Science.gov

Sample records for neoplastic non-random transformation

  1. Neoplastic transformation of human cells

    NASA Technical Reports Server (NTRS)

    Goth-Goldstein, Regine

    1995-01-01

    The goal of this project was to gain a better understanding of the cellular mechanisms of cancer induction by ionizing radiation as a risk assessment for workers subjected to high LET irradiation such as that found in space. The following ions were used for irradiation: Iron, Argon, Neon, and Lanthanum. Two tests were performed: growth in low serum and growth in agar were used as indicators of cell transformation. The specific aims of this project were to: (1) compare the effectiveness of various ions on degree of transformation of a single dose of the same RBE; (2) determine if successive irradiations with the same ion (Ge 600 MeV/u) increases the degree of transformation; (3) test if clones with the greatest degree of transformation produce tumors in nude mice; and (4) construct a cell hybrid of a transformed and control (non-transformed) clone. The cells used for this work are human mammary epithelial cells with an extended lifespan and selected for growth in MEM + 10% serum.

  2. Neoplastic cell transformation by heavy ions.

    PubMed

    Suzuki, M; Watanabe, M; Suzuki, K; Nakano, K; Kaneko, I

    1989-12-01

    We have studied the induction of morphological transformation by heavy ions. Golden hamster embryo cells were irradiated with 95 MeV 14N ions (530 keV/microns), 22 MeV 4He ions (36 keV/microns), and 22 MeV 4He ions with a 100-microns Al absorber (77 keV/microns) which were generated by a cyclotron at the Institute of Physical and Chemical Research in Japan. Colonies were considered to contain neoplastically transformed cells when the cells were densely stacked and made a crisscross pattern. It was shown that the induction of transformation was much more effective with 14N and 4He ions than with gamma or X rays. The relative biological effectiveness (RBE) relative to 60Co gamma rays was 3.3 for 14N ions, 2.4 for 4He ions, and 3.3 for 4He ions with a 100-microns Al absorber. The relationship between RBE and linear energy transfer was qualitatively similar for both cell death and transformation. PMID:2594968

  3. Neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation

    SciTech Connect

    Thraves, P.; Salehi, Z.; Dritschilo, A.; Rhim, J.S. )

    1990-02-01

    Efforts to investigate the progression of events that cause human cells to become neoplastic in response to ionizing radiation have been aided by the development of tissue culture systems of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus type 12 and simian virus 40 have been transformed by exposure to x-ray irradiation. Such transformants showed morphological alterations, formed colonies in soft agar, and induced carcinomas when transplanted into nude mice, whereas primary human epidermal keratinocytes exposed to radiation in this manner failed to show any evidence of transformation. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of a DNA tumor virus and radiation, indicating a multistep process for radiation-induced neoplastic conversion. This in vitro system may be useful as a tool for dissecting the process of radiation-induced neoplastic transformation of human epithelial cells and for detecting previously unreported human oncogenes.

  4. Neoplastic Transformation Induced by Carbon Ions

    SciTech Connect

    Bettega, Daniela Calzolari, Paola; Hessel, Petra; Stucchi, Claudio G.; Weyrather, Wilma K.

    2009-03-01

    Purpose: The objective of this experiment was to compare the oncogenic potential of carbon ion beams and conventional photon beams for use in radiotherapy. Methods and Materials: The HeLa X human skin fibroblast cell line CGL1 was irradiated with carbon ions of three different energies (270, 100, and 11.4 MeV/u). Inactivation and transformation data were compared with those for 15 MeV photons. Results: Inactivation and transformation frequencies for the 270 MeV/u carbon ions were similar to those for 15-MeV photons. The maximal relative biologic effectiveness (RBE{sub {alpha}}) values for 100MeV/u and 11.4 MeV/u carbon ions, respectively, were as follows: inactivation, 1.6 {+-} 0.2 and 6.7 {+-} 0.7; and transformation per surviving cell, 2.5 {+-} 0.6 and 12 {+-} 3. The curve for dose-transformation per cell at risk exhibited a maximum that was shifted toward lower doses at lower energies. Conclusions: Transformation induction per cell at risk for carbon ions in the entrance channel was comparable to that for photons, whereas for the lower energies, 100 MeV/u and 11 MeV/u, which are representative of the energies delivered to the tumor margins and volume, respectively, the probability of transformation in a single cell was greater than it was for photons. In addition, at isoeffective doses with respect to cell killing, the 11.4-MeV/u beam was more oncogenic than were photons.

  5. Neoplastic transformation and tumorigenesis by the human protooncogene MYC.

    PubMed Central

    Ramsay, G M; Moscovici, G; Moscovici, C; Bishop, J M

    1990-01-01

    Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abundant expression of MYC can transform both embryonic fibroblasts and hematopoietic cells and elicit granulocytic leukemias in chickens. Transformation by MYC is accompanied by changes in diverse aspects of cellular phenotype, including morphology, ability to grow in suspension, rate of proliferation, the structure of the cytoskeleton, and the composition of the extracellular matrix. Nevertheless, the biological potency of MYC is inherently constrained when compared to that of the retroviral oncogene v-myc. Our findings enlarge on previous descriptions of neoplastic transformation by MYC and sustain the view that ungoverned expression of the gene can contribute to the genesis of human tumors. Images PMID:2156260

  6. Cellular neoplastic transformation induced by 916 MHz microwave radiation.

    PubMed

    Yang, Lei; Hao, Dongmei; Wang, Minglian; Zeng, Yi; Wu, Shuicai; Zeng, Yanjun

    2012-08-01

    There has been growing concern about the possibility of adverse health effects resulting from exposure to microwave radiations, such as those emitted by mobile phones. The purpose of this study was to investigate the cellular neoplastic transformation effects of electromagnetic fields. 916 MHz continuous microwave was employed in our study to simulate the electromagnetic radiation of mobile phone. NIH/3T3 cells were adopted in our experiment due to their sensitivity to carcinogen or cancer promoter in environment. They were divided randomly into one control group and three microwave groups. The three microwave groups were exposed to 916 MHz EMF for 2 h per day with power density of 10, 50, and 90 w/m(2), respectively, in which 10 w/m(2) was close to intensity near the antenna of mobile phone. The morphology and proliferation of NIH/3T3 cells were examined and furthermore soft agar culture and animal carcinogenesis assay were carried out to determine the neoplastic promotion. Our experiments showed NIH/3T3 cells changed in morphology and proliferation after 5-8 weeks exposure and formed clone in soft agar culture after another 3-4 weeks depending on the exposure intensity. In the animal carcinogenesis study, lumps developed on the back of SCID mice after being inoculated into exposed NIH/3T3 cells for more than 4 weeks. The results indicate that microwave radiation can promote neoplastic transformation of NIH/3T3cells. PMID:22395787

  7. Mechanisms of radiation-induced neoplastic cell transformation

    SciTech Connect

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  8. Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens

    PubMed Central

    Kakunaga, Takeo

    1978-01-01

    Cultured fibroblast cells derived from a skin biopsy sample taken from normal human adult were exposed to a potent carcinogen, 4-nitroquinoline 1-oxide. Alterations of cell growth pattern such as higher density and piling up of cells were noticed in some fractions of cultures that were successively subcultured after nitroquinoline oxide treatment. Morphologically altered cells retained this growth pattern and became established lines of transformed cells without showing the limited life-span characteristic of normal cells in culture. The transformed cells showed a higher saturation density and the ability to grow in soft agar, properties that are usually correlated with neoplastic transformation of cells in culture. Selection of preexisting transformed human cells as a mechanism of this observed transformation seemed unlikely because clones of these normal cells could also be used to assess the transforming effect of nitroquinoline oxide. Preliminary results suggest that numerous cell divisions were required for the development of the transformation after nitroquinoline oxide treatment of these human cells. When the transformed cell lines were injected subcutaneously into nude (athymic) mice, solid tumors were produced at the site of inoculation. Treatment with N-methyl-N′-nitro-N-nitrosoguanidine also induced cell transformation, in a manner similar to treatment with nitroquinoline oxide. However, transformation was not induced with (i) 4-aminoquinoline 1-oxide (a noncarcinogenic derivative of 4-nitroquinoline 1-oxide), (ii) 3-methylcholanthrene (a carcinogen that cannot be metabolically activated by the target cells employed), or (iii) the solvent dimethyl sulfoxide. Images PMID:418410

  9. Neoplastic cell transformation by high-LET radiation: Molecular mechanisms

    NASA Astrophysics Data System (ADS)

    Chui-Hsu Yang, Tracy; Craise, Laurie M.; Mei, Man-Tong; Tobias, Cornelius A.

    Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step processes, we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 Å may cause cell transformation and that two DNA breaks formed within 20 Å may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At

  10. Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents.

    PubMed

    Franke, A A; Cooney, R V; Custer, L J; Mordan, L J; Tanaka, Y

    1998-01-01

    Evaluation of unknown biological effects of chemicals including food plant products requires the assessment of bioactivity and bioavailability. Epidemiologic studies show consistently a cancer protective effect of fruit and vegetable consumption, but there is little understanding of which phytochemicals account for this observation. Commonly studied antioxidant micronutrients are less consistently correlated with cancer protection relative to the food groups themselves, suggesting that other phytochemicals or a combination of food products play key roles in preventing cancer. We investigated the effects of the predominant dietary flavonoids and isoflavonoids at inhibiting neoplastic transformation induced by 3-methylcholanthrene in C3H 10T1/2 murine fibroblasts. We found that most phenolic agents tested were equal to or superior to known chemopreventive agents such as carotenoids or vitamins in effectiveness. Hesperetin, hesperidin and catechin were the most potent agents among the flavonoids tested, inhibiting transformation completely when applied at 1.0 microM after exposure to the carcinogen. Structure-activity comparison revealed that among the compounds tested, flavonoids with a vicinal diphenol structure in ring 'B' and a saturated 'C' ring exhibited the strongest effects. Most agents tested showed dose-dependent patterns. Interestingly, the soy isoflavonoids were weakly active except when applied in combination, suggesting a synergistic effect. In addition, HPLC techniques were developed for determining the bioavailability of isoflavonoids in human biological fluids including urine, plasma and breast milk. We observed a relatively fast absorption, distribution and elimination of isoflavonoids including a biphasic pattern probably due to enterohepatic circulation. Total peak isoflavone levels in urine, plasma and in breast milk were found to be 60 microM, 2 microM and 0.2 microM, respectively and were reached 8-12 hours after consumption of soy foods. Levels

  11. The melanocyte differentiation program predisposes to metastasis following neoplastic transformation.

    PubMed Central

    Gupta, Piyush B.; Kuperwasser, Charlotte; Brunet, Jean-Philippe; Ramaswamy, Sridhar; Kuo, Wen-Lin; Gray, Joe W.; Naber, Stephen P.; Weinberg, Robert A.

    2006-01-01

    The aggressive clinical behavior of melanoma has led to the hypothesis that the developmental origins of melanocytes in the neural crest might be relevant for their metastatic propensity. We demonstrate that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, while human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Importantly, these melanomas exhibit a metastasis spectrum similar to that observed in human patients. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi reveals that Slug, a master regulator of neural crest cell specification and migration, correlates in its expression pattern with other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present prior to neoplastic transformation can play a pivotal role in governing melanoma's progression. PMID:16142232

  12. Relationship of Chromosome Changes to Neoplastic Cell Transformation

    PubMed Central

    DiPaolo, Joseph A.; Popescu, Nicolae C.

    1976-01-01

    Chromosomal abnormalities are a frequent concomitant of neoplasia, and although it is tempting to relate these mutations and alterations in chromatin (DNA) function to cancer, their relationship to the initiation or progression of carcinogenesis is unknown. Mammalian cells in culture, after interacting with chemical carcinogens, often exhibit chromosome damage consisting of breaks and exchanges of chromatid material. The pattern of damage of banded metaphases indicates that negative bands are especially vulnerable to the action of chemical carcinogens, probably because of differential chromatin condensation. Damage to individual chromosomes may be random or nonrandom, depending on the species. Cell death can be correlated with chromatid alterations that occur shortly after treatment with chemical carcinogens. There is also a correlation between mutagenic and carcinogenic activity of some chemical carcinogens and the frequency of sister chromatid exchanges. The question of whether specific chromosome changes are absolutely required for neoplastic transformation cannot be answered because of conflicting data and diverse results from studies even with known carcinogens. Cell transformation may occur without any visible chromosome changes. A universal specific numerical or visible structural chromosomal alteration is not necessarily associated with chemical or viral transformation. Chromosome changes are independent of the etiologic agents: different carcinogens may produce transformation associated with the same abnormal chromosomes, but not all transformed lines invariably exhibit the same abnormality, even with the same chemical. In some species, chromosome having nucleolar organizer regions may be more frequently involved in numerical or structural deviations. Progressively growing tumors also may occur as a result of the proliferation of transformed cells without detectable chromosome changes, indicating that tumorigenicity need not be related to an imbalance of

  13. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  14. Kinetic Modeling of Damage Repair, Genome Instability, and Neoplastic Transformation

    SciTech Connect

    Stewart, Robert D

    2007-03-17

    Inducible repair and pathway interactions may fundamentally alter the shape of dose-response curves because different mechanisms may be important under low- and high-dose exposure conditions. However, the significance of these phenomena for risk assessment purposes is an open question. This project developed new modeling tools to study the putative effects of DNA damage induction and repair on higher-level biological endpoints, including cell killing, neoplastic transformation and cancer. The project scope included (1) the development of new approaches to simulate the induction and base excision repair (BER) of DNA damage using Monte Carlo methods and (2) the integration of data from the Monte Carlo simulations with kinetic models for higher-level biological endpoints. Methods of calibrating and testing such multiscale biological simulations were developed. We also developed models to aid in the analysis and interpretation of data from experimental assays, such as the pulsed-field gel electrophoresis (PFGE) assay used to quantity the amount of DNA damage caused by ionizing radiation.

  15. Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

    NASA Technical Reports Server (NTRS)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1989-01-01

    Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

  16. Neoplastic transformation of hamster embyro cells by heavy ions.

    PubMed

    Han, Z; Suzuki, H; Suzuki, F; Suzuki, M; Furusawa, Y; Kato, T; Ikenaga, M

    1998-01-01

    We have studied the induction of morphological transformation of Syrian hamster embryo cells by low doses of heavy ions with different linear energy transfer (LET), ranging from 13 to 400 keV/micrometer. Exponentially growing cells were irradiated with 12C or 28Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), inoculated to culture dishes, and transformed colonies were identified when the cells were densely stacked and showed a crisscross pattern. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to 250 kVp X-rays showed an initial increase with LET, reaching a maximum value of about 7 at 100 keV/micrometer, and then decreased with the further increase in LET. Thus, we confirmed that high LET heavy ions are significantly more effective than X-rays for the induction of in vitro cell transformation. PMID:11542417

  17. Neoplastic cell transformation by energetic heavy ions and its modification with chemical agents

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Tobias, C. A.

    1984-01-01

    One of the major deleterious late effects of ionizing radiation is related to the induction of neoplasms. In the present report recent experimental results on neoplastic cell transformation by heavy ions are presented, and possible means to circumvent the carcinogenic effect of space radiation are discussed. Biological effects observed in experiments involving the use of energetic heavy ions accelerated at the Bevalac suggest that many of the biological effects observed in earlier space flight experiments may be due to space radiation, particularly cosmic rays. It is found that the effect of radiation on cell transformation is dose-rate dependent. The frequency of neoplastic transformation for a given dose decreases with a decrease of dose rate of Co-60 gamma rays. It is found that various chemical agents give radiation protection, including DMSO.

  18. The Route to HPV-Associated Neoplastic Transformation: A Review of the Literature.

    PubMed

    Tulay, Pinar; Serakinci, Nedime

    2016-01-01

    Human papillomaviruses (HPVs)-small, nonenveloped viruses with double-stranded circular DNA-are believed to have a role in the progression of cancer. However, the exact mechanisms are not well established. The interference of HPV proteins, especially E6 and E7, in the cell cycle is considered to be the main pathway. It is still questioned whether the expression of these proteins or the viral load is more important in neoplastic transformation. Furthermore, HPV is believed to adapt mechanisms to evade the host cell immune system; persistent HPV infection may also play a role in oncogenic transformation by causing genomic instability and local immune suppression. These factors may cause accumulation of genomic alterations within the host cell and integration of the viral genome into the host genome. In recent years, epigenetic modifications, such as methylation, have also been considered to take part in neoplastic transformation. All of these alterations to the genome may be favorable to the development of cancer. This article highlights the association of HPV in neoplastic transformation and cancer progression. PMID:27278883

  19. MOLECULAR MECHANISM OF SUPPRESSION OF NEOPLASTIC TRANSFORMATION BY LOW DOSES OF LOW LET RADIATION

    SciTech Connect

    J.LESIE REDPATH, PH.D.

    2011-03-29

    We are currently funded (9/01-8/04) by the DOE Low Dose Radiation Research Program to examine mechanisms underlying the suppression of neoplastic transformation in vitro by low doses of low LET radiation. For the new studies proposed under Notice 04-21, we intend to follow up on our observation that upregulation of DNA repair may be an important factor and that its importance is dose-dependent. The experimental system will be the human hybrid cell neoplastic transformation assay that we are currently using. We propose to test the following hypothesis: Down-regulation of DNA dsb repair will abrogate the low dose suppression of neoplastic transformation. Using the technique of RNA silencing, it is proposed to test the effect of down-regulation of the two major DNA dsb repair pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ), on the dose response relationship for neoplastic transformation. Based on prior studies, we predict that this will result in abrogation of the suppressive effect at doses in the range 1 to 10 cGy, but not at lower doses. The proposed experiments will also help address the question as to which of the two DNA repair pathways may be the most important in causing suppression of transformation. HR is a pathway that is predominant in S and G2 phase cells and is known to be less error-prone than the NHEJ pathway that is predominant in G1 phase. We hypothesize that down-regulation of HR will result in the most effective abrogation of suppression. An important component of this study will be the determination of the how abrogation of DNA dsb repair impacts the spontaneous transformation frequency, presumably a consequence of endogeneous DNA damage. Experiments will be carried out using partially synchronized populations of cells enriched for G1 and S/G2 respectively. In addition to the endpoint of neoplastic transformation the impact of down-regulation of HR and NHEJ on the formation and disappearance of the DNA dsb marker

  20. The neoplastic transformation potential of mammography X rays and atomic bomb spectrum radiation.

    PubMed

    Heyes, G J; Mill, A J

    2004-08-01

    Considerable controversy currently exists regarding the biological effectiveness of 29 kVp X rays which are used for mammography screening. This issue must be resolved to enable proper evaluation of radiation risks from breast screening. Here a definitive assessment of the biological effectiveness of 29 kVp X rays compared to the quality of radiation to which the atomic bomb survivors were exposed is presented for the first time. The standard radiation sources used were (a) an atomic bomb simulation spectrum and (b) 2.2 MeV electrons from a strontium-90/yttrium-90 (90Sr/90Y) radioactive source. The biological end point used was neoplastic transformation in vitro in CGL1 (HeLa x human fibroblast hybrid) cells. No significant difference was observed for the biological effectiveness of the two high-energy sources for neoplastic transformation. A limiting relative biological effectiveness (RBE(M)) of 4.42 +/- 2.02 was observed for neoplastic transformation by 29 kVp X rays compared to these two sources. This compares with values of 4.67 +/- 3.93 calculated from previously published data and 3.58 +/- 1.77 when the reference radiation was 200 and 220 kVp X rays. This suggests that the risks associated with mammography screening may be approximately five times higher than previously assumed and that the risk-benefit relationship of mammography exposures may need to be re-examined. PMID:15387138

  1. Neoplastic cell transformation by energetic heavy ions and its modification with chemical agents.

    PubMed

    Yang, T C; Tobias, C A

    1984-01-01

    For many years we have been interested in understanding the potential carcinogenic effects of cosmic rays. We have studied the oncogenic effects of cosmic rays with accelerator-produced heavy particle radiation and with a cultured mammalian cell system--C3H10T1/2 cells. Our quantitative data obtained with carbon, neon, silicon, and iron particles showed that RBE is both dose and LET dependent for neoplastic cell transformation. RBE is higher at lower dose, and RBE increases with LET up to about 200 keV/micrometer. In nonproliferation confluent cells, heavy-ion induced transformation damage may not be repairable, although a dose modifying factor of about 1.7 was observed for X-ray radiation. Our recent studies with super-heavy high-energy particles, e.g., 960 MeV/U U235 ions (LET = 1900 keV/micrometer), indicate that these ions with a high inactivation cross-section can cause neoplastic cell transformation. The induction of cell transformation by radiation can be modified with various chemicals. We have found that the presence of DMSO (either during or many days after irradiation) decreased the transformation frequency significantly. It is, therefore, potentially possible to reduce the oncogenic effect of cosmic rays in space through some chemical protection. PMID:11539629

  2. Neoplastic cell transformation by energetic heavy ions and its modification with chemical agents

    NASA Astrophysics Data System (ADS)

    Yang, T. C.; Tobias, C. A.

