prior to and during irradiation, and at this temperature the rate of development of cells was such that the two different exposure times both occupied a period during which the cell sensitivity was approximately constant. Immediately subsequent to irradiation, the roots were returned to 19°C. and examined cytologically. All chromatid aberrations were less frequent after low dose rate treatment, but only the chromatid interchange reduction was significant. The average time for which breaks are available for reunion, calculated from Lea's G function, was found to be 12 hours (95 per cent C.L. 6 to 24 hours). PMID:14442001

  14. Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants

    NASA Technical Reports Server (NTRS)

    Asaad, N. A.; Zeng, Z. C.; Guan, J.; Thacker, J.; Iliakis, G.

    2000-01-01

    The radiosensitizing effect of caffeine has been associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints, but several lines of evidence also implicate inhibition of DNA repair. The role of DNA repair inhibition in caffeine radiosensitization remains uncharacterized, and it is unknown which repair process, or lesion, is affected. We show that a radiosensitive cell line, mutant for the RAD51 homolog XRCC2 and defective in homologous recombination repair (HRR), displays significantly diminished caffeine radiosensitization that can be restored by expression of XRCC2. Despite the reduced radiosensitization, caffeine effectively abrogates checkpoints in S and G2 phases in XRCC2 mutant cells indicating that checkpoint abrogation is not sufficient for radiosensitization. Another radiosensitive line, mutant for XRCC3 and defective in HRR, similarly shows reduced caffeine radiosensitization. On the other hand, a radiosensitive mutant (irs-20) of DNA-PKcs with a defect in non-homologous end-joining (NHEJ) is radiosensitized by caffeine to an extent comparable to wild-type cells. In addition, rejoining of radiation-induced DNA DSBs, that mainly reflects NHEJ, remains unaffected by caffeine in XRCC2 and XRCC3 mutants, or their wild-type counterparts. These observations suggest that caffeine targets steps in HRR but not in NHEJ and that abrogation of checkpoint response is not sufficient to explain radiosensitization. Indeed, immortalized fibroblasts from AT patients show caffeine radiosensitization despite the checkpoint defects associated with ATM mutation. We propose that caffeine radiosensitization is mediated by inhibition of stages in DNA DSB repair requiring HRR and that checkpoint disruption contributes by allowing these DSBs to transit into irreparable states. Thus, checkpoints may contribute to genomic stability by promoting error-free HRR.

  15. The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation

    PubMed Central

    Liu, Xi; Liu, Yan; Zhang, Pengcheng; Jin, Xiaodong; Zheng, Xiaogang; Ye, Fei; Chen, Weiqiang; Li, Qiang

    2016-01-01

    Reductive drug-functionalized gold nanoparticles (AuNPs) have been proposed to enhance the damage of X-rays to cells through improving hydroxyl radical production by secondary electrons. In this work, polyethylene glycol-capped AuNPs were conjugated with tirapazamine (TPZ) moiety, and then thioctyl TPZ (TPZs)-modified AuNPs (TPZs-AuNPs) were synthesized. The TPZs-AuNPs were characterized by transmission electron microscopy, ultraviolet-visible spectra, dynamic light scattering, and inductively coupled plasma mass spectrometry to have a size of 16.6±2.1 nm in diameter and a TPZs/AuNPs ratio of ~700:1. In contrast with PEGylated AuNPs, the as-synthesized TPZs-AuNPs exhibited 20% increment in hydroxyl radical production in water at 2.0 Gy, and 19% increase in sensitizer enhancement ratio at 10% survival fraction for human hepatoma HepG2 cells under X-ray irradiation. The production of reactive oxygen species in HepG2 cells exposed to X-rays in vitro demonstrated a synergistic radiosensitizing effect of AuNPs and TPZ moiety. Thus, the reductive drug-conjugated TPZs-AuNPs as a kind of AuNP radiosensitizer with low gold loading provide a new strategy for enhancing the efficacy of radiation therapy. PMID:27555772

  16. [6]-Gingerol enhances the radiosensitivity of gastric cancer via G2/M phase arrest and apoptosis induction.

    PubMed

    Luo, Youjun; Chen, Xue; Luo, Lumeng; Zhang, Qi; Gao, Caixia; Zhuang, Xibing; Yuan, Sujuan; Qiao, Tiankui

    2018-05-01

    Ionizing radiation (IR) is the main modality for locoregional control of unresectable gastric cancer (GC). [6]-Gingerol is an active major phenolic compound isolated from ginger (Zingiber officinale Roscoe), and it has been demonstrated to possess antitumor activity in previous studies. In the present study, we aimed to evaluate the potential activity of [6]-gingerol as a radiosensitizer and to further explore the underlying mechanism. A CCK-8 assay revealed that [6]-gingerol inhibited the cell viability of HGC-27 cells in a dose-dependent manner (P<0.05). Colony formation assay indicated that pretreatment of [6]-gingerol prior to IR decreased the clonogenic survival of HGC-27 cells. Notably, the combination of [6]-gingerol with IR enhanced IR-induced cell cycle arrest at the G2/M phase compared with IR alone (41.3% in IR alone vs. 53.5% in [6]-gingerol+IR; P=0.006), and increased IR-induced apoptosis compared with IR alone (9.6% in IR alone group vs. 15.1% in [6]-gingerol+IR; P=0.07). DAPI staining detected the apoptotic nuclear morphological changes in the cells treated with [6]-gingerol and/or IR. Furthermore, western blotting and qRT-PCR revealed that [6]-gingerol pretreatment following IR downregulated the protein expression of cyclin B1, cyclin A2, CDC2 and cyclin D1, upregulated the mRNA expression of p27, and induced active caspase-9, active caspase-3 and cytochrome c. In conclusion, the present study demonstrated that [6]-gingerol enhanced radiosensitivity of GC cells, and that the mechanisms involved at least G2/M phase arrest and apoptosis induction.

  17. Etoposide radiosensitizes p53-defective cholangiocarcinoma cell lines independent of their G2 checkpoint efficacies

    PubMed Central

    Hematulin, Arunee; Meethang, Sutiwan; Utapom, Kitsana; Wongkham, Sopit; Sagan, Daniel

    2018-01-01

    Radiotherapy has been accounted as the most comprehensive cancer treatment modality over the past few decades. However, failure of this treatment modality occurs in several malignancies due to the resistance of cancer cells to radiation. It was previously reported by the present authors that defective cell cycle checkpoints could be used as biomarkers for predicting the responsiveness to radiation in individual patients with cholangiocarcinoma (CCA). However, identification of functional defective cell cycle checkpoints from cells from a patient's tissues is cumbersome and not applicable in the clinic. The present study evaluated the radiosensitization potential of etoposide in p53-defective CCA KKU-M055 and KKU-M214 cell lines. Treatment with etoposide enhanced the responsiveness of two p53-defective CCA cell lines to radiation independent of G2 checkpoint function. In addition, etoposide treatment increased radiation-induced cell death without altering the dominant mode of cell death of the two cell lines. These findings indicate that etoposide could be used as a radiation sensitizer for p53-defective tumors, independent of the function of G2 checkpoint. PMID:29541168

  18. Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia.

    PubMed

    Latt, S A; Stetten, G; Juergens, L A; Buchanan, G R; Gerald, P S

    1975-10-01

    Sister chromatid exchanges, which may reflect chromosome repair in response to certain types of DNA damage, provide a means of investigating the increased chromosome fragility characteristic of Fanconi's anemia. By a recently developed technique using 33258 Hoechst and 5-bromodeoxyuridine, it was observed that the baseline frequency of sister chromatid exchanges in phytohemagglutinin-stimulated lymphocytes from four males with Fanconi's anemia differed little from that of normal lymphocytes. However, addition of the bifunctional alkylating agent mitomycin C (0.01 or 0.03 mug/ml) to the Fanconi's anemia cells during culture induces less than half of the increase in exchanges found in identically treated normal lymphocytes. This reduced increment in exchanges in accompanied by a partial suppression of mitosis and a marked increase in chromatid breaks and rearrangements. Many of these events occur at sites of incomplete chromatid interchange. The increase in sister chromatid exchanges induced in Fanconi's anemia lymphocytes by the monofunctional alkylating agent ethylmethane sulfonate (0.25 mg/ml) was slightly less than that in normal cells. Lymphocytes from two sets of parents of the patients with Fanconi's anemia exhibited a normal response to alkylating agents, while dermal fibroblasts from two different patients with Fanconi's anemia reacted to mitomycin C with an increase in chromatid breaks, but a nearly normal increment of sister chromatid exchanges. The results suggest that chromosomal breaks and rearrangements in Fanconi's anemia lymphocytes may result from a defect in a form of repair of DNA damage.

  19. WE-G-BRE-08: Radiosensitization by Olaparib Eluting Nanospheres

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tangutoori, S; Kumar, R; Sridhar, S

    2014-06-15

    Purpose: Permanent prostate brachytherapy often uses inert bio-absorbable spacers to achieve the desired geometric distribution of sources within the prostate. Transforming these spacers into implantable nanoplatforms for chemo-radiation therapy (INCeRT) provides a means of providing sustained in-situ release of radiosensitizers in the prostate to enhance the therapeutic ratio of the procedure. Olaparib, a PARP inhibitor, suppresses DNA repair processes present during low dose rate continuous irradiation. This work investigates the radiosensitizing/DNA damage repair inhibition by NanoOlaparib eluting nanospheres. Methods: Human cell line PC3 (from ATCC), was maintained in F12-k medium supplemented with fetal bovine serum. Clonogenic assay kit (from Fischermore » Scientific) was used to fix and stain the cells to determine the long term effects of irradiation. Nanoparticle size and zeta potential of nanospheres were determined using a Zeta particle size analyzer. The incorporation of Olaparib in nanospheres was evaluated by HPLC. Irradiation was performed in a small animal irradiator operating at 220 KeV.The long term effects of radio-sensitization with olaparib and nanoolaparib was determined using the clonogenic assay at 2 Gy and 4 Gy doses. The cells were allowed to grow for around 10 doubling cycles, The colonies were fixed and stained using clonogenic assay kit. The excess stain was washed off using DI water and the images were taken using a digital camera. Results: Radiosensitization studies were carried out in prostate cancer cell line, PC3 radiation at 0, 2 and 4Gy doses. Strongest dose response was observed with nanoolaparib treated cells compared to untreated cells. Conclusion: A two stage drug release of drug eluting nanospheres from a biodegradable spacer has been suggested for sustained in-situ release of Olaparib to suppress DNA repair processes during prostate brachytherapy. The Olaparib eluting nanospheres had the same in-vitro radiosensitizing

  20. Radiosensitizing effects of neem (Azadirachta indica) oil.

    PubMed

    Kumar, Ashok; Rao, A R; Kimura, H

    2002-02-01

    Radiosensitization by neem oil was studied using Balbc/3T3 cells and SCID cells. Neem oil enhanced the radiosensitivity of the cells when applied both during and after x-irradiation under aerobic conditions. Neem oil completely inhibited the repair of sublethal damage and potentially lethal damage repair in Balbc/3T3 cells. The cytofluorimeter data show that neem oil treatment before and after x-irradiation reduced the G(2) + M phase, thus inhibiting the expression of the radiation induced arrest of cells in the G(2) phase of the cell cycle. However, SCIK cells (derived from the SCID mouse), deficient in DSB repair, treated with neem oil did not show any enhancement in the radiosensitivity. There was no effect of neem oil on SLD repair or its inhibition in SCIK cells. These results suggest that neem oil enhanced the radiosensitivity of cells by interacting with residual damage after x-irradiation, thereby converting the sublethal damage or potentially lethal damage into lethal damage, inhibiting the double-strand break repair or reducing the G(2) phase of the cell cycle. Copyright 2002 John Wiley & Sons, Ltd.

  1. The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.

    PubMed

    Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui

    2017-05-10

    This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.

  2. The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats

    PubMed Central

    Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui

    2017-01-01

    This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function. PMID:28489060

  3. Indirect intergenic suppression of a radiosensitive mutant of Sordaria macrospora defective in sister-chromatid cohesiveness.

    PubMed

    Huynh, A D; Leblon, G; Zickler, D

    1986-01-01

    Six ultra violet (UV) mutageneses were performed on the spo76 UV-sensitive mutant of Sordaria macrospora. Spo76 shows an early centromere cleavage associated with an arrest at the first meiotic division and therefore does not form ascospores. Moreover, it exhibits altered pairing structure (synaptonemal complex), revealing a defect in the sister-chromatid cohesiveness. From 37 revertants which partially restored sporulation, 34 extragenic suppressors of spo76 were isolated. All suppressors are altered in chromosomal pairing but, unlike spo76, show a wild type centromere cleavage. The 34 suppressors were assigned to six different genes and mapped. Only one of the suppressor genes is involved in repair functions.

  4. Highly efficient radiosensitization of human glioblastoma and lung cancer cells by a G-quadruplex DNA binding compound.

    PubMed

    Merle, Patrick; Gueugneau, Marine; Teulade-Fichou, Marie-Paule; Müller-Barthélémy, Mélanie; Amiard, Simon; Chautard, Emmanuel; Guetta, Corinne; Dedieu, Véronique; Communal, Yves; Mergny, Jean-Louis; Gallego, Maria; White, Charles; Verrelle, Pierre; Tchirkov, Andreï

    2015-11-06

    Telomeres are nucleoprotein structures at the end of chromosomes which stabilize and protect them from nucleotidic degradation and end-to-end fusions. The G-rich telomeric single-stranded DNA overhang can adopt a four-stranded G-quadruplex DNA structure (G4). Stabilization of the G4 structure by binding of small molecule ligands enhances radiosensitivity of tumor cells, and this combined treatment represents a novel anticancer approach. We studied the effect of the platinum-derived G4-ligand, Pt-ctpy, in association with radiation on human glioblastoma (SF763 and SF767) and non-small cell lung cancer (A549 and H1299) cells in vitro and in vivo. Treatments with submicromolar concentrations of Pt-ctpy inhibited tumor proliferation in vitro with cell cycle alterations and induction of apoptosis. Non-toxic concentrations of the ligand were then combined with ionizing radiation. Pt-ctpy radiosensitized all cell lines with dose-enhancement factors between 1.32 and 1.77. The combined treatment led to increased DNA breaks. Furthermore, a significant radiosensitizing effect of Pt-ctpy in mice xenografted with glioblastoma SF763 cells was shown by delayed tumor growth and improved survival. Pt-ctpy can act in synergy with radiation for efficient killing of cancer cells at concentrations at which it has no obvious toxicity per se, opening perspectives for future therapeutic applications.

  5. Progress towards understanding the nature of chromatid breakage.

    PubMed

    Bryant, P E; Gray, L J; Peresse, N

    2004-01-01

    The wide range of sensitivities of stimulated T-cells from different individuals to radiation-induced chromatid breakage indicates the involvement of several low penetrance genes that appear to link elevated chromatid breakage to cancer susceptibility. The mechanisms of chromatid breakage are not yet fully understood. However, evidence is accumulating that suggests chromatid breaks are not simply expanded DNA double-strand breaks (DSB). Three models of chromatid breakage are considered. The classical breakage-first and the Revell "exchange" models do not accord with current evidence. Therefore a derivative of Revell's model has been proposed whereby both spontaneous and radiation-induced chromatid breaks result from DSB signaling and rearrangement processes from within large looped chromatin domains. Examples of such rearrangements can be observed by harlequin staining whereby an exchange of strands occurs immediately adjacent to the break site. However, these interchromatid rearrangements comprise less than 20% of the total breaks. The rest are thought to result from intrachromatid rearrangements, including a very small proportion involving complete excision of a looped domain. Work is in progress with the aim of revealing these rearrangements, which may involve the formation of inversions adjacent to the break sites. It is postulated that the disappearance of chromatid breaks with time results from the completion of such rearrangements, rather than from the rejoining of DSB. Elevated frequencies of chromatid breaks occur in irradiated cells with defects in both nonhomologous end-joining (NHEJ) and homologous recombination (HR) pathways, however there is little evidence of a correlation between reduced DSB rejoining and disappearance of chromatid breaks. Moreover, at least one treatment which abrogates the disappearance of chromatid breaks with time leaves DSB rejoining unaffected. The I-SceI DSB system holds considerable promise for the elucidation of these

  6. Complex chromatid-isochromatid exchanges following irradiation with heavy ions?

    PubMed

    Loucas, B D; Eberle, R L; Durante, M; Cornforth, M N

    2004-01-01

    We describe a peculiar and relatively rare type of chromosomal rearrangement induced in human peripheral lymphocytes that were ostensibly irradiated in G(0) phase of the cell cycle by accelerated heavy ions, and which, to the best of our knowledge, have not been previously described. The novel rearrangements which were detected using mFISH following exposure to 500 MeV/nucleon and 5 GeV/n 56Fe particles, but were not induced by either 137Cs gamma rays or 238Pu alpha particles, can alternatively be described as either complex chromatid-isochromatid or complex chromatid-chromosome exchanges. Different mechanisms potentially responsible for their formation are discussed. Copyright 2003 S. Karger AG, Basel

  7. High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Gotoh, E.; Durante, M.; Wu, H.; George, K.; Furusawa, Y.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

    2000-01-01

    PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

  8. [Changes in cellular radiosensitivity after low dose irradiation].

    PubMed

    Pelevina, I I; Aleshchenko, A V; Antoshchina, M M; Kudriashova, O V; Riabchenko, N I; Akleev, A V

    2012-01-01

    When the adaptive response (AR) was studied on human blood lymphocytes, a new dependence was discovered. This dependence defines the direction of the radiosensitivity change after a low dose of irradiation. Using micronucleus (MN) test with cytochalasin B the dependence between the cell reaction after low level irradiation and radiosensititvity (the effect after irradiation at the dose of 1 Gy) was observed. The negative correlation between the frequency of AR manifestation, sensibilization, intermediate links and radiosensitivity was discovered. This regularity is observed in the population of Moscow, Obninsk, Chelyabinsk region (irradiated and control) inhabitants, Chernobyl accident liquidators, Moscow children, in individuals with Hodgkin's lymphoma before and during treatment. The negative correlation is also noted by AR determination with two irradiation schemes: in one or two different cell cycle phases (G1-G1 or G1-G2). Similar links are observed using the chromosome methaphase analysis (the frequency of cells with chromosome aberrations). So, the results of the experiments conducted allow us to suppose that the connection between the cell radiosensitivity and a different type of reaction after low dose irradiation--from AR to the increase in radiosensitivity (sensibilization) is a general regularity. AR is induced by low level irradiation and high cell radiosensitivity, while sensibilization is induced by low radiosensitivity. Since AR and sensibilization can be induced not only by irradiation, but many different chemicals and physical agents, the described correlation can be observed in the case of different exposures. Cellular AR and sensibilization are integral indexes depending on many genetic and epigenetic factors, as well as on the initiation of a large number of events. However, the discovered mechanisms of interrelations are still difficult to explain.

  9. Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Ito, H.; Wu, H.; Cucinotta, F. A.

    2001-01-01

    We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

  10. Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests

    PubMed Central

    Kriegs, Malte; Kasten-Pisula, Ulla; Riepen, Britta; Hoffer, Konstantin; Struve, Nina; Myllynen, Laura; Braig, Friederike; Binder, Mascha; Rieckmann, Thorsten; Grénman, Reidar; Petersen, Cordula; Dikomey, Ekkehard; Rothkamm, Kai

    2016-01-01

    The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells. PMID:27281611

  11. How-to-Do-It: Demonstrating Sister Chromatid Exchanges.

    ERIC Educational Resources Information Center

    Dye, Frank J.

    1988-01-01

    Outlines procedures for demonstrating and preparing a permanent slide of sister chromatid exchanges and recombination events between the two chromatids of a single chromosome. Provides the name of an additional resource for making preparations of exchanges. (RT)

  12. Growth inhibition and radiosensitization of glioblastoma and lung cancer cells by siRNA silencing of tumor necrosis factor receptor-associated factor 2

    PubMed Central

    Zheng, Min; Morgan-Lappe, Susan E.; Yang, Jie; Bockbrader, Katrina M.; Pamarthy, Deepika; Thomas, Dafydd; Fesik, Stephen W.; Sun, Yi

    2008-01-01

    Radiotherapy combined with chemotherapy is the treatment of choice for glioblastoma and locally advanced lung cancer, but radioresistance of these two types of cancer remains a significant therapeutic hindrance. To identify molecular target(s) for radiosensitization, we screened a siRNA library targeting all protein kinases and E3 ubiquitin ligases in the human genome and identified TRAF2 (TNF Receptor-associated factor 2). Silencing of TRAF2 using siRNA caused a significant growth suppression of glioblastoma U251 cells and moderately sensitized these radioresistant cells to radiation. Overexpression of a RING deleted dominant negative TRAF2 mutant, also conferred radiosensitivity; whereas over-expression of wild type TRAF2 significantly protected cells from radiation-induced killing. Likewise, siRNA silencing of TRAF2 in radioresistant lung cancer H1299 cells caused growth suppression and radiosensitization, whereas overexpression of wild type TRAF2 enhanced radioresistance in a RING ligase-dependent manner. Moreover, siRNA silencing of TRAF2 in UM-SCC-1 head and neck cancer cells also conferred radiosensitization. Further support for the role of TRAF2 in cancer comes from the observations that TRAF2 is overexpressed in both lung adenocarcinoma tissues and multiple lung cancer cell lines. Importantly, TRAF2 expression was very low in normal bronchial epithelial NL20 cells, and TRAF2 silencing had a minimal effect on NL20 growth and radiation sensitivity. Mechanistically, TRAF2 silencing blocks the activation of the NF-kB signaling pathway, and down-regulates a number of G2/M cell cycle control proteins, resulting in enhanced G2/M arrest, growth suppression, and radiosensitization. Our studies suggest that TRAF2 is an attractive drug target for anti-cancer therapy and for radiosensitization. PMID:18794145