    For many years we have been interested in understanding the potential carcinogenic effects of cosmic rays. We have studied the oncogenic effects of cosmic rays with accelerator-produced heavy particle radiation and with a cultured mammalian cell system--C3H10T1/2 cells. Our quantitative data obtained with carbon, neon, silicon, and iron particles showed that RBE is both dose and LET dependent for neoplastic cell transformation. RBE is higher at lower dose, and RBE increases with LET up to about 200 keV/μm. In nonproliferation confluent cells, heavy-ion induced transformation damage may not be repairable, although a dose modifying factor of about 1.7 was observed for X-ray radiation. Our recent studies with super-heavy high-energy particles, e.g., 960 MeV/u U235 ions (LET = 1900 keV/μm), indicate that these ions with a high inactivation cross-section can cause neoplastic cell transformation. The induction of cell transformation by radiation can be modified with various chemicals. We have found that the presence of DMSO (either during or many days after irradiation) decreased the transformation frequency significantly. It is, therefore, potentially possible to reduce the oncogenic effect of cosmic rays in space through some chemical protection.

  3. Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

    PubMed

    Russo, Francesco; Linsalata, Michele; Orlando, Antonella

    2014-10-01

    Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism. PMID:25309063

  4. Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals.

    PubMed Central

    Tsutsui, T; Barrett, J C

    1997-01-01

    Estrogens are clearly carcinogenic in humans and rodents but the mechanisms by which these hormones induce cancer are only partially understood. Stimulation of cell proliferation and gene expression by binding to the estrogen receptor is one important mechanism in hormonal carcinogenesis; however, estrogenicity is not sufficient to explain the carcinogenic activity of all estrogens because some estrogens are not carcinogenic. Estrogens are nonmutagenic in many assays but exhibit specific types of genotoxic activity under certain conditions. We have studied extensively the mechanisms by which estrogens induce neoplastic transformation in a model in vitro system and our findings are summarized in this review. 17beta-Estradiol (E2) and diethylstilbestrol (DES) and their metabolites induce morphological and neoplastic transformation of Syrian hamster embryo (SHE) cells that express no measurable levels of estrogen receptor. Treatment of the cells with E2 or DES fails to induce DNA damage, chromosome aberrations and gene mutations in SHE cells but results in numerical chromosome aberrations (aneuploidy) that could arise from microtubule disruption or disfunction of mitotic apparatus. Estrogen-induced genotoxicity is detected in cells following treatment with estrogen metabolites or following exogenous metabolic activation of estrogens. The estrogens induce DNA adduct formation that is detected by 32P-postlabeling. Both aneuploidy induction and DNA damage caused by DNA adduct formation correlate with the estrogen-induced cell transformation and may be important in hormonal carcinogenesis. We propose that multiple effects of estrogens acting together cause genetic alterations leading to cell transformation. PMID:9168005

  5. Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation12

    PubMed Central

    Drosos, Yiannis; Neale, Geoffrey; Ye, Jianming; Paul, Leena; Kuliyev, Emin; Maitra, Anirban; Means, Anna L; Washington, M Kay; Rehg, Jerold; Finkelstein, David B; Sosa-Pineda, Beatriz

    2016-01-01

    The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness. PMID:26992918

  6. Generation of tumor-specific transplantation antigens by UV radiation can occur independently of neoplastic transformation.

    PubMed

    Hostetler, L W; Ananthaswamy, H N; Kripke, M L

    1986-10-15

    The purpose of this study was to determine whether the UV-associated antigens present on tumors induced in mice by chronic UV irradiation could be induced by in vitro irradiation of cells that were already tumorigenic, or whether their occurrence was associated with the primary neoplastic transformation event. Cells of a nonantigenic, spontaneous fibrosarcoma cell line were exposed to UV radiation in vitro, were cloned, and were tested for antigenic properties. A large number of the clones obtained after UV irradiation of the fibrosarcoma cells were highly antigenic (20 of 39), whereas clones derived from unirradiated cultures were not (0 of 10). The antigenic variants did not induce cross-protection among themselves, but induced only variant-specific immunity in vivo. Several antigenic variants were tested for susceptibility to the action of UV-induced suppressor cells, which seem to recognize a common determinant shared among UV-induced tumors. The variants tested were indeed subject to the activity of the UV-induced suppressor lymphocytes. These results demonstrate that the unique antigenic properties exhibited by UV-induced murine skin cancers are also exhibited by cells exposed to UV radiation in vitro. In addition, they imply that the UV-associated antigens arise as a consequence of exposing cells to UV radiation and that they can occur independently of an initial neoplastic transformation event. PMID:3760572

  7. The G protein-coupled estrogen receptor as a modulator of neoplastic transformation.

    PubMed

    Jacenik, Damian; Cygankiewicz, Adam I; Krajewska, Wanda M

    2016-07-01

    Estrogens play a crucial role in the regulation of physiological and pathophysiological processes. These hormones act through specific receptors, most notably the canonical estrogen receptors α and β (ERα and ERβ) and their truncated forms as well as the G protein-coupled estrogen receptor (GPER). Several studies have shown that GPER is expressed in many normal and cancer cells, including those of the breast, endometrium, ovary, testis and lung. Hormonal imbalance is one possible cause of cancer development. An accumulating body of evidence indicates that GPER is involved in the regulation of cancer cell proliferation, migration and invasion, it may act as a mediator of microRNA, and is believed to modulate the inflammation associated with neoplastic transformation. Furthermore, used in various treatment regimens anti-estrogens such as tamoxifen, raloxifen and fulvestrant (ICI 182.780), antagonists/modulators of canonical estrogen receptors, were found to be GPER agonists. This review presents the current knowledge about the potential role of GPER in neoplastic transformation. PMID:27107933

  8. Measuring neoplastic transformation in the hamster cheek pouch using Fourier domain low-coherence interferometry

    NASA Astrophysics Data System (ADS)

    Graf, Robert N.; Chen, Xiaoxin; Brown, William; Wax, Adam

    2008-02-01

    Fourier Domain Low Coherence Interferometry (fLCI) is a promising technique which combines the depth resolution of low coherence interferometry with the sensitivity of light scattering spectroscopy for probing the health of epithelial tissue layers. Our new fLCI system configuration utilizes a white light Xe arc lamp source and a 4-f interferometer which re-images light scattered from the sample onto the detection plane. The system employs an imaging spectrometer at the detection plane to acquire depth resolved profiles from 252 adjacent spatial points without the need for any scanning. The limited spatial coherence of the light source requires the resolution of adjacent spatial points for the generation of depth information. Depth-resolved spectral information is recovered by performing a short-time Fourier transform on the detected spectra, similar to spectroscopic optical coherence tomography. Wavelength dependent variations in scattering intensity are analyzed as a function of depth to obtain information about the neoplastic transformation of the probed cells. Previous studies have demonstrated fLCI as an excellent technique for probing the scatterer morphology of simple phantoms and of in vitro cancer cell monolayers. We now seek to assess the ability of the new fLCI system to measure the health of subsurface tissue layers using the hamster cheek pouch model. Seven hamsters will have one cheek pouch treated with the known carcinogen DMBA. At the conclusion of the 24 week treatment period the animals will be anesthetized and the cheek pouches will be extracted. We will use the fLCI optical system to measure the neoplastic transformation of the in situ subsurface tissue layers in both the normal and DMBA-treated cheek pouches. Traditional histological analysis will be used to verify the fLCI measurements. We expect our results to establish the feasibility of fLCI to distinguish between healthy and dysplastic epithelial tissues in the hamster cheek pouch.

  9. c-Myc dependent initiation of genomic instability during neoplastic transformation.

    PubMed

    Taylor, C; Jalava, A; Mai, S

    1997-01-01

    The dihydrofolate reductase (DHFR) gene is a target of c-Myc in genomic instability. The induced overexpression of c-Myc in cell lines is followed by the amplification and rearrangement of the DHFR gene. Furthermore, the constitutive upregulation of c-Myc protein coincides with genomic instability of the DHFR gene in lymphoid, non-lymphoid and in tumor lines. The amplification of the DHFR gene is locus-specific and independent of species origins. We have now addressed the question whether inducible deregulation of c-Myc is followed by DHFR gene amplification in vivo. We show that the DHFR gene is a target of c-Myc-dependent neoplasia in vivo and propose a role for genomic instability during the initiation of neoplastic transformation. PMID:9308243

  10. DUAL ION EXPOSURE VS. SPLIT-DOSE EXPOSURES IN HUMAN CELL NEOPLASTIC TRANSFORMATION.

    SciTech Connect

    BENNETT, P.V.; CUTTER, N.C.; SUTHERLAND, B.M.

    2006-06-05

    Since radiation fields of space contain many-fold more protons than high atomic number, high energy (HZE) particles, cells in astronaut crews will experience on average several proton hits before an HZE hit. Thus radiation regimes of proton exposure before HZE particle exposure simulate space radiation exposure, and measurement of the frequency of neoplastic transformation of human primary cells to anchorage-independent growth simulates in initial step in cancer induction. Previously our group found that exposure to 20 cGy 1 GeV/n protons followed within about 1 hr by a HZE ion (20 cGy 1 GeV/n Fe or Ti ions) hit gave about a 3-fold increase in transformation frequency ([1]). To provide insight into the H-HZE induced increased transformation frequencies, we asked if split doses of the same ion gave similar increased transformation frequencies. However, the data show that the split dose of 20 cGy plus 20 cGy of either H or HZE ions gave about the same effect as the 40 cGy uninterrupted dose, quite different from the effect of the mixed ion H + HZE irradiation. We also asked if lower proton doses than 20 cGy followed 15 minutes later by 20 cGy of HZE ions gave greater than additive transformation frequencies. Substantial increases in transformation levels were observed for all proton doses tested, including 1 cGy. These results point to the signal importance of protons in affecting the effect of space radiation on human cells.

  11. Role of pHi, and proton transporters in oncogene-driven neoplastic transformation

    PubMed Central

    Reshkin, Stephan Joel; Greco, Maria Raffaella; Cardone, Rosa Angela

    2014-01-01

    The change of a normal, healthy cell to a transformed cell is the first step in the evolutionary arc of a cancer. While the role of oncogenes in this ‘passage’ is well known, the role of ion transporters in this critical step is less known and is fundamental to our understanding the early physiological processes of carcinogenesis. Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics leading to a reversal of the normal tissue intracellular to extracellular pH gradient (ΔpHi to ΔpHe). When this perturbation in pH dynamics occurs during carcinogenesis is less clear. Very early studies using the introduction of different oncogene proteins into cells observed a concordance between neoplastic transformation and a cytoplasmic alkalinization occurring concomitantly with a shift towards glycolysis in the presence of oxygen, i.e. ‘Warburg metabolism’. These processes may instigate a vicious cycle that drives later progression towards fully developed cancer where the reversed pH gradient becomes ever more pronounced. This review presents our understanding of the role of pH and the NHE1 in driving transformation, in determining the first appearance of the cancer ‘hallmark’ characteristics and how the use of pharmacological approaches targeting pH/NHE1 may open up new avenues for efficient treatments even during the first steps of cancer development. PMID:24493748

  12. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation - Final Technical Report

    SciTech Connect

    John Leslie Redpath

    2007-01-17

    The objective of the research was to examine mechanisms underlying the suppressive effects of low doses (<10 cGy) of low-LET radiation on the endpoint of neoplastic transformation in vitro. The findings indicated a role for upregulation of DNA repair but not of antioxidants.

  13. Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens.

    PubMed

    Russo, Jose; Tahin, Quivo; Lareef, M Hasan; Hu, Yun-Fu; Russo, Irma H

    2002-01-01

    Sporadic breast cancer, the most common cancer diagnosed in American and Northern European women, is gradually increasing in incidence in most Western countries. Prevention would be the most efficient way of eradicating this disease. This goal, however, cannot be accomplished until the specific agent(s) or mechanisms that initiate the neoplastic process are identified. Experimental studies have demonstrated that mammary cancer is a hormone-dependent multistep process that can be induced by a variety of compounds and mechanisms, that is, hormones, chemicals, radiation, and viruses, in addition to or in combination with genetic factors. Although estrogens have been shown to play a central role in breast cancer development, their carcinogenicity on human breast epithelial cells (HBECs) has not yet been clearly demonstrated. Breast cancer initiates in the undifferentiated lobules type 1, which are composed of three cell types: highly proliferating cells that are estrogen-receptor negative (ER-), nonproliferating cells that are ER positive (ER+), and very few (<1%) ER+ cells that proliferate. Interestingly, endogenous 17beta-estradiol (E(2)) is metabolized by the cytochrome P450 enzyme isoforms CYP1A1 and CYP1B1, which also activate benzo[a]pyrene (B[a]P), a carcinogen contained in cigarette smoke. We postulate that if estrogens are carcinogenic in HBECs, they should induce the same transformation phenotypes induced by chemical carcinogens and ultimately genomic changes observed in spontaneously developing primary breast cancers. To test this hypothesis we compared the transforming potential of E(2) on the HBEC MCF-10F with that of B[a]P. Both E(2) and B[a]P induced anchorage-independent growth, colony formation in agar methocel, and loss of ductulogenic capacity in collagen gel, all parameters indicative of cell transformation. In addition, the DNA of E(2)-transformed cells expressed LOH in chromosome 11 at 11q23.3, 11q24.2-q25, and LOH at 13q12-q13. B[a]P-induced cell

  14. Neoplastic transformation of rat liver epithelial cells is enhanced by non-transferrin-bound iron

    PubMed Central

    Messner, Donald J; Kowdley, Kris V

    2008-01-01

    Background Iron overload is associated with liver toxicity, cirrhosis, and hepatocellular carcinoma in humans. While most iron circulates in blood as transferrin-bound iron, non-transferrin-bound iron (NTBI) also becomes elevated and contributes to toxicity in the setting of iron overload. The mechanism for iron-related carcinogenesis is not well understood, in part due to a shortage of suitable experimental models. The primary aim of this study was to investigate NTBI-related hepatic carcinogenesis using T51B rat liver epithelial cells, a non-neoplastic cell line previously developed for carcinogenicity and tumor promotion studies. Methods T51B cells were loaded with iron by repeated addition of ferric ammonium citrate (FAC) to the culture medium. Iron internalization was documented by chemical assay, ferritin induction, and loss of calcein fluorescence. Proliferative effects were determined by cell count, toxicity was determined by MTT assay, and neoplastic transformation was assessed by measuring colony formation in soft agar. Cyclin levels were measured by western blot. Results T51B cells readily internalized NTBI given as FAC. Within 1 week of treatment at 200 μM, there were significant but well-tolerated toxic effects including a decrease in cell proliferation (30% decrease, p < 0.01). FAC alone induced little or no colony formation in soft agar. In contrast, FAC addition to cells previously initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resulted in a concentration dependent increase in colony formation. This was first detected at 12 weeks of FAC treatment and increased at longer times. At 16 weeks, colony formation increased more than 10 fold in cells treated with 200 μM FAC (p < 0.001). The iron chelator desferoxamine reduced both iron uptake and colony formation. Cells cultured with 200 μM FAC showed decreased cyclin D1, decreased cyclin A, and increased cyclin B1. Conclusion These results establish NTBI as a tumor promoter in T51B rat liver

  15. Analysis of the multistage process of neoplastic transformation of human fibroblasts

    SciTech Connect

    McCormick, J.J.

    1994-12-31

    Normal human cells in culture have never been neoplastically transformed by carcinogens. One explanation is that the life span of the cells is too short for them to acquire the necessary changes. To test this, we transfected diploid fibroblasts with a plasmid carrying v-myc gene and a selectable marker. A drug resistant clone expressing v-myc was passaged to the end of its life span. A few cells continued to proliferate and gave rise to a diploid, infinite life span that has normal growth control and in nontumorigenic. Analysis indicated that one more change, in addition to unregulated expression of v-myc, was involved in generating these cells. They spontaneously gave rise to a near-diploid strain with a stable karyotype of 34 chromosomes, including 2 markers. This strain, MSU-1.1, grows more rapidly, is less dependent on growth factors, but does not form large colonies in agar and is not tumorigenic. At least two additional changes were involved in generating this strain. To determine the number and kinds of additional changes required to transform MSU-1.1 cells to oncogenes in vectors engineering for overexpression, and selected for focus-formation. The focus-derived cells were growth factor independent, formed large colonies in agar, and produced sarcomas with a short latency. These malignant cells had acquired two additional changes, but no change in karyotype. Exposure of MSU-1.1 cells to carcinogens and selection for foci also yielded malignant cells. Those analyzed to date show loss of 1 or 2 more chromosomes and of p53 function.

  16. Neoplastic transformation of mouse mammary epithelial cells by in vitro exposure to N-methyl-N-nitrosourea

    SciTech Connect

    Miyamoto, S.; Guzman, R.C.; Osborn, R.C.; Nandi, S.

    1988-01-01

    High-efficiency neoplastic transformation of mouse mammary epithelial cells in primary collagen gel culture was induced by N-methyl-N-nitrosoureau (MNU). Mammary epithelial cells, isolated from virgin BALB/c mice, were embedded within collagen gels and grown in a serum-free medium containing prolactin, progesterone, and linoleic acid. The cells were then treated with MNU on day 3 of culture and subsequently at weekly intervals for up to 4 weeks. Eleven to 14 days after the final carcinogen treatment, the cells were removed from the collagen gels and injected into the cleared mammary fat pads of syngeneic hosts to assay for transformed cell populations. A single exposure or multiple exposures of these cells to MNU was effective in inducing tumorigenic cells that produced palpable tumors as early as 6 weeks after transplantation. Two treatments with MNU were optimal for neoplastic transformation and produced tumors in 79% of the injected fat pads. All the tumors originated at the examination at the site of injection and had extensive central necroses. Histological examination indicated that the tumors were mammary carcinomas. Secondary transplantation of tumor pieces into intact mammary glands produced palpable carcinomas of the same histology within 1-8 weeks. This system provides a distinct means to study the mechanism of mammary neoplastic transformation at cellular and molecular levels.

  17. Althaea rosea Cavanil and Plantago major L. suppress neoplastic cell transformation through the inhibition of epidermal growth factor receptor kinase.

    PubMed

    Choi, Eun-Sun; Cho, Sung-Dae; Shin, Ji-Ae; Kwon, Ki Han; Cho, Nam-Pyo; Shim, Jung-Hyun

    2012-10-01

    For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications. PMID:22767187

  18. Radiation-resistant B-1 cells: A possible initiating cells of neoplastic transformation.

    PubMed

    Guimarães-Cunha, Caroline Ferreira; Alvares-Saraiva, Anuska Marcelino; de Souza Apostolico, Juliana; Popi, Ana Flavia

    2016-07-01

    The role of B-1 cells in the hyperproliferative hematologic disease has been described. Several reports bring evidences that B-1 cells are the main cell population in the chronic lymphatic leukemia. It is also described that these cells have an important involvement in the lupus erythematous systemic. The murine model used to investigate both disease models is NZB/NZW. Data from literature point that mutation in micro-RNA 15a and 16 are the responsible for the B-1 hyperplasia in these mice. Interestingly, it was demonstrated that NZB/NZW B-1 cells are radioresistant, contrariwise to observe in other mouse lineage derived B-1 cells and B-2 cells. However, some reports bring evidences that a small percentage of B-1 cells in healthy mice are also able to survive to irradiation. Herein, we aim to investigate the malignant potential of ionizing-radiation resistant B-1 cells in vitro. Our main goal is to establish a model that mimics the neoplastic transformation originate to a damage exposure of DNA, and not only related to intrinsic mutations. Data shown here demonstrated that radiation-resistant B-1 cells were able to survive long periods in culture. Further, these cells show proliferation index increase in relation to non-irradiated B-1 cells. In addition, radiation resistant B-1 cells showed hyperploid, morphologic alterations, increased induction of apoptosis after anti-IgM stimulation. Based on these results, we could suggest that radiation resistant B-1 cells showed some modifications in that could be related to induction of malignant potential. PMID:26898918

  19. Inhibition of chemically-induced neoplastic transformation by a novel tetrasodium diphosphate astaxanthin derivative.

    PubMed

    Hix, Laura M; Frey, Dean A; McLaws, Mark D; Østerlie, Marianne; Lockwood, Samuel F; Bertram, John S

    2005-09-01

    Carotenoids have been implicated in numerous epidemiological studies as being protective against cancer at many sites, and their chemopreventive properties have been confirmed in laboratory studies. Astaxanthin (AST), primarily a carotenoid of marine origin, responsible for the pink coloration of salmon, shrimp and lobster, has received relatively little attention. As with other carotenoids, its highly lipophilic properties complicate delivery to model systems. To overcome this issue we have synthesized a novel tetrasodium diphosphate astaxanthin (pAST) derivative with aqueous dispersibility of 25.21 mg/ml. pAST was delivered to C3H/10T1/2 cells in an aqueous/ethanol solution and compared with non-esterified AST dissolved in tetrahydrofuran. We show pAST to (i) upregulate connexin 43 (Cx43) protein expression; (ii) increase the formation of Cx43 immunoreactive plaques; (iii) upregulate gap junctional intercellular communication (GJIC); and (iv) cause 100% inhibition of methylcholanthrene-induced neoplastic transformation at 10(-6) M. In all these assays, pAST was superior to non-esterified AST itself; in fact, pAST exceeded the potency of all other previously tested carotenoids in this model system. Cleavage of pAST to non-esterified (free) AST and uptake into cells was also verified by HPLC; however, levels of free AST were approximately 100-fold lower than in cells treated with AST itself, suggesting that pAST possesses intrinsic activity. The dual properties of water dispersibility (enabling parenteral administration in vivo) and increased potency should prove extremely useful in the future development of cancer chemopreventive agents. PMID:15888493

  20. Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

    PubMed Central

    2012-01-01

    Background Marek’s Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the non-neoplastic cells (CD30lo) form the majority of population. MD is a unique natural in-vivo model of human CD30hi lymphomas with both natural CD30hi lymphomagenesis and spontaneous regression. The exact mechanism of neoplastic transformation from CD30lo expressing phenotype to CD30hi expressing neoplastic phenotype is unknown. Here, using microarray, proteomics and Systems Biology modeling; we compare the global gene expression of CD30lo and CD30hi cells to identify key pathways of neoplastic transformation. We propose and test a specific mechanism of neoplastic transformation, and genetic resistance, involving the MDV oncogene Meq, host gene products of the Nuclear Factor Kappa B (NF-κB) family and CD30; we also identify a novel Meq protein interactome. Results Our results show that a) CD30lo lymphocytes are pre-neoplastic precursors and not merely reactive lymphocytes; b) multiple transformation mechanisms exist and are potentially controlled by Meq; c) Meq can drive a feed-forward cycle that induces CD30 transcription, increases CD30 signaling which activates NF-κB, and, in turn, increases Meq transcription; d) Meq transcriptional repression or activation of the CD30 promoter generally correlates with polymorphisms in the CD30 promoter distinguishing MD-lymphoma resistant and susceptible chicken genotypes e) MDV oncoprotein Meq interacts with proteins involved in physiological processes central to lymphomagenesis. Conclusions In the context of the MD lymphoma microenvironment (and potentially in other CD30hi lymphomas as well), our results show that the neoplastic transformation is a continuum and the non-neoplastic cells are actually pre-neoplastic precursor

  1. The Syrian hamster embryo (SHE) cell transformation system: a biologically relevant in vitro model--with carcinogen predicting capabilities--of in vivo multistage neoplastic transformation.

    PubMed

    Isfort, R J; LeBoeuf, R A

    1995-01-01

    Neoplastic transformation is a multistep process that can be modeled in vitro using Syrian hamster embryo (SHE) cells. SHE cells multistage transformation involves several intermediate stages, including morphological transformation, immortality, acquisition of tumorigenicity, and malignant progression. Analysis of the molecular alterations that occur at each stage indicated that morphological transformation results from both carcinogen-induced irreversible chromosomal/genetic mutations and reversible genetic events, including altered DNA methylation. Morphological transformation results from a block in the cellular differentiation of progenitor and determined stem-like cells in the SHE cell population via alternation in the expression of the H19 tumor suppressor gene and other genes. Immortality results from genetic mutations in growth factor responsiveness, including loss of growth suppression by TGF beta and autocrine growth factor production, and genomic stability, resulting in genomic instability and an increased mutation rate. Acquisition of tumorigenicity involves loss of tumor suppressor gene function, altered mitogenic signal transduction, mutation of oncogenes, acquisition of anchorage independent growth, and chromosomal aberrations. Malignant progression is associated with alterations in extracellular matrix growth characteristics, alterations in cytoskeleton structure, elevated fibrinolytic activity, secretion of proteases, and changes in extracellular matrix protein secretion. Together, these changes model the alterations observed during in vivo neoplastic transformation and possibly explain why the SHE assay, as a carcinogen screening tool, is able to identify carcinogens with a 80 to 85% accuracy. PMID:9012585

  2. Different Roles of Negative and Positive Components of the Circadian Clock in Oncogene-induced Neoplastic Transformation.

    PubMed

    Katamune, Chiharu; Koyanagi, Satoru; Shiromizu, Shoya; Matsunaga, Naoya; Shimba, Shigeki; Shibata, Shigenobu; Ohdo, Shigehiro

    2016-05-13

    In mammals, circadian rhythms in physiological function are generated by a molecular oscillator driven by transcriptional-translational feedback loop consisting of negative and positive regulators. Disruption of this circadian clock machinery is thought to increase the risk of cancer development, but the potential contributions of each component of circadian clock to oncogenesis have been little explored. Here we reported that negative and positive transcriptional regulators of circadian feedback loop had different roles in oncogene-induced neoplastic transformation. Mouse embryonic fibroblasts prepared from animals deficient in negative circadian clock regulators, Period2 (Per2) or Cryptochrome1/2 (Cry1/2), were prone to transformation induced by co-expression of H-ras(V12) and SV40 large T antigen (SV40LT). In contrast, mouse embryonic fibroblasts prepared from mice deficient in positive circadian clock regulators, Bmal1 or Clock, showed resistance to oncogene-induced transformation. In Per2 mutant and Cry1/2-null cells, the introduction of oncogenes induced expression of ATF4, a potent repressor of cell senescence-associated proteins p16INK4a and p19ARF. Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation. Conversely, in Bmal1-null and Clock mutant cells, the expression of ATF4 was not induced by oncogene introduction, which allowed constitutive expression of p16INK4a and p19ARF triggering cellular senescence. Although genetic ablation of either negative or positive transcriptional regulators of the circadian clock leads to disrupted rhythms in physiological functions, our findings define their different contributions to neoplastic cellular transformation. PMID:26961881

  3. Autophagy-deficiency in hepatic progenitor cells leads to the defects of stemness and enhances susceptibility to neoplastic transformation.

    PubMed

    Xue, Feng; Hu, Lei; Ge, Ruiliang; Yang, Lixue; Liu, Kai; Li, Yunyun; Sun, Yanfu; Wang, Kui

    2016-02-01

    Autophagy is a highly conserved and lysosome-dependent degradation process which assists in cell survival and tissue homeostasis. Although previous reports have shown that deletion of the essential autophagy gene disturbs stem cell maintenance in some cell types such as hematopoietic and neural cells, it remains unclear how autophagy-deficiency influences hepatic progenitor cells (HPCs). Here we report that Atg5-deficiency in HPCs delays HPC-mediated rat liver regeneration in vivo. In vitro researches further demonstrate that loss of autophagy decreases the abilities of colony and spheroid formations, and disrupts the induction of hepatic differentiation in HPCs. Meanwhile, autophagy-deficiency increases the accumulations of damaged mitochondria and mitochondrial reactive oxygen species (mtROS) and suppresses homologous recombination (HR) pathway of DNA damage repair in HPCs. Moreover, in both diethylnitrosamine (DEN) and CCl4 models, autophagy-deficiency accelerates neoplastic transformation of HPCs. In conclusion, these findings demonstrate that autophagy contributes to stemness maintenance and reduces susceptibility to neoplastic transformation in HPCs. PMID:26607902

  4. Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro.

    PubMed

    Dyshlovoy, Sergey A; Tabakmakher, Kseniya M; Hauschild, Jessica; Shchekaleva, Regina K; Otte, Katharina; Guzii, Alla G; Makarieva, Tatyana N; Kudryashova, Ekaterina K; Fedorov, Sergey N; Shubina, Larisa K; Bokemeyer, Carsten; Honecker, Friedemann; Stonik, Valentin A; von Amsberg, Gunhild

    2016-01-01

    Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1-6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1-4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P⁺ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. PMID:27428983

  5. Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

    PubMed Central

    Dyshlovoy, Sergey A.; Tabakmakher, Kseniya M.; Hauschild, Jessica; Shchekaleva, Regina K.; Otte, Katharina; Guzii, Alla G.; Makarieva, Tatyana N.; Kudryashova, Ekaterina K.; Fedorov, Sergey N.; Shubina, Larisa K.; Bokemeyer, Carsten; Honecker, Friedemann; Stonik, Valentin A.; von Amsberg, Gunhild

    2016-01-01

    Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1–6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1–4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P+ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. PMID:27428983

  6. Increased Frequency of Spontaneous Neoplastic Transformation in Progeny of Bystander Cells from Cultures Exposed to Densely Ionizing Radiation

    PubMed Central

    Buonanno, Manuela; de Toledo, Sonia M.; Azzam, Edouard I.

    2011-01-01

    An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons. PMID:21738697

  7. Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation.

    PubMed

    Buonanno, Manuela; de Toledo, Sonia M; Azzam, Edouard I

    2011-01-01

    An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs), modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon) or sparsely ionizing protons (1 GeV). An increase (P<0.05) in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons. PMID:21738697

  8. Multistep nature of X-ray-induced neoplastic transformation in golden hamster embryo cells: expression of transformed phenotypes and stepwise changes in karyotypes

    SciTech Connect

    Suzuki, K.; Suzuki, F.; Watanabe, M.; Nikaido, O.

    1989-04-15

    We have examined the expression of transformed phenotypes and genetic changes associated with the expression of each transformed phenotype after X-ray irradiation. Unirradiated cells grown at a constant growth rate until 8 passages (population doubling number, 15) exhibited little morphological change and ceased to divide thereafter. X-irradiated cells escaped from senescence and showed morphological alteration and anchorage independence after a population doubling number of 20. The acquisition of tumorigenicity in nude mice was observed much later (35 population doublings after irradiation). From cytogenetic analysis, all anchorage-independent clones were consistently found to have trisomy of chromosome 7. Furthermore, cells derived from tumors contained three copies of chromosome 9q in addition to the trisomy of chromosome 7. We have not detected any augmented expression of v-Ha-ras- and v-myc-related oncogenes with RNA dot-blot analysis and could not find activation of any type of oncogenes by NIH3T3 transfection experiments. Our studies demonstrated that X-ray-induced neoplastic transformation is a multistep phenomenon and that the numerical change of specific chromosomes may play an important role in the expression of each transformed phenotype. The results suggest that different endogenous oncogenes, other than the ras gene family and myc oncogene, could be responsible for the progressive nature of neoplastic transformation.

  9. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation

    PubMed Central

    Nolan-Stevaux, Olivier; Lau, Janet; Truitt, Morgan L.; Chu, Gerald C.; Hebrok, Matthias; Fernández-Zapico, Martin E.; Hanahan, Douglas

    2009-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by the deregulation of the hedgehog signaling pathway. The Sonic Hedgehog ligand (Shh), absent in the normal pancreas, is highly expressed in pancreatic tumors and is sufficient to induce neoplastic precursor lesions in mouse models. We investigated the mechanism of Shh signaling in PDAC carcinogenesis by genetically ablating the canonical bottleneck of hedgehog signaling, the transmembrane protein Smoothened (Smo), in the pancreatic epithelium of PDAC-susceptible mice. We report that multistage development of PDAC tumors is not affected by the deletion of Smo in the pancreas, demonstrating that autocrine Shh–Ptch–Smo signaling is not required in pancreatic ductal cells for PDAC progression. However, the expression of Gli target genes is maintained in Smo-negative ducts, implicating alternative means of regulating Gli transcription in the neoplastic ductal epithelium. In PDAC tumor cells, we find that Gli transcription is decoupled from upstream Shh–Ptch–Smo signaling and is regulated by TGF-β and KRAS, and we show that Gli1 is required both for survival and for the KRAS-mediated transformed phenotype of cultured PDAC cancer cells. PMID:19136624

  10. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells

    PubMed Central

    Zhang, Shiwu; Mercado-Uribe, Imelda; Sood, Anil; Bast, Robert C.; Liu, Jinsong

    2016-01-01

    Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID:27382431

  11. Point Mutations in c-Myc Uncouple Neoplastic Transformation from Multiple Other Phenotypes in Rat Fibroblasts

    PubMed Central

    Graves, J. Anthony; Rothermund, Kristi; Wang, Tao; Qian, Wei; Van Houten, Bennett; Prochownik, Edward V.

    2010-01-01

    Deregulation of c-Myc (Myc) occurs in many cancers. In addition to transforming various cell types, Myc also influences additional transformation-associated cellular phenotypes including proliferation, survival, genomic instability, reactive oxygen species production, and metabolism. Although Myc is wild type in most cancers (wtMyc), it occasionally acquires point mutations in certain lymphomas. Some of these mutations confer a survival advantage despite partially attenuating proliferation and transformation. Here, we have evaluated four naturally-occurring or synthetic point mutations of Myc for their ability to affect these phenotypes, as well as to promote genomic instability, to generate reactive oxygen species and to up-regulate aerobic glycolysis and oxidative phosphorylation. Our findings indicate that many of these phenotypes are genetically and functionally independent of one another and are not necessary for transformation. Specifically, the higher rate of glucose metabolism known to be associated with wtMyc deregulation was found to be independent of transformation. One mutation (Q131R) was greatly impaired for nearly all of the studied Myc phenotypes, yet was able to retain some ability to transform. These findings indicate that, while the Myc phenotypes examined here make additive contributions to transformation, none, with the possible exception of increased reliance on extracellular glutamine for survival, are necessary for achieving this state. PMID:21060841

  12. Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells

    PubMed Central

    Lohcharoenkal, Warangkana; Wang, Liying; Stueckle, Todd A.; Park, Jino; Tse, William; Dinu, Cerasela-Zoica; Rojanasakul, Yon

    2014-01-01

    Rapid development and deployment of engineered nanomaterials such as carbon nanotubes (CNTs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their long-term effects which have not been well addressed. We demonstrated here that prolonged exposure of human mesothelial cells to single-walled CNT (SWCNT) induced neoplastic-like transformation as indicated by anchorage-independent cell growth and increased cell invasiveness. Such transformation was associated with an up-regulation of H-Ras and activation of ERK1/2. Downregulation of H-Ras by siRNA or inactivation of ERK by chemical inhibitor effectively inhibited the aggressive phenotype of SWCNT-exposed cells. Integrin alpha V and cortactin, but not epithelial-mesenchymal transition (EMT) transcriptional regulators, were up-regulated in the SWCNT-exposed cells, suggesting their role in the aggressive phenotype. Cortactin expression was shown to be controlled by the H-Ras/ERK signaling. Thus, our results indicate a novel role of H-Ras/ERK signaling and cortactin in the aggressive transformation of human mesothelial cells by SWCNT. PMID:24971065

  13. Mobile phone base station radiation does not affect neoplastic transformation in BALB/3T3 cells.

    PubMed

    Hirose, H; Suhara, T; Kaji, N; Sakuma, N; Sekijima, M; Nojima, T; Miyakoshi, J

    2008-01-01

    A large-scale in vitro study focusing on low-level radiofrequency (RF) fields from mobile radio base stations employing the International Mobile Telecommunication 2000 (IMT-2000) cellular system was conducted to test the hypothesis that modulated RF fields affect malignant transformation or other cellular stress responses. Our group previously reported that DNA strand breaks were not induced in human cells exposed to 2.1425 GHz Wideband Code Division Multiple Access (W-CDMA) radiation up to 800 mW/kg from mobile radio base stations employing the IMT-2000 cellular system. In the current study, BALB/3T3 cells were continuously exposed to 2.1425 GHz W-CDMA RF fields at specific absorption rates (SARs) of 80 and 800 mW/kg for 6 weeks and malignant cell transformation was assessed. In addition, 3-methylcholanthrene (MCA)-treated cells were exposed to RF fields in a similar fashion, to assess for effects on tumor promotion. Finally, the effect of RF fields on tumor co-promotion was assessed in BALB/3T3 cells initiated with MCA and co-exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA). At the end of the incubation period, transformation dishes were fixed, stained with Giemsa, and scored for morphologically transformed foci. No significant differences in transformation frequency were observed between the test groups exposed to RF signals and the sham-exposed negative controls in the non-, MCA-, or MCA plus TPA-treated cells. Our studies found no evidence to support the hypothesis that RF fields may affect malignant transformation. Our results suggest that exposure to low-level RF radiation of up to 800 mW/kg does not induce cell transformation, which causes tumor formation. PMID:17694516

  14. Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells.

    PubMed Central

    Berlingieri, M T; Manfioletti, G; Santoro, M; Bandiera, A; Visconti, R; Giancotti, V; Fusco, A

    1995-01-01

    Elevated expression of the three high-mobility group I (HMGI) proteins (HMGI, HMGY, and HMGI-C) has previously been correlated with the presence of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells and in experimental thyroid, lung, mammary, and skin carcinomas. Northern (RNA) blot and run-on analyses demonstrated that the induction of HMGI genes in transformed thyroid cells occurs at the transcriptional level. An antisense methodology to block HMGI-C protein synthesis was then used to analyze the role of this protein in the process of thyroid cell transformation. Transfection of an antisense construct for the HMGI-C cDNA into normal thyroid cells, followed by infection with transforming myeloproliferative sarcoma virus or Kirsten murine sarcoma virus, generated cell lines that expressed significant levels of the retroviral transforming oncogenes v-mos or v-ras-Ki and removed the dependency on thyroid-stimulating hormones. However, in contrast with untransfected cells or cells transfected with the sense construct, those containing the antisense construct did not demonstrate the appearance of any malignant phenotypic markers (growth in soft agar and tumorigenicity in athymic mice). A great reduction of the HMGI-C protein levels and the absence of the HMGI(Y) proteins was observed in the HMGI-C antisense-transfected, virally infected cells. Therefore, the HMGI-C protein seems to play a key role in the transformation of these thyroid cells. PMID:7862147

  15. A conundrum in molecular toxicology: molecular and biological changes during neoplastic transformation of human cells.