  13. Mechanics of Sister Chromatids studied with a Polymer Model English</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Zhang, Yang; Isbaner, Sebastian; Heermann, Dieter</p> <p>2013-10-01</p> <p>Sister <span class="hlt">chromatid</span> cohesion denotes the phenomenon that sister <span class="hlt">chromatids</span> are initially attached to each other in mitosis to guarantee the error-free distribution into the daughter cells. Cohesion is mediated by binding proteins and only resolved after mitotic chromosome condensation is completed. However, the amount of attachement points required to maintain sister <span class="hlt">chromatid</span> cohesion while still allowing proper chromosome condensation is not known yet. Additionally the impact of cohesion on the mechanical properties of chromosomes also poses an interesting problem. In this work we study the conformational and mechanical properties of sister <span class="hlt">chromatids</span> by means of computer simulations. We model both protein-mediated cohesion between sister <span class="hlt">chromatids</span> and chromosome condensation with a dynamic binding mechanisms. We show in a phase diagram that only specific link concentrations lead to connected and fully condensed <span class="hlt">chromatids</span> that do not intermingle with each other nor separate due to entropic forces. Furthermore we show that dynamic bonding between <span class="hlt">chromatids</span> decrease the Young's modulus compared to non-bonded <span class="hlt">chromatids</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27527863','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27527863"><span>Radiation induces premature <span class="hlt">chromatid</span> separation via the miR-142-3p/Bod1 pathway in carcinoma cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pan, Dong; Du, Yarong; Ren, Zhenxin; Chen, Yaxiong; Li, Xiaoman; Wang, Jufang; Hu, Burong</p> <p>2016-09-13</p> <p>Radiation-induced genomic instability plays a vital role in carcinogenesis. Bod1 is required for proper chromosome biorientation, and Bod1 depletion increases premature <span class="hlt">chromatid</span> separation. MiR-142-3p influences cell cycle progression and inhibits proliferation and invasion in cervical carcinoma cells. We found that radiation induced premature <span class="hlt">chromatid</span> separation and altered miR-142-3p and Bod1 expression in 786-O and A549 cells. Overexpression of miR-142-3p increased premature <span class="hlt">chromatid</span> separation and <span class="hlt">G</span><span class="hlt">2</span>/M cell cycle arrest in 786-O cells by suppressing Bod1 expression. We also found that either overexpression of miR-142-3p or knockdown of Bod1 sensitized 786-O and A549 cells to X-ray radiation. Overexpression of Bod1 inhibited radiation- and miR-142-3p-induced premature <span class="hlt">chromatid</span> separation and increased resistance to radiation in 786-O and A549 cells. Taken together, these results suggest that radiation alters miR-142-3p and Bod1 expression in carcinoma cells, and thus contributes to early stages of radiation-induced genomic instability. Combining ionizing radiation with epigenetic regulation may help improve cancer therapies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5376001','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5376001"><span>Celecoxib enhances the <span class="hlt">radiosensitivity</span> of HCT116 cells in a COX-<span class="hlt">2</span> independent manner by up-regulating BCCIP</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xu, Xiao-Ting; Hu, Wen-Tao; Zhou, Ju-Ying; Tu, Yu</p> <p>2017-01-01</p> <p>It has been reported that celecoxib, a cyclooxygenase-<span class="hlt">2</span> (COX-<span class="hlt">2</span>)-selective nonsteroidal anti-inflammatory drug (NSAID), regulates the <span class="hlt">radiosensitivity</span> of several cancer cells. BCCIP (BRCA<span class="hlt">2</span> and CDKN1A interacting protein) plays a critical role in maintaining the critical functions of p53 in tumor suppression and response to therapy. However, whether the effect of celecoxib on the <span class="hlt">radiosensitivity</span> of colorectal cancer (CRC) cells is dependent on BCCIP is largely unclear. In this study, we found that celecoxib enhanced the <span class="hlt">radiosensitivity</span> of HeLa (a human cervical carcinoma cell line), A549 (a human lung carcinoma cell line), and HCT116 cells (a human CRC cells line). Among these cells, COX-<span class="hlt">2</span> expression was undetected in HCT116 cells. Treatment with celecoxib significantly increased BCCIP expression in COX-<span class="hlt">2</span> negative HCT116 cells. Knockdown of BCCIP obviously abrogated the enhanced <span class="hlt">radiosensitivity</span> of HCT116 cells induced by celecoxib. A combination of celecoxib and irradiation treatment induced much more γ-H<span class="hlt">2</span>AX foci formation, higher levels of radiation injury-related proteins phosphorylation, <span class="hlt">G</span><span class="hlt">2</span>/M arrest, apoptosis, and p53 and p21 expression, and lower levels of Cyclin B1 in HCT116 cells than those in cells treated with irradiation alone. However, these changes were undetected in BCCIP-silenced HCT116 cells. Therefore, these data suggest that BCCIP gene may be a <span class="hlt">radiosensitivity</span>-related gene in CRC. Celecoxib affects the functions of p53 and inhibits the recovery from the irradiation-induced injury by up-regulating the expression of BCCIP, and subsequently regulates the expressions of genes such as p21 and Cyclin B1 to enhance the <span class="hlt">radiosensitivity</span> of HCT116 cells in a COX-<span class="hlt">2</span> independent manner. PMID:28386336</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22696985-inhibiting-dna-pk-sub-cs-radiosensitizes-human-osteosarcoma-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22696985-inhibiting-dna-pk-sub-cs-radiosensitizes-human-osteosarcoma-cells"><span>Inhibiting DNA-PK{sub CS} <span class="hlt">radiosensitizes</span> human osteosarcoma cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Mamo, Tewodros; Mladek, Ann C.; Shogren, Kris L.</p> <p></p> <p>Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for <span class="hlt">radiosensitizers</span>. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK{sub CS}), is an attractive option for the <span class="hlt">radiosensitization</span> of osteosarcoma. In this study, the expression of DNA-PK{sub CS} in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PK{sub CS} inhibitor, KU60648, was investigated as a <span class="hlt">radiosensitizing</span> strategy for osteosarcoma cells in vitro. DNA-PK{submore » CS} was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U<span class="hlt">2</span>OS cells by <span class="hlt">2</span>.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the <span class="hlt">G</span><span class="hlt">2</span>/M transition point increased by 55% and 45%, while the percentage of cells with >20 γH<span class="hlt">2</span>AX foci were enhanced by 59% and 107% for 143B and U<span class="hlt">2</span>OS cells, respectively. These results indicate that the DNA-PK{sub CS} inhibitor, KU60648, is a promising <span class="hlt">radiosensitizing</span> agent for osteosarcoma. - Highlights: • DNA-PKcs is consistently expressed in human osteosarcoma tissue and cell lines. • The DNA-PKcs inhibitor, KU60648, effectively <span class="hlt">radiosensitizes</span> osteosarcoma cells. • Combining KU60648 with radiation increases <span class="hlt">G</span><span class="hlt">2</span>/M accumulation and DNA damage.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3674063','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3674063"><span>Sister <span class="hlt">chromatid</span> segregation in meiosis II</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wassmann, Katja</p> <p>2013-01-01</p> <p>Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister <span class="hlt">chromatids</span>, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister <span class="hlt">chromatids</span> together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed—deprotected”—for sister <span class="hlt">chromatid</span> segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection. PMID:23574717</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2363568','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2363568"><span>Combined RAF1 protein expression and p53 mutational status provides a strong predictor of cellular <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Warenius, H M; Jones, M; Gorman, T; McLeish, R; Seabra, L; Barraclough, R; Rudland, P</p> <p>2000-01-01</p> <p>The tumour suppressor gene, p53, and genes coding for positive signal transduction factors can influence transit through cell-cycle checkpoints and modulate <span class="hlt">radiosensitivity</span>. Here we examine the effects of RAF1 protein on the rate of exit from a <span class="hlt">G</span><span class="hlt">2</span>/M block induced by γ-irradiation in relation to intrinsic cellular <span class="hlt">radiosensitivity</span> in human cell lines expressing wild-type p53 (wtp53) protein as compared to mutant p53 (mutp53) protein. Cell lines which expressed mutp53 protein were all relatively radioresistant and exhibited no relationship between RAF1 protein and cellular <span class="hlt">radiosensitivity</span>. Cell lines expressing wtp53 protein, however, showed a strong relationship between RAF1 protein levels and the <span class="hlt">radiosensitivity</span> parameter SF<span class="hlt">2</span>. In addition, when post-irradiation perturbation of <span class="hlt">G</span><span class="hlt">2</span>/M transit was compared using the parameter T50 (time after the peak of <span class="hlt">G</span><span class="hlt">2</span>/M delay at which 50% of the cells had exited from a block induced by <span class="hlt">2</span> Gy of irradiation), RAF1 was related to T50 in wtp53, but not mutp53, cell lines. Cell lines which expressed wtp53 protein and high levels of RAF1 had shorter T50s and were also more <span class="hlt">radiosensitive</span>. These results suggest a cooperative role for wtp53 and RAF1 protein in determining cellular <span class="hlt">radiosensitivity</span> in human cells, which involves control of the <span class="hlt">G</span><span class="hlt">2</span>/M checkpoint. © 2000 Cancer Research Campaign PMID:10993658</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/4120663-dose-rate-mitotic-cycle-duration-sensitivity-cell-transitions-from-g1-yields-g2-yields-protracted-gamma-radiation-root-meristems','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/4120663-dose-rate-mitotic-cycle-duration-sensitivity-cell-transitions-from-g1-yields-g2-yields-protracted-gamma-radiation-root-meristems"><span>Dose rate, mitotic cycle duration, and sensitivity of cell transitions from <span class="hlt">G</span>1 $Yields$ S and <span class="hlt">G</span><span class="hlt">2</span> $Yields$ M to protracted gamma radiation in root meristems</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Evans, L.S.; Hof, J.V.</p> <p>1975-11-01</p> <p>Experiments were designed to determine the relative <span class="hlt">radiosensitivity</span> of the cell transition points of <span class="hlt">G</span>1 $Yields$ S and <span class="hlt">G</span><span class="hlt">2</span> $Yields$ M in root meristems of several plant species. Label and mitotic indices and microspectrophotometry were used to measure the proportions of cells in each mitotic cycle stage in root meristems after protracted gamma radiation. The criterion of <span class="hlt">radiosensitivity</span> was the dose rate needed to produce a tissue with less than 1 percent cells in S and none in M after 3 days of continuous exposure. The results show that DNA is the primary radiation target in proliferative root meristems andmore » that the cycle duration stipulates the time interval of vulnerability. In each species, nonrandom reproducible cell proportions were established with <span class="hlt">2</span>C:4C:8C amounts of nuclear DNA after 3 days of exposure. Roots of Helianthus annuus, Crepis capillaris, and Tradescantia clone 02 had 80 percent cells with a <span class="hlt">2</span>C amount of DNA and 20 percent had a 4C amount of DNA. In these species the transition point of <span class="hlt">G</span>1 $Yields$ S was more <span class="hlt">radiosensitive</span> than <span class="hlt">G</span><span class="hlt">2</span> $Yields$ M. Roots of Pisum sativum and Triticum aestivum had cell proportions at <span class="hlt">2</span>C:4C:8C amounts of DNA in frequencies of 0.10 to 0.20:0.40 to 0.60:0.30 to 0.40. In these two species 0.30 to 0.40 cells underwent radiation-induced endoreduplication that resulted from a rapid inhibition of cell transit from <span class="hlt">G</span><span class="hlt">2</span> $Yields$ M and a slower impairment of <span class="hlt">G</span>1 $Yields$ S. Cells increased from <span class="hlt">2</span>C to 4C and from 4C to 8C amounts of DNA during irradiation. The proportions of nuclei with <span class="hlt">2</span>C:4C:8C amounts of DNA were dependent in part upon the relative <span class="hlt">radiosensitivity</span> of the <span class="hlt">G</span>1 $Yields$ S and <span class="hlt">G</span><span class="hlt">2</span> $Yields$ M control points. The data show the relative <span class="hlt">radiosensitivity</span> of the transition points from <span class="hlt">G</span>1 $Yields$ S and from <span class="hlt">G</span><span class="hlt">2</span> $Yields$ M was species specific and unrelated to the cycle duration and mean nuclear DNA content of the plant species. (auth)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22606211-radiosensitization-parp-inhibition-proton-beam-irradiation-incancer-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22606211-radiosensitization-parp-inhibition-proton-beam-irradiation-incancer-cells"><span><span class="hlt">Radiosensitization</span> by PARP inhibition to proton beam irradiation in cancer cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hirai, Takahisa; Division of Chemotherapy and Clinical Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo; Saito, Soichiro</p> <p></p> <p>The poly(ADP-ribose) polymerase (PARP)-1 regulates DNA damage responses and promotes base excision repair. PARP inhibitors have been shown to enhance the cytotoxicity of ionizing radiation in various cancer cells and animal models. We have demonstrated that the PARP inhibitor (PARPi) AZD2281 is also an effective <span class="hlt">radiosensitizer</span> for carbon-ion radiation; thus, we speculated that the PARPi could be applied to a wide therapeutic range of linear energy transfer (LET) radiation as a <span class="hlt">radiosensitizer</span>. Institutes for biological experiments using proton beam are limited worldwide. This study was performed as a cooperative research at heavy ion medical accelerator in Chiba (HIMAC) in Nationalmore » Institute of Radiological Sciences. HIMAC can generate various ion beams; this enabled us to compare the <span class="hlt">radiosensitization</span> effect of the PARPi on cells subjected to proton and carbon-ion beams from the same beam line. After physical optimization of proton beam irradiation, the <span class="hlt">radiosensitization</span> effect of the PARPi was assessed in the human lung cancer cell line, A549, and the pancreatic cancer cell line, MIA PaCa-<span class="hlt">2</span>. The effect of the PARPi, AZD2281, on <span class="hlt">radiosensitization</span> to Bragg peak was more significant than that to entrance region. The PARPi increased the number of phosphorylated H<span class="hlt">2</span>AX (γ-H<span class="hlt">2</span>AX) foci and enhanced <span class="hlt">G</span><span class="hlt">2</span>/M arrest after proton beam irradiation. This result supports our hypothesis that a PARPi could be applied to a wide therapeutic range of LET radiation by blocking the DNA repair response. - Highlights: • Effective <span class="hlt">radiosensitizers</span> for particle radiation therapy have not been reported. • PARP inhibitor treatment <span class="hlt">radiosensitized</span> after proton beam irradiation. • The sensitization at Bragg peak was greater than that at entrance region. • DSB induction and <span class="hlt">G</span><span class="hlt">2</span>/M arrest is involved in the sensitization mechanism.« less</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_1");'>1</a></li> <li class="active"><span>2</span></li> <li><a href="#" onclick='return showDiv("page_3");'>3</a></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_2 --> <div id="page_3" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_1");'>1</a></li> <li><a href="#" onclick='return showDiv("page_2");'>2</a></li> <li class="active"><span>3</span></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="41"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29152122','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29152122"><span>Cisplatin <span class="hlt">radiosensitizes</span> radioresistant human mesenchymal stem cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rühle, Alexander; Perez, Ramon Lopez; Glowa, Christin; Weber, Klaus-Josef; Ho, Anthony D; Debus, Jürgen; Saffrich, Rainer; Huber, Peter E; Nicolay, Nils H</p> <p>2017-10-20</p> <p>Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment <span class="hlt">radiosensitized</span> human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated <span class="hlt">radiosensitivity</span> was associated with a cell cycle shift of MSCs towards the <span class="hlt">radiosensitive</span> <span class="hlt">G</span><span class="hlt">2</span>/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent <span class="hlt">radiosensitization</span> effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014AIPC.1614...78R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014AIPC.1614...78R"><span>Synthesis and <span class="hlt">radiosensitization</span> properties of hydrogen peroxide and sodium hyaluronate complex</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Rosli, Nur Ratasha Alia Md.; Mohamed, Faizal; Heng, Cheong Kai; Rahman, Irman Abdul; Ahmad, Ainee Fatimah; Mohamad, Hur Munawar Kabir</p> <p>2014-09-01</p> <p>Cancer cells which are large in size are resistant towards radiation therapy due to the presence of large amount of anti-oxidative enzymes and hypoxic cancer cells. Thus <span class="hlt">radiosensitizer</span> agents have been developed to enhance the therapeutic effect of radiotherapy by increasing the sensitivity of these cancer cells towards radiation. This study is conducted to investigate the <span class="hlt">radiosensitization</span> properties of <span class="hlt">radiosensitizer</span> complex containing hydrogen peroxide and sodium hyaluronate. Combination with sodium hyaluronate may decrease reactivity of hydrogen peroxide but maintain the oxygen concentration needed for <span class="hlt">radiosensitizing</span> effect. Hep<span class="hlt">G</span><span class="hlt">2</span> cancer cells are cultured as the mean of test subject. Cancer cell samples which are targeted and not targeted with these <span class="hlt">radiosensitizers</span> are irradiated with <span class="hlt">2</span>Gy single fractionated dose. Results obtained shows that the cancer cells which are not targeted with <span class="hlt">radiosensitizers</span> has a cell viability of 98.80±0.37% after a time interval of 48 hours and has even repopulated over 100% after a 72 hour time interval. This shows that the cancer cells are resistant towards radiation. However, when the cancer cells are targeted with <span class="hlt">radiosensitizers</span> prior to irradiation, there is a reduction of cell viability by 25.50±10.81% and 10.30±5.10% at time intervals of 48 and 72 hours respectively. This indicates that through the use of these <span class="hlt">radiosensitizers</span>, cancer cells are more sensitive towards radiation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6721582-comparison-cytological-effects-three-hypoxic-cell-radiosensitizers','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6721582-comparison-cytological-effects-three-hypoxic-cell-radiosensitizers"><span>A comparison of the cytological effects of three hypoxic cell <span class="hlt">radiosensitizers</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Spunberg, J.J.; Geard, C.R.; Rutledge-Freeman, M.H.</p> <p>1982-07-01</p> <p>Misonidazole has entered Phase III clinical trials as a hypoxic cell <span class="hlt">radiosensitizer</span>. Neurotoxocity is the major dose-limiting factor and has prompted the development of two further compounds with reduced lipophilicity and shorter half-life in vivo. Aside from the short-term problem of neurotoxicity, other potential long-term consequences should be considered. Such is the purpose of this investigation where the cytological effects of three <span class="hlt">radiosensitizers</span> upon oxic and hypoxic Chinese hamster V-79 cells have been examined. Two newer compounds, desmethylmisonidazole and Stanford Research compound 2508, were compared with their clinically used predecessor misonidazole. Under aerated conditions, cell killing was increased with SR-2508more » in a concentration and time dependent manner, so as to exceed by more than three times the level produced by the other two drugs at 5 mM for 72 hours.Cell progression into mitosis was also markedly reduced by as much as 1/10,000 of control values. However, as the three compounds induced similar frequencies of sister <span class="hlt">chromatid</span> exchange (SCE) and chromosome aberration, the enhanced cytotoxic effect of SR-2508 appears to be mediated via an interphase rather than a post-mitotic cell death. Cells were made hypoxic and treated with the three drugs for 4 hr, then mitoses sequentially collected for 16 hr. The three compounds produced similar levels of cell killing, slowing of cell cycle progression, SCE's and chromosome aberrations, with cycle-specific effect on S and <span class="hlt">G</span>-I phase cells for SCE induction. These results indicate that desmethylmisonidazole and misonidazole have similar cytotoxic and clastogenic properties under oxic and hypoxic conditions. SR-2508 is relatively more toxic to aerated cells and may deserve close clinical observation for toxicity to normal tissues.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11444040','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11444040"><span>Splitting the chromosome: cutting the ties that bind sister <span class="hlt">chromatids</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nasmyth, K; Peters, J M; Uhlmann, F</p> <p>2001-01-01</p> <p>In eukaryotic cells, replicated DNA molecules remain physically connected from their synthesis in S phase until they are separated during anaphase. This phenomenon, called sister <span class="hlt">chromatid</span> cohesion, is essential for the temporal separation of DNA replication and mitosis and for the equal separation of the duplicated genome. Recent work has identified a number of chromosomal proteins required for cohesion. In this review we discuss how these proteins may connect sister <span class="hlt">chromatids</span> and how they are removed from chromosomes to allow sister <span class="hlt">chromatid</span> separation at the onset of anaphase.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22308352-synthesis-radiosensitization-properties-hydrogen-peroxide-sodium-hyaluronate-complex','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22308352-synthesis-radiosensitization-properties-hydrogen-peroxide-sodium-hyaluronate-complex"><span>Synthesis and <span class="hlt">radiosensitization</span> properties of hydrogen peroxide and sodium hyaluronate complex</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Rosli, Nur Ratasha Alia Md.; Mohamed, Faizal; Heng, Cheong Kai</p> <p>2014-09-03</p> <p>Cancer cells which are large in size are resistant towards radiation therapy due to the presence of large amount of anti-oxidative enzymes and hypoxic cancer cells. Thus <span class="hlt">radiosensitizer</span> agents have been developed to enhance the therapeutic effect of radiotherapy by increasing the sensitivity of these cancer cells towards radiation. This study is conducted to investigate the <span class="hlt">radiosensitization</span> properties of <span class="hlt">radiosensitizer</span> complex containing hydrogen peroxide and sodium hyaluronate. Combination with sodium hyaluronate may decrease reactivity of hydrogen peroxide but maintain the oxygen concentration needed for <span class="hlt">radiosensitizing</span> effect. Hep<span class="hlt">G</span><span class="hlt">2</span> cancer cells are cultured as the mean of test subject. Cancer cell samplesmore » which are targeted and not targeted with these <span class="hlt">radiosensitizers</span> are irradiated with <span class="hlt">2</span>Gy single fractionated dose. Results obtained shows that the cancer cells which are not targeted with <span class="hlt">radiosensitizers</span> has a cell viability of 98.80±0.37% after a time interval of 48 hours and has even repopulated over 100% after a 72 hour time interval. This shows that the cancer cells are resistant towards radiation. However, when the cancer cells are targeted with <span class="hlt">radiosensitizers</span> prior to irradiation, there is a reduction of cell viability by 25.50±10.81% and 10.30±5.10% at time intervals of 48 and 72 hours respectively. This indicates that through the use of these <span class="hlt">radiosensitizers</span>, cancer cells are more sensitive towards radiation.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4214429','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4214429"><span>Alternative meiotic <span class="hlt">chromatid</span> segregation in the holocentric plant Luzula elegans</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Heckmann, Stefan; Jankowska, Maja; Schubert, Veit; Kumke, Katrin; Ma, Wei; Houben, Andreas</p> <p>2014-01-01</p> <p>Holocentric chromosomes occur in a number of independent eukaryotic lineages. They form holokinetic kinetochores along the entire poleward <span class="hlt">chromatid</span> surfaces, and owing to this alternative chromosome structure, species with holocentric chromosomes cannot use the two-step loss of cohesion during meiosis typical for monocentric chromosomes. Here we show that the plant Luzula elegans maintains a holocentric chromosome architecture and behaviour throughout meiosis, and in contrast to monopolar sister centromere orientation, the unfused holokinetic sister centromeres behave as two distinct functional units during meiosis I, resulting in sister <span class="hlt">chromatid</span> separation. Homologous non-sister <span class="hlt">chromatids</span> remain terminally linked after metaphase I, by satellite DNA-enriched chromatin threads, until metaphase II. They then separate at anaphase II. Thus, an inverted sequence of meiotic sister <span class="hlt">chromatid</span> segregation occurs. This alternative meiotic process is most likely one possible adaptation to handle a holocentric chromosome architecture and behaviour during meiosis. PMID:25296379</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2776007','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2776007"><span>Effect of borax on immune cell proliferation and sister <span class="hlt">chromatid</span> exchange in human chromosomes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pongsavee, Malinee</p> <p>2009-01-01</p> <p>Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister <span class="hlt">chromatid</span> exchange in human chromosomes. The MTT assay and Sister <span class="hlt">Chromatid</span> Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.<span class="hlt">2</span>, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.<span class="hlt">2</span>, 0.3 and 0.6 mg/ml significantly induced sister <span class="hlt">chromatid</span> exchange in human chromosomes (P < 0.05). Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister <span class="hlt">chromatid</span> exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human. PMID:19878537</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8248278','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8248278"><span>Enhancement of antineoplastic effect and attenuation of sister <span class="hlt">chromatid</span> exchanges by prostaglandin E<span class="hlt">2</span> in Ehrlich ascites tumour cells treated with cyclophosphamide in vivo.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mourelatos, D; Kritsi, Z; Mioglou, E; Dozi-Vassiliades, J</p> <p>1993-09-01</p> <p>Reduced sister <span class="hlt">chromatid</span> exchanges (SCE) frequency in response to cyclophosphamide (CP) was observed when Ehrlich ascites tumour (EAT) cells were exposed in vivo to <span class="hlt">2</span> micrograms/<span class="hlt">g</span> body weight of prostaglandin E<span class="hlt">2</span> (PGE<span class="hlt">2</span>). 1 h before i.p. injection of 5-bromodeoxyuridine (BrdUrd) adsorbed to activated charcoal, EAT-bearing mice treated i.p. with CP appeared to have increased SCE rates and cell division delays. PGE<span class="hlt">2</span> had no effect on survival and in inhibiting tumour growth. CP had only a slight non-significant effect on survival and in inhibiting tumour growth. In mice treated with the combined CP (5 micrograms/<span class="hlt">g</span> bd wt) plus PGE<span class="hlt">2</span> (<span class="hlt">2</span> micrograms/<span class="hlt">g</span> bd wt) a significant enhancement (P < 0.01) of survival time was accompanied by inhibition of tumour growth (P < 0.01) in comparison with the untreated controls. These data imply that SCEs might result from errors in a repair process which might involve a PGE<span class="hlt">2</span> sensitive step.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6880485-radiosensitivity-different-tissues-from-carrot-root-different-phases-growth-culture','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6880485-radiosensitivity-different-tissues-from-carrot-root-different-phases-growth-culture"><span><span class="hlt">Radiosensitivity</span> of different tissues from carrot root at different phases of growth in culture</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Degani, N.; Pickholtz, D.</p> <p>1980-09-01</p> <p>The present work compares the effect of ..gamma..-radiation dose and time in culture on the growth of cambium and phloem carrot (Daucus carota) root explants. It was found that the phloem is more <span class="hlt">radiosensitive</span> than the cambium and that both tissues were more <span class="hlt">radiosensitive</span> when irradiated on excision at the <span class="hlt">G</span>/sub 1/ phase rather than at the end of the lag phase on the ninth day of growth in culture when cells were predominantly at the <span class="hlt">G</span>/sub <span class="hlt">2</span>/ phase. The nuclear volumes of cells from both tissues were similar but were larger at the end of the more radioresistant lagmore » phase than those of the <span class="hlt">G</span>/sub 1/ phase on excision. However, nuclear volume could not account for the differences in <span class="hlt">radiosensitivity</span> between either the tissues or irradiation times in culture.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2946792','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2946792"><span><span class="hlt">Radiosensitization</span> of Cancer Cells by Hydroxychalcones</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L.; Sekhar, Konjeti R.</p> <p>2010-01-01</p> <p>Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited <span class="hlt">radiosensitizing</span> properties. The hydroxychalcones, <span class="hlt">2</span>′,5′-dihydroxychalcone (D-601) and <span class="hlt">2,2</span>′-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The <span class="hlt">radiosensitization</span> ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A<span class="hlt">2</span> (CYP1A<span class="hlt">2</span>), suggesting that the metabolite of D-601 is essential for <span class="hlt">radiosensitization</span>. The study demonstrated the ability of hydroxychalcones to <span class="hlt">radiosensitize</span> cancer cells and provides new leads for developing novel radiation sensitizers. PMID:20826087</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11862455','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11862455"><span>Colchicine promotes a change in chromosome structure without loss of sister <span class="hlt">chromatid</span> cohesion in prometaphase I-arrested bivalents.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rodríguez, E M; Parra, M T; Rufas, J S; Suja, J A</p> <p>2001-12-01</p> <p>In somatic cells colchicine promotes the arrest of cell division at prometaphase, and chromosomes show a sequential loss of sister <span class="hlt">chromatid</span> arm and centromere cohesion. In this study we used colchicine to analyse possible changes in chromosome structure and sister <span class="hlt">chromatid</span> cohesion in prometaphase I-arrested bivalents of the katydid Pycnogaster cucullata. After silver staining we observed that in colchicine-arrested prometaphase I bivalents, and in contrast to what was found in control bivalents, sister kinetochores appeared individualised and sister <span class="hlt">chromatid</span> axes were completely separated all along their length. However, this change in chromosome structure occurred without loss of sister <span class="hlt">chromatid</span> arm cohesion. We also employed the MPM-<span class="hlt">2</span> monoclonal antibody against mitotic phosphoproteins on control and colchicine-treated spermatocytes. In control metaphase I bivalents this antibody labelled the tightly associated sister kinetochores and the interchromatid domain. By contrast, in colchicine-treated prometaphase I bivalents individualised sister kinetochores appeared labelled, but the interchromatid domain did not show labelling. These results support the notion that MPM-<span class="hlt">2</span> phosphoproteins, probably DNA topoisomerase IIalpha, located in the interchromatid domain act as "chromosomal staples" associating sister <span class="hlt">chromatid</span> axes in metaphase I bivalents. The disappearance of these chromosomal staples would induce a change in chromosome structure, as reflected by the separation of sister kinetochores and sister axes, but without a concomitant loss of sister <span class="hlt">chromatid</span> cohesion.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20826087','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20826087"><span><span class="hlt">Radiosensitization</span> of cancer cells by hydroxychalcones.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pruitt, Rory; Sasi, Nidhish; Freeman, Michael L; Sekhar, Konjeti R</p> <p>2010-10-15</p> <p>Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited <span class="hlt">radiosensitizing</span> properties. The hydroxychalcones, <span class="hlt">2</span>',5'-dihydroxychalcone (D-601) and <span class="hlt">2,2</span>'-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The <span class="hlt">radiosensitization</span> ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A<span class="hlt">2</span> (CYP1A<span class="hlt">2</span>), suggesting that the metabolite of D-601 is essential for <span class="hlt">radiosensitization</span>. The study demonstrated the ability of hydroxychalcones to <span class="hlt">radiosensitize</span> cancer cells and provides new leads for developing novel radiation sensitizers. Copyright © 2010 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3514784','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3514784"><span>Cell elongation is an adaptive response for clearing long <span class="hlt">chromatid</span> arms from the cleavage plane</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kotadia, Shaila; Montembault, Emilie; Sullivan, William</p> <p>2012-01-01</p> <p>Chromosome segregation must be coordinated with cell cleavage to ensure correct transmission of the genome to daughter cells. Here we identify a novel mechanism by which Drosophila melanogaster neuronal stem cells coordinate sister <span class="hlt">chromatid</span> segregation with cleavage furrow ingression. Cells adapted to a dramatic increase in <span class="hlt">chromatid</span> arm length by transiently elongating during anaphase/telophase. The degree of cell elongation correlated with the length of the trailing <span class="hlt">chromatid</span> arms and was concomitant with a slight increase in spindle length and an enlargement of the zone of cortical myosin distribution. Rho guanine-nucleotide exchange factor (Pebble)–depleted cells failed to elongate during segregation of long <span class="hlt">chromatids</span>. As a result, Pebble-depleted adult flies exhibited morphological defects likely caused by cell death during development. These studies reveal a novel pathway linking trailing <span class="hlt">chromatid</span> arms and cortical myosin that ensures the clearance of <span class="hlt">chromatids</span> from the cleavage plane at the appropriate time during cytokinesis, thus preserving genome integrity. PMID:23185030</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22796462','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22796462"><span>Localized delivery of chemotherapy to the cervix for <span class="hlt">radiosensitization</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hodge, Lucy S; Downs, Levi S; Chura, Justin C; Thomas, Sajeena G; Callery, Patrick S; Soisson, A Patrick; Kramer, Paul; Wolfe, Stephen S; Tracy, Timothy S</p> <p>2012-10-01</p> <p>Chemoradiation is the mainstay of therapy for advanced cervical cancer, with the most effective treatment regimens involving combinations of <span class="hlt">radiosensitizing</span> agents. However, administration of <span class="hlt">radiosensitizing</span> chemotherapeutics concurrently with pelvic radiation is not without side effects. The aim of this study was to examine the utility of localized drug delivery as a means of improving drug targeting of <span class="hlt">radiosensitizing</span> chemotherapeutics to the cervix while limiting systemic toxicities. An initial proof-of-concept study was performed in 14 healthy women following local administration of diazepam utilizing a novel cervical delivery device (CerviPrep™). Uterine vein and peripheral blood samples were collected and diazepam was measured using a GC-MS method. In the follow-up study, gemcitabine was applied to the cervix in 17 women undergoing hysterectomy for various gynecological malignancies. Cervical tissue, uterine vein blood samples, and peripheral plasma were collected, and gemcitabine and its deaminated metabolite <span class="hlt">2',2</span>'-difluorodeoxyuridine (dFdU) were measured using HPLC-UV and LC/MS methods. Targeted delivery of diazepam to the cervix was consistent with parent drug detectable in the uterine vein of 13 of 14 women. In the second study, pharmacologically relevant concentrations of gemcitabine (0.01-6.6 nmol/<span class="hlt">g</span> tissue) were detected in the cervical tissue of 11 of 16 available specimens with dFdU measureable in 15 samples (0.04-8.8 nmol/<span class="hlt">g</span> tissue). Neither gemcitabine nor its metabolites were detected in the peripheral plasma of any subject. Localized drug delivery to the cervix is possible and may be useful in limiting toxicity associated with intravenous administration of chemotherapeutics for <span class="hlt">radiosensitization</span>. Copyright © 2012 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23519742','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23519742"><span>In vitro and in vivo <span class="hlt">radiosensitization</span> induced by hydroxyapatite nanoparticles.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chu, Sheng-Hua; Karri, Surya; Ma, Yan-Bin; Feng, Dong-Fu; Li, Zhi-Qiang</p> <p>2013-07-01</p> <p>Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of <span class="hlt">radiosensitivity</span> induced by nano-HAPs. In vitro <span class="hlt">radiosensitization</span> of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using γH<span class="hlt">2</span>AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor <span class="hlt">radiosensitivity</span> was investigated in a subcutaneous and an orthotopic model. Nano-HAPs enhanced each cell line's <span class="hlt">radiosensitivity</span> when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the <span class="hlt">G</span><span class="hlt">2</span> cell cycle checkpoint. The number of γH<span class="hlt">2</span>AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation. These results show that nano-HAPs can enhance the <span class="hlt">radiosensitivity</span> of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29284117','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29284117"><span>Knockdown of AMPKα decreases ATM expression and increases <span class="hlt">radiosensitivity</span> under hypoxia and nutrient starvation in an SV40-transformed human fibroblast cell line, LM217.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Murata, Yasuhiko; Hashimoto, Takuma; Urushihara, Yusuke; Shiga, Soichiro; Takeda, Kazuya; Jingu, Keiichi; Hosoi, Yoshio</p> <p>2018-01-22</p> <p>Presence of unperfused regions containing cells under hypoxia and nutrient starvation contributes to radioresistance in solid human tumors. It is well known that hypoxia causes cellular radioresistance, but little is known about the effects of nutrient starvation on <span class="hlt">radiosensitivity</span>. We have reported that nutrient starvation induced decrease of mTORC1 activity and decrease of <span class="hlt">radiosensitivity</span> in an SV40-transformed human fibroblast cell line, LM217, and that nutrient starvation induced increase of mTORC1 activity and increase of <span class="hlt">radiosensitivity</span> in human liver cancer cell lines, Hep<span class="hlt">G</span><span class="hlt">2</span> and HuH6 (Murata et al., BBRC 2015). Knockdown of mTOR using small interfering RNA (siRNA) for mTOR suppressed <span class="hlt">radiosensitivity</span> under nutrient starvation alone in Hep<span class="hlt">G</span><span class="hlt">2</span> cells, which suggests that mTORC1 pathway regulates <span class="hlt">radiosensitivity</span> under nutrient starvation alone. In the present study, effects of hypoxia and nutrient starvation on <span class="hlt">radiosensitivity</span> were investigated using the same cell lines. LM217 and Hep<span class="hlt">G</span><span class="hlt">2</span> cells were used to examine the effects of hypoxia and nutrient starvation on cellular <span class="hlt">radiosensitivity</span>, mTORC1 pathway including AMPK, ATM, and HIF-1α, which are known as regulators of mTORC1 activity, and glycogen storage, which is induced by HIF-1 and HIF-<span class="hlt">2</span> under hypoxia and promotes cell survival. Under hypoxia and nutrient starvation, AMPK activity and ATM expression were increased in LM217 cells and decreased in Hep<span class="hlt">G</span><span class="hlt">2</span> cells compared with AMPK activity under nutrient starvation alone or ATM expression under hypoxia alone. Under hypoxia and nutrient starvation, <span class="hlt">radiosensitivity</span> was decreased in LM217 cells and increased in Hep<span class="hlt">G</span><span class="hlt">2</span> cells compared with <span class="hlt">radiosensitivity</span> under hypoxia alone. Under hypoxia and nutrient starvation, knockdown of AMPK decreased ATM activity and increased radiation sensitivity in LM217 cells. In both cell lines, mTORC1 activity was decreased under hypoxia and nutrient starvation. Under hypoxia alone, knockdown of mTOR slightly increased ATM</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26122845','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26122845"><span>Defects in the Fanconi Anemia Pathway and <span class="hlt">Chromatid</span> Cohesion in Head and Neck Cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Stoepker, Chantal; Ameziane, Najim; van der Lelij, Petra; Kooi, Irsan E; Oostra, Anneke B; Rooimans, Martin A; van Mil, Saskia E; Brink, Arjen; Dietrich, Ralf; Balk, Jesper A; Ylstra, Bauke; Joenje, Hans; Feller, Stephan M; Brakenhoff, Ruud H</p> <p>2015-09-01</p> <p>Failure to repair DNA damage or defective sister <span class="hlt">chromatid</span> cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non-Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister <span class="hlt">chromatid</span> cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG<span class="hlt">2</span> resulted in inadequate sister <span class="hlt">chromatid</span> cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective <span class="hlt">chromatid</span> cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and <span class="hlt">chromatid</span> cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. ©2015 American Association for Cancer Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86942','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86942"><span>Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister <span class="hlt">Chromatid</span> Cohesion</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Hanna, Joseph S.; Kroll, Evgueny S.; Lundblad, Victoria; Spencer, Forrest A.</p> <p>2001-01-01</p> <p>CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of either CTF4 or CTF18 causes sister <span class="hlt">chromatid</span> cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister <span class="hlt">chromatid</span> cohesion. We find that Ctf18p, an RFC1-like protein, directly interacts with Rfc<span class="hlt">2</span>p, Rfc3p, Rfc4p, and Rfc5p. However, Ctf18p is not a component of biochemically purified proliferating cell nuclear antigen loading RF-C, suggesting the presence of a discrete complex containing Ctf18p, Rfc<span class="hlt">2</span>p, Rfc3p, Rfc4p, and Rfc5p. Recent identification and characterization of the budding yeast polymerase κ, encoded by TRF4, strongly supports a hypothesis that the DNA replication machinery is required for proper sister <span class="hlt">chromatid</span> cohesion. Analogous to the polymerase switching role of the bacterial and human RF-C complexes, we propose that budding yeast RF-CCTF18 may be involved in a polymerase switch event that facilities sister <span class="hlt">chromatid</span> cohesion. The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process. PMID:11287619</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22462015-activating-pten-cox-inhibitors-antagonizes-radiation-induced-akt-activation-contributing-radiosensitization','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22462015-activating-pten-cox-inhibitors-antagonizes-radiation-induced-akt-activation-contributing-radiosensitization"><span>Activating PTEN by COX-<span class="hlt">2</span> inhibitors antagonizes radiation-induced AKT activation contributing to <span class="hlt">radiosensitization</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Meng, Zhen; Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081; Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn</p> <p>2015-05-01</p> <p>Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-<span class="hlt">2</span> inhibitors can induce <span class="hlt">radiosensitization</span>, the underlying mechanism is not fully understood. In this study, we showed that COX-<span class="hlt">2</span> selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocationmore » and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-<span class="hlt">2</span> selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-<span class="hlt">2</span> inhibitors could enhance <span class="hlt">radiosensitization</span> at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-<span class="hlt">2</span> inhibitor, celecoxib, could enhance <span class="hlt">radiosensitization</span>. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-<span class="hlt">2</span> inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-<span class="hlt">2</span> inhibitor enhanced <span class="hlt">radiosensitization</span> through activating PTEN.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25553380','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25553380"><span>Selective <span class="hlt">chromatid</span> segregation mechanism for Bruchus wings piebald color.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Klar, Amar J S</p> <p>2015-01-01</p> <p>The mechanisms of asymmetric organ development have been under intensive investigation for years, yet the proposed mechanisms remain controversial (1-3). The female Bruchus quadrimaculatus beetle insect develops two black-colored spots bilaterally located on each upper elytra wing by an unknown mechanism. Fifty percent of the P (for piebald, two colors) gene homozygous mutant insects, described in 1925, had a normal left elytrum (with two black spots) and an abnormal right elytrum (with two red spots) and the balance supported the converse lateralized pigment arrangement (4). Rather than supporting the conventional morphogen model for the wings pigmentation development, their biological origin is explained here with the somatic strand-specific epigenetic imprinting and selective sister <span class="hlt">chromatid</span> segregation (SSIS) mechanism (5). We propose that the P gene product performs the selective sister <span class="hlt">chromatid</span> segregation function to produce symmetric cell division of a specific cell during embryogenesis to result in the bilateral symmetric development of elytra black color spots and that the altered <span class="hlt">chromatid</span> segregation pattern of the mutant causes asymmetric cell division to confer the piebald phenotype. </p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_1");'>1</a></li> <li><a href="#" onclick='return showDiv("page_2");'>2</a></li> <li class="active"><span>3</span></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_3 --> <div id="page_4" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_2");'>2</a></li> <li><a href="#" onclick='return showDiv("page_3");'>3</a></li> <li class="active"><span>4</span></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="61"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23417411','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23417411"><span>Histone hyperacetylation during meiosis interferes with large-scale chromatin remodeling, axial <span class="hlt">chromatid</span> condensation and sister <span class="hlt">chromatid</span> separation in the mammalian oocyte.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Feikun; Baumann, Claudia; Viveiros, Maria M; De La Fuente, Rabindranath</p> <p>2012-01-01</p> <p>Histone acetylation regulates higher-order chromatin structure and function and is critical for the control of gene expression. Histone deacetylase inhibitors (HDACi) are currently under investigation as novel cancer therapeutic drugs. Here, we show that female germ cells are extremely susceptible to chromatin changes induced by HDACi. Our results indicate that exposure to trichostatin A (TSA) at nanomolar levels interferes with major chromatin remodeling events in the mammalian oocyte leading to chromosome instability. High resolution analysis of chromatin structure and live-cell imaging revealed a striking euchromatin decondensation associated with histone H4 hyperacetylation following exposure to 15 nM TSA in >90% of pre-ovulatory oocytes. Dynamic changes in large-scale chromatin structure were detected after <span class="hlt">2</span> h of exposure and result in the formation of misaligned chromosomes in >75% (P<0.05) of in vitro matured oocytes showing chromosome lagging as well as abnormal sister <span class="hlt">chromatid</span> separation at anaphase I. Abnormal axial <span class="hlt">chromatid</span> condensation during meiosis results in the formation of elongated chromosomes exhibiting hyperacetylation of histone H4 at lysine 5 and lysine 16 at interstitial chromosome segments, but not pericentric heterochromatin, while highly decondensed bivalents exhibit prominent histone H3 phosphorylation at centromeric domains. Notably, no changes were observed in the chromosomal localization of the condensin protein SMC4. These results indicate that HDAC activity is required for proper chromosome condensation in the mammalian oocyte and that HDACi may induce abnormal chromosome segregation by interfering with both chromosome-microtubule interactions, as well as sister <span class="hlt">chromatid</span> separation. Thus, HDACi, proposed for cancer therapy, may disrupt the epigenetic status of female germ cells, predisposing oocytes to aneuploidy at previously unrecognized low doses.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3688012','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3688012"><span>In vitro and in vivo <span class="hlt">radiosensitization</span> induced by hydroxyapatite nanoparticles</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chu, Sheng-Hua; Karri, Surya; Ma, Yan-Bin; Feng, Dong-Fu; Li, Zhi-Qiang</p> <p>2013-01-01</p> <p>Background Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of <span class="hlt">radiosensitivity</span> induced by nano-HAPs. Methods In vitro <span class="hlt">radiosensitization</span> of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using γH<span class="hlt">2</span>AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor <span class="hlt">radiosensitivity</span> was investigated in a subcutaneous and an orthotopic model. Results Nano-HAPs enhanced each cell line's <span class="hlt">radiosensitivity</span> when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the <span class="hlt">G</span><span class="hlt">2</span> cell cycle checkpoint. The number of γH<span class="hlt">2</span>AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation. Conclusions These results show that nano-HAPs can enhance the <span class="hlt">radiosensitivity</span> of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe. PMID:23519742</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22058923-simultaneous-inhibition-egfr-pi3k-enhances-radiosensitivity-human-breast-cancer','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22058923-simultaneous-inhibition-egfr-pi3k-enhances-radiosensitivity-human-breast-cancer"><span>Simultaneous Inhibition of EGFR and PI3K Enhances <span class="hlt">Radiosensitivity</span> in Human Breast Cancer</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Li Ping; Zhang Qing; Torossian, Artour</p> <p>2012-07-01</p> <p>Purpose: Mutations in the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/Akt signaling transduction pathway are common in cancer. This pathway is imperative to the <span class="hlt">radiosensitivity</span> of cancer cells. We aimed to investigate the <span class="hlt">radiosensitizing</span> effects of the simultaneous inhibition of EGFR and PI3K in breast cancer cells. Methods and Materials: MCF-7 cell lines with low expression of EGFR and wild-type PTEN and MDA-MB-468 cell lines with high expression of EGFR and mutant PTEN were used. The <span class="hlt">radiosensitizing</span> effects by the inhibition of EGFR with AG1478 and/or PI3K with Ly294002 were determined by colony formation assay, Western blot was used tomore » investigate the effects on downstream signaling. Flow cytometry was used for apoptosis and cell cycle analysis. Mice-bearing xenografts of MDA-MB-468 breast cancer cells were also used to observe the <span class="hlt">radiosensitizing</span> effect. Results: Simultaneous inhibition of EGFR and PI3K greatly enhanced <span class="hlt">radiosensitizing</span> effect in MDA-MB-468 in terms of apoptosis and mitotic death, either inhibition of EGFR or PI3K alone could enhance <span class="hlt">radiosensitivity</span> with a dose-modifying factor (DMF{sub SF<span class="hlt">2</span>}) of 1.311 and 1.437, <span class="hlt">radiosensitizing</span> effect was further enhanced by simultaneous inhibition of EGFR and PI3K with a DMF{sub SF<span class="hlt">2</span>} at <span class="hlt">2</span>.698. DNA flow cytometric analysis indicated that dual inhibition combined with irradiation significantly induced <span class="hlt">G</span>0/<span class="hlt">G</span>1 phase arrest in MDA-MB-468 cells. The expression of phosphor-Akt and phosphor-Erk1/<span class="hlt">2</span> (induced by irradiation and PI3K inhibitor) were fully attenuated by simultaneous treatment with both inhibitors in combination with irradiation. In addition, dual inhibition combined with irradiation induced dramatic tumor growth delay in MDA-MB-468 xenografts. Conclusions: Our study indicated that simultaneous inhibition of EGFR and PI3K could further sensitize the cancer cells to irradiation compared to the single inhibitor with irradiation in vitro and in vivo. The approach may</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1585081','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1585081"><span>Effect of chloramphenicol on sister <span class="hlt">chromatid</span> exchange in bovine fibroblasts.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Arruga, M V; Catalan, J; Moreno, C</p> <p>1992-03-01</p> <p>The genotoxic potential of different chloramphenicol concentrations (5, 20, 40 and 60 micrograms ml-1) was investigated in bovine fibroblast primary lines by sister <span class="hlt">chromatid</span> exchange assay. Chloramphenicol acted for long enough to ensure similar effects to persistent storage in the kidney. In this experiment 10 micrograms ml-1 of 5-bromodeoxyuridine was added for 60 hours for all doses of chloramphenicol and to the control. When the tissue culture cells were exposed to increasing doses, increased numbers of sister <span class="hlt">chromatid</span> exchanges developed. Differences were significantly different to the control.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2928865','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2928865"><span>Topoisomerase IIα maintains genomic stability through decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint signaling</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bower, Jacquelyn J.; Karaca, Gamze F.; Zhou, Yingchun; Simpson, Dennis A.; Cordeiro-Stone, Marila; Kaufmann, William K.</p> <p>2010-01-01</p> <p>Topoisomerase IIα (topoIIα) is an essential mammalian enzyme that topologically modifies DNA and is required for chromosome segregation during mitosis. Previous research suggests that inhibition of topoII decatenatory activity triggers a <span class="hlt">G</span><span class="hlt">2</span> checkpoint response, which delays mitotic entry due to insufficient decatenation of daughter <span class="hlt">chromatids</span>. Here we examine the effects of both topoIIα and topoIIβ on decatenatory activity in cell extracts, DNA damage and decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint function, and the frequencies of p16INK4A allele loss and gain. In diploid human fibroblast lines, depletion of topoIIα by siRNA was associated with severely reduced decatenatory activity, delayed progression from <span class="hlt">G</span><span class="hlt">2</span> into mitosis, and insensitivity to <span class="hlt">G</span><span class="hlt">2</span> arrest induced by the topoII catalytic inhibitor ICRF-193. Furthermore, interphase nuclei of topoIIα-depleted cells displayed increased frequencies of losses and gains of the tumor suppressor genetic locus p16INK4A. This study demonstrates that the topoIIα protein is required for decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint function, and inactivation of decatenation and the decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint leads to abnormal chromosome segregation and genomic instability. PMID:20562910</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22056362-can-drugs-enhance-hypofractionated-radiotherapy-novel-method-modeling-radiosensitization-using-vitro-data','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22056362-can-drugs-enhance-hypofractionated-radiotherapy-novel-method-modeling-radiosensitization-using-vitro-data"><span>Can Drugs Enhance Hypofractionated Radiotherapy? A Novel Method of Modeling <span class="hlt">Radiosensitization</span> Using In Vitro Data</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Ohri, Nitin; Dicker, Adam P.; Lawrence, Yaacov Richard, E-mail: yaacovla@gmail.com</p> <p>2012-05-01</p> <p>Purpose: Hypofractionated radiotherapy (hRT) is being explored for a number of malignancies. The potential benefit of giving concurrent chemotherapy with hRT is not known. We sought to predict the effects of combined modality treatments by using mathematical models derived from laboratory data. Methods and Materials: Data from 26 published clonogenic survival assays for cancer cell lines with and without the use of <span class="hlt">radiosensitizing</span> chemotherapy were collected. The first three data points of the RT arm of each assay were used to derive parameters for the linear quadratic (LQ) model, the multitarget (MT) model, and the generalized linear quadratic (<span class="hlt">g</span>LQ) model.more » For each assay and model, the difference between the predicted and observed surviving fractions at the highest tested RT dose was calculated. The <span class="hlt">g</span>LQ model was fitted to all the data from each RT cell survival assay, and the biologically equivalent doses in <span class="hlt">2</span>-Gy fractions (EQD<span class="hlt">2</span>s) of clinically relevant hRT regimens were calculated. The increase in cell kill conferred by the addition of chemotherapy was used to estimate the EQD<span class="hlt">2</span> of hRT along with a <span class="hlt">radiosensitizing</span> agent. For comparison, this was repeated using conventionally fractionated RT regimens. Results: At a mean RT dose of 8.0 Gy, the average errors for the LQ, MT, and <span class="hlt">g</span>LQ models were 1.63, 0.83, and 0.56 log units, respectively, favoring the <span class="hlt">g</span>LQ model (p < 0.05). <span class="hlt">Radiosensitizing</span> chemotherapy increased the EQD<span class="hlt">2</span> of hRT schedules by an average of 28% to 82%, depending on disease site. This increase was similar to the gains predicted for the addition of chemotherapy to conventionally fractionated RT. Conclusions: Based on published in vitro assays, the <span class="hlt">g</span>LQ equation is superior to the LQ and MT models in predicting cell kill at high doses of RT. Modeling exercises demonstrate that significant increases in biologically equivalent dose may be achieved with the addition of <span class="hlt">radiosensitizing</span> agents to hRT. Clinical study of this approach is warranted.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2567865','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2567865"><span>Shugoshin1 May Play Important Roles in Separation of Homologous Chromosomes and Sister <span class="hlt">Chromatids</span> during Mouse Oocyte Meiosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yin, Shen; Ai, Jun-Shu; Shi, Li-Hong; Wei, Liang; Yuan, Ju; Ouyang, Ying-Chun; Hou, Yi; Chen, Da-Yuan; Schatten, Heide; Sun, Qing-Yuan</p> <p>2008-01-01</p> <p>Background Homologous chromosomes separate in meiosis I and sister <span class="hlt">chromatids</span> separate in meiosis II, generating haploid gametes. To address the question why sister <span class="hlt">chromatids</span> do not separate in meiosis I, we explored the roles of Shogoshin1 (Sgo1) in chromosome separation during oocyte meiosis. Methodology/Principal Findings Sgo1 function was evaluated by exogenous overexpression to enhance its roles and RNAi to suppress its roles during two meioses of mouse oocytes. Immunocytochemistry and chromosome spread were used to evaluate phenotypes. The exogenous Sgo1 overexpression kept homologous chromosomes and sister <span class="hlt">chromatids</span> not to separate in meiosis I and meiosis II, respectively, while the Sgo1 RNAi promoted premature separation of sister <span class="hlt">chromatids</span>. Conclusions Our results reveal that prevention of premature separation of sister <span class="hlt">chromatids</span> in meiosis I requires the retention of centromeric Sgo1, while normal separation of sister <span class="hlt">chromatids</span> in meiosis II requires loss of centromeric Sgo1. PMID:18949044</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2969851','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2969851"><span>BubR1- and Polo-Coated DNA Tethers Facilitate Poleward Segregation of Acentric <span class="hlt">Chromatids</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Royou, Anne; Gagou, Mary E.; Karess, Roger; Sullivan, William</p> <p>2010-01-01</p> <p>Summary The mechanisms that safeguard cells against chromosomal instability (CIN) are of great interest, as CIN contributes to tumorigenesis. To gain insight into these mechanisms, we studied the behavior of cells entering mitosis with damaged chromosomes. We used the endonuclease I-CreI to generate acentric chromosomes in Drosophila larvae. While I-CreI expression produces acentric chromosomes in the majority of neuronal stem cells, remarkably, it has no effect on adult survival. Our live studies reveal that acentric <span class="hlt">chromatids</span> segregate efficiently to opposite poles. The acentric <span class="hlt">chromatid</span> poleward movement is mediated through DNA tethers decorated with BubR1, Polo, INCENP, and Aurora-B. Reduced BubR1 or Polo function results in abnormal segregation of acentric <span class="hlt">chromatids</span>, a decrease in acentric chromosome tethering, and a great reduction in adult survival. We propose that BubR1 and Polo facilitate the accurate segregation of acentric <span class="hlt">chromatids</span> by maintaining the integrity of the tethers that connect acentric chromosomes to their centric partners. PMID:20141837</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21039720-celecoxib-induced-tumor-cell-radiosensitization-inhibiting-radiation-induced-nuclear-egfr-transport-dna-repair-cox-independent-mechanism','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21039720-celecoxib-induced-tumor-cell-radiosensitization-inhibiting-radiation-induced-nuclear-egfr-transport-dna-repair-cox-independent-mechanism"><span>Celecoxib Induced Tumor Cell <span class="hlt">Radiosensitization</span> by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-<span class="hlt">2</span> Independent Mechanism</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.</p> <p>2008-01-01</p> <p>Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating <span class="hlt">radiosensitization</span> of human tumor cells by the selective cyclooxygenase (COX)-<span class="hlt">2</span> inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by {gamma}H{sub <span class="hlt">2</span>}AX foci assay. Results: Celecoxib treatment resulted in a pronounced <span class="hlt">radiosensitization</span> of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not <span class="hlt">radiosensitized</span>. The observedmore » <span class="hlt">radiosensitization</span> could neither be correlated with basal COX-<span class="hlt">2</span> expression pattern nor with basal production of prostaglandin E<span class="hlt">2</span>, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-<span class="hlt">2</span>-deficient HCT116 cells, which were <span class="hlt">radiosensitized</span>, but not in FaDu and HH4dd cells, which resisted celecoxib-induced <span class="hlt">radiosensitization</span>. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual {gamma}H<span class="hlt">2</span>AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced <span class="hlt">radiosensitivity</span> by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-<span class="hlt">2</span> activity. This novel observation may have therapeutic implications such that COX-<span class="hlt">2</span> inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-<span class="hlt">2</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28445939','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28445939"><span>Epigenetic therapy with inhibitors of histone methylation suppresses DNA damage signaling and increases glioma cell <span class="hlt">radiosensitivity</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gursoy-Yuzugullu, Ozge; Carman, Chelsea; Serafim, Rodolfo Bortolozo; Myronakis, Marios; Valente, Valeria; Price, Brendan D</p> <p>2017-04-11</p> <p>Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor <span class="hlt">radiosensitivity</span>, particularly in tumors with significant therapeutic resistance. Here, we demonstrate that inhibitors of the H4K20 methyltransferase SETD8 (UNC-0379) and the H3K9 methyltransferase <span class="hlt">G</span>9a (BIX-01294) are effective <span class="hlt">radiosensitizers</span> of human glioma cells. UNC-0379 blocked H4K20 methylation and reduced recruitment of the 53BP1 protein to DSBs, although this loss of 53BP1 caused only limited changes in <span class="hlt">radiosensitivity</span>. In contrast, loss of H3K9 methylation through <span class="hlt">G</span>9a inhibition with BIX-01294 increased <span class="hlt">radiosensitivity</span> of a panel of glioma cells (SER<span class="hlt">2</span>Gy range: 1.5 - <span class="hlt">2</span>.9). Further, loss of H3K9 methylation reduced DSB signaling dependent on H3K9, including reduced activation of the Tip60 acetyltransferase, loss of ATM signaling and reduced phosphorylation of the KAP-1 repressor. In addition, BIX-0194 inhibited DSB repair through both the homologous recombination and nonhomologous end-joining pathways. Inhibition of <span class="hlt">G</span>9a and loss of H3K9 methylation is therefore an effective approach for increasing <span class="hlt">radiosensitivity</span> of glioma cells. These results suggest that combining inhibitors of histone methyltransferases which are critical for DSB repair with radiation therapy may provide a new therapeutic route for sensitizing gliomas and other tumors to radiation therapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4674330','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4674330"><span>Silibinin preferentially <span class="hlt">radiosensitizes</span> prostate cancer by inhibiting DNA repair signaling</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Nambiar, Dhanya K.; Rajamani, Paulraj; Deep, Gagan; Jain, Anil K.; Agarwal, Rajesh; Singh, Rana P.</p> <p>2015-01-01</p> <p>Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. To develop a novel and selective <span class="hlt">radiosensitizer</span>, we studied the <span class="hlt">radiosensitizing</span> effects and associated mechanisms of silibinin in prostate cancer (PCa). The <span class="hlt">radiosensitizing</span> effect of silibinin with ionizing radiation (IR) was assessed on radioresistant PCa cell lines by clonogenic, cell cycle, cell death and DNA repair assays. Tumor xenograft growth, immunohistochemical (IHC) analysis of tumor tissues, and toxicity-related parameters were measured in vivo. Silibinin (25 μM) enhanced IR (<span class="hlt">2</span>.5-10 Gy)-caused inhibition (up to 96%, P<0.001) of colony formation selectively in PCa cells, and prolonged and enhanced IR-caused <span class="hlt">G</span><span class="hlt">2</span>/M arrest, apoptosis and ROS production. Mechanistically, silibinin inhibited IR-induced DNA repair (ATM and Chk1/<span class="hlt">2</span>) and EGFR signaling and attenuated the levels of anti-apoptotic proteins. Specifically, silibinin suppressed IR-induced nuclear translocation of EGFR and DNA-PK, an important mediator of DSB repair, leading to an increased number of γ-H<span class="hlt">2</span>AX (ser139) foci suggesting lesser DNA repair. In vivo, silibinin strongly <span class="hlt">radiosensitized</span> DU145 tumor xenograft inhibition (84%, P<0.01) with higher apoptotic response (10-fold, P<0.01) and reduced repair of DNA damage, and rescued the mice from IR-induced toxicity and hematopoietic injury. Overall, silibinin enhanced the radiotherapeutic response via suppressing IR-induced pro-survival signaling and DSB repair by inhibiting nuclear translocation of EGFR and DNA-PK. Since silibinin is already in phase II clinical trial for PCa patients, the present finding has translational relevance for radioresistant PCa. PMID:26516160</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26516160','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26516160"><span>Silibinin Preferentially <span class="hlt">Radiosensitizes</span> Prostate Cancer by Inhibiting DNA Repair Signaling.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nambiar, Dhanya K; Rajamani, Paulraj; Deep, Gagan; Jain, Anil K; Agarwal, Rajesh; Singh, Rana P</p> <p>2015-12-01</p> <p>Radiotherapy, a frequent mode of cancer treatment, is often restricted by dose-related toxicity and development of therapeutic resistance. To develop a novel and selective <span class="hlt">radiosensitizer</span>, we studied the <span class="hlt">radiosensitizing</span> effects and associated mechanisms of silibinin in prostate cancer. The <span class="hlt">radiosensitizing</span> effect of silibinin with ionizing radiation (IR) was assessed on radioresistant prostate cancer cell lines by clonogenic, cell cycle, cell death, and DNA repair assays. Tumor xenograft growth, immunohistochemical (IHC) analysis of tumor tissues, and toxicity-related parameters were measured in vivo. Silibinin (25 μmol/L) enhanced IR (<span class="hlt">2</span>.5-10 Gy)-caused inhibition (up to 96%, P < 0.001) of colony formation selectively in prostate cancer cells, and prolonged and enhanced IR-caused <span class="hlt">G</span><span class="hlt">2</span>-M arrest, apoptosis, and ROS production. Mechanistically, silibinin inhibited IR-induced DNA repair (ATM and Chk1/<span class="hlt">2</span>) and EGFR signaling and attenuated the levels of antiapoptotic proteins. Specifically, silibinin suppressed IR-induced nuclear translocation of EGFR and DNA-PK, an important mediator of DSB repair, leading to an increased number of γ-H<span class="hlt">2</span>AX (ser139) foci suggesting lesser DNA repair. In vivo, silibinin strongly <span class="hlt">radiosensitized</span> DU145 tumor xenograft inhibition (84%, P < 0.01) with higher apoptotic response (10-fold, P < 0.01) and reduced repair of DNA damage, and rescued the mice from IR-induced toxicity and hematopoietic injury. Overall, silibinin enhanced the radiotherapeutic response via suppressing IR-induced prosurvival signaling and DSB repair by inhibiting nuclear translocation of EGFR and DNA-PK. Because silibinin is already in phase II clinical trial for prostate cancer patients, the present finding has translational relevance for radioresistant prostate cancer. ©2015 American Association for Cancer Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21436126-enhancement-p53-mutant-human-colorectal-cancer-cells-radiosensitivity-flavonoid-fisetin','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21436126-enhancement-p53-mutant-human-colorectal-cancer-cells-radiosensitivity-flavonoid-fisetin"><span>Enhancement of P53-Mutant Human Colorectal Cancer Cells <span class="hlt">Radiosensitivity</span> by Flavonoid Fisetin</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Chen Wenshu; Lee Yijang; Yu Yichu</p> <p></p> <p>Purpose: The aim of this study was to investigate whether fisetin is a potential <span class="hlt">radiosensitizer</span> for human colorectal cancer cells, which are relatively resistant to radiotherapy. Methods and Materials: Cell survival was examined by clonogenic survival assay, and DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The effects of treatments on cell cycle distribution and apoptosis were examined by flow cytometry. Western blot analysis was performed to ascertain the protein levels of {gamma}-H<span class="hlt">2</span>AX, phospho-Chk<span class="hlt">2</span>, active caspase-3, PARP cleavage, phospho-p38, phospho-AKT, and phospho-ERK1/<span class="hlt">2</span>. Results: Fisetin pretreatment enhanced the <span class="hlt">radiosensitivity</span> of p53-mutant HT-29 human colorectal cancer cellsmore » but not human keratocyte HaCaT cells; it also prolonged radiation-induced <span class="hlt">G</span>{sub <span class="hlt">2</span>}/M arrest, enhanced radiation-induced cell growth arrest in HT-29 cells, and suppressed radiation-induced phospho-H<span class="hlt">2</span>AX (Ser-139) and phospho-Chk<span class="hlt">2</span> (Thr-68) in p53-mutant HT-29 cells. Pretreatment with fisetin enhanced radiation-induced caspase-dependent apoptosis in HT-29 cells. Fisetin pretreatment augmented radiation-induced phosphorylation of p38 mitogen-activated protein kinase, which is involved in caspase-mediated apoptosis, and SB202190 significantly reduced apoptosis and <span class="hlt">radiosensitivity</span> in fisetin-pretreated HT-29 cells. By contrast, both phospho-AKT and phospho-ERK1/<span class="hlt">2</span>, which are involved in cell proliferation and antiapoptotic pathways, were suppressed after irradiation combined with fisetin pretreatment. Conclusions: To our knowledge, this study is the first to provide evidence that fisetin exerts a <span class="hlt">radiosensitizing</span> effect in p53-mutant HT-29 cells. Fisetin could potentially be developed as a novel <span class="hlt">radiosensitizer</span> against radioresistant human cancer cells.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3981926','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3981926"><span>Vascular endothelial growth factor-C enhances <span class="hlt">radiosensitivity</span> of lymphatic endothelial cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kesler, Cristina T.; Kuo, Angera; Wong, Hon-Kit; Masuck, David J.; Shah, Jennifer L.; Kozak, Kevin; Held, Kathryn D.; Padera, Timothy P.</p> <p>2013-01-01</p> <p>Radiation therapy after lymph node dissection increases the risk of developing painful and incurable lymphedema in breast cancer patients. Lymphedema occurs when lymphatic vessels become unable to maintain proper fluid balance. The sensitivity of lymphatic endothelial cells (LECs) to ionizing radiation has not been reported to date. Here, the <span class="hlt">radiosensitivity</span> of LECs in vitro has been determined using clonogenic survival assays. The ability of various growth factors to alter LEC <span class="hlt">radiosensitivity</span> was also examined. Vascular endothelial growth factor (VEGF)-C enhanced <span class="hlt">radiosensitivity</span> when LECs were treated prior to radiation. VEGF-C-treated LECs exhibited higher levels of entry into the cell cycle at the time of radiation, with a greater number of cells in the S and <span class="hlt">G</span><span class="hlt">2</span>/M phases. These LECs showed higher levels of H<span class="hlt">2</span>A.X—an indicator of DNA damage—after radiation. VEGF-C did not increase cell death as a result of radiation. Instead, it increased the relative number of quiescent LECs. These data suggest that abundant VEGF-C or lymphangiogenesis may predispose patients to radiation-induced lymphedema by impairing lymphatic vessel repair through induction of LEC quiescence. PMID:24201897</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5060660-sister-chromatid-exchanges-induced-inhaled-anesthetics','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5060660-sister-chromatid-exchanges-induced-inhaled-anesthetics"><span>Sister <span class="hlt">chromatid</span> exchanges induced by inhaled anesthetics</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>White,A.E.; Takehisa, S.; Eger II, E.I.</p> <p>1970-05-01</p> <p>There is sufficient evidence that anesthetics may cause cancer to justify a test of their carcinogenic potential. Baden et al., using the Ames test, a rapid and inexpensive genetic indicator of carcinogenicity, have shown that among currently used anesthetics fluorxene alone caused bacterial mutations. The authors used the sister <span class="hlt">chromatid</span> exchange (SCE) technique, another rapid assay of mutagenic-carcinogenic potential. The frequency of sister <span class="hlt">chromatid</span> exchanges in Chinese hamster ovary cells increases when the cell cultures are exposed to mutagen-carcinogens, particulary in the presence of a metabolic activating system. With this test system a one-hour exposure to 1 MAC nitrous oxide,more » diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane, or chloroform did not increase SCE values. Divinyl ether, fluroxene and ethyl vinyl ether increased SCE values in the same circumstances. Results of this study of mammalian cells suggest that no currently used anesthetic is a mutagen-carcinogen. The results also suggest that anesthetics containing a vinyl moiety may be mutagen-carcinogens.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29716622','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29716622"><span>A novel small molecule inhibitor of MDM<span class="hlt">2</span>-p53 (APG-115) enhances <span class="hlt">radiosensitivity</span> of gastric adenocarcinoma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yi, Hanjie; Yan, Xianglei; Luo, Qiuyun; Yuan, Luping; Li, Baoxia; Pan, Wentao; Zhang, Lin; Chen, Haibo; Wang, Jing; Zhang, Yubin; Zhai, Yifan; Qiu, Miao-Zhen; Yang, Da-Jun</p> <p>2018-05-02</p> <p>Gastric cancer is the leading cause of cancer related death worldwide. Radiation alone or combined with chemotherapy plays important role in locally advanced and metastatic gastric adenocarcinoma. MDM<span class="hlt">2</span>-p53 interaction and downstream signaling affect cellular response to DNA damage which leads to cell cycle arrest and apoptosis. Therefore, restoring p53 function by inhibiting its interaction with MDM<span class="hlt">2</span> is a promising therapeutic strategy for cancer. APG-115 is a novel small molecule inhibitor which blocks the interaction of MDM<span class="hlt">2</span> and p53. In this study, we investigated that the <span class="hlt">radiosensitivity</span> of APG-115 in gastric adenocarcinoma in vitro and in vivo. The role of APG-115 in six gastric cancer cells viability in vitro was determined by CCK-8 assay. The expression level of MDM<span class="hlt">2</span>, p21, PUMA and BAX in AGS and MKN45 cell lines was measured via real-time PCR (RT-PCR). The function of treatment groups on cell cycle and cell apoptosis were detected through Flow Cytometry assay. Clonogenic assays were used to measure the <span class="hlt">radiosensitivity</span> of APG-115 in p53 wild type gastric cancer cell lines. Western blot was conducted to detect the protein expressions of mdm<span class="hlt">2</span>-p53 signal pathway. Xenograft models in nude mice were established to explore the <span class="hlt">radiosensitivity</span> role of APG-115 in gastric cancer cells in vivo. We found that <span class="hlt">radiosensitization</span> by APG-115 occurred in p53 wild-type gastric cancer cells. Increasing apoptosis and cell cycle arrest was observed after administration of APG-115 and radiation. <span class="hlt">Radiosensitivity</span> of APG-115 was mainly dependent on MDM<span class="hlt">2</span>-p53 signal pathway. In vivo, APG-115 combined with radiation decreased xenograft tumor growth much more significantly than either single treatment. Moreover, the number of proliferating cells (Ki-67) significantly decreased in combination group compared with single treatment group. In summary, we found that combination of MDM<span class="hlt">2</span>-p53 inhibitor (APG-115) and radiotherapy can enhance antitumor effect both in vitro and in vivo. This</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/5369196','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/5369196"><span><span class="hlt">Radiosensitivity</span> in plants</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Nauman, A F</p> <p>1979-01-01</p> <p>The report presents a compilation of available data on the sensitivity of plants to ionizing radiation, and provides basic information on methods of determining such sensitivities, or of estimating <span class="hlt">radiosensitivities</span> by calcuation of the nuclear factors upon which they depend. The scope of the data presented here is necessarily limited to the most generally useful radiobiological end points and to the most commonly-used types of radiation. Many of the factors which influence <span class="hlt">radiosensitivity</span>, particularly nuclear factors, will be discussed. Emphasis will be upon whole-plant studies done at Brookhaven National Laboratory by A.H. Sparrow and his associates, since these studies aremore » the source of most of the available <span class="hlt">radiosensitivity</span> data and of all the sensitivity predictions listed here. Data presented here include summaries of experimentally-determined <span class="hlt">radiosensitivities</span> at various end points for both herbaceous and woody higher plants, and for a few species of ferns and lower plants. The algae and fungi have not been considered here due to space limitations.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29100427','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29100427"><span>Aberrant rhythmic expression of cryptochrome<span class="hlt">2</span> regulates the <span class="hlt">radiosensitivity</span> of rat gliomas.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fan, Wang; Caiyan, Li; Ling, Zhu; Jiayun, Zhao</p> <p>2017-09-29</p> <p>In this study, we investigated the role of the clock regulatory protein cryptochrome <span class="hlt">2</span> (Cry<span class="hlt">2</span>) in determining the <span class="hlt">radiosensitivity</span> of C6 glioma cells in a rat model. We observed that Cry<span class="hlt">2</span> mRNA and protein levels showed aberrant rhythmic periodicity of 8 h in glioma tissues, compared to 24 h in normal brain tissue. Cry<span class="hlt">2</span> mRNA and protein levels did not respond to irradiation in normal tissues, but both were increased at the ZT4 (low Cry<span class="hlt">2</span>) and ZT8 (high Cry<span class="hlt">2</span>) time points in gliomas. Immunohistochemical staining of PCNA and TUNEL assays demonstrated that high Cry<span class="hlt">2</span> expression in glioma tissues was associated with increased cell proliferation and decreased apoptosis. Western blot analysis showed that glioma cell fate was independent of p53, but was probably dependent on p73, which was more highly expressed at ZT4 (low Cry<span class="hlt">2</span>) than at ZT8 (high Cry<span class="hlt">2</span>). Levels of both p53 and p73 were unaffected by irradiation in normal brain tissues. These findings suggest aberrant rhythmic expression of Cry<span class="hlt">2</span> influence on <span class="hlt">radiosensitivity</span> in rat gliomas.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28869599','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28869599"><span>Taxane-mediated <span class="hlt">radiosensitization</span> derives from chromosomal missegregation on tripolar mitotic spindles orchestrated by AURKA and TPX<span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Orth, M; Unger, K; Schoetz, U; Belka, C; Lauber, K</p> <p>2018-01-04</p> <p>Taxane-based radiochemotherapy is a central treatment option for various cancer entities in locally advanced stages. The therapeutic synergism of this combined modality approach due to taxane-mediated <span class="hlt">radiosensitization</span> of cancer cells is well-known. However, the underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of taxane-based radiochemotherapy are currently not available. Here, we show that clinically relevant doses of Paclitaxel, the prototype taxane, stimulate a tripolar mode of mitosis leading to chromosomal missegregation and aneuploidization rather than interfering with cell cycle progression. This distinct mitotic phenotype was interlinked with Paclitaxel-mediated <span class="hlt">radiosensitization</span> via overexpression of mitotic Aurora kinase A (AURKA) and its cofactor TPX<span class="hlt">2</span> whose knockdown rescued the bipolar mode of cell division and largely attenuated the <span class="hlt">radiosensitizing</span> effects of Paclitaxel. In the cancer genome atlas (TCGA) lung adenocarcinoma cohort, high expression levels of AURKA and TPX<span class="hlt">2</span> were associated with specifically improved overall survival upon taxane-based radiochemotherapy, but not in case of non-taxane-based radiochemotherapy, chemo- or radiotherapy only. Thus, our data provide insights into Paclitaxel-mediated <span class="hlt">radiosensitization</span> on a mechanistic and molecular level and identify AURKA and TPX<span class="hlt">2</span> as the first potential mechanism-based, predictive markers of taxane-based radiochemotherapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199498','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199498"><span>The Chromosomal Association of the Smc5/6 Complex Depends on Cohesion and Predicts the Level of Sister <span class="hlt">Chromatid</span> Entanglement</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jeppsson, Kristian; Carlborg, Kristian K.; Nakato, Ryuichiro; Berta, Davide G.; Lilienthal, Ingrid; Kanno, Takaharu; Lindqvist, Arne; Brink, Maartje C.; Dantuma, Nico P.; Katou, Yuki; Shirahige, Katsuhiko; Sjögren, Camilla</p> <p>2014-01-01</p> <p>The cohesin complex, which is essential for sister <span class="hlt">chromatid</span> cohesion and chromosome segregation, also inhibits resolution of sister <span class="hlt">chromatid</span> intertwinings (SCIs) by the topoisomerase Top<span class="hlt">2</span>. The cohesin-related Smc5/6 complex (Smc5/6) instead accumulates on chromosomes after Top<span class="hlt">2</span> inactivation, known to lead to a buildup of unresolved SCIs. This suggests that cohesin can influence the chromosomal association of Smc5/6 via its role in SCI protection. Using high-resolution ChIP-sequencing, we show that the localization of budding yeast Smc5/6 to duplicated chromosomes indeed depends on sister <span class="hlt">chromatid</span> cohesion in wild-type and top<span class="hlt">2</span>-4 cells. Smc5/6 is found to be enriched at cohesin binding sites in the centromere-proximal regions in both cell types, but also along chromosome arms when replication has occurred under Top<span class="hlt">2</span>-inhibiting conditions. Reactivation of Top<span class="hlt">2</span> after replication causes Smc5/6 to dissociate from chromosome arms, supporting the assumption that Smc5/6 associates with a Top<span class="hlt">2</span> substrate. It is also demonstrated that the amount of Smc5/6 on chromosomes positively correlates with the level of missegregation in top<span class="hlt">2</span>-4, and that Smc5/6 promotes segregation of short chromosomes in the mutant. Altogether, this shows that the chromosomal localization of Smc5/6 predicts the presence of the <span class="hlt">chromatid</span> segregation-inhibiting entities which accumulate in top<span class="hlt">2</span>-4 mutated cells. These are most likely SCIs, and our results thus indicate that, at least when Top<span class="hlt">2</span> is inhibited, Smc5/6 facilitates their resolution. PMID:25329383</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_2");'>2</a></li> <li><a href="#" onclick='return showDiv("page_3");'>3</a></li> <li class="active"><span>4</span></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_4 --> <div id="page_5" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_3");'>3</a></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li class="active"><span>5</span></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="81"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24666614','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24666614"><span>Artemisinin derivative artesunate induces <span class="hlt">radiosensitivity</span> in cervical cancer cells in vitro and in vivo.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Luo, Judong; Zhu, Wei; Tang, Yiting; Cao, Han; Zhou, Yuanyuan; Ji, Rong; Zhou, Xifa; Lu, Zhongkai; Yang, Hongying; Zhang, Shuyu; Cao, Jianping</p> <p>2014-03-25</p> <p>Cervical cancer is the third most common type of cancer in women worldwide and radiotherapy remains its predominant therapeutic treatment. Artesunate (ART), a derivative of artemisinin, has shown <span class="hlt">radiosensitization</span> effect in previous studies. However, such effects of ART have not yet been revealed for cervical cancer cells. The effect of ART on <span class="hlt">radiosensitivity</span> of human cervical cancer cell lines HeLa and SiHa was assessed using the clonogenic assay. Cell cycle progression and apoptosis alterations were analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect the changes of microvessel density, apoptosis and cell cycle distribution. Microarray was used to analyze differentially expressed genes. ART increased the <span class="hlt">radiosensitivity</span> of HeLa cells (SER=1.43, P<0.001) but not of SiHa cells. Apoptosis and the <span class="hlt">G</span><span class="hlt">2</span>-M phase transition induced by X-ray irradiation (IR) were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor growth of xenografts from HeLa but not SiHa cells was significantly inhibited by irradiation combined with ART (tumor volume reduction of 72.34% in IR+ART group vs. 41.22% in IR group in HeLa cells and 48.79% in IR+ART group vs. 44.03% in IR alone group in SiHa cells). Compared with the irradiated group, cell apoptosis was increased and the <span class="hlt">G</span><span class="hlt">2</span>/M cell cycle arrest was enhanced in the group receiving irradiation combined with ART. Furthermore, compared with radiation alone, X-ray irradiation plus ART affected the expression of 203 genes that function in multiple pathways including RNA transport, the spliceosome, RNA degradation and p53 signaling. ART potently abrogates the <span class="hlt">G</span><span class="hlt">2</span> checkpoint control in HeLa cells. ART can induce <span class="hlt">radiosensitivity</span> of HeLa cells in vitro and in vivo.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5436250','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5436250"><span>Foretinib Enhances the <span class="hlt">Radiosensitivity</span> in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chen, Guang-Zong; Dai, Wang-Shu; Zhu, Hong-Cheng; Song, Hong-Mei; Yang, Xi; Wang, Yuan-Dong; Min, Hua; Lu, Qian; Liu, Shu; Sun, Xin-Chen; Zeng, Xiao-Ning</p> <p>2017-01-01</p> <p>As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of <span class="hlt">radiosensitivity</span> in esophageal cancer. The present study investigated the <span class="hlt">radiosensitization</span> effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and <span class="hlt">G</span><span class="hlt">2</span>/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of <span class="hlt">radiosensitization</span> in esophageal cancer, and foretinib increased the <span class="hlt">radiosensitivity</span> in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential <span class="hlt">radiosensitizer</span> for the treatment of esophageal cancer. PMID:28529610</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26171054','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26171054"><span><span class="hlt">Radiosensitization</span> of human glioma cells by tamoxifen is associated with the inhibition of PKC-ι activity in vitro.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Lei; Yuan, Xiaopeng; Wang, Jie; Gu, Cheng; Zhang, Haowen; Yu, Jiahua; Liu, Fenju</p> <p>2015-07-01</p> <p>The present study aimed to investigate the <span class="hlt">radiosensitizing</span> effects of tamoxifen (TAM), a non-steroidal anti-estrogen drug, in human glioma A172 and U251 cells in vitro . A colony-forming assay revealed that TAM enhances <span class="hlt">radiosensitivity</span> in A172 and U251 cells. Treatment with TAM also increased the percentage of apoptotic cells subsequent to ionizing radiation, and increased the expression of apoptotic markers, including cleaved caspase-3 and poly(ADP-ribose) polymerase. Ionizing radiation induced <span class="hlt">G</span><span class="hlt">2</span>/M phase arrest, which was alleviated within 24 h when the radiation-induced DNA damage was repaired. However, flow cytometry analysis revealed that TAM treatment delayed the recovery of cell cycle progression. Additional examination demonstrated that TAM-mediated protein kinase C-ι (PKC-ι) inhibition may lead to the activation of pro-apoptotic B-cell lymphoma <span class="hlt">2</span>-associated death promoter, and the dephosphorylation of cyclin-dependent kinase 7, resulting in increased cell apoptosis and sustained <span class="hlt">G</span><span class="hlt">2</span>/M phase arrest following exposure to radiation. The present data indicate that the <span class="hlt">radiosensitizing</span> effects of TAM on glioma cells are partly due to the inhibition of PKC-ι activity in vitro .</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27698471','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27698471"><span>Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively <span class="hlt">radiosensitize</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Adams, Stephen R; Yang, Howard C; Savariar, Elamprakash N; Aguilera, Joe; Crisp, Jessica L; Jones, Karra A; Whitney, Michael A; Lippman, Scott M; Cohen, Ezra E W; Tsien, Roger Y; Advani, Sunil J</p> <p>2016-10-04</p> <p>Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent <span class="hlt">radiosensitizing</span> drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent <span class="hlt">radiosensitizing</span> drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively <span class="hlt">radiosensitize</span> to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately <span class="hlt">radiosensitize</span> tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their <span class="hlt">radiosensitizing</span> capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER<span class="hlt">2</span>+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based <span class="hlt">radiosensitization</span> using antibodies to restrict <span class="hlt">radiosensitizer</span> delivery.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5059467','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5059467"><span>Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively <span class="hlt">radiosensitize</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Adams, Stephen R.; Yang, Howard C.; Savariar, Elamprakash N.; Aguilera, Joe; Crisp, Jessica L.; Jones, Karra A.; Whitney, Michael A.; Lippman, Scott M.; Cohen, Ezra E. W.; Tsien, Roger Y.; Advani, Sunil J.</p> <p>2016-01-01</p> <p>Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent <span class="hlt">radiosensitizing</span> drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent <span class="hlt">radiosensitizing</span> drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively <span class="hlt">radiosensitize</span> to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately <span class="hlt">radiosensitize</span> tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their <span class="hlt">radiosensitizing</span> capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER<span class="hlt">2</span>+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based <span class="hlt">radiosensitization</span> using antibodies to restrict <span class="hlt">radiosensitizer</span> delivery. PMID:27698471</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28810535','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28810535"><span>Curcumin enhances the <span class="hlt">radiosensitivity</span> of renal cancer cells by suppressing NF-κB signaling pathway.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Gang; Wang, Ziming; Chong, Tie; Yang, Jie; Li, Hongliang; Chen, Haiwen</p> <p>2017-10-01</p> <p>The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the <span class="hlt">radiosensitivity</span> of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment. The expression of NF-κB signaling related proteins in ACHN cells and xenografts was detected by western blot analysis. The results showed that curcumin significantly increased <span class="hlt">radiosensitivity</span> of ACHN cells by inhibiting the cell proliferation and DNA damage repair, causing cell cycle arrest at <span class="hlt">G</span><span class="hlt">2</span>/M phase, inducing apoptosis in vitro, and suppressing the growth of xenografts in vivo. In addition, curcumin enhanced <span class="hlt">radiosensitivity</span> was through markedly inhibiting IR-induced NF-κB signaling by modulating the related protein expressions including NF-κBP65, I-κB, VEGF, COX<span class="hlt">2</span>, and Bcl-<span class="hlt">2</span> in ACHN cells, which was further strengthened by NF-κB inhibitor PDTC treatment. Thus, curcumin may confer <span class="hlt">radiosensitivity</span> on RCC via inhibition of NF-κB activation and its downstream regulars, suggesting the potential application of curcumin as an adjuvant in radiotherapy of RCC. Copyright © 2017. Published by Elsevier Masson SAS.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=19750006349&hterms=Organization+cell&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3DOrganization%2Bcell','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=19750006349&hterms=Organization+cell&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3DOrganization%2Bcell"><span>The temporal organization of processes of cell reproduction and its connection with rhythms of <span class="hlt">radiosensitivity</span> of the body</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Druzhinin, Y. P.; Romanov, Y. A.; Vatsek, A.</p> <p>1974-01-01</p> <p><span class="hlt">Radiosensitivity</span> of individual phases of the mitotic cycle was studied in synchronous cell cultures and in several biological objects. It was found that <span class="hlt">radiosensitivity</span> changed essentially according to phases of the mitotic cycle, depending on the kind of cells, evaluation criteria and the radiation dosage. Tests on partially synchronized HeLa cell populations, according to the criterion of survival, showed them most sensitive during mitosis, as well as in later <span class="hlt">G</span> sub 1- or early DNA-synthesizing stages. With radiation in doses of 300 rad, the proportion of surviving cells showed a sensitivity directly before DNA synthesis of approximately 4 times higher than the later S-phase and during the major portion of <span class="hlt">G</span> sub 1- and <span class="hlt">G</span> sub <span class="hlt">2</span>-periods. Sensitivity of cells in mitosis was approximately 3 times higher than in late <span class="hlt">G</span> sub 1- and early S-phases.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21743463','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21743463"><span>Cleavage of cohesin rings coordinates the separation of centrioles and <span class="hlt">chromatids</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf</p> <p>2011-07-10</p> <p>Cohesin pairs sister <span class="hlt">chromatids</span> by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase <span class="hlt">2</span>A (Sgo1-PP<span class="hlt">2</span>A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-<span class="hlt">chromatid</span> separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10189155','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10189155"><span>Sister <span class="hlt">chromatid</span> exchange analysis in workers exposed to noise and vibration.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Silva, M J; Carothers, A; Castelo Branco, N A; Dias, A; Boavida, M G</p> <p>1999-03-01</p> <p>There has been a growing interest in the combined effects of noise and vibration. In a population of aeronautical workers diagnosed with vibroacoustic disease (VAD), a large incidence of malignancy was detected. These workers were exposed to large pressure amplitude (LPA) (> or = 90 dB SPL) noise, with energy content concentrated within the low frequency (LF) bands (< or = 500 Hz) and whole-body vibration (WBV). To our knowledge, there are no studies conducted in humans or animals that address the issue of the potential genotoxic effects of vibration combined with noise. In the present study, the levels of sister <span class="hlt">chromatid</span> exchanges (SCE) and of cells with high frequencies of SCE (HFC) were analyzed in peripheral blood lymphocytes of workers employed in various occupations within the aeronautical industry. SCE and HFC were analyzed in lymphocytes of 50 workers occupationally exposed to noise and vibration and of 34 office-worker controls (<span class="hlt">G</span>0). The exposed group included: 10 hand-vibrating tool operators (<span class="hlt">G</span>1), 15 engine test cell technicians (<span class="hlt">G</span><span class="hlt">2</span>), 12 aircraft run-up technicians (<span class="hlt">G</span>3) and 13 Portuguese Air Force helicopter pilots (<span class="hlt">G</span>4). Groups <span class="hlt">2</span>-4 were exposed to WBV and LPALF noise; group 1 was exposed to LPA high frequency noise and local vibration. Statistical analysis of the mean SCE count per cell was carried out by multiple regression analysis comparing various predictor variables: type of exposure, duration of exposure, age, and cigarette consumption. Only cigarette consumption and type of exposure were found to be significantly correlated with the mean SCE frequency. After allowing for the effects of smoking, the analysis indicates that: 1) there was no significant difference between <span class="hlt">G</span>1 and <span class="hlt">G</span>0 (p > 0.05); <span class="hlt">2</span>) the differences between <span class="hlt">G</span><span class="hlt">2</span> and <span class="hlt">G</span>0, <span class="hlt">G</span>3 and <span class="hlt">G</span>0, <span class="hlt">G</span>4 and <span class="hlt">G</span>0 were all highly significant (p < 0.001); 3) there was no significant difference between <span class="hlt">G</span><span class="hlt">2</span> and <span class="hlt">G</span>3 (p > 0.05), nor between <span class="hlt">G</span><span class="hlt">2</span> and <span class="hlt">G</span>3 combined and <span class="hlt">G</span>4 (p > 0.05); and 4) <span class="hlt">G</span><span class="hlt">2</span> and <span class="hlt">G</span>4 combined had a</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3614460','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3614460"><span>Chloronitroimidazoles as <span class="hlt">radiosensitizers</span> of hypoxic cells in vitro.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wideł, M; Watras, J; Suwiński, J; Salwińska, E</p> <p>1987-01-01</p> <p>Some results of the first more complex studies in vitro on <span class="hlt">radio-sensitizing</span> efficiency, cytotoxicity and reactivity with blood-thiols of a series of 4- or 5-nitroimidazoles substituted in the 5, 4 or <span class="hlt">2</span> position with chlorine are presented. The derivatives of 4-nitroimidazole substituted in 5 position ("ortho" position) with Cl show higher <span class="hlt">radiosensitizing</span> efficiency than one may expect from their reduction potential, E1/<span class="hlt">2</span>. At the same time they are extremely toxic, especially for aerobic cells. It is considered that high biological activity of ortho-substituted 4-nitroimidazoles is connected with their considerable chemical reactivity towards thiols and suppression of those natural protective compounds in the cells. The corresponding 5-nitro isomers are about tenfold weaker sensitizers, and simultaneously much less cytotoxic, either in aerobic or in hypoxic conditions. The chloro-4(5)-nitroimidazoles nonsubstituted at N-1 and ionizable in aqueous solution are relatively weaker at the same time less toxic <span class="hlt">radiosensitizers</span>. It is evaluated that potential application in radiotherapy may have those chloronitroimidazoles which show low aerobic cytotoxicity, moderate <span class="hlt">radiosensitizing</span> ability and no reactivity towards thiols. On the basis of the study in vitro, we have selected such a compound: 1-methyl-<span class="hlt">2</span>-chloro-4-nitroimidazole (P13) for screening in vivo.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28978184','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28978184"><span>Poly-(ADP-ribose)-polymerase inhibitors as <span class="hlt">radiosensitizers</span>: a systematic review of pre-clinical and clinical human studies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lesueur, Paul; Chevalier, François; Austry, Jean-Baptiste; Waissi, Waisse; Burckel, Hélène; Noël, Georges; Habrand, Jean-Louis; Saintigny, Yannick; Joly, Florence</p> <p>2017-09-15</p> <p>Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential <span class="hlt">radiosensitizers</span>, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality. Furthermore the replication-dependent activity of PARP inhibitor helps to maintain the differential effect between tumoral and healthy tissues. Inhibition of chromatin remodeling, <span class="hlt">G</span><span class="hlt">2</span>/M arrest, vasodilatory effect induced by PARP inhibitor, also participate to their <span class="hlt">radio-sensitization</span> effect. Here, after highlighting mechanisms of PARP inhibitors <span class="hlt">radiosensitization</span> we methodically searched PubMed, Google Scholar, Cochrane Databases and meeting proceedings for human pre-clinical and clinical studies that evaluated PARP inhibitor <span class="hlt">radiosensitizing</span> effect. Enhancement ratio, when available, was systematically reported. Sixty four studies finally met our selection criteria and were included in the analysis. Only three pre-clinical studies didn't find any <span class="hlt">radiosensitizing</span> effect. Median enhancement ratio vary from 1,3 for prostate tumors to 1,5 for lung cancers. Nine phase I or II trials assessed safety data. PARP inhibitors are promising <span class="hlt">radiosensitizers</span>, but need more clinical investigation. The next ten years will be determining for judging their real potential.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22202468-rosiglitazone-enhances-radiosensitivity-p53-mutant-ht-human-colorectal-cancer-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22202468-rosiglitazone-enhances-radiosensitivity-p53-mutant-ht-human-colorectal-cancer-cells"><span>Rosiglitazone enhances the <span class="hlt">radiosensitivity</span> of p53-mutant HT-29 human colorectal cancer cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Chiu, Shu-Jun, E-mail: chiusj@mail.tcu.edu.tw; Institute of Radiation Sciences, Tzu Chi Technology College, Hualien, Taiwan; Hsaio, Ching-Hui</p> <p>2010-04-09</p> <p>Combined-modality treatment has improved the outcome in cases of various solid tumors, and <span class="hlt">radiosensitizers</span> are used to enhance the radiotherapeutic efficiency. Rosiglitazone, a synthetic ligand of peroxisome proliferator-activated receptors {gamma} used in the treatment of type-<span class="hlt">2</span> diabetes, has been shown to reduce tumor growth and metastasis in human cancer cells, and may have the potential to be used as a <span class="hlt">radiosensitizer</span> in radiotherapy for human colorectal cancer cells. In this study, rosiglitazone treatment significantly reduced the cell viability of p53-wild type HCT116 cells but not p53-mutant HT-29 cells. Interestingly, rosiglitazone pretreatment enhanced <span class="hlt">radiosensitivity</span> in p53-mutant HT-29 cells but not HCT116more » cells, and prolonged radiation-induced <span class="hlt">G</span>{sub <span class="hlt">2</span>}/M arrest and enhanced radiation-induced cell growth inhibition in HT-29 cells. Pretreatment with rosiglitazone also suppressed radiation-induced H<span class="hlt">2</span>AX phosphorylation in response to DNA damage and AKT activation for cell survival; on the contrary, rosiglitazone pretreatment enhanced radiation-induced caspase-8, -9, and -3 activation and PARP cleavage in HT-29 cells. In addition, pretreatment with a pan-caspase inhibitor, zVAD-fmk, attenuated the levels of caspase-3 activation and PARP cleavage in radiation-exposed cancer cells in combination with rosiglitazone pretreatment. Our results provide proof for the first time that rosiglitazone suppresses radiation-induced survival signals and DNA damage response, and enhances the radiation-induced apoptosis signaling cascade. These findings can assist in the development of rosiglitazone as a novel <span class="hlt">radiosensitizer</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4533307','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4533307"><span><span class="hlt">Radiosensitivity</span> in HeLa cervical cancer cells overexpressing glutathione S-transferase π 1</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>YANG, LIANG; LIU, REN; MA, HONG-BIN; YING, MING-ZHEN; WANG, YA-JIE</p> <p>2015-01-01</p> <p>The aims of the present study were to investigate the effect of overexpressed exogenous glutathione S-transferase π 1 (GSTP1) gene on the <span class="hlt">radiosensitivity</span> of the HeLa human cervical cancer cell line and conduct a preliminarily investigation into the underlying mechanisms of the effect. The full-length sequence of human GSTP1 was obtained by performing a polymerase chain reaction (PCR) using primers based on the GenBank sequence of GSTP1. Subsequently, the gene was cloned into a recombinant eukaryotic expression plasmid, and the resulting construct was confirmed by restriction analysis and DNA sequencing. A HeLa cell line that was stably expressing high levels of GSTP1 was obtained through stable transfection of the constructed plasmids using lipofectamine and screening for <span class="hlt">G</span>418 resistance, as demonstrated by reverse transcription-PCR. Using the transfected HeLa cells, a colony formation assay was conducted to detect the influence of GSTP1 overexpression on the cell <span class="hlt">radiosensitivity</span>. Furthermore, flow cytometry was used to investigate the effect of GSTP1 overexpression on cell cycle progression, with the protein expression levels of the cell cycle regulating factor cyclin B1 detected using western blot analysis. Colony formation and <span class="hlt">G</span><span class="hlt">2</span>/M phase arrest in the GSTP1-expressing cells were significantly increased compared with the control group (P<0.01). In addition, the expression of cyclin B1 was significantly reduced in the GSTP1-expressing cells. These results demonstrated that increased expression of GSTP1 inhibits <span class="hlt">radiosensitivity</span> in HeLa cells. The mechanism underlying this effect may be associated with the ability of the GSTP1 protein to reduce cyclin B1 expression, resulting in significant <span class="hlt">G</span><span class="hlt">2</span>/M phase arrest. PMID:26622693</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26622693','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26622693"><span><span class="hlt">Radiosensitivity</span> in HeLa cervical cancer cells overexpressing glutathione S-transferase π 1.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Liang; Liu, Ren; Ma, Hong-Bin; Ying, Ming-Zhen; Wang, Ya-Jie</p> <p>2015-09-01</p> <p>The aims of the present study were to investigate the effect of overexpressed exogenous glutathione S-transferase π 1 ( GSTP1 ) gene on the <span class="hlt">radiosensitivity</span> of the HeLa human cervical cancer cell line and conduct a preliminarily investigation into the underlying mechanisms of the effect. The full-length sequence of human GSTP1 was obtained by performing a polymerase chain reaction (PCR) using primers based on the GenBank sequence of GSTP1. Subsequently, the gene was cloned into a recombinant eukaryotic expression plasmid, and the resulting construct was confirmed by restriction analysis and DNA sequencing. A HeLa cell line that was stably expressing high levels of GSTP1 was obtained through stable transfection of the constructed plasmids using lipofectamine and screening for <span class="hlt">G</span>418 resistance, as demonstrated by reverse transcription-PCR. Using the transfected HeLa cells, a colony formation assay was conducted to detect the influence of GSTP1 overexpression on the cell <span class="hlt">radiosensitivity</span>. Furthermore, flow cytometry was used to investigate the effect of GSTP1 overexpression on cell cycle progression, with the protein expression levels of the cell cycle regulating factor cyclin B1 detected using western blot analysis. Colony formation and <span class="hlt">G</span> <span class="hlt">2</span> /M phase arrest in the GSTP1 -expressing cells were significantly increased compared with the control group (P<0.01). In addition, the expression of cyclin B1 was significantly reduced in the GSTP1 -expressing cells. These results demonstrated that increased expression of GSTP1 inhibits <span class="hlt">radiosensitivity</span> in HeLa cells. The mechanism underlying this effect may be associated with the ability of the GSTP1 protein to reduce cyclin B1 expression, resulting in significant <span class="hlt">G</span> <span class="hlt">2</span> /M phase arrest.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/4069583','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/4069583"><span>Abnormal centromere-<span class="hlt">chromatid</span> apposition (ACCA) and Peters' anomaly.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wertelecki, W; Dev, V G; Superneau, D W</p> <p>1985-08-01</p> <p>Abnormal centromere-<span class="hlt">chromatid</span> apposition (ACCA) was noted in a patient with Peters' anomaly. Previous reports of ACCA emphasized its association with tetraphocomelia and other congenital malformations (Roberts, SC Phocomelia, Pseudothalidomide Syndromes). This report expands the array of congenital malformations associated with ACCA and emphasizes the diagnostic importance of ocular defects for the ascertainment of additional cases of ACCA and its possible relationship with abnormal cell division.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25194916','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25194916"><span>"Breaking up is hard to do": the formation and resolution of sister <span class="hlt">chromatid</span> intertwines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Baxter, Jonathan</p> <p>2015-02-13</p> <p>The absolute necessity to resolve every intertwine between the two strands of the DNA double helix provides a massive challenge to the cellular processes that duplicate and segregate chromosomes. Although the overwhelming majority of intertwines between the parental DNA strands are resolved during DNA replication, there are numerous chromosomal contexts where some intertwining is maintained into mitosis. These mitotic sister <span class="hlt">chromatid</span> intertwines (SCIs) can be found as; short regions of unreplicated DNA, fully replicated and intertwined sister <span class="hlt">chromatids</span>--commonly referred to as DNA catenation--and as sister <span class="hlt">chromatid</span> linkages generated by homologous recombination-associated processes. Several overlapping mechanisms, including intra-chromosomal compaction, topoisomerase action and Holliday junction resolvases, ensure that all SCIs are removed before they can prevent normal chromosome segregation. Here, I discuss why some DNA intertwines persist into mitosis and review our current knowledge of the SCI resolution mechanisms that are employed in both prokaryotes and eukaryotes, including how deregulating SCI formation during DNA replication or disrupting the resolution processes may contribute to aneuploidy in cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20708344','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20708344"><span>Association between genetic polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH<span class="hlt">2</span>, MLH1, MSH3, and MGMT genes and <span class="hlt">radiosensitivity</span> in breast cancer patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe</p> <p>2011-09-01</p> <p>Clinical <span class="hlt">radiosensitivity</span> varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH<span class="hlt">2</span> (<span class="hlt">g</span>IVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. <span class="hlt">Radiosensitivity</span> developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH<span class="hlt">2</span> <span class="hlt">g</span>IVS12-6nt-C allele (HR=53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of <span class="hlt">radiosensitivity</span> (HR=38.26; 95% CI, 1.19-1232.52). To our knowledge, this is the first report to find an association between MSH<span class="hlt">2</span> and MSH3 genetic variants and the development of <span class="hlt">radiosensitivity</span> in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be involved in cellular response to radiotherapy. Genetic</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018CPL...692..374W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018CPL...692..374W"><span>5-(Halomethyl)uridine derivatives as potential antitumor <span class="hlt">radiosensitizers</span>: A DFT study</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wang, Shoushan; Zhang, Min; Liu, Peng; Xie, Shilei; Cheng, Faliang; Wang, Lishi</p> <p>2018-01-01</p> <p>Considering the fact that the efficiency of the uridine-5-methyl radical in producing cytotoxic DNA intrastrand cross-link lesions is greatly higher than that of the uridine-5-yl radical, the <span class="hlt">radiosensitizing</span> action of 5-(halomethyl)uridines (5-XCH<span class="hlt">2</span>U, X = F, Cl, or Br) is studied in the present work. It is found that 5-XCH<span class="hlt">2</span>U has sufficient electron affinity to capture a pre-hydrated or a hydrated electron, and electron attachment leads to significantly facile X- elimination forming the uridine-5-methyl radical. All these three halogenated uridine derivatives are shown to be potential <span class="hlt">radiosensitizers</span>, with their <span class="hlt">radiosensitizing</span> abilities increased in an order 5-FCH<span class="hlt">2</span>U < 5-ClCH<span class="hlt">2</span>U ≈ 5-BrCH<span class="hlt">2</span>U.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29207170','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29207170"><span>BMI-1 suppression increases the <span class="hlt">radiosensitivity</span> of oesophageal carcinoma via the PI3K/Akt signaling pathway.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Xing-Xiao; Ma, Ming; Sang, Mei-Xiang; Zhang, Xue-Yuan; Liu, Zhi-Kun; Song, Heng; Zhu, Shu-Chai</p> <p>2018-02-01</p> <p>B-cell‑specific Moloney murine leukaemia virus integration site-1 (BMI-1) contributes to the growth of tumour cells post-irradiation (IR). The aim of the present study was to characterize the effects of BMI-1 on cell viability, <span class="hlt">radiosensitivity</span> and its mechanisms of action in oesophageal squamous cell cancer (ESCC). Western blotting and immunohistochemistry were employed to evaluate the protein expression of BMI-1 in ESCC cells and specimens, respectively. Additionally, the protein expression levels of BMI-1, H<span class="hlt">2</span>AK119ub and γH<span class="hlt">2</span>AX in ESCC cells were detected following different doses of IR and at different times after IR. The protein expression levels of MDC1 and 53BP1 were also measured. Flow cytometry and MTT assays were used to determine cell cycle progression, apoptosis and cell viability. The phosphatidylinositol 3-kinase inhibitor LY294002 and the agonist IGF-1 were employed to suppress or induce the phosphorylation of Akt to determine whether BMI-1 induces radioresistance in ESCC cells via activation of the PI3K/Akt pathway. The expression of BMI-1 was higher in ESCC tissues and cells compared with that in normal oesophageal tissues and cells. In addition, BMI-1 was positively related to tumour size and lymph node metastases and negatively to the overall survival of ESCC patients. IR induced the expression of BMI-1, H<span class="hlt">2</span>AK119ub and γH<span class="hlt">2</span>AX in a dose- and time-dependent manner. BMI-1 knockdown lowered the expression of γH<span class="hlt">2</span>AX, MDC1 and 53BP1, suppressed cell viability and increased <span class="hlt">radiosensitivity</span>. <span class="hlt">G</span><span class="hlt">2</span>/M phase arrest was eliminated; this was followed by an increased proportion of cells entering the <span class="hlt">G</span>0/<span class="hlt">G</span>1 phase after IR and BMI-1 knockdown via the upregulation of P16 and downregulation of cyclin D<span class="hlt">2</span> and cyclin-dependent kinase-4. Moreover, BMI-1 knockdown increased cell apoptosis, downregulated MCL-1 and p-Akt and upregulated Bax. Additionally, the inhibitory effect of the downregulation of p-Akt by LY294002 on tumour cell viability was identical to that of</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28781233','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28781233"><span>Phospho-H1 Decorates the Inter-<span class="hlt">chromatid</span> Axis and Is Evicted along with Shugoshin by SET during Mitosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Krishnan, Swathi; Smits, Arne H; Vermeulen, Michiel; Reinberg, Danny</p> <p>2017-08-17</p> <p>Precise control of sister <span class="hlt">chromatid</span> separation during mitosis is pivotal to maintaining genomic integrity. Yet, the regulatory mechanisms involved are not well understood. Remarkably, we discovered that linker histone H1 phosphorylated at S/T18 decorated the inter-<span class="hlt">chromatid</span> axial DNA on mitotic chromosomes. Sister <span class="hlt">chromatid</span> resolution during mitosis required the eviction of such H1S/T18ph by the chaperone SET, with this process being independent of and most likely downstream of arm-cohesin dissociation. SET also directed the disassembly of Shugoshins in a polo-like kinase 1-augmented manner, aiding centromere resolution. SET ablation compromised mitotic fidelity as evidenced by unresolved sister <span class="hlt">chromatids</span> with marked accumulation of H1S/T18ph and centromeric Shugoshin. Thus, chaperone-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. Our findings also elucidate the functional implications of the decades-old observation of mitotic linker histone phosphorylation, serving as a paradigm to explore the role of linker histones in bio-signaling processes. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_3");'>3</a></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li class="active"><span>5</span></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_5 --> <div id="page_6" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li class="active"><span>6</span></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="101"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3748914','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3748914"><span>Celecoxib enhances <span class="hlt">radiosensitivity</span> of hypoxic glioblastoma cells through endoplasmic reticulum stress</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Suzuki, Kenshi; Gerelchuluun, Ariungerel; Hong, Zhengshan; Sun, Lue; Zenkoh, Junko; Moritake, Takashi; Tsuboi, Koji</p> <p>2013-01-01</p> <p>Background Refractoriness of glioblastoma multiforme (GBM) largely depends on its radioresistance. We investigated the <span class="hlt">radiosensitizing</span> effects of celecoxib on GBM cell lines under both normoxic and hypoxic conditions. Methods Two human GBM cell lines, U87MG and U251MG, and a mouse GBM cell line, GL261, were treated with celecoxib or γ-irradiation either alone or in combination under normoxic and hypoxic conditions. <span class="hlt">Radiosensitizing</span> effects were analyzed by clonogenic survival assays and cell growth assays and by assessing apoptosis and autophagy. Expression of apoptosis-, autophagy-, and endoplasmic reticulum (ER) stress–related genes was analyzed by immunoblotting. Results Celecoxib significantly enhanced the <span class="hlt">radiosensitivity</span> of GBM cells under both normoxic and hypoxic conditions. In addition, combined treatment with celecoxib and γ-irradiation induced marked autophagy, particularly in hypoxic cells. The mechanism underlying the <span class="hlt">radiosensitizing</span> effect of celecoxib was determined to be ER stress loading on GBM cells. Conclusion Celecoxib enhances the <span class="hlt">radiosensitivity</span> of GBM cells by a mechanism that is different from cyclooxygenase-<span class="hlt">2</span> inhibition. Our results indicate that celecoxib may be a promising <span class="hlt">radiosensitizing</span> drug for clinical use in patients with GBM. PMID:23658321</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21362226-radiosensitization-effect-sti-pancreatic-cancer-cells-vitro','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21362226-radiosensitization-effect-sti-pancreatic-cancer-cells-vitro"><span><span class="hlt">Radiosensitization</span> Effect of STI-571 on Pancreatic Cancer Cells In Vitro</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Chung, Hye Won; Wen, Jing; Lim, Jong-Baeck</p> <p>2009-11-01</p> <p>Purpose: To examine STI-571-induced <span class="hlt">radiosensitivity</span> in human pancreatic cancer cells in vitro. Methods and Materials: Three human pancreatic cancer cell lines (Bxpc-3, Capan-1, and MiaPaCa-<span class="hlt">2</span>) exhibiting different expression levels of c-Kit and platelet-derived growth factor receptor beta (PDGFRbeta) and showing different K-ras mutation types were used. For evaluation of the antitumor activity of STI-571 in combination with radiation, clonogenic survival assays, Western blot analysis, and the annexin V/propidium iodide assay with microscopic evaluation by 4',6-diamidino-<span class="hlt">2</span>-phenylindole were conducted. Results: Dramatic phosphorylated (p)-c-Kit and p-PDGFRbeta attenuation, a modest dose- and time-dependent growth inhibition, and significant <span class="hlt">radiosensitization</span> were observed after STI-571 treatment inmore » view of apoptosis, although the levels of growth inhibition and increased <span class="hlt">radiosensitization</span> were different according to cell lines. The grades of <span class="hlt">radiosensitivity</span> corresponded to the attenuation levels of p-c-Kit and p-PDGFRbeta by STI-571, particularly to those of p-c-Kit, and the <span class="hlt">radiosensitivity</span> was partially affected by K-ras mutation in pancreatic cancer cells. Among downstream pathways associated with c-Kit or PDGFRbeta, p-PLCgamma was more closely related to <span class="hlt">radiosensitivity</span> compared with p-Akt1 or p-extracellular signal-regulated kinase 1. Conclusion: STI-571 enhances radiation response in pancreatic cancer cells. This effect is affected by the attenuation levels of p-c-Kit or p-PDGFRbeta, and K-ras mutation status. Among them, p-c-Kit plays more important roles in the <span class="hlt">radiosensitivity</span> in pancreatic cancer compared with p-PDGFRbeta or K-ras mutation status.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1998603','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1998603"><span>Frequency of sister <span class="hlt">chromatid</span> exchange and chromosomal aberrations in asbestos cement workers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fatma, N; Jain, A K; Rahman, Q</p> <p>1991-02-01</p> <p>Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister <span class="hlt">chromatid</span> exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were <span class="hlt">chromatid</span> gap and break types.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27156191','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27156191"><span>Electrophilic 5-Substituted Uracils as Potential <span class="hlt">Radiosensitizers</span>: A Density Functional Theory Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Makurat, Samanta; Chomicz-Mańka, Lidia; Rak, Janusz</p> <p>2016-08-18</p> <p>Although 5-bromo-<span class="hlt">2</span>'-deoxyuridine (5BrdU) possesses significant <span class="hlt">radiosensitizing</span> power in vitro, clinical studies do not confirm any advantages of radiotherapy employing 5BrdU. This situation calls for a continuous search for efficient <span class="hlt">radiosensitizers</span>. Using the proposed mechanism of <span class="hlt">radiosensitization</span> by 5BrdU, we propose a series of 5-substituted uracils, XYU, that should undergo efficient dissociative electron attachment. The DFT-calculated thermodynamic and kinetic data concerning the XYU degradations induced by electron addition suggests that some of the scrutinized derivatives have much better characteristics than 5BrdU itself. Synthesis of these promising candidates for <span class="hlt">radiosensitizers</span>, followed by studies of their <span class="hlt">radiosensitizing</span> properties in DNA context, and ultimately in cancer cells, are further steps to confirm their potential applicability in anticancer treatment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040112575&hterms=cells+cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dcells%2Bcancer','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040112575&hterms=cells+cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D70%26Ntt%3Dcells%2Bcancer"><span>Cell killing and <span class="hlt">chromatid</span> damage in primary human bronchial epithelial cells irradiated with accelerated 56Fe ions</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Suzuki, M.; Piao, C.; Hall, E. J.; Hei, T. K.</p> <p>2001-01-01</p> <p>We examined cell killing and <span class="hlt">chromatid</span> damage in primary human bronchial epithelial cells irradiated with high-energy 56Fe ions. Cells were irradiated with graded doses of 56Fe ions (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at Brookhaven National Laboratory. The survival curves for cells plated 1 h after irradiation (immediate plating) showed little or no shoulder. However, the survival curves for cells plated 24 h after irradiation (delayed plating) had a small initial shoulder. The RBE for 56Fe ions compared to 137Cs gamma rays was 1.99 for immediate plating and <span class="hlt">2</span>.73 for delayed plating at the D10. The repair ratio (delayed plating/immediate plating) was 1.67 for 137Cs gamma rays and 1.22 for 56Fe ions. The dose-response curves for initially measured and residual <span class="hlt">chromatid</span> fragments detected by the Calyculin A-mediated premature chromosome condensation technique showed a linear response. The results indicated that the induction frequency for initially measured fragments was the same for 137Cs gamma rays and 56Fe ions. On the other hand, approximately 85% of the fragments induced by 137Cs gamma rays had rejoined after 24 h of postirradiation incubation; the corresponding amount for 56Fe ions was 37%. Furthermore, the frequency of <span class="hlt">chromatid</span> exchanges induced by gamma rays measured 24 h after irradiation was higher than that induced by 56Fe ions. No difference in the amount of <span class="hlt">chromatid</span> damage induced by the two types of radiations was detected when assayed 1 h after irradiation. The results suggest that high-energy 56Fe ions induce a higher frequency of complex, unrepairable damage at both the cellular and chromosomal levels than 137Cs gamma rays in the target cells for radiation-induced lung cancers.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28810896','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28810896"><span>Silencing the Girdin gene enhances <span class="hlt">radio-sensitivity</span> of hepatocellular carcinoma via suppression of glycolytic metabolism.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yu, Li; Sun, Yifan; Li, Jingjing; Wang, Yan; Zhu, Yuxing; Shi, Yong; Fan, Xiaojun; Zhou, Jianda; Bao, Ying; Xiao, Jie; Cao, Ke; Cao, Peiguo</p> <p>2017-08-15</p> <p>Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the <span class="hlt">radio-sensitivity</span> of hepatocellular carcinoma remains unclear. A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular <span class="hlt">radiosensitivity</span>. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the <span class="hlt">radiosensitivity</span> of hepatoma in vivo. shRNA-induced Girdin silencing suppressed glycolysis and enhanced the <span class="hlt">radio-sensitivity</span> of hepatic cell lines, Hep<span class="hlt">G</span><span class="hlt">2</span> and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis. Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=43487&Lab=ORD&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=43487&Lab=ORD&keyword=bone&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>EVIDENCE FOR THE CHROMOSOMAL REPLICONS AS UNITS OF SISTER <span class="hlt">CHROMATID</span> EXCHANGES</span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>Current hypotheses of sister <span class="hlt">chromatid</span> exchange (SCE) formation postulate that sites of SCE induction are associated with active replicons or replicon clusters. We have applied the FCC-SCD technique to in vivo studies of mouse bone marrow cells that have been treated with cycloph...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16566725','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16566725"><span>Mechanism of <span class="hlt">radiosensitization</span> by porphyrins.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Luksiene, Zivile; Labeikyte, Danute; Juodka, Benediktas; Moan, Johan</p> <p>2006-01-01</p> <p>According to our previous data, hematoporphyrin dimethyl ether (HPde) at concentrations useful for photodynamic therapy can <span class="hlt">radiosensitize</span> aggressive Ehrlich ascite carcinoma (EAT) to <span class="hlt">2</span>Gy irradiation inducing total tumour growth inhibition. The aim of this study was to further investigate the possible mechanism of <span class="hlt">radiosensitization</span> of EAT by dicarboxylic porphyrin-HPde. Our results reveal that HPde is inducing several rearrangements in the EAT cells: 1.<span class="hlt">2</span> x 10-6 M of the photosensitizer diminishes the number of cells in mitosis by a factor of 3, increases the number of cells in the S phase of the cell cycle, modifies the activities of antioxidant enzymes glutation S-transferase (GST) and DT-diaphorase (DTD), and eventually induces slight apoptosis. Moreover, it was shown that HPde is a ligand of peripheral benzodiazepine receptor (PBR). Named "house keeper," PBR is usually responsible for all these perturbations, which, in our case, act in concert with the following ionizing radiation, producing the interaction of two antiproliferative/destructive factors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26520689','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26520689"><span>EphA<span class="hlt">2</span> modulates <span class="hlt">radiosensitive</span> of hepatocellular carcinoma cells via p38/mitogen-activated protein kinase-mediated signal pathways.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jin, Qiao; Li, Xiangjun; Cao, Peiguo</p> <p>2015-10-01</p> <p>This experiment was conducted to investigate the role of EPH receptor A<span class="hlt">2</span> (EphA<span class="hlt">2</span>) in the modulation of <span class="hlt">radiosensitivity</span> of hepatic cellular cancer (HCC) cells and to determine whether p38/mitogen-activated protein kinase (p38MAPK) signaling mediated EphA<span class="hlt">2</span> function in this respect. The protein expressions of EphA<span class="hlt">2</span> and phosphorylated p38MAPK were tested in HCC and normal hepatic tissues. In HCC 97H cells, EphA<span class="hlt">2</span> was overexpressed and knocked out by transfection with EphA<span class="hlt">2</span> expression vector and EphA<span class="hlt">2</span>-ShRNA, respectively, prior to cell exposure to low-dose irradiation. Significantly upregulated EphA<span class="hlt">2</span> and phosphorylated p38MAPK were observed in HCC tissues, compared with those in normal hepatic tissues. Low-dose irradiation (1 Gy) only caused minor damage to HCC 97H cells, as assessed by alterations in cell viability, apoptosis rate, and cell healing capacity (p = 0.072, p = 0.078, and p = 0.069 respectively). However, EphA<span class="hlt">2</span> knock-out in HCC 97H cells induced significant reduction in cell viability and cell healing capacity after these cells were subjected to low-dose irradiation. Apoptosis rate underwent dramatic increase (p < 0.01). By contrast, EphA<span class="hlt">2</span> overexpression in HCC 97H cells reversed these effects and enhanced cell colony formation rate, thus displaying remarkable attenuation of <span class="hlt">radiosensitivity</span> of HCC 97H cells. Further, SB203580, a specific inhibitor of p38MAPK, was added to HCC 97H cells over-expressing EphA<span class="hlt">2</span>. The effect of EphA<span class="hlt">2</span> overexpression on the <span class="hlt">radiosensitivity</span> of HCC 97H cells was abrogated. Thus, the present study indicates that EphA<span class="hlt">2</span> have the ability to negatively regulate the <span class="hlt">radiosensitivity</span> of HCC 97H cells, which mainly depends on 38MAPK-mediated signal pathways. Copyright © 2015. Published by Elsevier Taiwan.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016NatSR...629678D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016NatSR...629678D"><span>The High <span class="hlt">Radiosensitizing</span> Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier</p> <p>2016-07-01</p> <p>We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as <span class="hlt">radiosensitizers</span>. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of <span class="hlt">radiosensitizing</span> nanoparticles in the tumor area is sufficient (0.1 μ<span class="hlt">g/g</span> of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21172474-replication-dependent-radiosensitization-human-glioma-cells-inhibition-poly-adp-ribose-polymerase-mechanisms-therapeutic-potential','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21172474-replication-dependent-radiosensitization-human-glioma-cells-inhibition-poly-adp-ribose-polymerase-mechanisms-therapeutic-potential"><span>Replication-Dependent <span class="hlt">Radiosensitization</span> of Human Glioma Cells by Inhibition of Poly(ADP-Ribose) Polymerase: Mechanisms and Therapeutic Potential</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Dungey, Fiona A.; Loeser, Dana A.; Chalmers, Anthony J.</p> <p>2008-11-15</p> <p>Purpose: Current treatments for glioblastoma multiforme are inadequate and limited by the radiation sensitivity of normal brain. Because glioblastoma multiforme are rapidly proliferating tumors within nondividing normal tissue, the therapeutic ratio might be enhanced by combining radiotherapy with a replication-specific <span class="hlt">radiosensitizer</span>. KU-0059436 (AZD2281) is a potent and nontoxic inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) undergoing a Phase II clinical trial as a single agent. Methods and Materials: Based on previous observations that the <span class="hlt">radiosensitizing</span> effects of PARP inhibition are more pronounced in dividing cells, we investigated the mechanisms underlying <span class="hlt">radiosensitization</span> of human glioma cells by KU-0059436, evaluating the replication dependence ofmore » this effect and its therapeutic potential. Results: KU-0059436 increased the <span class="hlt">radiosensitivity</span> of four human glioma cell lines (T98<span class="hlt">G</span>, U373-MG, UVW, and U87-MG). <span class="hlt">Radiosensitization</span> was enhanced in populations synchronized in S phase and abrogated by concomitant exposure to aphidicolin. Sensitization was further enhanced when the inhibitor was combined with a fractionated radiation schedule. KU-0059436 delayed repair of radiation-induced DNA breaks and was associated with a replication-dependent increase in {gamma}H<span class="hlt">2</span>AX and Rad51 foci. Conclusion: The results of our study have shown that KU-0059436 increases <span class="hlt">radiosensitivity</span> in a replication-dependent manner that is enhanced by fractionation. A mechanism is proposed whereby PARP inhibition increases the incidence of collapsed replication forks after ionizing radiation, generating persistent DNA double-strand breaks. These observations indicate that KU-0059436 is likely to enhance the therapeutic ratio achieved by radiotherapy in the treatment of glioblastoma multiforme. A Phase I clinical trial is in development.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29533136','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29533136"><span>The use of the term '<span class="hlt">radiosensitivity</span>' through history of radiation: from clarity to confusion.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Britel, Manon; Bourguignon, Michel; Foray, Nicolas</p> <p>2018-05-01</p> <p>The term '<span class="hlt">radiosensitivity</span>' appeared for the first time at the beginning of the 20th century, few years after the discovery of X-rays. Initially used by French and German radiologists, it illustrated the risk of radiation-induced (RI) skin reactions. From the 1950s, '<span class="hlt">radiosensitivity</span>' was progressively found to describe other features of RI response such as RI cancers or cataracts. To date, such confusion may raise legal issues and complexify the message addressed to general public. Here, through an historical review, we aimed to better understand how this confusion appeared. To support our historical review, a quantitative and qualitative wording analysis of the '<span class="hlt">radiosensitivity</span>' occurrences and its derived terms was performed with Google books, Pubmed, Web of Science™ databases, and in all the ICRP publications. While '<span class="hlt">radiosensitivity</span>' was historically related to RI adverse tissue events attributable to cell death, the first efforts to quantify the RI risk specific to each organ/tissue revealed some different semantic fields that are not necessarily compatible together (e.<span class="hlt">g</span>. adverse tissue events for skin, cataracts for eyes, RI cancer for breast or thyroid). To avoid such confusion, we propose to keep the historical definition of '<span class="hlt">radiosensitivity</span>' to any clinical and cellular consequences of radiation attributable to cell death and to introduce the term 'radiosusceptibility' to describe the RI cancers or any feature that is attributable to cell transformation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26311052','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26311052"><span>Long non-coding RNA MALAT1 modulates <span class="hlt">radiosensitivity</span> of HR-HPV+ cervical cancer via sponging miR-145.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lu, Hongzhi; He, Yu; Lin, Lin; Qi, Zhengqin; Ma, Li; Li, Li; Su, Ying</p> <p>2016-02-01</p> <p>Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA playing oncogenic role in several cancers, including cervical cancer. However, its role in <span class="hlt">radiosensitivity</span> of cervical cancer is not yet well understood. This study explored the role of MALAT1 in <span class="hlt">radiosensitivity</span> of high-risk human papillomavirus (HR-HPV)-positive cervical cancer and whether there is a ceRNA mechanism which participated in its regulation over <span class="hlt">radiosensitivity</span>. Based on tissue samples from 50 cervical cancer cases and 25 healthy controls, we found MALAT1 expression was significantly higher in radioresistant than in <span class="hlt">radiosensitive</span> cancer cases. In addition, MALAT1 and miR-145 expression inversely changed in response to irradiation in HR-HPV+ cervical cancer cells. By using clonogenic assay and flow cytometry analysis of cell cycle distribution and apoptosis, we found CaSki and Hela cells with knockdown of MALAT1 had significantly lower colony formation, higher ratio of <span class="hlt">G</span><span class="hlt">2</span>/M phase block and higher ratio of cell apoptosis. By performing RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay, we confirmed that miR-145 and MALAT1 were in the same Ago<span class="hlt">2</span> complex and there was a reciprocal repression between them. Then, we explored the function of MALAT1-miR-145 in <span class="hlt">radiosensitivity</span> of cervical cancers cells and demonstrated that si-MALAT1 and miR-145 had some level of synergic effect in reducing cancer cell colony formation, cell cycle regulation, and inducing apoptosis. These findings provide an important clue about microRNA-lncRNA interaction in the mechanism of radioresistance of cervical cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040087659&hterms=pathways&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D80%26Ntt%3Dpathways','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040087659&hterms=pathways&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D80%26Ntt%3Dpathways"><span>An overactivated ATR/CHK1 pathway is responsible for the prolonged <span class="hlt">G</span><span class="hlt">2</span> accumulation in irradiated AT cells</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Wang, Xiang; Khadpe, Jay; Hu, Baocheng; Iliakis, George; Wang, Ya</p> <p>2003-01-01</p> <p>Induction of checkpoint responses in <span class="hlt">G</span>1, S, and <span class="hlt">G</span><span class="hlt">2</span> phases of the cell cycle after exposure of cells to ionizing radiation (IR) is essential for maintaining genomic integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating this response in all three phases of the cell cycle. However, cells lacking functional ATM exhibit a prolonged <span class="hlt">G</span><span class="hlt">2</span> arrest after IR, suggesting regulation by an ATM-independent checkpoint response. The mechanism for this ataxia telangiectasia (AT)-independent <span class="hlt">G</span><span class="hlt">2</span>-checkpoint response remains unknown. We report here that the <span class="hlt">G</span><span class="hlt">2</span> checkpoint in irradiated human AT cells derives from an overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the IR-induced prolonged <span class="hlt">G</span><span class="hlt">2</span> checkpoint and <span class="hlt">radiosensitizes</span> AT cells to killing. These results link the activation of ATR/CHK1 with the prolonged <span class="hlt">G</span><span class="hlt">2</span> arrest in AT cells and show that activation of this <span class="hlt">G</span><span class="hlt">2</span> checkpoint contributes to the survival of AT cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28423495','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28423495"><span>Afatinib <span class="hlt">radiosensitizes</span> head and neck squamous cell carcinoma cells by targeting cancer stem cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Macha, Muzafar A; Rachagani, Satyanarayana; Qazi, Asif Khurshid; Jahan, Rahat; Gupta, Suprit; Patel, Anery; Seshacharyulu, Parthasarathy; Lin, Chi; Li, Sicong; Wang, Shuo; Verma, Vivek; Kishida, Shosei; Kishida, Michiko; Nakamura, Norifumi; Kibe, Toshiro; Lydiatt, William M; Smith, Russell B; Ganti, Apar K; Jones, Dwight T; Batra, Surinder K; Jain, Maneesh</p> <p>2017-03-28</p> <p>The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the <span class="hlt">radiosensitizing</span> activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro <span class="hlt">radiosensitivity</span> of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, <span class="hlt">G</span>1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK<span class="hlt">2</span>/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH<span class="hlt">2</span>AX by afatinib. Overall, afatinib reduces tumorigenicity and <span class="hlt">radiosensitizes</span> HNSCC cells. It holds promise for future clinical development as a novel <span class="hlt">radiosensitizer</span> by improving CSC eradication.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5400558','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5400558"><span>Afatinib <span class="hlt">radiosensitizes</span> head and neck squamous cell carcinoma cells by targeting cancer stem cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Macha, Muzafar A; Rachagani, Satyanarayana; Qazi, Asif Khurshid; Jahan, Rahat; Gupta, Suprit; Patel, Anery; Seshacharyulu, Parthasarathy; Lin, Chi; Li, Sicong; Wang, Shuo; Verma, Vivek; Kishida, Shosei; Kishida, Michiko; Nakamura, Norifumi; Kibe, Toshiro; Lydiatt, William M; Smith, Russell B; Ganti, Apar K; Jones, Dwight T; Batra, Surinder K; Jain, Maneesh</p> <p>2017-01-01</p> <p>The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the <span class="hlt">radiosensitizing</span> activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro <span class="hlt">radiosensitivity</span> of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, <span class="hlt">G</span>1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK<span class="hlt">2</span>/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH<span class="hlt">2</span>AX by afatinib. Overall, afatinib reduces tumorigenicity and <span class="hlt">radiosensitizes</span> HNSCC cells. It holds promise for future clinical development as a novel <span class="hlt">radiosensitizer</span> by improving CSC eradication. PMID:28423495</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21372117-prostate-specific-natural-health-products-dietary-supplements-radiosensitize-normal-prostate-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21372117-prostate-specific-natural-health-products-dietary-supplements-radiosensitize-normal-prostate-cells"><span>Prostate-Specific Natural Health Products (Dietary Supplements) <span class="hlt">Radiosensitize</span> Normal Prostate Cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.</p> <p></p> <p>Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements <span class="hlt">radiosensitized</span> normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity wasmore » assessed using cell proliferation assays [3-(4,5-dimethylthiazol-<span class="hlt">2</span>-yl)-<span class="hlt">2</span>,5-diphenyl tetrazolium bromide] and cellular <span class="hlt">radiosensitivity</span> using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH<span class="hlt">2</span>AX. Results: The cell growth and <span class="hlt">radiosensitivity</span> of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [<span class="hlt">2</span>mug/mL], Trinovin [10mug/mL], and Prostate Rx [50 mug/mL]). However, both Trinovin (10mug/mL) and Prostate Rx (6mug/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular <span class="hlt">radiosensitivity</span> of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential <span class="hlt">radiosensitization</span> of normal prostate cells.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3744569','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3744569"><span>Icaritin Synergistically Enhances the <span class="hlt">Radiosensitivity</span> of 4T1 Breast Cancer Cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lv, Wenlong; Zhang, Mei; Chen, Chun; Yang, Shanmin; Li, Shan; Zhang, Lurong; Han, Deping; Zhang, Weijian</p> <p>2013-01-01</p> <p>Icaritin (ICT) is a hydrolytic form of icariin isolated from plants of the genus Epimedium. This study was to investigate the <span class="hlt">radiosensitization</span> effect of icaritin and its possible underlying mechanism using murine 4T1 breast cancer cells. The combination of Icaritin at 3 µM or 6 µM with 6 or 8 Gy of ionizing radiation (IR) in the clonogenic assay yielded an ER (enhancement ratio) of 1.18 or 1.28, CI (combination index) of 0.38 or 0.19 and DRI (dose reducing index) of <span class="hlt">2</span>.51 or 5.07, respectively. These strongly suggest that Icaritin exerted a synergistic killing (?) effect with radiation on the tumor cells. This effect might relate with bioactivities of ICT: 1) exert an anti-proliferative effect in a dose- and time-dependent manner, which is different from IR killing effect but likely work together with the IR effect; <span class="hlt">2</span>) suppress the IR-induced activation of two survival paths, ERK1/<span class="hlt">2</span> and AKT; 3) induce the <span class="hlt">G</span><span class="hlt">2</span>/M blockage, enhancing IR killing effect; and 4) synergize with IR to enhance cell apoptosis. In addition, ICT suppressed angiogenesis in chick embryo chorioallantoic membrane (CAM) assay. Taken together, ICT is a new <span class="hlt">radiosensitizer</span> and can enhance anti-cancer effect of IR or other therapies. PMID:23977023</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/8613683','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/8613683"><span>Lethality of radiation-induced chromosome aberrations in human tumour cell lines with different <span class="hlt">radiosensitivities</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Coco-Martin, J M; Ottenheim, C P; Bartelink, H; Begg, A C</p> <p>1996-03-01</p> <p>In order to find an explanation for the eventual disappearance of all chromosome aberrations in two <span class="hlt">radiosensitive</span> human tumour cell lines, the type and stability of different aberration types was investigated in more detail. To classify the aberrations into unstable and stable types, three-colour fluorescence in situ hybridization was performed, including a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification of the aberrations principally by the presence (stable) or not (unstable) of a single centromere per chromosome. Unstable-type aberrations were found to disappear within 7 days (several divisions) in the two <span class="hlt">radiosensitive</span> and the two radioresistant tumour lines investigated. Stable-type aberrations were found to remain at an approximately constant level over the duration of the experiment (14 days; 8-10 divisions) in the two radioresistant lines. In contrast, the majority of these stable-type aberrations had disappeared by 14 days in the two <span class="hlt">radiosensitive</span> lines. The previous findings of disappearance of total aberrations in <span class="hlt">radiosensitive</span> cells was therefore not due to a reduced induction of stable-type aberrations, but the complete disappearance of cells with this aberration type. These results could not be explained by differences in apoptosis or <span class="hlt">G</span>1 blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type aberrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor for <span class="hlt">radiosensitivity</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22812492','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22812492"><span>Fundamental mechanisms of DNA <span class="hlt">radiosensitization</span>: damage induced by low-energy electrons in brominated oligonucleotide trimers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Park, Yeunsoo; Polska, Katarzyna; Rak, Janusz; Wagner, J Richard; Sanche, Léon</p> <p>2012-08-16</p> <p>The replacement of nucleobases with brominated analogs enhances DNA <span class="hlt">radiosensitivity</span>. We examine the chemistry of low-energy electrons (LEEs) in this sensitization process by experiments with thin films of the oligonucleotide trimers TBrXT, where BrX = 5-BrU (5-bromouracil), 5-BrC (5-bromocytosine), 8-BrA (8-bromoadenine), or 8-Br<span class="hlt">G</span> (8-bromoguanine). The products induced from irradiation of thin (∼ <span class="hlt">2</span>.5 nm) oligonucleotide films, with 10 eV electrons, under ultrahigh vacuum (UHV) are analyzed by HPLC-UV. The number of damaged brominated trimers ranges from about 12 to 15 × 10(-3) molecules per incident electron, whereas under the identical conditions, these numbers drop to 4-7 × 10(-3) for the same, but nonbrominated oligonucleotides. The results of HPLC analysis show that the main degradation pathway of trinucleotides containing brominated bases involve debromination (i.e., loss of the bromine atom and its replacement with a hydrogen atom). The electron-induced sum of products upon bromination increases by factors of <span class="hlt">2</span>.1 for the pyrimidines and 3.<span class="hlt">2</span> for the purines. Thus, substitution of any native nucleobase with a brominated one in simple models of DNA increases LEE-induced damage to DNA and hence its <span class="hlt">radiosensitivity</span>. Furthermore, besides the brominated pyrimidines that have already been tested in clinical trials, brominated purines not only appear to be promising sensitizers for radiotherapy, but could provide a higher degree of <span class="hlt">radiosensitization</span>.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_4");'>4</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li class="active"><span>6</span></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_6 --> <div id="page_7" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li class="active"><span>7</span></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="121"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1216365','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1216365"><span>Lack of Spontaneous Sister <span class="hlt">Chromatid</span> Exchanges in Somatic Cells of DROSOPHILA MELANOGASTER</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Gatti, M.; Santini, G.; Pimpinelli, S.; Olivieri, G.</p> <p>1979-01-01</p> <p>Neural ganglia of wild type third-instar larvae of Drosophila melanogaster were incubated for 13 hours at various concentrations of BUdR (1, 3, 9, 27 µg/ml). Metaphases were collected with colchicine, stained with Hoechst 33258, and scored under a fluorescence microscope. Metaphases in which the sister <span class="hlt">chromatids</span> were clearly differentiated were scored for the presence of sister-<span class="hlt">chromatid</span> exchanges (SCEs). At the lowest concentration of BUdR (1 µg/ml), no SCEs were observed in either male or female neuroblasts. The SCEs were found at the higher concentrations of BUdR (3, 9 and 27 µg/ml) and with a greater frequency in females than in males. Therefore SCEs are not a spontaneous phenomenon in D. melanogaster, but are induced by BUdR incorporated in the DNA. A striking nonrandomness was found in the distribution of SCEs along the chromosomes. More than a third of the SCEs were clustered in the junctions between euchromatin and heterochromatin. The remaining SCEs were preferentially localized within the heterochromatic regions of the X chromosome and the autosomes and primarily on the entirely heterochromatic Y chromosome.—In order to find an alternative way of measuring the frequency of SCEs in Drosophila neuroblasts, the occurrence of double dicentric rings was studied in two stocks carrying monocentric ring-X chromosomes. One ring chromosome, C(1)TR 94–<span class="hlt">2</span>, shows a rate of dicentric ring formation corresponding to the frequency of SCEs observed in the BUdR-labelled rod chromosomes. The other ring studied, R(1)<span class="hlt">2</span>, exhibits a frequency of SCEs higher than that observed with both C(1)TR 94–<span class="hlt">2</span> and rod chromosomes. PMID:109350</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1783675','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1783675"><span>Roles of the sister <span class="hlt">chromatid</span> cohesion apparatus in gene expression, development, and human syndromes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Dorsett, Dale</p> <p>2006-01-01</p> <p>The sister <span class="hlt">chromatid</span> cohesion apparatus mediates physical pairing of duplicated chromosomes. This pairing is essential for appropriate distribution of chromosomes into the daughter cells upon cell division. Recent evidence shows that the cohesion apparatus, which is a significant structural component of chromosomes during interphase, also affects gene expression and development. The Cornelia de Lange (CdLS) and Roberts/SC phocomelia (RBS/SC) genetic syndromes in humans are caused by mutations affecting components of the cohesion apparatus. Studies in Drosophila suggest that effects on gene expression are most likely responsible for developmental alterations in CdLS. Effects on <span class="hlt">chromatid</span> cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits. PMID:16819604</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017EPJD...71..241F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017EPJD...71..241F"><span>γH<span class="hlt">2</span>AX/53BP1 foci as a potential pre-treatment marker of HNSCC tumors <span class="hlt">radiosensitivity</span> - preliminary methodological study and discussion</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Falk, Martin; Horakova, Zuzana; Svobodova, Marketa; Masarik, Michal; Kopecna, Olga; Gumulec, Jaromir; Raudenska, Martina; Depes, Daniel; Bacikova, Alena; Falkova, Iva; Binkova, Hana</p> <p>2017-09-01</p> <p>In order to improve patients' post-treatment quality of life, a shift from surgery to non-surgical (chemo)radio-treatment is recognized in head and neck oncology. However, about half of HNSCC tumors are resistant to irradiation and an efficient marker of individual tumor <span class="hlt">radiosensitivity</span> is still missing. We analyzed whether various parameters of DNA double strand break (DSB) repair determined in vitro can predict, prior to clinical treatment initiation, the <span class="hlt">radiosensitivity</span> of tumors. We compared formation and decrease of γH<span class="hlt">2</span>AX/53BP1 foci in 48 h after irradiating tumor cell primocultures with <span class="hlt">2</span> Gy of γ-rays. To better understand complex tumor behavior, three different cell type primocultures - CD90-, CD90+, and a mixed culture of these cells - were isolated from 1 clinically radioresistant, <span class="hlt">2</span> <span class="hlt">radiosensitive</span>, and 4 undetermined HPV-HNSCC tumors and followed separately. While DSB repair was delayed and the number of persisting DSBs increased in the <span class="hlt">radiosensitive</span> tumors, the results for the radioresistant tumor were similar to cultured normal human skin fibroblasts. Hence, DSB repair kinetics/efficiency may correlate with clinical response to radiotherapy for a subset of HNSCC tumors but the size (and therefore practical relevance) of this subset remains to be determined. The same is true for contribution of different cell type primocultures to tumor radioresistance.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3979685','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3979685"><span>Differential <span class="hlt">Radiosensitivity</span> Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Little, John B.; Kato, Takamitsu A.; Shih, Hung-Ying; Xie, Xian-Jin; Wilson Jr., Paul F.; Brogan, John R.; Kurimasa, Akihiro; Chen, David J.; Bedford, Joel S.; Chen, Benjamin P. C.</p> <p>2014-01-01</p> <p>We have examined cell-cycle dependence of chromosomal aberration induction and cell killing after high or low dose-rate γ irradiation in cells bearing DNA-PKcs mutations in the S2056 cluster, the T2609 cluster, or the kinase domain. We also compared sister <span class="hlt">chromatid</span> exchanges (SCE) production by very low fluences of α-particles in DNA-PKcs mutant cells, and in homologous recombination repair (HRR) mutant cells including Rad51C, Rad51D, and Fancg/xrcc9. Generally, chromosomal aberrations and cell killing by γ-rays were similarly affected by mutations in DNA-PKcs, and these mutant cells were more sensitive in <span class="hlt">G</span>1 than in S/<span class="hlt">G</span><span class="hlt">2</span> phase. In <span class="hlt">G</span>1-irradiated DNA-PKcs mutant cells, both chromosome- and <span class="hlt">chromatid</span>-type breaks and exchanges were in excess than wild-type cells. For cells irradiated in late S/<span class="hlt">G</span><span class="hlt">2</span> phase, mutant cells showed very high yields of <span class="hlt">chromatid</span> breaks compared to wild-type cells. Few exchanges were seen in DNA-PKcs-null, Ku80-null, or DNA-PKcs kinase dead mutants, but exchanges in excess were detected in the S2506 or T2609 cluster mutants. SCE induction by very low doses of α-particles is resulted from bystander effects in cells not traversed by α-particles. SCE seen in wild-type cells was completely abolished in Rad51C- or Rad51D-deficient cells, but near normal in Fancg/xrcc9 cells. In marked contrast, very high levels of SCEs were observed in DNA-PKcs-null, DNA-PKcs kinase-dead and Ku80-null mutants. SCE induction was also abolished in T2609 cluster mutant cells, but was only slightly reduced in the S2056 cluster mutant cells. Since both non-homologous end-joining (NHEJ) and HRR systems utilize initial DNA lesions as a substrate, these results suggest the possibility of a competitive interference phenomenon operating between NHEJ and at least the Rad51C/D components of HRR; the level of interaction between damaged DNA and a particular DNA-PK component may determine the level of interaction of such DNA with a relevant HRR component. PMID:24714417</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27889450','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27889450"><span>RPA Mediates Recruitment of MRX to Forks and Double-Strand Breaks to Hold Sister <span class="hlt">Chromatids</span> Together.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Seeber, Andrew; Hegnauer, Anna Maria; Hustedt, Nicole; Deshpande, Ishan; Poli, Jérôme; Eglinger, Jan; Pasero, Philippe; Gut, Heinz; Shinohara, Miki; Hopfner, Karl-Peter; Shimada, Kenji; Gasser, Susan M</p> <p>2016-12-01</p> <p>The Mre11-Rad50-Xrs<span class="hlt">2</span> (MRX) complex is related to SMC complexes that form rings capable of holding two distinct DNA strands together. MRX functions at stalled replication forks and double-strand breaks (DSBs). A mutation in the N-terminal OB fold of the 70 kDa subunit of yeast replication protein A, rfa1-t11, abrogates MRX recruitment to both types of DNA damage. The rfa1 mutation is functionally epistatic with loss of any of the MRX subunits for survival of replication fork stress or DSB recovery, although it does not compromise end-resection. High-resolution imaging shows that either the rfa1-t11 or the rad50Δ mutation lets stalled replication forks collapse and allows the separation not only of opposing ends but of sister <span class="hlt">chromatids</span> at breaks. Given that cohesin loss does not provoke visible sister separation as long as the RPA-MRX contacts are intact, we conclude that MRX also serves as a structural linchpin holding sister <span class="hlt">chromatids</span> together at breaks. Copyright © 2016 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24852491','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24852491"><span>Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister <span class="hlt">chromatid</span> exchange evaluations.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schreiner, Ceinwen A; Hoffman, Gary M; Gudi, Ramadevi; Clark, Charles R</p> <p>2014-11-01</p> <p>Micronucleus and sister <span class="hlt">chromatid</span> exchange (SCE) tests were performed for vapor condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert-butyl ether (<span class="hlt">G</span>/MTBE), ethyl tert butyl ether (<span class="hlt">G</span>/ETBE), t-amyl methyl ether (<span class="hlt">G</span>/TAME), diisopropyl ether (<span class="hlt">G</span>/DIPE), t-butyl alcohol (TBA), or ethanol (<span class="hlt">G</span>/EtOH). Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0, 2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over 4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test). Blood was collected from the abdominal aorta for the SCE test and femurs removed for the micronucleus test. Blood cell cultures were treated with 5μ<span class="hlt">g</span>/ml bromodeoxyuridine (BrdU) for SCE evaluation. No significant increases in micronucleated immature erythrocytes were observed for any test material. Statistically significant increases in SCE were observed in rats given BGVC alone or in female rats given <span class="hlt">G</span>/MTBE. <span class="hlt">G</span>/TAME induced increased SCE in both sexes at the highest dose only. Although DNA perturbation was observed for several samples, DNA damage was not expressed as increased micronuclei in bone marrow cells. Inclusion of oxygenates in gasoline did not increase the effects of gasoline alone or produce a cytogenetic hazard. Copyright © 2014 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23681662','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23681662"><span>A CO-FISH assay to assess sister <span class="hlt">chromatid</span> segregation patterns in mitosis of mouse embryonic stem cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sauer, Stephan; Burkett, Sandra S; Lewandoski, Mark; Klar, Amar J S</p> <p>2013-05-01</p> <p>Sister <span class="hlt">chromatids</span> contain identical DNA sequence but are chiral with respect to both their helical handedness and their replication history. Emerging evidence from various model organisms suggests that certain stem cells segregate sister <span class="hlt">chromatids</span> nonrandomly to either maintain genome integrity or to bias cellular differentiation in asymmetric cell divisions. Conventional methods for tracing of old vs. newly synthesized DNA strands generally lack resolution for individual chromosomes and employ halogenated thymidine analogs with profound cytotoxic effects on rapidly dividing cells. Here, we present a modified chromosome orientation fluorescence in situ hybridization (CO-FISH) assay, where identification of individual chromosomes and their replication history is achieved in subsequent hybridization steps with chromosome-specific DNA probes and PNA telomere probes. Importantly, we tackle the issue of BrdU cytotoxicity and show that our method is compatible with normal mouse ES cell biology, unlike a recently published related protocol. Results from our CO-FISH assay show that mitotic segregation of mouse chromosome 7 is random in ES cells, which contrasts previously published results from our laboratory and settles a controversy. Our straightforward protocol represents a useful resource for future studies on <span class="hlt">chromatid</span> segregation patterns of in vitro-cultured cells from distinct model organisms.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=19750006348&hterms=hematopoiesis&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D30%26Ntt%3Dhematopoiesis','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=19750006348&hterms=hematopoiesis&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D30%26Ntt%3Dhematopoiesis"><span>Daily rhythms of <span class="hlt">radiosensitivity</span> of animals and several determining causes</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Druzhinin, Y. P.; Malyutina, T. S.; Seraya, V. M.; Rodina, G. P.; Vatsek, A.; Rakova, A.</p> <p>1974-01-01</p> <p>Daily rhythms of <span class="hlt">radiosensitivity</span> in rats and mice were determined by survival rates after acute total radiation at the same dosage at different times of the day. <span class="hlt">Radiosensitivity</span> differed in animals of different species and varieties. Inbred mice exhibited one or two increases in <span class="hlt">radiosensitivity</span> during the dark, active period of the day. These effects were attributed to periodic changes in the state of stem hematopoietic cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19800018569','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19800018569"><span>Change in <span class="hlt">radiosensitivity</span> of rats during hypokinetic stress</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Chernov, I. P.</p> <p>1980-01-01</p> <p>The laws governing stress modification of radiation sickness in relation to hypokinetic stress were investigated. It was found that gamma irradiation (800 rad) of rats on the third day of exposure to hypokinesia increased the <span class="hlt">radiosensitivity</span> of the animals which was determined by the survival rate and the dynamics of body weight and the weight of some internal organs. The same radiation dose was given on the 20th day of hypokinesia and on the third day of recovery from the 20 day hypokinesia decreased the <span class="hlt">radiosensitivity</span> of rats. It is concluded that the variations in the <span class="hlt">radiosensitivity</span> observed may be due to a stress effect of hypokinesia.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23894523','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23894523"><span>Cytosolic phospholipaseA<span class="hlt">2</span> inhibition with PLA-695 <span class="hlt">radiosensitizes</span> tumors in lung cancer animal models.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Thotala, Dinesh; Craft, Jeffrey M; Ferraro, Daniel J; Kotipatruni, Rama P; Bhave, Sandeep R; Jaboin, Jerry J; Hallahan, Dennis E</p> <p>2013-01-01</p> <p>Lung cancer remains the leading cause of cancer deaths in the United States and the rest of the world. The advent of molecularly directed therapies holds promise for improvement in therapeutic efficacy. Cytosolic phospholipase A<span class="hlt">2</span> (cPLA<span class="hlt">2</span>) is associated with tumor progression and radioresistance in mouse tumor models. Utilizing the cPLA<span class="hlt">2</span> specific inhibitor PLA-695, we determined if cPLA<span class="hlt">2</span> inhibition <span class="hlt">radiosensitizes</span> non small cell lung cancer (NSCLC) cells and tumors. Treatment with PLA-695 attenuated radiation induced increases of phospho-ERK and phospho-Akt in endothelial cells. NSCLC cells (LLC and A549) co-cultured with endothelial cells (bEND3 and HUVEC) and pre-treated with PLA-695 showed <span class="hlt">radiosensitization</span>. PLA-695 in combination with irradiation (IR) significantly reduced migration and proliferation in endothelial cells (HUVEC & bEND3) and induced cell death and attenuated invasion by tumor cells (LLC &A549). In a heterotopic tumor model, the combination of PLA-695 and radiation delayed growth in both LLC and A549 tumors. LLC and A549 tumors treated with a combination of PLA-695 and radiation displayed reduced tumor vasculature. In a dorsal skin fold model of LLC tumors, inhibition of cPLA<span class="hlt">2</span> in combination with radiation led to enhanced destruction of tumor blood vessels. The anti-angiogenic effects of PLA-695 and its enhancement of the efficacy of radiotherapy in mouse models of NSCLC suggest that clinical trials for its capacity to improve radiotherapy outcomes are warranted.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10827941','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10827941"><span>Splitting the chromosome: cutting the ties that bind sister <span class="hlt">chromatids</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nasmyth, K; Peters, J M; Uhlmann, F</p> <p>2000-05-26</p> <p>In eukaryotic cells, sister DNA molecules remain physically connected from their production at S phase until their separation during anaphase. This cohesion is essential for the separation of sister <span class="hlt">chromatids</span> to opposite poles of the cell at mitosis. It also permits chromosome segregation to take place long after duplication has been completed. Recent work has identified a multisubunit complex called cohesin that is essential for connecting sisters. Proteolytic cleavage of one of cohesin's subunits may trigger sister separation at the onset of anaphase.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3096717','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3096717"><span>Revised genetic requirements for the decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint: the role of ATM</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bower, Jacquelyn J.; Zhou, Yingchun; Zhou, Tong; Simpson, Dennis A.; Arlander, Sonnet J.; Paules, Richard S.; Cordeiro-Stone, Marila; Kaufmann, William K.</p> <p>2010-01-01</p> <p>The decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint is proposed to delay cellular progression from <span class="hlt">G</span><span class="hlt">2</span> into mitosis when intertwined daughter <span class="hlt">chromatids</span> are insufficiently decatenated. Previous studies indicated that the ATM- and Rad3-related (ATR) checkpoint kinase, but not the ataxia telangiectasia-mutated (ATM) kinase, was required for decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint function. Here, we show that the method used to quantify decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint function can influence the identification of genetic requirements for the checkpoint. Normal human diploid fibroblast (NHDF) lines responded to the topoisomerase II (topo II) catalytic inhibitor ICRF-193 with a stringent <span class="hlt">G</span><span class="hlt">2</span> arrest and a reduction in the mitotic index. While siRNA-mediated depletion of ATR and CHEK1 increased the mitotic index in ICRF-193 treated NHDF lines, depletion of these proteins did not affect the mitotic entry rate, indicating that the decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint was functional. These results suggest that ATR and CHEK1 are not required for the decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint, but may influence mitotic exit after inhibition of topo II. A re-evaluation of ataxia telangiectasia (AT) cell lines using the mitotic entry assay indicated that ATM was required for the decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint. Three NHDF cell lines responded to ICRF-193 with a mean 98% inhibition of the mitotic entry rate. Examination of the mitotic entry rates in AT fibroblasts upon treatment with ICRF-193 revealed a significantly attenuated decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint response, with a mean 59% inhibition of the mitotic entry rate. In addition, a normal lymphoblastoid line exhibited a 95% inhibition of the mitotic entry rate after incubation with ICRF-193, whereas two AT lymphoblastoid lines displayed only 36% and 20% inhibition of the mitotic entry rate. Stable depletion of ATM in normal human fibroblasts with short hairpin RNA also attenuated decatenation <span class="hlt">G</span><span class="hlt">2</span> checkpoint function by an average of 40%. Western immunoblot analysis demonstrated that treatment with ICRF</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/562332','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/562332"><span>Taxonomic and developmental aspects of <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Harrison, F.L.; Anderson, S.L.</p> <p>1996-11-01</p> <p>Considerable information is available on the effects of radioactivity on adult and early life stages of organisms. The preponderance of data is on mortality after a single irradiation with relatively high doses. Unfortunately, because experiments were carried out under different conditions and for different time periods, the validity of comparing the results from different laxonomic groups is questionable. In general, the conclusions are that there is a relationship (1) between radioresistance to high doses of acute radiation and taxonomy of the organism, primitive forms being more radioresistant than complex vertebrates and (<span class="hlt">2</span>) between <span class="hlt">radiosensitivity</span> and developmental stage, early life stagesmore » being more sensitive than later stages. The first conclusion may be related to the capability of the organism to repopulate cells and to differentiate and redifferentiate them; the second to the rate of cellular division and to the degree of differentiation. In question, however, is the relevance of the responses from high levels of acute radiation to that of the responses to long-term exposure to low levels of radiation, which are ecologically of more interest. Data from studies of the effects of acute and chronic exposure on development of gametes and zygotes indicate that, for some fishes and invertebrates, responses at the cellular and molecular levels show effect levels comparable to those observed in some mammals. Acute doses between 0,05 and 0.5Cy and dose rates between 0.02 to 0.<span class="hlt">2</span>mCy/h appear to define critical ranges in which detrimental effects on fertility are first observed in a variety of <span class="hlt">radiosensitive</span> organisms. To better understand inherent <span class="hlt">radiosensitivity</span>, we need more information on the ability of cells to repopulate and differentiate and to prevent or repair damage to biological critical molecules, such as DNA, because these factors may alter significantly organisms` responses to radiation.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27379201','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27379201"><span>Comparison of Individual <span class="hlt">Radiosensitivity</span> to γ-Rays and Carbon Ions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M; Ricoul, Michelle; Sabatier, Laure</p> <p>2016-01-01</p> <p>Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in <span class="hlt">radiosensitivity</span> in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual <span class="hlt">radiosensitivity</span> following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine <span class="hlt">radiosensitivity</span> at the dose of <span class="hlt">2</span> Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly <span class="hlt">radiosensitive</span> individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term "relative dose effect" (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At <span class="hlt">2</span> Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze <span class="hlt">radiosensitivity</span> at other doses (0.<span class="hlt">2</span>-15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4904030','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4904030"><span>Comparison of Individual <span class="hlt">Radiosensitivity</span> to γ-Rays and Carbon Ions</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M.; Ricoul, Michelle; Sabatier, Laure</p> <p>2016-01-01</p> <p>Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in <span class="hlt">radiosensitivity</span> in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual <span class="hlt">radiosensitivity</span> following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine <span class="hlt">radiosensitivity</span> at the dose of <span class="hlt">2</span> Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly <span class="hlt">radiosensitive</span> individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term “relative dose effect” (RDE). This ratio is advantageous, as it allows for simple comparison of dose–response curves. At <span class="hlt">2</span> Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze <span class="hlt">radiosensitivity</span> at other doses (0.<span class="hlt">2</span>–15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/478292-chromosomal-radiosensitivity-sub-phase-lymphocytes-indicator-cancer-predisposition','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/478292-chromosomal-radiosensitivity-sub-phase-lymphocytes-indicator-cancer-predisposition"><span>Chromosomal <span class="hlt">radiosensitivity</span> in <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase lymphocytes as an indicator of cancer predisposition</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Scott, D.; Spreadborough, A.R.; Jones, L.A.</p> <p></p> <p>Sanford et al. have reported that <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase cells from many heritable cancer-prone conditions exhibit higher yields of X-ray-induced chromosome damage than those found in the majority of healthy controls. We have applied their protocol to lymphocytes of a group of control and cancer-prone individuals to see if we could confirm these observations. For control donors we observed higher aberration yields, different kinetics and more interexperiment variability than found by Sanford et al. These differences could not be attributed to unavoidable minor variations in procedures (e.<span class="hlt">g</span>. serum batches, glassware washing methods), but the difference in X-ray qualities used in themore » two laboratories may have made a small contribution to the discrepancies. We attribute some of our experimental variability to the fact that, to varying extents in different experiments, centrifugation of cells prior to irradiation can slow down the progression of cells into metaphase and that cells can continue to repair during the harvesting procedure (centrifugation and hypotonic treatment). We have applied the assay to cases of ataxia telangiectasia (AT, homozygotes and heterozygotes), xeroderma pigmentosum (homozygotes and heterozygotes), familiar adenomatous polyposis and the syndromes Li-Fraumeni, basal cell nevus, Down`s and Fanconi`s but have been unable to discriminate between these groups and controls except for AT homozygotes. By including a control sample in parallel with samples from cancer-prone groups we found a significant difference in mean aberration yields between controls and AT homozygotes and heterozygotes, but not for the other groups. Since technical features could explain the discrepancies between our laboratories, we have devised our own <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase assay which appears to be giving promising results. 35 refs., 24 figs., 6 tabs.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16309949','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16309949"><span>Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister <span class="hlt">chromatid</span> exchange.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Stanimirovic, Zoran; Stevanovic, Jevrosima; Jovanovic, Slobodan; Andjelkovic, Marko</p> <p>2005-12-30</p> <p>Apitol, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister <span class="hlt">chromatid</span> exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35+/-0.18%, 8.31+/-0.20% and 12.33+/-0.25%, respectively), the proliferative index (PI = 1.83+/-0.01, 1.84+/-0.01 and 1.88+/-0.02, respectively) and the frequency of sister <span class="hlt">chromatid</span> exchange (SCE = 8.19+/-1.81, 8.78+/-1.80 and 13.46+/-1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15797924','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15797924"><span>Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and <span class="hlt">chromatid</span> exchange formation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Abdel-Halim, H I; Natarajan, A T; Mullenders, L H F; Boei, J J W A</p> <p>2005-04-15</p> <p><span class="hlt">Chromatid</span> interchanges induced by the DNA cross-linking agent mitomycin C (MMC) are over-represented in human chromosomes containing large heterochromatic regions. We found that nearly all exchange breakpoints of chromosome 9 are located within the paracentromeric heterochromatin and over 70% of exchanges involving chromosome 9 are between its homologues. We provide evidence that the required pairing of chromosome 9 heterochromatic regions occurs in <span class="hlt">G</span>(0)/<span class="hlt">G</span>(1) and S-phase cells as a result of an active cellular process initiated upon MMC treatment. By contrast, no pairing was observed for a euchromatic paracentromeric region of the equal-sized chromosome 8. The MMC-induced pairing of chromosome 9 heterochromatin is observed in a subset of cells; its percentage closely mimics the frequency of homologous interchanges found at metaphase. Moreover, the absence of pairing in cells derived from XPF patients correlates with an altered spectrum of MMC-induced exchanges. Together, the data suggest that the heterochromatin-specific pairing following MMC treatment reflects the initiation of DNA cross-link repair and the formation of exchanges.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3716600','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3716600"><span>Cytosolic PhospholipaseA<span class="hlt">2</span> Inhibition with PLA-695 <span class="hlt">Radiosensitizes</span> Tumors in Lung Cancer Animal Models</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ferraro, Daniel J.; Kotipatruni, Rama P.; Bhave, Sandeep R.; Jaboin, Jerry J.; Hallahan, Dennis E.</p> <p>2013-01-01</p> <p>Lung cancer remains the leading cause of cancer deaths in the United States and the rest of the world. The advent of molecularly directed therapies holds promise for improvement in therapeutic efficacy. Cytosolic phospholipase A<span class="hlt">2</span> (cPLA<span class="hlt">2</span>) is associated with tumor progression and radioresistance in mouse tumor models. Utilizing the cPLA<span class="hlt">2</span> specific inhibitor PLA-695, we determined if cPLA<span class="hlt">2</span> inhibition <span class="hlt">radiosensitizes</span> non small cell lung cancer (NSCLC) cells and tumors. Treatment with PLA-695 attenuated radiation induced increases of phospho-ERK and phospho-Akt in endothelial cells. NSCLC cells (LLC and A549) co-cultured with endothelial cells (bEND3 and HUVEC) and pre-treated with PLA-695 showed <span class="hlt">radiosensitization</span>. PLA-695 in combination with irradiation (IR) significantly reduced migration and proliferation in endothelial cells (HUVEC & bEND3) and induced cell death and attenuated invasion by tumor cells (LLC &A549). In a heterotopic tumor model, the combination of PLA-695 and radiation delayed growth in both LLC and A549 tumors. LLC and A549 tumors treated with a combination of PLA-695 and radiation displayed reduced tumor vasculature. In a dorsal skin fold model of LLC tumors, inhibition of cPLA<span class="hlt">2</span> in combination with radiation led to enhanced destruction of tumor blood vessels. The anti-angiogenic effects of PLA-695 and its enhancement of the efficacy of radiotherapy in mouse models of NSCLC suggest that clinical trials for its capacity to improve radiotherapy outcomes are warranted. PMID:23894523</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22056314-gefitinib-radiosensitizes-stem-like-glioma-cells-inhibition-epidermal-growth-factor-receptor-akt-dna-pk-signaling-accompanied-inhibition-dna-double-strand-break-repair','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22056314-gefitinib-radiosensitizes-stem-like-glioma-cells-inhibition-epidermal-growth-factor-receptor-akt-dna-pk-signaling-accompanied-inhibition-dna-double-strand-break-repair"><span>Gefitinib <span class="hlt">Radiosensitizes</span> Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg; Zhu Congju; Wong Yinling</p> <p></p> <p>Purpose: We compared <span class="hlt">radiosensitivity</span> of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC <span class="hlt">radiosensitivity</span> by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: <span class="hlt">Radiosensitivity</span> of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub <span class="hlt">2</span>}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival,more » {gamma}-H{sub <span class="hlt">2</span>}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced <span class="hlt">G</span>{sub <span class="hlt">2</span>}/M arrest and increased {gamma}-H{sub <span class="hlt">2</span>}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub <span class="hlt">2</span>}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_5");'>5</a></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li class="active"><span>7</span></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_7 --> <div id="page_8" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li class="active"><span>8</span></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="141"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22516386','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22516386"><span>Gefitinib <span class="hlt">radiosensitizes</span> stem-like glioma cells: inhibition of epidermal growth factor receptor-Akt-DNA-PK signaling, accompanied by inhibition of DNA double-strand break repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kang, Khong Bee; Zhu, Congju; Wong, Yin Ling; Gao, Qiuhan; Ty, Albert; Wong, Meng Cheong</p> <p>2012-05-01</p> <p>We compared <span class="hlt">radiosensitivity</span> of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC <span class="hlt">radiosensitivity</span> by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. <span class="hlt">Radiosensitivity</span> of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H(<span class="hlt">2</span>)AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H(<span class="hlt">2</span>)AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced <span class="hlt">G</span>(<span class="hlt">2</span>)/M arrest and increased γ-H(<span class="hlt">2</span>)AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H(<span class="hlt">2</span>)AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, <span class="hlt">G</span>(<span class="hlt">2</span>)/M arrest, and DNA DSBs, compared with nonstem</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25059546','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25059546"><span>Andrographolide <span class="hlt">radiosensitizes</span> human esophageal cancer cell line ECA109 to radiation in vitro.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Z-M; Kang, Y-H; Yang, X; Wang, J-F; Zhang, Q; Yang, B-X; Zhao, K-L; Xu, L-P; Yang, L-P; Ma, J-X; Huang, G-H; Cai, J; Sun, X-C</p> <p>2016-01-01</p> <p>To explore the <span class="hlt">radiosensitivity</span> of andrographolide on esophageal cancer cell line ECA109. The inhibition effects of andrographolide were measured using 3-(4,5-dimethyl-<span class="hlt">2</span>-thiazolyl)-<span class="hlt">2</span>,5-diphenyl-<span class="hlt">2</span>H-tetrazolium (MTT) assay. Clonogenic survival assay was used to evaluate the effects of andrographolide on the <span class="hlt">radiosensitivity</span> of esophageal cancer cells. Immunofluorescence was employed to examine Bax expression. The changes in cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of NF-κb/Cleaved-Caspase3/Bax/Bcl-<span class="hlt">2</span> was measured using Western blot analysis. DNA damage was detected via γ-H<span class="hlt">2</span>AX foci counting. With a clear dose and time effects, andrographolide was found to inhibit the proliferation of esophageal cell line ECA109. The results of the clonogenic survival assay show that andrographolide could markedly enhance <span class="hlt">radiosensitivity</span> (P < 0.05) with a sensitizing enhancement ratio of 1.28. Andrographolide caused a dose-dependent increase in Cleaved-Caspase3/Bax protein expression and a decrease in Bcl-<span class="hlt">2</span>/NF-κb expression. Apoptosis in andrographolide-treated ECA-109 increased significantly compared with the apoptosis in the simple drug and radiation combined with drug groups (P < 0.001; P < 0.05). Moreover, compared with the independent radiation group, the andrographolide combined with radiation group increased the number of DNA double chain breaks. Andrographolide can increase the <span class="hlt">radiosensitivity</span> of esophageal cell line ECA109. This result may be associated with the decrease in the NF-κb level and the induced apoptosis of esophageal cancer cells. © 2014 International Society for Diseases of the Esophagus.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24121106','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24121106"><span>Differential response of DU145 and PC3 prostate cancer cells to ionizing radiation: role of reactive oxygen species, GSH and Nrf<span class="hlt">2</span> in <span class="hlt">radiosensitivity</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jayakumar, Sundarraj; Kunwar, Amit; Sandur, Santosh K; Pandey, Badri N; Chaubey, Ramesh C</p> <p>2014-01-01</p> <p>Radioresistance is the major impediment in radiotherapy of many cancers including prostate cancer, necessitating the need to understand the factors contributing to radioresistance in tumor cells. In the present study, the role of cellular redox and redox sensitive transcription factor, Nrf<span class="hlt">2</span> in the <span class="hlt">radiosensitivity</span> of prostate cancer cell lines PC3 and DU145, has been investigated. Differential <span class="hlt">radiosensitivity</span> of PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. Their redox status was measured using DCFDA and DHR probes. Expression of Nrf<span class="hlt">2</span> and its dependent genes was measured by EMSA and real time PCR. Knockdown studies were done using shRNA transfection. PC3 and DU145 cells differed significantly in their <span class="hlt">radiosensitivity</span> as observed by clonogenic survival, apoptosis and neutral comet assays. Both basal and inducible levels of ROS were higher in PC3 cells than that of DU145 cells. DU145 cells showed higher level of basal GSH content and GSH/GSSG ratio than that of PC3 cells. Further, significant increase in both basal and induced levels of Nrf<span class="hlt">2</span> and its dependent genes was observed in DU145 cells. Knock-down experiments and pharmacological intervention studies revealed the involvement of Nrf<span class="hlt">2</span> in differential radio-resistance of these cells. Cellular redox status and Nrf<span class="hlt">2</span> levels play a causal role in radio-resistance of prostate cancer cells. The pivotal role Nrf<span class="hlt">2</span> has been shown in the radioresistance of tumor cells and this study will further help in exploiting this factor in <span class="hlt">radiosensitization</span> of other tumor cell types. © 2013.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22690883-enterolactone-novel-radiosensitizer-human-breast-cancer-cell-lines-through-impaired-dna-repair-increased-apoptosis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22690883-enterolactone-novel-radiosensitizer-human-breast-cancer-cell-lines-through-impaired-dna-repair-increased-apoptosis"><span>Enterolactone: A novel <span class="hlt">radiosensitizer</span> for human breast cancer cell lines through impaired DNA repair and increased apoptosis</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Bigdeli, Bahareh, E-mail: bhr.bigdeli@ut.ac.ir</p> <p></p> <p>Introduction: Radiotherapy is a potent treatment against breast cancer, which is the most commonly diagnosed cancer among women. However, the emergence of radioresistance due to increased DNA repair leads to radiotherapeutic failure. Applying polyphenols combined with radiation is a more promising method leading to better survival. Enterolactone, a phytoestrogenic polyphenol, has been reported to inhibit an important radioresistance signaling pathway, therefore we conjectured that enterolactone could enhance <span class="hlt">radiosensitivity</span> in breast cancer. To assess this hypothesis, radiation response of enterolactone treated MDA-MB-231 and T47D cell lines and corresponding cellular mechanisms were investigated. Methods: Cytotoxicity of enterolactone was measured via MTT assay.more » Cells were treated with enterolactone before X-irradiation, and clonogenic assay was used to evaluate <span class="hlt">radiosensitivity</span>. Cell cycle distribution and apoptosis were measured by flow cytometric analysis. In addition, DNA damages and corresponding repair, chromosomal damages, and aberrations were assessed by comet, micronucleus, and cytogenetic assays, respectively. Results: Enterolactone decreased the viability of cells in a concentration- and time dependent manner. Enterolactone significantly enhanced <span class="hlt">radiosensitivity</span> of cells by abrogating <span class="hlt">G</span><span class="hlt">2</span>/M arrest, impairing DNA repair, and increasing radiation-induced apoptosis. Furthermore, increased chromosomal damages and aberrations were detected in cells treated with enterolactone combined with X-rays than X-ray alone. These effects were more prominent in T47D than MDA-MB-231 cells. Discussion: To our knowledge, this is the first report that enterolactone is a novel <span class="hlt">radiosensitizer</span> for breast cancer irrespective of estrogen receptor status. Authors propose enterolactone as a candidate for combined therapy to decrease the radiation dose delivered to patients and subsequent side effects. - Highlights: • Enterolactone is proposed to be a novel</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27129153','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27129153"><span>Repurposing cephalosporin antibiotics as pro-senescent <span class="hlt">radiosensitizers</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Labay, Edwardine; Mauceri, Helena J; Efimova, Elena V; Flor, Amy C; Sutton, Harold G; Kron, Stephen J; Weichselbaum, Ralph R</p> <p>2016-06-07</p> <p>Radiation therapy remains a significant therapeutic modality in the treatment of cancer. An attractive strategy would be to enhance the benefits of ionizing radiation (IR)with <span class="hlt">radiosensitizers</span>. A high-content drug repurposing screen of approved and investigational agents, natural products and other small molecules has identified multiple candidates that blocked repair of IR damage in vitro. Here, we validated a subset of these hits in vitro and then examined effects on tumor growth after IR in a murine tumor model. Based on robust <span class="hlt">radiosensitization</span> in vivo and other favorable properties of cephalexin, we conducted additional studies with other beta-lactam antibiotics. When combined with IR, each cephalosporin tested increased DNA damage and slowed tumor growth without affecting normal tissue toxicity. Our data implicate reactive oxygen species in the mechanism by which cephalosporins augment the effects of IR. This work provides a rationale for using commonly prescribed beta-lactam antibiotics as non-toxic <span class="hlt">radiosensitizers</span> to enhance the therapeutic ratio of radiotherapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5085128','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5085128"><span>Repurposing cephalosporin antibiotics as pro-senescent <span class="hlt">radiosensitizers</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Flor, Amy C.; Sutton, Harold G.; Kron, Stephen J.; Weichselbaum, Ralph R.</p> <p>2016-01-01</p> <p>Radiation therapy remains a significant therapeutic modality in the treatment of cancer. An attractive strategy would be to enhance the benefits of ionizing radiation (IR)with <span class="hlt">radiosensitizers</span>. A high-content drug repurposing screen of approved and investigational agents, natural products and other small molecules has identified multiple candidates that blocked repair of IR damage in vitro. Here, we validated a subset of these hits in vitro and then examined effects on tumor growth after IR in a murine tumor model. Based on robust <span class="hlt">radiosensitization</span> in vivo and other favorable properties of cephalexin, we conducted additional studies with other beta-lactam antibiotics. When combined with IR, each cephalosporin tested increased DNA damage and slowed tumor growth without affecting normal tissue toxicity. Our data implicate reactive oxygen species in the mechanism by which cephalosporins augment the effects of IR. This work provides a rationale for using commonly prescribed beta-lactam antibiotics as non-toxic <span class="hlt">radiosensitizers</span> to enhance the therapeutic ratio of radiotherapy. PMID:27129153</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1843567','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1843567"><span>[Synthesis of 1-substituted nitroimidazoles and its evaluation as <span class="hlt">radiosensitizing</span> agents].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Adams, D R; Martul, R; Alvarez, M V; López Zumel, M C; Espada, M</p> <p>1991-01-01</p> <p>The synthesis of various substituted nitroimidazoles with lipophilic and hydrophilic side chains as potential <span class="hlt">radiosensitizing</span> agents is described. The starting material employed was 4(5)-nitroimidazole, which was alkylated via the sodium salt with various chloro-methylated, substituted alcohols and esters, in order to obtain analogues of misonidazole, metronidazole and desmethylmisonidazole of known <span class="hlt">radiosensitizing</span> and bactericidal activity. Some final products were assayed for their <span class="hlt">radiosensitizing</span> properties giving negative results under the testing conditions used.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5441663','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5441663"><span>Efficacy of <span class="hlt">radiosensitizing</span> doped titania nanoparticles under hypoxia and preparation of an embolic microparticle</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Morrison, Rachel A; Rybak-Smith, Malgorzata J; Thompson, James M; Thiebaut, Bénédicte; Hill, Mark A; Townley, Helen E</p> <p>2017-01-01</p> <p>The aim of this study was to develop a manufacturing protocol for large-scale production of doped titania <span class="hlt">radiosensitizing</span> nanoparticles (NPs) to establish their activity under hypoxia and to produce a multimodal <span class="hlt">radiosensitizing</span> embolic particle for cancer treatment. We have previously shown that <span class="hlt">radiosensitizing</span> NPs can be synthesized from titania doped with rare earth elements, especially gadolinium. To translate this technology to the clinic, a crucial step is to find a suitable, scalable, high-throughput method. Herein, we have described the use of flame spray pyrolysis (FSP) to generate NPs from titanium and gadolinium precursors to produce titania NPs doped with 5 at% gadolinium. The NPs were fully characterized, and their capacity to act as <span class="hlt">radiosensitizers</span> was confirmed by clonogenic assays. The integrity of the NPs in vitro was also ascertained due to the potentially adverse effects of free gadolinium in the body. The activity of the NPs was then studied under hypoxia since this is often a barrier to effective radiotherapy. In vitro <span class="hlt">radiosensitization</span> experiments were performed with both the hypoxia mimetics deferoxamine and cobalt chloride and also under true hypoxia (oxygen concentration of 0.<span class="hlt">2</span>%). It was shown that the <span class="hlt">radiosensitizing</span> NPs were able to cause a significant increase in cell death even after irradiation under hypoxic conditions such as those found in tumors. Subsequently, the synthesized NPs were used to modify polystyrene embolization microparticles. The NPs were sintered to the surface of the microparticles by heating at 230°C for 15 minutes. This resulted in a good coverage of the surface and to generate embolization particles that were shown to be <span class="hlt">radiosensitizing</span>. Such multimodal particles could therefore result in occlusion of the tumor blood vessels in conjunction with localized reactive oxygen species generation, even under hypoxic conditions such as those found in the center of tumors. PMID:28572729</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28572729','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28572729"><span>Efficacy of <span class="hlt">radiosensitizing</span> doped titania nanoparticles under hypoxia and preparation of an embolic microparticle.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Morrison, Rachel A; Rybak-Smith, Malgorzata J; Thompson, James M; Thiebaut, Bénédicte; Hill, Mark A; Townley, Helen E</p> <p>2017-01-01</p> <p>The aim of this study was to develop a manufacturing protocol for large-scale production of doped titania <span class="hlt">radiosensitizing</span> nanoparticles (NPs) to establish their activity under hypoxia and to produce a multimodal <span class="hlt">radiosensitizing</span> embolic particle for cancer treatment. We have previously shown that <span class="hlt">radiosensitizing</span> NPs can be synthesized from titania doped with rare earth elements, especially gadolinium. To translate this technology to the clinic, a crucial step is to find a suitable, scalable, high-throughput method. Herein, we have described the use of flame spray pyrolysis (FSP) to generate NPs from titanium and gadolinium precursors to produce titania NPs doped with 5 at% gadolinium. The NPs were fully characterized, and their capacity to act as <span class="hlt">radiosensitizers</span> was confirmed by clonogenic assays. The integrity of the NPs in vitro was also ascertained due to the potentially adverse effects of free gadolinium in the body. The activity of the NPs was then studied under hypoxia since this is often a barrier to effective radiotherapy. In vitro <span class="hlt">radiosensitization</span> experiments were performed with both the hypoxia mimetics deferoxamine and cobalt chloride and also under true hypoxia (oxygen concentration of 0.<span class="hlt">2</span>%). It was shown that the <span class="hlt">radiosensitizing</span> NPs were able to cause a significant increase in cell death even after irradiation under hypoxic conditions such as those found in tumors. Subsequently, the synthesized NPs were used to modify polystyrene embolization microparticles. The NPs were sintered to the surface of the microparticles by heating at 230°C for 15 minutes. This resulted in a good coverage of the surface and to generate embolization particles that were shown to be <span class="hlt">radiosensitizing</span>. Such multimodal particles could therefore result in occlusion of the tumor blood vessels in conjunction with localized reactive oxygen species generation, even under hypoxic conditions such as those found in the center of tumors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/4694450-radiosensitivity-birds','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/4694450-radiosensitivity-birds"><span>THE <span class="hlt">RADIOSENSITIVITY</span> OF BIRDS</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Kushnuruk, V.A.</p> <p>1962-01-01</p> <p>ABS>Earlier reports suggest that the <span class="hlt">radiosensitivity</span> of birds varies according to the systematic position of the species in question. To study this question in greater detail, birds belonging to different species were exposed to x rays and the LD/sub 50/ for 30 days recorded. During exposure, the birds were kept in a small cage but could move freely. Five different species were investigated: the greenfinch (Chloris chloris L.), goldfinch (Carduelis carduelis L.), linnet (Acantis cannabina L.), house sparrow (Passer domesticus), and the canary (Serinus canarina L.). It appeared that the <span class="hlt">radiosensitivity</span> of the birds moved within a fairly narrow rangemore » quite independently of the species. The LD/ sub 50/ for 30 days varied in the 5 species in question between 400 and 625 r. All birds showed disorders of the coordination of movements, in the reflex governing the picking of food, in flight, and in perching. (OTS)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/391300-induction-sister-chromatid-exchange-presence-gadolinium-dtpa-its-reduction-dimethyl-sulfoxide','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/391300-induction-sister-chromatid-exchange-presence-gadolinium-dtpa-its-reduction-dimethyl-sulfoxide"><span>Induction of sister <span class="hlt">chromatid</span> exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Yamazaki, Etsuo; Fukuda, Hozumi; Shibuya, Hitoshi</p> <p></p> <p>The authors investigate the frequency of sister <span class="hlt">chromatid</span> exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister <span class="hlt">chromatid</span> exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. The increase in frequency of SCE seen after the addition of Gd-DTPA wasmore » decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related. 14 refs., 6 tabs.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18000863','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18000863"><span>Polymorphisms in nonhomologous end-joining genes associated with breast cancer risk and chromosomal <span class="hlt">radiosensitivity</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Willems, Petra; Claes, Kathleen; Baeyens, Ans; Vandersickel, Veerle; Werbrouck, Joke; De Ruyck, Kim; Poppe, Bruce; Van den Broecke, Rudy; Makar, Amin; Marras, Emanuela; Perletti, Gianpaolo; Thierens, Hubert; Vral, Anne</p> <p>2008-02-01</p> <p>As enhanced chromosomal <span class="hlt">radiosensitivity</span> (CRS) results from non- or misrepaired double strand breaks (DSBs) and is a hallmark for breast cancer and single nucleotide polymorphisms (SNPs) in DSB repair genes, such as non homologous end-joining (NHEJ) genes, could be involved in CRS and genetic predisposition to breast cancer. In this study, we investigated the association of five SNPs in three different NHEJ genes with breast cancer in a population-based case-control setting. The total patient population composed of a selected group of patients with a family history of the disease and an unselected group, consisting mainly of sporadic cases. SNP analysis showed that the c.2099-2408<span class="hlt">G</span>>A SNP (XRCC5Ku80) [corrected] has a significant, positive odds ratio (OR) of <span class="hlt">2</span>.81 (95% confidence interval (CI): 1.30-6.05) for the heterozygous (He) and homozygous variant (HV) genotypes in the selected patient group. For the c.-1310 C><span class="hlt">G</span> SNP (XRCC6Ku70)[corrected] a significant OR of 1.85 (95%CI: 1.01-3.41) was found for the He genotype in the unselected patient group. On the contrary, the HV genotype of c.1781<span class="hlt">G</span>>T (XRCC6Ku70) [corrected] displays a significant, negative OR of 0.43 (95%CI: 0.18-0.99) in the total patient population. The He+HV genotypes of the c.2099-2408<span class="hlt">G</span>>A SNP (XRCC5Ku80) [corrected] also showed high and significant ORs in the group of "<span class="hlt">radiosensitive</span>," familial breast cancer patients. In conclusion, our results provide preliminary evidence that the variant allele of c.-1310C><span class="hlt">G</span> (XRCC6Ku70) [corrected]and c.2099-2408<span class="hlt">G</span>>A (XRCC5Ku80) [corrected] are risk alleles for breast cancer as well as CRS. The HV genotype of c.1781<span class="hlt">G</span>>T (XRCC6Ku70) [corrected] on the contrary, seems to protect against breast cancer and ionizing radiation induced micronuclei. (c) 2007 Wiley-Liss, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29285242','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29285242"><span>Roscovitine strongly enhances the effect of olaparib on <span class="hlt">radiosensitivity</span> for HPV neg. but not for HPV pos. HNSCC cell lines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ziemann, Frank; Seltzsam, Steve; Dreffke, Kristin; Preising, Stefanie; Arenz, Andrea; Subtil, Florentine S B; Rieckmann, Thorsten; Engenhart-Cabillic, Rita; Dikomey, Ekkehard; Wittig, Andrea</p> <p>2017-12-01</p> <p>At present, advanced stage human Papillomavirus (HPV) negative and positive head and neck squamous cell carcinoma (HNSCC) are treated by intense multimodal therapy that includes radiochemotherapy, which are associated with relevant side effects. Patients with HPV positive tumors possess a far better prognosis than those with HPV negative cancers. Therefore, new therapeutic strategies are needed to improve the outcome especially of the latter one as well as quality of life for all HNSCC patients. Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and <span class="hlt">2</span>. Surprisingly, all HPV positive cell lines were found to be defective in HR. In contrast, HPV negative strains demonstrated efficient HR, which was completely suppressed by roscovitine. In line with this, for HPV negative but not for HPV positive cell lines, treatment with roscovitine resulted in a pronounced enhancement of the radiation-induced <span class="hlt">G</span><span class="hlt">2</span> arrest as well as a significant increase in <span class="hlt">radiosensitivity</span>. Due to a defect in HR, all HPV positive cell lines were efficiently <span class="hlt">radiosensitized</span> by the PARP-1 inhibitor olaparib. In contrast, in HPV negative cell lines a significant <span class="hlt">radiosensitization</span> by olaparib was only achieved when combined with roscovitine.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2006cosp...36..488S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2006cosp...36..488S"><span>Effects of low-level chronic irradiation on <span class="hlt">radiosensitivity</span> of mammals: modeling and experimental studies</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Smirnova, O. A.; Yonezawa, M.</p> <p></p> <p>Effects of low dose rate chronic irradiation on <span class="hlt">radiosensitivity</span> of mammals mice are studied by experimental and modeling methods Own and reference experiments show that priming chronic low-level short-term and long-term exposures to radiation induce respectively elevated <span class="hlt">radiosensitivity</span> and lowered <span class="hlt">radiosensitivity</span> radioresistance in mice The manifestation of these <span class="hlt">radiosensitization</span> and radioprotection effects are respectively increased and decreased mortality of preirradiated specimens after challenge acute irradiation in comparison with those for previously unexposed ones Taking into account that the reason of the animal death in the experiments was the hematopoietic syndrome the biophysical models of the critical body system hematopoiesis are used to simulate the dynamics of the major hematopoietic lines in mice exposed to challenge acute irradiation following the chronic one Juxtaposition of the modeling results obtained and the relevant experimental data shows that the <span class="hlt">radiosensitization</span> effect of chronic low-level short-term less than 1 month preirradiation on mice is due to increased <span class="hlt">radiosensitivity</span> of lymphopoietic granulocytopoietic and erythropoietic systems accompanied by increased or close to the normal level <span class="hlt">radiosensitivity</span> of thrombocytopoietic system which are induced by the above-indicated exposure In turn the radioprotection effect of chronic low-level long-term more than 1 month preirradiation on mice is caused by decreased <span class="hlt">radiosensitivity</span> radioresistance of the granulocytopoietic system which</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017NRL....12..523H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017NRL....12..523H"><span>Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in Hep<span class="hlt">G</span><span class="hlt">2</span> Tumor-Bearing Nude Mice</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B.; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng</p> <p>2017-09-01</p> <p>Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. <span class="hlt">Radiosensitizers</span> can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64Cu-AGuIX accumulates to high levels in the Hep<span class="hlt">G</span><span class="hlt">2</span> xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the Hep<span class="hlt">G</span><span class="hlt">2</span> cells. In radiation therapy studies, a decrease in 18F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic <span class="hlt">radiosensitizer</span> for PET imaging to guide radiotherapy for liver cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28875472','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28875472"><span>Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in Hep<span class="hlt">G</span><span class="hlt">2</span> Tumor-Bearing Nude Mice.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng</p> <p>2017-09-06</p> <p>Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. <span class="hlt">Radiosensitizers</span> can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64 Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64 Cu-AGuIX accumulates to high levels in the Hep<span class="hlt">G</span><span class="hlt">2</span> xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the Hep<span class="hlt">G</span><span class="hlt">2</span> cells. In radiation therapy studies, a decrease in 18 F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic <span class="hlt">radiosensitizer</span> for PET imaging to guide radiotherapy for liver cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29388453','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29388453"><span>53BP1 loss suppresses the <span class="hlt">radiosensitizing</span> effect of icotinib hydrochloride in colorectal cancer cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huang, Ai; Yao, Jing; Liu, Tao; Lin, Zhenyu; Zhang, Sheng; Zhang, Tao; Ma, Hong</p> <p>2018-04-01</p> <p>This study aimed to investigate the influence of the expression of P53-binding protein 1 (53BP1), a key component in DNA damage repair pathways, on the <span class="hlt">radiosensitizing</span> effect of icotinib hydrochloride in colorectal cancer and to elucidate the mechanisms underlying this influence. Real-time RT-PCR and Western blotting were performed to verify the gene-knockout effect of 53BP1 small hairpin RNA (ShRNA), and colony formation assay was employed to investigate the influence of 53BP1 downregulation on the <span class="hlt">radiosensitizing</span> effect of icotinib hydrochloride in HCT116 cells. Cell apoptosis, cell cycle distributions, and histone H<span class="hlt">2</span>AX (γ-H<span class="hlt">2</span>AX) fluorescence foci after 53BP1 knockdown were evaluated. Relative protein expression in the ataxia telangiectasia mutated kinase (ATM)-checkpoint kinase-<span class="hlt">2</span> (CHK<span class="hlt">2</span>)-P53 pathway was measured by Western blot analysis to unravel the molecular mechanisms linking the pathway to the above phenomena. Icotinib hydrochloride increased the <span class="hlt">radiosensitivity</span> of HCT116 cells; however, this effect was suppressed by the downregulation of 53BP1 expression, a change that inhibited cell apoptosis, increased the percentage of HCT116 cells arrested in S-phase and inhibited the protein expression of key molecules in the ATM-CHK<span class="hlt">2</span>-P53 apoptotic pathway. Our studies confirmed that the loss of 53BP1 serves as a negative regulator of the <span class="hlt">radiosensitizing</span> effect of icotinib in part by suppressing the ATM-CHK<span class="hlt">2</span>-P53 apoptotic pathway.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5753566-effect-anemia-tumor-radiosensitivity-under-normo-hyperbaric-conditions','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5753566-effect-anemia-tumor-radiosensitivity-under-normo-hyperbaric-conditions"><span>Effect of anemia on tumor <span class="hlt">radiosensitivity</span> under normo and hyperbaric conditions</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Rojas, A.; Stewart, F.A.; Smith, K.A.</p> <p>1987-11-01</p> <p>The effect of chronic anemia on tumor <span class="hlt">radiosensitivity</span> in a murine tumor has been investigated. Anemia was induced by bilateral kidney irradiation given several months before tumor implantation. Anemic, anemic transfused, and normal non-anemic age-matched tumor bearing animals were irradiated with X rays (<span class="hlt">2</span> F/24 hr) either in air, air plus misonidazole, or under hyperbaric oxygen. The most resistant response was that of tumors grown in normal mice treated in air. Anemia produced an increase in <span class="hlt">radiosensitivity</span> which was further enhanced by red blood cell replacement. The most sensitive overall response was seen in the anemic-transfused group treated with HBO.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5048120','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5048120"><span>miR-26b enhances <span class="hlt">radiosensitivity</span> of hepatocellular carcinoma cells by targeting EphA<span class="hlt">2</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jin, Qiao; Li, Xiang Jun; Cao, Pei Guo</p> <p>2016-01-01</p> <p>Objective(s): Although low-dose radiotherapy (RT) that involves low collateral damage is more suitable for hepatocellular carcinoma (HCC) than traditional high-dose RT, but to achieve satisfactory therapeutic effect with low-dose RT, it is necessary to sensitize HCC cells to irradiation. This study was aimed to determine whether <span class="hlt">radiosensitivity</span> of HCC cells can be enhanced using miR-26b by targeting erythropoietin producing human hepatocelluar A<span class="hlt">2</span> (EphA<span class="hlt">2</span>). Materials and Methods: The levels of miR-26b and EphA<span class="hlt">2</span> expression in multiple HCC cell lines were assessed by qPCR and western blotting, respectively, and compared with those in a hepatic cell line. HCC 97H cells were transfected with miR-26b mimics, EphA<span class="hlt">2</span>-ShRNA or EphA<span class="hlt">2</span> over-expression vector before exposure to low-dose irradiation. Results: Different degrees of miR-26b down-regulation and EphA<span class="hlt">2</span> up-regulation were observed in all HCC cell lines, among which the HCC 97H cell line expressed the lowest level of miR-26b and highest level of EphA<span class="hlt">2</span>. EphA<span class="hlt">2</span> was verified as the target of miR-26b by dual luciferase reporter assay. HCC 97H cells transfected with miR-26b mimics or EphA<span class="hlt">2</span>-ShRNA reduced the expression of EphA<span class="hlt">2</span> protein, with significantly lower cell proliferation rate and cell invasion ability and higher apoptosis rate in response to low-dose irradiation than those in the non-transfected cells. These results were reversed after EphA<span class="hlt">2</span> was overexpressed by transfection with the EphA<span class="hlt">2</span> overexpression vector. Co-transfection with miR-26b mimics and EphA<span class="hlt">2</span> overexpression vector barely altered EphA<span class="hlt">2</span> expression level and cell response to low-dose irradiation. Conclusion: These data suggest that miR-26b enhances <span class="hlt">radiosensitivity</span> of HCC 97H cells by targeting EphA<span class="hlt">2</span> protein. PMID:27746866</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27746866','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27746866"><span>miR-26b enhances <span class="hlt">radiosensitivity</span> of hepatocellular carcinoma cells by targeting EphA<span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jin, Qiao; Li, Xiang Jun; Cao, Pei Guo</p> <p>2016-08-01</p> <p>Although low-dose radiotherapy (RT) that involves low collateral damage is more suitable for hepatocellular carcinoma (HCC) than traditional high-dose RT, but to achieve satisfactory therapeutic effect with low-dose RT, it is necessary to sensitize HCC cells to irradiation. This study was aimed to determine whether <span class="hlt">radiosensitivity</span> of HCC cells can be enhanced using miR-26b by targeting erythropoietin producing human hepatocelluar A<span class="hlt">2</span> (EphA<span class="hlt">2</span>). The levels of miR-26b and EphA<span class="hlt">2</span> expression in multiple HCC cell lines were assessed by qPCR and western blotting, respectively, and compared with those in a hepatic cell line. HCC 97H cells were transfected with miR-26b mimics, EphA<span class="hlt">2</span>-ShRNA or EphA<span class="hlt">2</span> over-expression vector before exposure to low-dose irradiation. Different degrees of miR-26b down-regulation and EphA<span class="hlt">2</span> up-regulation were observed in all HCC cell lines, among which the HCC 97H cell line expressed the lowest level of miR-26b and highest level of EphA<span class="hlt">2</span>. EphA<span class="hlt">2</span> was verified as the target of miR-26b by dual luciferase reporter assay. HCC 97H cells transfected with miR-26b mimics or EphA<span class="hlt">2</span>-ShRNA reduced the expression of EphA<span class="hlt">2</span> protein, with significantly lower cell proliferation rate and cell invasion ability and higher apoptosis rate in response to low-dose irradiation than those in the non-transfected cells. These results were reversed after EphA<span class="hlt">2</span> was overexpressed by transfection with the EphA<span class="hlt">2</span> overexpression vector. Co-transfection with miR-26b mimics and EphA<span class="hlt">2</span> overexpression vector barely altered EphA<span class="hlt">2</span> expression level and cell response to low-dose irradiation. These data suggest that miR-26b enhances <span class="hlt">radiosensitivity</span> of HCC 97H cells by targeting EphA<span class="hlt">2</span> protein.