    PubMed

    Milo, G E; Shuler, C F; Lee, H; Casto, B C

    1995-12-01

    The process of multistage carcinogenesis lends itself to the concept that the effects of carcinogens are mediated through dose-related, multi-hit, linear changes. Multiple in vitro model systems have been developed that are designed to examine the cellular changes associated with the progression of cells through the different stages in the process; however, these systems may have inherent limitations due to the cell lines used for these studies, the manner of assessing the effects of the carcinogens, and the subsequent growth and differentiation of the exposed cells. Each of these variables results in increasing levels of uncertainty relative to the correlation of the events with the actual process of human tumor development. Therefore, the prediction of the ultimate effect of any carcinogen is difficult. Moreover, relationships between individual biological endpoints resulting from carcinogen treatment appear at best to be approximations. The presence of an activated carcinogen inside the cell can give rise to multiple outcomes, only some of which may be critical events. For example, site-specific modification of the 12th and 13th codons of H-ras is different than that in the adjacent 14th and 15th codons. It is interesting to speculate what effect these differences might have on a biological outcome, e.g., transformation to anchorage-independent growth. The use of different model systems to examine the effects of activated carcinogens also creates additional problems. Comparisons of in vitro transformed cells with similar cells isolated from human tumors indicate that the culture environment appears to influence the expression of a particular phenotype, in that human tumor cells in culture express many of the same parameters as those found in cells transformed with carcinogens in vitro. If the process of transformation is linear, then less aggressive phenotypes should progress to a more aggressive transformed stage. However, in carcinogen-transformed human cells

  16. Mechanisms underlying the adaptive response against spontaneous neoplastic transformation induced by low doses of low LET radiation, Final Technical Report

    SciTech Connect

    J. Leslie Redpath, Ph.D.

    2006-01-23

    The goal of this project was to investigate mechanisms underlying the adaptive response seen following exposure of HeLa x skin fibroblast human hybrid cells to low doses of low LET radiation. It was proposed to investigate the contributions of three possible mechanisms. These were: 1. Upregulation of cellular antioxidant status. 2. Upregulation of DNA repair. 3. Upregulation of gap junction intracellular communication. We have completed the study of the role of upregulation of reduced glutathione (GSH) as a possible mechanism underlying our observed suppression of transformation frequency at low radiation doses. We have also completed our study of the possible role of upregulation of DNA repair in the observed adaptive response against neoplastic transformation. We concluded that upregulation of DNA repair may be more important in modulating transformation at the higher dose. A manuscript describing the above studies has been submitted published in Carcinogenesis 24:1961-1965, 2003. Finally, we have completed two studies of the possible role of upregulation of gap junction intercellular communication (GJIC) in modulating transformation frequency at low doses of low LET radiation. This research was published in Radiation Research 162:646-654, 2004. In order to optimize the opportunity for GJIC, we then carried out a study where confluent cultures were irradiated. The results indicated, that while the degree of low dose suppression was somewhat reduced compared to that seen for subconfluent cultures, it was not completely absent. This research has been submitted for publication. Our research program was of sufficient interest to generate two invited reviews, and five invited presentations.

  17. Neoplastic transformation of oral lichen: case report and review of the literature

    PubMed Central

    Abbate, G; Foscolo, AM; Gallotti, M; Lancella, A; Mingo, F

    2006-01-01

    Summary Aim of the present investigation was to analyse the possible malignant transformation of oral lichen planus to carcinoma, especially in the atrophic erosive forms and those displaying plaques involving the top of the tongue. A review has been made of the literature, from 1986 to the present day. This search outlines the relationship between oral lichen planus, hepatitis C virus infection, Epstein-Barr virus infection and the importance of periodic follow-up in all patients with oral lichen planus. The case is described of malignant transformation of oral lichen planus to oral cancer in a female presenting asymptomatic hepatitis C virus infection. The clinical history confirms the most important aspects of the relationship between oral lichen planus and oral cancer. Oral lichen planus should be considered as a precancerous lesion, particularly in patients presenting hepatitis C virus infection, requiring follow-up, at close intervals, starting from 3 months after diagnosis. PMID:18383758

  18. [Radiation-induced, irreparable, hereditary changes in cells promoting their neoplastic transformation].

    PubMed

    Kuzin, A M; Vagabova, M E; Iurov, S S

    1988-01-01

    In experiments with model plant tumors (Kalanchoe-ti plasmid Agrobact. tumefaciens C-58D) it was shown that exposure of the recipient plant to low-level gamma-radiation of 2 Gy induced changes in cells that were not repaired over two months promoting tumoral transformations in them. Those changes were shown to persist in the offspring of the exposed somatic cells. PMID:3363091

  19. Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product.

    PubMed Central

    Vallone, D; Battista, S; Pierantoni, G M; Fedele, M; Casalino, L; Santoro, M; Viglietto, G; Fusco, A; Verde, P

    1997-01-01

    The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation. PMID:9311991

  20. Karyotypic changes with neoplastic conversion in morphologically transformed golden hamster embryo cells induced by X-rays

    SciTech Connect

    Watanabe, M.; Suzuki, K.; Kodama, S. )

    1990-02-01

    Chromosomes from nine morphologically transformed (MT) cell lines (designated MT14 to MT22) of Golden hamster embryo cells induced by X-rays and from tumor-derived cell lines (MT14T to MT22T), obtained after injection of MT cells, were analyzed by the Giemsa banding method. MT cell lines showed a variety of numerical abnormalities. All of the MT cell lines involved trisomy of chromosomes 11 (80 to 100% of cells in each cell line) and 3 (8% of MT22 cells and 100% in other cell lines). Although the latent period for tumor growth differed greatly, eight of nine MT cell lines (MT14 to MT21) produced tumors at the site of injection. All tumor-derived cell lines involved trisomy of chromosome 3 at a 100% rate of incidence. Seven of nine tumor-derived cell lines (MT15T to MT18T, MT20T to MT22T) lost one chromosome 11 from the trisomic condition, resulting in disomy of chromosome 11. These results suggest that trisomies of chromosomes 11 and 3 may play a role in X-ray-induced neoplastic progression.

  1. Metastasis suppressors Nm23H1 and Nm23H2 differentially regulate neoplastic transformation and tumorigenesis.

    PubMed

    Tong, Yao; Yung, Lisa Y; Wong, Yung H

    2015-06-01

    Nm23H1 and H2 are prototypical metastasis suppressors with diverse functions, but recent studies suggest that they may also regulate tumorigenesis. Here, we employed both cellular and in vivo assays to examine the effect of Nm23H1 and H2 on tumorigenesis induced by oncogenic Ras and/or p53 deficiency. Co-expression of Nm23H1 but not H2 in NIH3T3 cells effectively suppressed neoplastic transformation and tumorigenesis induced by the oncogenic H-Ras G12V mutant. Overexpression of Nm23H1 but not H2 also inhibited tumorigenesis by human cervical cancer HeLa cells with p53 deficiency. However, in human non-small-cell lung carcinoma H1299 cells harboring N-Ras Q61K oncogenic mutation and p53 deletion, overexpression of Nm23H1 did not affect tumorigenesis in nude mice assays, while overexpression of Nm23H2 enhanced tumor growth with elevated expression of the c-Myc proto-oncogene. Collectively, these results suggest that Nm23H1 and H2 have differential abilities to modulate tumorigenesis. PMID:25748386

  2. CDK1 Phosphorylation of YAP Promotes Mitotic Defects and Cell Motility and Is Essential for Neoplastic Transformation

    PubMed Central

    Yang, Shuping; Zhang, Lin; Liu, Miao; Chong, Rong; Ding, Shi-Jian; Chen, Yuanhong; Dong, Jixin

    2013-01-01

    The Yes-associated protein YAP is a downstream effector of the Hippo pathway of cell cycle control which plays important roles in tumorigenesis. Hippo-mediated phosphorylation YAP, mainly at S127, inactivates YAP function. In this study, we define a mechanism for positive regulation of YAP activity that is critical for its oncogenic function. Specifically, we found that YAP is phosphorylated in vitro and in vivo by the cell cycle kinase CDK1 at T119, S289, and S367 during G2/M phase of the cell cycle. We also found that ectopic expression of a phosphomimetic YAP mutant (YAP3D, harboring T119D/S289D/S367D) was sufficient to induce mitotic defects in immortalized epithelial cells, including centrosome amplification, multipolar spindles and chromosome missegregation. Finally, we documented that mitotic phosphorylation of YAP was sufficient to promote cell migration and invasion in a manner essential for neoplastic cell transformation. In support of our findings, CDK1 inhibitors largely suppressed cell motility mediated by activated YAP-S127A but not the phosphomimetic mutant YAP3D. Collectively, our results reveal a previously unrecognized mechanism for controlling the activity of YAP that is crucial for its oncogenic function mediated by mitotic dysregulation. PMID:24101154

  3. Neoplastic-like transformation effect of single-walled and multi-walled carbon nanotubes compared to asbestos on human lung small airway epithelial cells

    PubMed Central

    Wang, Liying; Stueckle, Todd A.; Mishra, Anurag; Derk, Raymond; Meighan, Terence; Castranova, Vincent; Rojanasakul, Yon

    2015-01-01

    Accumulating evidence indicates that carbon nanotubes (CNTs) are biopersistent and can cause lung damage. With similar fibrous morphology and mode of exposure to asbestos, a known human carcinogen, growing concern has arisen for elevated risk of CNT-induced lung carcinogenesis; however, relatively little is known about the long-term carcinogenic effect of CNT. Neoplastic transformation is a key early event leading to carcinogenesis. We studied the ability of single- and multi-walled CNTs to induce neoplastic transformation of human lung epithelial cells compared to asbestos. Long-term (6-month) exposure of the cells to occupationally relevant concentrations of CNT in culture caused a neoplastic-like transformation phenotype as demonstrated by increased cell proliferation, anchorage-independent growth, invasion and angiogenesis. Whole-genome expression signature and protein expression analyses showed that single- and multi-walled CNTs shared similar signaling signatures which were distinct from asbestos. These results provide novel toxicogenomic information and suggest distinct particle-associated mechanisms of neoplasia promotion induced by CNTs and asbestos. PMID:23634900

  4. Neoplastic transformation and tumorigenesis associated with overexpression of imup-1 and imup-2 genes in cultured NIH/3T3 mouse fibroblasts

    SciTech Connect

    Ryoo, Zae Young . E-mail: jaewoong64@hanmail.net; Jung, Boo Kyoung; Lee, Sang Ryeul; Kim, Myoung Ok; Kim, Sung Hyun; Kim, Hyo Jin; Ahn, Jung Yong; Lee, Tae-Hoon; Cho, Youl Hee; Park, Jae Hak; Kim, Jin Kyeoung

    2006-10-27

    Immortalization-upregulated protein 1 (IMUP-1) and immortalization-upregulated protein 2 (IMUP-2) genes have been recently cloned and are known to be involved in SV40-mediated immortalization. IMUP-1 and IMUP-2 genes were strongly expressed in various cancer cell lines and tumors, suggesting the possibility that they might be involved in tumorigenicity. To directly elucidate the functional role of IMUP-1 and IMUP-2 on neoplastic transformation and tumorigenicity, we stably transfected IMUP-1 and IMUP-2 into NIH/3T3 mouse fibroblast cells. Cellular characteristics of the neoplastic transformation were assessed by transformation foci, growth in soft agar, and tumor development in nude mice. We found that IMUP-1 and IMUP-2 overexpressing cells showed altered growth properties, anchorage-independent growth in soft agar and inducing tumor in nude mice. Furthermore, IMUP-1 and IMUP-2 transformants proliferated in reduced serum and shortened cell cycle. These results suggest that ectopic overexpression of IMUP-1 and IMUP-2 may play an important role in acquiring a transformed phenotype, tumorigenicity in vivo, and be related to cellular proliferation.

  5. Focus formation and neoplastic transformation by herpes simplex virus type 2 inactivated intracellularly by 5-bromo-2'-deoxyuridine and near UV light

    SciTech Connect

    Manak, M.M.; Aurelian, L.; Ts'o, P.O.

    1981-01-01

    The induction of focus formation in low serum and of neoplastic transformation of Syrian hamster embryo cells was examined after the expression of herpes simplex virus type 2 functions. Syrian hamster embryo cells infected at a high multiplicity (5 PFU/cell) with 5-bromo-2'-deoxyuridine-labeled herpes simplex virus type 2 (11% substitution of thymidine residues) were exposed to near UV light irradiation at various times postinfection. This procedure specifically inactivated the viral genome, while having little, if any, effect on the unlabeled cellular DNA. Focus formation in 1% serum and neoplastic transformation were observed in cells exposed to virus inactivated before infection, but the frequency was enhanced (15- to 27-fold) in cells in which the virus was inactivated at 4 to 8 h postinfection. Only 2 to 45 independently isolated foci were capable of establishing tumorigenic lines. The established lines exhibited phenotypic alterations characteristic of a transformed state, including reduced serum requirement, anchorage-independent growth, and tumorigenicity. They retained viral DNA sequences and, even at relatively late passage, expressed viral antigens, including ICP 10.

  6. A panel of in vitro tests to evaluate genotoxic and morphological neoplastic transformation potential on Balb/3T3 cells by pristine and remediated titania and zirconia nanoparticles.

    PubMed

    Stoccoro, Andrea; Di Bucchianico, Sebastiano; Uboldi, Chiara; Coppedè, Fabio; Ponti, Jessica; Placidi, Claudia; Blosi, Magda; Ortelli, Simona; Costa, Anna Luisa; Migliore, Lucia

    2016-09-01

    The FP7 Sanowork project was aimed to minimise occupational hazard and exposure to engineered nanomaterials (ENM) through the surface modification in order to prevent possible health effects. In this frame, a number of nanoparticles (NP) have been selected, among which zirconium (ZrO2) and titanium (TiO2) dioxide. In this study, we tested ZrO2 NP and TiO2 NP either in their pristine (uncoated) form, or modified with citrate and/or silica on their surface. As benchmark material, Aeroxide® P25 was used. We assessed cytotoxicity, genotoxicity and induction of morphological neoplastic transformation of NP by using a panel of in vitro assays in an established mammalian cell line of murine origin (Balb/3T3). Cell viability was evaluated by means of colony-forming efficiency assay (CFE). Genotoxicity was investigated by cytokinesis-block micronucleus cytome assay (CBMN cyt) and comet assay, and by the use of the restriction enzymes EndoIII and Fpg, oxidatively damaged DNA was detected; finally, the morphological neoplastic transformation of NP was assayed in vitro by cell transformation assay (CTA). Our results show that the surface remediation has not been effective in modifying cyto- and genotoxic properties of the nanomaterials tested; indeed, in the case of remediation of zirconia and titania with citrate, there is a tendency to emphasise the toxic effects. The use of a panel of assays, such as those we have employed, allowing the evaluation of multiple endpoints, including cell transformation, seems particularly advisable especially in the case of long-term exposure effects in the same cell type. PMID:27056944

  7. Dr. Josef Steiner Cancer Research Prize Lecture: the role of physiological cell death in neoplastic transformation and in anti-cancer therapy.

    PubMed

    Strasser, A

    1999-05-17

    Cell death is a physiological process which is required for normal development and existence of multi-cellular organisms. Physiological cell death, or apoptosis, is controlled by an evolutionarily conserved mechanism. Abnormalities in this process are implicated as a cause or contributing factor in a variety of diseases. Inhibition of apoptosis can promote neoplastic transformation, particularly in combination with dysregulated cell-cycle control, and can influence the response of tumour cells to anti-cancer therapy. Molecular biological and biochemical approaches are used to find missing cell-death regulators and to define signalling cascades, while experiments in genetically modified mice will identify the essential function of these molecules. Discoveries from cell death research should provide clues for designing therapies for a variety of diseases, including degenerative disorders, auto-immunity and cancer. PMID:10225436

  8. Rat Protein Tyrosine Phosphatase η Suppresses the Neoplastic Phenotype of Retrovirally Transformed Thyroid Cells through the Stabilization of p27Kip1

    PubMed Central

    Trapasso, Francesco; Iuliano, Rodolfo; Boccia, Angelo; Stella, Antonella; Visconti, Roberta; Bruni, Paola; Baldassarre, Gustavo; Santoro, Massimo; Viglietto, Giuseppe; Fusco, Alfredo

    2000-01-01

    The r-PTPη gene encodes a rat receptor-type protein tyrosine phosphatase whose expression is negatively regulated by neoplastic cell transformation. Here we first demonstrate a dramatic reduction in DEP-1/HPTPη (the human homolog of r-PTPη) expression in a panel of human thyroid carcinomas. Subsequently, we show that the reexpression of the r-PTPη gene in highly malignant rat thyroid cells transformed by retroviruses carrying the v-mos and v-ras-Ki oncogenes suppresses their malignant phenotype. Cell cycle analysis demonstrated that r-PTPη caused G1 growth arrest and increased the cyclin-dependent kinase inhibitor p27Kip1 protein level by reducing the proteasome-dependent degradation rate. We propose that the r-PTPη tumor suppressor activity is mediated by p27Kip1 protein stabilization, because suppression of p27Kip1 protein synthesis using p27-specific antisense oligonucleotides blocked the growth-inhibitory effect induced by r-PTPη. Furthermore, we provide evidence that in v-mos- or v-ras-Ki-transformed thyroid cells, the p27Kip1 protein level was regulated by the mitogen-activated protein (MAP) kinase pathway and that r-PTPη regulated p27Kip1 stability by preventing v-mos- or v-ras-Ki-induced MAP kinase activation. PMID:11094075

  9. Nuclear Factor kappa B is central to Marek’s Disease herpesvirus induced neoplastic transformation of CD30 expressing lymphocytes in-vivo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Marek’s Disease (MD) is a hyperproliferative, lymphomatous, neoplastic disease of chickens caused by the oncogenic Gallid herpesvirus type 2 (GaHV-2; MDV). Like several human lymphomas the neoplastic MD lymphoma cells overexpress the CD30 antigen (CD30hi) and are in minority, while the n...

  10. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    SciTech Connect

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  11. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    PubMed Central

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a six month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. PMID:22521957

  12. Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes

    SciTech Connect

    Chamaon, Kathrin; Kirches, Elmar; Kanakis, Dimitrios; Braeuninger, Stefan; Dietzmann, Knut; Mawrin, Christian . E-mail: christian.mawrin@medizin.uni-magdeburg.de

    2005-05-27

    The reasons for overexpression of the oncogene pituitary tumor transforming gene (PTTG) in tumors are still not fully understood. A possible influence of the insulin-like growth factor I (Igf-I) may be of interest, since enhanced Igf-I signalling was reported in various human tumors. We examined the influence of Igf-I and insulin on PTTG expression in human astrocytoma cells in comparison to proliferating non-neoplastic rat embryonal astrocytes. PTTG mRNA expression and protein levels were increased in malignant astrocytes treated with Igf-I or insulin, whereas in rat embryonic astrocytes PTTG expression and protein levels increased only when cells were exposed to Igf-I. Enhanced transcription did not occur after treatment with inhibitors of phosphoinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), blocking the two basic signalling pathways of Igf-I and insulin. In addition to this transcriptional regulation, both kinases directly bind to PTTG, suggesting a second regulatory route by phosphorylation. However, the interaction of endogenous PTTG with MAPK and PI3K, as well as PTTG phosphorylation were independent from Igf-I or insulin. The latter results were also found in human testis, which contains high PTTG levels as well as in nonneoplastic astrocytes. This suggest, that PI3K and MAPK signalling is involved in PTTG regulation not only in malignant astrocytomas but also in non-tumorous cells.

  13. Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha.

    PubMed Central

    Santoni-Rugiu, E.; Nagy, P.; Jensen, M. R.; Factor, V. M.; Thorgeirsson, S. S.

    1996-01-01

    We have previously shown that co-expression of c-myc and transforming growth factor (TGF)-alpha as transgenes in mouse liver results in major enhancement of neoplastic development in this organ as compared with expression of either of these transgenes alone. In this report we describe in detail the progression from liver cell dysplasia to hepatocellular carcinomas (HCCs) occurring in the liver of c-myc/TGF-alpha and c-myc transgenic mice. Despite morphological similarities in the sequence of events between the two transgenic lines, the dramatic acceleration, extent, and severity of hepatic lesions in c-myc/TGF-alpha mice clearly demonstrated the synergistic effects of this transgenic combination. Although c-myc/TGF-alpha and c-myc females displayed longer latency and lower tumor incidence, the pathological changes were the same as those seen in the male mice, including the formation of HCCs, which are absent in TGF-alpha single-transgenic females. Tumors in single- and double-transgenic mice showed induction of the endogenous c-myc and TGF-alpha and, most frequently, unchanged or decreased epidermal growth factor receptor, further indicating the collaborative role of c-myc and TGF-alpha in providing a selective growth advantage to tumor cells independently of the epidermal growth factor receptor levels. To identify possible tumor precursors, we focused particularly on the dysplastic changes preceding and accompanying the appearance of preneoplastic and neoplastic lesions in the double-transgenic mice. Early on, these changes were characterized by the appearance of large dysplastic hepatocytes, mostly pericentrally, expressing high levels of TGF-alpha and uPA, as well as TGF-beta 1, particularly in apoptotic cells. After a short period of replication and expansion into the liver parenchyma, as well as penetration into the central veins, these cells underwent apoptotic cell death while preneoplastic and neoplastic lesions were forming. The peritumorous tissues also

  14. PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth

    PubMed Central

    Wang, Zhe; Ermakova, Svetlana P.; Xiao, JuanJuan; Lu, Tao; Xue, PeiPei; Zvyagintseva, Tatyana N.; Xiong, Hua; Shao, Chen; Yan, Wei; Duan, Qiuhong; Zhu, Feng

    2016-01-01

    The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo. PMID:26936995

  15. Enhanced neoplastic transformation by mammography X rays relative to 200 kVp X rays: indication for a strong dependence on photon energy of the RBE(M) for various end points.