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_6");'>6</a></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li class="active"><span>8</span></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_8 --> <div id="page_9" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li class="active"><span>9</span></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="161"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/20850003-tgf-beta-polymorphisms-late-clinical-radiosensitivity-patients-treated-gynecologic-tumors','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/20850003-tgf-beta-polymorphisms-late-clinical-radiosensitivity-patients-treated-gynecologic-tumors"><span>TGF{beta}1 polymorphisms and late clinical <span class="hlt">radiosensitivity</span> in patients treated for gynecologic tumors</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Ruyck, Kim de; Van Eijkeren, Marc; Claes, Kathleen</p> <p>2006-07-15</p> <p>Purpose: To investigate the association between six transforming growth factor {beta}1 gene (TGF{beta}1) polymorphisms (-1.552delAGG, -800<span class="hlt">G</span>>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT). Methods and Materials: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC<span class="hlt">2</span>+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites inmore » TGF{beta}1. Results: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p = 0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical <span class="hlt">radiosensitivity</span>. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish <span class="hlt">radiosensitive</span> from nonradiosensitive patients. Conclusions: The present study shows that homozygous variant TGF{beta}1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical <span class="hlt">radiosensitivity</span> after gynecologic RT.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22570057-tu-campus-enhancing-tumor-specific-radiosensitization-using-molecular-targeted-gold-nanorods','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22570057-tu-campus-enhancing-tumor-specific-radiosensitization-using-molecular-targeted-gold-nanorods"><span>TU-F-CAMPUS-T-03: Enhancing the Tumor Specific <span class="hlt">Radiosensitization</span> Using Molecular Targeted Gold Nanorods</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Diagaradjane, P; Deorukhkar, A; Sankaranarayanapillai, M</p> <p>2015-06-15</p> <p>Purpose: Gold nanoparticle (GNP) mediated <span class="hlt">radiosensitization</span> has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific <span class="hlt">radiosensitization</span> for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and inmore » vitro <span class="hlt">radiosensitization</span> were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo <span class="hlt">radiosensitization</span> potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/<span class="hlt">g</span> of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant <span class="hlt">radiosensitization</span> was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced <span class="hlt">radiosensitization</span> effect observed with very low intratumoral concentrations of gold and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19800009409','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19800009409"><span>Differentiation and <span class="hlt">radiosensitivity</span> of hemopoietic stem cells of mice during hypokinesia</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Shvets, V. N.</p> <p>1980-01-01</p> <p>The potential for differentiation and <span class="hlt">radiosensitivity</span> of the stem hemopoietic cells (KOE) under conditions of initial and later hypokinesia is examined. It is established that in the initial period of hypokinesia (3 days) when a stress reaction prevails, changes occur in the erythroid differentiation and <span class="hlt">radiosensitivity</span> of KOE. This effect is associated with redistribution of T-lymphocytes that increase in number in the bone marrow of mice during hypokinesia. At later periods of hypokinesia (30 days) when changes in the organism are related to hypokinesia proper, differentiation and <span class="hlt">radiosensitivity</span> of KOE were normalized.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22202886-clonal-cell-populations-unresponsive-radiosensitization-induced-telomerase-inhibition','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22202886-clonal-cell-populations-unresponsive-radiosensitization-induced-telomerase-inhibition"><span>Clonal cell populations unresponsive to <span class="hlt">radiosensitization</span> induced by telomerase inhibition</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun</p> <p></p> <p>Research highlights: {yields} In our present manuscript, we have clearly showed an interesting but problematic obstacle of a <span class="hlt">radiosensitization</span> strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this <span class="hlt">radiosensitization</span> occasionally arise. {yields} The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. {yields} The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. {yields} P53 status is not associated with the occurrence of unsensitized clone. {yields} Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeuticmore » regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to <span class="hlt">radiosensitization</span> after telomere shortening. After extensive division of individual transformed clones of mTERC{sup -/-} cells, about 22% of clones were unresponsive to <span class="hlt">radiosensitization</span> even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC{sup -/-} clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the <span class="hlt">radiosensitization</span> generally mediated by telomere shortening.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27313684','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27313684"><span>MiR-593 mediates curcumin-induced <span class="hlt">radiosensitization</span> of nasopharyngeal carcinoma cells via MDR1.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fan, Haoning; Shao, Meng; Huang, Shaohui; Liu, Ying; Liu, Jie; Wang, Zhiyuan; Diao, Jianxin; Liu, Yuanliang; Tong, L I; Fan, Qin</p> <p>2016-06-01</p> <p>Curcumin (Cur) exhibits <span class="hlt">radiosensitization</span> effects to a variety of malignant tumors. The present study investigates the <span class="hlt">radiosensitizing</span> effect of Cur on nasopharyngeal carcinoma (NPC) cells and whether its mechanism is associated with microRNA-593 (miR-593) and multidrug resistance gene 1 (MDR1). A clonogenic assay was performed to measure the <span class="hlt">radiosensitizing</span> effect. The expression of miR-593 and MDR1 was analyzed by quantitative polymerase chain reaction (qPCR) or western blot assay. A transplanted tumor model was established to identify the <span class="hlt">radiosensitizing</span> effect in vivo . A luciferase-based reporter was constructed to evaluate the effect of direct binding of miR-593 to the putative target site on the 3' UTR of MDR1. The clonogenic assay showed that Cur enhanced the <span class="hlt">radiosensitivity</span> of cells. Cur (100 mg/kg) combined with 4 Gy irradiation inhibited the growth of a transplanted tumor model in vivo , resulting in the higher inhibition ratio compared with the radiotherapy-alone group. These results demonstrated that Cur had a <span class="hlt">radiosensitizing</span> effect on NPC cells in vivo and in vitro ; Cur-mediated upregulation of miR-593 resulted in reduced MDR1 expression, which may promote <span class="hlt">radiosensitivity</span> of NPC cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29392699','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29392699"><span>Evaluation of Radioresponse and <span class="hlt">Radiosensitizers</span> in Glioblastoma Organotypic Cultures.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bayin, N Sumru; Ma, Lin; Placantonakis, Dimitris G; Barcellos-Hoff, Mary Helen</p> <p>2018-01-01</p> <p>Glioblastoma (GBM), a deadly primary brain malignancy, manifests pronounced radioresistance. Identifying agents that improve the sensitivity of tumor tissue to radiotherapy is critical for improving patient outcomes. The response to ionizing radiation is regulated by both cell-intrinsic and -extrinsic mechanisms. In particular, the tumor microenvironment is known to promote radioresistance in GBM. Therefore, model systems used to test <span class="hlt">radiosensitizing</span> agents need to take into account the tumor microenvironment. We recently showed that GBM explant cultures represent an adaptable ex vivo platform for rapid and personalized testing of <span class="hlt">radiosensitizers</span>. These explants preserve the cellular composition and tissue architecture of parental patient tumors and therefore capture the microenvironmental context that critically determines the response to radiotherapy. This chapter focuses on the detailed protocol for testing candidate <span class="hlt">radiosensitizing</span> agents in GBM explants.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1174934','DOE-PATENT-XML'); return false;" href="https://www.osti.gov/servlets/purl/1174934"><span>Metalloporphyrins and their uses as <span class="hlt">radiosensitizers</span> for radiation therapy</span></a></p> <p><a target="_blank" href="http://www.osti.gov/doepatents">DOEpatents</a></p> <p>Miura, Michiko; Slatkin, Daniel N.</p> <p>2004-07-06</p> <p>The present invention covers <span class="hlt">radiosensitizers</span> containing as an active ingredient halogenated derivatives of boronated porphyrins containing multiple carborane cages having the structure ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron--capture therapy and photodynamic therapy. The present invention also covers methods for using these <span class="hlt">radiosensitizers</span> in tumor imaging and cancer treatment.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11748978','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11748978"><span>Sister <span class="hlt">chromatid</span> exchange rate and alkaline comet assay scores in patients with ovarian cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Baltaci, Volkan; Kayikçioğlu, Fulya; Alpas, Idil; Zeyneloğlu, Hulusi; Haberal, Ali</p> <p>2002-01-01</p> <p>Sister <span class="hlt">chromatid</span> exchange (SCE) frequencies were studied in patients with different types of ovarian malignancies and in healthy volunteers. The level of DNA damage in patients with ovarian malignancy and control subjects has also been studied by alkaline single cell gel electrophoresis (SCGE), also known as the comet assay. Peripheral blood was collected from 30 patients after histological confirmation of malignancy and 20 healthy female volunteers. The cells were evaluated according to their grade of damage. We found that the sister <span class="hlt">chromatid</span> exchange frequencies of cancer cases were significantly greater than that of controls (P < 0.001). The frequency of exchange in chromosomal groups A, B, and C, which include chromosomes 1-12, was higher than that of the other chromosomal groups in both groups. Comparison of the results of the alkaline comet assay in patient and control subjects showed a significant difference in the number of damaged cells. The frequency of limited migrated and extensive migrated cells in the women with ovarian malignancies was higher than that of control women (P < 0.001). SCE and SCGE can be used successfully to monitor DNA damage in women with ovarian cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5389604-targeting-radiosensitizers-dna-attachment-intercalating-group-nitroimidazole-linked-phenanthridines','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5389604-targeting-radiosensitizers-dna-attachment-intercalating-group-nitroimidazole-linked-phenanthridines"><span>Targeting <span class="hlt">radiosensitizers</span> to DNA by attachment of an intercalating group: Nitroimidazole-linked phenanthridines</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Cowan, D.S.; Panicucci, R.; McClelland, R.A.</p> <p></p> <p>The nitroimidazole-linked phenanthridine series of compounds (NLP-1, <span class="hlt">2</span>, and 3) were synthesized under the assumption that it should be possible to enhance the molar efficiency of <span class="hlt">2</span>-nitroimidazoles as hypoxic cell <span class="hlt">radiosensitizers</span> and cytotoxins by targeting them to their likely site of action, DNA. The targeting group chosen was the phenanthridine moiety, the major component of the classical DNA intercalating compound, ethidium bromide. The sole difference between the compounds is the length of the hydrocarbon chain linking the nitroimidazole to the phenanthridine. The phenanthridine group with a three-carbon side chain, P-1, was also synthesized to allow studies on the effect ofmore » the targeting group by itself. The ability of the compounds to bind to DNA is inversely proportional to their linker chain length with binding constant values ranging from approximately 1 {times} 10(5) mol-1 for NLP-<span class="hlt">2</span> to 6 {times} 10(5) mol-1 for NLP-3. The NLP compounds show selective toxicity to hypoxic cells at 37 degrees C at external drug concentrations 10-40 times lower than would be required for untargeted <span class="hlt">2</span>-nitroimidazoles such as misonidazole in vitro. Toxicity to both hypoxic and aerobic cells is dependent on the linker chain: the shorter the chain, the greater the toxicity. In addition, the NLP compounds <span class="hlt">radiosensitize</span> hypoxic cells at external drug concentrations as low as 0.05 mM with almost the full oxygen effect being observed at a concentration of 0.5 mM. These concentrations are 10-100 times lower than would be required for similar <span class="hlt">radiosensitization</span> using misonidazole. <span class="hlt">Radiosensitizing</span> ability is independent of linker chain length. The present compounds represent prototypes for further studies of the efficacy and mechanism of action of <span class="hlt">2</span>-nitroimidazoles targeted to DNA by linkage to an intercalating group.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5150255','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5150255"><span>Enhancing <span class="hlt">radiosensitization</span> in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bhatia, Shilpa; Hirsch, Kellen; Sharma, Jaspreet; Oweida, Ayman; Griego, Anastacia; Keysar, Stephen; Jimeno, Antonio; Raben, David; Krasnoperov, Valery; Gill, Parkash S.; Pasquale, Elena B.; Wang, Xiao-Jing; Karam, Sana D.</p> <p>2016-01-01</p> <p>Members of the Eph family of receptor tyrosine kinases have been implicated in a wide array of human cancers. The EphB4 receptor is ubiquitously expressed in head and neck squamous cell carcinoma (HNSCC) and has been shown to impart tumorigenic and invasive characteristics to these cancers. In this study, we investigated whether EphB4 receptor targeting can enhance the <span class="hlt">radiosensitization</span> of HNSCC. Our data show that EphB4 is expressed at high to moderate levels in HNSCC cell lines and patient-derived xenograft (PDX) tumors. We observed decreased survival fractions in HNSCC cells following EphB4 knockdown in clonogenic assays. An enhanced <span class="hlt">G</span><span class="hlt">2</span> cell cycle arrest with activation of DNA damage response pathway and increased apoptosis was evident in HNSCC cells following combined EphB4 downregulation and radiation compared to EphB4 knockdown and radiation alone. Data using HNSCC PDX models showed significant reduction in tumor volume and enhanced delay in tumor regrowth following sEphB4-HSA administration with radiation compared to single agent treatment. sEphB4-HSA is a protein known to block the interaction between the EphB4 receptor and its ephrin-B<span class="hlt">2</span> ligand. Overall, our findings emphasize the therapeutic relevance of EphB4 targeting as a <span class="hlt">radiosensitizer</span> that can be exploited for the treatment of human head and neck carcinomas. PMID:27941840</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078076','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078076"><span>Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-<span class="hlt">chromatid</span> cohesion in human cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kang, Jungseog; Chaudhary, Jaideep; Dong, Hui; Kim, Soonjoung; Brautigam, Chad A.; Yu, Hongtao</p> <p>2011-01-01</p> <p>Human Shugoshin 1 (Sgo1) protects centromeric sister-<span class="hlt">chromatid</span> cohesion during prophase and prevents premature sister-<span class="hlt">chromatid</span> separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-<span class="hlt">chromatid</span> cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1α is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1–INCENP and HP1–Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1α is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres. PMID:21346195</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26793285','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26793285"><span>Cisplatin <span class="hlt">Radiosensitization</span> of DNA Irradiated with <span class="hlt">2</span>-20 eV Electrons: Role of Transient Anions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bao, Qianhong; Chen, Yunfeng; Zheng, Yi; Sanche, Léon</p> <p>2014-06-20</p> <p>Platinum chemotherapeutic agents, such as cisplatin ( cis -diamminedichloroplatinum(II)), can act as <span class="hlt">radiosensitizers</span> when bound covalently to nuclear DNA in cancer cells. This <span class="hlt">radiosensitization</span> is largely due to an increase in DNA damage induced by low-energy secondary electrons, produced in large quantities by high-energy radiation. We report the yields of single- and double-strand breaks (SSB and DSB) and interduplex cross-links (CL) induced by electrons of 1.6-19.6 eV (i.e., the yield functions) incident on 5 monolayer (ML) films of cisplatin-DNA complexes. These yield functions are compared with those previously recorded with 5 ML films of unmodified plasmid DNA. Binding of five cisplatin molecules to plasmid DNA (3197 base pairs) enhances SSB, DSB, and CL by factors varying, from 1.<span class="hlt">2</span> to <span class="hlt">2</span>.8, 1.4 to 3.5, and 1.<span class="hlt">2</span> to <span class="hlt">2</span>.7, respectively, depending on electron energy. All yield functions exhibit structures around 5 and 10 eV that can be attributed to enhancement of bond scission, via the initial formation of core-excited resonances associated with π → π * transitions of the bases. This increase in damage is interpreted as arising from a modification of the parameters of the corresponding transient anions already present in nonmodified DNA, particularly those influencing molecular dissociation. Two additional resonances, specific to cisplatin-modified DNA, are formed at 13.6 and 17.6 eV in the yield function of SSB. Furthermore, cisplatin binding causes the induction of DSB by electrons of 1.6-3.6 eV, i.e., in an energy region where a DSB cannot be produced by a single electron in pure DNA. Breaking two bonds with a subexcitation-energy electron is tentatively explained by a charge delocalization mechanism, where a single electron occupies simultaneously two σ * bonds linking the Pt atom to guanine bases on opposite strands.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22645708-targeting-phosphatidylinositol-kinase-iii-radiosensitization-potential-model-drug-repositioning-using-anti-hepatitis-viral-agent','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22645708-targeting-phosphatidylinositol-kinase-iii-radiosensitization-potential-model-drug-repositioning-using-anti-hepatitis-viral-agent"><span>Targeting Phosphatidylinositol 4-Kinase IIIα for <span class="hlt">Radiosensitization</span>: A Potential Model of Drug Repositioning Using an Anti-Hepatitis C Viral Agent</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Kwon, Jeanny; Kim, Dan Hyo; Park, Ji Min</p> <p></p> <p>Purpose: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect <span class="hlt">radiosensitivity</span> and examine whether anti–hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a <span class="hlt">radiosensitizer</span> in human cancer cells. Methods and Materials: U251, BT474, and Hep<span class="hlt">G</span><span class="hlt">2</span> cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed. Results: Of the 4 PI4K isotypes, specific inhibition of IIIα increased <span class="hlt">radiosensitivity</span>. For pharmacologic inhibition of PI4K IIIα, we screened 9 anti-HCV agents by half-maximal inhibitorymore » concentration assay. Simeprevir was selected, and its inhibition of PI4K IIIα activity was confirmed. Combination of simeprevir treatment and radiation significantly attenuated expression of phospho-phospho-PKC and phospho-Akt and increased radiation-induced cell death in tested cell lines. Pretreatment with simeprevir prolonged γH<span class="hlt">2</span>AX foci formation and down-regulation of phospho-DNA-PKcs, indicating impairment of nonhomologous end-joining repair. Cells pretreated with simeprevir exhibited mixed modes of cell death, including apoptosis and autophagy. Conclusion: These data demonstrate that targeting PI4K IIIα using an anti-HCV agent is a viable approach to enhance the therapeutic efficacy of radiation therapy in various human cancers, such as glioma, breast, and hepatocellular carcinoma.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25812437','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25812437"><span>Simple <span class="hlt">radiosensitizing</span> of hypoxic tumor tissues by N<span class="hlt">2</span>O/Br(-) mixture.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Billik, P</p> <p>2015-07-01</p> <p>The <span class="hlt">radiosensitization</span> model of hypoxic tumor tissues based on the N<span class="hlt">2</span>O/Br(-) mixture is described. The well-documented radiolysis of water in the presence of N<span class="hlt">2</span>O and Br(-) ions at a low concentration supports this model. An aqueous solution saturated with N<span class="hlt">2</span>O gas during the radiolysis generates OH radicals in a large extent. In N<span class="hlt">2</span>O/Br- media at pH<9, Br<span class="hlt">2</span> is formed. Br<span class="hlt">2</span> hydrolyzes in an aqueous solution to form a very reactive hypobromous (HOBr) acid. Such process is described by the following chemical reaction: H<span class="hlt">2</span>O + Br(-) + N<span class="hlt">2</span>O + ionizing radiation (IR) --> HOBr + OH(-). In vivo formed HOBr as a long-lived product with a high biological activity induces the hypoxic tumor cell damage via many unique mechanisms. A local application or inhalation of an N<span class="hlt">2</span>O-O<span class="hlt">2</span> mixture before or during the radiotherapy to enhance the saturation of tissues with N<span class="hlt">2</span>O is a key prerequisite. Since the extracellular concentration of Br(-) ions is very low (0.02-0.05 mM), an oral or local application of NaBr should be used to shift the extracellular concentration of Br(-) ions to the mM region. Copyright © 2015 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3583813','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3583813"><span><span class="hlt">Radiosensitization</span> in prostate cancer: mechanisms and targets</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2013-01-01</p> <p>Prostate cancer is the second most commonly diagnosed cancer in American men over the age of 45 years and is the third most common cause of cancer related deaths in American men. In 2012 it is estimated that 241,740 men will be diagnosed with prostate cancer and 28,170 men will succumb to prostate cancer. Currently, radiation therapy is one of the most common definitive treatment options for localized prostate cancer. However, significant number of patients undergoing radiation therapy will develop locally persistent/recurrent tumours. The varying response rates to radiation may be due to 1) tumor microenvironment, <span class="hlt">2</span>) tumor stage/grade, 3) modality used to deliver radiation, and 4) dose of radiation. Higher doses of radiation has not always proved to be effective and have been associated with increased morbidity. Compounds designed to enhance the killing effects of radiation, <span class="hlt">radiosensitizers</span>, have been extensively investigated over the past decade. The development of <span class="hlt">radiosensitizing</span> agents could improve survival, improve quality of life and reduce costs, thus benefiting both patients and healthcare systems. Herin, we shall review the role and mechanisms of various agents that can sensitize tumours, specifically prostate cancer. PMID:23351141</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29762138','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29762138"><span>Theranostic gold-magnetite hybrid nanoparticles for MRI-guided <span class="hlt">radiosensitization</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Maniglio, D; Benetti, F; Minati, L; Jovicich, J; Valentini, A; Speranza, G; Migliaresi, C</p> <p>2018-08-03</p> <p>The main limitation of drug-enhanced radiotherapy concerns the difficulty to evaluate the effectiveness of cancer targeting after drug administration hindering the standardization of therapies based on current <span class="hlt">radiosensitizing</span> compounds. The challenge regards the development of systems able to combine imaging and radiotherapy enhancement in order to perform highly reliable cancer theragnosis. For these reasons, gold-magnetite hybrid nanoparticles (H-NPs) are proposed as innovative theranostic nanotools for imaging-guided <span class="hlt">radiosensitization</span> in cancer treatment. In this work we propose a novel method for the synthesis of hydrophilic and superparamagnetic Tween20-stabilized gold-magnetite H-NPs. Morphology and chemical composition of nanoparticles were assessed by transmission electron microscopy, x-ray diffraction analysis and ion-coupled plasma optical emission spectroscopy. Colloidal stability and magnetic properties of nanoparticles were determined by dynamic light scattering and magnetometry. The potentialities of H-NPs for magnetic resonance imaging were studied using a human 4T-MRI scanner. Nanoparticles were proven to induce concentration-dependent contrast enhancement in T<span class="hlt">2</span>*-weighted MR-images. The cytotoxicity, the cellular uptake and the <span class="hlt">radiosensitization</span> activity of H-NPs were investigated in human osteosarcoma MG63 cell cultures and murine 3T3 fibroblasts, using specific bioassays and laser scanning confocal microscopy. H-NPs did not exhibit significant toxicity and were demonstrated to be internalized by cells. A significant x-ray enhancement at specific H-NPs exposure concentrations was evidenced on MG63 cell line.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2007AdSpR..40.1408S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2007AdSpR..40.1408S"><span>Effects of low-level chronic irradiation on the <span class="hlt">radiosensitivity</span> of mammals: Modeling studies</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Smirnova, O. A.</p> <p></p> <p>Mathematical models of the major hematopoietic lines are used to study the modifying effects of low-level chronic preirradiation on <span class="hlt">radiosensitivity</span> of mammals which resulted in their reduced <span class="hlt">radiosensitivity</span> (acquired radioresistance) and elevated <span class="hlt">radiosensitivity</span> (hypersensitivity) to the subsequent radiation exposure. These effects of preirradiation manifest themselves, respectively, in decreased and increased mortality of preirradiated experimental animals (mice) after challenge acute exposure in comparison with that for previously nonirradiated ones. Analysis of the modeling results reveals the biological mechanisms of these radioprotection and <span class="hlt">radiosensitization</span> effects, and enables one to estimate the ranges of dose rate and duration of chronic preirradiation where these effects are realized. Juxtapositions of the modeling predictions with the relevant experimental data show their qualitative agreement. All this testifies to the importance of accounting the nonlinear effect of low-level chronic irradiation on <span class="hlt">radiosensitivity</span> of the hematopoiesis system and organism as a whole, when the radiation risk for astronauts on long-term space missions is estimated. The developed models of hematopoiesis can be used, after appropriate identification, as a component of the mathematical tools for radiation risk assessment.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6098026-nlp-dna-intercalating-hypoxic-cell-radiosensitizer-cytotoxin','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6098026-nlp-dna-intercalating-hypoxic-cell-radiosensitizer-cytotoxin"><span>NLP-1: a DNA intercalating hypoxic cell <span class="hlt">radiosensitizer</span> and cytotoxin</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Panicucci, R.; Heal, R.; Laderoute, K.</p> <p></p> <p>The <span class="hlt">2</span>-nitroimidazole linked phenanthridine, NLP-1 (5-(3-(<span class="hlt">2</span>-nitro-1-imidazoyl)-propyl)-phenanthridinium bromide), was synthesized with the rationale of targeting the nitroimidazole to DNA via the phenanthridine ring. The drug is soluble in aqueous solution (greater than 25 mM) and stable at room temperature. It binds to DNA with a binding constant 1/30 that of ethidium bromide. At a concentration of 0.5 mM, NLP-1 is 8 times more toxic to hypoxic than aerobic cells at 37 degrees C. This concentration is 40 times less than the concentration of misonidazole, a non-intercalating <span class="hlt">2</span>-nitroimidazole, required for the same degree of hypoxic cell toxicity. The toxicity of NLP-1 ismore » reduced at least 10-fold at 0 degrees C. Its ability to <span class="hlt">radiosensitize</span> hypoxic cells is similar to misonidazole at 0 degrees C. Thus the putative targeting of the <span class="hlt">2</span>-nitroimidazole, NLP-1, to DNA, via its phenanthridine group, enhances its hypoxic toxicity, but not its <span class="hlt">radiosensitizing</span> ability under the present test conditions. NLP-1 represents a lead compound for intercalating <span class="hlt">2</span>-nitroimidazoles with selective toxicity for hypoxic cells.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12132876','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12132876"><span>Comparative study of sister <span class="hlt">chromatid</span> exchange induction and antitumor effects by homo-aza-steroidal esters of [p-[bis(<span class="hlt">2</span>-chloroethyl)amino]phenyl]butyric acid.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Camoutsis, C; Catsoulacos, D; Karayiann, V; Papageorgiou, A; Mourelatos, D; Mioglou, E; Kritsi, Z; Nikolaropoulos, S</p> <p>2001-01-01</p> <p>The present work was undertaken in order to test the hypothesis that the Sister <span class="hlt">Chromatid</span> Exchange (SCE) assay in vitro can be used for the prediction of in vivo tumor response to newly synthesized potential chemotherapeutics. The effect of three homo-aza-steroidal esters containing the -CONH- in the steroidal nucleus, 1, <span class="hlt">2</span>, and 3 on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The three substances induced statistically significant enhancement of SCEs and of cell division delays. Compounds 1 and 3 were identified, on a molar basis, as more effective inducers of SCEs and of cell division delays compared with compound <span class="hlt">2</span>. Compounds 1 and 3 had upon both experimental tumors better therapeutic effects compared with compound <span class="hlt">2</span> at equitoxic doses. Therefore, the order of the antitumor effectiveness of the three compounds coincided with the order of the cytogenetic effects they induced.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25681274','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25681274"><span>Tumor <span class="hlt">radiosensitization</span> by monomethyl auristatin E: mechanism of action and targeted delivery.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Buckel, Lisa; Savariar, Elamprakash N; Crisp, Jessica L; Jones, Karra A; Hicks, Angel M; Scanderbeg, Daniel J; Nguyen, Quyen T; Sicklick, Jason K; Lowy, Andrew M; Tsien, Roger Y; Advani, Sunil J</p> <p>2015-04-01</p> <p>Intrinsic tumor resistance to radiotherapy limits the efficacy of ionizing radiation (IR). Sensitizing cancer cells specifically to IR would improve tumor control and decrease normal tissue toxicity. The development of tumor-targeting technologies allows for developing potent <span class="hlt">radiosensitizing</span> drugs. We hypothesized that the anti-tubulin agent monomethyl auristatin E (MMAE), a component of a clinically approved antibody-directed conjugate, could function as a potent <span class="hlt">radiosensitizer</span> and be selectively delivered to tumors using an activatable cell-penetrating peptide targeting matrix metalloproteinases and RGD-binding integrins (ACPP-cRGD-MMAE). We evaluated the ability of MMAE to <span class="hlt">radiosensitize</span> both established cancer cells and a low-passage cultured human pancreatic tumor cell line using clonogenic and DNA damage assays. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule- and dose-dependent manner, correlating with mitotic arrest. <span class="hlt">Radiosensitization</span> was evidenced by decreased clonogenic survival and increased DNA double-strand breaks in irradiated cells treated with MMAE. MMAE in combination with IR resulted in increased DNA damage signaling and activation of CHK1. To test a therapeutic strategy of MMAE and IR, PANC-1 or HCT-116 murine tumor xenografts were treated with nontargeted free MMAE or tumor-targeted MMAE (ACPP-cRGD-MMAE). While free MMAE in combination with IR resulted in tumor growth delay, tumor-targeted ACPP-cRGD-MMAE with IR produced a more robust and significantly prolonged tumor regression in xenograft models. Our studies identify MMAE as a potent <span class="hlt">radiosensitizer</span>. Importantly, MMAE <span class="hlt">radiosensitization</span> can be localized to tumors by targeted activatable cell-penetrating peptides. ©2015 American Association for Cancer Research.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_7");'>7</a></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li class="active"><span>9</span></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_9 --> <div id="page_10" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li class="active"><span>10</span></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="181"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4458508','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4458508"><span>Tumor <span class="hlt">radiosensitization</span> by monomethyl auristatin E: mechanism of action and targeted delivery</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Crisp, Jessica L.; Jones, Karra A.; Hicks, Angel M.; Scanderbeg, Daniel J.; Nguyen, Quyen T.; Sicklick, Jason K.; Lowy, Andrew M.; Tsien, Roger Y.; Advani, Sunil J.</p> <p>2015-01-01</p> <p>Intrinsic tumor resistance to radiotherapy limits the efficacy of ionizing radiation (IR). Sensitizing cancer cells specifically to IR would improve tumor control and decrease normal tissue toxicity. The development of tumor targeting technologies allows for developing potent <span class="hlt">radiosensitizing</span> drugs. We hypothesized that the anti-tubulin agent monomethyl auristatin E (MMAE), a component of a clinically approved antibody-directed conjugate, could function as a potent <span class="hlt">radiosensitizer</span> and be selectively delivered to tumors using an activatable cell penetrating peptide targeting matrix metalloproteinases and RGD binding integrins (ACPP-cRGD-MMAE). We evaluated the ability of MMAE to <span class="hlt">radiosensitize</span> both established cancer cells and a low passage cultured human pancreatic tumor cell line using clonogenic and DNA damage assays. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule and dose dependent manner correlating with mitotic arrest. <span class="hlt">Radiosensitization</span> was evidenced by decreased clonogenic survival and increased DNA double strand breaks in irradiated cells treated with MMAE. MMAE in combination with IR resulted in increased DNA damage signaling and activation of CHK1. To test a therapeutic strategy of MMAE and IR, PANC-1 or HCT-116 murine tumor xenografts were treated with non-targeted free MMAE or tumor targeted MMAE (ACPP-cRGD-MMAE). While free MMAE in combination with IR resulted in tumor growth delay, tumor targeted ACPP-cRGD-MMAE with IR produced a more robust and significantly prolonged tumor regression in xenograft models. Our studies identify MMAE as a potent <span class="hlt">radiosensitizer</span>. Importantly, MMAE <span class="hlt">radiosensitization</span> can be localized to tumors by targeted activatable cell penetrating peptides. PMID:25681274</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22648697-wee1-kinase-inhibitor-azd1775-radiosensitizes-hepatocellular-carcinoma-regardless-tp53-mutational-status-through-induction-replication-stress','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22648697-wee1-kinase-inhibitor-azd1775-radiosensitizes-hepatocellular-carcinoma-regardless-tp53-mutational-status-through-induction-replication-stress"><span>Wee1 Kinase Inhibitor AZD1775 <span class="hlt">Radiosensitizes</span> Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Cuneo, Kyle C., E-mail: kcuneo@umich.edu; Morgan, Meredith A.; Davis, Mary A.</p> <p>2016-06-01</p> <p>Purpose: Wee1 kinase inhibitors are effective <span class="hlt">radiosensitizers</span> in cells lacking a <span class="hlt">G</span>{sub 1} checkpoint. In this study we examined the potential effect of Wee1 kinase inhibition on inducing replication stress in hepatocellular carcinoma (HCC). Methods and Materials: Five independent datasets from the Oncomine database comparing gene expression in HCC compared to normal tissue were combined and specific markers associated with Wee1 sensitivity were analyzed. We then performed a series of in vitro experiments to study the effect of Wee1 inhibition on irradiated HCC cell lines with varying p53 mutational status. Clonogenic survival assays and flow cytometry using anti-γH<span class="hlt">2</span>AX and phospho-histone H3more » antibodies with propidium iodide were performed to study the effect of AZD1775 on survival, cell cycle, and DNA repair. Additionally, nucleoside enriched medium was used to examine the effect of altering nucleotide pools on Wee1 targeted radiation sensitization. Results: Our analysis of the Oncomine database found high levels of CDK1 and other cell cycle regulators indicative of Wee1 sensitivity in HCC. In our in vitro experiments, treatment with AZD1775 <span class="hlt">radiosensitized</span> and chemosensitized Hep3B, Huh7, and Hep<span class="hlt">G</span><span class="hlt">2</span> cell lines and was associated with delayed resolution of γH<span class="hlt">2</span>AX foci and the induction of pan-nuclear γH<span class="hlt">2</span>AX staining. Wee1 inhibition attenuated radiation-induced <span class="hlt">G</span>{sub <span class="hlt">2</span>} arrest in the Hep3B (TP53 null) and Huh7 (TP53 mutant) cell lines but not in the TP53 wild-type cell line Hep<span class="hlt">G</span><span class="hlt">2</span>. Supplementation with nucleosides reversed the radiation-sensitizing effect of AZD1775 and reduced the amount of cells with pan-nuclear γH<span class="hlt">2</span>AX staining after radiation. Conclusions: Radiation sensitization with Wee1 inhibition occurs in cells regardless of their p53 mutational status. In this study we show for the first time that replication stress via the overconsumption of nucleotides plays an important role in AZD1775-induced radiation sensitization.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29848680','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29848680"><span>SN-38 Acts as a <span class="hlt">Radiosensitizer</span> for Colorectal Cancer by Inhibiting the Radiation-induced Up-regulation of HIF-1α.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Okuno, Takayuki; Kawai, Kazushige; Hata, Keisuke; Murono, Koji; Emoto, Shigenobu; Kaneko, Manabu; Sasaki, Kazuhito; Nishikawa, Takeshi; Tanaka, Toshiaki; Nozawa, Hiroaki</p> <p>2018-06-01</p> <p>Hypoxia offers resistance to therapy in human solid tumors. The aim of the study was to investigate whether SN-38, the active metabolite of irinotecan, acts as a <span class="hlt">radiosensitizer</span> through inhibition of hypoxia-inducible factor (HIF)-1α in the human colorectal cancer (CRC) cells. HT29 and SW480 cells were cultured with SN-38 (0-4 μM) immediately after irradiation (0-8 Gy). HIF-1α expression was assessed using flow-cytometry and western blot analysis. Cell proliferation was evaluated by the calcein assay. Apoptosis and cell cycle were determined by flow-cytometry. Radiation up-regulated HIF-1α, and SN-38 inhibited the radiation-induced HIF-1α. The combination of radiation and SN-38 inhibited cell proliferation more than radiation alone; treatment with SN-38 after radiation exposure did not increase the number of apoptotic cells, whereas, it enhanced the S and <span class="hlt">G</span> <span class="hlt">2</span> /M cell-cycle arrest and decreased the population of cells in <span class="hlt">G</span> 1 Conclusion: SN-38 inhibits the radiation-induced up-regulation of HIF-1α and acts as a <span class="hlt">radiosensitizer</span> by inducing cell-cycle arrest in CRC cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010AIPC.1204..243W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010AIPC.1204..243W"><span>Chromosomal <span class="hlt">Radiosensitivity</span> in Lymphocytes of Cervix Cancer Patients—Correlation with Side Effect after Radiotherapy</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wegierek-Ciuk, Aneta; Lankoff, Anna; Lisowska, Halina; Banasik-Nowak, Anna; Arabski, Michał; Kedzierawski, Piotr; Florek, Agnieszka; Wojcik, Andrzej</p> <p>2010-01-01</p> <p>It is well known that cancer patients receiving similar radiotherapy treatments differ widely in normal tissue reactions ranging from undetectable to unacceptably severe levels. Therefore, an important goal of radiobiological research is to establish a test which would allow identifying individual <span class="hlt">radiosensitivity</span> of patients prior to radiotherapy. The aim of the presented study is to assess the relationship between lymphocyte intrinsic <span class="hlt">radiosensitivity</span> in vitro and early reaction of normal tissue in cervix cancer patients treated by radiotherapy. The following endpoints are analyzed in vitro: frequency of micronuclei, the kinetics of DNA repair and apoptosis. Acute normal tissue reaction to radiotherapy in the skin, bladder and rectum are scored according to the EORTC/RTOG scale. Our results show a wide inter-individual variability in chromosomal <span class="hlt">radiosensitivity</span> in vitro. The majority of patients show a Grade 0, 1 or <span class="hlt">2</span> reaction for all organs studied. No statistically significant correlation has been observed between the in vitro results in lymphocytes and the degree of early normal tissue and organ reaction.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4692194','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4692194"><span>Roadmap to clinical use of gold nanoparticles for <span class="hlt">radiosensitization</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Schuemann, J.; Berbeco, R.; Chithrani, B. D.; Cho, S.; Kumar, R.; McMahon, S.; Sridhar, S.; Krishnan, S.</p> <p>2015-01-01</p> <p>The past decade has seen a dramatic increase in interest in the use of Gold Nanoparticles (GNPs) as radiation sensitizers for radiotherapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs’ efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X-rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated <span class="hlt">radiosensitization</span> to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes and preparations. As a result, mechanisms of uptake and <span class="hlt">radiosensitization</span> have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their <span class="hlt">radiosensitizing</span> properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as <span class="hlt">radiosensitizers</span>, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage. PMID:26700713</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5906031','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5906031"><span>Inhibition of STAT-3 Results in <span class="hlt">Radiosensitization</span> of Human Squamous Cell Carcinoma</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bonner, James A.; Trummell, Hoa Q.; Willey, Christopher D.; Plants, Brian A.; Raisch, Kevin P.</p> <p>2009-01-01</p> <p>Background Signal Transducer and Activator of Transcription – 3 (STAT-3) is a downstream component of the Epidermal Growth Factor Receptor (EGFr) signaling process that may facilitate the resistance of tumor cells to conventional cancer treatments. Studies were performed to determine if inhibition of this downstream protein may produce <span class="hlt">radiosensitization</span>. Methods/Results A431 cells (human squamous cell carcinoma cells with EGFr overexpression) were found to be sensitized to radiation after treatment with STAT-3 small interfering RNA (siRNA). Therefore, a short hairpin RNA (shRNA) against STAT-3 was designed and cloned into a pBABE vector system modified for shRNA expression. Following transfection, clone <span class="hlt">2</span>.1 was selected for further study as it showed a dramatic reduction of STAT-3 protein (and mRNA) when compared to A431 parental cells or a negative control shRNA cell line (transfected with STAT-3 shRNA with <span class="hlt">2</span> base pairs mutated). A431 <span class="hlt">2</span>.1 showed doubling times of 25-31 h as compared to 18-24 h for the parental cell line. The A431 shRNA knockdown STAT-3 cells A431 were more sensitive to radiation than A431 parental or negative STAT-3 control cells. Conclusion A431 cells stably transfected with shRNA against STAT-3 resulted in enhanced <span class="hlt">radiosensitivity</span>. Further work will be necessary to determine whether inhibition of STAT-3 phosphorylation is a necessary step for the <span class="hlt">radiosensitization</span> that is induced by inhibition of EGFr. PMID:19616333</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7168826','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7168826"><span>Cyclophosphamide induced in vivo sister <span class="hlt">chromatid</span> exchanges (SCE) in Mus musculus. I: Strain differences and empirical association with relative chromosome size.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Reimer, D L; Singh, S M</p> <p>1982-01-01</p> <p>The inducibility of sister <span class="hlt">chromatid</span> exchanges (SCEs) by cyclophosphamide (CP) in bone marrow cells was evaluated in vivo in the three genetic strains of mice (C3H/s, C57BL/6J, and Balb/c). Female mice (10 to 12 wks old, mean = 22.9<span class="hlt">g</span>, SD = 3.<span class="hlt">2</span><span class="hlt">g</span>) were administered with nine hourly injections of 214.19 mg/kg 5-Bromo-<span class="hlt">2</span>' deoxyuridine (BrdU) followed by 0, 0.048, 0.449, 4.585 or 46.93 mg/kg CP and 4 mg/kg colcemid. SCEs were evaluated following differential staining procedures of Perry and Wolff (1974). The base-line SCEs were similar in all strains with about ten SCEs/cell. Increasing CP concentrations yielded an increased level of SCEs. Most cells showed extensive damage in CP doses exceeding 4.55 mg/kg. No SCE evaluation was possible beyond this concentration. Strain differences were evident at every dose of CP, and Balb/c was the least susceptible strain to SCE induction. F1 hybrids involving C3H/s female and Balb/c male showed SCE values closer to Balb/c. Data on the association between chromosome length and frequency of SCEs are provided. They empirically establish a positive correlation (r = 0.90) between the two features. Most induced SCEs were interstitially located rather than terminally positioned on the chromosome.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/7302781-corynebacterium-parvum-induced-radiosensitivity-cycling-changes-hematopoietic-spleen-colony-forming-units','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/7302781-corynebacterium-parvum-induced-radiosensitivity-cycling-changes-hematopoietic-spleen-colony-forming-units"><span>Corynebacterium parvum-induced <span class="hlt">radiosensitivity</span> and cycling changes of hematopoietic spleen colony-forming units</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Maruyama, Y.; Magura, C.; Feola, J.</p> <p>1977-07-01</p> <p>Ten days after total-body irradiation with 550 rads of /sup 60/Co, spleen colonies were observed in adult C57BL mice. A change in <span class="hlt">radiosensitivity</span> induced by Corynebacterium parvum, as measured by increased numbers of colony-forming units that survived the 550 rads, began shortly after C. parvum stimulation and extended for at least 7 days before irradiation. C. parvum given 4-24 hours before, followed by high specific activity (/sup 3/H)thymidine (HSATT) 1 hour before total-body irradiation greatly reduced survival of the stem cells that formed spleen colonies (CFU/sub s/) and CFU/sub s/ <span class="hlt">radiosensitivity</span> to control levels. The HSATT sensitivity by ''suicide'' assaymore » in vivo and the time-response change in <span class="hlt">radiosensitivity</span> corresponded with the decrease in <span class="hlt">radiosensitivity</span>, which showed that CFU/sub s/ were stimulated by C. parvum administration and entered the S-phase shortly after stimulation. The data indicated a resting population close to the S-phase. After stimulation, this population entered S-phase. Syngeneic mouse lymphoma cells injected iv 24 hours earlier did not elicit any effect as a stimulus to CFU/sub s/ <span class="hlt">radiosensitivity</span> change.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16131840','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16131840"><span>Telomere sister <span class="hlt">chromatid</span> exchange in telomerase deficient murine cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Yisong; Giannone, Richard J; Liu, Yie</p> <p>2005-10-01</p> <p>We have recently demonstrated that several types of genomic rearrangements (i.e., telomere sister <span class="hlt">chromatid</span> exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells' gained ability to protect chromosome ends with eroded telomeres allowing them to escape "end crisis". However, the possibility that ES cells were more permissive to genomic rearrangements than other cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19507186','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19507186"><span><span class="hlt">Radiosensitization</span> of HT-29 cells and xenografts by the nitric oxide donor DETANONOate.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gao, Xiaohuan; Saha, Debabrata; Kapur, Payal; Anthony, Thomas; Livingston, Edward H; Huerta, Sergio</p> <p>2009-08-01</p> <p>Mechanisms of radioresistance in rectal cancer remain unclear. To determine mechanisms of radioresistance in rectal cancer cells and to assess the role of the nitric oxide donor DETANONOate as a <span class="hlt">radiosensitizing</span> agent. Survival was determined by clonogenic assays, apoptosis by PARP-1 cleavage, and phenotypic differences by Western blot analysis. SCID mice bearing HT-29 xenografts were treated with ionizing radiation (IR) [<span class="hlt">2</span>.0 Gy x 5], DETANONOate [0.4 mg/kg i.p.], or combination treatment. Colorectal cancer HT-29-p53-null cells were resistant and HCT-116-p53 wild-type cells sensitive to IR, which correlated with cleaved PARP-1. Increased levels of p21 occurred in HCT-116 cells, while Bcl-<span class="hlt">2</span> and survivin were elevated in HT-29 cells. <span class="hlt">Radiosensitization</span> was achieved with a substantial elevation of cleaved PARP-1 in DETANONOate-HT-29-treated versus control cells, which was accompanied by elevation of p21, p27, and BAX, and a concomitant decrease in Bcl-<span class="hlt">2</span>. SCID mice bearing HT-29 xenografts demonstrated a 37.6%, 51.1%, and 70.1% inhibition in tumor growth in mice receiving IR, DETANONOate, and combination treatment versus control, respectively. Radioresistant HT-29 cells are p53-null and have substantially decreased levels of p21. DETANONOate <span class="hlt">radiosensitized</span> HT-29 cells in vitro and in vivo by an additive effect in apoptosis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22867891','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22867891"><span>Short hairpin RNA suppression of thymidylate synthase produces DNA mismatches and results in excellent <span class="hlt">radiosensitization</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Flanagan, Sheryl A; Cooper, Kristin S; Mannava, Sudha; Nikiforov, Mikhail A; Shewach, Donna S</p> <p>2012-12-01</p> <p>To determine the effect of short hairpin ribonucleic acid (shRNA)-mediated suppression of thymidylate synthase (TS) on cytotoxicity and <span class="hlt">radiosensitization</span> and the mechanism by which these events occur. shRNA suppression of TS was compared with 5-fluoro-<span class="hlt">2</span>'-deoxyuridine (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29 colon cancer cells. Cytotoxicity and <span class="hlt">radiosensitization</span> were measured by clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid (DNA) were analyzed by high-pressure liquid chromatography and as pSP189 plasmid mutations, respectively. TS shRNA produced profound (≥ 90%) and prolonged (≥ 8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd increased TS expression. TS shRNA also produced more specific and prolonged effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA suppression allowed accumulation of cells in S-phase, although its effects were not as long-lasting as those of FdUrd. Both treatments resulted in phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was equally effective as FdUrd in eliciting <span class="hlt">radiosensitization</span> (radiation enhancement ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar increase in the number and type of pSP189 mutations. TS shRNA produced less cytotoxicity than FdUrd but was equally effective at <span class="hlt">radiosensitizing</span> tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is sufficient to elicit <span class="hlt">radiosensitization</span> with FdUrd, but it only partially explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for the depletion of dTTP thymidine triphosphate and consequent DNA mismatches underlying <span class="hlt">radiosensitization</span>. Importantly, sh</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20630917','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20630917"><span>Genotoxic assessment in peripheral blood lymphocytes of post-polio individuals using sister <span class="hlt">chromatid</span> exchange analysis and micronucleus assay.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bhattacharya, Saurabh Kumar; Saraswathy, Radha; Sivakumar, E</p> <p>2011-07-01</p> <p>Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organism levels. Past studies in virus have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, in the present study, we attempt to characterize damage occurring through genotoxic agents like 5-bromo-<span class="hlt">2</span>-deoxyuridine, BrdU, using sister <span class="hlt">chromatid</span> exchange technique and the formation of micronuclei (MN) in the peripheral lymphocytes of the post-polio syndrome sequelae affected by poliovirus. Analysis of structural chromosomal aberrations (CAs) and involvement of the specific chromosome break were pursued in this study. They revealed a significantly higher incidence of CAs (<span class="hlt">chromatid</span> and chromosome breaks) in patients compared with controls, where the specific chromosome break has emerged as specific. Also, the maximum numbers of breaks were found to be in chromosome 1 at the position 1p36.1. The results also suggest a correlation between CAs and content of MN.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19460134','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19460134"><span>The combination effect of sodium butyrate and 5-Aza-<span class="hlt">2</span>'-deoxycytidine on <span class="hlt">radiosensitivity</span> in RKO colorectal cancer and MCF-7 breast cancer cell lines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cho, Hang Joo; Kim, Sin Young; Kim, Kee Hwan; Kang, Won Kyung; Kim, Ji Il; Oh, Seong Tack; Kim, Jeong Soo; An, Chang Hyeok</p> <p>2009-05-21</p> <p>The overall level of chromatin compaction is an important mechanism of <span class="hlt">radiosensitivity</span>, and modification of DNA methylation and histone deacetylation may increase <span class="hlt">radiosensitivity</span> by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC) inhibitor, and the two agents combined on <span class="hlt">radiosensitivity</span> in human colon and breast cancer cell lines. In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB), the demethylating agent 5-Aza-<span class="hlt">2</span>'-deoxycytidine(5-aza-DC), and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods. After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p < 0.001). The survival fraction was lowest when the two agents, 5-aza-DC and SB were combined with radiation in both RKO and MCF-cell lines. In conclusion, 5-aza-DC and SB can enhance <span class="hlt">radiosensitivity</span> in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27115167','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27115167"><span>Rockets, <span class="hlt">radiosensitizers</span>, and RRx-001: an origin story part I.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Oronsky, Bryan; Scicinski, Jan; Ning, Shoucheng; Peehl, Donna; Oronsky, Arnold; Cabrales, Pedro; Bednarski, Mark; Knox, Susan</p> <p>2016-03-01</p> <p>From Adam and Eve, to Darwinism, origin stories attempt to fill in the blanks, connect the dots, and define the turning points that are fundamental to subsequent developments. The purpose of this review is to present the origin story of a one-of-a-kind anticancer agent, RRx-001, which emerged from the aerospace industry as a putative <span class="hlt">radiosensitizer</span>; not since the dynamite-to-dilator transformation of nitroglycerin in 1878 or the post-World War II explosive-to-elixir conversion of hydralazine, an ingredient in rocket fuel, to an antihypertensive, an antidepressant and an antituberculant, has energetic chemistry been harnessed for therapeutic purposes. This is Part 1 of the <span class="hlt">radiosensitization</span> story; Parts <span class="hlt">2</span> and 3, which detail the crossover activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21372116-differential-radiosensitizing-effect-valproic-acid-differentiation-versus-self-renewal-promoting-culture-conditions','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21372116-differential-radiosensitizing-effect-valproic-acid-differentiation-versus-self-renewal-promoting-culture-conditions"><span>Differential <span class="hlt">Radiosensitizing</span> Effect of Valproic Acid in Differentiation Versus Self-Renewal Promoting Culture Conditions</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Debeb, Bisrat G.; Xu Wei; Mok, Henry</p> <p>2010-03-01</p> <p>Purpose: It has been shown that valproic acid (VA) enhances the proliferation and self-renewal of normal hematopoietic stem cells and that breast cancer stem/progenitor cells can be resistant to radiation. From these data, we hypothesized that VA would fail to <span class="hlt">radiosensitize</span> breast cancer stem/progenitor cells grown to three-dimensional (3D) mammospheres. Methods and Materials: We used the MCF7 breast cancer cell line grown under stem cell-promoting culture conditions (3D mammosphere) and standard nonstem cell monolayer culture conditions (two-dimensional) to examine the effect of pretreatment with VA on radiation sensitivity in clonogenic survival assays and on the expression of embryonic stem cellmore » transcription factors. Results: 3D-cultured MCF-7 cells expressed higher levels of Oct4, Nanog, and Sox<span class="hlt">2</span>. The 3D passage enriched self-renewal and increased radioresistance in the 3D mammosphere formation assays. VA <span class="hlt">radiosensitized</span> adherent cells but radioprotected 3D cells in single-fraction clonogenic assays. Moreover, fractionated radiation sensitized VA-treated adherent MCF7 cells but did not have a significant effect on VA-treated single cells grown to mammospheres. Conclusion: We have concluded that VA might preferentially <span class="hlt">radiosensitize</span> differentiated cells compared with those expressing stem cell surrogates and that stem cell-promoting culture is a useful tool for in vitro evaluation of novel cancer therapeutic agents and <span class="hlt">radiosensitizers</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23953409','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23953409"><span><span class="hlt">Radiosensitivity</span> and effect of hypoxia in HPV positive head and neck cancer cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sørensen, Brita Singers; Busk, Morten; Olthof, Nadine; Speel, Ernst-Jan; Horsman, Michael R; Alsner, Jan; Overgaard, Jens</p> <p>2013-09-01</p> <p>HPV associated Head and Neck Squamous Cell Carcinoma (HNSCC) represents a distinct subgroup of HNSCC characterized by a favorable prognosis and a distinct molecular biology. Previous data from the randomized DAHANCA 5 trial indicated that HPV positive tumors did not benefit from hypoxic modifications by Nimorazole during radiotherapy, whereas a significant benefit was observed in the HPV negative tumors. However, more studies have demonstrated equal frequencies of hypoxic tumors among HPV-positive and HPV-negative tumors. The aim of the present study was to determine <span class="hlt">radiosensitivity</span>, the impact of hypoxia and the effect of Nimorazole in HPV positive and HPV negative cell lines. The used cell lines were: UDSCC<span class="hlt">2</span>, UMSCC47 and UPCISCC90 (HPV positive) and FaDuDD, UTSCC33 and UTSCC5 (HPV negative). Cells were cultured under normoxic or hypoxic conditions, and gene expression levels of previously established hypoxia induced genes were assessed by qPCR. Cells were irradiated with various doses under normoxia, hypoxia or hypoxia +1mM Nimorazole, and the clonogenic survival was determined. The HPV positive and HPV negative cell lines exhibited similar patterns of upregulation of hypoxia induced genes in response to hypoxia. The HPV positive cell lines were up to <span class="hlt">2</span>.4 times more radiation sensitive than HPV negative cell lines. However, all HPV positive cells displayed the same response to hypoxia in <span class="hlt">radiosensitivity</span>, with an OER in the range <span class="hlt">2.3-2</span>.9, and a sensitizer effect of Nimorazole of 1.13-1.29, similar to HPV negative cells. Although HPV positive cells had a markedly higher <span class="hlt">radiosensitivity</span> compared to HPV negative cells, they displayed the same relative radioresistance under hypoxia and the same relative sensitizer effect of Nimorazole. The clinical observation that HPV positive patients do not seem to benefit from Nimorazole treatment is not due to inherent differences in hypoxia sensitivity or response to Nimorazole, but can be accounted for by the overall higher</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=39928&Lab=ORD&keyword=infusion&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=39928&Lab=ORD&keyword=infusion&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>INDUCTION, ACCUMULATION, AND PERSISTENCE OF SISTER <span class="hlt">CHROMATID</span> EXCHANGES IN WOMEN WITH BREAST CANCER RECEIVING CYCLOPHOSPHAMIDE, ANDRIAMYCIN, AND 5-FLUOROACIL CHEMOTHERAPY</span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>The induction, stimulation, and persistence of sister <span class="hlt">chromatid</span> exchanges (SCE's) and high SCE frequency cells (HFC's) was measured in peripheral lymphocytes of women with breast cancer before chemotherapy and on multiple occasions during and after therapy. Chemotherapy consisted...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22416970-suppression-autophagy-augments-radiosensitizing-effects-stat3-inhibition-human-glioma-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22416970-suppression-autophagy-augments-radiosensitizing-effects-stat3-inhibition-human-glioma-cells"><span>Suppression of autophagy augments the <span class="hlt">radiosensitizing</span> effects of STAT3 inhibition on human glioma cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Yuan, Xiaopeng; Du, Jie; Hua, Song</p> <p></p> <p>Radiotherapy is an essential component of the standard therapy for newly diagnosed glioblastoma. To increase the <span class="hlt">radiosensitivity</span> of glioma cells is a feasible solution to improve the therapeutic effects. It has been suggested that inhibition of signal transducer and activator of transcription 3 (STAT3) can <span class="hlt">radiosensitize</span> glioma cells, probably via the activation of mitochondrial apoptotic pathway. In this study, human malignant glioma cells, U251 and A172, were treated with an STAT3 inhibitor, WP1066, or a short hairpin RNA plasmid targeting STAT3 to suppress the activation of STAT3 signaling. The <span class="hlt">radiosensitizing</span> effects of STAT3 inhibition were confirmed in glioma cells. Intriguingly,more » combination of ionizing radiation exposure and STAT3 inhibition triggered a pronounced increase of autophagy flux. To explore the role of autophagy, glioma cells were treated with 3-methyladenine or siRNA for autophagy-related gene 5, and it was demonstrated that inhibition of autophagy further strengthened the <span class="hlt">radiosensitizing</span> effects of STAT3 inhibition. Accordingly, more apoptotic cells were induced by the dual inhibition of autophagy and STAT3 signaling. In conclusion, our data revealed a protective role of autophagy in the <span class="hlt">radiosensitizing</span> effects of STAT3 inhibition, and inhibition of both autophagy and STAT3 might be a potential therapeutic strategy to increase the <span class="hlt">radiosensitivity</span> of glioma cells. - Highlights: • Inactivation of STAT3 signaling <span class="hlt">radiosensitizes</span> malignant glioma cells. • STAT3 inhibition triggers a significant increase of autophagy flux induced by ionizing radiation in glioma cells. • Suppression of autophagy further strengthens the <span class="hlt">radiosensitizing</span> effects of STAT3 inhibition in glioma cells. • Dual inhibition of autophagy and STAT3 induce massive apoptotic cells upon exposure to ionizing radiation.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28452253','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28452253"><span>Radiation dose rate affects the <span class="hlt">radiosensitization</span> of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Khoshgard, Karim; Kiani, Parvaneh; Haghparast, Abbas; Hosseinzadeh, Leila; Eivazi, Mohammad Taghi</p> <p>2017-08-01</p> <p>The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced <span class="hlt">radiosensitivity</span> by dextran-coated iron oxide in cancer cells. HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 μ<span class="hlt">g</span>/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more <span class="hlt">radiosensitivity</span> effect by increasing the dose rate and nanoparticles concentration. <span class="hlt">Radiosensitization</span> enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 μ<span class="hlt">g</span>/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the <span class="hlt">radiosensitization</span> induced by the dextran-coated iron nanoparticles in these cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16327218','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16327218"><span>Prediction of cellular <span class="hlt">radiosensitivity</span> from DNA damage induced by gamma-rays and carbon ion irradiation in canine tumor cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wada, Seiichi; Van Khoa, Tran; Kobayashi, Yasuhiko; Funayama, Tomoo; Ogihara, Kikumi; Ueno, Shunji; Ito, Nobuhiko</p> <p>2005-11-01</p> <p>Diseases of companion animals are shifting from infectious diseases to neoplasms (cancer), and since radiation therapy is one of the effective choices available for cancer treatment, the application of radiotherapy in veterinary medicine is likely to increase. However tumor tissues have different <span class="hlt">radiosensitivities</span>, and therefore it is important to determine the intrinsic <span class="hlt">radiosensitivity</span> of tumors in individual patients in advance of radiotherapy. We have studied the relationship between the surviving cell fraction measured by a clonogenic assay and DNA double strand breaks detected by a comet assay under neutral conditions in three canine tumor cell lines, after gamma-ray and carbon ion irradiation. In all the cell lines, cell death assessed by the clonogenic assay was much higher following irradiation with carbon ions than with gamma-rays. The initial and residual (4 hr) DNA damage due to gamma-ray and carbon ion irradiation were higher in a <span class="hlt">radiosensitive</span> cell line than in a radioresistant cell line. The surviving cell fraction at <span class="hlt">2</span> Gy (SF<span class="hlt">2</span>) showed a tendency for correlation with both the initial and residual DNA damage. In particular, the residual damage per Gy was significantly correlated with SF<span class="hlt">2</span>, regardless of the type of radiation. This indicates that cellular <span class="hlt">radiosensitivity</span> can be predicted by detection of radiation-induced residual DNA damage.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_8");'>8</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li class="active"><span>10</span></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_10 --> <div id="page_11" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li class="active"><span>11</span></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="201"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2004RaPC...71..137B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2004RaPC...71..137B"><span><span class="hlt">Radiosensitization</span>: enhancing the radiation inactivation of foodborne bacteria</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Borsa, J.; Lacroix, M.; Ouattara, B.; Chiasson, F.</p> <p>2004-09-01</p> <p>Irradiation of meat products to kill pathogens can be limited by radiation-induced detriment of sensory quality. Since such detriment is directly related to dose, one approach to reduce it is by devising means to lower the dose of radiation required for processing. Increasing the radiation sensitivity of the target microorganisms would lower the dose required for a given level of microbial kill. In this work, the radiation sensitivities of inoculated Escherichia coli and Salmonella typhi in ground beef were examined under a variety of conditions. Results showed that specific manipulations of treatment conditions significantly increased the radiation sensitivity of the test organisms, ranging from a few percent to several-fold reduction in D10. In particular, radiation sensitization could be effected by certain additives, including carvacrol, thymol and trans-cinnamaldehyde, and also by certain compositions of modified atmosphere in the package headspace. A combination of additives and modified atmosphere effected a greater <span class="hlt">radiosensitization</span> effect than could be achieved by either factor applied alone. <span class="hlt">Radiosensitization</span> could be demonstrated with irradiation of either fresh or frozen ground meat. The <span class="hlt">radiosensitization</span> phenomenon may be of practical utility in enhancing the technical effectiveness and feasibility of irradiation of a variety of meat and other food products.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/978252-telomere-sister-chromatid-exchange-telomerase-deficient-murine-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/978252-telomere-sister-chromatid-exchange-telomerase-deficient-murine-cells"><span>Telomere sister <span class="hlt">chromatid</span> exchange in telomerase deficient murine cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Wang, Yisong; Giannone, Richard J; Liu, Yie</p> <p>2005-01-01</p> <p>We have recently demonstrated that several types of genomic rearrangements (i.e., telomere sister <span class="hlt">chromatid</span> exchange (T-SCE), genomic-SCE, or end-to-end fusions) were more often detected in long-term cultured murine telomerase deficient embryonic stem (ES) cells than in freshly prepared murine splenocytes, even through they possessed similar frequencies of critically short telomeres. The high rate of genomic rearrangements in telomerase deficient ES cells, when compared to murine splenocytes, may reflect the cultured cells' gained ability to protect chromosome ends with eroded telomeres allowing them to escape 'end crisis'. However, the possibility that ES cells were more permissive to genomic rearrangements than othermore » cell types or that differences in the microenvironment or genetic background of the animals might consequentially determine the rate of T-SCEs or other genomic rearrangements at critically short telomeres could not be ruled out.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10584846','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10584846"><span>Enhanced <span class="hlt">radiosensitivity</span> of malignant glioma cells after adenoviral p53 transduction.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Broaddus, W C; Liu, Y; Steele, L L; Gillies, G T; Lin, P S; Loudon, W G; Valerie, K; Schmidt-Ullrich, R K; Fillmore, H L</p> <p>1999-12-01</p> <p>The goal of this study was to determine whether adenoviral vector-mediated expression of human wildtype p53 can enhance the <span class="hlt">radiosensitivity</span> of malignant glioma cells that express native wild-type p53. The p53 gene is thought to function abnormally in the majority of malignant gliomas, although it has been demonstrated to be mutated in only approximately 30%. This has led to studies in which adenoviral transduction with wild-type human p53 has been investigated in an attempt to slow tumor cell growth. Recent studies suggest that reconstitution of wild-type p53 can render cells more susceptible to radiation-mediated death, primarily by p53-mediated apoptosis. Rat RT<span class="hlt">2</span> glioma cells were analyzed for native p53 status by reverse transcriptase-polymerase chain reaction and sequence analysis and for p53 expression by Western blot analysis. Clonogenic survival and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were used to characterize RT<span class="hlt">2</span> cell <span class="hlt">radiosensitivity</span> and apoptosis, respectively, with and without prior transduction with p53-containing and control adenoviral vectors. Animal survival length was monitored after intracerebral implantation with transduced and nontransduced RT<span class="hlt">2</span> cells, with and without cranial radiation. The RT<span class="hlt">2</span> cells were demonstrated to express native rat wild-type p53 and to markedly overexpress human p53 following adenoviral p53 transduction. The combination of p53 transduction followed by radiation resulted in marked decreases in RT<span class="hlt">2</span> cell survival and increases in apoptosis at radiation doses from <span class="hlt">2</span> to 6 Gy. Animals receiving cranial radiation after intracerebral implantation with RT<span class="hlt">2</span> cells previously transduced with p53 survived significantly longer than control animals (p<0.01). The ability to enhance the <span class="hlt">radiosensitivity</span> of malignant glioma cells that express wild-type p53 by using adenoviral transduction to induce overexpression of p53 offers hope for this approach as a therapeutic strategy</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22562899-mo-fg-bra-modulation-clinical-orthovoltage-ray-spectrum-further-enhances-radiosensitization-cancer-cells-targeted-gold-nanoparticles','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22562899-mo-fg-bra-modulation-clinical-orthovoltage-ray-spectrum-further-enhances-radiosensitization-cancer-cells-targeted-gold-nanoparticles"><span>MO-FG-BRA-02: Modulation of Clinical Orthovoltage X-Ray Spectrum Further Enhances <span class="hlt">Radiosensitization</span> of Cancer Cells Targeted with Gold Nanoparticles</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Wolfe, T; Reynoso, F; Cho, J</p> <p>2015-06-15</p> <p>Purpose: To assess the potential to amplify <span class="hlt">radiosensitization</span> of cancer cells targeted with gold nanoparticles by augmenting selective spectral components of X-ray beam. Methods: Human prostate cancer cells were treated for 24h with gold nanorods conjugated to goserelin acetate or pegylated, systematically washed and irradiated with 250 kVp X-rays (25mA, 0.25mm Cu- filter, 8x8cm{sup <span class="hlt">2</span>} field size, 50cm SSD) with or without an additional 0.25 mm Erbium (Er) filter. As demonstrated in a companion Monte Carlo study, Er-filter acted as an external target to feed Erbium K-shell X-ray fluorescence photons (∼50 keV) into the 250 kVp beam. After irradiation, wemore » performed measurements of clonogenic viability with doses between 0 -6Gy, irreparable DNA damage assay to measure double-strand breaks via γH<span class="hlt">2</span>AX-foci staining, and production of stable reactive oxygen species (ROS). Results: The clonogenic assay for the group treated with conjugated nanoparticles showed <span class="hlt">radiosensitization</span> enhancement factor (REF), calculated at the 10% survival fraction aisle, of (1.62±0.07) vs. (1.23±0.04) with/without the Er-filter in the 250 kVp beam, respectively. The group treated with pegylated nanoparticles, albeit retained in modest amounts within the cells, also showed statistically significant REF (1.13±0.09) when the Erbium filter was added to the beam. No significant <span class="hlt">radiosensitization</span> was observed for other groups. Measurements of ROS levels showed increments of (1.9±0.<span class="hlt">2</span>) vs. (1.4±0.1) for combined treatment with targeted nanoparticles and Er-filtered beam. γH<span class="hlt">2</span>AX-foci showed 50% increase for the same treatment combination, confirming the enhanced <span class="hlt">radiosensitization</span> in a consistent fashion. Conclusion: Our study demonstrates the feasibility of enhancing <span class="hlt">radiosensitization</span> of cancer cells by combining actively targeted gold nanoparticles and modulating the X-ray spectrum in the desired energy range. The established technique will not only help develop strategies to</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2734174','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2734174"><span>The Cellular Phenotype of Roberts Syndrome Fibroblasts as Revealed by Ectopic Expression of ESCO<span class="hlt">2</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>van der Lelij, Petra; van Gosliga, Djoke; Oostra, Anneke B.; Steltenpool, Jûrgen; de Groot, Jan; Scheper, Rik J.; Wolthuis, Rob M.; Waisfisz, Quinten; Darroudi, Firouz; Joenje, Hans; de Winter, Johan P.</p> <p>2009-01-01</p> <p>Cohesion between sister <span class="hlt">chromatids</span> is essential for faithful chromosome segregation. In budding yeast, the acetyltransferase Eco1/Ctf7 establishes cohesion during DNA replication in S phase and in response to DNA double strand breaks in <span class="hlt">G</span><span class="hlt">2</span>/M phase. In humans two Eco1 orthologs exist: ESCO1 and ESCO<span class="hlt">2</span>. Both proteins are required for proper sister <span class="hlt">chromatid</span> cohesion, but their exact function is unclear at present. Since ESCO<span class="hlt">2</span> has been identified as the gene defective in the rare autosomal recessive cohesinopathy Roberts syndrome (RBS), cells from RBS patients can be used to elucidate the role of ESCO<span class="hlt">2</span>. We investigated for the first time RBS cells in comparison to isogenic controls that stably express V5- or GFP-tagged ESCO<span class="hlt">2</span>. We show that the sister <span class="hlt">chromatid</span> cohesion defect in the transfected cell lines is rescued and suggest that ESCO<span class="hlt">2</span> is regulated by proteasomal degradation in a cell cycle-dependent manner. In comparison to the corrected cells RBS cells were hypersensitive to the DNA-damaging agents mitomycin C, camptothecin and etoposide, while no particular sensitivity to UV, ionizing radiation, hydroxyurea or aphidicolin was found. The cohesion defect of RBS cells and their hypersensitivity to DNA-damaging agents were not corrected by a patient-derived ESCO<span class="hlt">2</span> acetyltransferase mutant (W539<span class="hlt">G</span>), indicating that the acetyltransferase activity of ESCO<span class="hlt">2</span> is essential for its function. In contrast to a previous study on cells from patients with Cornelia de Lange syndrome, another cohesinopathy, RBS cells failed to exhibit excessive chromosome aberrations after irradiation in <span class="hlt">G</span><span class="hlt">2</span> phase of the cell cycle. Our results point at an S phase-specific role for ESCO<span class="hlt">2</span> in the maintenance of genome stability. PMID:19738907</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22278306-radioprotection-cell-cycle-arrest-intestinal-epithelial-cells-darinaparsin-tumor-radiosensitizer','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22278306-radioprotection-cell-cycle-arrest-intestinal-epithelial-cells-darinaparsin-tumor-radiosensitizer"><span>Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor <span class="hlt">Radiosensitizer</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Tian, Junqiang; Doi, Hiroshi; Saar, Matthias</p> <p>2013-12-01</p> <p>Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and <span class="hlt">radiosensitizer</span> of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS <span class="hlt">radiosensitizing</span> effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome.more » The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both <span class="hlt">G</span>1/S and <span class="hlt">G</span><span class="hlt">2</span>/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17521756','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17521756"><span><span class="hlt">Radiosensitization</span> of tumour cell lines by the polyphenol Gossypol results from depressed double-strand break repair and not from enhanced apoptosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kasten-Pisula, Ulla; Windhorst, Sabine; Dahm-Daphi, Jochen; Mayr, Georg; Dikomey, Ekkehard</p> <p>2007-06-01</p> <p>New drugs are needed to increase the efficiency of radiotherapy in order to improve the therapeutic outcome of tumour patients. In this respect, the polyphenol Gossypol might be of interest, because of its effect on apoptosis and DNA repair, which is either mediated directly or indirectly via the inositol phosphate metabolism. It was investigated, whether these effects result in enhanced <span class="hlt">radiosensitivity</span> of tumour cells. Tumour cell lines investigated: A549, FaDu, H1299, MCF7 and Du145. Cell cycle distribution was determined by FACS analysis, apoptosis was measured by DAPI staining and caspase3/7 activity. Double-strand breaks (DSB) were investigated via gammaH<span class="hlt">2</span>AX-foci and cell survival by colony formation assay. The level of inositol phosphates was determined by HPLC, protein expression by Western blot. In A549 cells, Gossypol at concentrations 1microM strongly affects proliferation with only a modest arrest in the <span class="hlt">G</span>1-phase, but with no increase in the fraction of apoptotic cells or the number of additional DSB. Additional DSB were only seen in FaDu cells, where Gossypol (<span class="hlt">2</span>microM) was extremely toxic with a plating efficiency <0.002. When combined with irradiation, incubation with Gossypol (1-<span class="hlt">2</span>microM) was found to result in an enhanced <span class="hlt">radiosensitivity</span> with, however, a substantial variation. While there was a strong <span class="hlt">radiosensitization</span> for FaDu and Du145 cells, there was an intermediate response for A549 cells, but almost no effect for H1299 and MCF7 cells. This sensitization was not caused from an elevated rate of apoptosis, but primarily resulted from reduced DSB repair capacity. The reduction in DSB repair could be ascribed neither to changes in the level of repair proteins relevant for non-homologous end-joining (Ku70, Ku80, DNA-PKcs) nor to changes in the level of higher phosphorylated inositols, whereby the latter were even found to be enhanced by Gossypol. For some tumour cell lines treatment with low concentrations of Gossypol can be used to inhibit DSB</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4716812','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4716812"><span>Cisplatin <span class="hlt">Radiosensitization</span> of DNA Irradiated with <span class="hlt">2</span>–20 eV Electrons: Role of Transient Anions</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bao, Qianhong; Chen, Yunfeng; Zheng, Yi; Sanche, Léon</p> <p>2015-01-01</p> <p>Platinum chemotherapeutic agents, such as cisplatin (cis-diamminedichloroplatinum(II)), can act as <span class="hlt">radiosensitizers</span> when bound covalently to nuclear DNA in cancer cells. This <span class="hlt">radiosensitization</span> is largely due to an increase in DNA damage induced by low-energy secondary electrons, produced in large quantities by high-energy radiation. We report the yields of single- and double-strand breaks (SSB and DSB) and interduplex cross-links (CL) induced by electrons of 1.6–19.6 eV (i.e., the yield functions) incident on 5 monolayer (ML) films of cisplatin–DNA complexes. These yield functions are compared with those previously recorded with 5 ML films of unmodified plasmid DNA. Binding of five cisplatin molecules to plasmid DNA (3197 base pairs) enhances SSB, DSB, and CL by factors varying, from 1.<span class="hlt">2</span> to <span class="hlt">2</span>.8, 1.4 to 3.5, and 1.<span class="hlt">2</span> to <span class="hlt">2</span>.7, respectively, depending on electron energy. All yield functions exhibit structures around 5 and 10 eV that can be attributed to enhancement of bond scission, via the initial formation of core-excited resonances associated with π → π* transitions of the bases. This increase in damage is interpreted as arising from a modification of the parameters of the corresponding transient anions already present in nonmodified DNA, particularly those influencing molecular dissociation. Two additional resonances, specific to cisplatin-modified DNA, are formed at 13.6 and 17.6 eV in the yield function of SSB. Furthermore, cisplatin binding causes the induction of DSB by electrons of 1.6–3.6 eV, i.e., in an energy region where a DSB cannot be produced by a single electron in pure DNA. Breaking two bonds with a subexcitation-energy electron is tentatively explained by a charge delocalization mechanism, where a single electron occupies simultaneously two σ* bonds linking the Pt atom to guanine bases on opposite strands. PMID:26793285</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22212331-downregulation-mir-expression-inhibits-proliferation-induces-apoptosis-enhances-radiosensitivity-hypoxic-human-hepatoma-cells-vitro','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22212331-downregulation-mir-expression-inhibits-proliferation-induces-apoptosis-enhances-radiosensitivity-hypoxic-human-hepatoma-cells-vitro"><span>Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances <span class="hlt">radiosensitivity</span> in hypoxic human hepatoma cells in vitro</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Yang, Wei, E-mail: detachedy@yahoo.com.cn; Sun, Ting; Cao, Jianping</p> <p>2012-05-01</p> <p>Hypoxia is a common feature of solid tumors and an important contributor to tumor radioresistance. miR-210 is the most consistently and robustly induced microRNA under hypoxia in different types of tumor cells and normal cells. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, Hep<span class="hlt">G</span><span class="hlt">2</span> and HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an increased hypoxia inducible factor-1{alpha} (HIF-1{alpha}) and miR-210 expression and cell arrest in the <span class="hlt">G</span>{sub 0}/<span class="hlt">G</span>{sub 1} phase inmore » all cell lines. miR-210 downregulation significantly suppressed cell viability, induced cell arrest in the <span class="hlt">G</span>{sub 0}/<span class="hlt">G</span>{sub 1} phase, increased apoptotic rate and enhanced <span class="hlt">radiosensitivity</span> in hypoxic human hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. Taken together, these data suggest that miR-210 might be a potential therapeutic target and specific inhibition of miR-210 expression in combination with radiotherapy might be expected to exert strong anti-tumor effect on hypoxic human hepatoma cells. -- Highlights: Black-Right-Pointing-Pointer miR-210 downregulation <span class="hlt">radiosensitized</span> hypoxic hepatoma. Black-Right-Pointing-Pointer AIFM3 was identified as a direct target gene of miR-210. Black-Right-Pointing-Pointer miR-210 might be a therapeutic target to hypoxic hepatoma.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27647179','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27647179"><span>Inhibiting CD146 by its Monoclonal Antibody AA98 Improves <span class="hlt">Radiosensitivity</span> of Cervical Cancer Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cheng, Huawen</p> <p>2016-09-20</p> <p>BACKGROUND Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low <span class="hlt">radiosensitivity</span> found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating <span class="hlt">radiosensitivity</span> of cervical cancer cells. MATERIAL AND METHODS CD146 protein expression was compared in normal cells, cervical cancer cells with lower <span class="hlt">radiosensitivity</span>, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low <span class="hlt">radiosensitivity</span>, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. RESULTS CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower <span class="hlt">radiosensitivity</span>. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. CONCLUSIONS These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing <span class="hlt">radiosensitivity</span> of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating <span class="hlt">radiosensitivity</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28260889','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28260889"><span>Gold nanoparticles and electroporation impose both separate and synergistic <span class="hlt">radiosensitizing</span> effects in HT-29 tumor cells: an in vitro study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rezaee, Zohre; Yadollahpour, Ali; Bayati, Vahid; Negad Dehbashi, Fereshteh</p> <p>2017-01-01</p> <p>Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. Despite recent improvements in RT efficiency, the side effects of ionizing radiation (IR) in normal tissues are a dose-limiting factor that restricts higher doses in tumor treatment. One approach to enhance the efficiency of RT is the application of <span class="hlt">radiosensitizers</span> to selectively increase the dose at the tumor site. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as <span class="hlt">radiosensitizers</span> for RT. This study aims to investigate the sensitizing effects of EP, GNPs, and combined GNPs-EP on the dose enhancement factor (DEF) for 6 MV photon energy. <span class="hlt">Radiosensitizing</span> effects of EP, GNPs, and combinations of GNPs-EP were comparatively investigated in vitro for intestinal colon cancer (HT-29) and Chinese hamster ovary (CHO) cell lines by MTT assay and colony formation assay at 6 MV photon energy in six groups: IR (control group), GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR. Treatment of both cell lines with EP, GNPs, and combined GNPs-EP significantly enhanced the response of cells to irradiation. However, the HT-29 showed higher DEF values for all groups. In addition, the DEF value for HT-29 cells for GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR was, respectively, 1.17, 1.47, 1.36, <span class="hlt">2</span>.61, and <span class="hlt">2</span>.89, indicating synergistic <span class="hlt">radiosensitizing</span> effect for the GNPs (24 h)+EP+IR group. Furthermore, the synergistic effect was observed just for HT-29 tumor cell lines. Combined GNPs-EP protocols induced synergistic <span class="hlt">radiosensitizing</span> effect in HT-29 cells, and the effect is also tumor specific. This combined therapy can be beneficially used for the treatment of intrinsically less <span class="hlt">radiosensitive</span> tumors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6010333','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6010333"><span>The brain-penetrant clinical ATM inhibitor AZD1390 <span class="hlt">radiosensitizes</span> and improves survival of preclinical brain tumor models</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wang, Yingchun; Chen, Kan; Zhang, Lingli; Zhang, Tianwei; Yang, Zhenfan; Riches, Lucy; Trinidad, Antonio G.; Pike, Kurt G.; Wilson, Joanne; Smith, Aaron; Colclough, Nicola; Johnström, Peter; Varnäs, Katarina; Takano, Akihiro; Ling, Stephanie; Orme, Jonathan; Stott, Jonathan; Barrett, Ian; Jones, Gemma; Allen, Jasmine; Kahn, Jenna; Sule, Amrita; Cronin, Anna; Chapman, Melissa; Illingworth, Ruth; Pass, Martin</p> <p>2018-01-01</p> <p>Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell hypersensitivity to IR. We report the primary pharmacology of the clinical-grade, exquisitely potent (cell IC50, 0.78 nM), highly selective [>10,000-fold over kinases within the same phosphatidylinositol 3-kinase–related kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically optimized for BBB penetration confirmed in cynomolgus monkey brain positron emission tomography (PET) imaging of microdosed 11C-labeled AZD1390 (Kp,uu, 0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with radiation to induce <span class="hlt">G</span><span class="hlt">2</span> cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 <span class="hlt">radiosensitizes</span> glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more <span class="hlt">radiosensitized</span> than wild type. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. We established a pharmacokinetic-pharmacodynamic-efficacy relationship by correlating free brain concentrations, tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase-3) induction, tumor regression, and survival. On the basis of the data presented here, AZD1390 is now in early clinical development for use as a <span class="hlt">radiosensitizer</span> in central nervous system malignancies. PMID:29938225</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29938225','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29938225"><span>The brain-penetrant clinical ATM inhibitor AZD1390 <span class="hlt">radiosensitizes</span> and improves survival of preclinical brain tumor models.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Durant, Stephen T; Zheng, Li; Wang, Yingchun; Chen, Kan; Zhang, Lingli; Zhang, Tianwei; Yang, Zhenfan; Riches, Lucy; Trinidad, Antonio G; Fok, Jacqueline H L; Hunt, Tom; Pike, Kurt G; Wilson, Joanne; Smith, Aaron; Colclough, Nicola; Reddy, Venkatesh Pilla; Sykes, Andrew; Janefeldt, Annika; Johnström, Peter; Varnäs, Katarina; Takano, Akihiro; Ling, Stephanie; Orme, Jonathan; Stott, Jonathan; Roberts, Caroline; Barrett, Ian; Jones, Gemma; Roudier, Martine; Pierce, Andrew; Allen, Jasmine; Kahn, Jenna; Sule, Amrita; Karlin, Jeremy; Cronin, Anna; Chapman, Melissa; Valerie, Kristoffer; Illingworth, Ruth; Pass, Martin</p> <p>2018-06-01</p> <p>Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation or pharmacological inhibition results in tumor cell hypersensitivity to IR. We report the primary pharmacology of the clinical-grade, exquisitely potent (cell IC 50 , 0.78 nM), highly selective [>10,000-fold over kinases within the same phosphatidylinositol 3-kinase-related kinase (PIKK) family], orally bioavailable ATM inhibitor AZD1390 specifically optimized for BBB penetration confirmed in cynomolgus monkey brain positron emission tomography (PET) imaging of microdosed 11 C-labeled AZD1390 ( K p,uu , 0.33). AZD1390 blocks ATM-dependent DDR pathway activity and combines with radiation to induce <span class="hlt">G</span> <span class="hlt">2</span> cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 <span class="hlt">radiosensitizes</span> glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more <span class="hlt">radiosensitized</span> than wild type. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone. We established a pharmacokinetic-pharmacodynamic-efficacy relationship by correlating free brain concentrations, tumor phospho-ATM/phospho-Rad50 inhibition, apoptotic biomarker (cleaved caspase-3) induction, tumor regression, and survival. On the basis of the data presented here, AZD1390 is now in early clinical development for use as a <span class="hlt">radiosensitizer</span> in central nervous system malignancies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22267869-inhibition-hsp27-radiosensitizes-head-neck-cancer-modulating-deoxyribonucleic-acid-repair','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22267869-inhibition-hsp27-radiosensitizes-head-neck-cancer-modulating-deoxyribonucleic-acid-repair"><span>Inhibition of Hsp27 <span class="hlt">Radiosensitizes</span> Head-and-Neck Cancer by Modulating Deoxyribonucleic Acid Repair</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Guttmann, David M.; Hart, Lori; Du, Kevin</p> <p></p> <p>Purpose: To present a novel method of tumor <span class="hlt">radiosensitization</span> through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Methods and Materials: Clonogenic survival assays, immunoblotting, the proximity ligation assay, and γH<span class="hlt">2</span>AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Results: Hsp27 LNA and Hsp27 shRNA <span class="hlt">radiosensitized</span> head-and-neck cancer cellmore » lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the <span class="hlt">radiosensitizing</span> effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. Conclusions: These results support a <span class="hlt">radiosensitizing</span> property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23849696','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23849696"><span>Inhibition of Hsp27 <span class="hlt">radiosensitizes</span> head-and-neck cancer by modulating deoxyribonucleic acid repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Guttmann, David M; Hart, Lori; Du, Kevin; Seletsky, Andrew; Koumenis, Constantinos</p> <p>2013-09-01</p> <p>To present a novel method of tumor <span class="hlt">radiosensitization</span> through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Clonogenic survival assays, immunoblotting, the proximity ligation assay, and γH<span class="hlt">2</span>AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Hsp27 LNA and Hsp27 shRNA <span class="hlt">radiosensitized</span> head-and-neck cancer cell lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the <span class="hlt">radiosensitizing</span> effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. These results support a <span class="hlt">radiosensitizing</span> property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer. Copyright © 2013. Published by Elsevier Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26123368','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26123368"><span>Location of <span class="hlt">radiosensitive</span> organs inside pediatric anthropomorphic phantoms: Data required for dosimetry.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Inkoom, Stephen; Raissaki, Maria; Perisinakis, Kostas; Maris, Thomas G; Damilakis, John</p> <p>2015-12-01</p> <p>The aim of this study was to determine the location of <span class="hlt">radiosensitive</span> organs in the interior of four pediatric anthropomorphic phantoms for dosimetric purposes. Four pediatric anthropomorphic phantoms representing the average individual as newborn, 1-year-old, 5-year-old and 10-year-old child underwent head, thorax and abdomen CT scans. CT and MRI scans of all children aged 0-16 years performed during a 5-year-period in our hospital were reviewed, and 503 were found to be eligible for normal anatomy. Anterior-posterior and lateral dimensions of twelve of the above children closely matched that of the phantoms' head, thoracic and abdominal region in each four phantoms. The mid-sagittal and mid-coronal planes were drawn on selected matching axial images of patients and phantoms. Multiple points outlining large <span class="hlt">radiosensitive</span> organs in patient images were identified at each slice level and their orthogonal distances from the mid-sagittal and mid-coronal planes were measured. In small organs, the coordinates of organs' centers were similarly determined. The outlines and centers of all <span class="hlt">radiosensitive</span> organs were reproduced using the coordinates of each organ on corresponding phantoms' transverse images. The locations of the following <span class="hlt">radiosensitive</span> organs in the interior of the four phantoms was determined: brain, eye lenses, salivary glands, thyroid, lungs, heart, thymus, esophagus, breasts, adrenals, liver, spleen, kidneys, stomach, gallbladder, small bowel, pancreas, colon, ovaries, bladder, prostate, uterus and rectum. The production of charts of <span class="hlt">radiosensitive</span> organs inside pediatric anthropomorphic phantoms was feasible and may provide users reliable data for positioning of dosimeters during direct organ dose measurements. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26716839','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26716839"><span>DNA-Dependent Protein Kinase As Molecular Target for <span class="hlt">Radiosensitization</span> of Neuroblastoma Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dolman, M Emmy M; van der Ploeg, Ida; Koster, Jan; Bate-Eya, Laurel Tabe; Versteeg, Rogier; Caron, Huib N; Molenaar, Jan J</p> <p>2015-01-01</p> <p>Tumor cells might resist therapy with ionizing radiation (IR) by non-homologous end-joining (NHEJ) of IR-induced double-strand breaks. One of the key players in NHEJ is DNA-dependent protein kinase (DNA-PK). The catalytic subunit of DNA-PK, i.e. DNA-PKcs, can be inhibited with the small-molecule inhibitor NU7026. In the current study, the in vitro potential of NU7026 to <span class="hlt">radiosensitize</span> neuroblastoma cells was investigated. DNA-PKcs is encoded by the PRKDC (protein kinase, DNA-activated, catalytic polypeptide) gene. We showed that PRKDC levels were enhanced in neuroblastoma patients and correlated with a more advanced tumor stage and poor prognosis, making DNA-PKcs an interesting target for <span class="hlt">radiosensitization</span> of neuroblastoma tumors. Optimal dose finding for combination treatment with NU7026 and IR was performed using NGP cells. One hour pre-treatment with 10 μM NU7026 synergistically sensitized NGP cells to 0.63 Gy IR. <span class="hlt">Radiosensitizing</span> effects of NU7026 increased in time, with maximum effects observed from 96 h after IR-exposure on. Combined treatment of NGP cells with 10 μM NU7026 and 0.63 Gy IR resulted in apoptosis, while no apoptotic response was observed for either of the therapies alone. Inhibition of IR-induced DNA-PK activation by NU7026 confirmed the capability of NGP cells to, at least partially, resist IR by NHEJ. NU7026 also synergistically <span class="hlt">radiosensitized</span> other neuroblastoma cell lines, while no synergistic effect was observed for low DNA-PKcs-expressing non-cancerous fibroblasts. Results obtained for NU7026 were confirmed by PRKDC knockdown in NGP cells. Taken together, the current study shows that DNA-PKcs is a promising target for neuroblastoma <span class="hlt">radiosensitization</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1128680','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1128680"><span>DNA single strand breakage, DNA adducts, and sister <span class="hlt">chromatid</span> exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Popp, W; Vahrenholz, C; Schell, C; Grimmer, G; Dettbarn, G; Kraus, R; Brauksiepe, A; Schmeling, B; Gutzeit, T; von Bülow, J; Norpoth, K</p> <p>1997-01-01</p> <p>OBJECTIVES: To investigate the specificity of biological monitoring variables (excretion of phenanthrene and pyrene metabolites in urine) and the usefulness of some biomarkers of effect (alkaline filter elution, 32P postlabelling assay, measurement of sister <span class="hlt">chromatid</span> exchange) in workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: 29 coke oven workers and a standardised control group were investigated for frequencies of DNA single strand breakage, DNA protein cross links (alkaline filter elution assay), sister <span class="hlt">chromatid</span> exchange, and DNA adducts (32P postlabelling assay) in lymphocytes. Phenanthrene and pyrene metabolites were measured in 24 hour urine samples. 19 different PAHs (including benzo(a)pyrene, pyrene, and phenanthrene) were measured at the workplace by personal air monitoring. The GSTT1 activity in erythrocytes and lymphocyte subpopulations in blood was also measured. RESULTS: Concentrations of phenanthrene, pyrene, and benzo(a)pyrene in air correlated well with the concentration of total PAHs in air; they could be used for comparisons of different workplaces if the emission compositions were known. The measurement of phenanthrene metabolites in urine proved to be a better biological monitoring variable than the measurement of 1-hydroxypyrene. Significantly more DNA strand breaks in lymphocytes of coke oven workers were found (alkaline filter elution assay); the DNA adduct rate was not significantly increased in workers, but correlated with exposure to PAHs in a semiquantitative manner. The number of sister <span class="hlt">chromatid</span> exchanges was lower in coke oven workers but this was not significant; thus counting sister <span class="hlt">chromatid</span> exchanges was not a good variable for biomonitoring of coke oven workers. Also, indications for immunotoxic influences (changes in lymphocyte subpopulations) were found. CONCLUSIONS: The measurement of phenanthrene metabolites in urine seems to be a better biological monitoring variable for exposure to PAHs than</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29770473','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29770473"><span>Icotinib enhances lung cancer cell <span class="hlt">radiosensitivity</span> in vitro and in vivo by inhibiting MAPK/ERK and AKT activation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fu, Yonghong; Zhang, Sen; Wang, Dongjie; Wang, Jing</p> <p>2018-05-16</p> <p>Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing <span class="hlt">radiosensitivity</span>. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell <span class="hlt">radiosensitivity</span> and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed. Cell apoptosis was also analyzed by flow cytometry, while western blotting was performed to examine the activation of EGFR and its downstream kinases in H1650 cells after Icotinib and radiation treatment. Furthermore, a xenograft animal model was established to evaluate the <span class="hlt">radiosensitivity</span> of Icotinib in vivo and to confirm its mechanism. Our results demonstrate that pretreatment with Icotinib reduced clonogenic survival after radiation, inhibited EGFR activation, and increased radiation-induced apoptosis in H1650 cells. The phosphorylation of protein kinase B (AKT), extracellular regulated protein kinase 1/<span class="hlt">2</span> (ERK1/<span class="hlt">2</span>), and EGFR was inhibited after Icotinib and radiation combination treatment in vitro and in vivo compared with individual treatments. Combination treatment also affected the expression of the DNA repair protein H<span class="hlt">2</span>A histone family member X (γ-H<span class="hlt">2</span>AX). In conclusion, our results reveal that Icotinib enhances <span class="hlt">radiosensitivity</span> in lung cancers in vitro and in vivo and the mechanism of this may involve blocking the EGFR-AKT and MAPK-ERK pathways and limiting DNA repair. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27705054','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27705054"><span>Enhancement of <span class="hlt">radiosensitivity</span> of melanoma cells by pegylated gold nanoparticles under irradiation of megavoltage electrons.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mousavi, Mehdi; Nedaei, Hassan Ali; Khoei, Samideh; Eynali, Samira; Khoshgard, Karim; Robatjazi, Mostafa; Iraji Rad, Rasoul</p> <p>2017-02-01</p> <p>Gold nanoparticles (GNP) have significant potential as <span class="hlt">radiosensitizer</span> agents due to their distinctive properties. Several studies have shown that the surface modification of nanoparticles with methyl polyethylene glycol (mPEG) can increase their biocompatibility. However, the present study investigated the <span class="hlt">radiosensitization</span> effects of mPEG-coated GNP (mPEG-GNP) in B16F10 murine melanoma cells under irradiation of 6 MeV Electron beam. The synthesized GNP were characterized by UV-Visible spectroscopy, dynamic light scattering, transmission electron microscopy, and zeta potential. Enhancement of <span class="hlt">radiosensitization</span> was evaluated by the clonogenic assay at different radiation doses of megavoltage electron beams. It was observed that mPEG-GNP with a hydrodynamic size of approximately 50 nm are almost spherical and cellular uptake occurred at all concentrations. Both proliferation efficiency and survival fraction decreased with increasing mPEG-GNP concentration. Furthermore, significant GNP sensitization occurred with a maximum dose enhancement factor of 1.22 at a concentration of 30 μM. Pegylated-GNP are taken up by B16F10 cancer cells and cause <span class="hlt">radiosensitization</span> in the presence of 6 MeV electrons. The <span class="hlt">radiosensitization</span> effects of GNP may probably be due to biological processes. Therefore, the underlying biological mechanisms beyond the physical dose enhancement need to be further clarified.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li class="active"><span>11</span></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_11 --> <div id="page_12" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li class="active"><span>12</span></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="221"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19100922','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19100922"><span><span class="hlt">Radiosensitization</span> by inhibiting STAT1 in renal cell carcinoma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hui, Zhouguang; Tretiakova, Maria; Zhang, Zhongfa; Li, Yan; Wang, Xiaozhen; Zhu, Julie Xiaohong; Gao, Yuanhong; Mai, Weiyuan; Furge, Kyle; Qian, Chao-Nan; Amato, Robert; Butler, E Brian; Teh, Bin Tean; Teh, Bin S</p> <p>2009-01-01</p> <p>Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (<span class="hlt">G</span>-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10(-8) for clear cell; and p = 3.6 x 10(-4) for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the <span class="hlt">radiosensitivity</span> in both RCC cell lines. This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. <span class="hlt">Radiosensitization</span> in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4696738','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4696738"><span>DNA-Dependent Protein Kinase As Molecular Target for <span class="hlt">Radiosensitization</span> of Neuroblastoma Cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Dolman, M. Emmy M.; van der Ploeg, Ida; Koster, Jan; Bate-Eya, Laurel Tabe; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.</p> <p>2015-01-01</p> <p>Tumor cells might resist therapy with ionizing radiation (IR) by non-homologous end-joining (NHEJ) of IR-induced double-strand breaks. One of the key players in NHEJ is DNA-dependent protein kinase (DNA-PK). The catalytic subunit of DNA-PK, i.e. DNA-PKcs, can be inhibited with the small-molecule inhibitor NU7026. In the current study, the in vitro potential of NU7026 to <span class="hlt">radiosensitize</span> neuroblastoma cells was investigated. DNA-PKcs is encoded by the PRKDC (protein kinase, DNA-activated, catalytic polypeptide) gene. We showed that PRKDC levels were enhanced in neuroblastoma patients and correlated with a more advanced tumor stage and poor prognosis, making DNA-PKcs an interesting target for <span class="hlt">radiosensitization</span> of neuroblastoma tumors. Optimal dose finding for combination treatment with NU7026 and IR was performed using NGP cells. One hour pre-treatment with 10 μM NU7026 synergistically sensitized NGP cells to 0.63 Gy IR. <span class="hlt">Radiosensitizing</span> effects of NU7026 increased in time, with maximum effects observed from 96 h after IR-exposure on. Combined treatment of NGP cells with 10 μM NU7026 and 0.63 Gy IR resulted in apoptosis, while no apoptotic response was observed for either of the therapies alone. Inhibition of IR-induced DNA-PK activation by NU7026 confirmed the capability of NGP cells to, at least partially, resist IR by NHEJ. NU7026 also synergistically <span class="hlt">radiosensitized</span> other neuroblastoma cell lines, while no synergistic effect was observed for low DNA-PKcs-expressing non-cancerous fibroblasts. Results obtained for NU7026 were confirmed by PRKDC knockdown in NGP cells. Taken together, the current study shows that DNA-PKcs is a promising target for neuroblastoma <span class="hlt">radiosensitization</span>. PMID:26716839</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4696839','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4696839"><span>KPU-300, a Novel Benzophenone–Diketopiperazine–Type Anti-Microtubule Agent with a <span class="hlt">2</span>-Pyridyl Structure, Is a Potent <span class="hlt">Radiosensitizer</span> That Synchronizes the Cell Cycle in Early M Phase</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko</p> <p>2015-01-01</p> <p>KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and <span class="hlt">radiosensitization</span> using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable <span class="hlt">radiosensitization</span> was observed. To determine whether this <span class="hlt">radiosensitization</span> was truly due to the synchronization in M phase, we compared the <span class="hlt">radiosensitivity</span> of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel <span class="hlt">radiosensitizing</span> strategy using KPU-300. PMID:26716455</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26716455','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26716455"><span>KPU-300, a Novel Benzophenone-Diketopiperazine-Type Anti-Microtubule Agent with a <span class="hlt">2</span>-Pyridyl Structure, Is a Potent <span class="hlt">Radiosensitizer</span> That Synchronizes the Cell Cycle in Early M Phase.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko</p> <p>2015-01-01</p> <p>KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and <span class="hlt">radiosensitization</span> using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable <span class="hlt">radiosensitization</span> was observed. To determine whether this <span class="hlt">radiosensitization</span> was truly due to the synchronization in M phase, we compared the <span class="hlt">radiosensitivity</span> of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel <span class="hlt">radiosensitizing</span> strategy using KPU-300.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5457476-effect-hydrocortisone-radiosensitivity-hemopoietic-stem-cells-gamma-rays-mice-bone-marrow-spleen','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5457476-effect-hydrocortisone-radiosensitivity-hemopoietic-stem-cells-gamma-rays-mice-bone-marrow-spleen"><span>Effect of hydrocortisone on <span class="hlt">radiosensitivity</span> of hemopoietic stem cells. [. gamma. rays; mice; bone marrow; spleen</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Shvets, V.N.</p> <p></p> <p>Studies were made of the direction of differentiation and <span class="hlt">radiosensitivity</span> of CFU (colony-forming units) of bone marrow and spleen for 1 month after single injection of 5 mg hydrocortisone (HC) per mouse. It was found that there was a sharp change in direction of differentiation of CFU from different sources. Bone marrow CFU enhanced erythropoiesis and CFU of the spleen enhanced myelopoiesis, which is not inherent in the same CFU of normal mice. Determination of <span class="hlt">radiosensitivity</span> of CFU from different sources according to the spleen colony test failed to demonstrate any differences in value of D/sub 0/ and extrapolation number,more » whereas substantial changes in <span class="hlt">radiosensitivity</span> were demonstrated in the bone marrow colony test. <span class="hlt">Radiosensitivity</span> of marrow CFU diminished while that of the spleen increased, as compared to the control. It is assumed that these phenomena are due to redistribution of T lymphocytes in response to HC.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2009589','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2009589"><span>Sister <span class="hlt">chromatid</span> exchange in children of Seventh-Day Adventists and matched controls.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hermansen, R; Waksvik, H; Fønnebø, V</p> <p>1991-03-01</p> <p>The low risk of cancer in Seventh-Day Adventists (SDAs) has been suggested to be due to genetic selection. To investigate this claim we examined the sister <span class="hlt">chromatid</span> exchange (SCE) frequency in peripheral blood lymphocytes in 16 SDA children in Tromsø, all aged 0.5-8 years and 16 controls matched for sex and age. In 12 of 16 pairs, the SDA children had a lower SCE frequency than the controls. The mean difference was 4.06 (95% confidence interval -17.02-8.89, P = 0.51). There was no sex difference, and no correlation between age and SCE frequency. The genetic starting point with regard to SCE frequency seems to be the same for SDA children and controls.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27909463','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27909463"><span>Synthetic nanoparticles for delivery of radioisotopes and <span class="hlt">radiosensitizers</span> in cancer therapy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhao, Jun; Zhou, Min; Li, Chun</p> <p>2016-01-01</p> <p>Radiotherapy has been, and will continue to be, a critical modality to treat cancer. Since the discovery of radiation-induced cytotoxicity in the late 19th century, both external and internal radiation sources have provided tremendous benefits to extend the life of cancer patients. Despite the dramatic improvement of radiation techniques, however, one challenge persists to limit the anti-tumor efficacy of radiotherapy, which is to maximize the deposited dose in tumor while sparing the rest of the healthy vital organs. Nanomedicine has stepped into the spotlight of cancer diagnosis and therapy during the past decades. Nanoparticles can potentiate radiotherapy by specifically delivering radionuclides or <span class="hlt">radiosensitizers</span> into tumors, therefore enhancing the efficacy while alleviating the toxicity of radiotherapy. This paper reviews recent advances in synthetic nanoparticles for radiotherapy and <span class="hlt">radiosensitization</span>, with a focus on the enhancement of in vivo anti-tumor activities. We also provide a brief discussion on radiation-associated toxicities as this is an area that, up to date, has been largely missing in the literature and should be closely examined in future studies involving nanoparticle-mediated <span class="hlt">radiosensitization</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/4389520-synthesis-igm-igg-antibodies-mice-irradiated-rays-immunized-tetanus-toxoid','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/4389520-synthesis-igm-igg-antibodies-mice-irradiated-rays-immunized-tetanus-toxoid"><span>Synthesis of IgM and Ig<span class="hlt">G</span> antibodies in mice irradiated with x rays and immunized with tetanus toxoid (in Polish)</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Galazka, A.; Albrycht, H.; Aleksandrowicz, J.</p> <p>1972-01-01</p> <p>White mice were immunized with adsorbed tetanus toxoid 1 to <span class="hlt">2</span> hrs following irradiation with a dose of 300 R. The antibody response was tested in whole sera 7, 14, 28, and 42 days after immunization; it was found to be delayed and repressed compared with controls. In tests for antibody activity of different classes of immunoglobulins, isolated on Sephadex <span class="hlt">G</span>-200, the IgM- producing mechanisms were found to be highly <span class="hlt">radiosensitive</span>; peak of the response was greatly delayed (28 days); and peak titers were threefold lower than in controls. Ig<span class="hlt">G</span> antibody production also was delayed and in the initial periodmore » it was repressed. Six weeks after irradiation, Ig<span class="hlt">G</span> antibody levels were equal in the irradiated and control mice. The present results concerning <span class="hlt">radiosensitivity</span> of IgM-producing mechanisms are discordant with data of other authors, who immunized animals with other antigens or investigated the metabolism of immunoglobulins in irradiated but nonimmunized animals. (auth)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21451140-inhibition-stat3-erbb2-suppresses-tumor-growth-enhances-radiosensitivity-induces-mitochondria-dependent-apoptosis-glioma-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21451140-inhibition-stat3-erbb2-suppresses-tumor-growth-enhances-radiosensitivity-induces-mitochondria-dependent-apoptosis-glioma-cells"><span>Inhibition of STAT3 and ErbB<span class="hlt">2</span> Suppresses Tumor Growth, Enhances <span class="hlt">Radiosensitivity</span>, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Gao Ling; Li Fengsheng; Dong Bo</p> <p>2010-07-15</p> <p>Purpose: Constitutively activated signal transducer and activator of transcription 3 (STAT3) and ErbB<span class="hlt">2</span> are involved in the pathogenesis of many tumors, including astrocytoma. Inactivation of these molecules is reported to result in <span class="hlt">radiosensitization</span>. The purpose of this study was to investigate whether inhibition of STAT3, ErbB<span class="hlt">2</span>, or both could enhance radiotherapy in the human glioma model (U251 and U87 cell lines). Methods and Materials: The RNAi plasmids targeting STAT3 or ErbB<span class="hlt">2</span> were constructed, and their downregulatory effects on target proteins were examined by immunoblotting. After combination treatment of RNAi with or without irradiation, the cell viability was determined using 3-(4,5-Dimethyl-<span class="hlt">2</span>-thiazolyl)-<span class="hlt">2</span>,5-diphenyl-<span class="hlt">2</span>H-tetrazoliummore » bromide (MTT) and clonogenic assays. The in vivo effect of combined treatment was determined using the U251 xenograft model. The apoptosis caused by the inhibition of STAT3 and ErbB<span class="hlt">2</span> was detected, and the mechanism involved in the apoptosis was investigated, including increases in caspase proteins, mitochondrial damage, and the expression of key modulating protein of different apoptosis pathways. Results: Transfection of U251 cells with STAT3 or ErbB<span class="hlt">2</span> siRNA plasmids specifically reduced their target gene expressions. Inhibition of STAT3 or ErbB<span class="hlt">2</span> greatly decreased glioma cell survival after <span class="hlt">2</span>, 4, or 6 Gy irradiation. Inhibition of STAT3 and ErbB<span class="hlt">2</span> also enhanced radiation-induced tumor growth inhibition in the U251 xenograft model. Furthermore, the suppression of either STAT3 or ErbB<span class="hlt">2</span> could induce U251 cell apoptosis, which was related primarily to the mitochondrial apoptotic pathway. Conclusions: These results indicated that simultaneous inhibition of STAT3 and ErbB<span class="hlt">2</span> expression can promote potent antitumor activity and <span class="hlt">radiosensitizing</span> activity in human glioma.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1124670','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1124670"><span>Low-Dose Radiation Cataract and Genetic Determinants of <span class="hlt">Radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Kleiman, Norman Jay</p> <p></p> <p>The lens of the eye is one of the most <span class="hlt">radiosensitive</span> tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiationmore » exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining <span class="hlt">radiosensitivity</span>. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of <span class="hlt">radiosensitivity</span> and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28560406','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28560406"><span>Silencing of ATM expression by siRNA technique contributes to glioma stem cell <span class="hlt">radiosensitivity</span> in vitro and in vivo.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Yan; Li, Luchun; Wu, Zhijuan; Wang, Lulu; Wu, Yongzhong; Li, Dairong; Ma, Uiwen; Shao, Jianghe; Yu, Huiqing; Wang, Donglin</p> <p>2017-07-01</p> <p>Evidence has shown that both high expression of the ataxia-telangiectasia mutated (ATM) gene and glioma stem cells (GSCs) are responsible for radioresistance in glioma. Thus, we hypothesized that brain tumor <span class="hlt">radiosensitivity</span> may be enhanced via silencing of the ATM gene in GSCs. In the present study we successfully induced GSCs from two cell lines and used CD133 and nestin to identify GSCs. A lentivirus was used to deliver siRNA-ATMPuro (A group) to GSCs prior to radiation, while siRNA-HKPuro (N group) and GSCs (C group) were used as negative and blank controls, respectively. RT-qPCR and western blotting were performed to verify the efficiency of the siRNA-ATM technique. The expression of the ATM gene and ATM protein were significantly downregulated post-transfection. Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that the A group demonstrated weak cell proliferation and lower survival fractions post-irradiation compared to the C/N groups. Flow cytometry was used to examine the percentage of cell apoptosis and <span class="hlt">G</span><span class="hlt">2</span> phase arrest, which were both higher in the A group than in the C/N groups. We found that the comet tail percentage evaluated by comet assay was higher in the A group than in the C/N groups. After radiation treatment, three <span class="hlt">radiosensitive</span> genes [p53, proliferating cell nuclear antigen (PCNA), survivin] exhibited a decreasing tendency as determined by RT-qPCR. Mice underwent subcutaneous implantation, followed by radiation, and the resulting necrosis and hemorrhage were more obvious in the A group than in the N groups. In conclusion, silencing of ATM via the siRNA technique improved <span class="hlt">radiosensitivity</span> of GSCs both in vitro and in vivo.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22458470-mir-modulates-nsclc-cell-radio-sensitivity-through-directly-inhibiting-btg2-expression','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22458470-mir-modulates-nsclc-cell-radio-sensitivity-through-directly-inhibiting-btg2-expression"><span>miR-25 modulates NSCLC cell <span class="hlt">radio-sensitivity</span> through directly inhibiting BTG<span class="hlt">2</span> expression</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>He, Zhiwei, E-mail: carlhe@126.com; Liu, Yi, E-mail: cassieliu@126.com; Xiao, Bing, E-mail: rockg714@aliyun.com</p> <p>2015-02-13</p> <p>A large proportion of the NSCLC patients were insensitive to radiotherapy, but the exact mechanism is still unclear. This study explored the role of miR-25 in regulating sensitivity of NSCLC cells to ionizing radiation (IR) and its downstream targets. Based on measurement in tumor samples from NSCLC patients, this study found that miR-25 expression is upregulated in both NSCLC and radio-resistant NSCLC patients compared the healthy and <span class="hlt">radio-sensitive</span> controls. In addition, BTG expression was found negatively correlated with miR-25a expression in the both tissues and cells. By applying luciferase reporter assay, we verified two putative binding sites between miR-25 andmore » BTG<span class="hlt">2</span>. Therefore, BTG<span class="hlt">2</span> is a directly target of miR-25 in NSCLC cancer. By applying loss-and-gain function analysis in NSCLC cell lines, we demonstrated that miR-25-BTG<span class="hlt">2</span> axis could directly regulated BTG<span class="hlt">2</span> expression and affect radiotherapy sensitivity of NSCLC cells. - Highlights: • miR-25 is upregulated, while BTG<span class="hlt">2</span> is downregulated in radioresistant NSCLC patients. • miR-25 modulates sensitivity to radiation induced apoptosis. • miR-25 directly targets BTG<span class="hlt">2</span> and suppresses its expression. • miR-25 modulates sensitivity to radiotherapy through inhibiting BTG<span class="hlt">2</span> expression.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26303013','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26303013"><span>The yield of DNA double strand breaks determined after exclusion of those forming from heat-labile lesions predicts tumor cell <span class="hlt">radiosensitivity</span> to killing.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cheng, Yanlei; Li, Fanghua; Mladenov, Emil; Iliakis, George</p> <p>2015-09-01</p> <p>The <span class="hlt">radiosensitivity</span> to killing of tumor cells and in-field normal tissue are key determinants of radiotherapy response. In vitro <span class="hlt">radiosensitivity</span> of tumor- and normal-tissue-derived cells often predicts radiation response, but high determination cost in time and resources compromise utility as routine response-predictor. Efforts to use induction or repair of DNA double-strand-breaks (DSBs) as surrogate-predictors of cell <span class="hlt">radiosensitivity</span> to killing have met with limited success. Here, we re-visit this issue encouraged by our recent observations that ionizing radiation (IR) induces not only promptly-forming DSBs (prDSBs), but also DSBs developing after irradiation from the conversion to breaks of thermally-labile sugar-lesions (tlDSBs). We employ pulsed-field gel-electrophoresis and flow-cytometry protocols to measure total DSBs (tDSB=prDSB+tlDSBs) and prDSBs, as well as γH<span class="hlt">2</span>AX and parameters of chromatin structure. We report a fully unexpected and in many ways unprecedented correlation between yield of prDSBs and <span class="hlt">radiosensitivity</span> to killing in a battery of ten tumor cell lines that is not matched by yields of tDSBs or γH<span class="hlt">2</span>AX, and cannot be explained by simple parameters of chromatin structure. We propose the introduction of prDSBs-yield as a novel and powerful surrogate-predictor of cell <span class="hlt">radiosensitivity</span> to killing with potential for clinical application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/AD1034092','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/AD1034092"><span>Targeting MEK5 Enhances <span class="hlt">Radiosensitivity</span> of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2016-09-01</p> <p>AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances <span class="hlt">Radiosensitivity</span> of Human Prostate Cancer and Impairs Tumor- Associated...3. DATES COVERED 31 Aug 2015 - 30 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting MEK5 Enhances <span class="hlt">Radiosensitivity</span> of Human Prostate...therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28677687','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28677687"><span>TOPK modulates tumour-specific <span class="hlt">radiosensitivity</span> and correlates with recurrence after prostate radiotherapy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pirovano, Giacomo; Ashton, Thomas M; Herbert, Katharine J; Bryant, Richard J; Verrill, Clare L; Cerundolo, Lucia; Buffa, Francesca M; Prevo, Remko; Harrap, Iona; Ryan, Anderson J; Macaulay, Valentine; McKenna, William G; Higgins, Geoff S</p> <p>2017-08-08</p> <p>Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers. Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy. TOPK knockdown did not alter radiation response in normal tissues, but significantly enhanced <span class="hlt">radiosensitivity</span> in cancer cells. This result was recapitulated in TOPK knockout cells and with the TOPK inhibitor, OTS964. TOPK depletion altered the <span class="hlt">G</span> 1 /S transition and <span class="hlt">G</span> <span class="hlt">2</span> /M arrest in response to radiation. Furthermore, TOPK depletion increased chromosomal aberrations, multinucleation and apoptotic cell death after irradiation. These results suggest a possible role for TOPK in the radiation-induced DNA damage checkpoints. These findings have clinical relevance, as elevated TOPK protein expression was associated with poorer clinical outcomes in prostate cancer patients treated with radical radiotherapy. This study demonstrates that TOPK disruption may cause tumour-specific radiosensitisation in multiple different tumour types.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29022496','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29022496"><span>Antitumor and <span class="hlt">radiosensitizing</span> synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Medhat, Amina M; Azab, Khaled Sh; Said, Mahmoud M; El Fatih, Neama M; El Bakary, Nermeen M</p> <p>2017-10-01</p> <p>Considerable attention has been paid to the introduction of novel naturally occurring plant-derived <span class="hlt">radiosensitizer</span> compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic <span class="hlt">radiosensitizing</span> effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic <span class="hlt">radiosensitizing</span> efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-<span class="hlt">2</span> and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic <span class="hlt">radiosensitizing</span> efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26967057','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26967057"><span>A chemical screen for medulloblastoma identifies quercetin as a putative <span class="hlt">radiosensitizer</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H W; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A; Vandertop, W Peter; Noske, David P; Kaspers, Gertjan J L; Würdinger, Tom; Hulleman, Esther</p> <p>2016-06-14</p> <p>Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation.Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel <span class="hlt">radiosensitizer</span> for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the <span class="hlt">radiosensitizing</span> properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent <span class="hlt">radiosensitizer</span> for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22678954','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22678954"><span>Combining the LKB NTCP model with <span class="hlt">radiosensitivity</span> parameters to characterize toxicity of radionuclides based on a multiclonogen kidney model: a theoretical assessment.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lin, Hui; Jing, Jia; Xu, Liangfeng; Wu, Dongsheng; Xu, Yuanying</p> <p>2012-06-01</p> <p>The Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model is often used to estimate the damage level to normal tissue. However, it does not manifestly involve the influence of <span class="hlt">radiosensitivity</span> parameters. This work replaces the generalized mean equivalent uniform dose (<span class="hlt">g</span>EUD) with the equivalent uniform dose (EUD) in the LKB model to investigate the effect of a variety of radiobiological parameters on the NTCP to characterize the toxicity of five types of radionuclides. The dose for 50 % complication probability (D (50)) is replaced by the corresponding EUD for 50 % complication probability (EUD(50)). The properties of a variety of radiobiological characteristics, such as biologically effective dose (BED), NTCP, and EUD, for five types of radioisotope ((131)I, (186)Re, (188)Re, (90)Y, and (67)Cu) are investigated by various <span class="hlt">radiosensitivity</span> parameters such as intrinsic <span class="hlt">radiosensitivity</span> α, alpha-beta ratio α/β, cell repair half-time, cell mean clonogen doubling time, etc. The high-energy beta emitters ((90)Y and (188)Re) have high initial dose rate and mean absorbed dose per injected activity in kidney, and their kidney toxicity should be of greater concern if they are excreted through kidneys. The radiobiological effect of (188)Re changes most sharply with the radiobiological parameters due to its high-energy electrons and very short physical half-life. The dose for a probability of 50% injury within 5y (D (50/5)) 28 Gy for whole-kidney irradiation should be adjusted according to different radionuclides and different <span class="hlt">radiosensitivity</span> of individuals. The D (50/5) of individuals with low α/β or low α, or low biological clearance half-time, will be less than 28 Gy. The 50 % complication probability dose for (67)Cu and (188)Re could be 25 Gy and 22 Gy. The same mean absorbed dose generally corresponds to different degrees of damage for tissues of different <span class="hlt">radiosensitivity</span> and different radionuclides. The influence of various</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4041417','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4041417"><span>Histone H3 K79 methylation states play distinct roles in UV-induced sister <span class="hlt">chromatid</span> exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Rossodivita, Alyssa A.; Boudoures, Anna L.; Mecoli, Jonathan P.; Steenkiste, Elizabeth M.; Karl, Andrea L.; Vines, Eudora M.; Cole, Arron M.; Ansbro, Megan R.; Thompson, Jeffrey S.</p> <p>2014-01-01</p> <p>Histone post-translational modifications have been shown to contribute to DNA damage repair. Prior studies have suggested that specific H3K79 methylation states play distinct roles in the response to UV-induced DNA damage. To evaluate these observations, we examined the effect of altered H3K79 methylation patterns on UV-induced <span class="hlt">G</span>1/S checkpoint response and sister <span class="hlt">chromatid</span> exchange (SCE). We found that the di- and trimethylated states both contribute to activation of the <span class="hlt">G</span>1/S checkpoint to varying degrees, depending on the synchronization method, although methylation is not required for checkpoint in response to high levels of UV damage. In contrast, UV-induced SCE is largely a product of the trimethylated state, which influences the usage of gene conversion versus popout mechanisms. Regulation of H3K79 methylation by H<span class="hlt">2</span>BK123 ubiquitylation is important for both checkpoint function and SCE. H3K79 methylation is not required for the repair of double-stranded breaks caused by transient HO endonuclease expression, but does play a modest role in survival from continuous exposure. The overall results provide evidence for the participation of H3K79 methylation in UV-induced recombination repair and checkpoint activation, and further indicate that the di- and trimethylation states play distinct roles in these DNA damage response pathways. PMID:24748660</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29410075','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29410075"><span>The small molecule CS1 inhibits mitosis and sister <span class="hlt">chromatid</span> resolution in HeLa cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wu, Xingkang; Li, Zhenyu; Shen, Yuemao</p> <p>2018-05-01</p> <p>Mitosis, the most dramatic event in the cell cycle, involves the reorganization of virtually all cellular components. Antimitotic agents are useful for dissecting the mechanism of this reorganization. Previously, we found that the small molecule CS1 accumulates cells in <span class="hlt">G</span><span class="hlt">2</span>/M phase [1], but the mechanism of its action remains unknown. Cell cycle analysis, live cell imaging and nuclear staining were used. Chromosomal morphology was detected by chromosome spreading. The effects of CS1 on microtubules were confirmed by tubulin polymerization, colchicine tubulin-binding, cellular tubulin polymerization and immunofluorescence assays and by analysis of microtubule dynamics and molecular modeling. Histone phosphoproteomics was performed using mass spectrometry. Cell signaling cascades were analyzed using immunofluorescence, immunoprecipitation, immunoblotting, siRNA knockdown and chemical inhibition of specific proteins. The small molecule CS1 was shown to be an antimitotic agent. CS1 potently inhibited microtubule polymerization via interaction with the colchicine-binding pocket of tubulin in vitro and inhibited the formation of the spindle apparatus by reducing the bulk of growing microtubules in HeLa cells, which led to activation of the spindle assembly checkpoint (SAC) and mitotic arrest of HeLa cells. Compared with colchicine, CS1 impaired the progression of sister <span class="hlt">chromatid</span> resolution independent of cohesin dissociation, and this was reversed by the removal of CS1. Additionally, CS1 induced unique histone phosphorylation patterns distinct from those induced by colchicine. CS1 is a unique antimitotic small molecule and a powerful tool with unprecedented value over colchicine that makes it possible to specifically and conditionally perturb mitotic progression. Copyright © 2018 Elsevier B.V. All rights reserved.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li class="active"><span>12</span></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_12 --> <div id="page_13" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li class="active"><span>13</span></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="241"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23544166','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23544166"><span>DW-MRI as a Predictive Biomarker of <span class="hlt">Radiosensitization</span> of GBM through Targeted Inhibition of Checkpoint Kinases.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Williams, Terence M; Galbán, Stefanie; Li, Fei; Heist, Kevin A; Galbán, Craig J; Lawrence, Theodore S; Holland, Eric C; Thomae, Tami L; Chenevert, Thomas L; Rehemtulla, Alnawaz; Ross, Brian D</p> <p>2013-04-01</p> <p>The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms including checkpoint kinase (Chk1/<span class="hlt">2</span>)-mediated increased DNA repair capability, which can attenuate the effects of genotoxic chemotherapies and radiation. The goal of this study was to evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a biomarker for Chk1/<span class="hlt">2</span> inhibitors in combination with radiation for enhancement of treatment efficacy in GBM. We evaluated a specific small molecule inhibitor of Chk1/<span class="hlt">2</span>, AZD7762, in combination with radiation using in vitro human cell lines and in vivo using a genetically engineered GBM mouse model. DW-MRI and T1-contrast MRI were used to follow treatment effects on intracranial tumor cellularity and growth rates, respectively. AZD7762 inhibited clonal proliferation in a panel of GBM cell lines and increased <span class="hlt">radiosensitivity</span> in p53-mutated GBM cell lines to a greater extent compared to p53 wild-type cells. In vivo efficacy of AZD7762 demonstrated a dose-dependent inhibitory effect on GBM tumor growth rate and a reduction in tumor cellularity based on DW-MRI scans along with enhancement of radiation efficacy. DW-MRI was found to be a useful imaging biomarker for the detection of <span class="hlt">radiosensitization</span> through inhibition of checkpoint kinases. Chk1/<span class="hlt">2</span> inhibition resulted in antiproliferative activity, prevention of DNA damage-induced repair, and <span class="hlt">radiosensitization</span> in preclinical GBM tumor models, both in vitro and in vivo. The effects were found to be maximal in p53-mutated GBM cells. These results provide the rationale for integration of DW-MRI in clinical translation of Chk1/<span class="hlt">2</span> inhibition with radiation for the treatment of GBM.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22790088','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22790088"><span>The potential value of the neutral comet assay and the expression of genes associated with DNA damage in assessing the <span class="hlt">radiosensitivity</span> of tumor cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jayakumar, Sundarraj; Bhilwade, Hari N; Pandey, Badri N; Sandur, Santosh K; Chaubey, Ramesh C</p> <p>2012-10-09</p> <p>The assessment of tumor <span class="hlt">radiosensitivity</span> would be particularly useful in optimizing the radiation dose during radiotherapy. Therefore, the degree of correlation between radiation-induced DNA damage, as measured by the alkaline and the neutral comet assays, and the clonogenic survival of different human tumor cells was studied. Further, tumor <span class="hlt">radiosensitivity</span> was compared with the expression of genes associated with the cellular response to radiation damage. Five different human tumor cell lines were chosen and the <span class="hlt">radiosensitivity</span> of these cells was established by clonogenic assay. Alkaline and neutral comet assays were performed in γ-irradiated cells (<span class="hlt">2</span>-8Gy; either acute or fractionated). Quantitative PCR was performed to evaluate the expression of DNA damage response genes in control and irradiated cells. The relative <span class="hlt">radiosensitivity</span> of the cell lines assessed by the extent of DNA damage (neutral comet assay) immediately after irradiation (4Gy or 6Gy) was in agreement with <span class="hlt">radiosensitivity</span> pattern obtained by the clonogenic assay. The survival fraction of irradiated cells showed a better correlation with the magnitude of DNA damage measured by the neutral comet assay (r=-0.9; P<0.05; 6Gy) than evaluated by alkaline comet assay (r=-0.73; P<0.05; 6Gy). Further, a significant correlation between the clonogenic survival and DNA damage was observed in cells exposed to fractionated doses of radiation. Of 15 genes investigated in the gene expression study, HSP70, KU80 and RAD51 all showed significant positive correlations (r=0.9; P<0.05) with tumor <span class="hlt">radiosensitivity</span>. Our study clearly demonstrated that the neutral comet assay was better than alkaline comet assay for assessment of <span class="hlt">radiosensitivities</span> of tumor cells after acute or fractionated doses of irradiation. © 2012 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21095075','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21095075"><span>Cell-specific <span class="hlt">radiosensitization</span> by gold nanoparticles at megavoltage radiation energies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jain, Suneil; Coulter, Jonathan A; Hounsell, Alan R; Butterworth, Karl T; McMahon, Stephen J; Hyland, Wendy B; Muir, Mark F; Dickson, Glenn R; Prise, Kevin M; Currell, Fred J; O'Sullivan, Joe M; Hirst, David G</p> <p>2011-02-01</p> <p>Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP <span class="hlt">radiosensitization</span> at clinically relevant MV X-ray energies. Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. <span class="hlt">Radiosensitization</span> was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin. GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97-1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38). We have demonstrated <span class="hlt">radiosensitization</span> in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of <span class="hlt">radiosensitization</span>. Copyright © 2011 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4083825','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4083825"><span><span class="hlt">Radiosensitivity</span> and Induction of Apoptosis by High LET Carbon Ion Beam and Low LET Gamma Radiation: A Comparative Study</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ghorai, Atanu; Bhattacharyya, Nitai P.; Sarma, Asitikantha; Ghosh, Utpal</p> <p>2014-01-01</p> <p>Cancer treatment with high LET heavy ion beam, especially, carbon ion beam (12C), is becoming very popular over conventional radiotherapy like low LET gamma or X-ray. Combination of Poly(ADP-ribose) polymerase (PARP) inhibitor with xenotoxic drugs or conventional radiation (gamma or X-ray) is the newer approach for cancer therapy. The aim of our study was to compare the <span class="hlt">radiosensitivity</span> and induction of apoptosis by high LET 12C and low LET gamma radiation in HeLa and PARP-1 knocked down cells. We did comet assay to detect DNA breaks, clonogenic survival assay, and cell cycle analysis to measure recovery after DNA damage. We measured apoptotic parameters like nuclear fragmentation and caspase-3 activation. DNA damage, cell killing, and induction of apoptosis were significantly higher for 12C than gamma radiation in HeLa. Cell killing and apoptosis were further elevated upon knocking down of PARP-1. Both 12C and gamma induced <span class="hlt">G</span><span class="hlt">2</span>/M arrest although the 12C had greater effect. Unlike the gamma, 12C irradiation affects DNA replication as detected by S-phase delay in cell cycle analysis. So, we conclude that high LET 12C has greater potential over low LET gamma radiation in killing cells and <span class="hlt">radiosensitization</span> upon PARP-1 inhibition was several folds greater for 12C than gamma. PMID:25018892</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22278246-mir-enhances-radiosensitivity-glioblastoma-multiforme-cells-through-targeting-ataxiatelangiectasia-mutated','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22278246-mir-enhances-radiosensitivity-glioblastoma-multiforme-cells-through-targeting-ataxiatelangiectasia-mutated"><span>MiR-26a enhances the <span class="hlt">radiosensitivity</span> of glioblastoma multiforme cells through targeting of ataxia–telangiectasia mutated</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Guo, Pin; Lan, Jin; Ge, Jianwei</p> <p></p> <p>Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new <span class="hlt">radiosensitizers</span> are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance <span class="hlt">radiosensitivity</span> and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3′UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new <span class="hlt">radiosensitizer</span> ofmore » GBM. - Highlights: ●miR-26a directly target ATM in GBM cells. ●miR-26a enhances the <span class="hlt">radiosensitivity</span> of GBM cells. ●miR-26a could reduce the DNA repair capacity of GBM cells.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/978251-increase-telomere-sister-chromatid-exchange-murine-embryonic-stem-cells-possessing-critically-shortened-telomeres','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/978251-increase-telomere-sister-chromatid-exchange-murine-embryonic-stem-cells-possessing-critically-shortened-telomeres"><span>An increase in telomere sister <span class="hlt">chromatid</span> exchange in murine embryonic stem cells possessing critically shortened telomeres</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Wang, Yisong; Giannone, Richard J; Wu, Jun</p> <p></p> <p>Telomerase deficiency leads to a progressive loss of telomeric DNA that eventually triggers cell apoptosis in human primary cells during prolonged growth in culture. Rare survivors can maintain telomere length through either activation of telomerase or recombination-based telomere lengthening, and thus proliferate indefinitely. We have explored the possibility that telomeres may be maintained through telomere sister <span class="hlt">chromatid</span> exchange (T-SCE) in murine telomere reverse transcriptase-deficient (mTert -/-) splenocytes and ES cells. Because telomerase deficiency leads to gradual loss of telomeric DNA in mTert -/- splenocytes and ES cells and eventually to chromosomes with telomere signal-free ends (SFEs), we examined these cellmore » types for evidence of sister <span class="hlt">chromatid</span> exchange at telomeres, and observed an increase in T-SCEs only in a subset of mTert -/- splenocytes or ES cells that possessed multiple SFEs. Furthermore, T-SCEs were more often detected in ES cells than in splenocytes that harbored a similar frequency of SFEs. In mTert heterozygous (mTert +/-) ES cells or splenocytes, which are known to exhibit a decrease in average telomere length but no SFEs, no increase in T-SCE was observed. In addition to T-SCE, other genomic rearrangements (i.e., SCE) were also significantly increased in mTert -/- ES cells possessing critically short telomeres, but not in splenocytes. Our results suggest that animals and cell culture differ in their ability to carry out genomic rearrangements as a means of maintaining telomere integrity when telomeres become critically shortened.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3994494','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3994494"><span>Enhancement of recombinant myricetin on the <span class="hlt">radiosensitivity</span> of lung cancer A549 and H1299 cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2014-01-01</p> <p>Objective Myricetin, a common dietary flavonoid is widely distributed in fruits and vegetables, and is used as a health food supplement based on its immune function, anti-oxidation, anti-tumor, and anti-inflammatory properties. The aim of this study was to investigate the effects of myricetin on combination with radiotherapy enhance <span class="hlt">radiosensitivity</span> of lung cancer A549 and H1299 cells. Methods A549 cells and H1299 cells were exposed to X-ray with or without myricetin treatment. Colony formation assays, CCK-8 assay, flow cytometry and Caspase-3 level detection were used to evaluate the <span class="hlt">radiosensitization</span> activity of myricetin on cell proliferation and apoptosis in vitro. Nude mouse tumor xenograft model was built to assessed <span class="hlt">radiosensitization</span> effect of myricetin in vivo. Results Compared with the exposed group without myricetin treatment, the groups treated with myricetin showed significantly suppressed cell surviving fraction and proliferation, increased the cell apoptosis and increased Caspase-3 protein expression after X-ray exposure in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in irradiated mice treated with myricetin. Conclusions The study demonstrated both in vitro and in vivo evidence that combination of myricetin with radiotherapy can enhance tumor <span class="hlt">radiosensitivity</span> of pulmonary carcinoma A549 and H1299 cells, and myricetin could be a potential <span class="hlt">radiosensitizer</span> for lung cancer therapy. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5791518001210633 PMID:24650056</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199692','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4199692"><span>Regulation of Centromere Localization of the Drosophila Shugoshin MEI-S332 and Sister-<span class="hlt">Chromatid</span> Cohesion in Meiosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Nogueira, Cristina; Kashevsky, Helena; Pinto, Belinda; Clarke, Astrid; Orr-Weaver, Terry L.</p> <p>2014-01-01</p> <p>The Shugoshin (Sgo) protein family helps to ensure proper chromosome segregation by protecting cohesion at the centromere by preventing cleavage of the cohesin complex. Some Sgo proteins also influence other aspects of kinetochore-microtubule attachments. Although many Sgo members require Aurora B kinase to localize to the centromere, factors controlling delocalization are poorly understood and diverse. Moreover, it is not clear how Sgo function is inactivated and whether this is distinct from delocalization. We investigated these questions in Drosophila melanogaster, an organism with superb chromosome cytology to monitor Sgo localization and quantitative assays to test its function in sister-<span class="hlt">chromatid</span> segregation in meiosis. Previous research showed that in mitosis in cell culture, phosphorylation of the Drosophila Sgo, MEI-S332, by Aurora B promotes centromere localization, whereas Polo phosphorylation promotes delocalization. These studies also suggested that MEI-S332 can be inactivated independently of delocalization, a conclusion supported here by localization and function studies in meiosis. Phosphoresistant and phosphomimetic mutants for the Aurora B and Polo phosphorylation sites were examined for effects on MEI-S332 localization and chromosome segregation in meiosis. Strikingly, MEI-S332 with a phosphomimetic mutation in the Aurora B phosphorylation site prematurely dissociates from the centromeres in meiosis I. Despite the absence of MEI-S332 on meiosis II centromeres in male meiosis, sister <span class="hlt">chromatids</span> segregate normally, demonstrating that detectable levels of this Sgo are not essential for chromosome congression, kinetochore biorientation, or spindle assembly. PMID:25081981</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29866745','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29866745"><span>The XPO1 inhibitor Selinexor inhibits translation and enhances the <span class="hlt">radiosensitivity</span> of glioblastoma cells grown in vitro and in vivo.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wahba, Amy; Rath, Barbara H; O'Neill, John W; Camphausen, Kevin; Tofilon, Philip J</p> <p>2018-06-04</p> <p>Analysis of the radiation-induced translatome of glioblastoma stem-like cells (GSCs) identified an interacting network in which XPO1 serves as a major hub protein. To determine whether this nuclear export protein provides a target for <span class="hlt">radiosensitization</span>, we defined the effects of the clinically relevant XPO1 inhibitor Selinexor on the <span class="hlt">radiosensitivity</span> of glioblastoma cells. As determined by clonogenic survival analysis, Selinexor enhanced the <span class="hlt">radiosensitivity</span> of GSCs but not normal fibroblast cell lines. Based on γH<span class="hlt">2</span>AX foci and neutral comet analyses, Selinexor inhibited the repair of radiation-induced DNA double strand breaks in GSCs suggesting that the Selinexor-induced <span class="hlt">radiosensitization</span> is mediated by an inhibition of DNA repair. Consistent with a role for XPO1 in the nuclear to cytoplasm export of rRNA, Selinexor reduced 5S and 18S rRNA nuclear export in GSCs, which was accompanied by a decrease in gene translation efficiency, as determined from polysome profiles, as well as in protein synthesis. In contrast, rRNA nuclear export and protein synthesis were not reduced in normal cells treated with Selinexor. Orthotopic xenografts initiated from a GSC line were then used to define the in vivo response to Selinexor and radiation. Treatment of mice bearing orthotopic xenografts with Selinexor decreased tumor translational efficiency as determined from polysome profiles. Although Selinexor treatment alone had no effect on the survival of mice with brain tumors, it significantly enhanced the radiation-induced prolongation of survival. These results indicate that Selinexor enhances the <span class="hlt">radiosensitivity</span> of glioblastoma cells and suggest that this effect involves a global inhibition of gene translation. Copyright ©2018, American Association for Cancer Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23255546','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23255546"><span><span class="hlt">Radiosensitivity</span> of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Masunaga, S; Sakurai, Y; Tanaka, H; Hirayama, R; Matsumoto, Y; Uzawa, A; Suzuki, M; Kondo, N; Narabayashi, M; Maruhashi, A; Ono, K</p> <p>2013-01-01</p> <p>To detect the <span class="hlt">radiosensitivity</span> of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). EL4 tumour-bearing C57BL/J mice received 5-bromo-<span class="hlt">2</span>'-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with γ-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a (10)B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. Following γ-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced <span class="hlt">radiosensitivity</span> compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in <span class="hlt">radiosensitivity</span> in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in <span class="hlt">radiosensitivity</span> were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a (10)B-carrier, especially L-para-boronophenylalanine-(10)B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. The <span class="hlt">radiosensitivity</span> of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the (10)B-carrier used in the BNCR. The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12787819','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12787819"><span>Sister <span class="hlt">chromatid</span> exchanges and micronuclei analysis in lymphocytes of men exposed to simazine through drinking water.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Suárez, Susanna; Rubio, Arantxa; Sueiro, Rosa Ana; Garrido, Joaquín</p> <p>2003-06-06</p> <p>In some cities of the autonomous community of Extremadura (south-west of Spain), levels of simazine from 10 to 30 ppm were detected in tap water. To analyse the possible effect of this herbicide, two biomarkers, sister <span class="hlt">chromatid</span> exchanges (SCE) and micronuclei (MN), were used in peripheral blood lymphocytes from males exposed to simazine through drinking water. SCE and MN analysis failed to detect any statistically significant increase in the people exposed to simazine when compared with the controls. With respect to high frequency cells (HFC), a statistically significant difference was detected between exposed and control groups.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27220342','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27220342"><span>Zidovudine, abacavir and lamivudine increase the <span class="hlt">radiosensitivity</span> of human esophageal squamous cancer cell lines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng</p> <p>2016-07-01</p> <p>Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for <span class="hlt">radiosensitization</span> targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the <span class="hlt">radiosensitization</span> effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of <span class="hlt">2</span>, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the <span class="hlt">radiosensitization</span> of esophageal squamous cell cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27341700','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27341700"><span>Nontoxic concentration of DNA-PK inhibitor NU7441 <span class="hlt">radio-sensitizes</span> lung tumor cells with little effect on double strand break repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sunada, Shigeaki; Kanai, Hideki; Lee, Younghyun; Yasuda, Takeshi; Hirakawa, Hirokazu; Liu, Cuihua; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi</p> <p>2016-09-01</p> <p>High-linear energy transfer (LET) heavy ions have been increasingly employed as a useful alternative to conventional photon radiotherapy. As recent studies suggested that high LET radiation mainly affects the nonhomologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair, we further investigated this concept by evaluating the combined effect of an NHEJ inhibitor (NU7441) at a non-toxic concentration and carbon ions. NU7441-treated non-small cell lung cancer (NSCLC) A549 and H1299 cells were irradiated with X-rays and carbon ions (290 MeV/n, 50 keV/μm). Cell survival was measured by clonogenic assay. DNA DSB repair, cell cycle distribution, DNA fragmentation and cellular senescence induction were studied using a flow cytometer. Senescence-associated protein p21 was detected by western blotting. In the present study, 0.3 μM of NU7441, nontoxic to both normal and tumor cells, caused a significant <span class="hlt">radio-sensitization</span> in tumor cells exposed to X-rays and carbon ions. This concentration did not seem to cause inhibition of DNA DSB repair but induced a significant <span class="hlt">G</span><span class="hlt">2</span>/M arrest, which was particularly emphasized in p53-null H1299 cells treated with NU7441 and carbon ions. In addition, the combined treatment induced more DNA fragmentation and a higher degree of senescence in H1299 cells than in A549 cells, indicating that DNA-PK inhibitor contributes to various modes of cell death in a p53-dependent manner. In summary, NSCLC cells irradiated with carbon ions were <span class="hlt">radio-sensitized</span> by a low concentration of DNA-PK inhibitor NU7441 through a strong <span class="hlt">G</span><span class="hlt">2</span>/M cell cycle arrest. Our findings may contribute to further effective radiotherapy using heavy ions. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5558685','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5558685"><span>TOPK modulates tumour-specific <span class="hlt">radiosensitivity</span> and correlates with recurrence after prostate radiotherapy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pirovano, Giacomo; Ashton, Thomas M; Herbert, Katharine J; Bryant, Richard J; Verrill, Clare L; Cerundolo, Lucia; Buffa, Francesca M; Prevo, Remko; Harrap, Iona; Ryan, Anderson J; Macaulay, Valentine; McKenna, William G; Higgins, Geoff S</p> <p>2017-01-01</p> <p>Background: Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers. Methods: Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy. Results: TOPK knockdown did not alter radiation response in normal tissues, but significantly enhanced <span class="hlt">radiosensitivity</span> in cancer cells. This result was recapitulated in TOPK knockout cells and with the TOPK inhibitor, OTS964. TOPK depletion altered the <span class="hlt">G</span>1/S transition and <span class="hlt">G</span><span class="hlt">2</span>/M arrest in response to radiation. Furthermore, TOPK depletion increased chromosomal aberrations, multinucleation and apoptotic cell death after irradiation. These results suggest a possible role for TOPK in the radiation-induced DNA damage checkpoints. These findings have clinical relevance, as elevated TOPK protein expression was associated with poorer clinical outcomes in prostate cancer patients treated with radical radiotherapy. Conclusions: This study demonstrates that TOPK disruption may cause tumour-specific radiosensitisation in multiple different tumour types. PMID:28677687</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28371526','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28371526"><span>Development of a Hypoxic <span class="hlt">Radiosensitizer</span>-Prodrug Liposome Delivery DNA Repair Inhibitor Dbait Combination with Radiotherapy for Glioma Therapy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Liu, Hongmei; Cai, Yifan; Zhang, Yafei; Xie, Yandong; Qiu, Hui; Hua, Lei; Liu, Xuejiao; Li, Yuling; Lu, Jun; Zhang, Longzhen; Yu, Rutong</p> <p>2017-06-01</p> <p>Gliomas are highly radioresistant tumors, mainly due to hypoxia in the core region of the gliomas and efficient DNA double-strand break repair. However, the design of a <span class="hlt">radiosensitizer</span> incorporating the two above mechanisms is difficult and has rarely been reported. Thus, this study develops a hypoxic <span class="hlt">radiosensitizer</span>-prodrug liposome (MLP) to deliver the DNA repair inhibitor Dbait (MLP/Dbait) to achieve the simultaneous entry of <span class="hlt">radiosensitizers</span> with two different mechanisms into the glioma. MLP/Dbait effectively sensitizes glioma cells to X-ray radiotherapy (RT). Histological and microscopic examinations of dissected brain tissue confirm that MLP effectively delivers Dbait into the glioma. Furthermore, the combination of MLP/Dbait with RT significantly inhibits growth of the glioma, as assessed by in vivo bioluminescence imaging. These findings suggest that MLP is a promising candidate as a Dbait delivery system to enhance the effect of RT on glioma, owing to the synergistic effects of the two different <span class="hlt">radiosensitizers</span>. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28590163','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28590163"><span>Merotelic kinetochore attachment in oocyte meiosis II causes sister <span class="hlt">chromatids</span> segregation errors in aged mice.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cheng, Jin-Mei; Li, Jian; Tang, Ji-Xin; Hao, Xiao-Xia; Wang, Zhi-Peng; Sun, Tie-Cheng; Wang, Xiu-Xia; Zhang, Yan; Chen, Su-Ren; Liu, Yi-Xun</p> <p>2017-08-03</p> <p>Mammalian oocyte chromosomes undergo <span class="hlt">2</span> meiotic divisions to generate haploid gametes. The frequency of chromosome segregation errors during meiosis I increase with age. However, little attention has been paid to the question of how aging affects sister <span class="hlt">chromatid</span> segregation during oocyte meiosis II. More importantly, how aneuploid metaphase II (MII) oocytes from aged mice evade the spindle assembly checkpoint (SAC) mechanism to complete later meiosis II to form aneuploid embryos remains unknown. Here, we report that MII oocytes from naturally aged mice exhibited substantial errors in chromosome arrangement and configuration compared with young MII oocytes. Interestingly, these errors in aged oocytes had no impact on anaphase II onset and completion as well as <span class="hlt">2</span>-cell formation after parthenogenetic activation. Further study found that merotelic kinetochore attachment occurred more frequently and could stabilize the kinetochore-microtubule interaction to ensure SAC inactivation and anaphase II onset in aged MII oocytes. This orientation could persist largely during anaphase II in aged oocytes, leading to severe chromosome lagging and trailing as well as delay of anaphase II completion. Therefore, merotelic kinetochore attachment in oocyte meiosis II exacerbates age-related genetic instability and is a key source of age-dependent embryo aneuploidy and dysplasia.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016RaPC..128..134B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016RaPC..128..134B"><span>Actual questions raised by nanoparticle <span class="hlt">radiosensitization</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Brun, Emilie; Sicard-Roselli, Cécile</p> <p>2016-11-01</p> <p><span class="hlt">Radiosensitization</span> by metallic nanoparticles (NP) has been explored for more than a decade with promising results in vitro and in cellulo reported in a vast number of publications. Yet, few clinical trials are on-going. This could be related to the lack of selectivity of NP leading to massive quantities to be injected to observe an effect but also to the higher degree of complexity than first thought leading to an absence of consensus probably caused by the lack of standardization in pre-clinical studies. Given the wide panel of NP used, in terms of core nature, size, coating, not to mention of cell lines and irradiation modalities, cross-comparison of data is not a walk in the park. But only a thorough examination could help identifying the key parameters and the possible mechanisms involved. This step is crucial as it should provide guidance for designing the most efficient combination NP/radiation and rationally establishing clinical protocols. In this review, we will combine and confront cellular <span class="hlt">radiosensitization</span> results with in vitro and numerical experiments in order to give the more recent vision of this complex phenomenon. We decided to address a few hot topics such as the influence of the incident radiation energy, the localization of NP or the so-called ;biological; effect. We will highlight that among the barriers to break down, some are not restricted to the ;nano; community: an incontestable support could be offered by the ;radiation; community in the broadest sense.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/301871','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/301871"><span>Effect of salt solutions on <span class="hlt">radiosensitivity</span> of mammalian cells. I. Specific ion effects.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Raaphorst, G P; Kruuv, J</p> <p>1977-07-01</p> <p>The radiation isodose survival curve of cells subjected to a wide concentration range of sucrose solutions has two maxima separated by a minimum. Both cations and anions can alter the cellular <span class="hlt">radiosensitivity</span> above and beyond the osmotic effect observed for cells treated with sucrose solutions. The basic shape of the isodose curve can also be modulated by changes in temperature and solution exposure times. Some of these alterations in <span class="hlt">radiosensitivity</span> may be related to changes in the amount and structure of cellular water or macromolecular conformation or to the direct effect of the ions, expecially at high solute concentrations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21270338','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21270338"><span>Uroporphyrinogen decarboxylase is a <span class="hlt">radiosensitizing</span> target for head and neck cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ito, Emma; Yue, Shijun; Moriyama, Eduardo H; Hui, Angela B; Kim, Inki; Shi, Wei; Alajez, Nehad M; Bhogal, Nirmal; Li, Guohua; Datti, Alessandro; Schimmer, Aaron D; Wilson, Brian C; Liu, Peter P; Durocher, Daniel; Neel, Benjamin G; O'Sullivan, Brian; Cummings, Bernard; Bristow, Rob; Wrana, Jeff; Liu, Fei-Fei</p> <p>2011-01-26</p> <p>Head and neck cancer (HNC) is the eighth most common malignancy worldwide, comprising a diverse group of cancers affecting the head and neck region. Despite advances in therapeutic options over the last few decades, treatment toxicities and overall clinical outcomes have remained disappointing, thereby underscoring a need to develop novel therapeutic approaches in HNC treatment. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, was identified from an RNA interference-based high-throughput screen as a tumor-selective <span class="hlt">radiosensitizing</span> target for HNC. UROD knockdown plus radiation induced caspase-mediated apoptosis and cell cycle arrest in HNC cells in vitro and suppressed the in vivo tumor-forming capacity of HNC cells, as well as delayed the growth of established tumor xenografts in mice. This <span class="hlt">radiosensitization</span> appeared to be mediated by alterations in iron homeostasis and increased production of reactive oxygen species, resulting in enhanced tumor oxidative stress. Moreover, UROD was significantly overexpressed in HNC patient biopsies. Lower preradiation UROD mRNA expression correlated with improved disease-free survival, suggesting that UROD could potentially be used to predict radiation response. UROD down-regulation also <span class="hlt">radiosensitized</span> several different models of human cancer, as well as sensitized tumors to chemotherapeutic agents, including 5-fluorouracil, cisplatin, and paclitaxel. Thus, our study has revealed UROD as a potent tumor-selective sensitizer for both radiation and chemotherapy, with potential relevance to many human malignancies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4316198','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4316198"><span>Comprehensive Profiling of <span class="hlt">Radiosensitive</span> Human Cell Lines with DNA Damage Response Assays Identifies the Neutral Comet Assay as a Potential Surrogate for Clonogenic Survival</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Nahas, Shareef A.; Davies, Robert; Fike, Francesca; Nakamura, Kotoka; Du, Liutao; Kayali, Refik; Martin, Nathan T.; Concannon, Patrick; Gatti, Richard A.</p> <p>2015-01-01</p> <p>In an effort to explore the possible causes of human <span class="hlt">radiosensitivity</span> and identify more rapid assays for cellular <span class="hlt">radiosensitivity</span>, we interrogated a set of assays that evaluate cellular functions involved in recognition and repair of DNA double-strand breaks: (1) neutral comet assay, (<span class="hlt">2</span>) radiation-induced γ-H<span class="hlt">2</span>AX focus formation, (3) the temporal kinetics of structural maintenance of chromosomes 1 phosphorylation, (4) intra-S-phase checkpoint integrity, and (5) mitochondrial respiration. We characterized a unique panel of 19 “radiosensitive” human lymphoblastoid cell lines from individuals with undiagnosed diseases suggestive of a DNA repair disorder. <span class="hlt">Radiosensitivity</span> was defined by reduced cellular survival using a clonogenic survival assay. Each assay identified cell lines with defects in DNA damage response functions. The highest concordance rate observed, 89% (17/19), was between an abnormal neutral comet assay and reduced survival by the colony survival assay. Our data also suggested that the neutral comet assay would be a more rapid surrogate for analyzing DNA repair/processing disorders. PMID:21962002</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li class="active"><span>13</span></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_13 --> <div id="page_14" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li class="active"><span>14</span></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="261"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011SPIE.7901E..0EG','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011SPIE.7901E..0EG"><span>Comparison of microwave and magnetic nanoparticle hyperthermia <span class="hlt">radiosensitization</span> in murine breast tumors</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.</p> <p>2011-03-01</p> <p>Hyperthermia has been shown to be an effective <span class="hlt">radiosensitizer</span>. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor <span class="hlt">radiosensitization</span> potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the <span class="hlt">radiosensitization</span> effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater <span class="hlt">radiosensitization</span> / therapeutic ratio enhancement than other forms of hyperthermia delivery.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24815473','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24815473"><span><span class="hlt">Radio-sensitization</span> by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yao, Jian-Xin; Yao, Zhi-Feng; Li, Zhan-Feng; Liu, Yong-Biao</p> <p>2014-01-01</p> <p>The current study investigated the effects of Piper longumine on <span class="hlt">radio-sensitization</span> of human breast cancer MDA-MB-231 cells and underlying mechanisms. Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the <span class="hlt">radio-sensitizing</span> effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-<span class="hlt">2</span> and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF<span class="hlt">2</span>, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-<span class="hlt">2</span> with increased Bax. Piper longumine at a non-cytotoxic concentration can enhance the <span class="hlt">radio-sensitivity</span> of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4038454','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4038454"><span>Optimal energy for cell <span class="hlt">radiosensitivity</span> enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi</p> <p>2014-01-01</p> <p>Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel <span class="hlt">radiosensitizing</span> agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum <span class="hlt">radiosensitization</span> effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of <span class="hlt">radiosensitization</span> by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell <span class="hlt">radiosensitivity</span> enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the <span class="hlt">radiosensitization</span> effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24899803','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24899803"><span>Optimal energy for cell <span class="hlt">radiosensitivity</span> enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi</p> <p>2014-01-01</p> <p>Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel <span class="hlt">radiosensitizing</span> agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum <span class="hlt">radiosensitization</span> effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of <span class="hlt">radiosensitization</span> by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell <span class="hlt">radiosensitivity</span> enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the <span class="hlt">radiosensitization</span> effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4433451','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4433451"><span>Targeting MPS1 Enhances <span class="hlt">Radiosensitization</span> of Human Glioblastoma by Modulating DNA Repair Proteins</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Maachani, Uday B.; Kramp, Tamalee; Hanson, Ryan; Zhao, Shuping; Celiku, Orieta; Shankavaram, Uma; Colombo, Riccardo; Caplen, Natasha J.; Camphausen, Kevin; Tandle, Anita</p> <p>2015-01-01</p> <p>To ensure faithful chromosome segregation, cells use the spindle assembly checkpoint (SAC), which can be activated in aneuploid cancer cells. Targeting the components of SAC machinery required for the growth of aneuploid cells may offer a cancer cell specific therapeutic approach. In this study, the effects of inhibiting Monopolar spindle 1, MPS1 (TTK), an essential SAC kinase, on the <span class="hlt">radiosensitization</span> of glioblastoma (GBM) cells was analyzed. Clonogenic survival was used to determine the effects of the MPS1 inhibitor, NMS-P715 on <span class="hlt">radiosensitivity</span> in multiple model systems including: GBM cell lines, a normal astrocyte and a normal fibroblast cell line. DNA double strand breaks (DSBs) were evaluated using γH<span class="hlt">2</span>AX foci and cell death was measured by mitotic catastrophe evaluation. Transcriptome analysis was performed via unbiased microarray expression profiling. Tumor xenografts grown from GBM cells were used in tumor growth delay studies. Inhibition of MPS1 activity resulted in reduced GBM cell proliferation. Further, NMS-P715 enhanced the <span class="hlt">radiosensitivity</span> of GBM cells by decreased repair of DSBs and induction of post-radiation mitotic catastrophe. MNS-P715 in combination with fractionated doses of radiation significantly enhanced the tumor growth delay. Molecular profiling of MPS1 silenced GBM cells showed an altered expression of transcripts associated with DNA damage, repair and replication including the DNA-dependent protein kinase (PRKDC/DNAPK). Next, inhibition of MPS1 blocked two important DNA repair pathways. In conclusion, these results not only highlight a role for MPS1 kinase in DNA repair and as prognostic marker but also indicate it as a viable option in glioblastoma therapy. PMID:25722303</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6869884-radiosensitivity-fibroblasts-obtained-from-cafe-au-lait-spot-normal-appearing-skin-patient-neurofibromatosis-nf','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6869884-radiosensitivity-fibroblasts-obtained-from-cafe-au-lait-spot-normal-appearing-skin-patient-neurofibromatosis-nf"><span><span class="hlt">Radiosensitivity</span> of fibroblasts obtained from a cafe-au-lait spot and normal-appearing skin of a patient with neurofibromatosis (NF-6)</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hannan, M.A.; Smith, B.P.; Sigut, D.</p> <p></p> <p>Fibroblast cells derived from a cafe-au-lait spot and normal-appearing skin of a neurofibromatosis (NF-6) patient were studied for <span class="hlt">radiosensitivity</span> in comparison with two normal cell lines used as controls. No difference in <span class="hlt">radiosensitivity</span> was observed between the patient's cell lines and the controls using acute gamma-irradiation. However, a markedly increased <span class="hlt">radiosensitivity</span> of the fibroblasts obtained from the patient's skin of normal appearance was demonstrated after chronic gamma-irradiation. The cells from the cafe-au-lait spot showed intermediate sensitivity to chronic irradiation as compared with the control cell lines and the fibroblasts derived from the normal skin of the patient. These results showedmore » the usefulness of chronic irradiation in detecting increased cellular <span class="hlt">radiosensitivity</span> which may result from a unique DNA repair defect in an NF patient. We suggest that enhanced genetic changes in <span class="hlt">radiosensitive</span> NF patients may lead to formation of cafe-au-lait lesions and certain tumors. Such a transformation may be associated with production of radiotolerant cells.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29299946','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29299946"><span>A new approach for modeling patient overall <span class="hlt">radiosensitivity</span> and predicting multiple toxicity endpoints for breast cancer patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mbah, Chamberlain; De Ruyck, Kim; De Schrijver, Silke; De Sutter, Charlotte; Schiettecatte, Kimberly; Monten, Chris; Paelinck, Leen; De Neve, Wilfried; Thierens, Hubert; West, Catharine; Amorim, Gustavo; Thas, Olivier; Veldeman, Liv</p> <p>2018-05-01</p> <p>Evaluation of patient characteristics inducing toxicity in breast radiotherapy, using simultaneous modeling of multiple endpoints. In 269 early-stage breast cancer patients treated with whole-breast irradiation (WBI) after breast-conserving surgery, toxicity was scored, based on five dichotomized endpoints. Five logistic regression models were fitted, one for each endpoint and the effect sizes of all variables were estimated using maximum likelihood (MLE). The MLEs are improved with James-Stein estimates (JSEs). The method combines all the MLEs, obtained for the same variable but from different endpoints. Misclassification errors were computed using MLE- and JSE-based prediction models. For associations, p-values from the sum of squares of MLEs were compared with p-values from the Standardized Total Average Toxicity (STAT) Score. With JSEs, 19 highest ranked variables were predictive of the five different endpoints. Important variables increasing radiation-induced toxicity were chemotherapy, age, SATB<span class="hlt">2</span> rs2881208 SNP and nodal irradiation. Treatment position (prone position) was most protective and ranked eighth. Overall, the misclassification errors were 45% and 34% for the MLE- and JSE-based models, respectively. p-Values from the sum of squares of MLEs and p-values from STAT score led to very similar conclusions, except for the variables nodal irradiation and treatment position, for which STAT p-values suggested an association with <span class="hlt">radiosensitivity</span>, whereas p-values from the sum of squares indicated no association. Breast volume was ranked as the most significant variable in both strategies. The James-Stein estimator was used for selecting variables that are predictive for multiple toxicity endpoints. With this estimator, 19 variables were predictive for all toxicities of which four were significantly associated with overall <span class="hlt">radiosensitivity</span>. JSEs led to almost 25% reduction in the misclassification error rate compared to conventional MLEs. Finally, patient</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=19740060090&hterms=mitosis&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dmitosis','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=19740060090&hterms=mitosis&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Dmitosis"><span>Circadian rhythmometry of mammalian <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Haus, E.; Halberg, F.; Loken, M. K.; Kim, Y. S.</p> <p>1974-01-01</p> <p>In the case of human bone marrow, the largest number of mitoses is seen in the evening in diurnally active men, mitotic activity being at a minimum in the morning. The opposite pattern is observed for nocturnal animals such as rats and mice on a regimen of light during the daytime alternating with darkness during the night hours. The entirety of these rhythms plays an important role in the organism's responses to environmental stimuli, including its resistance to potentially harmful agents. Conditions under which circadian rhythms can be observed and validated by inferential statistical means are discussed while emphasizing how artifacts of the laboratory environment can be shown to obscure circadian periodic variations in <span class="hlt">radiosensitivity</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20050182934','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20050182934"><span>Towards <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span>: Systems of Technology Database Systems</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Maluf, David A.; Bell, David</p> <p>2005-01-01</p> <p>We present an approach and methodology for developing Government-to-Government (<span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span>) Systems of Technology Database Systems. <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> will deliver technologies for distributed and remote integration of technology data for internal use in analysis and planning as well as for external communications. <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> enables NASA managers, engineers, operational teams and information systems to "compose" technology roadmaps and plans by selecting, combining, extending, specializing and modifying components of technology database systems. <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> will interoperate information and knowledge that is distributed across organizational entities involved that is ideal for NASA future Exploration Enterprise. Key contributions of the <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> system will include the creation of an integrated approach to sustain effective management of technology investments that supports the ability of various technology database systems to be independently managed. The integration technology will comply with emerging open standards. Applications can thus be customized for local needs while enabling an integrated management of technology approach that serves the global needs of NASA. The <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> capabilities will use NASA s breakthrough in database "composition" and integration technology, will use and advance emerging open standards, and will use commercial information technologies to enable effective System of Technology Database systems.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3368509','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3368509"><span>Doxorubicin-mediated <span class="hlt">radiosensitivity</span> in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xu, Wen-Hong; Han, Min; Dong, Qi; Fu, Zhi-Xuan; Diao, Yuan-Yuan; Liu, Hai; Xu, Jing; Jiang, Hong-Liang; Zhang, Su-Zhan; Zheng, Shu; Gao, Jian-Qing; Wei, Qi-Chun</p> <p>2012-01-01</p> <p>Background The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin <span class="hlt">radiosensitivity</span> in multicellular spheroids from a non-small cell lung cancer cell line. Methods A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin <span class="hlt">radiosensitization</span> and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. Results Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are <span class="hlt">radiosensitive</span>, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher <span class="hlt">radiosensitivity</span> for the composite micelles loaded with doxorubicin than for free doxorubicin. Conclusion Our composite doxorubicin-loaded micelle was demonstrated to have <span class="hlt">radiosensitization</span>. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer. PMID:22679376</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12175307','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12175307"><span>DNA-targeted <span class="hlt">2</span>-nitroimidazoles: studies of the influence of the phenanthridine-linked nitroimidazoles, <span class="hlt">2</span>-NLP-3 and <span class="hlt">2</span>-NLP-4, on DNA damage induced by ionizing radiation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Buchko, Garry W; Weinfeld, Michael</p> <p>2002-09-01</p> <p>The nitroimidazole-linked phenanthridines <span class="hlt">2</span>-NLP-3 (5-[3-(<span class="hlt">2</span>-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide) and <span class="hlt">2</span>-NLP-4 (5-[3-(<span class="hlt">2</span>-nitro-1-imidazoyl)-butyl]-phenanthridinium bromide) are composed of the <span class="hlt">radiosensitizer</span>, <span class="hlt">2</span>-nitroimidazole, attached to the DNA intercalator phenanthridine by a 3- and 4-carbon linker, respectively. Previous in vitro assays showed both compounds to be 10-100 times more efficient as hypoxic cell <span class="hlt">radiosensitizers</span> (based on external drug concentrations) than the untargeted <span class="hlt">2</span>-nitroimidazole <span class="hlt">radiosensitizer</span>, misonidazole (Cowan et al., Radiat. Res. 127, 81-89, 1991). Here we have used a (32)P postlabeling assay and 5'-end-labeled oligonucleotide assay to compare the radiation-induced DNA damage generated in the presence of <span class="hlt">2</span>-NLP-3, <span class="hlt">2</span>-NLP-4, phenanthridine and misonidazole. After irradiation of the DNA under anoxic conditions, we observed a significantly greater level of 3'-phosphoglycolate DNA damage in the presence of <span class="hlt">2</span>-NLP-3 or <span class="hlt">2</span>-NLP-4 compared to irradiation of the DNA in the presence of misonidazole. This may account at least in part for the greater cellular <span class="hlt">radiosensitization</span> shown by the nitroimidazole-linked phenanthridines over misonidazole. Of the two nitroimidazole-linked phenanthridines, the better in vitro <span class="hlt">radiosensitizer</span>, <span class="hlt">2</span>-NLP-4, generated more 3'-phosphoglycolate in DNA than did <span class="hlt">2</span>-NLP-3. At all concentrations, phenanthridine had little effect on the levels of DNA damage, suggesting that the enhanced <span class="hlt">radiosensitization</span> displayed by <span class="hlt">2</span>-NLP-3 and <span class="hlt">2</span>-NLP-4 is due to the localization of the <span class="hlt">2</span>-nitroimidazole to the DNA by the phenanthridine substituent and not to <span class="hlt">radiosensitization</span> by the phenanthridine moiety itself.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22224430-poor-prognosis-associated-human-papillomavirus-genotypes-cervical-carcinoma-cannot-explained-intrinsic-radiosensitivity','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22224430-poor-prognosis-associated-human-papillomavirus-genotypes-cervical-carcinoma-cannot-explained-intrinsic-radiosensitivity"><span>Poor Prognosis Associated With Human Papillomavirus α7 Genotypes in Cervical Carcinoma Cannot Be Explained by Intrinsic <span class="hlt">Radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hall, John S.; Iype, Rohan; Armenoult, Lucile S.C.</p> <p>2013-04-01</p> <p>Purpose: To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic <span class="hlt">radiosensitivity</span>. Methods and Materials: HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA{sub 25}) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic <span class="hlt">radiosensitivity</span> was measured as surviving fraction at <span class="hlt">2</span> Gy (SF<span class="hlt">2</span>) using clonogenicmore » assays. Results: Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF<span class="hlt">2</span> of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF<span class="hlt">2</span> between α9 and α7 cell lines (n=14). Conclusion: The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic <span class="hlt">radiosensitivity</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25722303','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25722303"><span>Targeting MPS1 Enhances <span class="hlt">Radiosensitization</span> of Human Glioblastoma by Modulating DNA Repair Proteins.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Maachani, Uday Bhanu; Kramp, Tamalee; Hanson, Ryan; Zhao, Shuping; Celiku, Orieta; Shankavaram, Uma; Colombo, Riccardo; Caplen, Natasha J; Camphausen, Kevin; Tandle, Anita</p> <p>2015-05-01</p> <p>To ensure faithful chromosome segregation, cells use the spindle assembly checkpoint (SAC), which can be activated in aneuploid cancer cells. Targeting the components of SAC machinery required for the growth of aneuploid cells may offer a cancer cell-specific therapeutic approach. In this study, the effects of inhibiting Monopolar spindle 1, MPS1 (TTK), an essential SAC kinase, on the <span class="hlt">radiosensitization</span> of glioblastoma (GBM) cells were analyzed. Clonogenic survival was used to determine the effects of the MPS1 inhibitor NMS-P715 on <span class="hlt">radiosensitivity</span> in multiple model systems, including GBM cell lines, a normal astrocyte, and a normal fibroblast cell line. DNA double-strand breaks (DSB) were evaluated using γH<span class="hlt">2</span>AX foci, and cell death was measured by mitotic catastrophe evaluation. Transcriptome analysis was performed via unbiased microarray expression profiling. Tumor xenografts grown from GBM cells were used in tumor growth delay studies. Inhibition of MPS1 activity resulted in reduced GBM cell proliferation. Furthermore, NMS-P715 enhanced the <span class="hlt">radiosensitivity</span> of GBM cells by decreased repair of DSBs and induction of postradiation mitotic catastrophe. NMS-P715 in combination with fractionated doses of radiation significantly enhanced the tumor growth delay. Molecular profiling of MPS1-silenced GBM cells showed an altered expression of transcripts associated with DNA damage, repair, and replication, including the DNA-dependent protein kinase (PRKDC/DNAPK). Next, inhibition of MPS1 blocked two important DNA repair pathways. In conclusion, these results not only highlight a role for MPS1 kinase in DNA repair and as prognostic marker but also indicate it as a viable option in glioblastoma therapy. Inhibition of MPS1 kinase in combination with radiation represents a promising new approach for glioblastoma and for other cancer therapies. ©2015 American Association for Cancer Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016JChPh.144v4309H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016JChPh.144v4309H"><span>Dissociative electron attachment to the <span class="hlt">radiosensitizing</span> chemotherapeutic agent hydroxyurea</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Huber, S. E.; Śmiałek, M. A.; Tanzer, K.; Denifl, S.</p> <p>2016-06-01</p> <p>Dissociative electron attachment to hydroxyurea was studied in the gas phase for electron energies ranging from zero to 9 eV in order to probe its <span class="hlt">radiosensitizing</span> capabilities. The experiments were carried out using a hemispherical electron monochromator coupled with a quadrupole mass spectrometer. Diversified fragmentation of hydroxyurea was observed upon low energy electron attachment and here we highlight the major dissociation channels. Moreover, thermodynamic thresholds for various fragmentation reactions are reported to support the discussion of the experimental findings. The dominant dissociation channel, which was observed over a broad range of energies, is associated with formation of NCO-, water, and the amidogen (NH<span class="hlt">2</span>) radical. The second and third most dominant dissociation channels are associated with formation of NCNH- and NHCONH<span class="hlt">2</span>-, respectively, which are both directly related to formation of the highly reactive hydroxyl radical. Other ions observed with significant abundance in the mass spectra were NH<span class="hlt">2</span>-/O-, OH-, CN-, HNOH-, NCONH<span class="hlt">2</span>-, and ONHCONH<span class="hlt">2</span>-.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23452621','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23452621"><span>Molecular basis of 'hypoxic' breast cancer cell <span class="hlt">radio-sensitization</span>: phytochemicals converge on radiation induced Rel signaling.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Aravindan, Sheeja; Natarajan, Mohan; Herman, Terence S; Awasthi, Vibhudutta; Aravindan, Natarajan</p> <p>2013-03-04</p> <p>Heterogeneously distributed hypoxic areas are a characteristic property of locally advanced breast cancers (BCa) and generally associated with therapeutic resistance, metastases, and poor patient survival. About 50% of locally advanced BCa, where radiotherapy is less effective are suggested to be due to hypoxic regions. In this study, we investigated the potential of bioactive phytochemicals in <span class="hlt">radio-sensitizing</span> hypoxic BCa cells. Hypoxic (O<span class="hlt">2-2</span>.5%; N<span class="hlt">2</span>-92.5%; CO<span class="hlt">2</span>-5%) MCF-7 cells were exposed to 4 Gy radiation (IR) alone or after pretreatment with Curcumin (CUR), curcumin analog EF24, neem leaf extract (NLE), Genistein (GEN), Resveratrol (RES) or raspberry extract (RSE). The cells were examined for inhibition of NFκB activity, transcriptional modulation of 88 NFκB signaling pathway genes, activation and cellular localization of radio-responsive NFκB related mediators, eNos, Erk1/<span class="hlt">2</span>, SOD<span class="hlt">2</span>, Akt1/<span class="hlt">2</span>/3, p50, p65, pIκBα, TNFα, Birc-1, -<span class="hlt">2</span>, -5 and associated induction of cell death. EMSA revealed that cells exposed to phytochemicals showed complete suppression of IR-induced NFκB. Relatively, cells exposed EF24 revealed a robust inhibition of IR-induced NFκB. QPCR profiling showed induced expression of 53 NFκB signaling pathway genes after IR. Conversely, 53, 50, 53, 53, 53 and 53 of IR-induced genes were inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. In addition, 25, 29, 24, 16, 11 and 21 of 35 IR-suppressed genes were further inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. Immunoblotting revealed a significant attenuating effect of IR-modulated radio-responsive eNos, Erk1/<span class="hlt">2</span>, SOD<span class="hlt">2</span>, Akt1/<span class="hlt">2</span>/3, p50, p65, pIκBα, TNFα, Birc-1, -<span class="hlt">2</span> and -5 with EF24, NLE, CUR, GEN, RES or RSE. Annexin V-FITC staining showed a consistent and significant induction of IR-induced cell death with these phytochemicals. Notably, EF24 robustly conferred IR-induced cell death. Together, these data identifies the potential hypoxic cell <span class="hlt">radio-sensitizers</span> and further</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27002539','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27002539"><span><span class="hlt">Radiosensitizing</span> Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cao, Ning; Song, Seung Hyun; Maleki, Teimour; Shaffer, Michael; Stantz, Keith M; Cao, Minsong; Kao, Chinghai; Mendonca, Marc S; Ziaie, Babak; Ko, Song-Chu</p> <p>2016-04-01</p> <p>Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at <span class="hlt">2</span>.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the <span class="hlt">radiosensitization</span> effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to <span class="hlt">radiosensitize</span> pancreatic tumors, enhancing response to single-dose radiation therapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.loc.gov/pictures/collection/hh/item/hi0801.photos.367410p/','SCIGOV-HHH'); return false;" href="https://www.loc.gov/pictures/collection/hh/item/hi0801.photos.367410p/"><span>Overview of Shipyard coast line with Piers <span class="hlt">G</span>1, <span class="hlt">G</span><span class="hlt">2</span>, <span class="hlt">G</span>3, ...</span></a></p> <p><a target="_blank" href="http://www.loc.gov/pictures/collection/hh/">Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey</a></p> <p></p> <p></p> <p>Overview of Shipyard coast line with Piers <span class="hlt">G</span>-1, <span class="hlt">G</span>-<span class="hlt">2</span>, <span class="hlt">G</span>-3, <span class="hlt">G</span>-4, and <span class="hlt">G</span>-5 in view, view facing east-southeast - U.S. Naval Base, Pearl Harbor, Pier & Quay Walls, Entrance to Dry Dock No. <span class="hlt">2</span> & Repair Wharfs, east & west sides of Dry Dock No. <span class="hlt">2</span> & west side of Dry Dock No. 3, Pearl City, Honolulu County, HI</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20120000846','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20120000846"><span>The Vaporization of B<span class="hlt">2</span>O3(l) to B<span class="hlt">2</span>O3(<span class="hlt">g</span>) and B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>)</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Jacobson, Nathan S.; Myers, Dwight L.</p> <p>2011-01-01</p> <p>The vaporization of B<span class="hlt">2</span>O3 in a reducing environment leads to formation of both B<span class="hlt">2</span>O3(<span class="hlt">g</span>) and B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>). While formation of B<span class="hlt">2</span>O3(<span class="hlt">g</span>) is well understood, many questions about the formation of B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>) remain. Previous studies using B(s) + B<span class="hlt">2</span>O3(l) have led to inconsistent thermodynamic data. In this study, it was found that after heating, B(s) and B<span class="hlt">2</span>O3(l) appear to separate and variations in contact area likely led to the inconsistent vapor pressures of B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>). To circumvent this problem, an activity of boron is fixed with a two-phase mixture of FeB and Fe<span class="hlt">2</span>B. Both second and third law enthalpies of formation were measured for B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>) and B<span class="hlt">2</span>O3(<span class="hlt">g</span>). From these the enthalpies of formation at 298.15 K are calculated to be -479.9 +/- 41.5 kJ/mol for B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>) and -833.4 +/- 13.1 kJ/mol for B<span class="hlt">2</span>O3(<span class="hlt">g</span>). Ab initio calculations to determine the enthalpies of formation of B<span class="hlt">2</span>O<span class="hlt">2</span>(<span class="hlt">g</span>) and B<span class="hlt">2</span>O3(<span class="hlt">g</span>) were conducted using the W1BD composite method and show good agreement with the experimental values.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014AIPC.1614..570R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014AIPC.1614..570R"><span><span class="hlt">Radiosensitivity</span> study and radiation effects on morphology characterization of grey oyster mushroom Pleurotus sajor-caju</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Rashid, Rosnani Abdul; Daud, Fauzi; Senafi, Sahidan; Awang, Mat Rasol; Mohamad, Azhar; Mutaat, Hassan Hamdani; Maskom, Mohd Meswan</p> <p>2014-09-01</p> <p><span class="hlt">Radiosensitive</span> dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec-1. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The <span class="hlt">radiosensitivity</span> study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD50 to be equal at <span class="hlt">2.2</span> kGy. The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28694946','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28694946"><span>Design of an intelligent sub-50 nm nuclear-targeting nanotheranostic system for imaging guided intranuclear <span class="hlt">radiosensitization</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fan, Wenpei; Shen, Bo; Bu, Wenbo; Zheng, Xiangpeng; He, Qianjun; Cui, Zhaowen; Zhao, Kuaile; Zhang, Shengjian; Shi, Jianlin</p> <p>2015-03-01</p> <p>Clinically applied chemotherapy and radiotherapy is sometimes not effective due to the limited dose acting on DNA chains resident in the nuclei of cancerous cells. Herein, we develop a new theranostic technique of "intranuclear <span class="hlt">radiosensitization</span>" aimed at directly damaging the DNA within the nucleus by a remarkable synergetic chemo-/radiotherapeutic effect based on intranuclear chemodrug-sensitized radiation enhancement. To achieve this goal, a sub-50 nm nuclear-targeting rattle-structured upconversion core/mesoporous silica nanotheranostic system was firstly constructed to directly transport the <span class="hlt">radiosensitizing</span> drug Mitomycin C (MMC) into the nucleus for substantially enhanced synergetic chemo-/radiotherapy and simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging, which can lead to efficient cancer treatment as well as multi-drug resistance circumvention in vitro and in vivo . We hope the technique of intranuclear <span class="hlt">radiosensitization</span> along with the design of nuclear-targeting nanotheranostics will contribute greatly to the development of cancer theranostics as well as to the improvement of the overall therapeutic effectiveness.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li class="active"><span>14</span></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_14 --> <div id="page_15" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li class="active"><span>15</span></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="281"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22606221-dimethoxycurcumin-metabolically-stable-analogue-curcumin-enhances-radiosensitivity-cancer-cells-possible-involvement-ros-thioredoxin-reductase','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22606221-dimethoxycurcumin-metabolically-stable-analogue-curcumin-enhances-radiosensitivity-cancer-cells-possible-involvement-ros-thioredoxin-reductase"><span>Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the <span class="hlt">radiosensitivity</span> of cancer cells: Possible involvement of ROS and thioredoxin reductase</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Jayakumar, Sundarraj; Patwardhan, R.S.; Pal, Debojyoti</p> <p></p> <p>Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the <span class="hlt">radiosensitizing</span> effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent <span class="hlt">radiosensitizing</span> effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratiomore » and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of <span class="hlt">radiosensitizing</span> effect of DIMC underscoring the role of thioredoxin reductase in <span class="hlt">radiosensitization</span>. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. - Highlights: • DIMC enhances <span class="hlt">radiosensitivity</span> of cancer cells by inducing cell death. • DIMC with radiation disrupted the cellular redox and targeted cancer stem cells. • DNA repair is hampered when cells are treated with DIMC. • DIMC inhibited thioredoxin reductase in cancer cells.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6865499','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6865499"><span>Cyclophosphamide-induced in vivo sister <span class="hlt">chromatid</span> exchange in Mus Musculus. II: Effect of age and genotype on sister <span class="hlt">chromatid</span> exchange, micronuclei and metaphase index.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Reimer, D L; Singh, S M</p> <p>1983-01-01</p> <p>In vivo cyclophosphamide-induced sister <span class="hlt">chromatid</span> exchanges (SCEs) micronuclei, and metaphase indices were assessed in two age groups (10.8 +/- 0.9 weeks' an 33.1 +/- 1.3 weeks' old) of female mice from three genetic strains (C3H/S, C57BL/6J, and Balb/c). In general, older animals showed diminished SCE induction over their younger counterparts. The relative difference between individuals of the two ages is strain-dependent. Unlike C57BL/6J and Balb/c, strain C3H/S showed significantly lower SCE values in the older animals at every cyclophosphamide treatment. It may reflect on the possible involvement of genetic determinant(s) for the component(s) of SCE formation during aging. Frequencies of micronuclei, however, were consistently higher in older animals than in their younger counterparts. Furthermore, cytotoxicity of cyclophosphamide, as reflected in metaphase indices, was also higher in older animals. Lower metaphase indices associated with higher micronuclei levels in older individuals may suggest a decline in the rate of cellular replication in these animals. Furthermore, the lower metaphase indices associated with lower SCE values, and increasing micronuclei levels accompanied by decreasing SCE frequencies in older animals, may reflect reduced DNA repair ability during aging. These results support the hypothesis of genotype-dependent decline in the rate of DNA repair and replication during aging, particularly under stressed conditions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6339318','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6339318"><span>[Intragenic mitotic recombination induced by ultraviolet and gamma rays in <span class="hlt">radiosensitive</span> mutants of Saccharomyces cerevisiae yeasts].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zakharov, I A; Kasinova, G V; Koval'tsova, S V</p> <p>1983-01-01</p> <p>The effect of UV- and gamma-irradiation on the survival and intragenic mitotic recombination (gene conversion) of 5 <span class="hlt">radiosensitive</span> mutants was studied in comparison with the wild type. The level of spontaneous conversion was similar for RAD, rad<span class="hlt">2</span> and rad15, mutations xrs<span class="hlt">2</span> and xrs4 increasing and rad54 significantly decreasing it. The frequency of conversion induced by UV-light was greater in rad<span class="hlt">2</span>, rad15 and xrs<span class="hlt">2</span> mutants and lower in xrs4, as compared to RAD. Gamma-irradiation caused induction of gene conversion with an equal frequency in RAD, rad<span class="hlt">2</span>, rad15. Xrs<span class="hlt">2</span> and xrs4 mutations slightly decreased gamma-induced conversion. In rad54 mutant, UV-and gamma-induced conversion was practically absent. In the wild type yeast, a diploid strain is more resistant than a haploid, whereas in rad54 a diploid strain has the same or an increased sensitivity, as compared to a haploid strain (the "inverse ploidy effect"). This effect and also the block of induced mitotic recombination caused by rad54 indicate the presence in the yeast Saccharomyces cerevisiae of repair pathways of UV- and gamma-induced damages acting in diploid cells and realised by recombination. The data obtained as a result of many years' investigation of genetic effects in <span class="hlt">radiosensitive</span> mutants of yeast are summarised and considered.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3599951','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3599951"><span>Molecular basis of ‘hypoxic’ breast cancer cell <span class="hlt">radio-sensitization</span>: phytochemicals converge on radiation induced Rel signaling</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2013-01-01</p> <p>Background Heterogeneously distributed hypoxic areas are a characteristic property of locally advanced breast cancers (BCa) and generally associated with therapeutic resistance, metastases, and poor patient survival. About 50% of locally advanced BCa, where radiotherapy is less effective are suggested to be due to hypoxic regions. In this study, we investigated the potential of bioactive phytochemicals in <span class="hlt">radio-sensitizing</span> hypoxic BCa cells. Methods Hypoxic (O<span class="hlt">2-2</span>.5%; N<span class="hlt">2</span>-92.5%; CO<span class="hlt">2</span>-5%) MCF-7 cells were exposed to 4 Gy radiation (IR) alone or after pretreatment with Curcumin (CUR), curcumin analog EF24, neem leaf extract (NLE), Genistein (GEN), Resveratrol (RES) or raspberry extract (RSE). The cells were examined for inhibition of NFκB activity, transcriptional modulation of 88 NFκB signaling pathway genes, activation and cellular localization of radio-responsive NFκB related mediators, eNos, Erk1/<span class="hlt">2</span>, SOD<span class="hlt">2</span>, Akt1/<span class="hlt">2</span>/3, p50, p65, pIκBα, TNFα, Birc-1, -<span class="hlt">2</span>, -5 and associated induction of cell death. Results EMSA revealed that cells exposed to phytochemicals showed complete suppression of IR-induced NFκB. Relatively, cells exposed EF24 revealed a robust inhibition of IR-induced NFκB. QPCR profiling showed induced expression of 53 NFκB signaling pathway genes after IR. Conversely, 53, 50, 53, 53, 53 and 53 of IR-induced genes were inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. In addition, 25, 29, 24, 16, 11 and 21 of 35 IR-suppressed genes were further inhibited with EF24, NLE, CUR, GEN, RES and RSE respectively. Immunoblotting revealed a significant attenuating effect of IR-modulated radio-responsive eNos, Erk1/<span class="hlt">2</span>, SOD<span class="hlt">2</span>, Akt1/<span class="hlt">2</span>/3, p50, p65, pIκBα, TNFα, Birc-1, -<span class="hlt">2</span> and −5 with EF24, NLE, CUR, GEN, RES or RSE. Annexin V-FITC staining showed a consistent and significant induction of IR-induced cell death with these phytochemicals. Notably, EF24 robustly conferred IR-induced cell death. Conclusions Together, these data identifies the potential</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29921729','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29921729"><span>Integrating <span class="hlt">Radiosensitivity</span> and Immune Gene Signatures for Predicting Benefit of Radiotherapy in Breast Cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cui, Yi; Li, Bailiang; Pollom, Erqi Liu; Horst, Kathleen; Li, Ruijiang</p> <p>2018-06-19</p> <p>Breast cancer is a heterogeneous disease and not all patients respond equally to adjuvant radiotherapy. Predictive biomarkers are needed to select patients who will benefit from the treatment and spare others the toxicity and burden of radiation. We first trained and tested an intrinsic <span class="hlt">radiosensitivity</span> gene signature to predict local recurrence after radiotherapy in three cohorts of 948 patients. Next, we developed an antigen processing and presentation-based immune signature by maximizing the treatment interaction effect in 129 patients. To test their predictive value, we matched patients treated with or without radiotherapy in an independent validation cohort for clinicopathologic factors including age, ER status, HER<span class="hlt">2</span> status, stage, hormone-therapy, chemotherapy, and surgery. Disease specific survival (DSS) was the primary endpoint. Our validation cohort consisted of 1,439 patients. After matching and stratification by the <span class="hlt">radiosensitivity</span> signature, patients who received radiotherapy had better DSS than patients who did not in the radiation-sensitive group (hazard ratio [HR]=0.68, P=0.059, n=322), while a reverse trend was observed in the radiation-resistant group (HR=1.53, P=0.059, n=202). Similarly, patients treated with radiotherapy had significantly better DSS in the immuneeffective group (HR=0.46, P=0.0076, n=180), with no difference in DSS in the immunedefective group (HR=1.27, P=0.16, n=348). Both signatures were predictive of radiotherapy benefit (P interaction =0.007 and 0.005). Integration of <span class="hlt">radiosensitivity</span> and immune signatures further stratified patients into three groups with differential outcomes for those treated with or without radiotherapy (P interaction =0.003). The proposed signatures have the potential to select patients who are most likely to benefit from radiotherapy. Copyright ©2018, American Association for Cancer Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/4061465-radiosensitivity-antibody-responses-radioresistant-secondary-tetanus-antitoxin-responses','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/4061465-radiosensitivity-antibody-responses-radioresistant-secondary-tetanus-antitoxin-responses"><span><span class="hlt">Radiosensitivity</span> of antibody responses and radioresistant secondary tetanus antitoxin responses</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Stoner, R.; Terres, G.; Cottier, H.</p> <p>1976-01-01</p> <p>Primary tetanus antitoxin responses were increasingly repressed in mice when gamma radiation doses of 100 to 400 rads were delivered by whole-body exposure prior to immunization with fluid tetanus toxoid (FTT). Nearly normal secondary antitoxin responses were obtained in mice exposed to 600 rads of gamma radiation 4 days after secondary antigenic stimulation with FTT. A rapid transition from <span class="hlt">radiosensitivity</span> of the antibody-forming system on days 1 to 3 was followed by relative radioresistance on day 4 after the booster injection of toxoid. Studies on lymphoid cellular kinetics in popliteal lymph nodes after injection of $sup 3$H--thymidine ($sup 3$H--TdR) andmore » incorporation of $sup 3$H--L- histidine into circulating antitoxin were carried out. Analysis of tritium radioactivity in antigen--antibody precipitates of serums <span class="hlt">2</span> hr after injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after the booster in nonirradiated controls and about day 12, i.e., 8 days after irradiation, in experimental mice. The shift from <span class="hlt">radiosensitivity</span> to relative radioresistance was attributed to a marked peak of plasma-cell proliferation in the medulla of lymph nodes on day 3. Many medullary plasma cells survived and continued to proliferate after exposure to radiation. Germinal centers were destroyed by radiation within 1 day. Since antibody formation continued after exposure to radiation and after the loss of germinal centers, this supports the view that germinal-center cells were involved more in the generation of memory cells than in antibody synthesis. (auth)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/2687630','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/2687630"><span>Induction of sister <span class="hlt">chromatid</span> exchanges and cell division delays in human lymphocytes by the anti-tumour agent homo-aza-steroidal ester of p-bis(<span class="hlt">2</span>-chloroethyl)aminophenoxy acetic acid.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tselepi, M R; Demopoulos, N A; Catsoulacos, P</p> <p>1989-09-01</p> <p>3 beta-Hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam-p-bis(<span class="hlt">2</span>-chloroethyl) aminophenoxyacetate (NSC 294859) is a new modified steroidal alkylating agent. This compound was given by i.p. administration to mice bearing different types of tumour. It was found to exhibit good activity in L1210 and P388 leukaemias with maintenance of activity against advanced tumours. The treatment of colon 26 tumour and B16 melanoma resulted in positive antineoplastic activity. The drug was not shown to be active in a melphalan-resistant P388 line. In this study, NSC 294859 was found to be effective in causing statistically significant increases in sister-<span class="hlt">chromatid</span> exchange (SCE) rates and cell division delays. The alkylating agent component, p-bis-(<span class="hlt">2</span>-chloroethyl)aminophenoxy acetic acid, was shown to be less effective than the parent compound, while the modified steroid component, 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, showed no effect. There were no statistically significant differences among donors regarding the induction of SCEs and replication indices (RIs) for the compounds tested.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2000PhDT.......189D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2000PhDT.......189D"><span>Predicting normal tissue <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Dickson, Jeanette</p> <p></p> <p>Two methods of predicting normal cell <span class="hlt">radiosensitivity</span> were investigated in different patient groups. Plasma transforming growth factor beta one (TGFbeta1) levels were measured by ELISA, using a commercially available kit. Residual DNA double strand breaks were measured in normal epidermal fibroblasts following 150 Gy. After allowing 24 hours for repair, the DNA damage was assayed using pulsed field gel electrophoresis (PFGE). Pretreatment plasma TGFbeta1 levels were investigated retrospectively in patients with carcinoma of the cervix in relation to tumour control and late morbidity following radiotherapy. Plasma TGFbeta1 levels increased with increasing disease stage. They also correlated with two other known measures of tumour burden i.e. plasma levels of carcinoma antigen 125 (CA125) and tissue polypeptide antigen (TPA). Elevated pretreatment plasma TGFbeta1 levels predicted for a poor outcome both in terms of local control and overall survival. Plasma TGF?l levels did not predict for the development of radiotherapy morbidity of any grade. In conclusion pre-treatment plasma TGFbeta1 levels predict for tumour burden and tumour outcome in patients with carcinoma of the cervix. Changes in plasma TGFbeta1 levels measured prospectively may predict for radiation morbidity and should be investigated. A prospective study was undertaken in patients with carcinoma of the head and neck region. Changes in plasma TGFbeta1 levels between the start and the end of a course of radical radiotherapy were investigated in relation to the development of acute radiation toxicity. Patients were categorised according to the pattern of response of their TGFbeta1 levels over the course of their treatment. Those patients whose TGFbeta1 levels decreased, but did not normalise during radiotherapy were assigned to category <span class="hlt">2</span>. Category <span class="hlt">2</span> predicted for a severe acute reaction, as measured using the LENT SOMA score, with a sensitivity of 33% and a specificity of 100%. The positive predictive</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21124270-toxicity-profile-pharmacokinetic-study-phase-low-dose-schedule-dependent-radiosensitizing-paclitaxel-chemoradiation-regimen-inoperable-non-small-cell-lung-cancer','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21124270-toxicity-profile-pharmacokinetic-study-phase-low-dose-schedule-dependent-radiosensitizing-paclitaxel-chemoradiation-regimen-inoperable-non-small-cell-lung-cancer"><span>Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent <span class="hlt">Radiosensitizing</span> Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard</p> <p></p> <p>Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for <span class="hlt">radiosensitization</span> in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup <span class="hlt">2</span>}, 20 mg/m{sup <span class="hlt">2</span>}, and 25 mg/m{sup <span class="hlt">2</span>} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal <span class="hlt">G</span><span class="hlt">2</span>/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3more » pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup <span class="hlt">2</span>}), II (20 mg/m{sup <span class="hlt">2</span>}), and III (25 mg/m{sup <span class="hlt">2</span>}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.<span class="hlt">2</span> h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective <span class="hlt">radiosensitization</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21039644-transition-survival-from-low-dose-hyper-radiosensitivity-increased-radioresistance-independent-activation-atm-ser1981-activity','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21039644-transition-survival-from-low-dose-hyper-radiosensitivity-increased-radioresistance-independent-activation-atm-ser1981-activity"><span>Transition in Survival From Low-Dose Hyper-<span class="hlt">Radiosensitivity</span> to Increased Radioresistance Is Independent of Activation of ATM SER1981 Activity</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Krueger, Sarah A.; Collis, Spencer J.; Joiner, Michael C.</p> <p>2007-11-15</p> <p>Purpose: The molecular basis of low-dose hyper-<span class="hlt">radiosensitivity</span> (HRS) is only partially understood. The aim of this study was to define the roles of ataxia telangiectasia mutated (ATM) activity and the downstream ATM-dependent <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase cell cycle checkpoint in overcoming HRS and triggering radiation resistance. Methods and Materials: Survival was measured using a high-resolution clonogenic assay. ATM Ser1981 activation was measured by Western blotting. The role of ATM was determined in survival experiments after molecular (siRNA) and chemical (0.4 mM caffeine) inhibition and chemical (20 {mu}<span class="hlt">g</span>/mL chloroquine, 15 {mu}M genistein) activation 4-6 h before irradiation. Checkpoint responsiveness was assessed in eightmore » cell lines of differing HRS status using flow cytometry to quantify the progression of irradiated (0-<span class="hlt">2</span> Gy) <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase cells entering mitosis, using histone H3 phosphorylation analysis. Results: The dose-response pattern of ATM activation was concordant with the transition from HRS to radioresistance. However, ATM activation did not play a primary role in initiating increased radioresistance. Rather, a relationship was discovered between the function of the downstream ATM-dependent early <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase checkpoint and the prevalence and overcoming of HRS. Four cell lines that exhibited HRS failed to show low-dose (<0.3-Gy) checkpoint function. In contrast, four HRS-negative cell lines exhibited immediate cell cycle arrest for the entire 0-<span class="hlt">2</span>-Gy dose range. Conclusion: Overcoming HRS is reliant on the function of the early <span class="hlt">G</span>{sub <span class="hlt">2</span>}-phase checkpoint. These data suggest that clinical exploitation of HRS could be achieved by combining radiotherapy with chemotherapeutic agents that modulate this cell cycle checkpoint.