    PubMed

    Frankenberg, D; Kelnhofer, K; Bär, K; Frankenberg-Schwager, M

    2002-01-01

    The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates is that the gamma rays of Hiroshima and Nagasaki are considered to have biological efficiencies equal to those of other low-LET radiations up to 10 keV/microm, including mammography X rays. Microdosimetric and radiobiological data contradict this assumption. It is therefore of scientific and public interest to evaluate the efficiency of mammography X rays (25-30 kVp) to induce cancer. In this study, the efficiency of mammography X rays relative to 200 kVp X rays to induce neoplastic cell transformation was evaluated using cells of a human hybrid cell line (CGL1). For both radiations, a linear-quadratic dose-effect relationship was observed for neoplastic transformation of CGL1 cells; there was a strong linear component for the 29 kVp X rays. The RBE(M) of mammography X rays relative to 200 kVp X rays was determined to be about 4 for doses < or = 0.5 Gy. A comparison of the electron fluences for both X rays provides strong evidence that electrons with energies of < or = 15 keV can induce neoplastic transformation of CGL1 cells. Both the data available in the literature and the results of the present study strongly suggest an increase of RBE(M) for carcinogenesis in animals, neoplastic cell transformation, and clastogenic effects with decreasing photon energy or increasing LET to an RBE(M) approximately 8 for mammography X rays relative to 60Co gamma rays. PMID:11754647

  16. Fluorescence Spectroscopy of Neoplastic and Non-Neoplastic Tissues

    PubMed Central

    Ramanujam, Nirmala

    2000-01-01

    Abstract Fast and non-invasive, diagnostic techniques based on fluorescence spectroscopy have the potential to link the biochemical and morphologic properties of tissues to individual patient care. One of the most widely explored applications of fluorescence spectroscopy is the detection of endoscopically invisible, early neoplastic growth in epithelial tissue sites. Currently, there are no effective diagnostic techniques for these early tissue transformations. If fluorescence spectroscopy can be applied successfully as a diagnostic technique in this clinical context, it may increase the potential for curative treatment, and thus, reduce complications and health care costs. Steady-state, fluorescence measurements from small tissue regions as well as relatively large tissue fields have been performed. To a much lesser extent, time-resolved, fluorescence measurements have also been explored for tissue characterization. Furthermore, sources of both intrinsic (endogenous fluorophores) and extrinsic fluorescence (exogenous fluorophores) have been considered. The goal of the current report is to provide a comprehensive review on steady-state and time-resolved, fluorescence measurements of neoplastic and non-neoplastic, biologic systems of varying degrees of complexity. First, the principles and methodology of fluorescence spectroscopy are discussed. Next, the endogenous fluorescence properties of cells, frozen tissue sections and excised and intact bulk tissues are presented; fluorescence measurements from both animal and human tissue models are discussed. This is concluded with future perspectives. PMID:10933071

  17. Interval process model and non-random vibration analysis

    NASA Astrophysics Data System (ADS)

    Jiang, C.; Ni, B. Y.; Liu, N. Y.; Han, X.; Liu, J.

    2016-07-01

    This paper develops an interval process model for time-varying or dynamic uncertainty analysis when information of the uncertain parameter is inadequate. By using the interval process model to describe a time-varying uncertain parameter, only its upper and lower bounds are required at each time point rather than its precise probability distribution, which is quite different from the traditional stochastic process model. A correlation function is defined for quantification of correlation between the uncertain-but-bounded variables at different times, and a matrix-decomposition-based method is presented to transform the original dependent interval process into an independent one for convenience of subsequent uncertainty analysis. More importantly, based on the interval process model, a non-random vibration analysis method is proposed for response computation of structures subjected to time-varying uncertain external excitations or loads. The structural dynamic responses thus can be derived in the form of upper and lower bounds, providing an important guidance for practical safety analysis and reliability design of structures. Finally, two numerical examples and one engineering application are investigated to demonstrate the feasibility of the interval process model and corresponding non-random vibration analysis method.

  18. Neoplastic diseases of marine bivalves.

    PubMed

    Carballal, María J; Barber, Bruce J; Iglesias, David; Villalba, Antonio

    2015-10-01

    Two types of prevalent neoplastic diseases have been described in marine bivalves of commercial interest: disseminated neoplasia (DN) and gonadal neoplasia. The first involves the excessive proliferation of abnormal cells with unknown origin (probably of hemic source in some cases/species), disseminating through the circulatory system and infiltrating the connective tissue of various organs; the second consists of an abnormal proliferation of undifferentiated germinal cells of the gonad. These two types of bivalve neoplasia fit the criteria of malignant tumors: pleomorphic and undifferentiated cells, rapid and invasive growth, abundance of mitotic figures, metastasis and progressive development often resulting in the death of the affected individual. Different causes have been suggested regarding etiology: genetic alterations, virus, retrotranspons, and contaminants, although it could depend on the mollusk species; evidence of horizontal transmission of clonal cancer cells as the cause of DN spreading in clam Mya arenaria populations has been recently reported. In some species and populations, the neoplastic disorders affect only a few individuals, but in others reach high prevalence. Among the diagnostic methods, DN has been detected by histology and cytologic examination of hemolymph, and with developed specific antibodies. Recently, flow cytometry has also been applied, allowing detecting DNA quantity alteration. Several studies reported many genes and pathways critically involved in neoplastic transformation in Mya arenaria, Mytilus spp. and Ostrea edulis. These genetic studies will allow the development of diagnosis by PCR which can be used in biomonitoring studies. PMID:26146225

  19. Non-random patterns in viral diversity

    PubMed Central

    Anthony, Simon J.; Islam, Ariful; Johnson, Christine; Navarrete-Macias, Isamara; Liang, Eliza; Jain, Komal; Hitchens, Peta L.; Che, Xiaoyu; Soloyvov, Alexander; Hicks, Allison L.; Ojeda-Flores, Rafael; Zambrana-Torrelio, Carlos; Ulrich, Werner; Rostal, Melinda K.; Petrosov, Alexandra; Garcia, Joel; Haider, Najmul; Wolfe, Nathan; Goldstein, Tracey; Morse, Stephen S.; Rahman, Mahmudur; Epstein, Jonathan H.; Mazet, Jonna K.; Daszak, Peter; Lipkin, W. Ian

    2015-01-01

    It is currently unclear whether changes in viral communities will ever be predictable. Here we investigate whether viral communities in wildlife are inherently structured (inferring predictability) by looking at whether communities are assembled through deterministic (often predictable) or stochastic (not predictable) processes. We sample macaque faeces across nine sites in Bangladesh and use consensus PCR and sequencing to discover 184 viruses from 14 viral families. We then use network modelling and statistical null-hypothesis testing to show the presence of non-random deterministic patterns at different scales, between sites and within individuals. We show that the effects of determinism are not absolute however, as stochastic patterns are also observed. In showing that determinism is an important process in viral community assembly we conclude that it should be possible to forecast changes to some portion of a viral community, however there will always be some portion for which prediction will be unlikely. PMID:26391192

  20. Snail Family Members Unequally Trigger EMT and Thereby Differ in Their Ability to Promote the Neoplastic Transformation of Mammary Epithelial Cells

    PubMed Central

    Wierinckx, Anne; Lamblot, Christelle; Fauvet, Frédérique; Lachuer, Joël; Puisieux, Alain; Ansieau, Stéphane

    2014-01-01

    By fostering cell commitment to the epithelial-to-mesenchymal transition (EMT), SNAIL proteins endow cells with motility, thereby favoring the metastatic spread of tumor cells. Whether the phenotypic change additionally facilitates tumor initiation has never been addressed. Here we demonstrate that when a SNAIL protein is ectopically produced in non-transformed mammary epithelial cells, the cells are protected from anoikis and proliferate under low-adherence conditions: a hallmark of cancer cells. The three SNAIL proteins show unequal oncogenic potential, strictly correlating with their ability to promote EMT. SNAIL3 especially behaves as a poor EMT-inducer comforting the concept that the transcription factor functionally diverges from its two related proteins. PMID:24638100

  1. Glyoxalase I drives epithelial-to-mesenchymal transition via argpyrimidine-modified Hsp70, miR-21 and SMAD signalling in human bronchial cells BEAS-2B chronically exposed to crystalline silica Min-U-Sil 5: Transformation into a neoplastic-like phenotype.

    PubMed

    Antognelli, Cinzia; Gambelunghe, Angela; Muzi, Giacomo; Talesa, Vincenzo Nicola

    2016-03-01

    Glyoxalase I (Glo1) is the main scavenging enzyme of methylglyoxal (MG), a potent precursor of advanced glycation end products (AGEs). AGEs are known to control multiple biological processes, including epithelial to mesenchymal transition (EMT), a multistep phenomenon associated with cell transformation, playing a major role in a variety of diseases, including cancer. Crystalline silica is a well-known occupational health hazard, responsible for a great number of human pulmonary diseases, such as silicosis. There is still much debate concerning the carcinogenic role of crystalline silica, mainly due to the lack of a causal demonstration between silica exposure and carcinogenesis. It has been suggested that EMT might play a role in crystalline silica-induced lung neoplastic transformation. The aim of this study was to investigate whether, and by means of which mechanism, the antiglycation defence Glo1 is involved in Min-U-Sil 5 (MS5) crystalline silica-induced EMT in BEAS-2B human bronchial epithelial cells chronically exposed, and whether this is associated with the beginning of a neoplastic-like transformation process. By using gene silencing/overexpression and scavenging/inhibitory agents, we demonstrated that MS5 induced hydrogen peroxide-mediated c-Jun-dependent Glo1 up-regulation which resulted in a decrease in the Argpyrimidine-modified Hsp70 protein level which triggered EMT in a novel mechanism involving miR-21 and SMAD signalling. The observed EMT was associated with a neoplastic-like phenotype. The results obtained provide a causal in vitro demonstration of the MS5 pro-carcinogenic transforming role and more importantly they provide new insights into the mechanisms involved in this process, thus opening new paths in research concerning the in vivo study of the carcinogenic potential of crystalline silica. PMID:26784015

  2. [Tongue paralysis of neoplastic origin].

    PubMed

    Marco, M; Dalmau, J; Aguilar, M

    1989-10-01

    Tongue paralysis are often underestimated, particularly when isolated or having a chronic course. Sometimes, its early recognition may lead to the diagnosis of a tumor process, favorably modifying its course. We have retrospectively analyzed 13 cases of tongue paralysis of neoplastic etiology. In a woman, the paralysis was due to a lesion of the corticobulbar pathway whereas in the remaining 12, the alteration occurred in the hypoglossal nerve, particularly at extrabulbar intracranial and cranial base tract (10 cases). The clinical picture was due to the primary tumor in 9 patients, and due to bone or leptomeningeal metastases in the remaining four cases. In five cases, the lesion of the XII cranial nerve was essential for the diagnosis of the neoplasm or the neoplastic recurrence and in four cases, it was the only affected cranial nerve. PMID:2637769

  3. Non-random DNA fragmentation in next-generation sequencing

    PubMed Central

    Poptsova, Maria S.; Il'icheva, Irina A.; Nechipurenko, Dmitry Yu.; Panchenko, Larisa A.; Khodikov, Mingian V.; Oparina, Nina Y.; Polozov, Robert V.; Nechipurenko, Yury D.; Grokhovsky, Sergei L.

    2014-01-01

    Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed “reads” are assembled into a contiguous sequence. To reduce sequencing errors, every genome region should be sequenced several dozen times. This sequencing approach is based on the assumption that genomic DNA breaks are random and sequence-independent. However, previously we showed that for the sonicated restriction DNA fragments the rates of double-stranded breaks depend on the nucleotide sequence. In this work we analyzed genomic reads from NGS data and discovered that fragmentation methods based on the action of the hydrodynamic forces on DNA, produce similar bias. Consideration of this non-random DNA fragmentation may allow one to unravel what factors and to what extent influence the non-uniform coverage of various genomic regions. PMID:24681819

  4. Non-random DNA fragmentation in next-generation sequencing

    NASA Astrophysics Data System (ADS)

    Poptsova, Maria S.; Il'Icheva, Irina A.; Nechipurenko, Dmitry Yu.; Panchenko, Larisa A.; Khodikov, Mingian V.; Oparina, Nina Y.; Polozov, Robert V.; Nechipurenko, Yury D.; Grokhovsky, Sergei L.

    2014-03-01

    Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed ``reads'' are assembled into a contiguous sequence. To reduce sequencing errors, every genome region should be sequenced several dozen times. This sequencing approach is based on the assumption that genomic DNA breaks are random and sequence-independent. However, previously we showed that for the sonicated restriction DNA fragments the rates of double-stranded breaks depend on the nucleotide sequence. In this work we analyzed genomic reads from NGS data and discovered that fragmentation methods based on the action of the hydrodynamic forces on DNA, produce similar bias. Consideration of this non-random DNA fragmentation may allow one to unravel what factors and to what extent influence the non-uniform coverage of various genomic regions.

  5. Vulvovaginal reconstruction for neoplastic disease.

    PubMed

    Höckel, Michael; Dornhöfer, Nadja

    2008-06-01

    Current treatment of neoplastic disease that involves the external female genitalia aims to achieve local disease control, but not to restore form and function of these organs. Despite a growing trend to reduce the extent of surgical resection, impaired quality of life after surgery due to severe sexual dysfunction and disturbed body image is common. We postulate that the integration of surgical techniques for vulvar and vaginal reconstruction into primary treatment would improve aesthetic and functional results and therefore quality of life. We systematically searched the literature for surgical procedures designed and validated for vulvovaginal reconstruction. Various skin flaps, both with random vascularisation and those based on vascular territories (ie, axial pattern, fasciocutaneous, musculocutaneous, and bowel flaps), can restore important parts of vulvovaginal form and function with acceptable morbidity at the donor and recipient sites. Appropriate vulvovaginal reconstruction cannot be achieved by doing a few standardised procedures; rather, it necessitates specialists who are familiar with general principles of reconstructive surgery to master many techniques to select the optimum procedure for the individual patient. Vulvovaginal reconstructive surgery has limitations, particularly achievement of functional restoration in irradiated tissue. Physicians who treat women with neoplastic disease of the external genitalia should be aware of the current state of vulvovaginal reconstructive surgery. Prospective controlled clinical trials are warranted to assess the effect of vulvovaginal reconstruction on morbidity and quality of life after treatment. PMID:18510987

  6. Reducing bias in survival under non-random temporary emigration

    USGS Publications Warehouse

    Peñaloza, Claudia L.; Kendall, William L.; Langtimm, Catherine Ann

    2014-01-01

    Despite intensive monitoring, temporary emigration from the sampling area can induce bias severe enough for managers to discard life-history parameter estimates toward the terminus of the times series (terminal bias). Under random temporary emigration unbiased parameters can be estimated with CJS models. However, unmodeled Markovian temporary emigration causes bias in parameter estimates and an unobservable state is required to model this type of emigration. The robust design is most flexible when modeling temporary emigration, and partial solutions to mitigate bias have been identified, nonetheless there are conditions were terminal bias prevails. Long-lived species with high adult survival and highly variable non-random temporary emigration present terminal bias in survival estimates, despite being modeled with the robust design and suggested constraints. Because this bias is due to uncertainty about the fate of individuals that are undetected toward the end of the time series, solutions should involve using additional information on survival status or location of these individuals at that time. Using simulation, we evaluated the performance of models that jointly analyze robust design data and an additional source of ancillary data (predictive covariate on temporary emigration, telemetry, dead recovery, or auxiliary resightings) in reducing terminal bias in survival estimates. The auxiliary resighting and predictive covariate models reduced terminal bias the most. Additional telemetry data was effective at reducing terminal bias only when individuals were tracked for a minimum of two years. High adult survival of long-lived species made the joint model with recovery data ineffective at reducing terminal bias because of small-sample bias. The naïve constraint model (last and penultimate temporary emigration parameters made equal), was the least efficient, though still able to reduce terminal bias when compared to an unconstrained model. Joint analysis of several

  7. PNA: a marker of neoplastic progression and differentiation in the gastro-intestinal tract.

    PubMed

    Grigolato, P; Benetti, A; Berenzi, A; Villanacci, V; Tardanico, R

    1990-01-01

    We examined 35 cases of stomach carcinoma and 40 cases of colonic carcinoma with PNA associated with peroxidase (peanut agglutinin, lectin which binds to the terminal disaccharide galactose beta (1,3)-N-acetil-galacto-samine). In this way evaluation of the functional aspects of the normal-neoplastic sequence was undertaken. This method was carried out for histological and ultrastructural investigations. The results obtained in both cases showed a different reactivity in the evolution of neoplastic disease: in fact, positivity in dysplasia is finely granular intracytoplasmic, whereas in well-differentiated neoplastic transformation such a reactivity is preferentially localized along the cellular membranes, with restoration of gross positivity in the cytoplasm for the poorly-differentiated neoplasm. We therefore believe PNA to be a marker not only of neoplastic progression but of differentiation as well: we also hypothesize it to reveal glycoprotein groups with possible antigenic power, involved in immunologic interactions between tumor and host. PMID:2283482

  8. Does homeobox-related "positional" genomic information contribute to implantation of metastatic cancer cells at non-random sites?

    PubMed

    Anderson, K M; Darweesh, M; Jajah, A; Tsui, P; Guinan, P; Rubenstein, M

    2007-01-01

    Reasons for the lodgment of metastases from several types of solid cancer at apparently non-random sites have not been established. Recently, a group of genes expressed in human fibroblasts obtained from different anatomic locations was implicated in "positional" genomic information. Essentially, a Cartesian coordinate system identifying fibroblasts originally resident at anterior or more posterior, proximal or distal and dermal or non-dermal (heart, lung, etc.) locations was proposed. The determinants used for these identifications included HOX genes, central to embryonic segmental development, some of which are expressed in differentiated, post-embryonic cells. To the extent that HOX or other homeobox genes are expressed in ectodermal, mesodermal or endodermally-derived, malignantly transformed cells, they might contribute "positional" information to nidation of specific malignant clones at non-random sites. As understood in the past, interdiction of HOX or homeobox-related gene expression might reduce the probability of cancer cell implantation or alter their destinations in complex ways. Ideally, by interfering with HOX or other homeobox gene-related expression of antigenic determinants potentially contributing to their "homing" and nidation, reduced implantation of circulating cancer cells could render them more susceptible to systemic chemotherapy or immunotherapy, as demonstrated in mice. Furthermore, HOX or other homeobox genes or their products could provide novel intra- or extracellular targets for therapy. PMID:17695497

  9. TRANSFORMATION

    SciTech Connect

    LACKS,S.A.

    2003-10-09

    Transformation, which alters the genetic makeup of an individual, is a concept that intrigues the human imagination. In Streptococcus pneumoniae such transformation was first demonstrated. Perhaps our fascination with genetics derived from our ancestors observing their own progeny, with its retention and assortment of parental traits, but such interest must have been accelerated after the dawn of agriculture. It was in pea plants that Gregor Mendel in the late 1800s examined inherited traits and found them to be determined by physical elements, or genes, passed from parents to progeny. In our day, the material basis of these genetic determinants was revealed to be DNA by the lowly bacteria, in particular, the pneumococcus. For this species, transformation by free DNA is a sexual process that enables cells to sport new combinations of genes and traits. Genetic transformation of the type found in S. pneumoniae occurs naturally in many species of bacteria (70), but, initially only a few other transformable species were found, namely, Haemophilus influenzae, Neisseria meningitides, Neisseria gonorrheae, and Bacillus subtilis (96). Natural transformation, which requires a set of genes evolved for the purpose, contrasts with artificial transformation, which is accomplished by shocking cells either electrically, as in electroporation, or by ionic and temperature shifts. Although such artificial treatments can introduce very small amounts of DNA into virtually any type of cell, the amounts introduced by natural transformation are a million-fold greater, and S. pneumoniae can take up as much as 10% of its cellular DNA content (40).

  10. TRANSFORMER

    DOEpatents

    Baker, W.R.