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12175564','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12175564"><span>Individualization of radiotherapy in breast cancer patients: possible usefulness of a DNA damage assay to measure normal cell <span class="hlt">radiosensitivity</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ruiz de Almodóvar, José Mariano; Guirado, Damian; Isabel Núñez, María; López, Escarlata; Guerrero, Rosario; Valenzuela, María Teresa; Villalobos, Mercedes; del Moral, Rosario</p> <p>2002-03-01</p> <p>The purpose of this study was to determine whether the distribution of sensitivities in breast cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable the reliable identification of patients with abnormal sensitivities. <span class="hlt">Radiosensitivity</span> (x) was assessed in 226 samples of lymphocytes from unselected women with breast cancer and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gy and per DNA unit (200 Mbp). The existence of an inter-individual variation in the parameter (x) is described through the range (0.40-4.72 dsb/Gy/DNA unit) of values found, which have been fitted to the mathematical model defined by the log-normal distribution (mu = 0.42+/-0.03; sigma = 0.52+/-0.03; R(<span class="hlt">2</span>)=0.9475). A total of 189 patients received radiotherapy after surgical treatment. Among them, we have detected 15 patients who developed severe skin reactions and we have compared their <span class="hlt">radiosensitivity</span> values with the rest of patients treated. Our results suggest that DNA initial damage measured on lymphocytes offers an approach to predict the acute response of human normal tissues prior to radiotherapy. Values of x higher than 3.20 dsb/Gy/DNA unit theoretically should correspond to the highly <span class="hlt">radio-sensitive</span> patients. Using the experimental results, we have calculated the strength of the test by means of the area under the receiver operator characteristic curves (A(Z)) to determine whether the <span class="hlt">radiosensitivity</span> assay can discriminate between patients according to their radiation response. The value found (A(Z)=0.675+/-0.072) is indicative of a fair-poor discriminating capacity of the test to identify the patients with higher risk of developing a severe acute reaction during the radiotherapy treatment.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29549168','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29549168"><span>The DNA-PK Inhibitor VX-984 Enhances the <span class="hlt">Radiosensitivity</span> of Glioblastoma Cells Grown In Vitro and as Orthotopic Xenografts.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Timme, Cindy R; Rath, Barbara H; O'Neill, John W; Camphausen, Kevin; Tofilon, Philip J</p> <p>2018-06-01</p> <p>Radiotherapy is a primary treatment modality for glioblastomas (GBM). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSB), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the <span class="hlt">radiosensitivity</span> of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation. In a similar concentration-dependent manner, VX-984 treatment enhanced the <span class="hlt">radiosensitivity</span> of each GBM cell line as defined by clonogenic analysis. As determined by γH<span class="hlt">2</span>AX expression and neutral comet analyses, VX-984 inhibited the repair of radiation-induced DNA double-strand break in U251 and NSC11 GBM cells, suggesting that the VX-984-induced <span class="hlt">radiosensitization</span> is mediated by an inhibition of DNA repair. Extending these results to an in vivo model, treatment of mice with VX-984 inhibited radiation-induced DNA-PKcs phosphorylation in orthotopic brain tumor xenografts, indicating that this compound crosses the blood-brain tumor barrier at sufficient concentrations. For mice bearing U251 or NSC11 brain tumors, VX-984 treatment alone had no significant effect on overall survival; radiation alone increased survival. The survival of mice receiving the combination protocol was significantly increased as compared with control and as compared with radiation alone. These results indicate that VX-984 enhances the <span class="hlt">radiosensitivity</span> of brain tumor xenografts and suggest that it may be of benefit in the therapeutic management of GBM. Mol Cancer Ther; 17(6); 1207-16. ©2018 AACR . ©2018 American Association for Cancer Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2883706','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2883706"><span>The phosphatase and tensin homologue deleted on chromosome 10 mediates <span class="hlt">radiosensitivity</span> in head and neck cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pattje, W J; Schuuring, E; Mastik, M F; Slagter-Menkema, L; Schrijvers, M L; Alessi, S; van der Laan, B F A M; Roodenburg, J L N; Langendijk, J A; van der Wal, J E</p> <p>2010-01-01</p> <p>Background: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is ∼50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer. Methods: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy. Results: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: <span class="hlt">2.2</span>, 95% CI: 1.1–4.6; P=0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.<span class="hlt">2</span>–27.4; P=0.03) and extranodal spread (HR: <span class="hlt">2</span>.7; 95% CI: 1.<span class="hlt">2</span>–6.5; P=0.02). In vitro clonogenic <span class="hlt">radiosensitivity</span> assays confirmed that overexpression of PTEN resulted in increased radioresistance. Conclusion: Our study is the first report showing that expression of PTEN mediates <span class="hlt">radiosensitivity</span> in vitro and that increased expression in advanced HNSCC predicts worse LRC. PMID:20502457</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1198184-biomarkers-radiosensitivity-bomb-survivors-pregnant-time-bombings-hiroshima-nagasaki','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1198184-biomarkers-radiosensitivity-bomb-survivors-pregnant-time-bombings-hiroshima-nagasaki"><span>Biomarkers of <span class="hlt">Radiosensitivity</span> in A-Bomb Survivors Pregnant at the Time of Bombings in Hiroshima and Nagasaki</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Miles, Edward F.; Tatsukawa, Yoshimi; Funamoto, Sachiyo; ...</p> <p>2011-01-01</p> <p>Purpose . There is evidence in the literature of increased maternal <span class="hlt">radiosensitivity</span> during pregnancy. Materials and Methods . We tested this hypothesis using information from the atomic-bomb survivor cohort, that is, the Adult Health Study database at the Radiation Effects Research Foundation, which contains data from a cohort of women who were pregnant at the time of the bombings of Hiroshima and Nagasaki. Previous evaluation has demonstrated long-term radiation dose-response effects. Results/Conclusions . Data on approximately 250 women were available to assess dose-response rates for serum cholesterol, white blood cell count, erythrocyte sedimentation rate, and serum hemoglobin, and on approximatelymore » 85 women for stable chromosome aberrations, glycophorin A locus mutations, and naïve CD4 T-cell counts. Although there is no statistically significant evidence of increased <span class="hlt">radiosensitivity</span> in pregnant women, the increased slope of the linear trend line in the third trimester with respect to stable chromosome aberrations is suggestive of an increased <span class="hlt">radiosensitivity</span>.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18927295','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18927295"><span>DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for <span class="hlt">radiosensitivity</span> testing.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian</p> <p>2008-10-15</p> <p>Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced <span class="hlt">radiosensitivity</span>. Using a preclinical mouse model, the highly sensitive gammaH<span class="hlt">2</span>AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue <span class="hlt">radiosensitivity</span>. By enumerating gammaH<span class="hlt">2</span>AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-<span class="hlt">2</span> Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH<span class="hlt">2</span>AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH<span class="hlt">2</span>AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH<span class="hlt">2</span>AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue <span class="hlt">radiosensitivity</span>. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22224497-preclinical-evaluation-genexol-pm-nanoparticle-formulation-paclitaxel-novel-radiosensitizer-treatment-non-small-cell-lung-cancer','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22224497-preclinical-evaluation-genexol-pm-nanoparticle-formulation-paclitaxel-novel-radiosensitizer-treatment-non-small-cell-lung-cancer"><span>Preclinical Evaluation of Genexol-PM, a Nanoparticle Formulation of Paclitaxel, as a Novel <span class="hlt">Radiosensitizer</span> for the Treatment of Non-Small Cell Lung Cancer</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Werner, Michael E.; Cummings, Natalie D.; Sethi, Manish</p> <p>2013-07-01</p> <p>Purpose: A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a <span class="hlt">radiosensitizer</span> using non-small cell lung cancer (NSCLC) as a model disease. Methods and Materials: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a <span class="hlt">radiosensitizer</span> was evaluated inmore » vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration. Results: Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of −8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a <span class="hlt">radiosensitizer</span> showed it is an effective <span class="hlt">radiosensitizer</span> and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a <span class="hlt">radiosensitizer</span> demonstrated that it is more effective as a <span class="hlt">radiosensitizer</span> than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration. Conclusions: We have demonstrated that Genexol-PM is more effective than Taxol as a <span class="hlt">radiosensitizer</span> in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22097494','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22097494"><span>In vitro <span class="hlt">radiosensitizing</span> effects of ultrasmall gadolinium based particles on tumour cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P</p> <p>2011-09-01</p> <p>Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro <span class="hlt">radiosensitizing</span> properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient <span class="hlt">radiosensitizers</span> at an energy of 6 MeV for doses comprised between <span class="hlt">2</span> and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1977888','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1977888"><span>Host cell reactivation of gamma-irradiated adenovirus 5 in human cell lines of varying <span class="hlt">radiosensitivity</span>.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Eady, J. J.; Peacock, J. H.; McMillan, T. J.</p> <p>1992-01-01</p> <p>DNA repair processes play an important role in the determination of radiation response in both normal and tumour cells. We have investigated one aspect of DNA repair in a number of human cell lines of varying <span class="hlt">radiosensitivity</span> using the adenovirus 5 host cell reactivation assay (HCR). In this technique, gamma-irradiated virions are used to infect cells and the ability of the cellular repair systems to process this damage is assayed by a convenient immunoperoxidase method recognising viral structural antigen expression on the cell membrane 48 h after infection. Reduced HCR was exhibited by radioresistant HeLa cells and by a <span class="hlt">radiosensitive</span> neuroblastoma cell line, HX142. In contrast, an ataxia telangiectasia cell line, AT5 BIVA, did not show reduced HCR. On the basis of these results we can make no general conclusions about the relevance of HCR to cellular <span class="hlt">radiosensitivity</span>. We have extended these studies to determine whether our cell lines exhibited enhanced viral reactivation (ER) following a small priming dose of gamma-radiation given to the cells before viral infection. No evidence for this phenomenon was found either in normal or tumour cell lines. PMID:1637659</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21367577-lin28-let7-modulates-radiosensitivity-human-cancer-cells-activation-ras','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21367577-lin28-let7-modulates-radiosensitivity-human-cancer-cells-activation-ras"><span>Lin28-let7 Modulates <span class="hlt">Radiosensitivity</span> of Human Cancer Cells With Activation of K-Ras</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Oh, Jee-Sun.; Kim, Jae-Jin; Byun, Ju-Yeon</p> <p>2010-01-15</p> <p>Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling. Methods and Materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed. Results: The overexpression of let-7a decreased expression of K-Ras and <span class="hlt">radiosensitized</span> A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression andmore » <span class="hlt">radiosensitized</span> A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were <span class="hlt">radiosensitized</span> by this approach. Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22308345-radiosensitivity-study-radiation-effects-morphology-characterization-grey-oyster-mushroom-pleurotus-sajor-caju','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22308345-radiosensitivity-study-radiation-effects-morphology-characterization-grey-oyster-mushroom-pleurotus-sajor-caju"><span><span class="hlt">Radiosensitivity</span> study and radiation effects on morphology characterization of grey oyster mushroom Pleurotus sajor-caju</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Rashid, Rosnani Abdul; Awang, Mat Rasol; Mohamad, Azhar</p> <p>2014-09-03</p> <p><span class="hlt">Radiosensitive</span> dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec{sup −1}. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The <span class="hlt">radiosensitivity</span> study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD{sub 50} to be equal at <span class="hlt">2.2</span> kGy.more » The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.« less</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li class="active"><span>15</span></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_15 --> <div id="page_16" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li class="active"><span>16</span></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="301"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5061034','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5061034"><span>Everything Old Is New Again: Using Nelfinavir to <span class="hlt">Radiosensitize</span> Rectal Cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Meyn, Raymond E.; Krishnan, Sunil; Skinner, Heath D.</p> <p>2016-01-01</p> <p>Summary Repurposing agents approved for other indications to <span class="hlt">radiosensitize</span> tumors may be advantageous. The study by Hill and colleagues utilizes Nelfinavir, an HIV protease inhibitor, in combination with radiotherapy in rectal cancer in a prospective study. This combination may improve tumor perfusion and regression compared to radiotherapy alone. PMID:26920893</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016PhRvB..94u4429L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016PhRvB..94u4429L"><span>Long-range magnetic order in the Heisenberg pyrochlore antiferromagnets <span class="hlt">G</span> d<span class="hlt">2</span><span class="hlt">G</span> e<span class="hlt">2</span>O7 and <span class="hlt">G</span> d<span class="hlt">2</span>P t<span class="hlt">2</span>O7 synthesized under high pressure</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Li, X.; Cai, Y. Q.; Cui, Q.; Lin, C. J.; Dun, Z. L.; Matsubayashi, K.; Uwatoko, Y.; Sato, Y.; Kawae, T.; Lv, S. J.; Jin, C. Q.; Zhou, J.-S.; Goodenough, J. B.; Zhou, H. D.; Cheng, J.-G.</p> <p>2016-12-01</p> <p><span class="hlt">G</span> d<span class="hlt">2</span>S n<span class="hlt">2</span>O7 and <span class="hlt">G</span> d<span class="hlt">2</span>T i<span class="hlt">2</span>O7 have been regarded as good experimental realizations of the classical Heisenberg pyrochlore antiferromagnet with dipolar interaction. The former was found to adopt the Palmer-Chalker state via a single, first-order transition at TN≈1 K , while the latter enters a distinct, partially ordered state through two successive transitions at TN 1≈1 K and TN <span class="hlt">2</span>= 0.75 K . To shed more light on their distinct magnetic ground states, we have synthesized two more gadolinium-based pyrochlore oxides, <span class="hlt">G</span> d<span class="hlt">2</span><span class="hlt">G</span> e<span class="hlt">2</span>O7 and <span class="hlt">G</span> d<span class="hlt">2</span>P t<span class="hlt">2</span>O7 , under high-pressure conditions and performed detailed characterizations via x-ray powder diffraction, dc and ac magnetic susceptibility, and specific heat measurements down to 100 mK. We found that both compounds enter a long-range antiferromagnetically ordered state through a single, first-order transition at TN= 1.4 K for <span class="hlt">G</span> d<span class="hlt">2</span><span class="hlt">G</span> e<span class="hlt">2</span>O7 and TN= 1.56 K for <span class="hlt">G</span> d<span class="hlt">2</span>P t<span class="hlt">2</span>O7 , with the specific heat anomaly similar to that of <span class="hlt">G</span> d<span class="hlt">2</span>S n<span class="hlt">2</span>O7 rather than <span class="hlt">G</span> d<span class="hlt">2</span>T i<span class="hlt">2</span>O7 . Interestingly, the low-temperature magnetic specific heat values of both <span class="hlt">G</span> d<span class="hlt">2</span><span class="hlt">G</span> e<span class="hlt">2</span>O7 and <span class="hlt">G</span> d<span class="hlt">2</span>P t<span class="hlt">2</span>O7 were found to follow nicely the T3 dependence as expected for a three-dimensional antiferromagnet with gapless spin-wave excitations. We have rationalized the enhancement of TN in terms of the reduced Gd-Gd distances for the chemically pressurized <span class="hlt">G</span> d<span class="hlt">2</span><span class="hlt">G</span> e<span class="hlt">2</span>O7 and the addition of extra superexchange pathways through the empty Pt -eg orbitals for <span class="hlt">G</span> d<span class="hlt">2</span>P t<span class="hlt">2</span>O7 . Our current study has expanded the family of gadolinium-based pyrochlores and permits us to achieve a better understanding of their distinct magnetic properties in a more comprehensive perspective.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3993974','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3993974"><span>Validation of a <span class="hlt">Radiosensitivity</span> Molecular Signature in Breast Cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Eschrich, Steven A.; Fulp, William J.; Pawitan, Yudi; Foekens, John A.; Smid, Marcel; Martens, John W. M.; Echevarria, Michelle; Kamath, Vidya; Lee, Ji-Hyun; Harris, Eleanor E.; Bergh, Jonas; Torres-Roca, Javier F.</p> <p>2014-01-01</p> <p>Purpose Previously, we developed a <span class="hlt">radiosensitivity</span> molecular signature (RSI) that was clinically-validated in three independent datasets (rectal, esophageal, head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT) treated breast cancer patients. Experimental Design RSI was tested in two previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n=159) and Erasmus Medical Center (n=344). RSI was applied as previously described. Results We tested RSI in RT-treated patients (Karolinska). Patients predicted to be <span class="hlt">radiosensitive</span> (RS) had an improved 5 yr relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, p=0.0212) but there was no difference between RS/RR patients treated without RT (71% vs. 77%, p=0.6744), consistent with RSI being RT-specific (interaction term RSIxRT, p=0.05). Similarly, in the Erasmus dataset RT-treated RS patients had an improved 5-year distant-metastasis-free survival over RR patients (77% vs. 64%, p=0.0409) but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, p=0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR=5.53, p=0.0987, Erasmus, HR=1.64, p=0.0758) and in backward selection (removal alpha of 0.10) RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR=<span class="hlt">2</span>.64, p=0.0085). Conclusions RSI is validated in two independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in five independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. PMID:22832933</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/14982481','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/14982481"><span>Comparison of the X-radiation, drug and ultraviolet-radiation responses of clones isolated from a human colorectal tumor cell line.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Qutob, Sami S; Multani, Asha S; Pathak, S; Feng, Y; Kendal, Wayne S; Ng, Cheng E</p> <p>2004-03-01</p> <p>We isolated several clones with a wide range of responses to X radiation from an unirradiated human colorectal (HCT 116) tumor cell line. The responses of one of these clones (HCT116-Clone10) and nine other clones to either fractionated or acute (i.e. single, nonfractionated doses) X irradiation in vitro was similar to that of the parental cell line. By contrast, after the same types of treatment, another clone (HCT116-Clone<span class="hlt">2</span>) manifested a significantly increased survival whereas a third clone (HCT116-CloneK) manifested a significantly decreased survival relative to the parental cell line. This suggested that they were, respectively, a radioresistant and a <span class="hlt">radiosensitive</span> clone. All three clones (clones <span class="hlt">2</span>, 10, K) retained their tumorigenic phenotype and formed tumors in nude mice. <span class="hlt">G</span>-banding studies demonstrated that they were of human origin and were derived from the same parental cell line. The metaphases of HCT116-Clone<span class="hlt">2</span> demonstrated features commonly associated with genomic instability (i.e. mitotic catastrophe including chromosome and <span class="hlt">chromatid</span> breaks, dicentrics and additional nonclonal markers). Data obtained by quantitative fluorescence in situ hybridization (Q- FISH) analysis failed to demonstrate any apparent correlation between the <span class="hlt">radiosensitivity</span> and the relative telomere content of these three clones. Interestingly, HCT116-CloneK was the most resistant to several chemotherapeutic drugs (topotecan, camptothecin, etoposide and cisplatin) with diverse mechanisms of action. Also, there were no significant differences in the survivals of the three clones after treatment with UV radiation. Because of the lack of overlap among the relative sensitivities of these clones to X radiation, chemotherapeutic drugs and UV radiation, these clones may be useful models for evaluating the genetic basis of the response of human tumor cells to these treatment agents both in vitro and in vivo.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5906693-enhancement-radiosensitizing-effect-nitroimidazole-derivative-rk28-proliferation-metha-tumor-cells-combined-use-diethyldithiocarbamate','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5906693-enhancement-radiosensitizing-effect-nitroimidazole-derivative-rk28-proliferation-metha-tumor-cells-combined-use-diethyldithiocarbamate"><span>Enhancement of <span class="hlt">radiosensitizing</span> effect of the nitroimidazole derivative RK28 on the proliferation of MethA tumor cells in combined use with diethyldithiocarbamate</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Mashiba, Harukazu; Matsunaga, Keiko; Hata, Kazuo</p> <p>1991-01-01</p> <p>The <span class="hlt">radiosensitizing</span> effect of the nitroimidazole derivative RK28 and diethyldithiocarbamate (DDC), which is an inhibitor of superoxide dismutase activity, was examined in vitro by using Meth A tumor cells. The <span class="hlt">radiosensitizing</span> effect of 0.5 mM RK28 was observed in both of 10 Gy and 15 Gy irradiated groups. The addition of 5 {times} 10{sup {minus}7} M DDC also enhanced the radiation-induced proliferation inhibition. Marked enhancement of the anti-proliferative effect was observed in combined use of 0.<span class="hlt">2</span> mM or 0.5 mM RK28 with <span class="hlt">2</span> {times} 10 M or 5 {times} 10{sup {minus}7} M DDC. These results suggest that enhanced oxygen effectmore » could be expected through combined use of the ionizing irradiation with both of these agents.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=61071&keyword=SCG&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=61071&keyword=SCG&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>INVESTIGATION OF DNA REPAIR BY SISTER <span class="hlt">CHROMATID</span> EXCHANGE (SCE) ANALYSIS AND THE ALKALINE SINGLE CELL GEL ASSAY (SCG) IN MAMMALIAN GO-LYMPHOCYTES AFTER IN VITRO EXPOSURE TO ETHYLENE OXIDE (EO)</span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>Investigation ofDNA Repair by Sister <span class="hlt">Chromatid</span> Exchange (SCE) Analysis and the Alkaline Single Cell Gel Assay (SCG) in Mammalian Go-Lymphocytes after In Vitro Exposure to Ethylene Oxide (EO). <br><br>EO is a large volume chemical used primarily as an intermediate in manufacturing...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27784455','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27784455"><span>[Effects and its mechanism of Nimotuzumab on <span class="hlt">radiosensitivity</span> of esophageal carcinoma ECA-109 and TE-13 cell lines].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, J; Wang, W; Guo, Y; Jing, S W; Shang, K; Miao, M C; Wang, J; Wu, Y J; Liu, L N; Yu, J M</p> <p>2016-10-23</p> <p>Objective: To investigate the effects of nimotuzumab on <span class="hlt">radiosensitivity</span> of ECA-109 and TE-13 esophageal carcinoma cell lines and explore its possible mechanism. Methods: The ECA-109 and TE-13 cells were divided into control group, irradiation group, medicine group, and combined group (irradiation + medicine). In the combined group, ECA-109 and TE-13 cells were treated with nimotuzumab for 24 h before irradiation, and the cells were collected <span class="hlt">2</span> h after irradiation. The <span class="hlt">radiosensitizing</span> effects of nimotuzumab on ECA-109 and TE-13 cells were evaluated by clone formation assay. Cell apoptosis was detected by flow cytometry. Western blotting was used to evaluate the expression of EGFR, p-EGFR, DNA-PKcs, p-DNA-PKcs and γH<span class="hlt">2</span>AX. Results: The values of D q (quasithreshold dose), D 0 (mean lethal dose)and SF <span class="hlt">2</span> (surviving fraction at <span class="hlt">2</span> Gy) of ECA-109 and TE-13 cells in the combined group were significantly lower than those of the radiation group (for ECA-109 cells, 1.11 vs. 1.72, 1.40 vs. <span class="hlt">2</span>.14, 0.42 vs. 0.66, respectively; for TE-13 cells, 0.41 vs. 0.46, 0.43 vs. 0.65, 0.40 vs. 0.71, respectively (all P <0.05). The sensitivity enhancement ratio (SER) of ECA-109 and TE-13 cells were 1.35 and 1.43, respectively. Flow cytometry showed that the apoptosis rate of ECA-109 and TE-13 cells in the combined group were significantly higher than those of the radiation group [for ECA-109 cells, (41.31±1.52)% vs. (9.54±0.52)%; for TE-13 cells, (46.28±0.28)% vs. (11.32±0.31)%, both P <0.01]. Western blotting showed that the expression levels of EGFR and DNA-PKcs were not significantly different in all groups (all P >0.05). Compared with those of the control group, p-EGFR and p-DNA-PKcs of the radiation group were significantly higher in both cell lines ( P <0.05), and the γH<span class="hlt">2</span>AX levels in the radiation group and medicine group were significantly higher than that of the control group ( P <0.05). Compared with those of the radiation group and medicine group, p-EGFR and p-DNA-PKcs protein</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28535302','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28535302"><span>Inhibition of N-acetylglucosaminyltransferase V enhances the cetuximab-induced <span class="hlt">radiosensitivity</span> of nasopharyngeal carcinoma cells likely through EGFR N-glycan alterations.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huang, Xiaomin; Liu, Ting; Wang, Qiongyao; Zhu, Weiliang; Meng, Hui; Guo, Linlang; Wei, Ting; Zhang, Jian</p> <p>2017-05-23</p> <p>N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyses the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the <span class="hlt">radiosensitivity</span> of nasopharyngeal carcinoma (NPC). Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a <span class="hlt">radiosensitizer</span> in the treatment of NPC. In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. The results from two NPC cell lines (CNE1 and CNE<span class="hlt">2</span>) revealed that the silencing of GnT-V enhanced cetuximab-induced <span class="hlt">radiosensitivity</span> by decreasing the β-1-6 branching of oligosaccharides on the EGFR. GnT-V down-regulation combined with cetuximab decreased the survival fraction, healing rate and cell viability and increased the apoptosis rate. Concomitantly, the combination of cetuximab and irradiation did not change the EGFR mRNA and protein levels and decreased the β-1-6 branching on the EGFR. Subsequently, we further explored the signalling downstream of EGF, particularly the PI3K/Akt signalling pathway, and discovered that treatment consisting of GnT-V down-regulation, irradiation and cetuximab was negatively correlated with phospho-Akt and phspho-PI3K. Finally, an in vivo experiment with radiotherapy revealed that the combination of GnT-V down-regulation and cetuximab decelerated tumour growth. In summary, our study demonstrated that the combination of decreased GnT-V activity and cetuximab enhanced NPC <span class="hlt">radiosensitivity</span>, and the possible mechanism underlying this effect might involve the N-linked β1-6 branching of the EGFR. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21451150-ionizing-radiation-activates-amp-activated-kinase-ampk-target-radiosensitization-human-cancer-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21451150-ionizing-radiation-activates-amp-activated-kinase-ampk-target-radiosensitization-human-cancer-cells"><span>Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for <span class="hlt">Radiosensitization</span> of Human Cancer Cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Sanli, Toran; Rashid, Ayesha; Liu Caiqiong</p> <p>2010-09-01</p> <p>Purpose: Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for <span class="hlt">radiosensitization</span> of human cancer cells. Methods and Materials: Lung, prostate, and breast cancer cells were treated with IR (<span class="hlt">2</span>-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis. Results:more » IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti-AMPK {alpha} subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21{sup waf/cip} as well as the IR-induced <span class="hlt">G</span><span class="hlt">2</span>/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after <span class="hlt">2</span> Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after <span class="hlt">2</span> Gy further. Conclusions: We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21{sup waf/cip} and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM-AMPK-p21{sup waf/cip} pathway, (<span class="hlt">2</span>) be involved in regulation of the IR-induced <span class="hlt">G</span><span class="hlt">2</span>/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5471005','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5471005"><span>In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma using micro 18F-FDG PET/CT</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Shen, Li-Fang; Zhao, Xin; Zhou, Shui-Hong; Lu, Zhong-Jie; Zhao, Kui; Fan, Jun; Zhou, Min-Li</p> <p>2017-01-01</p> <p>Purpose Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with <span class="hlt">2</span>′-deoxy-<span class="hlt">2</span>’-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo. Materials and Methods To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-<span class="hlt">2</span> (<span class="hlt">2</span> × 107/mL × 0.<span class="hlt">2</span> mL) and Tu212 cells (<span class="hlt">2</span> × 107/mL × 0.<span class="hlt">2</span> mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 μ<span class="hlt">g</span>) and GLUT-1 AS-ODNs (100 μ<span class="hlt">g</span>) on the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated and the value of 18F-FDG-PET/CT was assessed after treating the xenografts. Results 10 Gy X-ray irradiation decreased the weight of Hep-<span class="hlt">2</span> xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-<span class="hlt">2</span> xenografts 8 days after treatment (p < 0.05) and in Tu212 xenografts 12 days after treatment (p < 0.001). Standardized uptake value (tumor/normal tissue</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28410229','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28410229"><span>In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma using micro 18F-FDG PET/CT.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shen, Li-Fang; Zhao, Xin; Zhou, Shui-Hong; Lu, Zhong-Jie; Zhao, Kui; Fan, Jun; Zhou, Min-Li</p> <p>2017-05-23</p> <p>Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with <span class="hlt">2</span>'-deoxy-<span class="hlt">2</span>'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo. To verify the above hypotheses, an in vivo model was applied by subcutaneously injecting Hep-<span class="hlt">2</span> (<span class="hlt">2</span> × 107/mL × 0.<span class="hlt">2</span> mL) and Tu212 cells (<span class="hlt">2</span> × 107/mL × 0.<span class="hlt">2</span> mL) into nude mice. The effects of HIF-1α antisense oligodeoxynucleotides (AS-ODNs) (100 μ<span class="hlt">g</span>) and GLUT-1 AS-ODNs (100 μ<span class="hlt">g</span>) on the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma were assessed by tumor volume and weight, microvessel density (MVD), apoptosis index (AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT was taken before and after the treatment of xenografts. The relationships between HIF-1α and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated and the value of 18F-FDG-PET/CT was assessed after treating the xenografts. 10 Gy X-ray irradiation decreased the weight of Hep-<span class="hlt">2</span> xenografts 8 and 12 days after treatment, and the weights of Tu212 xenografts 8 days after treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after treatment. There was a synergistic interaction among the three treatments (GLUT-1 AS-ODNs, HIF-1α AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis, decreasing MVD, and increasing necrosis in Hep-<span class="hlt">2</span> xenografts 8 days after treatment (p < 0.05) and in Tu212 xenografts 12 days after treatment (p < 0.001). Standardized uptake value (tumor/normal tissue)( SUVmaxT/N) did not show a statistically</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21451151-sodium-selenite-radiosensitizes-hormone-refractory-prostate-cancer-xenograft-tumors-intestinal-crypt-cells-vivo','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21451151-sodium-selenite-radiosensitizes-hormone-refractory-prostate-cancer-xenograft-tumors-intestinal-crypt-cells-vivo"><span>Sodium Selenite <span class="hlt">Radiosensitizes</span> Hormone-Refractory Prostate Cancer Xenograft Tumors but Not Intestinal Crypt Cells In Vivo</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Tian Junqiang; Ning Shouchen; Knox, Susan J., E-mail: sknox@stanford.ed</p> <p></p> <p>Purpose: We have previously shown that sodium selenite (SSE) increases radiation-induced cell killing of human prostate carcinoma cells in vitro. In this study we further evaluated the in vivo <span class="hlt">radiosensitizing</span> effect of SSE in prostate cancer xenograft tumors and normal <span class="hlt">radiosensitive</span> intestinal crypt cells. Methods and Materials: Immunodeficient (SCID) mice with hormone-independent LAPC-4 (HI-LAPC-4) and PC-3 xenograft tumors (approximately 200 mm{sup 3}) were divided into four groups: control (untreated), radiation therapy (XRT, local irradiation), SSE (<span class="hlt">2</span> mg/kg, intraperitoneally, 3 times/week), and XRT plus SSE. The XRT was given at the beginning of the regimen as a single dose of 5more » Gy for HI-LAPC-4 tumors and a single dose of 7 Gy followed by a fractional dose of 3 Gy/d for 5 days for PC-3 tumors. The tumor volume was measured 3 times per week. The <span class="hlt">radiosensitizing</span> effect of SSE on normal intestinal epithelial cells was assessed by use of a crypt cell microcolony assay. Results: In the efficacy study, SSE alone significantly inhibited the tumor growth in HI-LAPC-4 tumors but not PC-3 tumors. Sodium selenite significantly enhanced the XRT-induced tumor growth inhibition in both HI-LAPC-4 and PC-3 tumors. In the toxicity study, SSE did not affect the intestinal crypt cell survival either alone or in combination with XRT. Conclusions: Sodium selenite significantly enhances the effect of radiation on well-established hormone-independent prostate tumors and does not sensitize the intestinal epithelial cells to radiation. These results suggest that SSE may increase the therapeutic index of XRT for the treatment of prostate cancer.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6600802-radiosensitivity-thermosensitization-thermotolerant-chinese-hamster-cells-rif-tumors','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6600802-radiosensitivity-thermosensitization-thermotolerant-chinese-hamster-cells-rif-tumors"><span><span class="hlt">Radiosensitivity</span> and thermosensitization of thermotolerant Chinese hamster cells and RIF-1 tumors</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hartson-Eaton, M.; Malcolm, A.W.; Hahn, G.M.</p> <p>1984-07-01</p> <p>CHO cells subline HA-1 were made thermotolerant by a priming heat treatment(43/sup 0/C, 30 min). Later, 4, 16, or 24 hr, they were either irradiated or heated (43/sup 0/C, 30 min) and irradiated. Thermotolerance had no effect on the radiation sensitivity of the cells as measured by the D/sub 0/ value of the clonogenic survival curve. However the N value of the curve (width of shoulder) showed a significant increase at 24 hr, indicating an increased capacity to accumulate sublethal damage. The same priming treatment was given to RIF-1 tumors growing in C3H mice. Later, 24 hr, when the tumorsmore » were either irradiated or heated (43/sup 0/C, 30 min) and irradiated, it was found that thermotolerance had no effect on the <span class="hlt">radiosensitivity</span> of the cells as measured by in vitro assay. However, thermal <span class="hlt">radiosensitization</span> was not apparent 24 hr after the priming treatment.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22572280-we-gold-nanoparticles-radiosensitizers-what-does-take-go-from-bench-bedside','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22572280-we-gold-nanoparticles-radiosensitizers-what-does-take-go-from-bench-bedside"><span>WE-<span class="hlt">G</span>-303-02: Gold Nanoparticles as <span class="hlt">Radiosensitizers</span> - What Does It Take To Go From the Bench to the Bedside?</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Krishnan, S.</p> <p></p> <p>. Learning Objectives: Understand the physical bases of gold nanoparticle applications for <span class="hlt">radiosensitization</span> and x-ray fluorescence imaging Understand the parameters that define gold nanoparticle-mediated <span class="hlt">radiosensitization</span> in biological systems Understand the potential of magnetic nanoparticle characterization of the microenvironment Understand the various strategies for radiolabeling of nanoparticles and their applications S.C. and S.K. acknowledge support from MD Anderson Cancer Center, NIH (R01CA155446 and P30CA16672) and DoD (W81XWH-12-1-0198); J.W. acknowledges support from NIH (U54CA151662-01); W.C. acknowledges support from the University of Wisconsin-Madison, NIH (R01CA169365, P30CA014520, and T32CA009206), DoD (W81XWH-11-1-0644 and W81XWH-11-1-0648), and ACS (125246-RSG-13-099-01-CCE)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3724775','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3724775"><span>Very low sister-<span class="hlt">chromatid</span> exchange rate in Seventh-Day Adventists.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wulf, H C; Iversen, A S; Husum, B; Niebuhr, E</p> <p>1986-08-01</p> <p>42 Seventh-Day Adventists (SDAs) and 42 controls matched for sex, age and occupation had their sister-<span class="hlt">chromatid</span> exchange (SCE) examined in peripheral blood lymphocytes. This was done to examine if the SCE frequency was lower in this group of people, who are known to have a decreased cancer risk compared to the general population. The average SCE/cell in 30 cells from each person was 5.54 +/- 0.07 (mean +/- standard error of the mean) for the SDAs and 8.00 +/- 0.15 for the controls, the difference being statistically significant (p less than 0.00001). No difference in SCE frequency was found between SDAs eating only an ovo-lacto-vegetarian diet and those eating some fish or meat. The mitotic index (MI) was significantly higher and the replication index (RI) was significantly lower in SDAs than in controls. No correlation was found between gamma (a statistical transformation of SCEs/cell) and MI or RI within the groups of SDAs or controls. In the pooled data there was a negative correlation of gamma and MI and a positive correlation of gamma and RI. Of the interpersonal variation in gamma 8% and 14% could be explained by MI and RI. The finding of a lower SCE frequency in a group of SDAs who have a low risk of cancer might indirectly indicate a relation between SCE and cancer and encourages further studies of SCE and diet.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22660730-dissociative-electron-attachment-radiosensitizing-chemotherapeutic-agent-hydroxyurea','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22660730-dissociative-electron-attachment-radiosensitizing-chemotherapeutic-agent-hydroxyurea"><span>Dissociative electron attachment to the <span class="hlt">radiosensitizing</span> chemotherapeutic agent hydroxyurea</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Huber, S. E.; Tanzer, K.; Denifl, S.</p> <p></p> <p>Dissociative electron attachment to hydroxyurea was studied in the gas phase for electron energies ranging from zero to 9 eV in order to probe its <span class="hlt">radiosensitizing</span> capabilities. The experiments were carried out using a hemispherical electron monochromator coupled with a quadrupole mass spectrometer. Diversified fragmentation of hydroxyurea was observed upon low energy electron attachment and here we highlight the major dissociation channels. Moreover, thermodynamic thresholds for various fragmentation reactions are reported to support the discussion of the experimental findings. The dominant dissociation channel, which was observed over a broad range of energies, is associated with formation of NCO{sup −}, water,more » and the amidogen (NH{sub <span class="hlt">2</span>}) radical. The second and third most dominant dissociation channels are associated with formation of NCNH{sup −} and NHCONH{sub <span class="hlt">2</span>}{sup −}, respectively, which are both directly related to formation of the highly reactive hydroxyl radical. Other ions observed with significant abundance in the mass spectra were NH{sub <span class="hlt">2</span>}{sup −}/O{sup −}, OH{sup −}, CN{sup −}, HNOH{sup −}, NCONH{sub <span class="hlt">2</span>}{sup −}, and ONHCONH{sub <span class="hlt">2</span>}{sup −}.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013SPIE.8775E..0US','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013SPIE.8775E..0US"><span>Radiation dose to <span class="hlt">radiosensitive</span> organs in PET/CT myocardial perfusion examination using versatile optical fibre</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Salasiah, M.; Nordin, A. J.; Fathinul Fikri, A. S.; Hishar, H.; Tamchek, N.; Taiman, K.; Ahmad Bazli, A. K.; Abdul-Rashid, H. A.; Mahdiraji, G. A.; Mizanur, R.; Noor, Noramaliza M.</p> <p>2013-05-01</p> <p>Cardiac positron emission tomography (PET) provides a precise method in order to diagnose obstructive coronary artery disease (CAD), compared to single photon emission tomography (SPECT). PET is suitable for obese and patients who underwent pharmacologic stress procedures. It has the ability to evaluate multivessel coronary artery disease by recording changes in left ventricular function from rest to peak stress and quantifying myocardial perfusion (in mL/min/<span class="hlt">g</span> of tissue). However, the radiation dose to the <span class="hlt">radiosensitive</span> organs has become crucial issues in the Positron Emission Tomography/Computed Tomography(PET/CT) scanning procedure. The objective of this study was to estimate radiation dose to <span class="hlt">radiosensitive</span> organs of patients who underwent PET/CT myocardial perfusion examination at Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia in one month period using versatile optical fibres (Ge-B-doped Flat Fibre) and LiF (TLD-100 chips). All stress and rest paired myocardial perfusion PET/CT scans will be performed with the use of Rubidium-82 (82Rb). The optic fibres were loaded into plastic capsules and attached to patient's eyes, thyroid and breasts prior to the infusion of 82Rb, to accommodate the ten cases for the rest and stress PET scans. The results were compared with established thermoluminescence material, TLD-100 chips. The result shows that radiation dose given by TLD-100 and Germanium-Boron-doped Flat Fiber (Ge-B-doped Flat Fiber) for these five organs were comparable to each other where the p>0.05. For CT scans,thyroid received the highest dose compared to other organs. Meanwhile, for PET scans, breasts received the highest dose.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2007iioe.book....1Z','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2007iioe.book....1Z"><span>Measuring the performance of <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> services in Iran</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Zarei, Behrouz; Safdari, Maryam</p> <p></p> <p>To highlight the growth of e-government and the importance of its services it is essential to evaluate the performance of the service delivery to customers. Research indicates that traditional performance indexes are not suitable for this evaluation; moreover, it is noticeable that the e-government services are intangible and invisible. Among different e-government services, measurement of quality government to government (<span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span>) services has been less attractive for researchers while crucial for government policy-makers. This calls for a better understanding of the specific needs of users of these services in order to provide appropriate type and level of services that meets those needs. In this paper, the performance of the <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> services is measured in the Iranian context. For this purpose, SERVQUAL, which is a well-known method for assessing service quality, is employed. This study proposes and tests a five-factor of SERVQUAL instrument to explain user satisfaction and gap analysis, between expectations and perceptions of its customers, consisting thirty ministries and main governmental organizations. Based on a Chi-square test, factor analysis, gap analysis and correlations, it is concluded the gap between expectations and perceptions of <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> customers is significant and customer satisfaction of <span class="hlt">G</span><span class="hlt">2</span><span class="hlt">G</span> services is at low level.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3753417','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3753417"><span>Effect of Antisense Oligodeoxynucleotides Glucose Transporter-1 on Enhancement of <span class="hlt">Radiosensitivity</span> of Laryngeal Carcinoma</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yan, Sen-Xiang; Luo, Xing-Mei; Zhou, Shui-Hong; Bao, Yang-Yang; Fan, Jun; Lu, Zhong-Jie; Liao, Xin-Biao; Huang, Ya-Ping; Wu, Ting-Ting; Wang, Qin-Ying</p> <p>2013-01-01</p> <p>Purpose: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma. Methods: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma in vitro and in vivo. Results: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). Conclusion: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the <span class="hlt">radiosensitivity</span> of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1. PMID:23983599</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22900762','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22900762"><span>Experimental and theoretical investigation of homogeneous gaseous reaction of CO<span class="hlt">2</span>(<span class="hlt">g</span>) + nH<span class="hlt">2</span>O(<span class="hlt">g</span>) + nNH3(<span class="hlt">g</span>) → products (n = 1, <span class="hlt">2</span>).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Zhuangjie; Zhang, Baoquan</p> <p>2012-09-13</p> <p>Decreasing CO<span class="hlt">2</span> emissions into the atmosphere is key for reducing global warming. To facilitate the CO<span class="hlt">2</span> emission reduction efforts, our laboratory conducted experimental and theoretical investigations of the homogeneous gaseous reaction of CO<span class="hlt">2</span>(<span class="hlt">g</span>) + nH<span class="hlt">2</span>O(<span class="hlt">g</span>) + nNH3(<span class="hlt">g</span>) → (NH4)HCO3(s)/(NH4)<span class="hlt">2</span>CO3(s) (n = 1 and <span class="hlt">2</span>) using Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy and ab initio molecular orbital theory. Our FTIR-ATR experimental results indicate that (NH4)<span class="hlt">2</span>CO3(s) and (NH4)HCO3(s) are formed as aerosol particulate matter when carbon dioxide reacts with ammonia and water in the gaseous phase at room temperature. Ab initio study of this chemical system suggested that the reaction may proceed through formation of NH3·H<span class="hlt">2</span>O(<span class="hlt">g</span>), NH3·CO<span class="hlt">2</span>(<span class="hlt">g</span>), and CO<span class="hlt">2</span>·H<span class="hlt">2</span>O(<span class="hlt">g</span>) complexes. Subsequent complexes, NH3·H<span class="hlt">2</span>O·CO<span class="hlt">2</span> and (NH3)<span class="hlt">2</span>·H<span class="hlt">2</span>O·CO<span class="hlt">2</span>, can be formed by adding gaseous reactants to the NH3·H<span class="hlt">2</span>O(<span class="hlt">g</span>), NH3·CO<span class="hlt">2</span>(<span class="hlt">g</span>), and CO<span class="hlt">2</span>·H<span class="hlt">2</span>O(<span class="hlt">g</span>) complexes, respectively. The NH3·H<span class="hlt">2</span>O·CO<span class="hlt">2</span> and (NH3)<span class="hlt">2</span>·H<span class="hlt">2</span>O·CO<span class="hlt">2</span> complexes can then be rearranged to produce (NH4)HCO3 and (NH4)<span class="hlt">2</span>CO3 as final products via a transition state, and the NH3 molecule acts as a medium accepting and donating hydrogen atoms in the rearrangement process. Our computational results also reveal that the presence of an additional water molecule can reduce the activation energy of the rearrangement process. The high activation energy predicted in the present work suggests that the reaction is kinetically not favored, and our experimental observation of (NH4)HCO3(s) and (NH4)<span class="hlt">2</span>CO3(s) may be attributed to the high concentrations of reactants increasing the reaction rate of the title reactions in the reactor.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li class="active"><span>16</span></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_16 --> <div id="page_17" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="321"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24571173','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24571173"><span>Heat exposure enhances <span class="hlt">radiosensitivity</span> by depressing DNA-PK kinase activity during double strand break repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ihara, Makoto; Takeshita, Satoshi; Okaichi, Kumio; Okumura, Yutaka; Ohnishi, Takeo</p> <p>2014-03-01</p> <p>From the role of double strand DNA dependent protein kinase (DNA-PKcs) activity of non-homologous end joining (NHEJ) repair for DNA double strand breaks (DSBs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in X-ray irradiated cells. DNA-PKcs deficient mouse, Chinese hamster and human cultured cells were compared to the parental wild-type cells. The <span class="hlt">radiosensitivities</span>, the number of DSBs and DNA-PKcs activities after heat-treatment were measured. Both DNA-PKcs deficient cells and the wild-type cells showed increased <span class="hlt">radiosensitivities</span> after heat-treatment. The wild-type cells have two repair processes; fast repair and slow repair. In contrast, DNA-PKcs deficient cells have only the slow repair process. The fast repair component apparently disappeared by heat-treatment in the wild-type cells. In both cell types, additional heat exposure enhanced <span class="hlt">radiosensitivities</span>. Although DNA-PKcs activity was depressed by heat, the inactivated DNA-PKcs activity recovered during an incubation at 37 °C. DSB repair efficiency was dependent on the reactivation of DNA-PKcs activity. It was suggested that NHEJ is the major process used to repair X-ray-induced DSBs and utilises DNA-PKcs activity, but homologous recombination repair provides additional secondary levels of DSB repair. The thermo-sensitisation in X-ray-irradiated cells depends on the inhibition of NHEJ repair through the depression of DNA-PKcs activities.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21906280','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21906280"><span>Increased betulinic acid induced cytotoxicity and <span class="hlt">radiosensitivity</span> in glioma cells under hypoxic conditions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bache, Matthias; Zschornak, Martin P; Passin, Sarina; Kessler, Jacqueline; Wichmann, Henri; Kappler, Matthias; Paschke, Reinhard; Kaluđerović, Goran N; Kommera, Harish; Taubert, Helge; Vordermark, Dirk</p> <p>2011-09-09</p> <p>Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as <span class="hlt">radiosensitivity</span> under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and <span class="hlt">radiosensitivity</span> were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Under normoxic conditions, a half maximal inhibitory concentration (IC50) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was <span class="hlt">2</span>.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Our results suggest that BA is capable of</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/20972133-ectopically-htert-expressing-adult-human-mesenchymal-stem-cells-less-radiosensitive-than-telomerase-negative-counterpart','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/20972133-ectopically-htert-expressing-adult-human-mesenchymal-stem-cells-less-radiosensitive-than-telomerase-negative-counterpart"><span>Ectopically hTERT expressing adult human mesenchymal stem cells are less <span class="hlt">radiosensitive</span> than their telomerase negative counterpart</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Serakinci, Nedime; Christensen, Rikke; Graakjaer, Jesper</p> <p>2007-03-10</p> <p>During the past several years increasing evidence indicating that the proliferation capacity of mammalian cells is highly <span class="hlt">radiosensitive</span>, regardless of the species and the tissue of origin of the cells, has accumulated. It has also been shown that normal bone marrow cells of mice have a similar <span class="hlt">radiosensitivity</span> to other mammalian cells so far tested. In this study, we investigated the genetic effects of ionizing radiation (<span class="hlt">2</span>.5-15 Gy) on normal human mesenchymal stem cells and their telomerised counterpart hMSC-telo1. We evaluated overall genomic integrity, DNA damage/repair by applying a fluorescence-detected alkaline DNA unwinding assay together with Western blot analyses formore » phosphorylated H<span class="hlt">2</span>AX and Q-FISH was applied for investigation of telomeric damage. Our results indicate that hMSC and TERT-immortalized hMSCs can cope with relatively high doses of {gamma}-rays and that overall DNA repair is similar in the two cell lines. The telomeres were extensively destroyed after irradiation in both cell types suggesting that telomere caps are especially sensitive to radiation. The TERT-immortalized hMSCs showed higher stability at telomeric regions than primary hMSCs indicating that cells with long telomeres and high telomerase activity have the advantage of re-establishing the telomeric caps.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3615400','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3615400"><span><span class="hlt">Radiosensitivity</span> of pimonidazole-unlabelled intratumour quiescent cell population to γ-rays, accelerated carbon ion beams and boron neutron capture reaction</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Masunaga, S; Sakurai, Y; Tanaka, H; Hirayama, R; Matsumoto, Y; Uzawa, A; Suzuki, M; Kondo, N; Narabayashi, M; Maruhashi, A; Ono, K</p> <p>2013-01-01</p> <p>Objective To detect the <span class="hlt">radiosensitivity</span> of intratumour quiescent (Q) cells unlabelled with pimonidazole to accelerated carbon ion beams and the boron neutron capture reaction (BNCR). Methods EL4 tumour-bearing C57BL/J mice received 5-bromo-29-deoxyuridine (BrdU) continuously to label all intratumour proliferating (P) cells. After the administration of pimonidazole, tumours were irradiated with c-rays, accelerated carbon ion beams or reactor neutron beams with the prior administration of a 10B-carrier. Responses of intratumour Q and total (P+Q) cell populations were assessed based on frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of pimonidazole-unlabelled tumour cells was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. Results Following c-ray irradiation, the pimonidazole-unlabelled tumour cell fraction showed significantly enhanced <span class="hlt">radiosensitivity</span> compared with the whole tumour cell fraction, more remarkably in the Q than total cell populations. However, a significantly greater decrease in <span class="hlt">radiosensitivity</span> in the pimonidazole-unlabelled cell fraction, evaluated using a delayed assay or a decrease in radiation dose rate, was more clearly observed among the Q than total cells. These changes in <span class="hlt">radiosensitivity</span> were suppressed following carbon ion beam and neutron beam-only irradiaton. In the BNCR, the use of a 10B-carrier, especially L-para-boronophenylalanine-10B, enhanced the sensitivity of the pimonidazole-unlabelled cells more clearly in the Q than total cells. Conclusion The <span class="hlt">radiosensitivity</span> of the pimonidazole-unlabelled cell fraction depends on the quality of radiation delivered and characteristics of the 10B-carrier used in the BNCR. Advances in knowledge The pimonidazole-unlabelled subfraction of Q tumour cells may be a critical target in tumour control. PMID:23255546</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013mss..confEWG12L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013mss..confEWG12L"><span>Superiority of Low Energy 160 KV X-Rays Compared to High Energy 6 MV X-Rays in Heavy Element <span class="hlt">Radiosensitization</span> for Cancer Treatment</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Lim, Sara N.; Pradhan, Anil K.; Nahar, Sultana N.; Barth, Rolf F.; Yang, Weilian; Nakkula, Robin J.; Palmer, Alycia; Turro, Claudia</p> <p>2013-06-01</p> <p>High energy X-rays in the MeV range are generally employed in conventional radiation therapy from linear accelerators (LINAC) to ensure sufficient penetration depths. However, lower energy X-rays in the keV range may be more effective when coupled with heavy element (high-Z or HZ) <span class="hlt">radiosensitizers</span>. Numerical simulations of X-ray energy deposition for tumor phantoms sensitized with HZ <span class="hlt">radiosensitizers</span> were performed using the Monte Carlo code Geant4. The results showed enhancement in energy deposition to <span class="hlt">radiosensitized</span> phantoms relative to unsensitized phantoms for low energy X-rays in the keV range. In contrast, minimal enhancement was seen using high energy X-rays in the MeV range. Dose enhancement factors (DEFs) were computed and showed <span class="hlt">radiosensitization</span> only in the low energy range < 200 keV, far lower than the energy of the majority of photons in the LINAC energy range. In vitro studies were carried to demonstrate the tumoricidal effects of HZ sensitized F98 rat glioma cells following irradiation with both low energy 160 kV and high energy 6 MV X-ray sources. The platinum compound, pyridine terpyridine Pt(II) nitrate, was initially used because it was 7x less toxic that an equivalent amount of carboplatin in vitro studies. This would allow us to separate the radiotoxic and the chemotoxic effects of HZ sensitizers. Results from this study showed a 10-fold dose dependent reduction in surviving fractions (SF) of <span class="hlt">radiosensitized</span> cells treated with low energy 160 kV X-rays compared to those treated with 6 MV X-rays. This is in agreement with our simulations that show an increase in dose deposition in <span class="hlt">radiosensitized</span> tumors for low energy X-rays. Due to unforeen in vivo toxicity, however, another in vitro study was performed using the commonly used, Pt-based chemotherapeutic drug carboplatin which confirmed earlier results. This lays the ground work for a planned in vivo study using F98 glioma bearing rats. This study demonstrates that while high energy X-rays are</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25486738','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25486738"><span>[Individual variability of immunological markers, <span class="hlt">radiosensitivity</span> and oxidative status in blood lymphocytes of Moscow residents].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pelevina, I I; Aleshchenko, A V; Antoshchina, M M; Kudriashova, O M; Nikonova, M F; Riabchenko, N I; Serebrianyĭ, A M; Iarilin, A A</p> <p>2013-01-01</p> <p>Expression of activation (CD69) and proliferation (Ki67) markers, their connection with each other, with the oxidative status (reactive oxygen species--ROS) and with <span class="hlt">radiosensitivity</span> (determined by micronucleus test) have been studied on stimulated blood lymphocytes from Moscow inhabitants. It was shown that the content of T-lymphocytes with the expressed CD69 and the content of T-lymphocytes with the expressed Ki67 markers correlate (r = 0.571; p = 0.0004). We can suppose that expression of the CD69 marker (24 h after PHA stimulation) is needed for the cell cycle progression, but it is not enough for the high expression of Ki67 markers 48 h after stimulation (DNA synthesis phase). It was discovered that T-lymphocytes with the CD69 marker or T-lymphocytes with the Ki67 marker are connected by the negative correlation with the frequency of irradiated cell with micronucleus (MN) r = -0.487; p = 0.010; r = -0.440; p = 0.008, respectively. So we can suppose that lymphocyte <span class="hlt">radiosensitivity</span> decreased with the increase of expression activation and proliferation markers. It was shown that <span class="hlt">radiosensitivity</span> determined by MN test is not connected with the oxidative status determined by the reactive oxygen species content including superoxide anion radicals. It is possible to explain by the fact that the ROS concentration has been determined in non-stimulated lymphocytes, but frequencies of cells with MN - in the stimulated cells 48 h after stimulation. Using separate analysis of individual differences by the studied parameters that were determined in the same people, it was shown that individual differences are high enough in the same cases. For example, the <span class="hlt">radiosensitivity</span> when cells were irradiated 48 h after stimulation, ROS concentration, cell content with activation and proliferation markers. In conclusion, we can say that we failed to find important correlation between the parameters studied. However, the presence of individual differences in the marker expression</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7300853','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7300853"><span>Sister-<span class="hlt">chromatid</span> exchanges in lymphocytes in women with cancer of the breast.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Husum, B; Wulf, H C; Niebuhr, E</p> <p>1981-10-01</p> <p>Examination of sister-<span class="hlt">chromatid</span> exchanges (SCE) in lymphocytes may be useful for the evaluation of exposure to mutagens/carcinogens. Information of a possible association between SCE and cancer is scarce. We therefore examined SCE in peripheral lymphocytes in 131 women, aged 17-90 years (median 51.8 years), coming to operation because of a tumor of the breast. Venous blood samples were cultivated during PHA stimulation in the presence of BrdU. After treatment with colcemid (R), fixation, treatment with bisbenzimide and staining with Giemsa, 30 metaphases were scored in each specimen. 52 patients with peroperatively demonstrated carcinoma of the breast had 9.39 +/- 0.17 SCE/cell and the remaining 79 women with non-malignant fibroadenomatosis had 9.88 +/- 0.18 SCE/cell. By multiple regression analysis it appeared that the character of the tumor, the patient's age, hormone treatment and preoperative examination by mammography all were without significant influence on the SCE rate. A statistically significant correlation was found between SCE and cigarette smoking. THe 45 cigarette-smoking patients had 10.49 +/- 0.23 SCE/cell compared with 9.26 +/- 0.13 SCE/cell in the 86 non-smokers. It was concluded that spontaneous SCE in lymphocytes is not an indicator of carcinoma of the breast.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011JMoSt.992...65R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011JMoSt.992...65R"><span>Topology and dynamics of the interaction between 5-nitroimidazole <span class="hlt">radiosensitizers</span> and duplex DNA studied by a combination of docking, molecular dynamic simulations and NMR spectroscopy</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ramalho, Teodorico C.; França, Tanos C. C.; Cortopassi, Wilian A.; Gonçalves, Arlan S.; da Silva, Alan W. S.; da Cunha, Elaine F. F.</p> <p>2011-04-01</p> <p>In spite of recent progress, cancer is still one of the most serious health problems of mankind. Recently, it has been discovered that tumor hypoxia can be exploited for selective anticancer treatment using <span class="hlt">radiosensitizers</span> that are activated only under hypoxic conditions. The most commonly used <span class="hlt">radiosensitizers</span> are the 5-nitroimidazole derivatives. The toxicity of bioreductive anticancer drugs, such as <span class="hlt">radiosensitizers</span> is associated to their interaction with DNA. In this work, we have investigated the interaction between the model <span class="hlt">radiosensitizers</span> metronizole, nimorazole and secnidazole with salmon DNA in order to get insights on the drug-macromolecule interactions. To this end, we have employed NMR techniques (PFG NMR spectra and spin-lattice relaxation rates) in combination with theoretical tools, such as docking calculations and MD simulations. Initially, results show that the δ values are not the most appropriated NMR parameters to map the interaction topology of drug-macromolecule complexes. Furthermore our data indicate that <span class="hlt">radiosensitizers</span>, in the inactive form, interact considerably with DNA, significantly increasing its toxicity. In fact, we obtained a good agreement between that technique and docking and MD simulations. This suggests that improvements in the structures of these molecules in order to achieve new and more selective bioreductive anticancer drugs are still necessary.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040141414&hterms=protein+cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D80%26Ntt%3Dprotein%2Bcancer','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040141414&hterms=protein+cancer&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D80%26Ntt%3Dprotein%2Bcancer"><span>A deficiency in DNA repair and DNA-PKcs expression in the <span class="hlt">radiosensitive</span> BALB/c mouse</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Okayasu, R.; Suetomi, K.; Yu, Y.; Silver, A.; Bedford, J. S.; Cox, R.; Ullrich, R. L.</p> <p>2000-01-01</p> <p>We have studied the efficiency of DNA double strand break (DSB) rejoining in primary cells from mouse strains that show large differences in in vivo <span class="hlt">radiosensitivity</span> and tumor susceptibility. Cells from <span class="hlt">radiosensitive</span>, cancer-prone BALB/c mice showed inefficient end joining of gamma ray-induced DSBs as compared with cells from all of the other commonly used strains and F1 hybrids of C57BL/6 and BALB/c mice. The BALB/c repair phenotype was accompanied by a significantly reduced expression level of DNA-PKcs protein as well as a lowered DNA-PK activity level as compared with the other strains. In conjunction with published reports, these data suggest that natural genetic variation in nonhomologous end joining processes may have a significant impact on the in vivo radiation response of mice.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22594159-radiosensitizing-effect-psmc5-proteasome-atpase-h460-lung-cancer-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22594159-radiosensitizing-effect-psmc5-proteasome-atpase-h460-lung-cancer-cells"><span><span class="hlt">Radiosensitizing</span> effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Yim, Ji-Hye; Yun, Hong Shik; Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791</p> <p>2016-01-01</p> <p>The function of PSMC5 (proteasome 26S subunit, ATPase 5) in tumors, particularly with respect to cancer radioresistance, is not known. Here, we identified PSMC5 as a novel <span class="hlt">radiosensitivity</span> biomarker, demonstrating that <span class="hlt">radiosensitive</span> H460 cells were converted to a radioresistance phenotype by PSMC5 depletion. Exposure of H460 cells to radiation induced a marked accumulation of cell death-promoting reactive oxygen species, but this effect was blocked in radiation-treated H460 PSMC5-knockdown cells through downregulation of the p53-p21 pathway. Interestingly, PSMC5 depletion in H460 cells enhanced both AKT activation and MDM<span class="hlt">2</span> transcription, thereby promoting the degradation of p53 and p21 proteins. Furthermore, specific inhibitionmore » of AKT with triciribine or knockdown of MDM<span class="hlt">2</span> with small interfering RNA largely restored p21 expression in PSMC5-knockdown H460 cells. Our data suggest that PSMC5 facilitates the damaging effects of radiation in radiation-responsive H460 cancer cells and therefore may serve as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients. - Highlights: • PSMC5 is a radiation-sensitive biomarker in H460 cells. • PSMC5 depletion inhibits radiation-induced apoptosis in H460 cells. • PSMC5 knockdown blocks ROS generation through inhibition of the p53-p21 pathway. • PSMC5 knockdown enhances p21 degradation via AKT-dependent MDM<span class="hlt">2</span> stabilization.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4643289','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4643289"><span>Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce</p> <p>2015-01-01</p> <p>The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO<span class="hlt">2</span>) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO<span class="hlt">2</span> nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO<span class="hlt">2</span> nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μ<span class="hlt">g</span>/cm<span class="hlt">2</span> induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO<span class="hlt">2</span> nanoparticles induced serious forms of DNA damage such as <span class="hlt">chromatid</span> breaks, isochromatid lesions or <span class="hlt">chromatid</span> exchanges. Treatments of 0, 10, 50 and 100 μ<span class="hlt">g</span>/cm<span class="hlt">2</span> induced 3.3, 3.0, 3.0 and <span class="hlt">2</span>.7% metaphases with damage, respectively. No isochromatid lesions or <span class="hlt">chromatid</span> exchanges were detected. These data show that TiO<span class="hlt">2</span> nanoparticles are not cytotoxic or clastogenic to human skin cells. PMID:26568896</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26568896','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26568896"><span>Titanium Dioxide Nanoparticles are not Cytotoxic or Clastogenic in Human Skin Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Browning, Cynthia L; The, Therry; Mason, Michael D; Wise, John Pierce</p> <p>2014-11-01</p> <p>The application of nanoparticle technology is rapidly expanding. The reduced dimensionality of nanoparticles can give rise to changes in chemical and physical properties, often resulting in altered toxicity. People are exposed dermally to titanium dioxide (TiO <span class="hlt">2</span> ) nanoparticles in industrial and residential settings. The general public is increasingly exposed to these nanoparticles as their use in cosmetics, sunscreens and lotions expands. The toxicity of TiO <span class="hlt">2</span> nanoparticles towards human skin cells is unclear and understudied. We used a human skin fibroblast cell line to investigate the cytotoxicity and clastogenicity of TiO <span class="hlt">2</span> nanoparticles after 24 h exposure. In a clonogenic survival assay, treatments of 10, 50 and 100 μ<span class="hlt">g</span>/cm <span class="hlt">2</span> induced 97.8, 88.8 and 84.7% relative survival, respectively. Clastogenicity was assessed using a chromosomal aberration assay in order to determine whether TiO <span class="hlt">2</span> nanoparticles induced serious forms of DNA damage such as <span class="hlt">chromatid</span> breaks, isochromatid lesions or <span class="hlt">chromatid</span> exchanges. Treatments of 0, 10, 50 and 100 μ<span class="hlt">g</span>/cm <span class="hlt">2</span> induced 3.3, 3.0, 3.0 and <span class="hlt">2</span>.7% metaphases with damage, respectively. No isochromatid lesions or <span class="hlt">chromatid</span> exchanges were detected. These data show that TiO <span class="hlt">2</span> nanoparticles are not cytotoxic or clastogenic to human skin cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19345191','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19345191"><span>Separase is recruited to mitotic chromosomes to dissolve sister <span class="hlt">chromatid</span> cohesion in a DNA-dependent manner.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sun, Yuxiao; Kucej, Martin; Fan, Heng-Yu; Yu, Hong; Sun, Qing-Yuan; Zou, Hui</p> <p>2009-04-03</p> <p>Sister <span class="hlt">chromatid</span> separation is triggered by the separase-catalyzed cleavage of cohesin. This process is temporally controlled by cell-cycle-dependent factors, but its biochemical mechanism and spatial regulation remain poorly understood. We report that cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner. Separase binds to DNA in vitro, but its proteolytic activity, measured by its autocleavage, is not stimulated by DNA. Instead, biochemical characterizations suggest that DNA mediates cohesin cleavage by bridging the interaction between separase and cohesin. In human cells, a fraction of separase localizes to the mitotic chromosome. The importance of the chromosomal DNA in cohesin cleavage is further demonstrated by the observation that the cleavage of the chromosome-associated cohesins is sensitive to nuclease treatment. Our observations explain why chromosome-associated cohesins are specifically cleaved by separase and the soluble cohesins are left intact in anaphase.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20554944','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20554944"><span>Essential role of TRPC6 channels in <span class="hlt">G</span><span class="hlt">2</span>/M phase transition and development of human glioma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ding, Xia; He, Zhuohao; Zhou, Kechun; Cheng, Ju; Yao, Hailan; Lu, Dongliang; Cai, Rong; Jin, Yening; Dong, Bin; Xu, Yinghui; Wang, Yizheng</p> <p>2010-07-21</p> <p>Patients with glioblastoma multiforme, the most aggressive form of glioma, have a median survival of approximately 12 months. Calcium (Ca(<span class="hlt">2</span>+)) signaling plays an important role in cell proliferation, and some members of the Ca(<span class="hlt">2</span>+)-permeable transient receptor potential canonical (TRPC) family of channel proteins have demonstrated a role in the proliferation of many types of cancer cells. In this study, we investigated the role of TRPC6 in cell cycle progression and in the development of human glioma. TRPC6 protein and mRNA expression were assessed in glioma (n = 33) and normal (n = 17) brain tissues from patients and in human glioma cell lines U251, U87, and T98<span class="hlt">G</span>. Activation of TRPC6 channels was tested by platelet-derived growth factor-induced Ca(<span class="hlt">2</span>+) imaging. The effect of inhibiting TRPC6 activity or expression using the dominant-negative mutant TRPC6 (DNC6) or RNA interference, respectively, was tested on cell growth, cell cycle progression, <span class="hlt">radiosensitization</span> of glioma cells, and development of xenografted human gliomas in a mouse model. The green fluorescent protein (GFP) and wild-type TRPC6 (WTC6) were used as controls. Survival of mice bearing xenografted tumors in the GFP, DNC6, and WTC6 groups (n = 13, 15, and 13, respectively) was compared using Kaplan-Meier analysis. All statistical tests were two-sided. Functional TRPC6 was overexpressed in human glioma cells. Inhibition of TRPC6 activity or expression attenuated the increase in intracellular Ca(<span class="hlt">2</span>+) by platelet-derived growth factor, suppressed cell growth and clonogenic ability, induced cell cycle arrest at the <span class="hlt">G</span><span class="hlt">2</span>/M phase, and enhanced the antiproliferative effect of ionizing radiation. Cyclin-dependent kinase 1 activation and cell division cycle 25 homolog C expression regulated the cell cycle arrest. Inhibition of TRPC6 activity also reduced tumor volume in a subcutaneous mouse model of xenografted human tumors (P = .014 vs GFP; P < .001 vs WTC6) and increased mean survival in mice in an intracranial</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26843134','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26843134"><span>MicroRNA-26b Enhances the <span class="hlt">Radiosensitivity</span> of Hepatocellular Carcinoma Cells by Targeting EphA<span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jin, Qiao; Li, Xiang Jun; Cao, Pei Guo</p> <p>2016-02-01</p> <p>Sensitizing hepatocellular carcinoma (HCC) cells to irradiation is important to achieve satisfactory therapeutic effect with low-dose radiotherapy. Erythropoietin-producing hepatocellular carcinoma A<span class="hlt">2</span> (EphA<span class="hlt">2</span>) is a member of the Eph receptor family that constitutes the largest family of tyrosine kinase receptors. EphA<span class="hlt">2</span> overexpression is one of the poor prognostic factors in many progressive cancers. Importantly, EphA<span class="hlt">2</span> is a potential target of microRNA-26b (miR-26b), and miR-26b expression is down-regulated in several types of cancer. In this study, we measured the expression levels of miR-26b and EphA<span class="hlt">2</span> protein in seven human HCC cell lines by quantitative PCR and western blot analysis, respectively. Overall, lower miR-26b expression levels tended to be associated with higher EphA<span class="hlt">2</span> levels in HCC cell lines. Among the cell lines examined, 97H HCC cells expressed the lowest level of miR-26b and highest level of EphA<span class="hlt">2</span> protein. Thus, using 97H HCC cells, EphA<span class="hlt">2</span> mRNA was verified as the target of miR-26b by the luciferase reporter assay. Accordingly, a synthetic miR-26b, miR-26b mimics, was used to mimic the function of endogenous miR-26b. In 97H HCC cells transfected with miR-26b mimics or short-hairpin RNA targeting EphA<span class="hlt">2</span> mRNA, expression of EphA<span class="hlt">2</span> protein was reduced, which was associated with significantly lower proliferation rate and invasion ability and with higher apoptosis rate in response to low-dose irradiation, compared to control cells. In contrast, 97H HCC cells over-expressing EphA<span class="hlt">2</span> showed higher proliferation rate and invasion ability and lower apoptosis rate upon irradiation. These data suggest that miR-26b enhances the <span class="hlt">radiosensitivity</span> of 97H HCC cells by targeting EphA<span class="hlt">2</span> protein.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29860718','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29860718"><span><span class="hlt">Radiosensitizing</span> effects of miR-18a-5p on lung cancer stem-like cells via downregulating both ATM and HIF-1α.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chen, Xu; Wu, Lei; Li, Dezhi; Xu, Yanmei; Zhang, Luping; Niu, Kai; Kong, Rui; Gu, Jiaoyang; Xu, Zihan; Chen, Zhengtang; Sun, Jianguo</p> <p>2018-06-02</p> <p>Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR-18a-5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR-18a-5p increased the <span class="hlt">radiosensitivity</span> of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR-18a-5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF-1α) as the targets of miR-18a-5p. The mRNA and protein expressions of ATM and HIF-1α were dramatically downregulated by miR-18a-5p in vitro and in vivo. Clinically, plasma miR-18a-5p expression was significantly higher in <span class="hlt">radiosensitive</span> than in radioresistant group (P < .001). The cutoff value of miR-18a-5p ><span class="hlt">2</span>.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR-18a-5p-high group than in miR-18a-5p-low group (P < .001). A tendency demonstrated that the median local progression-free survival (PFS) from radiotherapy was longer in miR-18a-5p-high than in miR-18a-5p-low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR-18a-5p-high than in miR-18a-5p-low group (P = .281). The sensitivity and specificity of plasma miR-18a-5p to predict <span class="hlt">radiosensitivity</span> was 87% and 95%, respectively. Collectively, these results indicate that miR-18a-5p increases the <span class="hlt">radiosensitivity</span> in lung cancer cells and CD133 + stem-like cells via downregulating ATM and HIF-1α expressions. Plasma miR-18a-5p would be an available indicator of <span class="hlt">radiosensitivity</span> in lung cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22332534','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22332534"><span>[Exploration of relationship between the expression level of DNA polymerase beta and 60Co gamma-ray <span class="hlt">radiosensitivity</span>].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cui, Jie; Xu, Xin; Yang, Mo; Chen, Chen; Zhao, Wei; Wu, Mei; Zhang, Zun-zhen</p> <p>2011-11-01</p> <p>To explore the relationship between the expression level of DNA polymerase beta (pol beta) and 60Co gamma-ray <span class="hlt">radiosensitivity</span> and provide a basis on improving the efficiency of radiotherapy theoretically. pol beta wild-type cells (pol beta +/+), pol beta null cells (pol beta -/-) and pol beta overexpressed cells (polp beta oe) were applied as a model system. The <span class="hlt">radiosensitivity</span> of 60Co gamma-ray on the cell was detected by MTT assay and clone formation assay. The DCFH-DA fluorescent probe was used to examine the cellular ROS after 60Co gamma-rays radiation. MTT assay showed that after radiation by 60Co gamma-rays followed with 72 h incubation, the cell viabilities in the three kinds of cells decreased significantly with a dose-response relationship (r-/+ = -0.976, r-/- = -0.977, r(oe) = -0.982, P<0.05). In addition, the viability of pol beta -/- cell was lower than those of other two kinds of cells at the same dose (P<0.05). Likewise, the colony number and colony formation rate in all tested cells also decreased after exposure to 60Co gamma-rays. The ROS level in the three kinds of cells was enhanced after treatment with 60Co gamma-ray, and the ROS level in pol beta -/- cells was much higher than that in the other two kinds of cells (P<0.05). Cell death caused by 60Co gamma-ray may associated with the DNA oxidative damage mediated by ROS; Overexpression of pol beta could protect against oxidative DNA damage, thus the cell apoptosis/death, thereby leading to reducing the <span class="hlt">radiosensitivity</span> of 60Co gamma-rays, while null of DNA pol beta could increase <span class="hlt">radiosensitivity</span> of 60Co gamma-rays by compromising the DNA repair.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11746029','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11746029"><span>Cancer-prone syndrome of mosaic variegated aneuploidy and total premature <span class="hlt">chromatid</span> separation: report of five infants.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kajii, T; Ikeuchi, T; Yang, Z Q; Nakamura, Y; Tsuji, Y; Yokomori, K; Kawamura, M; Fukuda, S; Horita, S; Asamoto, A</p> <p>2001-11-15</p> <p>Five infants (two girls and three boys) from four families all had severe pre- and postnatal growth retardation, profound developmental delay, microcephaly, hypoplasia of the brain with Dandy-Walker complex or other posterior fossa malformations, and developed uncontrollable clonic seizures. Four infants developed Wilms tumors, and one showed cystic lesions in bilateral kidneys. All five infants showed variegated mosaic aneuploidy in cultured lymphocytes. In two infants whose chromosomes were prepared by us, 48.5%-83.<span class="hlt">2</span>% lymphocytes showed total premature <span class="hlt">chromatid</span> separation (PCS). Their parents had 3.5%-41.7% of their lymphocytes in total PCS. The remaining three infants and their parents, whose chromosomes were prepared at outside laboratories, tended to show lower frequencies of total PCS. Another five infants reported with the disorder were reviewed together with the five infants we described. Together, their clinical and cytogenetic manifestations were similar enough to suggest a syndrome. Seven of the 10 infants developed proven or probable Wilms tumors. The age at diagnosis of the tumors was younger than usual at <span class="hlt">2</span>-16 months. The tumors were bilateral in four infants and unilateral in three infants, and cystic changes were present in six infants. Two infants developed botryoid rhabdomyosarcoma. The carriers of the syndrome are thus liable to tumorigenesis. The possible role of mitotic checkpoint defects, proven in two infants with the syndrome (Matsuura et al. [2000: Am J Hum Genet 69:483-486]), was discussed in connection with tumor development and progression. Copyright 2001 Wiley-Liss, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4242527','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4242527"><span>Synthesis of <span class="hlt">G</span>-N<span class="hlt">2</span>-(CH<span class="hlt">2</span>)3-N<span class="hlt">2</span>-<span class="hlt">G</span> Trimethylene DNA interstrand cross-links</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Gruppi, Francesca; Salyard, Tracy L. Johnson; Rizzo, Carmelo J.</p> <p>2014-01-01</p> <p>The synthesis of <span class="hlt">G</span>-N<span class="hlt">2</span>-(CH<span class="hlt">2</span>)3-N<span class="hlt">2</span>-<span class="hlt">G</span> trimethylene DNA interstrand cross-links (ICLs) in a 5′-CG-3′ and 5′-GC-3′ sequence from oligodeoxynucleotides containing N<span class="hlt">2</span>-(3-aminopropyl)-<span class="hlt">2</span>′-deoxyguanosine and <span class="hlt">2</span>-fluoro-O6-(trimethylsilylethyl)inosine is presented. Automated solid-phase DNA synthesis was used for unmodified bases and modified nucleotides were incorporated via their corresponding phosphoramidite reagent by a manual coupling protocol. The preparation of the phosphoramidite reagents for incorporation of N<span class="hlt">2</span>-(3-aminopropyl)-<span class="hlt">2</span>′-deoxyguanosine is reported. The high-purity trimethylene DNA interstrand cross-link product is obtained through a nucleophilic aromatic substitution reaction between the N<span class="hlt">2</span>-(3-aminopropyl)-<span class="hlt">2</span>′-deoxyguanosine and <span class="hlt">2</span>-fluoro-O6-(trimethylsilylethyl)inosine containing oligodeoxynucleotides. PMID:25431636</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1982Sci...217..544B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1982Sci...217..544B"><span><span class="hlt">Radiosensitization</span> of Hypoxic Tumor Cells by Depletion of Intracellular Glutathione</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Bump, Edward A.; Yu, Ning Y.; Brown, J. Martin</p> <p>1982-08-01</p> <p>Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic <span class="hlt">radiosensitizer</span> misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_17 --> <div id="page_18" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="341"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6706007-radiosensitization-hypoxic-tumor-cells-depletion-intracellular-glutathione','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6706007-radiosensitization-hypoxic-tumor-cells-depletion-intracellular-glutathione"><span><span class="hlt">Radiosensitization</span> of hypoxic tumor cells by depletion of intracellular glutathione</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Bump, E.A.; Yu, N.Y.; Brown, J.M.</p> <p>1982-08-06</p> <p>Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic <span class="hlt">radiosensitizer</span> misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25211769','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25211769"><span>OVA-bound nanoparticles induce OVA-specific Ig<span class="hlt">G</span>1, Ig<span class="hlt">G</span><span class="hlt">2</span>a, and Ig<span class="hlt">G</span><span class="hlt">2</span>b responses with low IgE synthesis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yanase, Noriko; Toyota, Hiroko; Hata, Kikumi; Yagyu, Seina; Seki, Takahiro; Harada, Mitsunori; Kato, Yasuki; Mizuguchi, Junichiro</p> <p>2014-10-14</p> <p>There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific Ig<span class="hlt">G</span>1 antibody responses with low levels of IgE synthesis, representing helper T (Th)<span class="hlt">2</span>-mediated humoral immunity. OVA-specific Ig<span class="hlt">G</span><span class="hlt">2</span>a and Ig<span class="hlt">G</span><span class="hlt">2</span>b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including Ig<span class="hlt">G</span>1 and IgE antibodies, with only low levels of Ig<span class="hlt">G</span><span class="hlt">2</span>a/Ig<span class="hlt">G</span><span class="hlt">2</span>b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA Ig<span class="hlt">G</span><span class="hlt">2</span>b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-β in vitro, OVA-specific Ig<span class="hlt">G</span>1 or Ig<span class="hlt">G</span><span class="hlt">2</span>b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate Ig<span class="hlt">G</span>1 and Ig<span class="hlt">G</span><span class="hlt">2</span>b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both Ig<span class="hlt">G</span>1 and Ig<span class="hlt">G</span><span class="hlt">2</span>a/Ig<span class="hlt">G</span><span class="hlt">2</span>b antibody responses with low IgE synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20060028492','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20060028492"><span><span class="hlt">G</span><span class="hlt">2</span> Flywheel Module Design</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Jensen, Ralph H.; Dever, Timothy P.</p> <p>2006-01-01</p> <p>Design of a flywheel module, designated the <span class="hlt">G</span><span class="hlt">2</span> module, is described. The <span class="hlt">G</span><span class="hlt">2</span> flywheel is a 60,000 RPM, 525 W-hr, 1 kW system designed for a laboratory environment; it will be used for component testing and system demonstrations, with the goal of applying flywheels to aerospace energy storage and integrated power and attitude control (IPACS) applications. <span class="hlt">G</span><span class="hlt">2</span> has a modular design, which allows for new motors, magnetic bearings, touchdown bearings, and rotors to be installed without a complete redesign of the system. This design process involves several engineering disciplines, and requirements are developed for the speed, energy storage, power level, and operating environment. The <span class="hlt">G</span><span class="hlt">2</span> rotor system consists of a multilayer carbon fiber rim with a titanium hub on which the other components mount, and rotordynamics analysis is conducted to ensure rigid and flexible rotor modes are controllable or outside of the operating speed range. Magnetic bearings are sized using 1-D magnetic circuit analysis and refined using 3-D finite element analysis. The <span class="hlt">G</span><span class="hlt">2</span> magnetic bearing system was designed by Texas A&M and has redundancy which allows derated operation after the loss of some components, and an existing liquid cooled two pole permanent magnet motor/generator is used. The touchdown bearing system is designed with a squeeze film damper system allowing spin down from full operating speed in case of a magnetic bearing failure. The <span class="hlt">G</span><span class="hlt">2</span> flywheel will enable module level demonstrations of component technology, and will be a key building block in system level attitude control and IPACS demonstrations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/3365681','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/3365681"><span>Effect of betel chewing on the frequency of sister <span class="hlt">chromatid</span> exchanges in pregnant women and women using oral contraceptives.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ghosh, P K; Ghosh, R</p> <p>1988-06-01</p> <p>The incidence of sister <span class="hlt">chromatid</span> exchange (SCE) was investigated in the lymphocyte chromosomes of betel chewing and non-chewing normal women, pregnant women, and women using oral contraceptives. The frequency of SCE was found to be 7.82 +/- 0.24 and 8.27 +/- 0.27 in non-chewing pregnant women and women using oral contraceptives respectively, which were significantly higher than the mean value of 5.21 +/- 0.18 observed in non-chewing normal women. Betel chewing induced higher SCE in pregnant women and women using oral contraceptives, the frequencies being 11.79 +/- 0.38 and 12.51 +/- 0.44, respectively, which were significantly higher than the SCE frequency of 6.28 +/- 0.21 found in normal betel chewing females.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5858503','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5858503"><span>Metal-based NanoEnhancers for Future Radiotherapy: <span class="hlt">Radiosensitizing</span> and Synergistic Effects on Tumor Cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Liu, Yan; Zhang, Pengcheng; Li, Feifei; Jin, Xiaodong; Li, Jin; Chen, Weiqiang; Li, Qiang</p> <p>2018-01-01</p> <p>Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as <span class="hlt">radiosensitizers</span>. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in <span class="hlt">radiosensitization</span> and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed. PMID:29556359</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19002846','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19002846"><span>The effects of boric acid on sister <span class="hlt">chromatid</span> exchanges and chromosome aberrations in cultured human lymphocytes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Arslan, Mehmet; Topaktas, Mehmet; Rencuzogullari, Eyyüp</p> <p>2008-02-01</p> <p>The aim of this study was to determine the possible genotoxic effects of boric acid (BA) (E284), which is used as an antimicrobial agent in food, by using sister <span class="hlt">chromatid</span> exchange (SCEs) and chromosome aberration (CAs) tests in human peripheral lymphocytes. The human lymphocytes were treated with 400, 600, 800, and 1000 mug/mL concentrations of BA dissolved in dimethyl sulfoxide (DMSO), for 24 h and 48 h treatment periods. BA did not increase the SCEs for all the concentrations and treatment periods when compared to control and solvent control (DMSO). BA induced structural and total CAs at all the tested concentrations for 24 and 48 h treatment periods. The induction of the total CAs was dose dependent for the 24 h treatment period. However, BA did not cause numerical CAs. BA showed a cytotoxic effect by decreasing the replication index (RI) and mitotic index (MI). BA decreased the MI in a dose-dependent manner for the 24 h treatment period.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014RaPC...97..134K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014RaPC...97..134K"><span><span class="hlt">Radiosensitization</span> by fullerene-C60 dissolved in squalene on human malignant melanoma through lipid peroxidation and enhanced mitochondrial membrane potential</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Kato, Shinya; Kimura, Masatsugu; Miwa, Nobuhiko</p> <p>2014-04-01</p> <p>We examined fullerene-C60 dissolved in squalene (C60/Sqe) for the ability to potentiate the <span class="hlt">radiosensitization</span> under X-ray irradiation on human malignant melanoma HMV-II cells, which were treated with C60/Sqe and thereafter irradiated with X-ray. The cell proliferation for C60/Sqe was inhibited more markedly than for Sqe alone. Meanwhile, cell proliferation was almost unaltered for C60/squalane (Sqa) or Sqa, a hydrogenated form of Sqe, as compared to no-additive control. Thus <span class="hlt">radiosensitization</span> of C60/Sqe is attributed to peroxidation of unsaturated bonds of squalene by X-ray-excited C60 in contrast to squalane. The fluorescence images of HMV-II cells stained with Rhodamine123, an indicator for mitochondrial membrane potential, were monitored for 6 h after X-ray irradiation. C60/Sqe obviously exhibited more augmented fluorescence intensity on perinuclear region of HMV-II cells than Sqe alone. TBARS assay showed that the lipid peroxidation level as malondialdehyde-equivalent increased by combination of C60/Sqe and X-ray dose-dependently on X-ray doses. C60/Sqe exhibited lipid peroxidation more markedly by 1.<span class="hlt">2</span>-fold than Sqe alone. Thus the level of lipid peroxidation of squalene was sufficiently higher in C60/Sqe than in Sqe in the absence of C60 under X-ray irradiation, suggesting the combination of C60/Sqe and X-ray irradiation induced <span class="hlt">radiosensitization</span> on HMV-II cells by peroxidation of absorbed Sqe in mitochondrial membrane via oxidative stress mediated by fullerene-C60.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15815936','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15815936"><span>Cardiovascular effects of anti-<span class="hlt">G</span> suit inflation at 1 and <span class="hlt">2</span> <span class="hlt">G</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Montmerle, Stéphanie; Linnarsson, Dag</p> <p>2005-06-01</p> <p>We sought to determine to which pressure a full-coverage anti-<span class="hlt">G</span> suit needs to be inflated in order to obtain the same stroke volume during a brief exposure to twice the normal gravity (<span class="hlt">2</span> <span class="hlt">G</span>) as that at 1 <span class="hlt">G</span> without anti-<span class="hlt">G</span> suit inflation. Nine sitting subjects were studied at normal (1 <span class="hlt">G</span>) and during 20 s of exposure to <span class="hlt">2</span> <span class="hlt">G</span>. They wore anti-<span class="hlt">G</span> suits, which were inflated at both <span class="hlt">G</span>-levels to the following target pressures: 0, 70, 140 and 210 mmHg. Stroke volume was computed from cardiac output, which was measured by rebreathing. Heart rate and mean arterial pressure at heart level were recorded. Inflation to 70 mmHg compensated for the decrease in stroke volume and cardiac output caused by hypergravity. Mean arterial pressure at heart level was comparable at 1 <span class="hlt">G</span> and at <span class="hlt">2</span> <span class="hlt">G</span> and increased gradually and similarly with inflation (P<0.001) at both gravity levels. Thus, anti-<span class="hlt">G</span> suits act by increasing both preload and afterload but the two effects counteract each other in terms of cardiac output, so that cardiac output at <span class="hlt">2</span> <span class="hlt">G</span> is maintained at its 1 <span class="hlt">G</span> level. This effect is reached already at 70 mmHg of inflation. Greater inflation pressure further increases mean arterial pressure at heart level and compensates for the increased difference in hydrostatic pressure between heart and head in moderate hypergravity.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014acm..conf..415P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014acm..conf..415P"><span>The H,<span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> photometric system with scarce observational data</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Penttilä, A.; Granvik, M.; Muinonen, K.; Wilkman, O.</p> <p>2014-07-01</p> <p>The H,<span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> photometric system was officially adopted at the IAU General Assembly in Beijing, 2012. The system replaced the H,<span class="hlt">G</span> system from 1985. The 'photometric system' is a parametrized model V(α; params) for the magnitude-phase relation of small Solar System bodies, and the main purpose is to predict the magnitude at backscattering, H := V(0°), i.e., the (absolute) magnitude of the object. The original H,<span class="hlt">G</span> system was designed using the best available data in 1985, but since then new observations have been made showing certain features, especially near backscattering, to which the H,<span class="hlt">G</span> function has troubles adjusting to. The H,<span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> system was developed especially to address these issues [1]. With a sufficient number of high-accuracy observations and with a wide phase-angle coverage, the H,<span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> system performs well. However, with scarce low-accuracy data the system has troubles producing a reliable fit, as would any other three-parameter nonlinear function. Therefore, simultaneously with the H,<span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> system, a two-parameter version of the model, the H,<span class="hlt">G</span>_{12} system, was introduced [1]. The two-parameter version ties the parameters <span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> into a single parameter <span class="hlt">G</span>_{12} by a linear relation, and still uses the H,<span class="hlt">G</span>_1,<span class="hlt">G</span>_<span class="hlt">2</span> system in the background. This version dramatically improves the possibility to receive a reliable phase-curve fit to scarce data. The amount of observed small bodies is increasing all the time, and so is the need to produce estimates for the absolute magnitude/diameter/albedo and other size/composition related parameters. The lack of small-phase-angle observations is especially topical for near-Earth objects (NEOs). With these, even the two- parameter version faces problems. The previous procedure with the H,<span class="hlt">G</span> system in such circumstances has been that the <span class="hlt">G</span>-parameter has been fixed to some constant value, thus only fitting a single-parameter function. In conclusion, there is a definitive need for a reliable procedure to produce</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3829822','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3829822"><span>On the Role of low-energy electrons in the <span class="hlt">radiosensitization</span> of DNA by gold nanoparticles</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xiao, Fangxing; Zheng, Yi; Cloutier, Pierre; He, Yunhui; Hunting, Darel; Sanche, Léon</p> <p>2013-01-01</p> <p>Four different gold nanoparticle (GNP) preparations, including nude GNP and GNP coated either with thiolated undecane (S-C11H23), or with dithiolated diethylenetriaminepentaacetic (DTDTPA) or gadolinium (Gd) DTDTPA chelating agents were synthesized. The average diameters, for each type of nanoparticle are 5 nm, 10 and 13 nm, respectively. Dry films of plasmid DNA pGEM-3Zf(-), DNA with bound GNP and DNA with coated GNP were bombarded with 60 keV electrons. The yields of single and double strand breaks were measured as a function of exposure by electrophoresis. The binding of only one GNP without coating to DNA containing 3197 base pairs increases single and double strand breaks by a factor of <span class="hlt">2</span>.3 while for GNP coated with S-C11H23 this factor is reduced to 1.6. GNP coated with the DTDTPA and DTDTPA:Gd in same ratio with DNA, produce essentially no increment in damage. These results could be explained by the attenuation by the coatings of the intensity of low energy photoelectrons emitted from GNP. Thus, coatings of GNP may considerably attenuate short-range low energy electrons emitted from gold, leading to a considerable decrease of <span class="hlt">radiosensitization</span>. According to our results, the highest <span class="hlt">radiosensitization</span> should be obtained with GNP having the shortest possible ligand, directed to the DNA of cancer cells. PMID:22024607</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6842348-ultraviolet-induced-sister-chromatid-exchanges-cells-normal-brdurd-substituted-dna-influence-intercalating-substances-cysteine','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6842348-ultraviolet-induced-sister-chromatid-exchanges-cells-normal-brdurd-substituted-dna-influence-intercalating-substances-cysteine"><span>Ultraviolet-induced sister <span class="hlt">chromatid</span> exchanges in V-79 cells with normal and BrdUrd-substituted DNA and the influence of intercalating substances and cysteine</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Speit, G.; Mehnert, K.; Wolf, M.</p> <p>1982-06-01</p> <p>The influence of intercalating substances (proflavine, ethidium bromide) and of an SH compound (L-cysteine) on uv-induced sister <span class="hlt">chromatid</span> exchanges (SCEs) was investigated in V-79 cells with normal and BrdUrd-substituted DNA. The results are discussed in relation to the primary damages leading to SCE induction produced by uv irradiation. The data indicate that neither the pyrimidine dimers nor DNA single-strand breaks are the primary cause of SCE induction, and that the damages leading to SCEs by uv irradiation differ from those which cause chromosome aberrations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29595459','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29595459"><span>[Pseudolaric acid B induces <span class="hlt">G</span><span class="hlt">2</span>/M arrest and inhibits invasion and migration in Hep<span class="hlt">G</span><span class="hlt">2</span> hepatoma cells].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Shuai; Guo, Lianyi</p> <p>2018-01-01</p> <p>Objective To investigate the mechanisms of pseudolaric acid B (PAB) blocks cell cycle and inhibits invasion and migration in human hepatoma Hep<span class="hlt">G</span><span class="hlt">2</span> cells. Methods The proliferation effect of PAB on Hep<span class="hlt">G</span><span class="hlt">2</span> cells was evaluated by MTT assay. The effect of PAB on the cell cycle of Hep<span class="hlt">G</span><span class="hlt">2</span> cells was analyzed by flow cytometry. Immunofluorescence cytochemical staining was applied to observe the effect of PAB on the α-tubulin polymerization and expression in Hep<span class="hlt">G</span><span class="hlt">2</span> cells. Transwell TM chamber invasion assay and wound healing assay were performed to detect the influence of PAB on the migration and invasion ability of Hep<span class="hlt">G</span><span class="hlt">2</span> cells. Western blotting was used to determine the expressions of α-tubulin, E-cadherin and MMP-9 in Hep<span class="hlt">G</span><span class="hlt">2</span> cells after treated with PAB. Results PAB inhibited the proliferation of Hep<span class="hlt">G</span><span class="hlt">2</span> cells in a dose-dependent manner and blocked the cell cycle in <span class="hlt">G</span><span class="hlt">2</span>/M phase. PAB significantly changed the polymerization and decreased the expression of α-tubulin. The capacities of invasion and migration of Hep<span class="hlt">G</span><span class="hlt">2</span> cells treated by PAB were significantly depressed. The protein levels of α-tubulin and MMP-9 decreased while the E-cadherin protein level increased. Conclusion PAB can inhibits the proliferation of Hep<span class="hlt">G</span><span class="hlt">2</span> cells by down-regulating the expression of α-tubulin and influencing its polymerization, arresting Hep<span class="hlt">G</span><span class="hlt">2</span> cells in <span class="hlt">G</span><span class="hlt">2</span>/M phase. Meanwhile, PAB also can inhibit the invasion and migration of Hep<span class="hlt">G</span><span class="hlt">2</span> cells by lowering cytoskeleton α-tubulin and MMP-9, and increasing E-cadherin.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3667875','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3667875"><span>Novel Hsp90 inhibitor NVP-AUY922 <span class="hlt">radiosensitizes</span> prostate cancer cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Gandhi, Nishant; Wild, Aaron T.; Chettiar, Sivarajan T.; Aziz, Khaled; Kato, Yoshinori; Gajula, Rajendra P.; Williams, Russell D.; Cades, Jessica A.; Annadanam, Anvesh; Song, Danny; Zhang, Yonggang; Hales, Russell K.; Herman, Joseph M.; Armour, Elwood; DeWeese, Theodore L.; Schaeffer, Edward M.; Tran, Phuoc T.</p> <p>2013-01-01</p> <p>Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the “non-oncogene” addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded “client” proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H<span class="hlt">2</span>AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive <span class="hlt">radiosensitization</span> in both cell lines at low nanomolar doses with enhancement ratios between 1.4–1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced <span class="hlt">G</span><span class="hlt">2</span>-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies. PMID:23358469</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23358469','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23358469"><span>Novel Hsp90 inhibitor NVP-AUY922 <span class="hlt">radiosensitizes</span> prostate cancer cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gandhi, Nishant; Wild, Aaron T; Chettiar, Sivarajan T; Aziz, Khaled; Kato, Yoshinori; Gajula, Rajendra P; Williams, Russell D; Cades, Jessica A; Annadanam, Anvesh; Song, Danny; Zhang, Yonggang; Hales, Russell K; Herman, Joseph M; Armour, Elwood; DeWeese, Theodore L; Schaeffer, Edward M; Tran, Phuoc T</p> <p>2013-04-01</p> <p>Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the "non-oncogene" addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded "client" proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H<span class="hlt">2</span>AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive <span class="hlt">radiosensitization</span> in both cell lines at low nanomolar doses with enhancement ratios between 1.4-1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced <span class="hlt">G</span> <span class="hlt">2</span>-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6872102','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6872102"><span>Alkaline DNA fragmentation, DNA disentanglement evaluated viscosimetrically and sister <span class="hlt">chromatid</span> exchanges, after treatment in vivo with nitrofurantoin.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Parodi, S; Pala, M; Russo, P; Balbi, C; Abelmoschi, M L; Taningher, M; Zunino, A; Ottaggio, L; de Ferrari, M; Carbone, A; Santi, L</p> <p>1983-07-01</p> <p>Nitrofurantoin was not positive as a carcinogen in long term assays. In vitro it was positive in some short term tests and negative in others. We have examined Nitrofurantoin for its capability of inducing DNA damage in vivo. With the alkaline elution technique, Nitrofurantoin appeared clearly positive in all the tissues examined (liver, kidney, lung, spleen and bone marrow). In the liver we also observed some cross-linking effect. In bone marrow cells Nitrofurantoin was also clearly positive in terms of sister <span class="hlt">chromatid</span> exchanges (SCEs) induction. DNA damage in vivo was also examined with a viscosimetric method, more sensitive than alkaline elution. With this method the results were essentially negative, suggesting that the two methods detect different types of damage. In view of its positivity in many organs and in two short term tests in vivo, the carcinogenic potential of Nitrofurantoin should be reconsidered.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6936716-developmental-stage-dependent-radiosensitivity-neural-cells-ventricular-zone-telencephalon-mouse-rat-fetuses','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6936716-developmental-stage-dependent-radiosensitivity-neural-cells-ventricular-zone-telencephalon-mouse-rat-fetuses"><span>Developmental-stage-dependent <span class="hlt">radiosensitivity</span> of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hoshino, K.; Kameyama, Y.</p> <p>1988-03-01</p> <p>Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of <span class="hlt">radiosensitivity</span> estimated from the slopesmore » of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most <span class="hlt">radiosensitive</span> among the three different age groups. In order to confirm the presence of the highly <span class="hlt">radiosensitive</span> stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest <span class="hlt">radiosensitivity</span> in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17451994','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17451994"><span>Vicia root-mirconucleus and sister <span class="hlt">chromatid</span> exchange assays on the genotoxicity of selenium compounds.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yi, Huilan; Si, Liangyan</p> <p>2007-06-15</p> <p>Selenium (Se) is an important metalloid with industrial, environmental, biological and toxicological significance. Excessive selenium in soil and water may contribute to environmental selenium pollution, and affect plant growth and human health. By using Vicia faba micronucleus (MN) and sister <span class="hlt">chromatid</span> exchange (SCE) tests, possible genotoxicity of sodium selenite and sodium biselenite was evaluated in this study. The results showed that sodium selenite, at concentrations from 0.01 to 10.0mg/L, induced a 1.9-3.9-fold increase in MN frequency and a 1.5-1.6-fold increase in SCE frequency, with a statistically significantly difference from the control (P<0.05 and 0.01, respectively). Sodium selenite also caused mitotic delay and a 15-80% decrease in mitotic indices (MI), but at the lowest concentration (0.005mg/L), it slightly stimulated mitotic activity. Similarly, the frequencies of MN and SCE also increased significantly in sodium biselenite treated samples, with MI decline only at relatively higher effective concentrations. Results of the present study suggest that selenite is genotoxic to V. faba root cells and may be a genotoxic risk to human health.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3640092','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3640092"><span>Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced <span class="hlt">Radiosensitization</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Joh, Daniel Y.; Sun, Lova; Stangl, Melissa; Al Zaki, Ajlan; Murty, Surya; Santoiemma, Phillip P.; Davis, James J.; Baumann, Brian C.; Alonso-Basanta, Michelle; Bhang, Dongha; Kao, Gary D.; Tsourkas, Andrew; Dorsey, Jay F.</p> <p>2013-01-01</p> <p>Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the <span class="hlt">radiosensitization</span> of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell <span class="hlt">radiosensitization</span> to preferential targeting of tumor-associated vasculature. PMID:23638079</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26328938','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26328938"><span>IDH1(R132H) mutation causes a less aggressive phenotype and <span class="hlt">radiosensitizes</span> human malignant glioma cells independent of the oxygenation status.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kessler, Jacqueline; Güttler, Antje; Wichmann, Henri; Rot, Swetlana; Kappler, Matthias; Bache, Matthias; Vordermark, Dirk</p> <p>2015-09-01</p> <p>In malignant glioma the presence of the IDH1 mutation (IDH1(R132H)) is associated with better clinical outcome. However, it is unclear whether IDH1 mutation is associated with a less aggressive phenotype or directly linked to increased sensitivity to radiotherapy. We determined the influence of IDH1(R132H) mutant protein on proliferation and growth in 3D culture, migration, cell survival and <span class="hlt">radiosensitivity</span> in vitro under normoxia (21% O<span class="hlt">2</span>) and hypoxia (<1% O<span class="hlt">2</span>) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1(wt)) and mutated IDH1 (IDH1(R132H)). Overexpression of IDH1(R132H) in glioma cells resulted in slightly decreased cell proliferation, considerably reduced cell migration and caused differences in growth properties in 3D spheroid cultures. Furthermore, IDH1(R132H)-positive cells consistently demonstrated an increased <span class="hlt">radiosensitivity</span> in human malignant glioma cells U-251MG (DMF10: 1.52, p<0.01 and 1.42, p<0.01), U-343MG (DMF10: 1.78, p<0.01 and 1.75, p<0.01) and LN-229 (DMF10: 1.41, p<0.05 and 1.68, p<0.01) under normoxia and hypoxia, respectively. Our data indicate that IDH1(R132H) mutation causes both a less aggressive biological behavior and direct <span class="hlt">radiosensitization</span> of human malignant glioma cells. Targeting IDH1 appears to be an attractive approach in combination with radiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5159814','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5159814"><span>Comprehensive phenotypic analysis of knockout mice deficient in cyclin <span class="hlt">G</span>1 and cyclin <span class="hlt">G</span><span class="hlt">2</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ohno, Shouichi; Ikeda, Jun-ichiro; Naito, Yoko; Okuzaki, Daisuke; Sasakura, Towa; Fukushima, Kohshiro; Nishikawa, Yukihiro; Ota, Kaori; Kato, Yorika; Wang, Mian; Torigata, Kosuke; Kasama, Takashi; Uchihashi, Toshihiro; Miura, Daisaku; Yabuta, Norikazu; Morii, Eiichi; Nojima, Hiroshi</p> <p>2016-01-01</p> <p>Cyclin <span class="hlt">G</span>1 (Cyc<span class="hlt">G</span>1) and Cyclin <span class="hlt">G</span><span class="hlt">2</span> (Cyc<span class="hlt">G</span><span class="hlt">2</span>) play similar roles during the DNA damage response (DDR), but their detailed roles remain elusive. To investigate their distinct roles, we generated knockout mice deficient in Cyc<span class="hlt">G</span>1 (<span class="hlt">G</span>1KO) or Cyc<span class="hlt">G</span><span class="hlt">2</span> (<span class="hlt">G</span><span class="hlt">2</span>KO), as well as double knockout mice (DKO) deficient in both proteins. All knockouts developed normally and were fertile. Generation of mouse embryonic fibroblasts (MEFs) from these mice revealed that <span class="hlt">G</span><span class="hlt">2</span>KO MEFs, but not <span class="hlt">G</span>1KO or DKO MEFs, were resistant to DNA damage insults caused by camptothecin and ionizing radiation (IR) and underwent cell cycle arrest. Cyc<span class="hlt">G</span><span class="hlt">2</span>, but not Cyc<span class="hlt">G</span>1, co-localized with γH<span class="hlt">2</span>AX foci in the nucleus after γ-IR, and γH<span class="hlt">2</span>AX-mediated DNA repair and dephosphorylation of CHK<span class="hlt">2</span> were delayed in <span class="hlt">G</span><span class="hlt">2</span>KO MEFs. H<span class="hlt">2</span>AX associated with Cyc<span class="hlt">G</span>1, Cyc<span class="hlt">G</span><span class="hlt">2</span>, and protein phosphatase <span class="hlt">2</span>A (PP<span class="hlt">2</span>A), suggesting that γH<span class="hlt">2</span>AX affects the function of PP<span class="hlt">2</span>A via direct interaction with its B’γ subunit. Furthermore, expression of Cyc<span class="hlt">G</span><span class="hlt">2</span>, but not Cyc<span class="hlt">G</span>1, was abnormal in various cancer cell lines. Kaplan–Meier curves based on TCGA data disclosed that head and neck cancer patients with reduced Cyc<span class="hlt">G</span><span class="hlt">2</span> expression have poorer clinical prognoses. Taken together, our data suggest that reduced Cyc<span class="hlt">G</span><span class="hlt">2</span> expression could be useful as a novel prognostic marker of cancer. PMID:27982046</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_18 --> <div id="page_19" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="361"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040087649&hterms=ito&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dito','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040087649&hterms=ito&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D50%26Ntt%3Dito"><span>Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Kawata, Tetsuya; Ito, Hisao; Motoori, Ken; Ueda, Takuya; Shigematsu, Naoyuki; Furusawa, Yoshiya; Durante, Marco; George, Kerry; Wu, Honglu; Cucinotta, Francis A.</p> <p>2002-01-01</p> <p>The frequency of <span class="hlt">chromatid</span> breaks and the distribution of isochromatid breaks were measured in <span class="hlt">G</span><span class="hlt">2</span>-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of <span class="hlt">chromatid</span>-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12793753','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12793753"><span>Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kawata, Tetsuya; Ito, Hisao; Motoori, Ken; Ueda, Takuya; Shigematsu, Naoyuki; Furusawa, Yoshiya; Durante, Marco; George, Kerry; Wu, Honglu; Cucinotta, Francis A</p> <p>2002-12-01</p> <p>The frequency of <span class="hlt">chromatid</span> breaks and the distribution of isochromatid breaks were measured in <span class="hlt">G</span><span class="hlt">2</span>-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of <span class="hlt">chromatid</span>-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1684051','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1684051"><span><span class="hlt">Chromatid</span> repulsion associated with Roberts/SC phocomelia syndrome is reduced in malignant cells and not expressed in interspecies somatic-cell hybrids.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Krassikoff, N E; Cowan, J M; Parry, D M; Francke, U</p> <p>1986-01-01</p> <p>Different cell types from a female patient with Roberts/SC phocomelia syndrome were evaluated quantitatively for the presence of repulsion of heterochromatin and satellite regions of mitotic chromosomes. Whereas EBV-transformed lymphoblasts from an established cell line revealed these phenomena at frequencies equal to those in PHA-stimulated lymphocytes and cultured skin fibroblasts, aneuploid cells from a metastatic melanoma displayed them at 50% lower frequency. Cocultivation of the patient's fibroblasts with either an immortal Chinese hamster cell line or with a human male fibroblast strain carrying a t(4;6)(p14;q21) translocation showed that the phenomenon was not corrected or induced by a diffusible factor or by cell-to-cell contact. In each experiment, only the patient's metaphase spreads revealed <span class="hlt">chromatid</span> repulsion. In fusion hybrids between the patient's fibroblasts and an established Chinese hamster cell line, the human chromosomes behaved perfectly normally, suggesting that the gene product which is missing or mutant in Roberts/SC phocomelia syndrome is supplied by the Chinese hamster genome. Images Fig. 1 Fig. <span class="hlt">2</span> Fig. 3 PMID:3788975</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/15001586-dna-targeted-nitroimidazoles-studies-influence-phenanthridine-linked-nitroimidazoles-nlp-nlp-dna-damage-induced-ionizing-radiation','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/15001586-dna-targeted-nitroimidazoles-studies-influence-phenanthridine-linked-nitroimidazoles-nlp-nlp-dna-damage-induced-ionizing-radiation"><span>DNA-Targeted <span class="hlt">2</span>-Nitroimidazoles: Studies of the Influence of the Phenanthridine-Linked Nitroimidazoles, <span class="hlt">2</span>-NLP-3 and <span class="hlt">2</span>-NLP-4, on DNA Damage Induced by Ionizing Radiation</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Buchko, Garry W.; Weinfeld, Michael</p> <p></p> <p>The nitroimidazole-linked phenanthridines <span class="hlt">2</span>-NLP-3 (5-[3-(<span class="hlt">2</span>-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide) and <span class="hlt">2</span>-NLP-4 (5-[3-(<span class="hlt">2</span>-nitro-1-imidazoyl)-butyl1]-phenanthridinium bromide) are composed of the <span class="hlt">radiosensitizer</span>, <span class="hlt">2</span>-nitroimidazole, attached to the DNA intercalator phenanthridine via a 3- and 4-carbon linker, respectively. Previous in vitro assays show both compounds to be 10 - 100 times more efficient as hypoxic cell <span class="hlt">radiosensitizer</span>, misonidazole[Cowan et al., Radiat. Res. 127, 81-89, 1991]. Here we have used a 32P postlabeling assay and 5'-end labeled oligonucleotide assay to compare the radiogenic DNA damage generated in the presence of <span class="hlt">2</span>-NLP-3, <span class="hlt">2</span>-NLP-4 compared to irradiation in the presence of misonidazole. This may account, at least in part, for the greatermore » cellular <span class="hlt">radiosensitization</span> shown by the nitroimidazole-linked phenanthridines over misonidazole.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29186203','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29186203"><span>Chl1 DNA helicase and Scc<span class="hlt">2</span> function in chromosome condensation through cohesin deposition.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shen, Donglai; Skibbens, Robert V</p> <p>2017-01-01</p> <p>Chl1 DNA helicase promotes sister <span class="hlt">chromatid</span> cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister <span class="hlt">chromatid</span> separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister <span class="hlt">chromatids</span> (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc<span class="hlt">2</span> to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc<span class="hlt">2</span> also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc<span class="hlt">2</span> to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc<span class="hlt">2</span>-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc<span class="hlt">2</span> specifically in cohesin deposition, scc<span class="hlt">2</span>-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister <span class="hlt">chromatid</span> cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5706694','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5706694"><span>Chl1 DNA helicase and Scc<span class="hlt">2</span> function in chromosome condensation through cohesin deposition</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Shen, Donglai</p> <p>2017-01-01</p> <p>Chl1 DNA helicase promotes sister <span class="hlt">chromatid</span> cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister <span class="hlt">chromatid</span> separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister <span class="hlt">chromatids</span> (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc<span class="hlt">2</span> to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc<span class="hlt">2</span> also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc<span class="hlt">2</span> to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc<span class="hlt">2</span>-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc<span class="hlt">2</span> specifically in cohesin deposition, scc<span class="hlt">2</span>-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister <span class="hlt">chromatid</span> cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex. PMID:29186203</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016NatSR...631973G','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016NatSR...631973G"><span>A ruthenium polypyridyl intercalator stalls DNA replication forks, <span class="hlt">radiosensitizes</span> human cancer cells and is enhanced by Chk1 inhibition</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Gill, Martin R.; Harun, Siti Norain; Halder, Swagata; Boghozian, Ramon A.; Ramadan, Kristijan; Ahmad, Haslina; Vallis, Katherine A.</p> <p>2016-08-01</p> <p>Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)<span class="hlt">2</span>(PIP)]<span class="hlt">2</span>+ (dppz = dipyridophenazine, PIP = <span class="hlt">2</span>-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by <span class="hlt">G</span>1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H<span class="hlt">2</span>AX (γ-H<span class="hlt">2</span>AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)<span class="hlt">2</span>(PIP)]<span class="hlt">2</span>+ before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H<span class="hlt">2</span>AX expression, indicating the compound functions as a <span class="hlt">radiosensitizer</span>. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27558808','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27558808"><span>A ruthenium polypyridyl intercalator stalls DNA replication forks, <span class="hlt">radiosensitizes</span> human cancer cells and is enhanced by Chk1 inhibition.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gill, Martin R; Harun, Siti Norain; Halder, Swagata; Boghozian, Ramon A; Ramadan, Kristijan; Ahmad, Haslina; Vallis, Katherine A</p> <p>2016-08-25</p> <p>Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)<span class="hlt">2</span>(PIP)](<span class="hlt">2</span>+) (dppz = dipyridophenazine, PIP = <span class="hlt">2</span>-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by <span class="hlt">G</span>1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H<span class="hlt">2</span>AX (γ-H<span class="hlt">2</span>AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)<span class="hlt">2</span>(PIP)](<span class="hlt">2</span>+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H<span class="hlt">2</span>AX expression, indicating the compound functions as a <span class="hlt">radiosensitizer</span>. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5919709','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5919709"><span>Autophagy inhibition enhances <span class="hlt">radiosensitivity</span> of Eca-109 cells via the mitochondrial apoptosis pathway</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Tao, Hua; Qian, Pudong; Lu, Jincheng; Guo, Yesong; Zhu, Huanfeng; Wang, Feijiang</p> <p>2018-01-01</p> <p>Autophagy inhibition is crucial for the improvement of the efficacy of radiotherapy in cancer. The aim of the present study was to determine the potential therapeutic value of autophagy and its correlation with mitochondria in human esophageal carcinoma cells following treatment with ionizing radiation (IR). Autophagy in Eca-109 cells was induced under poor nutrient conditions. The formation of autophagic vacuoles was monitored using electron microscopy. In addition, cell apoptosis after IR and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. LC3, beclin-1, cytochrome c and apoptosis-related proteins were assayed by western blotting. A nude mouse xenograft model was also employed to verify the biological effects and mechanisms underlying autophagy in vivo. The formed autophagic vesicles and increased LC3 II/LC3 I ratio indicated marked induction of autophagy by Earle's balanced salt solution (EBSS) in Eca-109 cells. 3-Methyladenine or LY294002 significantly antagonized EBSS-induced autophagy and increased apoptosis of irradiated cells, suggesting that autophagy inhibition conferred <span class="hlt">radiosensitivity</span> in vitro. Notably, IR induced prominent release of cytochrome c and Bax activation, and decreased Bcl-<span class="hlt">2</span> and MMP expression in Eca-109 cells under poor nutrient conditions. Of note, these changes were more prominent following pretreatment with autophagy inhibitors. In vivo, IR treatment mildly delayed tumor growth, but the radiotherapeutic effect was improved significantly by abolishing autophagy. Furthermore, mitochondrial signaling was investigated in the Eca-109 xenograft nude mice model, and the results were consistent with the in vitro study. Therefore, the mitochondrial pathway may be associated with improvement of <span class="hlt">radiosensitivity</span> in Eca-109 cells. PMID:29620258</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6427432-intra-arterial-bromodeoxyuridine-radiosensitization-malignant-gliomas','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6427432-intra-arterial-bromodeoxyuridine-radiosensitization-malignant-gliomas"><span>Intra-arterial bromodeoxyuridine <span class="hlt">radiosensitization</span> of malignant gliomas</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hegarty, T.J.; Thornton, A.F.; Diaz, R.F.</p> <p>1990-08-01</p> <p>In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe,more » continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m<span class="hlt">2</span>/day X 8 1/<span class="hlt">2</span> weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/<span class="hlt">2</span> weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began <span class="hlt">2</span> weeks prior to and continued throughout the 6 1/<span class="hlt">2</span> week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR <span class="hlt">radiosensitization</span> is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20140008994','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20140008994"><span>UPSS and <span class="hlt">G</span><span class="hlt">2</span></span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Dito, Scott J.</p> <p>2014-01-01</p> <p>The Universal Propellant Servicing System (UPSS) is a dedicated mobile launcher propellant delivery method that will minimize danger and complexity in order to allow vehicles to be serviced and ultimately launched from a variety of locations previously not seen fit for space launch. The UPPS/<span class="hlt">G</span><span class="hlt">2</span> project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to the rocket for testing purposes. To accomplish this, the project is using the programming language/environment Gensym <span class="hlt">G</span><span class="hlt">2</span>. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. We have learned <span class="hlt">G</span><span class="hlt">2</span> through classes and trial-and-error, and are now in the process of building the application that will soon be able to be tested on apparatuses here at Kennedy Space Center, and eventually on the actual unit. The UPSS will bring near-autonomous control of launches to those that need it, as well it will be a great addition to NASA and KSC's operational viability and the opportunity to bring space launches to parts of the world, and in time constraints, once not thought possible.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3113765','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3113765"><span>Scc<span class="hlt">2</span> regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lin, Weiqiang; Jin, Hui; Liu, Xiuwen; Hampton, Kristin; Yu, Hong-Guo</p> <p>2011-01-01</p> <p>To tether sister <span class="hlt">chromatids</span>, a protein-loading complex, including Scc<span class="hlt">2</span>, recruits cohesin to the chromosome at discrete loci. Cohesin facilitates the formation of a higher-order chromosome structure that could also influence gene expression. How cohesin directly regulates transcription remains to be further elucidated. We report that in budding yeast Scc<span class="hlt">2</span> is required for sister-<span class="hlt">chromatid</span> cohesion during meiosis for two reasons. First, Scc<span class="hlt">2</span> is required for activating the expression of REC8, which encodes a meiosis-specific cohesin subunit; second, Scc<span class="hlt">2</span> is necessary for recruiting meiotic cohesin to the chromosome to generate sister-<span class="hlt">chromatid</span> cohesion. Using a heterologous reporter assay, we have found that Scc<span class="hlt">2</span> increases the activity of its target promoters by recruiting cohesin to establish an upstream cohesin-associated region in a position-dependent manner. Rec8-associated meiotic cohesin is required for the full activation of the REC8 promoter, revealing that cohesin has a positive feedback on transcriptional regulation. Finally, we provide evidence that chromosomal binding of cohesin is sufficient for target-gene activation during meiosis. Our data support a noncanonical role for cohesin as a transcriptional activator during cell differentiation. PMID:21508318</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29899866','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29899866"><span>Differential miRNA expression profiling reveals miR-205-3p to be a potential <span class="hlt">radiosensitizer</span> for low- dose ionizing radiation in DLD-1 cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Andaur, Rodrigo; Tapia, Julio C; Moreno, José; Soto, Leopoldo; Armisen, Ricardo; Marcelain, Katherine</p> <p>2018-05-29</p> <p>Enhanced <span class="hlt">radiosensitivity</span> at low doses of ionizing radiation (IR) (0.<span class="hlt">2</span> to 0.6 Gy) has been reported in several cell lines. This phenomenon, known as low doses hyper-<span class="hlt">radiosensitivity</span> (LDHRS), appears as an opportunity to decrease toxicity of radiotherapy and to enhance the effects of chemotherapy. However, the effect of low single doses IR on cell death is subtle and the mechanism underlying LDHRS has not been clearly explained, limiting the utility of LDHRS for clinical applications. To understand the mechanisms responsible for cell death induced by low-dose IR, LDHRS was evaluated in DLD-1 human colorectal cancer cells and the expression of 80 microRNAs (miRNAs) was assessed by qPCR array. Our results show that DLD-1 cells display an early DNA damage response and apoptotic cell death when exposed to 0.6 Gy. miRNA expression profiling identified 3 over-expressed (miR-205-3p, miR-1 and miR-133b) and <span class="hlt">2</span> down-regulated miRNAs (miR-122-5p, and miR-134-5p) upon exposure to 0.6 Gy. This miRNA profile differed from the one in cells exposed to high-dose IR (12 Gy), supporting a distinct low-dose radiation-induced cell death mechanism. Expression of a mimetic miR-205-3p, the most overexpressed miRNA in cells exposed to 0.6 Gy, induced apoptotic cell death and, more importantly, increased LDHRS in DLD-1 cells. Thus, we propose miR-205-3p as a potential <span class="hlt">radiosensitizer</span> to low-dose IR.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://muon-g-2.fnal.gov','SCIGOVWS'); return false;" href="http://muon-g-2.fnal.gov"><span>Muon <span class="hlt">g</span>-<span class="hlt">2</span></span></a></p> <p><a target="_blank" href="http://www.science.gov/aboutsearch.html">Science.gov Websites</a></p> <p></p> <p></p> <p>Related Links A Key Contribution from Brookhaven <em>Laboratory</em> The Big Move Muon Department Facebook <span class="hlt">g</span>-<span class="hlt">2</span> on is filled with an invisible sea of <em>virtual</em> particles that -in accordance with the laws of quantum presence and nature of these <em>virtual</em> particles with particle beams traveling in a magnetic field. The Muon</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1355514','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1355514"><span>Transformation and <span class="hlt">radiosensitivity</span> of human diploid skin fibroblasts transfected with activated ras oncogene and SV40 T-antigen.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Su, L N; Little, J B</p> <p>1992-08-01</p> <p>Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. Cells transfected with EJ ras alone showed no morphological alterations nor significant changes in <span class="hlt">radiosensitivity</span>. Cell clones expressing ras and/or SV40 T-antigen showed a reduced requirement for serum supplements, an increase in aneuploidy and chromosomal aberrations, and enhanced growth in soft agar as an early cellular response to SV40 T-antigen expression. The sequential order of transfection with SV40 T-antigen and ras influenced <span class="hlt">radio-sensitivity</span> but not the induction of morphological changes. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the <span class="hlt">radiosensitivity</span> of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5738888-enhanced-response-induction-sister-chromatid-exchange-gamma-radiation-neurofibromatosis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5738888-enhanced-response-induction-sister-chromatid-exchange-gamma-radiation-neurofibromatosis"><span>Enhanced response to the induction of sister <span class="hlt">chromatid</span> exchange by gamma radiation in neurofibromatosis</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hafez, M.; Abd el-Nabi, S.M.; el-Wehedi, G.</p> <p></p> <p>The study included 8 unrelated patients with neurofibromatosis, and 10 unrelated normal and healthy persons as controls. Whole blood samples were divided into plastic T flasks and exposed at room temperature to gamma rays. The radiation dose was 36 rad/minute, and the doses delivered were 0, 75, 150 and 300 rad. The lymphocytes were cultured in (RPMI) 1640 tissue culture medium and autologous serum (20%). Phytohemagglutinin and bromodeoxyuridine (Brdu) (10 microM) were added at initiation of culture and harvesting was done 64 to 68 hours after culture initiation. Slides were coded, differential staining was done, and sister <span class="hlt">chromatid</span> exchanges (SCEs)more » and aberrations (gaps, breaks, dicentrics, fragments and minutes) were counted. In the controls no significant increase in frequency of SCE has been found (P greater than 0.5). In the patients, the frequencies significantly increased with the increase of dose of irradiation (P less than 0.001). Furthermore, after irradiation, the incidence of gaps, breaks, and dicentrics were significantly increased in patients compared with controls. Moreover, the incidence increased with the increase in the dose of radiation. The results are discussed with a conclusion that the results add to the indication of a genetic predisposition to develop cancer in neurofibromatosis patients.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24236568','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24236568"><span>Osthole induces <span class="hlt">G</span><span class="hlt">2</span>/M cell cycle arrest and apoptosis in human hepatocellular carcinoma Hep<span class="hlt">G</span><span class="hlt">2</span> cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chao, Xu; Zhou, Xiaojun; Zheng, Gang; Dong, Changhu; Zhang, Wei; Song, Xiaomei; Jin, Tianbo</p> <p>2014-05-01</p> <p>Osthole [7-methoxy-8-(3-methyl-<span class="hlt">2</span>-butenyl) coumarin] isolated from the fruit of Cnidium monnieri (L.) Cuss, one of the commonly used Chinese medicines listed in the Shennong's Classic of Materia Medica in the Han Dynasty, had remarkable antiproliferative activity against human hepatocellular carcinoma Hep<span class="hlt">G</span><span class="hlt">2</span> cells in culture. This study evaluated the effects of osthole on cell growth, nuclear morphology, cell cycle distribution, and expression of apoptosis-related proteins in Hep<span class="hlt">G</span><span class="hlt">2</span> cells. Cytotoxic activity of osthole was determined by the MTT assay at various concentrations ranging from 0.004 to 1.0 µmol/ml in Hep<span class="hlt">G</span><span class="hlt">2</span> cells. Cell morphology was assessed by Hoechst staining and fluorescence microscopy. Apoptosis and cell-cycle distribution was determined by annexin V staining and flow cytometry. Apoptotic protein levels were assessed by Western blot. Osthole exhibited significant inhibition of the survival of Hep<span class="hlt">G</span><span class="hlt">2</span> cells and the half inhibitory concentration (IC₅₀) values were 0.186, 0.158 and 0.123 µmol/ml at 24, 48 and 72 h, respectively. Cells treated with osthole at concentrations of 0, 0.004, 0.02, 0.1 and 0.5 μmol/ml showed a statistically significant increase in the <span class="hlt">G</span><span class="hlt">2</span>/M fraction accompanied by a decrease in the <span class="hlt">G</span>0/<span class="hlt">G</span>1 fraction. The increase of apoptosis induced by osthole was correlated with down-regulation expression of anti-apoptotic Bcl-<span class="hlt">2</span> protein and up-regulation expression of pro-apoptotic Bax and p53 proteins. Osthole had significant growth inhibitory activity and the pro-apoptotic effect of osthole is mediated through the activation of caspases and mitochondria in Hep<span class="hlt">G</span><span class="hlt">2</span> cells. Results suggest that osthole has promising therapeutic potential against hepatocellular carcinoma.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/7223070-radiosensitization-mammalian-cells-diamide','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/7223070-radiosensitization-mammalian-cells-diamide"><span><span class="hlt">Radiosensitization</span> of mammalian cells by diamide</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Vos, O.; Grant, G.A.; Budke, L.</p> <p>1976-01-01</p> <p>The effect of diamide on the <span class="hlt">radiosensitivity</span> of T-cells was investigated under oxic and anoxic conditions. The compound was found to sensitize the cells under both conditions. Under oxic conditions, exposure for 10 min before and during irradiation to 0.1, 0.5, and 1.0 mm diamide produced dose-modifying factors of 0.81, 0.60, and 0.55, respectively. Under anoxic conditions exposure for 10 min before and during irradiation to 0.5 mm produced a dose-modifying factor of 0.34. When the cells in oxic conditions were exposed for just 20 min before irradiation, the sensitizing effect was smaller, but some sensitization effect was still apparentmore » after a 120 min interval between diamide treatment and irradiation. Diamide also sensitized the cells after irradiation but this effect was less than when it was present during irradiation. It is proposed that sensitization is due to lack of capacity for repair of radicals by hydrogen transfer and biochemical repair processes. (Author) (GRA)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4107263','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4107263"><span><span class="hlt">Radiosensitivity</span> of human ovarian carcinoma and melanoma cells to γ-rays and protons</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Keta, Otilija; Todorović, Danijela; Popović, Nataša; Korićanac, Lela; Cuttone, Giacomo; Petrović, Ivan</p> <p>2014-01-01</p> <p>Introduction Proton radiation offers physical advantages over conventional radiation. <span class="hlt">Radiosensitivity</span> of human 59M ovarian cancer and HTB140 melanoma cells was investigated after exposure to γ-rays and protons. Material and methods Irradiations were performed in the middle of a 62 MeV therapeutic proton spread out Bragg peak with doses ranging from <span class="hlt">2</span> to 16 Gy. The mean energy of protons was 34.88 ±<span class="hlt">2</span>.15 MeV, corresponding to the linear energy transfer of 4.7 ±0.<span class="hlt">2</span> keV/µm. Irradiations with γ-rays were performed using the same doses. Viability, proliferation and survival were assessed 7 days after both types of irradiation while analyses of cell cycle and apoptosis were performed 48 h after irradiation. Results Results showed that γ-rays and protons reduced the number of viable cells for both cell lines, with stronger inactivation achieved after irradiation with protons. Surviving fractions for 59M were 0.91 ±0.01 for γ-rays and 0.81 ±0.01 for protons, while those for HTB140 cells were 0.93 ±0.01 for γ-rays and 0.86 ±0.01 for protons. Relative biological effectiveness of protons, being <span class="hlt">2</span>.47 ±0.22 for 59M and <span class="hlt">2</span>.08 ±0.36 for HTB140, indicated that protons provoked better cell elimination than γ-rays. After proton irradiation proliferation capacity of the two cell lines was slightly higher as compared to γ-rays. Proliferation was higher for 59M than for HTB140 cells after both types of irradiation. Induction of apoptosis and <span class="hlt">G</span><span class="hlt">2</span> arrest detected after proton irradiation were more prominent in 59M cells. Conclusions The obtained results suggest that protons exert better antitumour effects on ovarian carcinoma and melanoma cells than γ-rays. The dissimilar response of these cells to radiation is related to their different features. PMID:25097591</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26894978','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26894978"><span>Mitochondrial stress controls the <span class="hlt">radiosensitivity</span> of the oxygen effect: Implications for radiotherapy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Richardson, Richard B; Harper, Mary-Ellen</p> <p>2016-04-19</p> <p>It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell <span class="hlt">radiosensitivity</span> and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of <span class="hlt">radiosensitivity</span> with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_19 --> <div id="page_20" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="381"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28579282','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28579282"><span>A <span class="hlt">radiosensitivity</span> gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jang, Bum-Sup; Kim, In Ah</p> <p>2017-09-01</p> <p>We investigated the link between the <span class="hlt">radiosensitivity</span> gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. We validated the identified gene signature related to <span class="hlt">radiosensitivity</span> and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset. To validate the gene signature, 1045 patients were selected and divided into two clusters using a consensus clustering algorithm based on their <span class="hlt">radiosensitive</span> (RS) or radioresistant (RR) designation according to their prognosis. Patients were also stratified as PD-L1-high or PD-L1-low based on the median value of CD274 mRNA expression level as surrogates of PD-L1. Patents assigned to the RS group had decreased risk of recurrence-free survival (RFS) rate than patients in the RR group by univariate analysis (HR 0.45, 95% CI 0.25-0.81, p=0.008) only when treated with RT. The RS group was independently associated with the PD-L1-high group, and CD274 mRNA expression was significantly higher in the RS group (p<0.001) than the RR group. In the PD-L1-high group, the RS group was associated with better RFS compared to the RR group (HR 0.37, 95% CI 0.16-0.87, p=0.022) in multivariate analysis. The level of PD-L1 expression may represent the immunogenicity of tumors, and thus, we speculated that the PD-L1-high group had more immunogenic tumors, which could be more sensitive to radiation-induced immunologic cell death. We first evaluated the predictive value of the <span class="hlt">radiosensitivity</span> gene signature and described a relationship with this <span class="hlt">radiosensitivity</span> gene signature and PD-L1. The <span class="hlt">radiosensitivity</span> gene signature and PD-L1 status were important factors for prediction of the clinical outcome of RT in patients with invasive breast cancer and may be used for selecting patients who will benefit from RT combined with anti-PD1/PDL1</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ars.usda.gov/research/publications/publication/?seqNo115=303655','TEKTRAN'); return false;" href="http://www.ars.usda.gov/research/publications/publication/?seqNo115=303655"><span><span class="hlt">Radiosensitization</span> of Aspergillus niger and Penicillium chrysogenum using basil essential oil and ionizing radiation for food decontamination.</span></a></p> <p><a target="_blank" href="https://www.ars.usda.gov/research/publications/find-a-publication/">USDA-ARS?s Scientific Manuscript database</a></p> <p></p> <p></p> <p>The Minimum Inhibitory Concentration (MIC) of basil oil, was determined for two pathogenic fungi of rice, Aspergillus niger and Penicillium chrysogenum. The antifungal activity of the basil oil in combination with ionising radiation was then investigated to determine if basil oil caused <span class="hlt">radiosensit</span>...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=249256','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=249256"><span>In vitro synthesis and processing of herpes simplex virus type <span class="hlt">2</span> <span class="hlt">gG</span>-<span class="hlt">2</span>, using cell-free transcription and translation systems.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Weldon, S K; Su, H K; Fetherston, J D; Courtney, R J</p> <p>1990-01-01</p> <p>Translation of in vitro-synthesized herpes simplex virus type <span class="hlt">2</span> (HSV-<span class="hlt">2</span>) <span class="hlt">gG</span>-<span class="hlt">2</span> mRNA in a reticulocyte lysate system was used to study the processing of HSV-<span class="hlt">2</span> <span class="hlt">gG</span>-<span class="hlt">2</span>. In the presence of canine pancreatic microsomal membranes, a single species that is protected from trypsin digestion was detected. This product comigrates with the 104,000-Mr (104K) high mannose intermediate seen in HSV-<span class="hlt">2</span>-infected-cell lysates. Endo-beta-N-acetylglucosaminidase H treatment of the in vitro-synthesized 104K protein yielded a single product migrating at 100 K. The 72K and 31K cleavage products of <span class="hlt">gG</span>-<span class="hlt">2</span> were not observed in the in vitro system. These data show that the molecular weight of the nonglycosylated form of the <span class="hlt">gG</span>-<span class="hlt">2</span> protein is 100,000 and that the cotranslational processing of this protein in the endoplasmic reticulum yields the 104K high-mannose intermediate. Images PMID:2154614</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20849637','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20849637"><span>Effects of osteopontin inhibition on <span class="hlt">radiosensitivity</span> of MDA-MB-231 breast cancer cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hahnel, Antje; Wichmann, Henri; Kappler, Matthias; Kotzsch, Matthias; Vordermark, Dirk; Taubert, Helge; Bache, Matthias</p> <p>2010-09-17</p> <p>Osteopontin (OPN) is a secreted glycophosphoprotein that is overexpressed in various tumors, and high levels of OPN have been associated with poor prognosis of cancer patients. In patients with head and neck cancer, high OPN plasma levels have been associated with poor prognosis following radiotherapy. Since little is known about the relationship between OPN expression and <span class="hlt">radiosensitivity</span>, we investigated the cellular and radiation induced effects of OPN siRNA in human MDA-MB-231 breast cancer cells. MDA-MB-231 cells were transfected with OPN-specific siRNAs and irradiated after 24 h. To verify the OPN knockdown, we measured the OPN mRNA and protein levels using qRT-PCR and Western blot analysis. Furthermore, the functional effects of OPN siRNAs were studied by assays to assess clonogenic survival, migration and induction of apoptosis. Treatment of MDA-MB-231 cells with OPN siRNAs resulted in an 80% decrease in the OPN mRNA level and in a decrease in extracellular OPN protein level. Transfection reduced clonogenic survival to 42% (p = 0.008), decreased the migration rate to 60% (p = 0.15) and increased apoptosis from 0.3% to 1.7% (p = 0.04). Combination of OPN siRNA and irradiation at <span class="hlt">2</span> Gy resulted in a further reduction of clonogenic survival to 27% (p < 0.001), decreased the migration rate to 40% (p = 0.03) and increased apoptosis to 4% (p < 0.005). Furthermore, OPN knockdown caused a weak <span class="hlt">radiosensitization</span> with an enhancement factor of 1.5 at 6 Gy (p = 0.09) and a dose modifying factor (DMF10) of 1.1. Our results suggest that an OPN knockdown improves radiobiological effects in MDA-MB-231 cells. Therefore, OPN seems to be an attractive target to improve the effectiveness of radiotherapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1990CPL...173..456T','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1990CPL...173..456T"><span>Observation of the spin-orbit components of the 3B <span class="hlt">2</span><span class="hlt">g</span>( 3A <span class="hlt">2</span><span class="hlt">g</span>) ground state in the system Ni <span class="hlt">2</span>+:MgF <span class="hlt">2</span> by fluorescence line narrowing</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Tonucci, R. J.; Jacobsen, S. M.; Yen, W. M.</p> <p>1990-10-01</p> <p>Using a tunable narrow-band infrared laser, we demonstrate for the first time infrared-fluorescnece line narrowing in the system Ni <span class="hlt">2</span>+:MgF <span class="hlt">2</span>. High-resolution emission spectra were obtained by pumping the lowest spin-orbit component B 3 ( 3T <span class="hlt">2</span><span class="hlt">g</span>) (orthorhombic notation with octahedral notation in parentheses) of the 3T <span class="hlt">2</span><span class="hlt">g</span> multiplet and observing the B 3( 3T <span class="hlt">2</span><span class="hlt">g</span>)→B 1, A, B <span class="hlt">2</span>( 3A <span class="hlt">2</span><span class="hlt">g</span>) luminescent transitions at low temperature. By tuning the narrow-band laser over the B 3( 3T <span class="hlt">2</span><span class="hlt">g</span>) band, resonant and non-resonant fluorescence were obtained which narrowed with respect to the inhomogeneously broadened profile, and additional lines were observed. The spectra can be understood in terms of a simultaneous excitation of two different subsets of Ni <span class="hlt">2</span>+ ions which have their B <span class="hlt">2</span>( 3A <span class="hlt">2</span><span class="hlt">g</span>)→B 3( 3T <span class="hlt">2</span><span class="hlt">g</span>) and A( 3A <span class="hlt">2</span><span class="hlt">g</span>)→B 3( 3T <span class="hlt">2</span><span class="hlt">g</span>) transitions in resonance with the laser. The A( 3A <span class="hlt">2</span><span class="hlt">g</span>) and B 1( 3A <span class="hlt">2</span><span class="hlt">g</span>) spin-orbit components of the ground-state multiplet lie 1.9 cm -1 and 6.5 cm -1 above the B <span class="hlt">2</span>( 3A <span class="hlt">2</span><span class="hlt">g</span>) ground state, respectively, at <span class="hlt">2</span> K.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27127936','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27127936"><span>Analysis of esophageal cancer cell lines exposed to X-ray based on <span class="hlt">radiosensitivity</span> influence by tumor necrosis factor-α.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Buhai; Ge, Yizhi; Gu, Xiang</p> <p>2016-10-06</p> <p>Assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the <span class="hlt">radiosensitivity</span> of esophageal cancer cell line in vitro. Three esophageal cancer cell line cells were exposed to X-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell growth curve, and flow cytometry was performed to assess the cell apoptosis. The <span class="hlt">radiosensitizing</span> effects of TNF-α were detected by cell colony formation assay. Western blotting was applied to observe the expression of NF-κB and caspase-3 protein in the exposed cells. Our results indicated that cellular inhibition rate increased over time, the strongest is combined group (P < 0.05). Western blotting showed that the decline expression of NF-κB protein was stated between only rhTNF-α and only X-ray radiation group and the maximum degree was manifested in combined group. Caspase-3 protein content expression just works opposite. Three kinds of cells in the NF-κB protein were similar without rhTNF-α. Then SEG1 NF-κB protein content was reduced more than other two kinds. We concluded that the cells treated with TNF-α showed significantly suppressed cell proliferation, increasing the cell apoptosis, and caspase-3 protein expression after X-ray exposure. TNF-α can enhance the <span class="hlt">radiosensitivity</span> of esophageal cancer to enhancing the effect of the former.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20010047492','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20010047492"><span>D1((<span class="hlt">2</span>)B<span class="hlt">2</span><span class="hlt">g</span>) to D0((<span class="hlt">2</span>)Au) Fluorescence from the Matrix-Isolated Perylene Cation Following Laser Excitation into the D5(<span class="hlt">2</span>)B3<span class="hlt">g</span>) and D<span class="hlt">2</span> ((<span class="hlt">2</span>)B3<span class="hlt">g</span>) Electronic States</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Chillier, Xavier D. F.; Stone, Bradley M.; Joblin, Christine; Salama, Farid; Allamandola, Louis J.; DeVincenzi, Donald L. (Technical Monitor)</p> <p>2001-01-01</p> <p>Fluorescence spectra of the perylene cation, pumped by direct laser excitation via the D(sub <span class="hlt">2)((2</span>)B(sub 3<span class="hlt">g</span>)) (left arrow) D(sub 0)((<span class="hlt">2</span>)A(sub u)) and D(sub 5)(<span class="hlt">2</span>)B(sub 3<span class="hlt">g</span>)) (left arrow) D(sub 0)((<span class="hlt">2</span>)A(sub u)) transitions, are presented. Direct excitation into the D5 or D<span class="hlt">2</span> states is followed by rapid non-radiative relaxation to D1 that, in turn,relaxes radiatively. Excitation spectroscopy across the D(sub <span class="hlt">2)((2</span>)B(sub 3<span class="hlt">g</span>)) (left arrow) D(sub 0)((<span class="hlt">2</span>)A(sub u)) transition near 730 nm shows that site splitting plays little or no role in determining the spectral substructure in the ion spectra. Tentative assignments for ground state vibrational frequencies are made by comparison of spectral intervals with calculated normal mode frequencies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3899331','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3899331"><span>Visualizing Vpr-Induced <span class="hlt">G</span><span class="hlt">2</span> Arrest and Apoptosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Murakami, Tomoyuki; Aida, Yoko</p> <p>2014-01-01</p> <p>Vpr is an accessory protein of human immunodeficiency virus type 1 (HIV-1) with multiple functions. The induction of <span class="hlt">G</span><span class="hlt">2</span> arrest by Vpr plays a particularly important role in efficient viral replication because the transcriptional activity of the HIV-1 long terminal repeat is most active in <span class="hlt">G</span><span class="hlt">2</span> phase. The regulation of apoptosis by Vpr is also important for immune suppression and pathogenesis during HIV infection. However, it is not known whether Vpr-induced apoptosis depends on the ability of Vpr to induce <span class="hlt">G</span><span class="hlt">2</span> arrest, and the dynamics of Vpr-induced <span class="hlt">G</span><span class="hlt">2</span> arrest and apoptosis have not been visualized. We performed time-lapse imaging to examine the temporal relationship between Vpr-induced <span class="hlt">G</span><span class="hlt">2</span> arrest and apoptosis using HeLa cells containing the fluorescent ubiquitination-based cell cycle indicator<span class="hlt">2</span> (Fucci<span class="hlt">2</span>). The dynamics of <span class="hlt">G</span><span class="hlt">2</span> arrest and subsequent long-term mitotic cell rounding in cells transfected with the Vpr-expression vector were visualized. These cells underwent nuclear mis-segregation after prolonged mitotic processes and then entered <span class="hlt">G</span>1 phase. Some cells subsequently displayed evidence of apoptosis after prolonged mitotic processes and nuclear mis-segregation. Interestingly, Vpr-induced apoptosis was seldom observed in S or <span class="hlt">G</span><span class="hlt">2</span> phase. Likewise, visualization of synchronized HeLa/Fucci<span class="hlt">2</span> cells infected with an adenoviral vector expressing Vpr clearly showed that Vpr arrests the cell cycle at <span class="hlt">G</span><span class="hlt">2</span> phase, but does not induce apoptosis at S or <span class="hlt">G</span><span class="hlt">2</span> phase. Furthermore, time-lapse imaging of HeLa/Fucci<span class="hlt">2</span> cells expressing SCAT3.1, a caspase-3-sensitive fusion protein, clearly demonstrated that Vpr induces caspase-3-dependent apoptosis. Finally, to examine whether the effects of Vpr on <span class="hlt">G</span><span class="hlt">2</span> arrest and apoptosis were reversible, we performed live-cell imaging of a destabilizing domain fusion Vpr, which enabled rapid stabilization and destabilization by Shield1. The effects of Vpr on <span class="hlt">G</span><span class="hlt">2</span> arrest and subsequent apoptosis were reversible. This study is the first to characterize the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28947820','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28947820"><span>Mps1 kinase-dependent Sgo<span class="hlt">2</span> centromere localisation mediates cohesin protection in mouse oocyte meiosis I.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>El Yakoubi, Warif; Buffin, Eulalie; Cladière, Damien; Gryaznova, Yulia; Berenguer, Inés; Touati, Sandra A; Gómez, Rocío; Suja, José A; van Deursen, Jan M; Wassmann, Katja</p> <p>2017-09-25</p> <p>A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister <span class="hlt">chromatids</span> together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo<span class="hlt">2</span> from Separase-mediated cleavage, in order to maintain sister <span class="hlt">chromatids</span> together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo<span class="hlt">2</span> localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H<span class="hlt">2</span>A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo<span class="hlt">2</span> in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo<span class="hlt">2</span> at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo<span class="hlt">2</span> from Separase-mediated cleavage ensuring that sister <span class="hlt">chromatids</span> are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo<span class="hlt">2</span> localisation to the centromere region.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11695861','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11695861"><span>Determination of aflatoxins B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> in spices using a multifunctional column clean-up.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Akiyama, H; Goda, Y; Tanaka, T; Toyoda, M</p> <p>2001-10-12</p> <p>A rapid and simple method using a multifunctional column, which contains lipophilic and charged active sites, was developed to analyse aflatoxins B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> in various spices, such as red pepper and nutmeg. After extraction by acetonitrile:water (9:1) and clean-up using MultiSep #228 column, the aflatoxins and aflatoxin-TFA derivatives are determined using LC with fluorescence detection. Recoveries of each aflatoxin B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> spiked to red pepper, white pepper, black pepper, nutmeg and tear grass at the level of 10 ng/<span class="hlt">g</span> were over 80-85% in all instances. The minimum detectable concentration for aflatoxins in red pepper was 0.5 ng/<span class="hlt">g</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23266768','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23266768"><span>Nuclease digestion and mass spectrometric characterization of oligodeoxyribonucleotides containing 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span>, 1,<span class="hlt">2</span>-Ap<span class="hlt">G</span>, and 1,3-GpXp<span class="hlt">G</span> cisplatin intrastrand cross-links.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Williams, Renee T; Nalbandian, Jenifer N; Tu, Audrey; Wang, Yinsheng</p> <p>2013-05-01</p> <p>The primary mode of action for cis-diamminedichloroplatinum (II), referred to as cisplatin, toward the treatment of solid malignancies is through formation of cross-links with DNA at purine sites, especially guanines. We prepared oligodeoxyribonucleotides (ODNs) containing a 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span>, 1,<span class="hlt">2</span>-Ap<span class="hlt">G</span>, or 1,3-GpXp<span class="hlt">G</span> cisplatin intrastrand cross-link and the corresponding ODNs modified with (15)N<span class="hlt">2</span>-labeled cisplatin, and characterized these ODNs with electrospray ionization mass spectrometry (ESI-MS) and tandem MS (MS/MS). We also employed LC-MS/MS to characterize the digestion products of these ODNs after treatment with a cocktail of 4 enzymes (nuclease P1, phosphodiesterases I and II, and alkaline phosphatase). 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span> was released from the ODNs as a dinucleoside monophosphate or a dinucleotide. Analyses of the digestion products of ODNs containing a 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span> cross-link on the 5' or 3' terminus revealed that the dinucleotide carries a terminal 5' phosphate. On the other hand, digestion of the 1,3-GpXp<span class="hlt">G</span> intrastrand cross-link yielded 3 dinucleoside products with 0, 1, or <span class="hlt">2</span> phosphate groups. The availability of the ODNs carrying the stable isotope-labeled lesions, MS/MS analyses of the cisplatin-modified ODNs, and the characterization of the enzymatic digestion products of these ODNs set the stage for the future LC-MS/MS quantification of the 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span>, 1,<span class="hlt">2</span>-Ap<span class="hlt">G</span>, and 1,3-GpXp<span class="hlt">G</span> lesions in cellular DNA. Copyright © 2012 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3625460','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3625460"><span>Nuclease Digestion and Mass Spectrometric Characterization of Oligodeoxyribonucleotides Containing 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span>, 1,<span class="hlt">2</span>-Ap<span class="hlt">G</span>, and 1,3-GpXp<span class="hlt">G</span> Cisplatin Intrastrand Cross-links</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Williams, Renee T.; Nalbandian, Jenifer; Tu, Audrey; Wang, Yinsheng</p> <p>2013-01-01</p> <p>Background The primary mode of action for cis-diamminedichloroplatinum (II), referred to as cisplatin, towards the treatment of solid malignancies is through formation of cross-links with DNA at purine sites, especially guanines. Methods We prepared oligodeoxyribonucleotides (ODNs) containing a 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span>, 1,<span class="hlt">2</span>-Ap<span class="hlt">G</span>, or 1,3-GpXp<span class="hlt">G</span> cisplatin intrastrand cross-link and the corresponding ODNs modified with 15N<span class="hlt">2</span>-labeled cisplatin, and characterized these ODNs with electrospray ionization mass spectrometry (ESI-MS) and tandem MS (MS/MS). We also employed LC-MS/MS to characterize the digestion products of these ODNs after treatment with a cocktail of 4 enzymes (nuclease P1, phosphodiesterases I and II, and alkaline phosphatase). Results 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span> was released from the ODNs as a dinucleoside monophosphate or a dinucleotide. Analyses of the digestion products of ODNs containing a 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span> cross-link on the 5′ or 3′ terminus revealed that the dinucleotide carries a terminal 5′ phosphate. On the other hand, digestion of the 1,3-GpXp<span class="hlt">G</span> intrastrand cross-link yielded 3 dinucleoside products with 0, 1, or <span class="hlt">2</span> phosphate groups. Results The availability of the ODNs carrying the stable isotope-labeled lesions, MS/MS analyses of the cisplatin-modified ODNs, and the characterization of the enzymatic digestion products of these ODNs set the stage for the future LC-MS/MS quantification of the 1,<span class="hlt">2</span>-Gp<span class="hlt">G</span>, 1,<span class="hlt">2</span>-Ap<span class="hlt">G</span>, and 1,3-GpXp<span class="hlt">G</span> lesions in cellular DNA. PMID:23266768</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1095188','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1095188"><span>Genetic Control of the Trigger for the <span class="hlt">G</span><span class="hlt">2</span>/M Checkpoint</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Hall, Eric J.; Smilenov, Lubomir B.; Young, Erik F.</p> <p></p> <p> culture system, the engagement of the <span class="hlt">G</span><span class="hlt">2</span>/M checkpoint only occurs at doses where most of the cells are bound for mitotic catastrophe. Further, compound haploinsufficiency of various <span class="hlt">radiosensitizing</span> genes does not impact the threshold of activation. The experiments confirm a threshold of activation for the <span class="hlt">G</span><span class="hlt">2</span>/M checkpoint, hinting at two separate radiation response programs acting below and above this threshold. Small RNA transfer in bystander effect biology: Small regulatory RNA molecules have now risen in prominence and utility. Specific examples are small interfering RNAs (siRNA) which are employed in cell level expression ablation projects and micro-RNAs (miRNA) which are a pool of short transcription products which serve to modulate the expression of other transcripts emerging from the genome in a meta-regulatory fine tuning of gene expression. The existing tenets of bystander effect radiation biology involve the communication of inflammatory mediators or direct intercellular communication of reactive oxygen/nitrogen species in cell-to-cell communicative organelles called gap junctions. By ablating gap junctions, reducing the ROS/inflammatory cytokine expression one can attenuate bystander effect signaling in cell culture systems. We hypothesized that miRNAs are a competent intercellular communication molecule and therefore a possible component of the bystander response. This view is supported by the observation that miRNA are secreted from cells in exosomes found in the circulation. This circulating pool reports disease type and severity in humans. We proposed use of microbeam irradiation technology at our facilities and enhancement of this capability with a new sorting technology which would allow us to sort irradiated and non-irradiated cells with absolute fidelity. Pursuing direct quantitative transfer assessment, we succeeded in designing and constructing a new add-on sorting appliance which harmonized with our existing instruments. The sorter allowed us to</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29435012','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29435012"><span>MicroRNA-9 functions as a tumor suppressor and enhances <span class="hlt">radio-sensitivity</span> in radio-resistant A549 cells by targeting neuropilin 1.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Xiong, Kai; Shao, Li Hong; Zhang, Hai Qin; Jin, Linlin; Wei, Wei; Dong, Zhuo; Zhu, Yue Quan; Wu, Ning; Jin, Shun Zi; Xue, Li Xiang</p> <p>2018-03-01</p> <p>Radiotherapy is commonly used to treat lung cancer but may not kill all cancer cells, which may be attributed to the radiotherapy resistance that often occurs in non-small cell lung cancer (NSCLC). At present, the molecular mechanism of radio-resistance remains unclear. Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF), was demonstrated to be associated with radio-resistance of NSCLC cells via the VEGF-phosphoinositide 3-kinase-nuclear factor-κB pathway in our previous study. It was hypothesized that certain microRNAs (miRs) may serve crucial functions in <span class="hlt">radio-sensitivity</span> by regulating NRP1. Bioinformatics predicted that NRP1 was a potential target of miR-9, and this was validated by luciferase reporter assays. Functionally, miR-9-transfected A549 cells exhibited a decreased proliferation rate, increased apoptosis rate and attenuated migratory and invasive abilities. Additionally, a high expression of miR-9 also significantly enhanced the <span class="hlt">radio-sensitivity</span> of A549 cells in vitro and in vivo . These data improve understanding of the mechanisms of cell radio-resistance, and suggest that miR-9 may be a molecular target for the prediction of <span class="hlt">radio-sensitivity</span> in NSCLC.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=393118','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=393118"><span><span class="hlt">G</span><span class="hlt">2</span> phase-specific proteins of HeLa cells.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Al-Bader, A A; Orengo, A; Rao, P N</p> <p>1978-01-01</p> <p>The objective of this study was to determine if HeLa cells irreversibly arrested in <span class="hlt">G</span><span class="hlt">2</span> phase of the cell cycle by a brief exposure to a nitrosourea compound were deficient in certain proteins when compared with <span class="hlt">G</span><span class="hlt">2</span>-synchronized cells. Total cellular proteins of <span class="hlt">G</span><span class="hlt">2</span>-synchronized, <span class="hlt">G</span><span class="hlt">2</span>-arrested, and S phase-synchronized cells were compared by two-dimensional polyacrylamide gel electrophoresis. The S phase cells differed from the <span class="hlt">G</span><span class="hlt">2</span>-synchronized and <span class="hlt">G</span><span class="hlt">2</span>-arrested cells by the absence of about 35 and 25 protein spots, respectively, of a total of nearly 150. At least nine protein spots in the molecular weight range of 4--5 X 10(4) that were present in the <span class="hlt">G</span><span class="hlt">2</span>-synchronized cells were absent in both the <span class="hlt">G</span><span class="hlt">2</span>-arrested and the S phase cells. Thus, these studies suggest that the missing proteins are probably necessary for the transition of cells from <span class="hlt">G</span><span class="hlt">2</span> phase to mitosis. Supplying the missing proteins to the <span class="hlt">G</span><span class="hlt">2</span>-arrested cells by fusion with <span class="hlt">G</span><span class="hlt">2</span>-synchronized cells facilitated the entry of the former into mitosis. Images PMID:282623</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3442196','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3442196"><span>Perturbation of Incenp function impedes anaphase <span class="hlt">chromatid</span> movements and chromosomal passenger protein flux at centromeres</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ahonen, Leena J.; Kukkonen, Anu M.; Pouwels, Jeroen; Bolton, Margaret A.; Jingle, Christopher D.; Stukenberg, P. Todd; Kallio, Marko J.</p> <p>2012-01-01</p> <p>Incenp is an essential mitotic protein that, together with Aurora B, Survivin, and Borealin, forms the core of the chromosomal passenger protein complex (CPC). The CPC regulates various mitotic processes and functions to maintain genomic stability. The proper subcellular localization of the CPC and its full catalytic activity require the presence of each core subunit in the complex. We have investigated the mitotic tasks of the CPC using a function blocking antibody against Incenp microinjected into cells at different mitotic phases. This method allowed temporal analysis of CPC functions without perturbation of complex assembly or activity prior to injection. We have also studied the dynamic properties of Incenp and Aurora B using fusion protein photobleaching. We found that in early mitotic cells, Incenp and Aurora B exhibit dynamic turnover at centromeres, which is prevented by the anti-Incenp antibody. In these cells, the loss of centromeric CPC turnover is accompanied by forced mitotic exit without the execution of cytokinesis. Introduction of anti-Incenp antibody into early anaphase cells causes abnormalities in sister <span class="hlt">chromatid</span> separation through defects in anaphase spindle functions. In summary, our data uncovers new mitotic roles for the CPC in anaphase and proposes that CPC turnover at centromeres modulates spindle assembly checkpoint signaling. PMID:18784935</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18784935','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18784935"><span>Perturbation of Incenp function impedes anaphase <span class="hlt">chromatid</span> movements and chromosomal passenger protein flux at centromeres.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ahonen, Leena J; Kukkonen, Anu M; Pouwels, Jeroen; Bolton, Margaret A; Jingle, Christopher D; Stukenberg, P Todd; Kallio, Marko J</p> <p>2009-02-01</p> <p>Incenp is an essential mitotic protein that, together with Aurora B, Survivin, and Borealin, forms the core of the chromosomal passenger protein complex (CPC). The CPC regulates various mitotic processes and functions to maintain genomic stability. The proper subcellular localization of the CPC and its full catalytic activity require the presence of each core subunit in the complex. We have investigated the mitotic tasks of the CPC using a function blocking antibody against Incenp microinjected into cells at different mitotic phases. This method allowed temporal analysis of CPC functions without perturbation of complex assembly or activity prior to injection. We have also studied the dynamic properties of Incenp and Aurora B using fusion protein photobleaching. We found that in early mitotic cells, Incenp and Aurora B exhibit dynamic turnover at centromeres, which is prevented by the anti-Incenp antibody. In these cells, the loss of centromeric CPC turnover is accompanied by forced mitotic exit without the execution of cytokinesis. Introduction of anti-Incenp antibody into early anaphase cells causes abnormalities in sister <span class="hlt">chromatid</span> separation through defects in anaphase spindle functions. In summary, our data uncovers new mitotic roles for the CPC in anaphase and proposes that CPC turnover at centromeres modulates spindle assembly checkpoint signaling.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5587752','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5587752"><span>FANCJ helicase controls the balance between short- and long-tract gene conversions between sister <span class="hlt">chromatids</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Nath, Sarmi; Somyajit, Kumar; Mishra, Anup; Scully, Ralph</p> <p>2017-01-01</p> <p>Abstract The FANCJ DNA helicase is linked to hereditary breast and ovarian cancers as well as bone marrow failure disorder Fanconi anemia (FA). Although FANCJ has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), the molecular mechanism underlying the tumor suppressor functions of FANCJ remains obscure. Here, we demonstrate that FANCJ deficient human and hamster cells exhibit reduction in the overall gene conversions in response to a site-specific chromosomal DSB induced by I-SceI endonuclease. Strikingly, the gene conversion events were biased in favour of long-tract gene conversions in FANCJ depleted cells. The fine regulation of short- (STGC) and long-tract gene conversions (LTGC) by FANCJ was dependent on its interaction with BRCA1 tumor suppressor. Notably, helicase activity of FANCJ was essential for controlling the overall HR and in terminating the extended repair synthesis during sister <span class="hlt">chromatid</span> recombination (SCR). Moreover, cells expressing FANCJ pathological mutants exhibited defective SCR with an increased frequency of LTGC. These data unravel the novel function of FANCJ helicase in regulating SCR and SCR associated gene amplification/duplications and imply that these functions of FANCJ are crucial for the genome maintenance and tumor suppression. PMID:28911102</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28786016','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28786016"><span>Radiobiological Characterization of Tuberous Sclerosis: a Delay in the Nucleo-Shuttling of ATM May Be Responsible for <span class="hlt">Radiosensitivity</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ferlazzo, Mélanie L; Bach-Tobdji, Mohamed Kheir Eddine; Djerad, Amar; Sonzogni, Laurène; Devic, Clément; Granzotto, Adeline; Bodgi, Larry; Bachelet, Jean-Thomas; Djefal-Kerrar, Assia; Hennequin, Christophe; Foray, Nicolas</p> <p>2018-06-01</p> <p>The tuberous sclerosis complex (TSC) syndrome is associated with numerous cutaneous pathologies (notably on the face), epilepsy, intellectual disability and developmental retardation and, overall, high occurrence of benign tumors in several organs, like angiofibromas, giant cell astrocytomas, renal angiomyolipomas, and pulmonary lymphangioleiomyomatosis. TSC is caused by mutations of either of the hamartin or tuberin proteins that are mainly cytoplasmic. Some studies published in the 1980s reported that TSC is associated with <span class="hlt">radiosensitivity</span>. However, its molecular basis in TSC cells is not documented enough. Here, we examined the functionality of the repair and signaling of radiation-induced DNA double-strand breaks (DSB) in fibroblasts derived from TSC patients. Quiescent TSC fibroblast cells elicited abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H<span class="hlt">2</span>AX histones. Irradiated TSC cells also presented a delay in the nucleo-shuttling of the ATM kinase, potentially due to a specific binding of ATM to mutated TSC protein in cytoplasm. Lastly, TSC fibroblasts showed abnormally high MRE11 nuclease activity suggesting genomic instability. A combination of biphosphonates and statins complemented these impairments by facilitating the nucleoshuttling of ATM and increasing the yield of recognized DSB. Our results showed that TSC belongs to the group of syndromes associated with low but significant defect of DSB signaling and delay in the ATM nucleo-shuttling associated with <span class="hlt">radiosensitivity</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24014377','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24014377"><span>Equol as a potent <span class="hlt">radiosensitizer</span> in estrogen receptor-positive and -negative human breast cancer cell lines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Taghizadeh, Bita; Ghavami, Laleh; Nikoofar, Alireza; Goliaei, Bahram</p> <p>2015-07-01</p> <p>Breast cancer is the most common cause of cancer death among women worldwide, and diet plays an important role in its prevention and progression. Radiotherapy has a limited but important role in the management of nearly every stage of breast cancer. We studied whether equol, the major metabolite of the soybean isoflavone daidzein, could enhance <span class="hlt">radiosensitivity</span> in two human breast cancer cell lines (T47D and MDA-MB-231). MTT assay was used to examine equol's effect on cell viability. Sensitivity of cells to equol, radiation and a combination of both was determined by colonogenic assays. Induction of apoptosis by equol, radiation and the combination of both was also determined by acridine orange/ethidium bromide double staining fluorescence microscopy. DNA strand breaks were assessed by Comet assay. MTT assay showed that equol (0.1-350 μM) inhibited MDA-MB-231 and T47D cell growth in a time- and dose-dependent manner. Treatment of cells with equol for 72 h (MDA-MB-231) and 24 h (T47D) was found to inhibit cell growth with IC50 values of 252 μM and 228 μM, respectively. Furthermore, pretreatment of cells with 50 μM equol for 72 h (MDA-MB-231) and 24 h (T47D) sensitized the cells to irradiation. Equol was also found to enhance radiation-induced apoptosis. Comet assay results showed that the <span class="hlt">radiosensitizing</span> effect of equol was accompanied by increased radiation-induced DNA damages. These results suggest for the first time that equol can be considered as a <span class="hlt">radiosensitizing</span> agent and its effects may be due to increasing cell death following irradiation, increasing the remaining radiation-induced DNA damage and thus reducing the surviving fraction of irradiated cells.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_20 --> <div id="page_21" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="401"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4145860','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4145860"><span>Hedgehog Pathway Inhibition <span class="hlt">Radiosensitizes</span> Non-Small Cell Lung Cancers</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T.; Aftab, Blake T.; Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John; Rudin, Charles M.; Tran, Phuoc T.; Hales, Russell K.</p> <p>2012-01-01</p> <p>Purpose Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras<span class="hlt">G</span>12D-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on <span class="hlt">radio-sensitivity</span>. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer. PMID:23182391</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23182391','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23182391"><span>Hedgehog pathway inhibition <span class="hlt">radiosensitizes</span> non-small cell lung cancers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T; Aftab, Blake T; Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M; Wong, John; Rudin, Charles M; Tran, Phuoc T; Hales, Russell K</p> <p>2013-05-01</p> <p>Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras(<span class="hlt">G</span>12D)-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on <span class="hlt">radiosensitivity</span>. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer. Copyright © 2013 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22224456-hedgehog-pathway-inhibition-radiosensitizes-non-small-cell-lung-cancers','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22224456-hedgehog-pathway-inhibition-radiosensitizes-non-small-cell-lung-cancers"><span>Hedgehog Pathway Inhibition <span class="hlt">Radiosensitizes</span> Non-Small Cell Lung Cancers</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T.</p> <p>2013-05-01</p> <p>Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntagmore » and radiation. In a transgenic mouse model of Kras{sup <span class="hlt">G</span>12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on <span class="hlt">radiosensitivity</span>. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23850982','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23850982"><span>Downlink power distributions for <span class="hlt">2</span><span class="hlt">G</span> and 3<span class="hlt">G</span> mobile communication networks.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Colombi, Davide; Thors, Björn; Persson, Tomas; Wirén, Niklas; Larsson, Lars-Eric; Jonsson, Mikael; Törnevik, Christer</p> <p>2013-12-01</p> <p>Knowledge of realistic power levels is key when conducting accurate EMF exposure assessments. In this study, downlink output power distributions for radio base stations in <span class="hlt">2</span><span class="hlt">G</span> and 3<span class="hlt">G</span> mobile communication networks have been assessed. The distributions were obtained from network measurement data collected from the Operations Support System, which normally is used for network monitoring and management. Significant amounts of data were gathered simultaneously for large sets of radio base stations covering wide geographical areas and different environments. The method was validated with in situ measurements. For the 3<span class="hlt">G</span> network, the 90th percentile of the averaged output power during high traffic hours was found to be 43 % of the maximum available power. The corresponding number for <span class="hlt">2</span><span class="hlt">G</span>, with two or more transceivers installed, was 65 % or below.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27052944','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27052944"><span>Inhibition of the Rac1-WAVE<span class="hlt">2</span>-Arp<span class="hlt">2</span>/3 signaling pathway promotes <span class="hlt">radiosensitivity</span> via downregulation of cofilin-1 in U251 human glioma cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhou, Tao; Wang, Chen-Han; Yan, Hua; Zhang, Rui; Zhao, Jin-Bing; Qian, Chun-Fa; Xiao, Hong; Liu, Hong-Yi</p> <p>2016-05-01</p> <p>The Ras-related C3 botulinum toxin substrate 1 (Rac1)-WASP-family verprolin-homologous protein-<span class="hlt">2</span> (WAVE<span class="hlt">2</span>)-actin-related protein <span class="hlt">2</span>/3 (Arp<span class="hlt">2</span>/3) signaling pathway has been identified to be involved in cell migration and invasion in various types of cancer cell. Cofilin‑1 (CFL‑1), which is regulated by the Rac1‑WAVE<span class="hlt">2</span>‑Arp<span class="hlt">2</span>/3 signaling pathway, may promote radioresistance in glioma. Therefore, the present study aimed to investigate the potential role of the Rac1‑WAVE<span class="hlt">2</span>‑Arp<span class="hlt">2</span>/3 signaling pathway in radioresistance in U251 human glioma cells and elucidate its affect on CFL‑1 expression. Western blot analysis was performed to evaluate the protein expression of CFL‑1. In the present study, Rac1 was inhibited by NSC 23766, WAVE<span class="hlt">2</span> was inhibited by transfection with short hairpin (sh)RNA‑WAVE<span class="hlt">2</span> using Lipofectamine™ 2000 and Arp<span class="hlt">2</span>/3 was inhibited by CK‑666. Cell viability was measured using the 3‑(4,5‑dimethylthiazol‑<span class="hlt">2</span>‑yl)-<span class="hlt">2</span>,5‑diphenyltetrazolium bromide assay, the cell migration ability was examined by a wound‑healing assay, and the cell invasion ability was assessed using a Transwell culture chamber system. The results showed that inhibition of the Rac1‑WAVE<span class="hlt">2</span>‑Arp<span class="hlt">2</span>/3 signaling pathway using NSC 23766, shRNA‑WAVE<span class="hlt">2</span> or CK‑666 reduced the cell viability, migration and invasion abilities in U251 human glioma cells, concordant with a reduced expression of CFL‑1. Furthermore, the expression of CFL‑1 was significantly increased in radioresistant U251 glioma cells when compared with normal U251 human glioma cells. These findings indicate that inhibition of the Rac1‑WAVE<span class="hlt">2</span>‑Arp<span class="hlt">2</span>/3 signaling pathway may promote <span class="hlt">radiosensitivity</span>, which may partially result from the downregulation of CFL‑1 in U251 human glioma cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3906892','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3906892"><span>Gold-Loaded Polymeric Micelles for Computed Tomography-Guided Radiation Therapy Treatment and <span class="hlt">Radiosensitization</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2013-01-01</p> <p>Gold nanoparticles (AuNPs) have generated interest as both imaging and therapeutic agents. AuNPs are attractive for imaging applications since they are nontoxic and provide nearly three times greater X-ray attenuation per unit weight than iodine. As therapeutic agents, AuNPs can sensitize tumor cells to ionizing radiation. To create a nanoplatform that could simultaneously exhibit long circulation times, achieve appreciable tumor accumulation, generate computed tomography (CT) image contrast, and serve as a <span class="hlt">radiosensitizer</span>, gold-loaded polymeric micelles (GPMs) were prepared. Specifically, 1.9 nm AuNPs were encapsulated within the hydrophobic core of micelles formed with the amphiphilic diblock copolymer poly(ethylene glycol)-b-poly(ε-capralactone). GPMs were produced with low polydispersity and mean hydrodynamic diameters ranging from 25 to 150 nm. Following intravenous injection, GPMs provided blood pool contrast for up to 24 h and improved the delineation of tumor margins via CT. Thus, GPM-enhanced CT imaging was used to guide radiation therapy delivered via a small animal radiation research platform. In combination with the <span class="hlt">radiosensitizing</span> capabilities of gold, tumor-bearing mice exhibited a 1.7-fold improvement in the median survival time, compared with mice receiving radiation alone. It is envisioned that translation of these capabilities to human cancer patients could guide and enhance the efficacy of radiation therapy. PMID:24377302</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27745900','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27745900"><span>Inhibition of <span class="hlt">G</span>0/<span class="hlt">G</span>1 Switch <span class="hlt">2</span> Ameliorates Renal Inflammation in Chronic Kidney Disease.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Matsunaga, Naoya; Ikeda, Eriko; Kakimoto, Keisuke; Watanabe, Miyako; Shindo, Naoya; Tsuruta, Akito; Ikeyama, Hisako; Hamamura, Kengo; Higashi, Kazuhiro; Yamashita, Tomohiro; Kondo, Hideaki; Yoshida, Yuya; Matsuda, Masaki; Ogino, Takashi; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Nakao, Takaharu; Yasuda, Kaori; Doi, Atsushi; Amamoto, Toshiaki; Aramaki, Hironori; Tsuda, Makoto; Inoue, Kazuhide; Ojida, Akio; Koyanagi, Satoru; Ohdo, Shigehiro</p> <p>2016-11-01</p> <p>Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of <span class="hlt">G</span> 0 /<span class="hlt">G</span> 1 switch <span class="hlt">2</span> (<span class="hlt">G</span>0s<span class="hlt">2</span>) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand <span class="hlt">2</span> (Ccl<span class="hlt">2</span>) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of <span class="hlt">G</span>0s<span class="hlt">2</span> in wild-type 5/6Nx mice was important for the transactivation of Ccl<span class="hlt">2</span> by p65. These pathologies were ameliorated by <span class="hlt">G</span>0s<span class="hlt">2</span> knockdown. Furthermore, a novel small-molecule inhibitor of <span class="hlt">G</span>0s<span class="hlt">2</span> expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that <span class="hlt">G</span>0s<span class="hlt">2</span> inhibitors may have applications in the treatment of CKD. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17509678','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17509678"><span><span class="hlt">Radiosensitization</span> of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jin, Cheng; Bai, Ling; Wu, Hong; Tian, Furong; Guo, Guozhen</p> <p>2007-09-01</p> <p>Paclitaxel and etanidazole are hypoxic <span class="hlt">radiosensitizers</span> that exhibit cytotoxic action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o/w and w/o/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC). The cellular uptake of nanoparticles for the human breast carcinoma cells (MCF-7) and the human carcinoma cervicis cells (HeLa) was evaluated by transmission electronic microscopy and fluorescence microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel and lower for etanidazole. The drug release was controlled over time. The cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell lines with drug-loaded nanoparticles demonstrated that released drug effectively sensitized hypoxic tumor cells to radiation. The <span class="hlt">radiosensitization</span> of paclitaxel+etanidazole nanoparticles was more significant than that of single drug-loaded nanoparticles.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20010048658&hterms=pregnancy&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3Dpregnancy','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20010048658&hterms=pregnancy&qs=N%3D0%26Ntk%3DAll%26Ntx%3Dmode%2Bmatchall%26Ntt%3Dpregnancy"><span>Effects of <span class="hlt">2</span>.0-<span class="hlt">g</span> 1.75-<span class="hlt">g</span> and 1.5-<span class="hlt">g</span> Hypergravity on Pregnancy Outcome in Rats (Rattus norvegicus)</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Mills, Nicole A.; Baer, Lisa A.; Ronca, April E.</p> <p>2001-01-01</p> <p>In 1995, ten pregnant female rats were launched on the Space Shuttle (STS-70) on Gestational day(<span class="hlt">G</span>) 11 of their 22-day pregnancy as part of the NASA/NIH.Rodent (R)<span class="hlt">2</span> Experiment. Following landing on <span class="hlt">G</span>20, fetuses were harvested from half of the dams, while the remaining five dams underwent birth. Spaceflight did not interrupt pregnancy, alter litter sizes, or affect body weights or gender ratios of the fetuses or neonates. In the present study we used the NASA/NIH.R<span class="hlt">2</span> experimental paradigm to analyze the effects of hypergravity on pregnancy outcome. On <span class="hlt">G</span>10, time-bred Sprague-Dawley rat dams were assigned to either <span class="hlt">G</span>20 or Birth conditions, then further assigned to Hypergravity (HG) <span class="hlt">2</span>.0-<span class="hlt">g</span>, HG 1.75-<span class="hlt">g</span>, HG 1.5-<span class="hlt">g</span>, Rotational Control (RC, 1.03), or Stationary Control (SC, 1.0-<span class="hlt">g</span>) treatments. Dams were exposed to continuous centrifugation from <span class="hlt">G</span>11 through <span class="hlt">G</span>20, with brief daily stops for animal health checks and maintenance. For both the <span class="hlt">G</span>20 and Birth dams, comparable litter sizes and litter gender ratios were observed across gravity conditions. However, centrifugation-exposed (HG and RC) fetuses and neonates showed significantly lower body masses (p less than 0.05) relative to SC offspring. HG <span class="hlt">2</span>.0-<span class="hlt">g</span> offspring weighed significantly less than those in all other gravity conditions (p less than 0.05). The observed reductions in offspring body mass at 1.5-<span class="hlt">g</span> and 1.75-<span class="hlt">g</span>, can be attributed to the rotational component of centrifugation, rather than to increased gravitational load, whereas <span class="hlt">2</span>.0-<span class="hlt">g</span> hypergravity exposure further exacerbated the gravity centrifugation effect on offspring body mass. Pregnant dams exposed to centrifugation weighed significantly less than SC dams (p less than 0.05), suggesting that centrifugation effects on maternal body mass may contribute to reduced size of the developing offspring. These findings are consistent with previous reports of non-pregnant adult animals suggesting that, whereas spaceflight has virtually no effect on body mass, centrifugation is</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=326991','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=326991"><span>Isolation and characterization of rabbit anti-m3 <span class="hlt">2,2</span>,7<span class="hlt">G</span> antibodies.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Luhrmann, R; Appel, B; Bringmann, P; Rinke, J; Reuter, R; Rothe, S; Bald, R</p> <p>1982-01-01</p> <p>Antibodies specific for intact <span class="hlt">2,2</span>,7-trimethylguanosine (m3 <span class="hlt">2,2</span>,7<span class="hlt">G</span>) were induced by immunization of rabbits with a nucleoside-human serum albumen (HSA) conjugate. Competition radioimmunoassay showed that the antibody distinguishes well between intact m3 <span class="hlt">2,2</span>,7<span class="hlt">G</span> and its alkali-hydrolysed form (m3 <span class="hlt">2,2</span>,7<span class="hlt">G</span>*). Antibody specificity is largely dependent on the presence of all three methyl groups in m3 <span class="hlt">2,2</span>,7<span class="hlt">G</span>: none of the less extensively methylated nucleosides m7<span class="hlt">G</span>, m<span class="hlt">2</span><span class="hlt">G</span> and m<span class="hlt">2</span> <span class="hlt">2,2</span><span class="hlt">G</span> is able to compete efficiently with the homologous hapten. Little or no competition was observed with m1<span class="hlt">G</span>, m1A, m6A, m5U and each of the four unmodified ribonucleosides. Binding studies with nucleoplasmic RNAs from Ehrlich ascites cells suggest that the antibody reacts specifically with the m3 <span class="hlt">2,2</span>,7<span class="hlt">G</span>-containing cap structure of the small nuclear U-RNAs (U-snRNAs). Thus the antibody should be a valuable tool for studying the role of the 5'-terminal regions of the U-snRNAs of eucaryotic cells. Images PMID:7155893</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20730658','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20730658"><span>Increased frequency of sister <span class="hlt">chromatid</span> exchanges and decrease in cell viability and proliferation kinetics in human peripheral blood lymphocytes after in vitro exposure to whole bee venom.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gajski, Goran; Garaj-Vrhovac, Vera</p> <p>2010-10-01</p> <p>The present study was aimed to investigate the impact of bee venom on frequency of sister <span class="hlt">chromatid</span> exchanges (SCE) and viability in human peripheral blood lymphocytes in vitro. In addition, the proportion of lymphocytes that undergo one, two or three cell divisions as well as proliferative rate index (PRI) have been determined. Aqueous solution of whole bee venom was added to whole blood samples in concentrations ranging from 0.1 microg/mL to 20 microg/mL in different lengths of time. Results showed that whole bee venom inhibited cell viability, resulting in a 22.86 +/- 1.14% and 51.21 +/- 0.58% reduction of viable cells at 1 hour and 6 hours, respectively. The mean SCE per cell in all the exposed samples was significantly higher than in the corresponding controls. In addition, the percentage of high frequency cells (HFC) for each sample was estimated using the pooled distribution of all SCE measurements. This parameter was also significantly higher compared to the control. Inhibition of proliferation was statistically significant for both exposure times and concentrations and was time and dose dependent. These data indicate that whole bee venom inhibited cell proliferation, resulting in a 36.87 +/- 5.89% and 38.43 +/- 1.96% reduction of proliferation at 1 hour and 6 hours, respectively. In conclusion, this report demonstrated that whole bee venom is capable of inducing DNA alterations by virtue of increasing sister <span class="hlt">chromatid</span> exchanges in addition to the cell viability decrease and inhibition of proliferation kinetics in human peripheral blood lymphocytes in vitro.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3699614','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3699614"><span>MEK1/<span class="hlt">2</span> inhibition enhances the <span class="hlt">radiosensitivity</span> of cancer cells by downregulating survival and growth signals mediated by EGFR ligands</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>CHUNG, EUN JOO; URICK, MARY ELLEN; KURSHAN, NAAMIT; SHIELD, WILLIAM; ASANO, HIROAKI; SMITH, PAUL D.; SCROGGINS, BRADLEY S.; BURKEEN, JEFFREY; CITRIN, DEBORAH E.</p> <p>2013-01-01</p> <p>The inhibition of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway through the suppression of mutated Ras or MAPK/extracellular signal-regulated kinase 1/<span class="hlt">2</span> (MEK1/<span class="hlt">2</span>) has been shown to sensitize tumor cells to ionizing radiation (IR). The molecular mechanisms of this sensitization however, are not yet fully understood. In this study, we investigated the role of transforming growth factor-α (TGF-α) in the <span class="hlt">radiosensitizing</span> effects of selumetinib, a selective inhibitor of MEK1/<span class="hlt">2</span>. The expression of epidermal growth factor receptor (EGFR) ligands was assessed by ELISA in both Ras wild-type and Ras mutant cells that were exposed to radiation with or without selumetinib. The effects of selumetinib on the TGF-α/EGFR signaling cascade in response to radiation were examined by western blot analysis, clonogenic assay and by determing the yield of mitotic catastrophe. The treatment of cells with selumetinib reduced the basal and IR-induced secretion of TGF-α in both Ras wild-type and Ras mutant cell lines in vitro and in vivo. The reduction of TGF-α secretion was accompanied with a reduction in phosphorylated tumor necrosis factor-α converting enzyme (TACE) in the cells treated with selumetinib with or without IR. The treatment of cells with selumetinib with or without IR inhibited the phosphorylation of EGFR and check-point kinase <span class="hlt">2</span> (Chk<span class="hlt">2</span>), and reduced the expression of survivin. Supplementation with exogenous TGF-α partially rescued the selumetinib-treated cells from IR-induced cell death, restored EGFR and Chk<span class="hlt">2</span> phosphorylation and increased survivin expression. These data suggest that the inhibition of MEK1/<span class="hlt">2</span> with selumetinib may provide a mechanism to sensitize tumor cells to IR in a fashion that prevents the activation of the TGF-α autocrine loop following IR. PMID:23588995</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26722253','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26722253"><span>Inhibition of DNA-PKcs enhances <span class="hlt">radiosensitivity</span> and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Lina; Liu, Yuanyuan; Sun, Chao; Yang, Xinrui; Yang, Zhen; Ran, Juntao; Zhang, Qiuning; Zhang, Hong; Wang, Xinyu; Wang, Xiaohu</p> <p>2015-11-01</p> <p>Non-small cell lung cancer (NSCLC) exhibits radioresistance to conventional rays, due to its DNA damage repair systems. NSCLC may potentially be sensitized to radiation treatment by reducing those factors that continuously enhance the repair of damaged DNA. In the present study, normal lung fibroblast MRC-5 and lung cancer A549 cells were treated with NU7026 and CGK733, which are inhibitors of the DNA-dependent protein kinase catalytic subunit (PKcs) and ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR), respectively, followed by exposure to X-rays and carbon ion irradiation. The cytotoxic activity, cell survival rate, DNA damage repair ability, cell cycle arrest and apoptosis rate of the treated cells were analyzed with MTT assay, colony formation assay, immunofluorescence and flow cytometry, respectively. The transcription and translation levels of the ATM, ATR and DNA-PKcs genes were detected by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results indicated that the <span class="hlt">radiosensitivity</span> and DNA repair ability of A549 cells were reduced, and the percentages of apoptotic cells and those arrested at the <span class="hlt">G</span> <span class="hlt">2</span> /M phase of the cell cycle were significantly increased, following ionizing radiation with inhibitor-pretreatment. The expression levels of ATM, ATR, DNA-PKcs and phosphorylated histone H<span class="hlt">2</span>AX, a biomarker for DNA double-strand breaks, were all upregulated at the transcriptional or translational level in A549 cells treated with carbon ion irradiation, compared with the control and X-rays-treated cells. In addition, the treatment with 5-50 µM NU7026 or CGK733 did not produce any obvious cytotoxicity in MRC-5 cells, and the effect of the DNA-PKcs-inhibitor on enhancing the <span class="hlt">radiosensitivity</span> of A549 cells was stronger than that observed for the ATM and ATR-inhibitor. These findings demonstrated a minor role for ATM and ATR in radiation-induced cell death, since the upregulation of</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009RaPC...78..567L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009RaPC...78..567L"><span>Bacterial <span class="hlt">radiosensitization</span> by using radiation processing in combination with essential oil: Mechanism of action</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Lacroix, Monique; Caillet, Stéphane; Shareck, Francois</p> <p>2009-07-01</p> <p>Spice extracts under the form of essential oils were tested for their efficiency to increase the relative <span class="hlt">radiosensitivity</span> of Listeria monocytogenes and Escherichia coli O157H7 in culture media. The two pathogens were treated by gamma-irradiation alone or in combination with oregano essential oil to evaluate their mechanism of action. The membrane murein composition, and the intracellular and extracellular concentration of ATP was determined. The bacterial strains were treated with two irradiation doses: 1.<span class="hlt">2</span> kGy to induce cell damage and 3.5 kGy to cause cell death for L. monocytogenes. A dose of 0.4 kGy to induce cell damages, 1.1 kGy to obtain viable but nonculturable (VBNC) state and 1.3 kGy to obtain a lethal dose was also applied on E. coli O157H7. Oregano essential oil was used at 0.020% and 0.025% (w/v), which is the minimum inhibitory concentration (MIC) for L. monocytogenes. For E. coli O157H7, a concentration of 0.006% and 0.025% (w/v) which is the minimum inhibitory concentration was applied. The use of essential oils in combination with irradiation has permitted an increase of the bacterial <span class="hlt">radiosensitization</span> by more than 3.1 times. All treatments had also a significant effect ( p⩽0.05) on the murein composition, although some muropeptides did not seem to be affected by the treatment. Each treatment influenced differently the relative percentage and number of muropeptides. There was a significant ( p⩽0.05) correlation between the reduction of intracellular ATP and increase in extracellular ATP following treatment of the cells with oregano oil. The reduction of intracellular ATP was even more important when essential oil was combined with irradiation, but irradiation of L. monocytogenes alone induced a significant decrease ( p⩽0.05) of the internal ATP without affecting the external ATP.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21124326-radiosensitization-human-vascular-endothelial-cells-through-hsp90-inhibition-allilamino-demethoxygeldanamycin','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21124326-radiosensitization-human-vascular-endothelial-cells-through-hsp90-inhibition-allilamino-demethoxygeldanamycin"><span><span class="hlt">Radiosensitization</span> of Human Vascular Endothelial Cells Through Hsp90 Inhibition With 17-N-Allilamino-17-Demethoxygeldanamycin</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Kabakov, Alexander E.; Makarova, Yulia M.; Malyutina, Yana V.</p> <p></p> <p>Purpose: In addition to invasive tumor cells, endothelial cells (ECs) of the tumor vasculature are an important target for anticancer radiotherapy. The purpose of the present work is to investigate how 17-N-allilamino-17-demethoxygeldanamycin (17AAG), known as an anticancer drug inhibiting heat shock protein 90 (Hsp90), modifies radiation responses of human vascular ECs. Methods and Materials: The ECs cultured from human umbilical veins were exposed to {gamma}-irradiation, whereas some EC samples were pretreated with growth factors and/or 17AAG. Postirradiation cell death/survival and morphogenesis were assessed by means of terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate nick end labeling or annexin V staining and clonogenicmore » and tube-formation assays. The 17AAG-affected expression and phosphorylation of radioresistance-related proteins were probed by means of immunoblotting. Dominant negative or constitutively activated Akt was transiently expressed in ECs to manipulate Akt activity. Results: It was found that nanomolar concentrations of 17AAG sensitize ECs to relatively low doses (<span class="hlt">2</span>-6 Gy) of {gamma}-irradiation and abolish the radioprotective effects of vascular endothelial growth factor and basic fibroblast growth factor. The drug-induced <span class="hlt">radiosensitization</span> of ECs seems to be caused by prevention of Hsp90-dependent phosphorylation (activation) of Akt that results in blocking the radioprotective phosphatidylinositol 3-kinase/Akt pathway. Conclusions: Clinically achievable concentrations of 17AAG can decrease the radioresistance intrinsic to vascular ECs and minimize the radioprotection conferred upon them by tumor-derived growth factors. These findings characterize 17AAG as a promising <span class="hlt">radiosensitizer</span> for the tumor vasculature.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/7688857','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/7688857"><span>Sister-<span class="hlt">chromatid</span> exchanges and cell-cycle kinetics in the lymphocytes of workers occupationally exposed to a chemical mixture in the tyre industry.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sasiadek, M</p> <p>1993-08-01</p> <p>Cytogenetic studies of clinically healthy workers employed in the rubber industry showed an increase in chromosome aberrations (CAs), sister-<span class="hlt">chromatid</span> exchanges (SCEs) and a decrease in proliferation indices (PIs). The aim of the present study was to establish, using the SCE and PI tests, genotoxic effects of hazardous chemicals in the rubber industry. An increase in mean SCEs in the lymphocytes of vulcanizers as compared to controls was observed. Since the PI in the exposed group was insignificantly decreased as compared to the controls, it could be concluded that the SCE test is the most sensitive cytogenetic test for the detection of a genotoxic effect of chemicals in the rubber industry. There was no evidence in the present study that the genotoxic effect of chemicals in the rubber industry was enhanced by cigarette smoking.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title48-vol3/pdf/CFR-2013-title48-vol3-chap2-appG.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title48-vol3/pdf/CFR-2013-title48-vol3-chap2-appG.pdf"><span>48 CFR Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> - [Reserved</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-10-01</p> <p>... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false [Reserved] <span class="hlt">G</span> Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> [Reserved] ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title48-vol3/pdf/CFR-2011-title48-vol3-chap2-appG.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title48-vol3/pdf/CFR-2011-title48-vol3-chap2-appG.pdf"><span>48 CFR Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> - [Reserved</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-10-01</p> <p>... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false [Reserved] <span class="hlt">G</span> Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> [Reserved] ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title48-vol3/pdf/CFR-2010-title48-vol3-chap2-appG.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title48-vol3/pdf/CFR-2010-title48-vol3-chap2-appG.pdf"><span>48 CFR Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> - [Reserved</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-10-01</p> <p>... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false [Reserved] <span class="hlt">G</span> Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> [Reserved] ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title48-vol3/pdf/CFR-2012-title48-vol3-chap2-appG.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title48-vol3/pdf/CFR-2012-title48-vol3-chap2-appG.pdf"><span>48 CFR Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> - [Reserved</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-10-01</p> <p>... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false [Reserved] <span class="hlt">G</span> Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> [Reserved] ...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title48-vol3/pdf/CFR-2014-title48-vol3-chap2-appG.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title48-vol3/pdf/CFR-2014-title48-vol3-chap2-appG.pdf"><span>48 CFR Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> - [Reserved</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-10-01</p> <p>... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false [Reserved] <span class="hlt">G</span> Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE Appendix <span class="hlt">G</span> to Chapter <span class="hlt">2</span> [Reserved] ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title12-vol5/pdf/CFR-2010-title12-vol5-sec563g-2.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title12-vol5/pdf/CFR-2010-title12-vol5-sec563g-2.pdf"><span>12 CFR 563<span class="hlt">g</span>.<span class="hlt">2</span> - Offering circular requirement.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-01-01</p> <p>... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Offering circular requirement. 563<span class="hlt">g</span>.<span class="hlt">2</span> Section 563<span class="hlt">g</span>.<span class="hlt">2</span> Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563<span class="hlt">g</span>.<span class="hlt">2</span> Offering circular requirement. (a) General. No savings association shall offer or sell, directly...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title26-vol8/pdf/CFR-2014-title26-vol8-sec1-642g-2.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title26-vol8/pdf/CFR-2014-title26-vol8-sec1-642g-2.pdf"><span>26 CFR 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> - Deductions included.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-04-01</p> <p>... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Deductions included. 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Section 1.642(<span class="hlt">g</span>... (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Deductions included. It...(<span class="hlt">g</span>) is applicable be treated in the same way. One deduction or portion of a deduction may be allowed...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title26-vol8/pdf/CFR-2013-title26-vol8-sec1-642g-2.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title26-vol8/pdf/CFR-2013-title26-vol8-sec1-642g-2.pdf"><span>26 CFR 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> - Deductions included.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-04-01</p> <p>... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Deductions included. 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Section 1.642(<span class="hlt">g</span>... (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Deductions included. It...(<span class="hlt">g</span>) is applicable be treated in the same way. One deduction or portion of a deduction may be allowed...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title26-vol8/pdf/CFR-2011-title26-vol8-sec1-642g-2.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title26-vol8/pdf/CFR-2011-title26-vol8-sec1-642g-2.pdf"><span>26 CFR 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> - Deductions included.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-04-01</p> <p>... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Deductions included. 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Section 1.642(<span class="hlt">g</span>... (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Deductions included. It...(<span class="hlt">g</span>) is applicable be treated in the same way. One deduction or portion of a deduction may be allowed...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title26-vol8/pdf/CFR-2012-title26-vol8-sec1-642g-2.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title26-vol8/pdf/CFR-2012-title26-vol8-sec1-642g-2.pdf"><span>26 CFR 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> - Deductions included.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-04-01</p> <p>... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Deductions included. 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Section 1.642(<span class="hlt">g</span>... (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Deductions included. It...(<span class="hlt">g</span>) is applicable be treated in the same way. One deduction or portion of a deduction may be allowed...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title26-vol8/pdf/CFR-2010-title26-vol8-sec1-642g-2.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title26-vol8/pdf/CFR-2010-title26-vol8-sec1-642g-2.pdf"><span>26 CFR 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> - Deductions included.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-04-01</p> <p>... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Deductions included. 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Section 1.642(<span class="hlt">g</span>... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(<span class="hlt">g</span>)-<span class="hlt">2</span> Deductions included. It is not required that the total deductions, or the total amount of any deduction, to which section 642(<span class="hlt">g</span>) is...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009IJMSp.280....6M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009IJMSp.280....6M"><span>Reactions of small negative ions with O<span class="hlt">2</span>(a 1[Delta]<span class="hlt">g</span>) and O<span class="hlt">2</span>(X 3[Sigma]<span class="hlt">g</span>-)</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Midey, Anthony; Dotan, Itzhak; Seeley, J. V.; Viggiano, A. A.</p> <p>2009-02-01</p> <p>The rate constants and product ion branching ratios were measured for the reactions of various small negative ions with O<span class="hlt">2</span>(X 3[Sigma]<span class="hlt">g</span>-) and O<span class="hlt">2</span>(a 1[Delta]<span class="hlt">g</span>) in a selected ion flow tube (SIFT). Only NH<span class="hlt">2</span>- and CH3O- were found to react with O<span class="hlt">2</span>(X) and both reactions were slow. CH3O- reacted by hydride transfer, both with and without electron detachment. NH<span class="hlt">2</span>- formed both OH-, as observed previously, and O<span class="hlt">2</span>-, the latter via endothermic charge transfer. A temperature study revealed a negative temperature dependence for the former channel and Arrhenius behavior for the endothermic channel, resulting in an overall rate constant with a minimum at 500 K. SF6-, SF4-, SO3- and CO3- were found to react with O<span class="hlt">2</span>(a 1[Delta]<span class="hlt">g</span>) with rate constants less than 10-11 cm3 s-1. NH<span class="hlt">2</span>- reacted rapidly with O<span class="hlt">2</span>(a 1[Delta]<span class="hlt">g</span>) by charge transfer. The reactions of HO<span class="hlt">2</span>- and SO<span class="hlt">2</span>- proceeded moderately with competition between Penning detachment and charge transfer. SO<span class="hlt">2</span>- produced a SO4- cluster product in <span class="hlt">2</span>% of reactions and HO<span class="hlt">2</span>- produced O3- in 13% of the reactions. CH3O- proceeded essentially at the collision rate by hydride transfer, again both with and without electron detachment. These results show that charge transfer to O<span class="hlt">2</span>(a 1[Delta]<span class="hlt">g</span>) occurs readily if the there are no restrictions on the ion beyond the reaction thermodynamics. The SO<span class="hlt">2</span>- and HO<span class="hlt">2</span>- reactions with O<span class="hlt">2</span>(a) are the only known reactions involving Penning detachment besides the reaction with O<span class="hlt">2</span>- studied previously [R.S. Berry, Phys. Chem. Chem. Phys., 7 (2005) 289-290].</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5120376-induction-sister-chromatid-exchange-preimplantation-mouse-embryos-vitro-sup-thymidine-ultraviolet-light-combination-caffeine','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5120376-induction-sister-chromatid-exchange-preimplantation-mouse-embryos-vitro-sup-thymidine-ultraviolet-light-combination-caffeine"><span>Induction of sister <span class="hlt">chromatid</span> exchange in preimplantation mouse embryos in vitro by /sup 3/H-thymidine or ultraviolet light in combination with caffeine</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Mueller, W.U.S.; Spindle, A.</p> <p>1986-01-01</p> <p>Preimplantation mouse embryos were exposed in vitro to /sup 3/H-thymidine (25, 100, or 250 Bq/ml) or ultraviolet (UV) light (1.35 or 4.05 J/m<span class="hlt">2</span>), either alone or in combination with caffeine (1 mM with /sup 3/H-thymidine and 0.5 mM with UV light). Exposure to /sup 3/H-thymidine lasted for <span class="hlt">2</span> days, from the two-cell stage to the late morula/early blastocyst stage, and UV radiation was applied acutely at the late morula/early blastocyst stage. The effects were quantified by the sister <span class="hlt">chromatid</span> exchange (SCE) assay. All three agents induced SCEs when used singly. /sup 3/H-thymidine was effective in inducing SCEs only at 250more » Bq/ml, whereas UV light was effective at both fluences. Although caffeine did not induce SCEs when it was added before exposure to bromodeoxyuridine (BrdUrd), which is used to visualize SCEs, it did induce SCEs when present during the entire culture period (/sup 3/H-thymidine experiments) or during incubation in BrdUrd (UV experiments). Caffeine markedly enhanced the SCE-inducing effect of UV light but did not influence the effect of /sup 3/H-thymidine.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28179317','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28179317"><span>Hypofractionated Palliative Radiotherapy with Concurrent <span class="hlt">Radiosensitizing</span> Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen".</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gamez, Mauricio E; Agarwal, Manuj; Hu, Kenneth S; Lukens, John N; Harrison, Louis B</p> <p>2017-02-01</p> <p>To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent <span class="hlt">radiosensitizing</span> chemotherapy for advanced head and neck cancer. We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles. 85.7 % of patients had objective response to therapy with five patients (23.8%) demonstrating complete response (CR) and thirteen patients (61.9%) demonstrating partial response (PR). Palliation of symptoms was achieved in all (100%) of the sixteen patients that completed the three cycles. Median overall survival and median progression-free survival were 7 and 4 months, respectively. QUAD-Shot palliative radiation therapy coupled with <span class="hlt">radiosensitizing</span> chemotherapy is efficacious and well-tolerated in patients with newly-diagnosed or recurrent head and neck cancer not amenable to curative therapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26224081','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26224081"><span>miR-375 Modulates <span class="hlt">Radiosensitivity</span> of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A through the p53 Pathway.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Song, Lili; Liu, Shikai; Zeng, Saitian; Zhang, Liang; Li, Xia</p> <p>2015-07-30</p> <p>Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer. qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on <span class="hlt">radiosensitivity</span> and the downstream regulative network were further explored in the cell line models. The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted <span class="hlt">radiosensitivity</span> of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis. The miR-375-UBE3A axis is important in modulating <span class="hlt">radiosensitivity</span> of HR-HPV (+) cervical cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28838342','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28838342"><span>The association between PAI-1 -675 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism and type <span class="hlt">2</span> diabetes mellitus.