    1959-08-25

    Transformers of a type adapted for use with extreme high power vacuum tubes where current requirements may be of the order of 2,000 to 200,000 amperes are described. The transformer casing has the form of a re-entrant section being extended through an opening in one end of the cylinder to form a coaxial terminal arrangement. A toroidal multi-turn primary winding is disposed within the casing in coaxial relationship therein. In a second embodiment, means are provided for forming the casing as a multi-turn secondary. The transformer is characterized by minimized resistance heating, minimized external magnetic flux, and an economical construction.

  11. Non-random structures in universal compression and the Fermi paradox

    NASA Astrophysics Data System (ADS)

    Gurzadyan, A. V.; Allahverdyan, A. E.

    2016-02-01

    We study the hypothesis of information panspermia assigned recently among possible solutions of the Fermi paradox ("where are the aliens?"). It suggests that the expenses of alien signaling can be significantly reduced, if their messages contained compressed information. To this end we consider universal compression and decoding mechanisms ( e.g. the Lempel-Ziv-Welch algorithm) that can reveal non-random structures in compressed bit strings. The efficiency of the Kolmogorov stochasticity parameter for detection of non-randomness is illustrated, along with the Zipf's law. The universality of these methods, i.e. independence from data details, can be principal in searching for intelligent messages.

  12. The potential influence of radiation-induced microenvironments in neoplastic progression

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

  13. The quality of control groups in non-randomized studies published in Journal of Hand Surgery

    PubMed Central

    Johnson, Shepard P.; Malay, Sunitha; Chung, Kevin C.

    2016-01-01

    Purpose To evaluate control group selection in non-randomized studies published in the Journal of Hand Surgery American (JHS). Methods We reviewed all papers published in JHS in 2013 to identify studies that used non-randomized control groups. Data collected included type of study design and control group characteristics. We then appraised studies to determine if authors discussed confounding and selection bias and how they controlled for confounding. Results Thirty-seven non-randomized studies were published in JHS in 2013. The source of control was either the same institution as the study group, a different institution, a database, or not provided in the manuscript. Twenty-nine (78%) studies statistically compared key characteristics between control and study group. Confounding was controlled with matching, exclusion criteria, or regression analysis. Twenty-two (59%) papers explicitly discussed the threat of confounding and 18(49%) identified sources of selection bias. Conclusions In our review of non-randomized studies published in JHS, papers had well-defined controls that were similar to the study group, allowing for reasonable comparisons. However, we identified substantial confounding and bias that were not addressed as explicit limitations, which might lead the reader to overestimate the scientific validity of the data. Clinical relevance Incorporating a brief discussion of control group selection in scientific manuscripts should help readers interpret the study more appropriately. Authors, reviewers, and editors should strive to address this component of clinical importance. PMID:25447000

  14. Bayesian hierarchical modeling for a non-randomized, longitudinal fall prevention trial with spatially correlated observations

    PubMed Central

    Murphy, T. E.; Allore, H. G.; Leo-Summers, L.; Carlin, B. P.

    2012-01-01

    Because randomization of participants is often not feasible in community-based health interventions, non-randomized designs are commonly employed. Non-randomized designs may have experimental units that are spatial in nature, such as zip codes that are characterized by aggregate statistics from sources like the U.S. census and the Centers for Medicare and Medicaid Services. A perennial concern with non-randomized designs is that even after careful balancing of influential covariates, bias may arise from unmeasured factors. In addition to facilitating the analysis of interventional designs based on spatial units, Bayesian hierarchical modeling can quantify unmeasured variability with spatially correlated residual terms. Graphical analysis of these spatial residuals demonstrates whether variability from unmeasured covariates is likely to bias the estimates of interventional effect. The Connecticut Collaboration for Fall Prevention is the first large-scale longitudinal trial of a community-wide healthcare intervention designed to prevent injurious falls in older adults. Over a two-year evaluation phase, this trial demonstrated a rate of fall-related utilization at hospitals and emergency departments by persons 70 years and older in the intervention area that was 11 per cent less than that of the usual care area, and a 9 per cent lower rate of utilization from serious injuries. We describe the Bayesian hierarchical analysis of this non-randomized intervention with emphasis on its spatial and longitudinal characteristics. We also compare several models, using posterior predictive simulations and maps of spatial residuals. PMID:21294148

  15. 42 CFR 421.505 - Termination and extension of non-random prepayment complex medical review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... complex medical review if a provider or supplier stops billing the code under review, shifts billing to... medical records, or engages in any other improper claims or billing-related activity to avoid non-random... complex medical review. 421.505 Section 421.505 Public Health CENTERS FOR MEDICARE & MEDICAID...

  16. 42 CFR 421.505 - Termination and extension of non-random prepayment complex medical review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... prepayment complex medical review if a provider or supplier stops billing the code under review, shifts... requests for medical records, or engages in any other improper claims or billing-related activity to avoid... billing error are no longer suspended for non-random prepayment complex medical review. (d) Periodic...

  17. 42 CFR 421.505 - Termination and extension of non-random prepayment complex medical review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... complex medical review if a provider or supplier stops billing the code under review, shifts billing to... medical records, or engages in any other improper claims or billing-related activity to avoid non-random... complex medical review. 421.505 Section 421.505 Public Health CENTERS FOR MEDICARE & MEDICAID...

  18. Organoids as Models for Neoplastic Transformation | Office of Cancer Genomics

    Cancer.gov

    Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines.

  19. Somatic mutation and cell differentiation in neoplastic transformation

    SciTech Connect

    Huberman, E.; Collart, F.R.

    1987-01-01

    In brief, the authors suggest that tumor formation may result from continuous expression of growth facilitating genes that, as a result of irreversible changes during the initiation step, are placed under the control of genes expressed during normal differentiation. Thus, to understand carcinogenesis, we must decipher the processes that lead to the acquisition of a mature phenotype in both normal and tumor cells and characterize the growth dependency of tumor cells to inducers of cell differentiation. Furthermore, the growth of a variety of tumors may be controlled through the use of inducers of maturation that activate genes located beyond the gene that is altered during tumor initiation. 22 refs., 3 figs.

  20. Human papilloma virus in neoplastic and non-neoplastic conditions of the external eye

    PubMed Central

    Karcioglu, Z.; Issa, T.

    1997-01-01

    AIM—Human papilloma virus (HPV) types 16 and 18 have been associated with neoplastic conditions of the conjunctiva. However, the presence of this virus has not been reported in non-neoplastic disorders of the external eye nor has it been studied in normal conjunctival tissues.
METHODS—Ninety six paraffin embedded tissue specimens with neoplastic and non-neoplastic lesions and 19 conjunctiva samples free from overt disease were studied for HPV types 16 and 18 positivity with the polymerase chain reaction.
RESULTS—HPV types 16 and 18 DNA were identified in 57% of in situ squamous cell carcinoma, in 55% of invasive squamous cell carcinoma, in 20% of climatic droplet keratopathy, in 35% of scarred corneas, and in 32% of normal conjunctival tissue obtained during routine cataract extractions.
CONCLUSION—These findings indicate that HPV types 16 and 18 are detectable with the polymerase chain reaction not only in epithelial neoplasms of the ocular mucous membrane but also in non-neoplastic lesions as well as in apparently healthy conjunctiva.

 PMID:9290377

  1. Identification of non-neoplastic and neoplastic gastric polyps using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Jiang, Shanghai; Kang, Deyong; Xu, Meifang; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2012-12-01

    Gastric polyps can be broadly defined as luminal lesions projecting above the plane of the mucosal surface. They are generally divided into non-neoplastic and neoplastic polyps. Accurate diagnosis of neoplastic polyps is important because of their well-known relationship with gastric cancer. Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) is one of the most important recent inventions in biological imaging. In this study, we used MPM to image the microstructure of gastric polyps, including fundic gland polyps, hyperplastic polyps, inflammatory fibroid polyps and adenomas, then compared with gold-standard hematoxylin- eosin(H-E)-stained histopathology. MPM images showed that different gastric polyps have different gland architecture and cell morphology. Dilated, elongated or branch-like hyperplastic polyps are arranged by columnar epithelial cells. Inflammatory fibroid polyps are composed of small, thin-walled blood vessels surrounded by short spindle cells. Fundic glands polyps are lined by parietal cells and chief cells, admixed with normal glands. Gastric adenomas are generally composed of tubules or villi of dysplastic epithelium, which usually show some degree of intestinal-type differentiation toward absorptive cells, goblet cells, endocrine cells. Our results demonstrated that MPM can be used to identify non- neoplastic and neoplastic gastric polyps without the need of any staining procedure.

  2. Neoplastic Reprogramming of Patient-Derived Adipose Stem Cells by Prostate Cancer Cell-Associated Exosomes

    PubMed Central

    Abd Elmageed, Zakaria Y.; Yang, Yijun; Thomas, Raju; Ranjan, Manish; Mondal, Debasis; Moroz, Krzysztof; Fang, Zhide; Rezk, Bashir M.; Moparty, Krishnarao; Sikka, Suresh C.; Sartor, Oliver; Abdel-Mageed, Asim B.

    2014-01-01

    Emerging evidence suggests that mesenchymal stem cells (MSCs) are often recruited to tumor sites but their functional significance in tumor growth and disease progression remains elusive. Herein we report that prostate cancer (PC) cell microenvironment subverts PC patient adipose-derived stem cells (pASCs) to undergo neoplastic transformation. Unlike normal ASCs, the pASCs primed with PC cell conditioned media (CM) formed prostate-like neoplastic lesions in vivo and reproduced aggressive tumors in secondary recipients. The pASC tumors acquired cytogenetic aberrations and mesenchymal-to-epithelial transition (MET) and expressed epithelial, neoplastic, and vasculogenic markers reminiscent of molecular features of PC tumor xenografts. Our mechanistic studies revealed that PC cell-derived exosomes are sufficient to recapitulate formation of prostate tumorigenic mimicry generated by CM-primed pASCs in vivo. In addition to down-regulation of the large tumor suppressor homolog2 (Lats2) and the programmed cell death protein 4 (PDCD4), a neoplastic transformation inhibitor, the tumorigenic reprogramming of pASCs was associated with trafficking by PC cell-derived exosomes of oncogenic factors, including H-ras and K-ras transcripts, oncomiRNAs miR-125b, miR-130b, and miR-155 as well as the Ras superfamily of GTPases Rab1a, Rab1b, and Rab11a. Our findings implicate a new role for PC cell-derived exosomes in clonal expansion of tumors through neoplastic reprogramming of tumor tropic ASCs in cancer patients. PMID:24715691

  3. CD44 and the adhesion of neoplastic cells.

    PubMed Central

    Rudzki, Z; Jothy, S

    1997-01-01

    and in predicting tumour behaviour. It can also contribute to better understanding of molecular mechanisms leading to neoplastic transformation. Images PMID:9231152

  4. [Non-neoplastic lesions of the mediastinum].

    PubMed

    Tzankov, A

    2016-09-01

    The mediastinum is a complex body region of limited space but containing numerous organs of different embryonic origins. A variety of lesions that are difficult to distinguish from each other can occur here. Non-neoplastic lesions of the mediastinum represent important differential diagnostic pitfalls to mediastinal tumors, clinically, radiologically and histopathologically. It is important to bear these lesions in mind and to adequately verify or exclude them before starting further differential diagnostic considerations on mediastinal neoplasms. The most common non-neoplastic lesions in this region include cysts and lymphadenopathies. Mediastinal cysts result from abnormal events in the branching of the tracheobronchial tree, the pharyngeal pouches, the primary intestines, the pleuropericardial membranes and the brain meninges or are complications of inflammatory and hydrostatic processes. The histogenesis of the lining epithelium and the cyst wall structure are decisive for the exact classification. The histopathologically most prevalent patterns of mediastinal lymphadenopathies are those accompanied by increased histiocytes and Castleman's disease. Sclerosis is a non-specific reaction pattern of the mediastinum and can be associated with many processes; therefore, when establishing the diagnosis of sclerosing mediastinitis, several differential diagnoses have to be excluded. Simple thymic hyperplasia can be accompanied by considerable increase in organ size with severe local symptoms, while follicular thymic hyperplasia is often associated with myasthenia gravis and represents the most common findings in non-thymoma thymectomy specimens. PMID:27465275

  5. Non-neoplastic salivary gland diseases.

    PubMed

    Arduino, P G; Carrozzo, M; Pentenero, M; Bertolusso, G; Gandolfo, S

    2006-05-01

    A wide range of non neoplastic disorders can affect the salivary glands, although the more common are: mumps, acute suppurative sialadenitis, Sjögren's syndrome and drug-induced xerostomia. Salivary dysfunction is not a normal consequence of old age, and can be due to systemic diseases, medications or head and neck radiotherapy. Diagnosis of salivary disorders begins with a careful medical history, followed by a cautious examination. While complaints of xerostomia may be indicative of a salivary gland disorder, salivary diseases can present without symptoms. Therefore, routine examination of salivary function must be part of any head, neck, and oral examination. Health-care professionals can play a vital role in identifying patients at risk for developing salivary dysfunction, and should provide appropriate preventive and interventive techniques that will help to preserving a person's health, function, and quality of life. The present work provides an overview of most of the non neoplastic disorders of the salivary glands, in which the general presentation, pathology, and treatments are discussed. PMID:16688102

  6. Non-Random Mating, Parent-of-Origin, and Maternal-Fetal Incompatibility Effects in Schizophrenia

    PubMed Central

    Kim, Yunjung; Ripke, Stephan; Kirov, George; Sklar, Pamela; Purcell, Shaun; Owen, Michael; O’Donovan, Michael C.; Sullivan, Patrick F.

    2014-01-01

    Although the association of common genetic variation in the extended MHC region with schizophrenia is the most significant yet discovered, the MHC region is one of the more complex regions of the human genome, with unusually high gene density and long-range linkage disequilibrium. The statistical test on which the MHC association is based is a relatively simple, additive model which uses logistic regression of SNP genotypes to predict case-control status. However, it is plausible that more complex models underlie this association. Using a well-characterized sample of trios, we evaluated more complex models by looking for evidence for: (a) non-random mating for HLA alleles, schizophrenia risk profiles, and ancestry; (b) parent-of-origin effects for HLA alleles; and (c) maternal-fetal genotype incompatibility in the HLA. We found no evidence for non-random mating in the parents of individuals with schizophrenia in terms of MHC genotypes or schizophrenia risk profile scores. However, there was evidence of non-random mating that appeared mostly to be driven by ancestry. We did not detect over-transmission of HLA alleles to affected offspring via the general TDT test (without regard to parent of origin) or preferential transmission via paternal or maternal inheritance. We evaluated the hypothesis that maternal-fetal HLA incompatibility may increase risk for schizophrenia using eight classical HLA loci. The most significant alleles were in HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 but none was significant after accounting for multiple comparisons. We did not find evidence to support more complex models of gene action, but statistical power may have been limiting. PMID:23177929

  7. Regulatory Considerations Of Waste Emplacement Within The WIPP Repository: Random Versus Non-Random Distribution

    SciTech Connect

    Casey, S. C.; Patterson, R. L.; Gross, M.; Lickliter, K.; Stein, J. S.

    2003-02-25

    The U.S. Department of Energy (DOE) is responsible for disposing of transuranic waste in the Waste Isolation Pilot Plant (WIPP) in southeastern New Mexico. As part of that responsibility, DOE must comply with the U.S. Environmental Protection Agency's (EPA) radiation protection standards in Title 40 Code of Federal Regulations (CFR), Parts 191 and 194. This paper addresses compliance with the criteria of 40 CFR Section 194.24(d) and 194.24(f) that require DOE to either provide a waste loading scheme for the WIPP repository or to assume random emplacement in the mandated performance and compliance assessments. The DOE established a position on waste loading schemes during the process of obtaining the EPA's initial Certification in 1998. The justification for utilizing a random waste emplacement distribution within the WIPP repository was provided to the EPA. During the EPA rulemaking process for the initial certification, the EPA questioned DOE on whether waste would be loaded randomly as modeled in long-term performance assessment (PA) and the impact, if any, of nonrandom loading. In response, DOE conducted an impact assessment for non-random waste loading. The results of this assessment supported the contention that it does not matter whether random or non-random waste loading is assumed for the PA. The EPA determined that a waste loading plan was unnecessary because DOE had assumed random waste loading and evaluated the potential consequences of non-random loading for a very high activity waste stream. In other words, the EPA determined that DOE was not required to provide a waste loading scheme because compliance is not affected by the actual distribution of waste containers in the WIPP.

  8. Pharmacological reactivity of neoplastic and non-neoplastic associated neovasculature to vasoconstrictors.

    PubMed

    Andrade, S P; Beraldo, W T

    1998-12-01

    Angiogenesis and the pharmacological responses of the tumour and non-tumour associated neovasculature have been investigated. Cannulated sponge discs in mice were used to host the angiogenic stimulators, while 133Xe washout was employed to assess local blood flow. Enhancement of blood flow was detected in implants bearing B16 cells, 3T3 cells and angiotensin II (AII)-treated at day 7. The responses of non-neoplastic associated neovasculature at day 14 post sponge implantation to the vasoconstrictors used endothelin-1 (Et-1), AII, platelet activating factor (PAF) and 5-hydroxytryptamine (5-HT) were dose-dependent. By contrast, the newly formed blood vessels induced by tumour cells were markedly insensitive to the vasoconstrictors agonists Et-1 and AII, while fully responsive to PAF and 5-HT. The vessels resulting from neoplastic stimulus exhibited altered pharmacological reactivity, suggesting that the characteristics of the neovasculature are dependent on the nature of the angiogenic stimuli. PMID:10319023

  9. Non-neoplastic salivary gland lesions: a 15-year study.

    PubMed

    Mohan, Harsh; Tahlan, Anita; Mundi, Irneet; Punia, R P S; Dass, Arjun

    2011-08-01

    The spectrum of salivary gland lesions is wide and the relative incidence of neoplastic versus non-neoplastic lesions is variable in different studies. A series of non-neoplastic salivary gland lesions is reviewed to analyze their spectrum and their relative frequency. This is a retrospective study of salivary gland excisions and biopsies received in our department from January 1994 to December 2008. Routine hematoxylin and eosin-stained sections of all the salivary gland excisions and biopsies received were analyzed. Of the 393 salivary gland excisions and biopsies received, 216 cases were reported as non-neoplastic (55%) and formed our study group; 177 (45%) were neoplastic. Non-neoplastic lesions were more frequent in major salivary glands (65.7%) and submandibular gland was the most commonly involved (66.2%). Lip was the most frequent site (81.7%) for minor salivary gland lesions. Inflammation was the predominant pathological finding (49.5%), of which non-specific chronic sialadenitis constituted the majority (86.9%). Sialolithiasis was present in 22 cases (20.6%); all of these cases were of non-specific chronic sialadenitis. Cysts were second in frequency (36.6%), of which mucocele was the most common (54.5%). There were 5.6% cases of benign lympho-epithelial lesions, while normal salivary gland tissue was seen in 6.5% cases. Non-neoplastic salivary gland diseases are more common than neoplastic diseases and have a wide disease spectrum. PMID:21170719

  10. Non-random biodiversity loss underlies predictable increases in viral disease prevalence

    PubMed Central

    Lacroix, Christelle; Jolles, Anna; Seabloom, Eric W.; Power, Alison G.; Mitchell, Charles E.; Borer, Elizabeth T.

    2014-01-01

    Disease dilution (reduced disease prevalence with increasing biodiversity) has been described for many different pathogens. Although the mechanisms causing this phenomenon remain unclear, the disassembly of communities to predictable subsets of species, which can be caused by changing climate, land use or invasive species, underlies one important hypothesis. In this case, infection prevalence could reflect the competence of the remaining hosts. To test this hypothesis, we measured local host species abundance and prevalence of four generalist aphid-vectored pathogens (barley and cereal yellow dwarf viruses) in a ubiquitous annual grass host at 10 sites spanning 2000 km along the North American West Coast. In laboratory and field trials, we measured viral infection as well as aphid fecundity and feeding preference on several host species. Virus prevalence increased as local host richness declined. Community disassembly was non-random: ubiquitous hosts dominating species-poor assemblages were among the most competent for vector production and virus transmission. This suggests that non-random biodiversity loss led to increased virus prevalence. Because diversity loss is occurring globally in response to anthropogenic changes, such work can inform medical, agricultural and veterinary disease research by providing insights into the dynamics of pathogens nested within a complex web of environmental forces. PMID:24352672

  11. How does non-random spontaneous activity contribute to brain development?

    PubMed

    Thivierge, Jean-Philippe

    2009-09-01

    Highly non-random forms of spontaneous activity are proposed to play an instrumental role in the early development of the visual system. However, both the fundamental properties of spontaneous activity required to drive map formation, as well as the exact role of this information remain largely unknown. Here, a realistic computational model of spontaneous retinal waves is employed to demonstrate that both the amplitude and frequency of waves may play determining roles in retinocollicular map formation. Furthermore, results obtained with different learning rules show that spike precision in the order of milliseconds may be instrumental to neural development: a rule based on precise spike interactions (spike-timing-dependent plasticity) reduced the density of aberrant projections to the SC to a markedly greater extent than a rule based on interactions at much broader time-scale (correlation-based plasticity). Taken together, these results argue for an important role of spontaneous yet highly non-random activity, along with temporally precise learning rules, in the formation of neural circuits. PMID:19196491

  12. Expression of Cytokeratin-19 and Thyroperoxidase in Relation to Morphological Features in Non-Neoplastic and Neoplastic Lesions of Thyroid

    PubMed Central

    Rajamani, Revathishree; Noorunnisa, Naseen; Durairaj, Manimaran

    2016-01-01

    Introduction Thyroperoxidase (TPO) is a protein involved in thyroid hormone synthesis. TPO gene suppression and mutation were involved in thyroid tumours. CK-19 plays important role in the structural integrity of epithelial cells. Reduced TPO expression with increased CK-19 immunoreactivity has been implicated as a marker for differentiating non neoplastic and neoplastic thyroid lesions. Aim To study the histopathological features of thyroid lesions and to evaluate the diagnostic role of thyroperoxidase and CK-19 in non-neoplastic and neoplastic thyroid lesions. Materials and Methods Prospective observational study of 65 thyroid specimens was studied for detailed histopathological examination and Expression of Immunohistochemical Markers Cytokeratin-19 (CK-19) and Thyroperoxidase. Results TPO IHC marker was expressed by non-neoplastic and benign lesions of thyroid but not in malignancy. CK-19 was expressed 100% in papillary carcinoma of thyroid and its variants, focal and weak staining noted in goitre and hyperplastic areas. Conclusion Most of the non-neoplastic and neoplastic lesions were diagnosed based on histopathological features. When the histopathological diagnosis are equivocal, immunohistochemical markers aids in diagnosing malignancy. Diffuse and strong TPO expression indicates non-neoplastic thyroid lesions whereas diffused and strong CK-19 expression indicates thyroid malignancy. PMID:27504290

  13. Non-random mating in classical lekking grouse species: seasonal and diurnal trends

    NASA Astrophysics Data System (ADS)

    Tsuji, L. J. S.; DeIuliis, G.; Hansell, R. I. C.; Kozlovic, D. R.; Sokolowski, M. B.

    This paper is the first to integrate both field and theoretical approaches to demonstrate that fertility benefits can be a direct benefit to females mating on the classical lek. Field data collected for male sharp-tailed grouse (Tympanuchus phasianellus), a classical lekking species, revealed potential fertility benefits for selective females. Adult males and individuals occupying centrally located territories on the lek were found to have significantly larger testes than juveniles and peripheral individuals. Further, using empirical data from previously published studies of classical lekking grouse species, time-series analysis was employed to illustrate that female mating patterns, seasonal and daily, were non-random. We are the first to show that these patterns coincide with times when male fertility is at its peak.

  14. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

    PubMed Central

    Khuong-Quang, Dong-Anh; Bechet, Denise; Gayden, Tenzin; Kool, Marcel; De Jay, Nicolas; Jacob, Karine; Gerges, Noha; Hutter, Barbara; Şeker-Cin, Huriye; Witt, Hendrik; Montpetit, Alexandre; Brunet, Sébastien; Lepage, Pierre; Bourret, Geneviève; Klekner, Almos; Bognár, László; Hauser, Peter; Garami, Miklós; Farmer, Jean-Pierre; Montes, Jose-Luis; Atkinson, Jeffrey; Lambert, Sally; Kwan, Tony; Korshunov, Andrey; Tabori, Uri; Collins, V. Peter; Albrecht, Steffen; Faury, Damien; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin; Jones, David T.W.; Jabado, Nada

    2015-01-01

    Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor. PMID:26378811

  15. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age.

    PubMed

    Fontebasso, Adam M; Shirinian, Margret; Khuong-Quang, Dong-Anh; Bechet, Denise; Gayden, Tenzin; Kool, Marcel; De Jay, Nicolas; Jacob, Karine; Gerges, Noha; Hutter, Barbara; Şeker-Cin, Huriye; Witt, Hendrik; Montpetit, Alexandre; Brunet, Sébastien; Lepage, Pierre; Bourret, Geneviève; Klekner, Almos; Bognár, László; Hauser, Peter; Garami, Miklós; Farmer, Jean-Pierre; Montes, Jose-Luis; Atkinson, Jeffrey; Lambert, Sally; Kwan, Tony; Korshunov, Andrey; Tabori, Uri; Collins, V Peter; Albrecht, Steffen; Faury, Damien; Pfister, Stefan M; Paulus, Werner; Hasselblatt, Martin; Jones, David T W; Jabado, Nada

    2015-10-13

    Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor. PMID:26378811

  16. Cancer related fatigue syndrome in neoplastic diseases.

    PubMed

    Franc, Magdalena; Michalski, Bogdan; Kuczerawy, Ilona; Szuta, Justyna; Skrzypulec-Plinta, Violetta

    2014-12-01

    Fatigue is one of the most important factors which has a considerable influence on treatment and the life quality of oncological patients. The fatigue syndrome is often diagnosed during cancer treatment and this syndrome is not related to the physical effort. Cancer related fatigue is a patient's subjective, psychologically, physically and emotionally based feeling. It is disproportionate to patient's daily activity. The pathogenesis of this syndrome remains still unknown. However, on the basis of various questionnaires, it is possible to test the disease's complex nature. Cancer related fatigue causes deterioration of patient's life along with lower motivation to struggle with the disease. It is thought that the factor which increases the incidence of cancer related fatigue is a long-term use of drugs such as opioids, benzodiazepine, and medicines containing codeine, tranquilizers, anxiolytics and antidepressants. On the basis of the results, one can choose an appropriate treatment method for cancer related fatigue such as rehabilitation, psychotherapy or public assistance. A great number of patients consider excessive fatigue a typical concomitant symptom in neoplastic disease; therefore, they do not report it. It is of a paramount importance to make patients aware of the fact that cancer related fatigue is a serious disease which can be treated. PMID:26327879

  17. Cancer related fatigue syndrome in neoplastic diseases

    PubMed Central

    Michalski, Bogdan; Kuczerawy, Ilona; Szuta, Justyna; Skrzypulec-Plinta, Violetta

    2014-01-01

    Fatigue is one of the most important factors which has a considerable influence on treatment and the life quality of oncological patients. The fatigue syndrome is often diagnosed during cancer treatment and this syndrome is not related to the physical effort. Cancer related fatigue is a patient's subjective, psychologically, physically and emotionally based feeling. It is disproportionate to patient's daily activity. The pathogenesis of this syndrome remains still unknown. However, on the basis of various questionnaires, it is possible to test the disease's complex nature. Cancer related fatigue causes deterioration of patient's life along with lower motivation to struggle with the disease. It is thought that the factor which increases the incidence of cancer related fatigue is a long-term use of drugs such as opioids, benzodiazepine, and medicines containing codeine, tranquilizers, anxiolytics and antidepressants. On the basis of the results, one can choose an appropriate treatment method for cancer related fatigue such as rehabilitation, psychotherapy or public assistance. A great number of patients consider excessive fatigue a typical concomitant symptom in neoplastic disease; therefore, they do not report it. It is of a paramount importance to make patients aware of the fact that cancer related fatigue is a serious disease which can be treated. PMID:26327879

  18. Matrix Metalloproteinases in Non-Neoplastic Disorders

    PubMed Central

    Tokito, Akinori; Jougasaki, Michihisa

    2016-01-01

    The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

  19. The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase

    PubMed Central

    Sciacovelli, Marco; Guzzo, Giulia; Morello, Virginia; Frezza, Christian; Zheng, Liang; Nannini, Nazarena; Calabrese, Fiorella; Laudiero, Gabriella; Esposito, Franca; Landriscina, Matteo; Defilippi, Paola; Bernardi, Paolo; Rasola, Andrea

    2013-01-01

    Summary We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target. PMID:23747254

  20. The neoplastic potential of rat tracheal epithelial cell lines induced by dibenzo(a, i)pyrene and 1-nitropyrene

    SciTech Connect

    Xiang, M.; Ong, T. |; Nath, J.

    1997-10-01

    The rat tracheal epithelial (RTE) cell transformation system is an important short-term assay for respiratory carcinogenesis. In our laboratories, studies have been performed using this assay system to determine the carcinogenic potential of dibenzo(a,i)pyrene (DBP) and 1-nitropyrene (1-NP), two compounds commonly contaminating occupational and environmental settings. RTE cells were exposed in vivo to DBP or 1-NP by intertracheal instillation. RTE cells were then isolated and plated on a medium for determination of cloning and transformation frequencies. Cell lines established from transformed cells induced by DBP and 1-NP were analyzed for their neoplastic potential with the soft agar cloning and the athymic nude mouse tumorigenicity assays. Results showed that: (1) incidence of transformed foci in cultures treated with DBP or 1-NP in vivo was significantly higher than that in the control cultures; (2) 8 and 25 cell lines were established from 28 and 48 transformed foci induced by DBP and 1-NP, respectively; (3) 3 of 5 cell lines from DBP and 5 anchorage independent growth in soft agar; (4) some of the cell lines from DBP and 1-NP induced transformed foci formed tumors after cells were injected in athymic nude mice. These results indicate that in vivo exposure to DBP and 1-NP can induce RTE cell transformation and that transformed cells induced by DBP and 1-NP may have neoplastic potential.

  1. Non-random nectar unloading interactions between foragers and their receivers in the honeybee hive

    NASA Astrophysics Data System (ADS)

    Goyret, Joaquín; Farina, Walter M.

    2005-09-01

    Nectar acquisition in the honeybee Apis mellifera is a partitioned task in which foragers gather nectar and bring it to the hive, where nest mates unload via trophallaxis (i.e. mouth-to-mouth transfer) the collected food for further storage. Because forager mates exploit different feeding places simultaneously, this study addresses the question of whether nectar unloading interactions between foragers and hive-bees are established randomly, as it is commonly assumed. Two groups of foragers were trained to exploit a different scented food source for 5 days. We recorded their trophallaxes with hive-mates, marking the latter ones according to the forager group they were unloading. We found non-random probabilities for the occurrence of trophallaxes between experimental foragers and hive-bees, instead, we found that trophallactic interactions were more likely to involve groups of individuals which had formerly interacted orally. We propose that olfactory cues present in the transferred nectar promoted the observed bias, and we discuss this bias in the context of the organization of nectar acquisition: a partitioned task carried out in a decentralized insect society.

  2. Random and non-random mating populations: Evolutionary dynamics in meiotic drive.

    PubMed

    Sarkar, Bijan

    2016-01-01

    Game theoretic tools are utilized to analyze a one-locus continuous selection model of sex-specific meiotic drive by considering nonequivalence of the viabilities of reciprocal heterozygotes that might be noticed at an imprinted locus. The model draws attention to the role of viability selections of different types to examine the stable nature of polymorphic equilibrium. A bridge between population genetics and evolutionary game theory has been built up by applying the concept of the Fundamental Theorem of Natural Selection. In addition to pointing out the influences of male and female segregation ratios on selection, configuration structure reveals some noted results, e.g., Hardy-Weinberg frequencies hold in replicator dynamics, occurrence of faster evolution at the maximized variance fitness, existence of mixed Evolutionarily Stable Strategy (ESS) in asymmetric games, the tending evolution to follow not only a 1:1 sex ratio but also a 1:1 different alleles ratio at particular gene locus. Through construction of replicator dynamics in the group selection framework, our selection model introduces a redefining bases of game theory to incorporate non-random mating where a mating parameter associated with population structure is dependent on the social structure. Also, the model exposes the fact that the number of polymorphic equilibria will depend on the algebraic expression of population structure. PMID:26524140

  3. Non random usage of T cell receptor alpha gene expression in atopy using anchored PCR.

    PubMed

    Mansur, A H; Gelder, C M; Holland, D; Campell, D A; Griffin, A; Cunliffe, W; Markham, A F; Morrison, J F

    1996-01-01

    The T cell receptor (TCR) alpha beta heterodimer recognises antigenic peptide fragments presented by Class II MHC. This interaction initiates T cell activation and cytokine release with subsequent recruitment of inflammatory cells. Previous work from our group suggests a qualitative difference in variable alpha gene expression in atopy as compared to non atopic controls. In this study we examine TCR alpha repertoire using anchored PCR to provide a quantitative assessment of the V alpha and J alpha repertoire. One atopic (DRB1*0701,DRB1*15: DRB4*0101, DRB5*01: DQB1* 0303, DQB1*601/2) and one non-atopic (DRB1*0701,DRB1*03011/2: DRB4*01, DRB3*0x: DQB1* 0303, DQB1*0201/2) control were studied. Variable gene usage was markedly limited in the atopic individual. V alpha 1, 3, 8 accounted for 60% and J alpha 12, 31 30% of the gene usage. There was evidence of preferential V alpha-J alpha gene pairing and clonal expansion. We conclude that there is a marked non random TCR alpha gene distribution in atopy using both V alpha family and anchored PCR. This may be due in part to antigen driven clonal expansion. PMID:9095269

  4. Human promoter genomic composition demonstrates non-random groupings that reflect general cellular function

    PubMed Central

    McNutt, Markey C; Tongbai, Ron; Cui, Wenwu; Collins, Irene; Freebern, Wendy J; Montano, Idalia; Haggerty, Cynthia M; Chandramouli, GVR; Gardner, Kevin

    2005-01-01

    Background The purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene. Results Using ProSpector, a web-based promoter search and annotation tool, we have applied an unbiased approach to analyze the transcription factor binding site frequencies of 1400 base pair genomic segments positioned at 1200 base pairs upstream and 200 base pairs downstream of the transcriptional start site of 7298 commonly studied human genes. Partitional clustering of the transcription factor binding site composition within these promoter segments reveals a small number of gene groups that are selectively enriched for gene ontology terms consistent with distinct aspects of cellular function. Significance ranking of the class-determining transcription factor binding sites within these clusters show substantial overlap between the gene ontology terms of the transcriptions factors associated with the binding sites and the gene ontology terms of the regulated genes within each group. Conclusion Thus, gene sorting by promoter composition alone produces partitions in which the "regulated" and the "regulators" cosegregate into similar functional classes. These findings demonstrate that the transcription factor binding site composition is non-randomly distributed between gene promoters in a manner that reflects and partially defines general gene class function. PMID:16232321

  5. Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring

    PubMed Central

    Miner, Daniel; Triesch, Jochen

    2016-01-01

    Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non-random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring. PMID:26866369

  6. Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring.

    PubMed

    Miner, Daniel; Triesch, Jochen

    2016-02-01

    Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non-random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring. PMID:26866369

  7. A Novel Role of E-Cadherin-Based Adherens Junctions in Neoplastic Cell Dissemination

    PubMed Central

    Gloushankova, Natalya A.

    2015-01-01

    Using confocal microscopy, we analyzed the behavior of IAR-6-1, IAR1170, and IAR1162 transformed epithelial cells seeded onto the confluent monolayer of normal IAR-2 epithelial cells. Live-cell imaging of neoplastic cells stably expressing EGFP and of normal epithelial cells stably expressing mKate2 showed that transformed cells retaining expression of E-cadherin were able to migrate over the IAR-2 epithelial monolayer and invade the monolayer. Transformed IAR cells invaded the IAR-2 monolayer at the boundaries between normal cells. Studying interactions of IAR-6-1 transformed cells stably expressing GFP-E-cadherin with the IAR-2 epithelial monolayer, we found that IAR-6-1 cells established E-cadherin-based adhesions with normal epithelial cells: dot-like dynamic E-cadherin-based adhesions in protrusions and large adherens junctions at the cell sides and rear. A comparative study of a panel of transformed IAR cells that differ by their ability to form E-cadherin-based AJs, either through loss of E-cadherin expression or through expression of a dominant negative E-cadherin mutant, demonstrated that E-cadherin-based AJs are key mediators of the interactions between neoplastic and normal epithelial cells. IAR-6-1DNE cells expressing a dominant-negative mutant form of E-cadherin with the mutation in the first extracellular domain practically lost the ability to adhere to IAR-2 cells and invade the IAR-2 epithelial monolayer. The ability of cancer cells to form E-cadherin-based AJs with the surrounding normal epithelial cells may play an important role in driving cancer cell dissemination in the body. PMID:26207916

  8. MGMT promoter methylation in non-neoplastic brain.

    PubMed

    Hsu, Chih-Yi; Ho, Hsiang-Ling; Chang-Chien, Yi-Chun; Chang, Yi-Wen; Ho, Donald Ming-Tak

    2015-02-01

    O(6)-methylguanine-DNA-methyltransferase (MGMT) is mainly regulated by cytosine-guanine island promoter methylation that is believed to occur only in neoplastic tissue. The present study was undertaken to investigate whether methylation occurs also in non-neoplastic brains by collecting 45 non-neoplastic brains from autopsies and 56 lobectomy specimens from epileptic surgeries. The promoter methylation status of MGMT was studied by methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ), while protein expression was studied by immunohistochemical stain (IHC). The methylation rates, as determined by MSP and PSQ, were 3.0 % (3/101) and 2.9 % (2/69), respectively. Of note, no case had positive result concomitantly from both MSP and PSQ (3 were MSP+/PSQ- and 2 were MSP-/PSQ+), and all the positive samples were further confirmed by cloning and Sanger sequencing. All the methylated cases, except for those having indeterminate IHC results from autopsy specimens, revealed no loss of MGMT protein expression and similar staining pattern to that of the unmethylated cases. In conclusion, the current study demonstrated that MGMT promoter methylation could occur in a low percentage of non-neoplastic brains but did not affect the status of protein expression, which could be regarded as a normal variation in non-neoplastic brains. PMID:25391970

  9. In vivo diagnostic accuracy of high resolution microendoscopy in differentiating neoplastic from non-neoplastic colorectal polyps: a prospective study

    PubMed Central

    Parikh, Neil; Perl, Daniel; Lee, Michelle H.; Shah, Brijen; Young, Yuki; Chang, Shannon S.; Shukla, Richa; Polydorides, Alexandros D.; Moshier, Erin; Godbold, James; Zhou, Elinor; Mitchaml, Josephine; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

    2013-01-01

    High-resolution microendoscopy (HRME) is a low-cost, “optical biopsy” technology that allows for subcellular imaging. The purpose of this study was to determine the in vivo diagnostic accuracy of the HRME for the differentiation of neoplastic from non-neoplastic colorectal polyps and compare it to that of high-definition white-light endoscopy (WLE) with histopathology as the gold standard. Three endoscopists prospectively detected a total of 171 polyps from 94 patients that were then imaged by HRME and classified in real-time as neoplastic (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory). HRME had a significantly higher accuracy (94%), specificity (95%), and positive predictive value (87%) for the determination of neoplastic colorectal polyps compared to WLE (65%, 39%, and 55%, respectively). When looking at small colorectal polyps (less than 10 mm), HRME continued to significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98% vs. 40%) and positive predictive value (92% vs. 55%). These trends continued when evaluating diminutive polyps (less than 5 mm) as HRME's accuracy (95%), specificity (98%), and positive predictive value (93%) were all significantly greater than their WLE counterparts (62%, 41%, and 53%, respectively). In conclusion, this in vivo study demonstrates that HRME can be a very effective modality in the differentiation of neoplastic and non-neoplastic colorectal polyps. A combination of standard white-light colonoscopy for polyp detection and HRME for polyp classification has the potential to truly allow the endoscopist to selectively determine which lesions can be left in situ, which lesions can simply be discarded, and which lesions need formal histopathologic analysis. PMID:24296752