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chen, L; Li, S-Y; Liu, M</p> <p>2017-08-15</p> <p>In this study, we aimed to analyze the association between plasminogen activator inhibitor 1 (PAI-1) -675 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism and type <span class="hlt">2</span> diabetes mellitus (T<span class="hlt">2</span>DM) risk. We included in 187 T<span class="hlt">2</span>DM patients and 186 heathy controls between 2014 and 2017 from Tianjin Gong An Hospital, China. All patients and controls were ethnically Chinese Han population. The primers and polymerase chain reaction (PCR) conditions were performed. Results from this case-control study suggested that PAI-1 -675 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism was not associated with T<span class="hlt">2</span>DM risk in four genetic models. Additionally, PAI-1 -675 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism was not associated with clinical and laboratory characteristics, such as age, gender, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, and HbA1c. In conclusion, this case-control study suggested that PAI-1 -675 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism was not associated with T<span class="hlt">2</span>DM risk in this population.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19500270','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19500270"><span>Micronuclear and sister <span class="hlt">chromatid</span> exchange analyses in peripheral lymphocytes of patients with oral lichen planus--a pilot study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ergun, S; Warnakulasuriya, S; Duman, N; Saruhanoğlu, A; Sevinç, B; Oztürk, S; Ozel, S; Cefle, K; Palanduz, S; Tanyeri, H</p> <p>2009-10-01</p> <p>The purpose of this study was to determine the genetic instability of peripheral blood lymphocytes from patients diagnosed with oral lichen planus (OLP) by investigation of frequencies of micronuclei (MN) and sister <span class="hlt">chromatid</span> exchange (SCE). A total of 22 newly diagnosed and untreated patients with OLP of same severity scores and twenty healthy controls participated in this study. They were all non-smokers with no previous history or family history of cancer. The periodontal status, flow rate and buffering capacity of whole mouth saliva were recorded. SCE and MN analyses were performed on peripheral blood lymphocytes of OLP patients and healthy controls. The frequencies of MN (50.00 +/- 22.36) and SCE (6.89 +/- 1.48) in OLP patients were found to be significantly elevated compared with that in normal individuals (25.20 +/- 9.52 and 5.93 +/- 1.31; z = 3.946, P = 0.0001; z = <span class="hlt">2</span>.346, P = 0.019). There were no significant differences in the MN frequency and SCE between the two subgroups with reticular or erosive types of OLP. These pilot data indicate an increased genomic instability in peripheral blood lymphocytes of a cohort of Turkish patients diagnosed with oral lichen planus as compared with that of healthy individuals. As patients with OLP may have an increased or potential risk for oral malignancy, these assays could be used in translational research to monitor beneficial effects of interventions and long-term prognosis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/6474091','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/6474091"><span>Ig<span class="hlt">G</span><span class="hlt">2</span> deficiency in sickle cell anaemia.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Natta, C L; Outschoorn, I M</p> <p>1984-08-01</p> <p>8 patients with known sickle cell anaemia were studied immunologically. The concentrations of the main immunoglobulin classes, Ig<span class="hlt">G</span> and IgA, were significantly higher than the levels in 11 normal age- and sex-matched black subjects (P less than 0.01). IgM levels were not significantly different in the two groups. There was a heterogeneity in the interaction of the Ig<span class="hlt">G</span> subclasses with Protein A, with low levels of Ig<span class="hlt">G</span><span class="hlt">2</span>. The Ig<span class="hlt">G</span><span class="hlt">2</span>:Ig<span class="hlt">G</span>1 ratios varied from 1:3.8 to 1:6 (normals 1:3). In 4 patients the absolute levels of Ig<span class="hlt">G</span><span class="hlt">2</span> as measured by radial immunodiffusion were lower than normal, thus confirming the chromatographic ratios. Since specific antibody is often restricted to a single subclass, the levels of Ig<span class="hlt">G</span> subclasses may be related to recurrent bacterial infections in these patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6067666-effect-medroxyprogesterone-acetate-provera-ovarian-radiosensitivity','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6067666-effect-medroxyprogesterone-acetate-provera-ovarian-radiosensitivity"><span>Effect of medroxyprogesterone acetate (Provera) on ovarian <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Jarrell, J.; YoungLai, E.V.; McMahon, A.</p> <p>1989-04-01</p> <p>Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a <span class="hlt">radiosensitizing</span> agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44.more » Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25604309','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25604309"><span>Novel poly (ADP-ribose) polymerase inhibitor, AZD2281, enhances <span class="hlt">radiosensitivity</span> of both normoxic and hypoxic esophageal squamous cancer cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhan, L; Qin, Q; Lu, J; Liu, J; Zhu, H; Yang, X; Zhang, C; Xu, L; Liu, Z; Cai, J; Ma, J; Dai, S; Tao, G; Cheng, H; Sun, X</p> <p>2016-04-01</p> <p>Radiotherapy plays an important role in the treatment of esophageal squamous cell carcinoma (ESCC). However, the outcome of radiotherapy in ESCC remains unsatisfactory because esophageal squamous cancer cells, particularly those under hypoxic condition, exhibit radioresistance. The aim of this study was to determine whether or not AZD2281, a potent poly (ADP-ribose) polymerase (PARP) inhibitor, could enhance the radiation sensitivity of two ESCC cell lines, namely ECA109 and TE13. The <span class="hlt">radiosensitizing</span> effect of AZD2281 was evaluated on the basis of cell death, clonogenic survival and tumor xenograft progression. AZD2281 alone was slightly toxic to ESCC cell lines. Apoptosis was increased and clonogenic survival was decreased in both cell lines when AZD2281 was combined with ionizing radiation (IR) under normoxic condition. AZD2281 enhanced IR-induced apoptosis to a more significant level under chronic hypoxic condition (0.<span class="hlt">2</span>% O(<span class="hlt">2</span>), 48 hour) than under normoxic condition. AZD2281 also slightly enhanced clonogenic cell death under chronic hypoxic condition compared with that under normoxic condition. This result could be associated with increased radiation-induced DNA double-strand breaks (DSB), decreased DSB repair and increased apoptosis of ESCC cells. Furthermore, homologous recombination (HR) protein Rad51 expression and focus formation were decreased in ESCC cells exposed to moderate chronic hypoxic condition (0.<span class="hlt">2</span>% O(<span class="hlt">2</span>), 48 hour); this result indicated that chronic hypoxic ESCC cells were HR deficient, possibly causing contextual synthetic lethality with PARP inhibitor in radiation sensitization. AZD2281 was also a radiation sensitizer in ESCC tumor xenograft models. Hence, in vitro and in vivo findings provide evidence that AZD2281 potently sensitizes ESCC cells to X-ray irradiation. The selective cell killing of HR-defective hypoxic cells contributes to <span class="hlt">radiosensitization</span> by PARP inhibitor in ESCC cells under hypoxic condition. © 2015 International Society for</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1390043','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1390043"><span>Critical Elements of Vehicle-to-Grid (V<span class="hlt">2</span><span class="hlt">G</span>) Economics</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Steward, Darlene M.</p> <p></p> <p>This report explores the critical elements of V<span class="hlt">2</span><span class="hlt">G</span> economics. Section <span class="hlt">2</span> summarizes the elements and costs of a V<span class="hlt">2</span><span class="hlt">G</span> system. Section 3 describes V<span class="hlt">2</span><span class="hlt">G</span> revenue-generating services and the business cases for providing these services. Section 4 notes real-world V<span class="hlt">2</span><span class="hlt">G</span> applications. Section 5 lists concerns related to V<span class="hlt">2</span><span class="hlt">G</span>. Section 6 concludes and summarizes V<span class="hlt">2</span><span class="hlt">G</span> cost and revenue elements.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24449714','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24449714"><span>Dosimetric verification for intensity-modulated arc therapy plans by use of <span class="hlt">2</span>D diode array, radiochromic film and <span class="hlt">radiosensitive</span> polymer gel.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hayashi, Naoki; Malmin, Ryan L; Watanabe, Yoichi</p> <p>2014-05-01</p> <p>Several tools are used for the dosimetric verification of intensity-modulated arc therapy (IMAT) treatment delivery. However, limited information is available for composite on-line evaluation of these tools. The purpose of this study was to evaluate the dosimetric verification of IMAT treatment plans using a <span class="hlt">2</span>D diode array detector (<span class="hlt">2</span>D array), radiochromic film (RCF) and <span class="hlt">radiosensitive</span> polymer gel dosimeter (RPGD). The specific verification plans were created for IMAT for two prostate cancer patients by use of the clinical treatment plans. Accordingly, the IMAT deliveries were performed with the <span class="hlt">2</span>D array on a gantry-mounting device, RCF in a cylindrical acrylic phantom, and the RPGD in two cylindrical phantoms. After the irradiation, the planar dose distributions from the <span class="hlt">2</span>D array and the RCFs, and the 3D dose distributions from the RPGD measurements were compared with the calculated dose distributions using the gamma analysis method (3% dose difference and 3-mm distance-to-agreement criterion), dose-dependent dose difference diagrams, dose difference histograms, and isodose distributions. The gamma passing rates of <span class="hlt">2</span>D array, RCFs and RPGD for one patient were 99.5%, 96.5% and 93.7%, respectively; the corresponding values for the second patient were 97.5%, 92.6% and 92.9%. Mean percentage differences between the RPGD measured and calculated doses in 3D volumes containing PTVs were -0.29 ± 7.1% and 0.97 ± 7.6% for the two patients, respectively. In conclusion, IMAT prostate plans can be delivered with high accuracy, although the 3D measurements indicated less satisfactory agreement with the treatment plans, mainly due to the dosimetric inaccuracy in low-dose regions of the RPGD measurements.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4967079','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4967079"><span>Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable <span class="hlt">radiosensitizers</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun</p> <p>2016-01-01</p> <p>Purpose: Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce <span class="hlt">radiosensitization</span> through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Methods: Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer to make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. Results: The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the 66Ga setting on a dose calibrator; activity decreased to <span class="hlt">2</span> μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (<span class="hlt">2</span>.05 × 106 counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27487895','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27487895"><span>Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable <span class="hlt">radiosensitizers</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun</p> <p>2016-08-01</p> <p>Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce <span class="hlt">radiosensitization</span> through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer to make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the (66)Ga setting on a dose calibrator; activity decreased to <span class="hlt">2</span> μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (<span class="hlt">2</span>.05 × 10(6) counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying (66)Ga</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22689406-development-bimetallic-zn-au-nanoparticles-potential-pet-imageable-radiosensitizers','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22689406-development-bimetallic-zn-au-nanoparticles-potential-pet-imageable-radiosensitizers"><span>Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable <span class="hlt">radiosensitizers</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Cho, Jongmin, E-mail: jongmin.cho@okstate.edu</p> <p>2016-08-15</p> <p>Purpose: Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce <span class="hlt">radiosensitization</span> through the secondary electrons produced from the gold shell when irradiated by various radiation sources. Methods: Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer tomore » make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays. Results: The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the {sup 66}Ga setting on a dose calibrator; activity decreased to <span class="hlt">2</span> μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (<span class="hlt">2</span>.05 × 10{sup 6} counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11287300','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11287300"><span>Frequency of sister-<span class="hlt">chromatid</span> exchange among greenhouse farmers exposed to pesticides.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shaham, J; Kaufman, Z; Gurvich, R; Levi, Z</p> <p>2001-04-05</p> <p>Sister-<span class="hlt">chromatid</span> exchange (SCE) was measured in peripheral lymphocytes of 104 greenhouse farmers exposed to pesticides and 44 unexposed workers. The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and, (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the farmers compared with the unexposed group (P < 0.01). Adjustment was made for smoking, age, education, and origin. The adjusted means of both SCE variables, were significantly elevated (P < 0.05) among the farmers who prepared and applied more than 70% of the pesticides by themselves compared with those who prepared and applied less than 70% of the pesticides by themselves. Both SCEs variables were also significantly elevated (P < 0.05) among farmers who were involved in more than 7.4 sprays per year compared with those with 7.4 or less sprays per year (P < 0.05). We found a tendency towards elevation of the two variables of SCEs among those who did not use protective measures while preparing the pesticides. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those farmers who were exposed to pesticides for more than 21 years than among those with less than 21 years of exposure. The variables that had the most influence on the elevation of SCEs were self-preparation of the pesticide mixtures and the number of sprayings per year. Because the farmers used a mixture of almost 24 different chemical classes it was impossible to attribute exposure to a specific pesticide or group of pesticides to single farmers. Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in greenhouse farmers indicates a potential cytogenetic hazard due to pesticides exposure.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015PMB....60.6719G','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015PMB....60.6719G"><span>Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-<span class="hlt">radiosensitivity</span>, increased radioresistance</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Gordon, J. J.; Snyder, K.; Zhong, H.; Barton, K.; Sun, Z.; Chetty, I. J.; Matuszak, M.; Ten Haken, R. K.</p> <p>2015-09-01</p> <p>In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence. Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade <span class="hlt">2</span> plus (<span class="hlt">G</span><span class="hlt">2</span>+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with <span class="hlt">G</span><span class="hlt">2</span>+ RP. Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-<span class="hlt">radiosensitivity</span> / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model. A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5576499','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5576499"><span>RK-33 <span class="hlt">Radiosensitizes</span> Prostate Cancer Cells by Blocking the RNA Helicase DDX3</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xie, Min; Vesuna, Farhad; Tantravedi, Saritha; Bol, Guus M.; Heerma van Voss, Marise R.; Nugent, Katriana; Malek, Reem; Gabrielson, Kathleen; van Diest, Paul J.; Tran, Phuoc T.; Raman, Venu</p> <p>2017-01-01</p> <p>Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. RK-33 treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) decreased proliferation and induced a <span class="hlt">G</span>1 phase cell-cycle arrest. Conversely, the low DDX3–expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a <span class="hlt">radiosensitizer</span>. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer. PMID:27634756</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6714357-immunosuppression-hypoxic-cell-radiosensitizers-phenomenon-potential-clinical-importance','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6714357-immunosuppression-hypoxic-cell-radiosensitizers-phenomenon-potential-clinical-importance"><span>Immunosuppression by hypoxic cell <span class="hlt">radiosensitizers</span>: a phenomenon of potential clinical importance</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Rockwell, S.; Kapp, D.S.</p> <p>1982-06-01</p> <p>The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of <span class="hlt">radiosensitizing</span> doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazolesmore » - the inhibition of cell-mediated immune responses. (JMT)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AIPC.1904b0071R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AIPC.1904b0071R"><span>Optimization of chromatographic conditions for determination of aflatoxin B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> by using liquid chromatography-mass Spectrometry</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ramadhaningtyas, Dillani Putri; Aryana, Nurhani; Aristiawan, Yosi; Styarini, Dyah</p> <p>2017-11-01</p> <p>The optimization of instrument condition and chromatographic separation for analysis of aflatoxin B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> using liquid chromatography tandem with mass spectrometer detector was conducted in the aim to provide more accurate and reliable analysis results. The aflatoxin known to be serious threat for human health as it is classified as the carcinogenic compounds. The aflatoxin B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> were selected due to its extensive contamination in various agricultural commodities. The best chromatographic separation was obtained using C-18 column with gradient elution of solvent 5 mM ammonium acetate and 0.1% formic acid in methanol at 7 minutes runtime analysis. The linearity of the detector showed satisfied results as the coefficient determination found to be 0.9994, 0.9996, 0.9998 and 0.9987 for aflatoxin B1, <span class="hlt">G</span>1, B<span class="hlt">2</span>, and <span class="hlt">G</span><span class="hlt">2</span> respectively in the range concentration from 1 to 20 ng/<span class="hlt">g</span>. The quantifier ion selected for the aflatoxin B1, B<span class="hlt">2</span>, <span class="hlt">G</span>1 and <span class="hlt">G</span><span class="hlt">2</span> was m/z 285.1, 259, 243 and 313 respectively. The instrument precision at these quantifier ions also showed satisfied result with %RSD was around 3.4 to 6.8%. The optimized method present in this study can be used for further sample analysis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26286029','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26286029"><span>VE-821, an ATR inhibitor, causes <span class="hlt">radiosensitization</span> in human tumor cells irradiated with high LET radiation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fujisawa, Hiroshi; Nakajima, Nakako Izumi; Sunada, Shigeaki; Lee, Younghyun; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi</p> <p>2015-08-19</p> <p>High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U<span class="hlt">2</span>OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of <span class="hlt">G</span><span class="hlt">2</span>/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor <span class="hlt">radiosensitizer</span> with carbon ion irradiation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title10-vol1/pdf/CFR-2011-title10-vol1-sec2-700.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title10-vol1/pdf/CFR-2011-title10-vol1-sec2-700.pdf"><span>10 CFR <span class="hlt">2</span>.700 - Scope of subpart <span class="hlt">G</span>.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-01-01</p> <p>... 10 Energy 1 2011-01-01 2011-01-01 false Scope of subpart <span class="hlt">G</span>. <span class="hlt">2</span>.700 Section <span class="hlt">2</span>.700 Energy NUCLEAR... Formal Adjudications § <span class="hlt">2</span>.700 Scope of subpart <span class="hlt">G</span>. The provisions of this subpart apply to and supplement... authorization for high-level radioactive waste repository noticed under §§ <span class="hlt">2</span>.101(f)(8) or <span class="hlt">2</span>.105(a)(5...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1990CP....142..445B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1990CP....142..445B"><span>Excitation of O <span class="hlt">2</span>(a 1Δ <span class="hlt">g</span>, b 1Σ <span class="hlt">g</span>+) and I( <span class="hlt">2</span>P 1/<span class="hlt">2</span>) by energy transfer from I <span class="hlt">2</span>(A, A' 3Π 1,<span class="hlt">2</span>u) in solid rare gases</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Böhling, R.; Becker, A. C.; Minaev, B. F.; Seranski, K.; Schurath, U.</p> <p>1990-04-01</p> <p>O <span class="hlt">2</span>a 1Δ <span class="hlt">g</span>, b 1Σ <span class="hlt">g</span>+ → X 3Σ <span class="hlt">g</span>- and I <span class="hlt">2</span>P 1/<span class="hlt">2</span>→ <span class="hlt">2</span>P 3/4 fluorescence occurs in I <span class="hlt">2</span>/O <span class="hlt">2</span>-doped rare gas matrices when I <span class="hlt">2</span> is excited with visible laser light. O <span class="hlt">2</span>(a 1Δ <span class="hlt">g</span>) and I( <span class="hlt">2</span>P 1/<span class="hlt">2</span>) are populated independently by near-resonant energy transfer from the metastable triplet states of I <span class="hlt">2</span>. The doublet splitting of the O <span class="hlt">2</span>a→X band, which peaks at 7879 and 7863 cm -1 in argon, is interpreted as sensitized emission from O <span class="hlt">2</span> trapped in distinct nearest neighbour positions of the donor 3I <span class="hlt">2</span>. Annealing reverses the intensity of the doublet, showing that the sites can be interconverted. It is suggested that the a→X emission rate is enhanced by the sensitizer, causing a lifetime reduction of the a 1Δ <span class="hlt">g</span> state from 79 s in pure argon to 21 and 3±1 s next to I <span class="hlt">2</span>. The long-lived O <span class="hlt">2</span>(a 1Δ <span class="hlt">g</span>) state is the precursor of I <span class="hlt">2</span>-sensitized emission from O <span class="hlt">2</span>(b 1Σ <span class="hlt">g</span>+). The lifetime of O <span class="hlt">2</span>(b 1Σ <span class="hlt">g</span>+) is reduced from 24.5 ms in pure argon to 17±1 ms in the presence of I <span class="hlt">2</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26722033','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26722033"><span><span class="hlt">Radiosensitivity</span> of Prostate Cancer Cell Lines for Irradiation from Beta Particle-emitting Radionuclide ¹⁷⁷Lu Compared to Alpha Particles and Gamma Rays.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Elgqvist, Jörgen; Timmermand, Oskar Vilhelmsson; Larsson, Erik; Strand, Sven-Erik</p> <p>2016-01-01</p> <p>The purpose of the present study was to investigate the <span class="hlt">radiosensitivity</span> of the prostate cancer cell lines LNCaP, DU145, and PC3 when irradiated with beta particles emitted from (177)Lu, and to compare the effect with irradiation using alpha particles or gamma rays. Cells were irradiated with beta particles emitted from (177)Lu, alpha particles from (241)Am, or gamma rays from (137)Cs. A non-specific polyclonal antibody was labeled with (177)Lu and used to irradiate cells in suspension with beta particles. A previously described in-house developed alpha-particle irradiator based on a (241)Am source was used to irradiate cells with alpha particles. External gamma-ray irradiation was achieved using a standard (137)Cs irradiator. Cells were irradiated to absorbed doses equal to 0, 0.5, 1, <span class="hlt">2</span>, 4, 6, 8, or 10 Gy. The absorbed doses were calculated as mean absorbed doses. For evaluation of cell survival, the tetrazolium-based WST-1 assay was used. After irradiation, WST-1 was added to the cell solutions, incubated, and then measured for level of absorbance at 450 nm, indicating the live and viable cells. LNCaP, DU145, and PC3 cell lines all had similar patterns of survival for the different radiation types. No significant difference in surviving fractions were observed between cells treated with beta-particle and gamma-ray irradiation, represented for example by the surviving fraction values (mean±SD) at <span class="hlt">2</span>, 6, and 10 Gy (SF<span class="hlt">2</span>, SF6, and SF10) for DU145 after beta-particle irradiation: 0.700±0.090, 0.186±0.050 and 0.056±0.010, respectively. A strong <span class="hlt">radiosensitivity</span> to alpha particles was observed, with SF<span class="hlt">2</span> values of 0.048±0.008, 0.018±0.006 and 0.015±0.005 for LNCaP, DU145, and PC3, respectively. The surviving fractions after irradiation using beta particles or gamma rays did not differ significantly at the absorbed dose levels and dose rates used. Irradiation using alpha particles led to a high level of cell killing. The results show that the beta-particle emitter</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3823782','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3823782"><span>The role of nitric oxide radicals in removal of hyper-<span class="hlt">radiosensitivity</span> by priming irradiation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Edin, Nina Jeppesen; Sandvik, Joe Alexander; Vollan, Hilde Synnøve; Reger, Katharina; Görlach, Agnes; Pettersen, Erik Olai</p> <p>2013-01-01</p> <p>In this study, a mechanism in which low-dose hyper-<span class="hlt">radiosensitivity</span> (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.<span class="hlt">2</span>–0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98<span class="hlt">G</span>) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation. PMID:23685670</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3418072','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3418072"><span>Selective cytotoxicity of PAMAM <span class="hlt">G</span>5 core–PAMAM <span class="hlt">G</span><span class="hlt">2</span>.5 shell tecto-dendrimers on melanoma cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Schilrreff, Priscila; Mundiña-Weilenmann, Cecilia; Romero, Eder Lilia; Morilla, Maria Jose</p> <p>2012-01-01</p> <p>Background The controlled introduction of covalent linkages between dendrimer building blocks leads to polymers of higher architectural order known as tecto-dendrimers. Because of the few simple steps involved in their synthesis, tecto-dendrimers could expand the portfolio of structures beyond commercial dendrimers, due to the absence of synthetic drawbacks (large number of reaction steps, excessive monomer loading, and lengthy chromatographic separations) and structural constraints of high-generation dendrimers (reduction of good monodispersity and ideal dendritic construction due to de Gennes dense-packing phenomenon). However, the biomedical uses of tecto-dendrimers remain unexplored. In this work, after synthesizing saturated shell core–shell tecto-dendrimers using amine-terminated polyamidoamine (PAMAM) generation 5 (<span class="hlt">G</span>5) as core and carboxyl-terminated PAMAM <span class="hlt">G</span><span class="hlt">2</span>.5 as shell (<span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 tecto-dendrimers), we surveyed for the first time the main features of their interaction with epithelial cells. Methods Structural characterization of <span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 was performed by polyacrylamide gel electrophoresis, matrix-assisted laser desorption time-of-flight mass spectrometry, and microscopic techniques; their hydrodynamic size and Z-potential was also determined. Cellular uptake by human epidermal keratinocytes, colon adenocarcinoma, and epidermal melanoma (SK-Mel-28) cells was determined by flow cytometry. Cytotoxicity was determined by mitochondrial activity, lactate dehydrogenase release, glutathione depletion, and apoptosis/necrosis measurement. Results The resultant 60%–67% saturated shell, 87,000-dalton <span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 (mean molecular weight) interacted with cells in a significantly different fashion in comparison to their building blocks and to its closest counterpart, PAMAM <span class="hlt">G</span>6.5. After being actively taken up by epithelial cells, <span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 caused cytotoxicity only on SK-Mel-28 cells, including depletion of intracellular glutathione and fast necrosis that was manifested above 5 μM <span class="hlt">G</span>5</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.osti.gov/sciencecinema/biblio/1259518','SCIGOVIMAGE-SCICINEMA'); return false;" href="http://www.osti.gov/sciencecinema/biblio/1259518"><span>Muon <span class="hlt">g</span>-<span class="hlt">2</span> Experiment Shimming</span></a></p> <p><a target="_blank" href="http://www.osti.gov/sciencecinema/">ScienceCinema</a></p> <p>Kiburg, Brendan</p> <p>2018-01-16</p> <p>The Muon <span class="hlt">g</span>-<span class="hlt">2</span> experiment at Fermilab will use as its primary instrument a 52-foot-wide electromagnet that creates a precise magnetic field. In this video, Fermilab's Brendan Kiburg explains the lengthy process of finely "shimming" that magnetic field into shape.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29280499','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29280499"><span><span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 core-shell tecto-dendrimer specifically targets reactive glia in brain ischemia.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Murta, Veronica; Schilrreff, Priscila; Rosciszewski, Gerardo; Morilla, Maria Jose; Ramos, Alberto Javier</p> <p>2018-03-01</p> <p>Secondary neuronal death is a serious stroke complication. This process is facilitated by the conversion of glial cells to the reactive pro-inflammatory phenotype that induces neurodegeneration. Therefore, regulation of glial activation is a compelling strategy to reduce brain damage after stroke. However, drugs have difficulties to access the CNS, and to specifically target glial cells. In the present work, we explored the use core-shell polyamidoamine tecto-dendrimer (<span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 PAMAM) and studied its ability to target distinct populations of stroke-activated glial cells. We found that <span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 tecto-dendrimer is actively engulfed by primary glial cells in a time- and dose-dependent manner showing high cellular selectivity and lysosomal localization. In addition, oxygen-glucose deprivation or lipopolysaccharides exposure in vitro and brain ischemia in vivo increase glial <span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 uptake; not being incorporated by neurons or other cell types. We conclude that <span class="hlt">G</span>5<span class="hlt">G</span><span class="hlt">2</span>.5 tecto-dendrimer is a highly suitable carrier for targeted drug delivery to reactive glial cells in vitro and in vivo after brain ischemia. © 2017 International Society for Neurochemistry.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25961455','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25961455"><span>Hypoxia-induced p53 modulates both apoptosis and <span class="hlt">radiosensitivity</span> via AKT.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Leszczynska, Katarzyna B; Foskolou, Iosifina P; Abraham, Aswin G; Anbalagan, Selvakumar; Tellier, Céline; Haider, Syed; Span, Paul N; O'Neill, Eric E; Buffa, Francesca M; Hammond, Ester M</p> <p>2015-06-01</p> <p>Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive. Here, we demonstrated that hypoxia-induced p53-dependent apoptosis is reliant on the DNA-binding and transactivation domains of p53 but not on the acetylation sites K120 and K164, which, in contrast, are essential for DNA damage-induced, p53-dependent apoptosis. Evaluation of hypoxia-induced transcripts in multiple cell lines identified a group of genes that are hypoxia-inducible proapoptotic targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D), pleckstrin domain-containing A3 (PHLDA3), sulfatase <span class="hlt">2</span> (SULF<span class="hlt">2</span>), B cell translocation gene <span class="hlt">2</span> (BTG<span class="hlt">2</span>), cytoplasmic FMR1-interacting protein <span class="hlt">2</span> (CYFIP<span class="hlt">2</span>), and KN motif and ankyrin repeat domains 3 (KANK3). These targets were also regulated by p53 in human cancers, including breast, brain, colorectal, kidney, bladder, and melanoma cancers. Downregulation of these hypoxia-inducible targets associated with poor prognosis, suggesting that hypoxia-induced apoptosis contributes to p53-mediated tumor suppression and treatment response. Induction of p53 targets, PHLDA3, and a specific INPP5D transcript mediated apoptosis in response to hypoxia through AKT inhibition. Moreover, pharmacological inhibition of AKT led to apoptosis in the hypoxic regions of p53-deficient tumors and consequently increased <span class="hlt">radiosensitivity</span>. Together, these results identify mediators of hypoxia-induced p53-dependent apoptosis and suggest AKT inhibition may improve radiotherapy response in p53-deficient tumors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4497762','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4497762"><span>Hypoxia-induced p53 modulates both apoptosis and <span class="hlt">radiosensitivity</span> via AKT</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Leszczynska, Katarzyna B.; Foskolou, Iosifina P.; Abraham, Aswin G.; Anbalagan, Selvakumar; Tellier, Céline; Haider, Syed; Span, Paul N.; O’Neill, Eric E.; Buffa, Francesca M.; Hammond, Ester M.</p> <p>2015-01-01</p> <p>Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive. Here, we demonstrated that hypoxia-induced p53-dependent apoptosis is reliant on the DNA-binding and transactivation domains of p53 but not on the acetylation sites K120 and K164, which, in contrast, are essential for DNA damage–induced, p53-dependent apoptosis. Evaluation of hypoxia-induced transcripts in multiple cell lines identified a group of genes that are hypoxia-inducible proapoptotic targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D), pleckstrin domain–containing A3 (PHLDA3), sulfatase <span class="hlt">2</span> (SULF<span class="hlt">2</span>), B cell translocation gene <span class="hlt">2</span> (BTG<span class="hlt">2</span>), cytoplasmic FMR1-interacting protein <span class="hlt">2</span> (CYFIP<span class="hlt">2</span>), and KN motif and ankyrin repeat domains 3 (KANK3). These targets were also regulated by p53 in human cancers, including breast, brain, colorectal, kidney, bladder, and melanoma cancers. Downregulation of these hypoxia-inducible targets associated with poor prognosis, suggesting that hypoxia-induced apoptosis contributes to p53-mediated tumor suppression and treatment response. Induction of p53 targets, PHLDA3, and a specific INPP5D transcript mediated apoptosis in response to hypoxia through AKT inhibition. Moreover, pharmacological inhibition of AKT led to apoptosis in the hypoxic regions of p53-deficient tumors and consequently increased <span class="hlt">radiosensitivity</span>. Together, these results identify mediators of hypoxia-induced p53-dependent apoptosis and suggest AKT inhibition may improve radiotherapy response in p53-deficient tumors. PMID:25961455</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1996PMB....41..205S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1996PMB....41..205S"><span>DOUGLAS LEA MEMORIAL LECTURE: From targets to genes: a brief history of <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Steel, G. Gordon</p> <p>1996-02-01</p> <p>The biological work of Douglas Lea spanned the period from 1934 to his early death in 1947, and during this short period he made important contributions to the theory of radiation action. He interpreted experimental data relating to the effects of radiation on viruses, bacteria, bean roots, etc in terms of the inactivation of discrete targets, which he identified with cellular genes. He thus laid the foundation of much subsequent research. It is now well recognized that mammalian cells differ substantially in <span class="hlt">radiosensitivity</span>, especially in the low-dose region of the survival curve. The dependence of <span class="hlt">radiosensitivity</span> on dose rate has been widely studied; this has practical significance for clinical radiotherapy as well as mechanistic implications. Since Lea's time there have been a number of efforts to describe models that can relate cell killing to radiation dose, dose rate, and track structure. So far these have not led to a comprehensive and widely accepted picture. Microdosimetric considerations lead to the concept of differing severity of lesions induced in DNA. Much is known about the sequence of processes that subsequently lead to cell inactivation: this can be divided into phases of induction, processing, and manifestation. Chromosomal events are currently attracting much attention, as they did in Lea's time. Considerable progress has also been made in identifying genes that control the repair of radiation damage. It has been found that mutation is frequently associated with the loss of a large segment of the genome around the damage site and this will have important implications for interactive processes between particle tracks.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29888014','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29888014"><span>Runaway Train: A Leaky <span class="hlt">Radiosensitive</span> SCID with Skin Lesions and Multiple Lymphomas.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fevang, Børre; Fagerli, Unn Merete; Sorte, Hanne; Aarset, Harald; Hov, Håkon; Langmyr, Marit; Keil, Thomas Morten; Bjørge, Ellen; Aukrust, Pål; Stray-Pedersen, Asbjørg; Gedde-Dahl, Tobias</p> <p>2018-01-01</p> <p>The nuclease Artemis is essential for the development of T-cell and B-cell receptors and repair of DNA double-strand breaks, and a loss of expression or function will lead to a <span class="hlt">radiosensitive</span> severe combined immunodeficiency with no functional T-cells or B-cells (T-B-SCID). Hypomorphic mutations in the Artemis gene can lead to a functional, but reduced, T-cell and B-cell repertoire with a more indolent clinical course called "leaky" SCID. Here, we present the case of a young man who had increasingly aggressive lymphoproliferative skin lesions from <span class="hlt">2</span> years of age which developed into multiple EBV+ B-cell lymphomas, where a hypomorphic mutation in the Artemis gene was found in a diagnostic race against time using whole exome sequencing. The patient was given a haploidentical stem cell transplant while in remission for his lymphomas and although the initial course was successful, he succumbed to a serious Pneumocystis jirovecii pneumonia 5 months after the transplant. The case underscores the importance of next-generation sequencing in the diagnosis of patients with suspected severe immunodeficiency.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29860067','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29860067"><span>Identification of a novel antisense long non-coding RNA PLA<span class="hlt">2</span><span class="hlt">G</span>16-AS that regulates the expression of PLA<span class="hlt">2</span><span class="hlt">G</span>16 in pigs.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Liu, Pengliang; Jin, Long; Zhao, Lirui; Long, Keren; Song, Yang; Tang, Qianzi; Ma, Jideng; Wang, Xun; Tang, Guoqing; Jiang, Yanzhi; Zhu, Li; Li, Xuewei; Li, Mingzhou</p> <p>2018-05-31</p> <p>Natural antisense transcripts (NATs) are widely present in mammalian genomes and act as pivotal regulator molecules to control gene expression. However, studies on the NATs of pigs are relatively rare. Here, we identified a novel antisense transcript, designated PLA<span class="hlt">2</span><span class="hlt">G</span>16-AS, transcribed from the phospholipase A<span class="hlt">2</span> group XVI locus (PLA<span class="hlt">2</span><span class="hlt">G</span>16) in the porcine genome, which is a well-known regulatory molecule of fat deposition. PLA<span class="hlt">2</span><span class="hlt">G</span>16-AS and PLA<span class="hlt">2</span><span class="hlt">G</span>16 were dominantly expressed in porcine adipose tissue, and were differentially expressed between Tibetan pigs and Rongchang pigs. In addition, PLA<span class="hlt">2</span><span class="hlt">G</span>16-AS has a weak sequence conservation among different vertebrates. PLA<span class="hlt">2</span><span class="hlt">G</span>16-AS was also shown to form an RNA-RNA duplex with PLA<span class="hlt">2</span><span class="hlt">G</span>16, and to regulate PLA<span class="hlt">2</span><span class="hlt">G</span>16 expression at the mRNA level. Moreover, the overexpression of PLA<span class="hlt">2</span><span class="hlt">G</span>16-AS increased the stability of PLA<span class="hlt">2</span><span class="hlt">G</span>16 mRNA in porcine cells. We envision that our findings of a NAT for a regulatory gene associated with lipolysis might further our understanding of the molecular regulation of fat deposition. Copyright © 2017. Published by Elsevier B.V.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2002NuPhB.620....3C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2002NuPhB.620....3C"><span>Supersymmetric M3-branes and <span class="hlt">G</span><span class="hlt">2</span> manifolds</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Cvetič, M.; Gibbons, G. W.; Lü, H.; Pope, C. N.</p> <p>2002-01-01</p> <p>We obtain a generalisation of the original complete Ricci-flat metric of <span class="hlt">G</span><span class="hlt">2</span> holonomy on R4×S 3 to a family with a nontrivial parameter λ. For generic λ the solution is singular, but it is regular when λ={-1,0,+1}. The case λ=0 corresponds to the original <span class="hlt">G</span><span class="hlt">2</span> metric, and λ={-1,1} are related to this by an S3 automorphism of the SU(<span class="hlt">2</span>) 3 isometry group that acts on the S3× S3 principal orbits. We then construct explicit supersymmetric M3-brane solutions in D=11 supergravity, where the transverse space is a deformation of this class of <span class="hlt">G</span><span class="hlt">2</span> metrics. These are solutions of a system of first-order differential equations coming from a superpotential. We also find M3-branes in the deformed backgrounds of new <span class="hlt">G</span><span class="hlt">2</span> holonomy metrics that include one found by A. Brandhuber, J. Gomis, S. Gubser and S. Gukov, and show that they also are supersymmetric.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_23 --> <div id="page_24" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="461"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17089052','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17089052"><span>The PCC assay can be used to predict <span class="hlt">radiosensitivity</span> in biopsy cultures irradiated with different types of radiation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Suzuki, Masao; Tsuruoka, Chizuru; Nakano, Takashi; Ohno, Tatsuya; Furusawa, Yoshiya; Okayasu, Ryuichi</p> <p>2006-12-01</p> <p>The aim of this study was to identify potential biomarkers for <span class="hlt">radiosensitivity</span> using the relationship between cell killing and the yield of excess chromatin fragments detected with the premature chromosome condensation (PCC) technique. This method was applied to primary cultured cells obtained from biopsies from patients. Six primary culture biopsies were obtained from 6 patients with carcinoma of the cervix before starting radiotherapy. The cultures were irradiated with two different LET carbon-ion beams (LET = 13 keV/microm, 77.1+/-<span class="hlt">2</span>.8 keV/microm) and 200 kV X-rays. The carbon-ion beams were produced by Heavy Ion Medical Accelerator in Chiba (HIMAC). PCC was performed using the polyethylene glycol-mediated cell fusion technique. The yield of excess chromatin fragments were measured by counting the number of unrejoined chromatin fragments detected with the PCC technique after a 24-h post-irradiation incubation period. Obtained results indicated that cultures which were more sensitive to killing were also more susceptible to the induction of excess chromatin fragments. Furthermore there was a good correlation between cell killing and excess chromatin fragments among the 6 cell cultures examined. There is also evidence that the induction of excess chromatin fragments increased with increasing LET as well as cell-killing effect in the same cell culture. The data reported here support the idea that the yield of excess chromatin fragments detected with the PCC technique might be useful for predicting the <span class="hlt">radiosensitivity</span> of cells contained in tumor tissue, and to predict responses to different radiation types.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017JPhCS.784a2009E','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017JPhCS.784a2009E"><span>Nuclear 3D organization and <span class="hlt">radiosensitivity</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Eidelman, Y. A.; Slanina, S. V.; Aleshchenko, A. V.; Sen'ko, O. V.; Kononkova, A. D.; Andreev, S. G.</p> <p>2017-01-01</p> <p>Current mechanisms of radiation-induced chromosomal aberration (CA) formation suggest misrepair of chromosomal lesions being in spatial proximity. In this case CAs have to depend on pattern of chromosomal contacts and on chromosome spatial organization in a cell nucleus. We were interested in whether variation of nucleus 3D organization results in difference of radiation induced CA formation frequency. Experimental data available do not provide information sufficient for definite conclusions. To have more deep insight in this issue we developed the biophysical modeling technique taking into account different levels of chromosome/nuclear organization and radiation damage of DNA and chromosomes. Computer experiments on gamma irradiation were carried out for two types of cells with different 3D organization of nuclei, preferentially peripheral and internal. CA frequencies were found to depend on spatial positioning of chromosomes within a nucleus which determines a pattern of interchromosomal contacts. For individual chromosomes this effect can be more pronounced than for genome averaged. Since significant part of aberrations, for example dicentrics, results in cell death, the proposed technique is capable of evaluating <span class="hlt">radiosensitivity</span> of cells, both normal and cancer, with the incorporation of 3D genome information. This predictive technology allows to reduce uncertainties of prognosis of biological effects of radiation compared to phenomenological methods and may have variety of biomedical applications, in particular, in cancer radiation therapy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22364634-galactic-center-cloud-g2-its-gas-streamer','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22364634-galactic-center-cloud-g2-its-gas-streamer"><span>THE GALACTIC CENTER CLOUD <span class="hlt">G</span><span class="hlt">2</span> AND ITS GAS STREAMER</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Pfuhl, Oliver; Gillessen, Stefan; Eisenhauer, Frank</p> <p>2015-01-10</p> <p>We present new, deep near-infrared SINFONI @ VLT integral field spectroscopy of the gas cloud <span class="hlt">G</span><span class="hlt">2</span> in the Galactic Center, from late 2013 August, 2014 April, and 2014 July. <span class="hlt">G</span><span class="hlt">2</span> is visible in recombination line emission. The spatially resolved kinematic data track the ongoing tidal disruption. The cloud reached minimum distance to the MBH of 1950 Schwarzschild radii. As expected for an observation near the pericenter passage, roughly half of the gas in 2014 is found at the redshifted, pre-pericenter side of the orbit, while the other half is at the post-pericenter, blueshifted side. We also present an orbital solutionmore » for the gas cloud <span class="hlt">G</span>1, which was discovered a decade ago in L'-band images when it was spatially almost coincident with Sgr A*. The orientation of the <span class="hlt">G</span>1 orbit in the three angles is almost identical to that of <span class="hlt">G</span><span class="hlt">2</span>, but it has a lower eccentricity and smaller semi-major axis. We show that the observed astrometric positions and radial velocities of <span class="hlt">G</span>1 are compatible with the <span class="hlt">G</span><span class="hlt">2</span> orbit, assuming that (1) <span class="hlt">G</span>1 was originally on the <span class="hlt">G</span><span class="hlt">2</span> orbit preceding <span class="hlt">G</span><span class="hlt">2</span> by 13 yr, and (<span class="hlt">2</span>) a simple drag force acted on it during pericenter passage. Taken together with the previously described tail of <span class="hlt">G</span><span class="hlt">2</span>, which we detect in recombination line emission and thermal broadband emission, we propose that <span class="hlt">G</span><span class="hlt">2</span> may be a bright knot in a much more extensive gas streamer. This matches purely gaseous models for <span class="hlt">G</span><span class="hlt">2</span>, such as a stellar wind clump or the tidal debris from a partial disruption of a star.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1976452','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1976452"><span><span class="hlt">G</span>-quadruplex induced stabilization by <span class="hlt">2</span>′-deoxy-<span class="hlt">2</span>′-fluoro-d-arabinonucleic acids (<span class="hlt">2</span>′F-ANA)</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Peng, Chang Geng; Damha, Masad J.</p> <p>2007-01-01</p> <p>The impact of <span class="hlt">2</span>′-deoxy-<span class="hlt">2</span>′-fluoroarabinonucleotide residues (<span class="hlt">2</span>′F-araN) on different <span class="hlt">G</span>-quadruplexes derived from a thrombin-binding DNA aptamer d(<span class="hlt">G</span><span class="hlt">2</span>T<span class="hlt">2</span><span class="hlt">G</span><span class="hlt">2</span>TGTG<span class="hlt">2</span>T<span class="hlt">2</span><span class="hlt">G</span><span class="hlt">2</span>), an anti-HIV phosphorothioate aptamer PS-d(T<span class="hlt">2</span><span class="hlt">G</span>4T<span class="hlt">2</span>) and a DNA telomeric sequence d(<span class="hlt">G</span>4T4<span class="hlt">G</span>4) via UV thermal melting (Tm) and circular dichroism (CD) experiments has been investigated. Generally, replacement of deoxyguanosines that adopt the anti conformation (anti-guanines) with <span class="hlt">2</span>′F-ara<span class="hlt">G</span> can stabilize <span class="hlt">G</span>-quartets and maintain the quadruplex conformation, while replacement of syn-guanines with <span class="hlt">2</span>′F-ara<span class="hlt">G</span> is not favored and results in a dramatic switch to an alternative quadruplex conformation. It was found that incorporation of <span class="hlt">2</span>′F-ara<span class="hlt">G</span> or T residues into a thrombin-binding DNA <span class="hlt">G</span>-quadruplex stabilizes the complex (ΔTm up to ∼+3°C/<span class="hlt">2</span>′F-araN modification); <span class="hlt">2</span>′F-araN units also increased the half-life in 10% fetal bovine serum (FBS) up to 48-fold. Two modified thrombin-binding aptamers (PG13 and PG14) show an approximately 4-fold increase in binding affinity to thrombin, as assessed via a nitrocellulose filter binding assay, both with increased thermal stability (∼1°C/<span class="hlt">2</span>′F-ANA modification increase in Tm) and nuclease resistance (4–7-fold) as well. Therefore, the <span class="hlt">2</span>′-deoxy-<span class="hlt">2</span>′-fluoro-d-arabinonucleic acid (<span class="hlt">2</span>′F-ANA) modification is well suited to tune (and improve) the physicochemical and biological properties of naturally occurring DNA <span class="hlt">G</span>-quartets. PMID:17636049</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28053929','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28053929"><span>Association of COX-<span class="hlt">2</span> Promoter Polymorphisms -765<span class="hlt">G</span>/C and -1195A/<span class="hlt">G</span> with Migraine.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mozaffari, Elahe; Doosti, Abbas; Arshi, Asghar; Faghani, Mostafa</p> <p>2016-12-01</p> <p>Migraine is a common debilitating primary headache disorder with current head pain attacks, which contributes to physical activity dysfunctions in chronic pain phase. PGE<span class="hlt">2</span> and PGI<span class="hlt">2</span> are two important prostaglandins synthesised by COX-<span class="hlt">2</span> enzymes, involved in migraine pain signals. COX-<span class="hlt">2</span> modulation is essential in treatment and pathogenesis of migraine. This study aimed to investigating the association between COX-<span class="hlt">2</span> gene polymorphisms with the risk of migraine susceptibility in migraine patients with related and unrelated parents. This case- control study was based on 100 migraine patients and 100 non-migraine subjects in Bushehr province, Iran in 2013. Genomic DNA of blood samples was extracted and genotyping of COX-<span class="hlt">2</span>-765<span class="hlt">G</span>>C (rs20417) and COX-<span class="hlt">2</span>-1195A><span class="hlt">G</span> (rs689466) gene variants was investigated by PCR-RFLP method. Statistical analyses were accomplished using the SPSS software package. There was a significant differences in the frequencies of the COX-<span class="hlt">2</span>-765<span class="hlt">G</span>>C and COX-<span class="hlt">2</span>-1195A><span class="hlt">G</span> genotypes between migraine patients and controls ( P ≤0.05). COX-<span class="hlt">2</span>-765CC , COX-<span class="hlt">2</span>-765CG , COX-<span class="hlt">2</span>-1195GG and COX-<span class="hlt">2</span>-1195AG genotypes can increase the risk of migraine significantly. As the first study in Iran, we are hopeful to achieve greater results about the relevancy of COX-<span class="hlt">2</span> gene, migraine and pain signals pathway by repeating these experiments on more samples.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011JChPh.135i4309P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011JChPh.135i4309P"><span>Collisional relaxation of O<span class="hlt">2</span>(X^3Σ _<span class="hlt">g</span>^ -, υ = 1) and O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) by atmospherically relevant species</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Pejaković, Dušan A.; Campbell, Zachary; Kalogerakis, Konstantinos S.; Copeland, Richard A.; Slanger, Tom G.</p> <p>2011-09-01</p> <p>Laboratory measurements are reported of the rate coefficient for collisional removal of O<span class="hlt">2</span>(X^3Σ _<span class="hlt">g</span>^ -, υ = 1) by O(3P), and the rate coefficients for removal of O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) by O<span class="hlt">2</span>, CO<span class="hlt">2</span>, and O(3P). A two-laser method is employed, in which the pulsed output of the first laser at 285 nm photolyzes ozone to produce oxygen atoms and O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1), and the output of the second laser detects O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) via resonance-enhanced multiphoton ionization. The kinetics of O<span class="hlt">2</span>(X^3Σ _<span class="hlt">g</span>^ -, υ = 1) + O(3P) relaxation is inferred from the temporal evolution of O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1), an approach enabled by the rapid collision-induced equilibration of the O<span class="hlt">2</span>(X^3Σ _<span class="hlt">g</span>^ -, υ = 1) and O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) populations in the system. The measured O<span class="hlt">2</span>(X^3Σ _<span class="hlt">g</span>^ -, υ = 1) + O(3P) rate coefficient is (<span class="hlt">2</span>.9 ± 0.6) × 10-12 cm3 s-1 at 295 K and (3.4 ± 0.6) × 10-12 cm3 s-1 at 240 K. These values are consistent with the previously reported result of (3.<span class="hlt">2</span> ± 1.0) × 10-12 cm3 s-1, which was obtained at 315 K using a different experimental approach [K. S. Kalogerakis, R. A. Copeland, and T. <span class="hlt">G</span>. Slanger, J. Chem. Phys. 123, 194303 (2005)]. For removal of O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) by O(3P), the upper limits for the rate coefficient are 4 × 10-13 cm3 s-1 at 295 K and 6 × 10-13 cm3 s-1 at 240 K. The rate coefficient for removal of O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) by O<span class="hlt">2</span> is (5.6 ± 0.6) × 10-11 cm3 s-1 at 295 K and (5.9 ± 0.5) × 10-11 cm3 s-1 at 240 K. The O<span class="hlt">2</span>(a1Δ<span class="hlt">g</span>, υ = 1) + CO<span class="hlt">2</span> rate coefficient is (1.5 ± 0.<span class="hlt">2</span>) × 10-14 cm3 s-1 at 295 K and (1.<span class="hlt">2</span> ± 0.1) × 10-14 cm3 s-1 at 240 K. The implications of the measured rate coefficients for modeling of atmospheric emissions are discussed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29372728','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29372728"><span>Ab initio and transition state theory study of the OH + HO<span class="hlt">2</span> → H<span class="hlt">2</span>O + O<span class="hlt">2</span>(3Σ<span class="hlt">g</span>-)/O<span class="hlt">2</span>(1Δ<span class="hlt">g</span>) reactions: yield and role of O<span class="hlt">2</span>(1Δ<span class="hlt">g</span>) in H<span class="hlt">2</span>O<span class="hlt">2</span> decomposition and in combustion of H<span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Monge-Palacios, M; Sarathy, S Mani</p> <p>2018-02-07</p> <p>Reactions of hydroxyl (OH) and hydroperoxyl (HO <span class="hlt">2</span> ) are important for governing the reactivity of combustion systems. We performed post-CCSD(T) ab initio calculations at the W3X-L//CCSD = FC/cc-pVTZ level to explore the triplet ground-state and singlet excited-state potential energy surfaces of the OH + HO <span class="hlt">2</span> → H <span class="hlt">2</span> O + O <span class="hlt">2</span> ( 3 Σ <span class="hlt">g</span> - )/O <span class="hlt">2</span> ( 1 Δ <span class="hlt">g</span> ) reactions. Using microcanonical and multistructural canonical transition state theories, we calculated the rate constant for the triplet and singlet channels over the temperature range 200-2500 K, represented by k(T) = 3.08 × 10 12 T 0.07  exp(1151/RT) + 8.00 × 10 12 T 0.32  exp(-6896/RT) and k(T) = <span class="hlt">2</span>.14 × 10 6 T 1.65  exp(-2180/RT) in cm 3 mol -1 s -1 , respectively. The branching ratios show that the yield of singlet excited oxygen is small (<0.5% below 1000 K). To ascertain the importance of singlet oxygen channel, our new kinetic information was implemented into the kinetic model for hydrogen combustion recently updated by Konnov (Combust. Flame, 2015, 162, 3755-3772). The updated kinetic model was used to perform H <span class="hlt">2</span> O <span class="hlt">2</span> thermal decomposition simulations for comparison against shock tube experiments performed by Hong et al. (Proc. Combust. Inst., 2013, 34, 565-571), and to estimate flame speeds and ignition delay times in H <span class="hlt">2</span> mixtures. The simulation predicted a larger amount of O <span class="hlt">2</span> ( 1 Δ <span class="hlt">g</span> ) in H <span class="hlt">2</span> O <span class="hlt">2</span> decomposition than that predicted by Konnov's original model. These differences in the O <span class="hlt">2</span> ( 1 Δ <span class="hlt">g</span> ) yield are due to the use of a higher ab initio level and a more sophisticated methodology to compute the rate constant than those used in previous studies, thereby predicting a significantly larger rate constant. No effect was observed on the rate of the H <span class="hlt">2</span> O <span class="hlt">2</span> decomposition and on the flame speeds and ignition delay times of different H <span class="hlt">2</span> -oxidizer mixtures. However, if the oxidizer is seeded with O 3 , small differences appear in the flame speed. Given that O <span class="hlt">2</span> ( 1 Δ <span class="hlt">g</span> ) is much more reactive than O</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22648621-radiosensitivity-patient-derived-glioma-stem-cell-dimensional-cultures-photon-proton-carbon-irradiation','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22648621-radiosensitivity-patient-derived-glioma-stem-cell-dimensional-cultures-photon-proton-carbon-irradiation"><span><span class="hlt">Radiosensitivity</span> of Patient-Derived Glioma Stem Cell 3-Dimensional Cultures to Photon, Proton, and Carbon Irradiation</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Chiblak, Sara; Tang, Zili; Molecular and Translational Radiation Oncology, Heidelberg Ion Therapy Center, Heidelberg Institute of Radiation Oncology, University of Heidelberg Medical School and National Center for Tumor Diseases, German Cancer Research Center, Heidelberg</p> <p></p> <p>Purpose: To investigate the <span class="hlt">radiosensitivity</span> of primary glioma stem cell (GSC) cultures with different CD133 status in a 3-dimensional (3D) model after photon versus proton versus carbon irradiation. Methods and Materials: Human primary GSC spheroid cultures were established from tumor specimens of six consented glioblastoma patients. Human U87MG was used as a classical glioblastoma radioresistant cell line. Cell suspensions were generated by mechanical dissociation of GSC spheroids and embedded in a semi-solid 3D matrix before irradiation. Spheroid-like colonies were manually counted by microscopy. Cells were also recovered and quantified by fluorescence. CD133 expression and DNA damage were evaluated by flow cytometry.more » Results: The fraction of CD133{sup +} cells varied between 0.014% and 96% in the six GSC cultures and showed a nonsignificant correlation with plating efficiency and survival fractions. The 4 most photon-radioresistant GSC cultures were NCH644, NCH421k, NCH441, and NCH636. Clonogenic survival for proton irradiation revealed relative biologic effectiveness (RBE) in the range of 0.7-1.20. However, carbon irradiation rendered the photon-resistant GSC cultures sensitive, with average RBE of 1.87-3.44. This effect was partly attributed to impaired capability of GSC to repair carbon ion–induced DNA double-strand breaks as determined by residual DNA repair foci. Interestingly, <span class="hlt">radiosensitivity</span> of U87 cells was comparable to GSC cultures using clonogenic survival as the standard readout. Conclusions: Carbon irradiation is effective in GSC eradication with similar RBE ranges approximately <span class="hlt">2</span>-3 as compared with non-stem GSC cultures (U87). Our data strongly suggest further exploration of GSC using classic radiobiology endpoints such as the here-used 3D clonogenic survival assay and integration of additional GSC-specific markers.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21587688-insulin-like-growth-factor-type-receptor-inhibitor-nvp-aew541-enhances-radiosensitivity-pten-wild-type-pten-deficient-human-prostate-cancer-cells','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21587688-insulin-like-growth-factor-type-receptor-inhibitor-nvp-aew541-enhances-radiosensitivity-pten-wild-type-pten-deficient-human-prostate-cancer-cells"><span>Insulin-Like Growth Factor-Type 1 Receptor Inhibitor NVP-AEW541 Enhances <span class="hlt">Radiosensitivity</span> of PTEN Wild-Type but Not PTEN-Deficient Human Prostate Cancer Cells</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Isebaert, Sofie F., E-mail: sofie.isebaert@med.kuleuven.be; Swinnen, Johannes V.; McBride, William H.</p> <p>2011-09-01</p> <p>Purpose: During the past decade, many clinical trials with both monoclonal antibodies and small molecules that target the insulin-like growth factor-type 1 receptor (IGF-1R) have been launched. Despite the important role of IGF-1R signaling in radioresistance, studies of such agents in combination with radiotherapy are lagging behind. Therefore, the aim of this study was to investigate the effect of the small molecule IGF-1R kinase inhibitor NVP-AEW541 on the intrinsic radioresistance of prostate cancer cells. Methods and Materials: The effect of NVP-AEW541 on cell proliferation, cell viability, IGF-1R signaling, <span class="hlt">radiosensitivity</span>, cell cycle distribution, and double strand break repair was determined inmore » three human prostate cancer cell lines (PC3, DU145, 22Rv1). Moreover, the importance of the PTEN pathway status was explored by means of transfection experiments with constitutively active Akt or inactive kinase-dead Akt. Results: NVP-AEW541 inhibited cell proliferation and decreased cell viability in a time-and dose-dependent manner in all three cell lines. <span class="hlt">Radiosensitization</span> was observed in the PTEN wild-type cell lines DU145 and 22Rv1 but not in the PTEN-deficient PC3 cell line. NVP-AEW541-induced <span class="hlt">radiosensitization</span> coincided with downregulation of phospho-Akt levels and high levels of residual double strand breaks. The importance of PTEN status in the <span class="hlt">radiosensitization</span> effect was confirmed by transfection experiments with constitutively active Akt or inactive kinase-dead Akt. Conclusions: NVP-AEW541 enhances the effect of ionizing radiation in PTEN wild-type, but not in PTEN-deficient, prostate cancer cells. Proper patient selection based on the PTEN status of the tumor will be critical to the achievement of optimal results in clinical trials in which the combination of radiotherapy and this IGF-1R inhibitor is being explored.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5579538','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5579538"><span>Conformational Dynamics Modulate Activation of the Ubiquitin Conjugating Enzyme Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2017-01-01</p> <p>The ubiquitin conjugating enzyme Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span> together with its cognate E3 ligase gp78 catalyzes the synthesis of lysine-48 polyubiquitin chains constituting signals for the proteasomal degradation of misfolded proteins in the endoplasmic reticulum. Here, we employ NMR spectroscopy in combination with single-turnover diubiquitin formation assays to examine the role of the RING domain from gp78 in the catalytic activation of Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span>∼Ub conjugates. We find that approximately 60% of the Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span>∼Ub conjugates occupy a closed conformation in the absence of gp78-RING, with the population increasing to 82% upon gp78-RING binding. As expected, strong mutations in the hydrophobic patch residues of the ∼Ub moiety result in Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span>∼Ub populating only open states with corresponding loss of the ubiquitin conjugation activity. Less disruptive mutations introduced into the hydrophobic patch of the ∼Ub moiety also destabilize the closed conformational state, yet the corresponding effect on the ubiquitin conjugation activity ranges from complete loss to an enhancement of the catalytic activity. These results present a picture in which Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span>’s active site is in a state of continual dynamic flux with the organization of the active site into a catalytically viable conformation constituting the rate-limiting step for a single ubiquitin ligation event. Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span>’s function as a highly specific K48-polyubiquitin chain elongator leads us to speculate that this may be a strategy by which Ube<span class="hlt">2</span><span class="hlt">g</span><span class="hlt">2</span> reduces the probability of nonproductive catalytic outcomes in the absence of available substrate. PMID:28884161</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3762617','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3762617"><span>Plasminogen activator inhibitor-1 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism is associated with type <span class="hlt">2</span> diabetes risk</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhao, Luqian; Huang, Ping</p> <p>2013-01-01</p> <p>A number of studies were performed to assess the association between plasminogen activator inhibitor-1 (PAI-1) 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism and susceptibility to type <span class="hlt">2</span> diabetes (T<span class="hlt">2</span>DM). However, the results were inconsistent and inconclusive. In the present study, the possible association was investigated by a meta-analysis. Eligible articles were identified for the period up to June 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models. Fourteen case-control studies with a total of 2487 cases and 3538 controls were eligible. In recessive model, PAI-1 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism was associated with T<span class="hlt">2</span>DM risk (OR = 1.23; 95% CI 1.07-1.41; P = 0.004). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR = 1.27; 95% CI 1.08-1.51; P = 0.005). This meta-analysis suggested that PAI-1 4<span class="hlt">G</span>/5<span class="hlt">G</span> polymorphism may be associated with T<span class="hlt">2</span>DM development. PMID:24040470</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=19990113086&qs=N%3D0%26Ntk%3DTitle%26Ntx%3Dmode%2Bmatchall%26Ntt%3DG','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=19990113086&qs=N%3D0%26Ntk%3DTitle%26Ntx%3Dmode%2Bmatchall%26Ntt%3DG"><span>Heterogeneous reactions of HNO3(<span class="hlt">g</span>) + NaCl(s) yields HCl(<span class="hlt">g</span>) + NaNO3(s) and N<span class="hlt">2</span>O5(<span class="hlt">g</span>) + NaCl(s) yields ClNO<span class="hlt">2</span>(<span class="hlt">g</span>) + NaNO3(s)</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Leu, Ming-Taun; Timonen, Raimo S.; Keyser, Leon F.; Yung, Yuk L.</p> <p>1995-01-01</p> <p>The heterogeneous reactions of HNO3(<span class="hlt">g</span>) + NaCl(s) yields HCl(<span class="hlt">g</span>) + NaNO3(s) (eq 1) and N<span class="hlt">2</span>O5(<span class="hlt">g</span>) + NaCl(s) yields ClNO<span class="hlt">2</span>(<span class="hlt">g</span>) + NaNO3(S) (eq <span class="hlt">2</span>) were investigated over the temperature range 223-296 K in a flow-tube reactor coupled to a quadrupole mass spectrometer. Either a chemical ionization mass spectrometer (CIMS) or an electron-impact ionization mass spectrometer (EIMS) was used to provide suitable detection sensitivity and selectivity. In order to mimic atmospheric conditions, partial pressures of HNO3 and N<span class="hlt">2</span>O5 in the range 6 x 10(exp -8) - <span class="hlt">2</span> x 10(exp -6) Torr were used. Granule sizes and surface roughness of the solid NaCl substrates were determined by using a scanning electron microscope. For dry NaCl substrates, decay rates of HNO3 were used to obtain gamma(1) = 0.013 +/- 0.004 (1sigma) at 296 K and > 0.008 at 223 K, respectively. The error quoted is the statistical error. After all corrections were made, the overall error, including systematic error, was estimated to be about a factor of <span class="hlt">2</span>. HCl was found to be the sole gas-phase product of reaction 1. The mechanism changed from heterogeneous reaction to predominantly physical adsorption when the reactor was cooled from 296 to 223 K. For reaction <span class="hlt">2</span> using dry salts, gamma(<span class="hlt">2</span>) was found to be less than 1.0 x 10(exp -4) at both 223 and 296 K. The gas-phase reaction product was identified as ClNO<span class="hlt">2</span> in previous studies using an infrared spectrometer. An enhancement in reaction probability was observed if water was not completely removed from salt surfaces, probably due to the reaction of N<span class="hlt">2</span>O5(<span class="hlt">g</span>) + H<span class="hlt">2</span>O(s) yields <span class="hlt">2</span>HNO3(<span class="hlt">g</span>). Our results are compared with previous literature values obtained using different experimental techniques and conditions. The implications of the present results for the enhancement of the hydrogen chloride column density in the lower stratosphere after the El Chichon volcanic eruption and for the chemistry of HCl and HNO3 in the marine troposphere are discussed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017NuPhB.920..157A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017NuPhB.920..157A"><span>BPS states in N = <span class="hlt">2</span> supersymmetric <span class="hlt">G</span><span class="hlt">2</span> and F4 models</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ahl Laamara, R.; Mellal, O.; Saidi, E. H.</p> <p>2017-07-01</p> <p>In BPS quiver theory of N = <span class="hlt">2</span> supersymmetric pure gauge models with gauge invariance <span class="hlt">G</span>, primitive BPS quivers Q0<span class="hlt">G</span> are of two types: Q0ADE and Q0BCFG. In this study, we first show that Q0ADE have outer-automorphism symmetries inherited from the outer-automorphisms of the Dynkin diagrams of ADE Lie algebras. Then, we extend the usual folding operation of Dynkin diagrams ADE → BCFG to obtain the two following things: (i) relate Q0BCFG quivers and their mutations to the Q0ADE ones and their mutations; and (ii) link the BPS chambers of the N = <span class="hlt">2</span>ADE theories with the corresponding BCFG ones. As an illustration of this construction, we derive the BPS and anti-BPS states of the strong chambers Qstg<span class="hlt">G</span><span class="hlt">2</span> and QstgF4 of the 4d N = <span class="hlt">2</span> pure <span class="hlt">G</span><span class="hlt">2</span> and F4 gauge models.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010cosp...38.3536P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010cosp...38.3536P"><span>Antiradiation Antitoxin Ig<span class="hlt">G</span> : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Popov, Dmitri; Maliev, Slava</p> <p></p> <p>Introduction: High doses of radiation induce apoptotic necrosis of <span class="hlt">radio-sensitive</span> cells. Mild doses of radiation induce apoptosis or controlled programmed death of <span class="hlt">radio-sensitive</span> cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin <span class="hlt">G</span> (Ig<span class="hlt">G</span>) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune Ig<span class="hlt">G</span> preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. <span class="hlt">2</span>.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016SPIE.9722E..0VK','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016SPIE.9722E..0VK"><span>Lanthanum fluoride nanoparticles for <span class="hlt">radiosensitization</span> of tumors</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Kudinov, Konstantin; Bekah, Devesh; Cooper, Daniel; Shastry, Sathvik; Hill, Colin; Bradforth, Stephen; Nadeau, Jay</p> <p>2016-03-01</p> <p>Dense inorganic nanoparticles have recently been identified as promising <span class="hlt">radiosensitizers</span>. In addition to dose enhancement through increased attenuation of ionizing radiation relative to biological tissue, scintillating nanoparticles can transfer energy to coupled photosensitizers to amplify production of reactive oxygen species, as well as provide UVvisible emission for optical imaging. Lanthanum fluoride is a transparent material that is easily prepared as nanocrystals, and which can provide radioluminescence at a number of wavelengths through simple substitution of lanthanum ions with other luminescent lanthanides. We have prepared lanthanum fluoride nanoparticles doped with cerium, terbium, or both, that have good spectral overlap with chlorine6 or Rose Bengal photosensitizer molecules. We have also developed a strategy for stable conjugation of the photosensitizers to the nanoparticle surface, allowing for high energy transfer efficiencies on a per molecule basis. Additionally, we have succeeded in making our conjugates colloidally stable under physiological conditions. Here we present our latest results, using nanoparticles and nanoparticle-photosensitizer conjugates to demonstrate radiation dose enhancement in B16 melanoma cells. The effects of nanoparticle treatment prior to 250 kVp x-ray irradiation were investigated through clonogenic survival assays and cell cycle analysis. Using a custom apparatus, we have also observed scintillation of the nanoparticles and conjugates under the same conditions that the cell samples are irradiated.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3970166','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3970166"><span>Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd<span class="hlt">2</span>−/−) Mice</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Berhane, Hebist; Epperly, Michael W.; Goff, Julie; Kalash, Ronny; Cao, Shaonan; Franicola, Darcy; Zhang, Xichen; Shields, Donna; Houghton, Frank; Wang, Hong; Wipf, Peter; Parmar, Kalindi; Greenberger, Joel S.</p> <p>2014-01-01</p> <p>FancD<span class="hlt">2</span> plays a central role in the human Fanconi anemia DNA damage response (DDR) pathway. Fancd<span class="hlt">2</span>−/− mice exhibit many features of human Fanconi anemia including cellular DNA repair defects. Whether the DNA repair defect in Fancd<span class="hlt">2</span>−/− mice results in radiologic changes in all cell lineages is unknown. We measured stress of hematopoiesis in long-term marrow cultures and <span class="hlt">radiosensitivity</span> in clonogenic survival curves, as well as comet tail intensity, total antioxidant stores and radiation-induced gene expression in hematopoietic progenitor compared to bone marrow stromal cell lines. We further evaluated radioprotection by a mitochondrial-targeted antioxidant GS-nitroxide, JP4-039. Hematopoiesis longevity in Fancd<span class="hlt">2</span>−/− mouse long-term marrow cultures was diminished and bone marrow stromal cell lines were <span class="hlt">radiosensitive</span> compared to Fancd<span class="hlt">2</span>+/+ stromal cells (Fancd<span class="hlt">2</span>−/− D0 = 1.4 ± 0.1 Gy, ñ = 5.0 ± 0.6 vs. Fancd<span class="hlt">2</span>+/+ D0 = 1.6 ± 0.1 Gy, ñ = 6.7 ± 1.6), P = 0.0124 for D0 and P = 0.0023 for ñ, respectively). In contrast, Fancd<span class="hlt">2</span>−/− IL-3-dependent hematopoietic progenitor cells were radioresistant (D0 = 1.71 ± 0.04 Gy and ñ = 5.07 ± 0.52) compared to Fancd<span class="hlt">2</span>+/+ (D0 = 1.39 ± 0.09 Gy and ñ = <span class="hlt">2</span>.31 ± 0.85, P = 0.001 for D0). CFU-GM from freshly explanted Fancd<span class="hlt">2</span>−/− marrow was also radioresistant. Consistent with <span class="hlt">radiosensitivity</span>, irradiated Fancd<span class="hlt">2</span>−/− stromal cells had higher DNA damage by comet tail intensity assay compared to Fancd<span class="hlt">2</span>+/+ cells (P < 0.0001), slower DNA damage recovery, lower baseline total antioxidant capacity, enhanced radiation-induced depletion of antioxidants, and increased CDKN1A-p21 gene transcripts and protein. Consistent with radioresistance, Fancd<span class="hlt">2</span>−/− IL-3-dependent hematopoietic cells had higher baseline and post irradiation total antioxidant capacity. While, there was no detectable alteration of radiation-induced cell cycle arrest with Fancd<span class="hlt">2</span>−/− stromal cells, hematopoietic progenitor cells showed reduced <span class="hlt">G</span><span class="hlt">2</span>/M</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/5551658','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/5551658"><span>5-Aminouracil treatment. A method for estimating <span class="hlt">G</span><span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Socher, S H; Davidson, D</p> <p>1971-02-01</p> <p>Treatment of Vicia faba lateral roots with a range of concentrations of 5-aminouracil (5-AU) indicate that cells are stopped at a particular point in interphase. The timing of the fall in mitotic index suggests that cells are held at the S - <span class="hlt">G</span>(<span class="hlt">2</span>) transition. When cells are held at this point, treatments with 5-AU can be used to estimate the duration of <span class="hlt">G</span>(<span class="hlt">2</span>) + mitosis/<span class="hlt">2</span> of proliferating cells. Treatment with 5-AU can also be used to demonstrate the presence of subpopulations of dividing cells that differ in their <span class="hlt">G</span>(<span class="hlt">2</span>) duration. Using this method, 5-AU-induced inhibition, we have confirmed that in V. faba lateral roots there are two populations of dividing cells: (a) a fast-dividing population, which makes up approximately 85% of the proliferating cell population and has a <span class="hlt">G</span>(<span class="hlt">2</span>) + mitosis/<span class="hlt">2</span> duration of 3.3 hr, and (b) a slow-dividing population, which makes up approximately 15% of dividing cells and has a <span class="hlt">G</span>(<span class="hlt">2</span>) duration in excess of 12 hr. These estimates are similar to those obtained from percentage labeled mitosis (PLM) curves after incorporation of thymidine-(3)H.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol17/pdf/CFR-2013-title40-vol17-sec79-53.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol17/pdf/CFR-2013-title40-vol17-sec79-53.pdf"><span>40 CFR 79.53 - Tier <span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer determination. Manufacturers shall determine... Sister <span class="hlt">Chromatid</span> Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol17/pdf/CFR-2012-title40-vol17-sec79-53.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol17/pdf/CFR-2012-title40-vol17-sec79-53.pdf"><span>40 CFR 79.53 - Tier <span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister <span class="hlt">Chromatid</span> Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol16/pdf/CFR-2011-title40-vol16-sec79-53.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol16/pdf/CFR-2011-title40-vol16-sec79-53.pdf"><span>40 CFR 79.53 - Tier <span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister <span class="hlt">Chromatid</span> Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_24 --> <div id="page_25" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="481"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol17/pdf/CFR-2014-title40-vol17-sec79-53.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol17/pdf/CFR-2014-title40-vol17-sec79-53.pdf"><span>40 CFR 79.53 - Tier <span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister <span class="hlt">Chromatid</span> Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol16/pdf/CFR-2010-title40-vol16-sec79-53.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol16/pdf/CFR-2010-title40-vol16-sec79-53.pdf"><span>40 CFR 79.53 - Tier <span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>..., Salmonella typhimurium Reverse Mutation Assay). (b) Manufacturer Determination. Manufacturers shall determine... Sister <span class="hlt">Chromatid</span> Exchange Assay, and § 79.68 Salmonella typhimurium Reverse Mutation Assay. Teratogenic...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28566733','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28566733"><span>A Benzothiazole Derivative (5<span class="hlt">g</span>) Induces DNA Damage And Potent <span class="hlt">G</span><span class="hlt">2</span>/M Arrest In Cancer Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hegde, Mahesh; Vartak, Supriya V; Kavitha, Chandagirikoppal V; Ananda, Hanumappa; Prasanna, Doddakunche S; Gopalakrishnan, Vidya; Choudhary, Bibha; Rangappa, Kanchugarakoppal S; Raghavan, Sathees C</p> <p>2017-05-31</p> <p>Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5<span class="hlt">g</span>) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5<span class="hlt">g</span> interfered with cell proliferation in both, cell lines and tumor cells leading to significant <span class="hlt">G</span><span class="hlt">2</span>/M arrest. 5<span class="hlt">g</span> treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed <span class="hlt">G</span><span class="hlt">2</span>/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL<span class="hlt">2</span> and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5<span class="hlt">g</span> treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5<span class="hlt">g</span> administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5<span class="hlt">g</span> as a potent biochemical inhibitor to induce <span class="hlt">G</span><span class="hlt">2</span>/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28971063','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28971063"><span>Nanoparticle Drones to Target Lung Cancer with <span class="hlt">Radiosensitizers</span> and Cannabinoids.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ngwa, Wilfred; Kumar, Rajiv; Moreau, Michele; Dabney, Raymond; Herman, Allen</p> <p>2017-01-01</p> <p>Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous ("sea") routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with <span class="hlt">radiosensitizers</span> and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19478548','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19478548"><span>Cytotoxic effects of <span class="hlt">2</span>-methoxyestradiol in the hepatocellular carcinoma cell line Hep<span class="hlt">G</span><span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>El Naga, Reem N Abou; El-Demerdash, Ebtehal; Youssef, Samar S; Abdel-Naim, Ashraf B; El-Merzabani, Mahmoud</p> <p>2009-01-01</p> <p>The study was designed to examine the potential cytotoxicity of <span class="hlt">2</span>-methoxyestradiol (<span class="hlt">2</span>ME<span class="hlt">2</span>), a natural 17beta-estradiol metabolite, in hepatocellular carcinoma and the possible underlying mechanisms for this cytotoxicity. The cell line Hep<span class="hlt">G</span><span class="hlt">2</span> was treated with different concentrations of <span class="hlt">2</span>ME<span class="hlt">2</span> for 48 and 72 h. Using the sulforhodamine B assay, Hep<span class="hlt">G</span><span class="hlt">2</span> was sensitive to the cytotoxic effect of <span class="hlt">2</span>ME<span class="hlt">2</span>. <span class="hlt">2</span>ME<span class="hlt">2</span> induced cell arrest at the <span class="hlt">G</span>(<span class="hlt">2</span>)/M phase and a significant high percentage of apoptotic cells compared to the control group. Also, <span class="hlt">2</span>ME<span class="hlt">2</span> induced a significant increase in caspase 9 enzymatic activity after 48 and 72 h of treatment compared with control values. The DNA laddering was observed only in cells treated for 72 h. Furthermore, <span class="hlt">2</span>ME<span class="hlt">2</span> induced a significant decrease in the expression levels of vascular endothelial growth factor (VEGF) gene compared to the control values. <span class="hlt">2</span>ME<span class="hlt">2</span> exerts cytotoxic activity in the Hep<span class="hlt">G</span><span class="hlt">2</span> cell line by preferential cell blocking at the <span class="hlt">G</span>(<span class="hlt">2</span>)/M phase as well as induction of apoptosis as evidenced by increased caspase 9 enzymatic activity and observed DNA laddering in <span class="hlt">2</span>ME<span class="hlt">2</span>-treated Hep<span class="hlt">G</span><span class="hlt">2</span> cells. In addition, a reduction in hypervascularity is an important postulated mechanism as indicated by the significant reduction in the expression of VGEF, one of the most important angiogenic factors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28076755','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28076755"><span>RAD51 Is a Selective DNA Repair Target to <span class="hlt">Radiosensitize</span> Glioma Stem Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>King, Harry O; Brend, Tim; Payne, Helen L; Wright, Alexander; Ward, Thomas A; Patel, Karan; Egnuni, Teklu; Stead, Lucy F; Patel, Anjana; Wurdak, Heiko; Short, Susan C</p> <p>2017-01-10</p> <p>Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant <span class="hlt">radiosensitization</span>. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX<span class="hlt">2</span> expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24245901','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24245901"><span>Aflatoxin (B1 , B<span class="hlt">2</span> , <span class="hlt">G</span>1 , and <span class="hlt">G</span><span class="hlt">2</span> ) contamination in rice of Mexico and Spain, from local sources or imported.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Suárez-Bonnet, Elena; Carvajal, Magda; Méndez-Ramírez, Ignacio; Castillo-Urueta, Pável; Cortés-Eslava, Josefina; Gómez-Arroyo, Sandra; Melero-Vara, José María</p> <p>2013-11-01</p> <p>Rice is an important cereal but it is often contaminated with aflatoxins (AFs). The purpose of this study was to identify and quantify AF (B1 , B<span class="hlt">2</span> , <span class="hlt">G</span>1 , and <span class="hlt">G</span><span class="hlt">2</span> ) in 67 rice samples cultivated in Mexico and Spain, and from imported crops collected in 2008 and 2009. The methodology was validated, the rice samples were concentrated and purified with immunoaffinity columns and were quantified by high-pressure liquid chromatography (HPLC). The average total AF (AFt) in the Spanish rice was 37.3 μ<span class="hlt">g</span>/kg, the range was from 1.6 to 1383 μ<span class="hlt">g</span>/kg, the most contaminated samples being from San Juan de Aznalfarache, Sevilla (AFt = 138.6 μ<span class="hlt">g</span>/kg), from Tortosa, Tarragona (AFt = 104.6 μ<span class="hlt">g</span>/kg), and Calasparra, Murcia (AFt = 103.9 μ<span class="hlt">g</span>/kg). The rice imported from France to Spain had AFt of 26.6 μ<span class="hlt">g</span>/kg and from Pakistan AFt of 18.4 μ<span class="hlt">g</span>/kg, showing less AF contamination than the local one. The rice which originated from Mexico contained (AFt = 16.9 μ<span class="hlt">g</span>/kg), and those imported from the United States (AFt = 14.4 μ<span class="hlt">g</span>/kg) and Uruguay (AFt = 15.6 μ<span class="hlt">g</span>/kg). The imported rice had better quality in terms of the presence of AFs. © 2013 Institute of Food Technologists®</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28117625','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28117625"><span>Autophagy influences the low-dose hyper-<span class="hlt">radiosensitivity</span> of human lung adenocarcinoma cells by regulating MLH1.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Qiong; Xiao, Zhuya; Lin, Zhenyu; Zhou, Jie; Chen, Weihong; Jie, Wuyun; Cao, Xing; Yin, Zhongyuan; Cheng, Jing</p> <p>2017-06-01</p> <p>To investigate the impact of autophagy on the low-dose hyper-<span class="hlt">radiosensitivity</span> (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR). Conversely, the <span class="hlt">radiosensitivity</span> of H460 cells, which express high levels of MLH1, conformed to the linear-quadratic (LQ) model. After down-regulating MLH1 expression, A549 cells showed increased HRS and inhibition of autophagy, whereas H460 cells exhibited HRS/IRR. The levels of mTOR, p-mTOR, and BNIP3 were reduced in cells harboring MLH1 shRNA, and the changes in the mTOR/p-mTOR ratio mirrored those in MLH1 expression. Low MLH1-expressing A549 cells may exhibit HRS. Both the mTOR/p-mTOR and BNIP3/Beclin-1 signaling pathways were found to be related to HRS, but only mTOR/p-mTOR is involved in the regulation of HRS via MLH1 and autophagy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010PMB....55.6039N','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010PMB....55.6039N"><span><span class="hlt">Radiosensitizer</span>-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Nagesha, D. K.; Tada, D. B.; Stambaugh, C. K. K.; Gultepe, E.; Jost, E.; Levy, C. O.; Cormack, R.; Makrigiorgos, G. M.; Sridhar, S.</p> <p>2010-10-01</p> <p>Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of <span class="hlt">radiosensitizers</span> through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these <span class="hlt">radiosensitizers</span> coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25296027','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25296027"><span>Investigation of gold nanoparticle <span class="hlt">radiosensitization</span> mechanisms using a free radical scavenger and protons of different energies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jeynes, J C G; Merchant, M J; Spindler, A; Wera, A-C; Kirkby, K J</p> <p>2014-11-07</p> <p>Gold nanoparticles (GNPs) have been shown to sensitize cancer cells to x-ray radiation, particularly at kV energies where photoelectric interactions dominate and the high atomic number of gold makes a large difference to x-ray absorption. Protons have a high cross-section for gold at a large range of relevant clinical energies, and so potentially could be used with GNPs for increased therapeutic effect.Here, we investigate the contribution of secondary electron emission to cancer cell <span class="hlt">radiosensitization</span> and investigate how this parameter is affected by proton energy and a free radical scavenger. We simulate the emission from a realistic cell phantom containing GNPs after traversal by protons and x-rays with different energies. We find that with a range of proton energies (1-250 MeV) there is a small increase in secondaries compared to a much larger increase with x-rays. Secondary electrons are known to produce toxic free radicals. Using a cancer cell line in vitro we find that a free radical scavenger has no protective effect on cells containing GNPs irradiated with 3 MeV protons, while it does protect against cells irradiated with x-rays. We conclude that GNP generated free radicals are a major cause of <span class="hlt">radiosensitization</span> and that there is likely to be much less dose enhancement effect with clinical proton beams compared to x-rays.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28603845','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28603845"><span>Three novel HBB mutations, c.-140C><span class="hlt">G</span> (-90 C><span class="hlt">G</span>), c.237_256delGGACAACCTCAAGGGCACCT (FS Cd 78/85 -20 bp), and c.315+<span class="hlt">2</span>T><span class="hlt">G</span> (IVS<span class="hlt">2:2</span> T><span class="hlt">G</span>). Update of the mutational spectrum of β-Thalassemia in Mexican mestizo patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rizo-de-la-Torre, L C; Ibarra, B; Sánchez-López, J Y; Magaña-Torres, M T; Rentería-López, V M; Perea-Díaz, F J</p> <p>2017-10-01</p> <p>Beta-thalassemia (β-thal) is frequent in Mexican patients with microcytosis and hypochromia. We report three novel mutations and analyze the actual mutational spectrum in Mexican population. One hundred and forty-nine β-thal Mexican mestizo patients were studied (154 alleles). ARMS-PCR was performed to identify Cd39C>T, IVS1:1<span class="hlt">G</span>>A, IVS1:110<span class="hlt">G</span>>A, -28A>C, initiation codonA><span class="hlt">G</span> and IVS1:5<span class="hlt">G</span>>A mutations, and gap-PCR for δβ-thal Spanish type. DNA sequencing of HBB gene was carried out in negative samples for the initial screening. Fifteen different HBB gene mutations were observed in 148 alleles; three of them are novel: -90C><span class="hlt">G</span>, 20 bp deletion (at codons 78/85), and IVS<span class="hlt">2:2</span>T><span class="hlt">G</span>; the mutation IVS1:6T>C that was observed for first time in our population; and eleven previously described mutations. Six alleles showed normal HBB sequence. To date, a total of 21 different mutations have been observed in Mexican patients; the four most frequent mutations are of Mediterranean origin: Cd39C>T (37.<span class="hlt">2</span>%), IVS1:1<span class="hlt">G</span>>A (17.3%), IVS1:110<span class="hlt">G</span>>A (13.9%), and δβ-thal Spanish type (9.0%), which represent 77.4% of the total studied alleles. Considering the novel mutations -90C><span class="hlt">G</span>, -20 bp Cd78/85, IVS<span class="hlt">2:2</span>T><span class="hlt">G</span> and the first observation of IVS1:6T>C, the molecular spectrum of β-thal in Mexicans comprises 21 different mutations, confirming the high allelic heterogeneity in Mexicans. © 2017 John Wiley & Sons Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012PhDT.......409C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012PhDT.......409C"><span>Development, Characterization and Validation of Trastuzumab-Modified Gold Nanoparticles for Molecularly Targeted <span class="hlt">Radiosensitization</span> of Breast Cancer</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Chattopadhyay, Niladri</p> <p></p> <p>The overexpression of the human epidermal growth factor receptor-<span class="hlt">2</span> (HER-<span class="hlt">2</span>) in 20--25% of human breast cancers was investigated as a target for development of a gold nanoparticle (AuNP) based <span class="hlt">radiosensitizer</span> for improving the efficacy of neoadjuvant X-radiation therapy of the disease. HER-<span class="hlt">2</span> targeted AuNPs were developed by covalently conjugating trastuzumab, a Health Canada approved monoclonal antibody for the treatment of HER-<span class="hlt">2</span>-overexpressing breast cancer, to 30 nm AuNPs. Trastuzumab conjugated AuNPs were efficiently internalized by HER-<span class="hlt">2</span>-overexpressing breast cancer cells (as assessed by darkfield microscopy and transmission electron microscopy) and increased DNA damage from X-radiation in these cells by more than 5-fold. To optimize delivery of AuNPs to HER-<span class="hlt">2</span>-overexpressing tumors, high resolution microSPECT/CT imaging was used to track the in vivo fate of 111In-labelled non-targeted and HER-<span class="hlt">2</span> targeted AuNPs following intravenous (i.v.) or intratumoral (i.t.) injection. For i.v. injection, the effects of GdCl3 (for deactivation of macrophages) and non-specific (anti-CD20) antibody rituximab (for blocking of Fc mediated liver and spleen uptake) were studied. It was found that HER-<span class="hlt">2</span> targeting via attachment of trastuzumab paradoxically decreased tumor uptake as a result of faster elimination of the targeted AuNPs from the blood while improving internalization in HER-<span class="hlt">2</span>-positive tumor cells as compared to non-targeted AuNPs. This phenomenon could be attributed to Fc-mediated recognition and subsequent sequestration of trastuzumab conjugated AuNP by the reticuloendothelial system (RES). Blocking of the RES did not increase tumor uptake of either HER-<span class="hlt">2</span> targeted or non-targeted AuNPs. Following i.t. injection, our results suggest that Au-NTs redistribute over time and traffick to the liver via the ipsilateral axillary lymph node leading to comparable exposure as seen with i.v. administration. In contrast, targeted AuNPs are bound and internalized by HER-<span class="hlt">2</span></p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014PMB....59.2249K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014PMB....59.2249K"><span><span class="hlt">Radiosensitization</span> effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Khoshgard, Karim; Hashemi, Bijan; Arbabi, Azim; Javad Rasaee, Mohammad; Soleimani, Masoud</p> <p>2014-05-01</p> <p>Due to the high atomic number of gold nanoparticles (GNPs), they are known as new <span class="hlt">radiosensitizer</span> agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose absorbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The <span class="hlt">radiosensitizing</span> effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to <span class="hlt">2</span> Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24733041','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24733041"><span><span class="hlt">Radiosensitization</span> effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Khoshgard, Karim; Hashemi, Bijan; Arbabi, Azim; Rasaee, Mohammad Javad; Soleimani, Masoud</p> <p>2014-05-07</p> <p>Due to the high atomic number of gold nanoparticles (GNPs), they are known as new <span class="hlt">radiosensitizer</span> agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose absorbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The <span class="hlt">radiosensitizing</span> effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to <span class="hlt">2</span> Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4699751','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4699751"><span>Anti-cancer Activity of Osmanthus matsumuranus Extract by Inducing <span class="hlt">G</span><span class="hlt">2</span>/M Arrest and Apoptosis in Human Hepatocellular Carcinoma Hep <span class="hlt">G</span><span class="hlt">2</span> Cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jin, Soojung; Park, Hyun-Jin; Oh, You Na; Kwon, Hyun Ju; Kim, Jeong-Hwan; Choi, Yung Hyun; Kim, Byung Woo</p> <p>2015-01-01</p> <p>Background: Osmanthus matsumuranus, a species of Oleaceae, is found in East Asia and Southeast Asia. The bioactivities of O. matsumuranus have not yet been fully understood. Here, we studied on the molecular mechanisms underlying anti-cancer effect of ethanol extract of O. matsumuranus (EEOM). Methods: Inhibitory effect of EEOM on cell growth and proliferation was determined by WST assay in various cancer cells. To investigate the mechanisms of EEOM-mediated cytotoxicity, Hep<span class="hlt">G</span><span class="hlt">2</span> cells were treated with various concentration of EEOM and analyzed the cell cycle arrest and apoptosis induction by flow cytometry, Western blot analysis, 4,6-diamidino-<span class="hlt">2</span>-phenylindole (DAPI) staining and DNA fragmentation. Results: EEOM showed the cytotoxic activities in a dose-dependent manner in various cancer cell lines but not in normal cells, and Hep<span class="hlt">G</span><span class="hlt">2</span> cells were most susceptible to EEOM-induced cytotoxicity. EEOM induced <span class="hlt">G</span><span class="hlt">2</span>/M arrest in Hep<span class="hlt">G</span><span class="hlt">2</span> cells associated with decreased expression of cyclin-dependent kinase 1 (CDK1), cyclin A and cylcin B, and increased expression of phospho-checkpoint kinase <span class="hlt">2</span>, p53 and CDK inhibitor p21. Immunofluorescence staining showed that EEOM-treated Hep<span class="hlt">G</span><span class="hlt">2</span> increased doublet nuclei and condensed actin, resulting in cell rounding. Furthermore, EEOM-mediated apoptosis was determined by Annexin V staining, chromatin condensation and DNA fragmentation. EEOM caused upregulation of FAS and Bax, activation of caspase-3, -8, -9, and fragmentation of poly ADP ribose polymerase. Conclusions: These results suggest that EEOM efficiently inhibits proliferation of Hep<span class="hlt">G</span><span class="hlt">2</span> cells by inducing both <span class="hlt">G</span><span class="hlt">2</span>/M arrest and apoptosis via intrinsic and extrinsic pathways, and EEOM may be used as a cancer chemopreventive agent in the food or nutraceutical industry. PMID:26734586</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26559846','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26559846"><span>A Herpes Simplex Virus <span class="hlt">2</span> (HSV-<span class="hlt">2</span>) <span class="hlt">g</span>D Mutant Impaired for Neural Tropism Is Superior to an HSV-<span class="hlt">2</span> <span class="hlt">g</span>D Subunit Vaccine To Protect Animals from Challenge with HSV-<span class="hlt">2</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Kening; Goodman, Kyle N; Li, Daniel Y; Raffeld, Mark; Chavez, Mayra; Cohen, Jeffrey I</p> <p>2016-01-01</p> <p>A recent phase 3 trial with soluble herpes simplex virus <span class="hlt">2</span> (HSV-<span class="hlt">2</span>) glycoprotein D (<span class="hlt">g</span>D<span class="hlt">2</span>t) in adjuvant failed to show protection against genital herpes. We postulated that live attenuated HSV-<span class="hlt">2</span> would provide more HSV antigens for induction of virus-specific antibodies and cellular immunity than would <span class="hlt">g</span>D<span class="hlt">2</span>t. We previously reported an HSV-<span class="hlt">2</span> mutant, HSV<span class="hlt">2</span>-<span class="hlt">g</span>D27, in which the nectin-1 binding domain of <span class="hlt">g</span>D<span class="hlt">2</span> is altered so that the virus is impaired for infecting neural cells, but not epithelial cells, in vitro and is impaired for infecting dorsal root ganglia in mice (K. Wang, J. D. Kappel, C. Canders, W. F. Davila, D. Sayre, M. Chavez, L. Pesnicak, and J. I. Cohen, J Virol 86:12891-12902, 2012, doi:10.1128/JVI.01055-12). Here we report that the mutations in HSV<span class="hlt">2</span>-<span class="hlt">g</span>D27 were stable when the virus was passaged in cell culture and during acute infection of mice. HSV<span class="hlt">2</span>-<span class="hlt">g</span>D27 was attenuated in mice when it was inoculated onto the cornea, intramuscularly (i.m.), intravaginally, and intracranially. Vaccination of mice i.m. with HSV<span class="hlt">2</span>-<span class="hlt">g</span>D27 provided better inhibition of challenge virus replication in the vagina than when the virus was used to vaccinate mice intranasally or subcutaneously. Comparison of i.m. vaccinations with HSV<span class="hlt">2</span>-<span class="hlt">g</span>D27 versus <span class="hlt">g</span>D<span class="hlt">2</span>t in adjuvant showed that HSV<span class="hlt">2</span>-<span class="hlt">g</span>D27 induced larger reductions of challenge virus replication in the vagina and reduced latent viral loads in dorsal root ganglia but induced lower serum neutralizing antibody titers than those obtained with <span class="hlt">g</span>D<span class="hlt">2</span>t in adjuvant. Taken together, our data indicate that a live attenuated HSV-<span class="hlt">2</span> vaccine impaired for infection of neurons provides better protection from vaginal challenge with HSV-<span class="hlt">2</span> than that obtained with a subunit vaccine, despite inducing lower titers of HSV-<span class="hlt">2</span> neutralizing antibodies in the serum. Genital herpes simplex is one of the most prevalent sexually transmitted diseases. Though HSV-<span class="hlt">2</span> disease is usually mild, it can be life threatening in neonates and immunocompromised persons. In addition, genital</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20160001320','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20160001320"><span><span class="hlt">G</span><span class="hlt">2</span> Autonomous Control for Cryogenic Delivery Systems</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Dito, Scott J.</p> <p>2014-01-01</p> <p>The Independent System Health Management-Autonomous Control (ISHM-AC) application development for cryogenic delivery systems is intended to create an expert system that will require minimal operator involvement and ultimately allow for complete autonomy when fueling a space vehicle in the time prior to launch. The <span class="hlt">G</span><span class="hlt">2</span>-Autonomous Control project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to a rocket for testing purposes. To develop this application, the project is using the programming language/environment Gensym <span class="hlt">G</span><span class="hlt">2</span>. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. We have learned <span class="hlt">G</span><span class="hlt">2</span> through training classes and subsequent application development, and are now in the process of building the application that will soon be used to test on cryogenic loading equipment here at the Kennedy Space Center Cryogenics Test Laboratory (CTL). The <span class="hlt">G</span><span class="hlt">2</span> ISHM-AC application will bring with it a safer and more efficient propellant loading system for the future launches at Kennedy Space Center and eventually mobile launches from all over the world.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22224387-hepatocytes-determine-hypoxic-microenvironment-radiosensitivity-colorectal-cancer-cells-through-production-nitric-oxide-targets-mitochondrial-respiration','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22224387-hepatocytes-determine-hypoxic-microenvironment-radiosensitivity-colorectal-cancer-cells-through-production-nitric-oxide-targets-mitochondrial-respiration"><span>Hepatocytes Determine the Hypoxic Microenvironment and <span class="hlt">Radiosensitivity</span> of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Jiang, Heng; Verovski, Valeri N.; Leonard, Wim</p> <p>2013-03-01</p> <p>Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assessmore » hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes <span class="hlt">radiosensitized</span> all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The <span class="hlt">radiosensitizing</span> effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and <span class="hlt">radiosensitization</span> of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016IJEEP..17..101J','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016IJEEP..17..101J"><span>Development of V<span class="hlt">2</span><span class="hlt">G</span> and <span class="hlt">G</span><span class="hlt">2</span>V Power Profiles and Their Implications on Grid Under Varying Equilibrium of Aggregated Electric Vehicles</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Jain, Prateek; Jain, Trapti</p> <p>2016-04-01</p> <p>The objective of this paper is to examine the vehicle-to-grid (V<span class="hlt">2</span><span class="hlt">G</span>) power capability of aggregated electric vehicles (EV) in the manner that they are being adopted by the consumers with their growing infiltration in the vehicles market. The proposed modeling of V<span class="hlt">2</span><span class="hlt">G</span> and grid-to-vehicle (<span class="hlt">G</span><span class="hlt">2</span>V) energy profiles blends the heterogeneous attributes namely, driven mileages, arrival and departure times, travel and parking durations, and speed dependent energy consumption of mobility trends. Three penetration percentages of 25 %, 50 % and 100 % resulting in varied compositions of battery electric vehicle (BEV) and plug-in hybrid electric vehicle (PHEV) in the system, as determined by the consumers' acceptance, have been considered to evaluate the grid capacity for V<span class="hlt">2</span><span class="hlt">G</span>. Distinct charge-discharge powers have been selected as per charging standards to match contemporary vehicles and infrastructure requirements. Charging and discharging approaches have been devised to replicate non-linear characteristics of Li-ion battery. Effects of simultaneous conjunction of V<span class="hlt">2</span><span class="hlt">G</span> and <span class="hlt">G</span><span class="hlt">2</span>V power curves with daily conventional load profile are quantified drawn upon workplace-discharging home-charging scheme. Results demonstrated a marked drop in load and hence in market price during morning hours which is hurriedly overcompensated by the hike during evening hours with rising penetration level and charge-discharge power.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2893262','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2893262"><span>Influence of homologous recombinational repair on cell survival and chromosomal aberration induction during the cell cycle in γ-irradiated CHO cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wilson, Paul F.; Hinz, John M.; Urbin, Salustra S.; Nham, Peter B.; Thompson, Larry H.</p> <p>2010-01-01</p> <p>The repair of DNA double-strand breaks (DSB) by homologous recombinational repair (HRR) underlies the high radioresistance and low mutability observed in S-phase mammalian cells. To evaluate the contributions of HRR and nonhomologous end-joining (NHEJ) to overall DSB repair capacity throughout the cell cycle after γ-irradiation, we compared HRR-deficient RAD51D-knockout 51D1 to CgRAD51D-complemented 51D1 (51D1.3) CHO cells for survival and chromosomal aberrations (CAs). Asynchronous cultures were irradiated with 150 or 300 cGy and separated by cell size using centrifugal elutriation. Cell survival of each synchronous fraction (~20 fractions total from early <span class="hlt">G</span>1 to late <span class="hlt">G</span><span class="hlt">2</span>/M) was measured by colony formation. 51D1.3 cells were most resistant in S, while 51D1 cells were most resistant in early <span class="hlt">G</span>1 (with survival and chromosome-type CA levels similar to 51D1.3) and became progressively more sensitive throughout S and <span class="hlt">G</span><span class="hlt">2</span>. Both cell lines experienced significantly reduced survival from late S into <span class="hlt">G</span><span class="hlt">2</span>. Metaphases were collected from every third elutriation fraction at the first post-irradiation mitosis and scored for CAs. 51D1 cells irradiated in S and <span class="hlt">G</span><span class="hlt">2</span> had ~<span class="hlt">2</span>-fold higher <span class="hlt">chromatid</span>-type CAs and a remarkable ~25-fold higher level of complex <span class="hlt">chromatid</span>-type exchanges compared to 51D1.3 cells. Complex exchanges in 51D1.3 cells were only observed in <span class="hlt">G</span><span class="hlt">2</span>. These results show an essential role for HRR in preventing gross chromosomal rearrangements in proliferating cells and, with our previous report of reduced survival of <span class="hlt">G</span><span class="hlt">2</span>-phase NHEJ-deficient prkdc CHO cells [Hinz et al. DNA Repair 4, 782–792, 2005], imply reduced activity/efficiency of both HRR and NHEJ as cells transition from S to <span class="hlt">G</span><span class="hlt">2</span>. PMID:20434408</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_25 --> <div class="footer-extlink text-muted" style="margin-bottom:1rem; text-align:center;">Some links on this page may take you to non-federal websites. 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