  10. Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation

    PubMed Central

    2015-01-01

    Background The assessment of cell-free circulating DNA fragments, also known as a "liquid biopsy" of the patient's plasma, is an important source for the discovery and subsequent non-invasive monitoring of cancer and other pathological conditions. Although the nucleosome-guided fragmentation patterns of cell-free DNA (cfDNA) have not yet been studied in detail, non-random representation of cfDNA sequencies may reflect chromatin features in the tissue of origin at gene-regulation level. Results In this study, we investigated the association between epigenetic landscapes of human tissues evident in the patterns of cfDNA in plasma by deep sequencing of human cfDNA samples. We have demonstrated that baseline characteristics of cfDNA fragmentation pattern are in concordance with the ones corresponding to cell lines-derived. To identify the loci differentially represented in cfDNA fragment, we mapped the transcription start sites within the sequenced cfDNA fragments and tested for association of these genomic coordinates with the relative strength and the patterns of gene expressions. Preselected sets of house-keeping and tissue specific genes were used as models for actively expressed and silenced genes. Developed measure of gene regulation was able to differentiate these two sets based on sequencing coverage near gene transcription start site. Conclusion Experimental outcomes suggest that cfDNA retains characteristics previously noted in genome-wide analysis of chromatin structure, in particular, in MNase-seq assays. Thus far the analysis of the DNA fragmentation pattern may aid further developing of cfDNA based biomarkers for a variety of human conditions. PMID:26693644

  11. Functional Redundancy Patterns Reveal Non-Random Assembly Rules in a Species-Rich Marine Assemblage

    PubMed Central

    Guillemot, Nicolas; Kulbicki, Michel; Chabanet, Pascale; Vigliola, Laurent

    2011-01-01

    The relationship between species and the functional diversity of assemblages is fundamental in ecology because it contains key information on functional redundancy, and functionally redundant ecosystems are thought to be more resilient, resistant and stable. However, this relationship is poorly understood and undocumented for species-rich coastal marine ecosystems. Here, we used underwater visual censuses to examine the patterns of functional redundancy for one of the most diverse vertebrate assemblages, the coral reef fishes of New Caledonia, South Pacific. First, we found that the relationship between functional and species diversity displayed a non-asymptotic power-shaped curve, implying that rare functions and species mainly occur in highly diverse assemblages. Second, we showed that the distribution of species amongst possible functions was significantly different from a random distribution up to a threshold of ∼90 species/transect. Redundancy patterns for each function further revealed that some functions displayed fast rates of increase in redundancy at low species diversity, whereas others were only becoming redundant past a certain threshold. This suggested non-random assembly rules and the existence of some primordial functions that would need to be fulfilled in priority so that coral reef fish assemblages can gain a basic ecological structure. Last, we found little effect of habitat on the shape of the functional-species diversity relationship and on the redundancy of functions, although habitat is known to largely determine assemblage characteristics such as species composition, biomass, and abundance. Our study shows that low functional redundancy is characteristic of this highly diverse fish assemblage, and, therefore, that even species-rich ecosystems such as coral reefs may be vulnerable to the removal of a few keystone species. PMID:22039543

  12. Intrauterine synechiae after myomectomy; laparotomy versus laparoscopy: Non-randomized interventional trial

    PubMed Central

    Asgari, Zahra; Hafizi, Leili; Hosseini, Rayhaneh; Javaheri, Atiyeh; Rastad, Hathis

    2015-01-01

    Background: Leiomyomata is the most frequent gynecological neoplasm. One of the major complications of myomectomy is intrauterine adhesion (synechiae). Objective: To evaluate and compare the rate and severity of synechiae formation after myomectomy by laparotomy and laparoscopy. Materials and Methods: In this non-randomized interventional trial, hysteroscopy was performed in all married fertile women who had undergone myomectomy (type 3-6 interamural and subserosal fibroids) via laparotomy and laparoscopy in Tehran’s Arash Hospital from 2010 to 2013. Three months after the operation, the occurrence rate and severity of intrauterine synechiae, and its relationship with type, number and location of myomas were investigated and compared in both groups. Results: Forty patients (19 laparoscopy and 21 laparotomy cases) were studied. Both groups were similar regarding the size, type (subserosal or intramural), number and location of myoma. The occurrence rate of synechiae in the laparoscopy and laparotomy group was 21% and 19%, respectively; showing no significant difference (p=0.99). Among all patients, no significant relationship was found between the endometrial opening (p=0.92), location (p=0.14) and type of myoma (p=0.08) with the occurrence rate of synechiae. However, a significant relationship was observed between myoma’s size (p=0.01) and the location of the largest myoma with the occurrence of synechiae (p=0.02). Conclusion: With favorable suturing methods, the outcome of intrauterine synechiae formation after myomectomy, either performed by laparotomy or laparoscopy, is similar. In all cases of myomectomy in reproductive-aged women, postoperative hysteroscopy is highly recommended to better screen intrauterine synechiae. PMID:26000007

  13. Non-random correlation structures and dimensionality reduction in multivariate climate data

    NASA Astrophysics Data System (ADS)

    Vejmelka, Martin; Pokorná, Lucie; Hlinka, Jaroslav; Hartman, David; Jajcay, Nikola; Paluš, Milan

    2015-05-01

    It is well established that the global climate is a complex phenomenon with dynamics driven by the interaction of a multitude of identifiable but intertwined subsystems. The identification, at some level, of these subsystems is an important step towards understanding climate dynamics. We present a method to determine the number of principal components representing non-random correlation structures in climate data, or components that cannot be generated by a surrogate model of independent stochastic processes replicating the auto-correlation structure of each time series. The purpose of the method is to automatically reduce the dimensionality of large climate datasets into spatially localised components suitable for further interpretation or, for example, for use as nodes in a complex network analysis of large-scale climate dynamics. We apply the method to two 2.5° resolution NCEP/NCAR reanalysis global datasets of monthly means: the sea level pressure (SLP) and the surface air temperature (SAT), and extract 60 components explaining 87 % variance and 68 components explaining 72 % variance, respectively. The obtained components are in agreement with previous results in that they recover many well-known climate modes previously identified using other approaches including regionally constrained principal component analysis. Selected SLP components are discussed in more detail with respect to their correlation with important climate indices and their relationship to other SLP and SAT components. Finally, we consider a subset of the obtained components that have not yet been explicitly identified by other authors but seem plausible in the context of regional climate observations discussed in literature.

  14. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.

    PubMed

    Verstovsek, Srdan; Manshouri, Taghi; Pilling, Darrell; Bueso-Ramos, Carlos E; Newberry, Kate J; Prijic, Sanja; Knez, Liza; Bozinovic, Ksenija; Harris, David M; Spaeth, Erika L; Post, Sean M; Multani, Asha S; Rampal, Raajit K; Ahn, Jihae; Levine, Ross L; Creighton, Chad J; Kantarjian, Hagop M; Estrov, Zeev

    2016-08-22

    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients' BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process. PMID:27481130

  15. Plastic bronchitis caused by neoplastic infiltrates in a child.

    PubMed

    Kuperman, Tamar; Wexler, Isaiah D; Shoseyov, David; Weintraub, Michael; Revel-Vilk, Shoshana; Kerem, Eitan

    2006-09-01

    We report on a case of a 7-year-old girl admitted for pneumonia not responding to oral antibiotics. During hospitalization, her pulmonary status deteriorated as a result of significant atelectasis. An extensive workup revealed an anaplastic large-cell lymphoma with neoplastic cells, found in both a biopsied lymph node and pleural fluid aspirate. Bronchoscopic examination showed nearly complete obstruction of the left side by bronchial casts composed of tumor cells, fibrin, and necrotic material, consistent with plastic bronchitis. Neoplastic infiltration of the bronchi should be considered in the differential diagnosis of disease entities causing plastic bronchitis in children. PMID:16779857

  16. Non-random distribution of DNA double-strand breaks induced by particle irradiation

    NASA Technical Reports Server (NTRS)

    Lobrich, M.; Cooper, P. K.; Rydberg, B.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Induction of DNA double-strand breaks (dsbs) in mammalian cells is dependent on the spatial distribution of energy deposition from the ionizing radiation. For high LET particle radiations the primary ionization sites occur in a correlated manner along the track of the particles, while for X-rays these sites are much more randomly distributed throughout the volume of the cell. It can therefore be expected that the distribution of dsbs linearly along the DNA molecule also varies with the type of radiation and the ionization density. Using pulsed-field gel and conventional gel techniques, we measured the size distribution of DNA molecules from irradiated human fibroblasts in the total range of 0.1 kbp-10 Mbp for X-rays and high LET particles (N ions, 97 keV/microns and Fe ions, 150 keV/microns). On a mega base pair scale we applied conventional pulsed-field gel electrophoresis techniques such as measurement of the fraction of DNA released from the well (FAR) and measurement of breakage within a specific NotI restriction fragment (hybridization assay). The induction rate for widely spaced breaks was found to decrease with LET. However, when the entire distribution of radiation-induced fragments was analysed, we detected an excess of fragments with sizes below about 200 kbp for the particles compared with X-irradiation. X-rays are thus more effective than high LET radiations in producing large DNA fragments but less effective in the production of smaller fragments. We determined the total induction rate of dsbs for the three radiations based on a quantitative analysis of all the measured radiation-induced fragments and found that the high LET particles were more efficient than X-rays at inducing dsbs, indicating an increasing total efficiency with LET. Conventional assays that are based only on the measurement of large fragments are therefore misleading when determining total dsb induction rates of high LET particles. The possible biological significance of this non-randomness

  17. Cell adhesion geometry regulates non-random DNA segregation and asymmetric cell fates in mouse skeletal muscle stem cells.

    PubMed

    Yennek, Siham; Burute, Mithila; Théry, Manuel; Tajbakhsh, Shahragim

    2014-05-22

    Cells of several metazoan species have been shown to non-randomly segregate their DNA such that older template DNA strands segregate to one daughter cell. The mechanisms that regulate this asymmetry remain undefined. Determinants of cell fate are polarized during mitosis and partitioned asymmetrically as the spindle pole orients during cell division. Chromatids align along the pole axis; therefore, it is unclear whether extrinsic cues that determine spindle pole position also promote non-random DNA segregation. To mimic the asymmetric divisions seen in the mouse skeletal stem cell niche, we used micropatterns coated with extracellular matrix in asymmetric and symmetric motifs. We show that the frequency of non-random DNA segregation and transcription factor asymmetry correlates with the shape of the motif and that these events can be uncoupled. Furthermore, regulation of DNA segregation by cell adhesion occurs within a defined time interval. Thus, cell adhesion cues have a major impact on determining both DNA segregation patterns and cell fates. PMID:24836002

  18. Radiation injury of the normal and neoplastic prostate

    SciTech Connect

    Bostwick, D.G.; Egbert, B.M.; Fajardo, L.F.

    1982-09-01

    Tissue samples from 40 patients with prostatic adenocarcinoma treated by radiation therapy were evaluated simultaneously by three observers to establish criteria for distinguishing residual tumor from radiation-induced atypia. Sections from 10 patients irradiated for nonprostatic pelvic neoplasms served as controls in addition to pretreatment biopsies from the determinate group. Patients had been treated by external x-irradiation, the majority receiving 6200-7400 rad to the prostate and pelvis over 7 to 8 weeks. Positive (tumor) biopsy incidence in the determinate group was 80% at 18 months, 40% at 36 months, and 43% in later samples. The following features were characteristic of radiation injury in the prostate: decreased ratio of the number of tumor glands to stroma, atrophy and squamous-like metaplasia of non-neoplastic glands with or without atypia, stromal fibrosis, arterial lumenal narrowing due to myointimal proliferation, foam cells within vessel walls, and fibrosis and atrophy of seminal vesicles. Criteria not useful for diagnosing radiation injury included architectural pattern or differentiation of tumor, cytologic features of tumor cells, inflammatory infiltrate, and ratio of normal glands to stroma. Ionizing radiation produced characteristic lesions in neoplastic and non-neoplastic prostatic glands, stroma, and blood vessels, and the sum of these changes was a reliable indicator of prior radiotherapy. An understanding of the morphologic effects of radiation injury of the prostate allowed distinction between residual prostatic adenocarcinoma and radiation-induced atypia of non-neoplastic glands.

  19. The post-pollination ethylene burst and the continuation of floral advertisement are harbingers of non-random mate selection in Nicotiana attenuata.

    PubMed

    Bhattacharya, Samik; Baldwin, Ian T

    2012-08-01

    The self-compatible plant Nicotiana attenuata grows in genetically diverse populations after fires, and produces flowers that remain open for 3 days and are visited by assorted pollinators. To determine whether and when post-pollination non-random mate selection occurs among self and non-self pollen, seed paternity and semi-in vivo pollen tube growth were determined in controlled single/mixed pollinations. Despite all pollen sources being equally proficient in siring seeds in single-genotype pollinations, self pollen was consistently selected in mixed pollinations, irrespective of maternal genotype. However, clear patterns of mate discrimination occurred amongst non-self pollen when mixed pollinations were performed soon after corollas open, including selection against hygromycin B resistance (transformation selectable marker) in wild-type styles and for it in transformed styles. However, mate choice among pollen genotypes was completely shut down in plants transformed to be unable to produce (irACO) or perceive (ETR1) ethylene. The post-pollination ethylene burst, which originates primarily from the stigma and upper style, was strongly correlated with mate selection in single and mixed hand-pollinations using eight pollen donors in two maternal ecotypes. The post-pollination ethylene burst was also negatively correlated with the continuation of emission of benzylacetone, the most abundant pollinator-attracting corolla-derived floral volatile. We conclude that ethylene signaling plays a pivotal role in mate choice, and the post-pollination ethylene burst and the termination of benzylacetone release are accurate predictors, both qualitatively and quantitatively, of pre-zygotic mate selection and seed paternity. PMID:22458597

  20. Micro-Raman spectroscopy Detects Individual Neoplastic and Normal Hematopoietic Cells

    SciTech Connect

    Chan, J W; Taylor, D; Zwerdling, T; Lane, S M; Ihara, K; Huser, T

    2005-01-18

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often non-specific, slow, biologically perturbing, or a combination, thereof. Here, we show that single-cell micro-Raman spectroscopy averts these shortcomings and can be used to discriminate between unfixed normal human lymphocytes and transformed Jurkat and Raji lymphocyte cell lines based on their biomolecular Raman signatures. We demonstrate that single-cell Raman spectra provide a highly reproducible biomolecular fingerprint of each cell type. Characteristic peaks, mostly due to different DNA and protein concentrations, allow for discerning normal lymphocytes from transformed lymphocytes with high confidence (p << 0.05). Spectra are also compared and analyzed by principal component analysis (PCA) to demonstrate that normal and transformed cells form distinct clusters that can be defined using just two principal components. The method is shown to have a sensitivity of 98.3% for cancer detection, with 97.2% of the cells being correctly classified as belonging to the normal or transformed type. These results demonstrate the potential application of confocal micro-Raman spectroscopy as a clinical tool for single cell cancer detection based on intrinsic biomolecular signatures, therefore eliminating the need for exogenous fluorescent labeling.

  1. Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations

    PubMed Central

    2011-01-01

    Premature activation of the hypothalamic-pituitary-gonadal (HPG) axis manifests as gonadotropin-dependent precocious puberty. The mechanisms behind HPG activation are complex and a clear etiology for early activation is often not elucidated. Though collectively uncommon, the neoplastic and developmental causes of gonadotropin-dependent precocious puberty are very important to consider, as a delay in diagnosis may lead to adverse patient outcomes. The intent of the current paper is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty. We discuss the common CNS lesions and human chorionic gonadotropin-secreting tumors that cause sexual precocity, review the relationship between therapeutic radiation and gonadotropin-dependent precocious puberty, and finally, provide an overview of the therapies available for height preservation in this unique patient population. PMID:21603196

  2. Microbial growth tests in anti-neoplastic injectable solutions.

    PubMed

    Paris, Isabelle; Paci, Angelo; Rey, Jean-Baptiste; Bourget, Philippe

    2005-03-01

    The Institut Gustave-Roussy (IGR) Department of Clinical Pharmacy (DCP) ensures the annual preparation of about 30 000 therapeutic batches of anti-neoplastic agents. High performance thin-layer chromatography (HPTLC) allows postproduction quality control of these batches. Although the centralized chemotherapy manufacturing unit has been recently ISO 9001:2000 certified, it was considered to improve the quality level of manufactured batches even further. The viability of micro-organisms (bacteria and fungi) in appropriate sterile media containing various anti-neoplastic agents at therapeutic concentration was assessed to demonstrate the lack of contamination during our manufacturing process in the isolator. After 14 days of incubation in these media, the results show the absence of contamination of the manufactured batches. This leads us to conclude that using sterile drugs and sterile medical devices in a sterile isolator allows the manufacture of sterile therapeutic batches with excellent confidence. PMID:16460598

  3. CD1a Reactivity in Non-neoplastic Adenohypophysis.

    PubMed

    Pisapia, David J; Rosenblum, Marc K; Lavi, Ehud

    2016-06-01

    Within the differential diagnosis of patients presenting with sellar or suprasellar lesions is Langerhans cell histiocytosis (LCH). CD1a staining is frequently used to identify the presence of an abnormal proliferation of Langerhans cells on histologic sections and contributes to the diagnosis of LCH. Here, we report that the MTB-1 monoclonal antibody against the CD1a antigen reacts to native adenohypophyseal epithelial cells. We show that immunohistochemistry for CD1a exhibits strong positivity in all autopsy and surgically resected non-neoplastic adenohypophysis tested. Thus, CD1a positivity by itself should be interpreted with caution, and we recommend the routine use of a panel of stains including CD1a, Langerin, and synaptophysin in conjunction with morphologic analysis before a diagnosis of LCH is rendered. In addition, we find that pituitary adenomas fail to stain for CD1a prompting consideration of the utility of this stain as a marker for non-neoplastic gland. PMID:26999501

  4. Neoplastic Meningitis from Solid Tumors: New Diagnostic and Therapeutic Approaches

    PubMed Central

    Zustovich, Fable; Farina, Patrizia; Della Puppa, Alessandro; Manara, Renzo; Cecchin, Diego; Brunello, Antonella; Cappetta, Alessandro; Zagonel, Vittorina

    2011-01-01

    Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. PMID:21795431

  5. A mosaic genetic screen for Drosophila neoplastic tumor suppressor genes based on defective pupation.

    PubMed

    Menut, Laurent; Vaccari, Thomas; Dionne, Heather; Hill, Joseph; Wu, Geena; Bilder, David

    2007-11-01

    The Drosophila neoplastic tumor suppressor genes (TSGs) coordinately control cell polarity and proliferation in epithelial and neuronal tissues. While a small group of neoplastic TSG mutations have been isolated and their corresponding genes cloned, the regulatory pathways that normally prevent inappropriate growth remain unclear. Identification of additional neoplastic TSGs may provide insight into this question. We report here the design of an efficient screen for isolating neoplastic TSG mutations utilizing genetically mosaic larvae. This screen is based on a defective pupation phenotype seen when a single pair of imaginal discs is homozygous for a neoplastic TSG mutation, which suggests that continuously proliferating cells can interfere with metamorphosis. Execution of this screen on two chromosome arms led to the identification of mutations in at least seven new neoplastic TSGs. The isolation of additional loci that affect hyperplastic as well as neoplastic growth indicates the utility of this screening strategy for studying epithelial growth control. PMID:17947427

  6. Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway

    PubMed Central

    2014-01-01

    Background Cervical cancer is a chronic inflammatory disease of multifactorial etiology usually presenting in sexually active women. Exposure of neoplastic cervical epithelial cells to seminal plasma (SP) has been shown to promote the growth of cancer cells in vitro and tumors in vivo by inducing the expression of inflammatory mediators including pro-inflammatory cytokines. IL-1α is a pleotropic pro-inflammatory cytokine induced in several human cancers and has been associated with virulent tumor phenotype and poorer prognosis. Here we investigated the expression of IL-1α in cervical cancer, the role of SP in the regulation of IL-1α in neoplastic cervical epithelial cells and the molecular mechanism underlying this regulation. Methods and results Real-time quantitative RT-PCR confirmed the elevated expression of IL-1α mRNA in cervical squamous cell carcinoma and adenocarcinoma tissue explants, compared with normal cervix. Using immunohistochemistry, IL-1α was localized to the neoplastically transformed squamous, columnar and glandular epithelium in all cases of squamous cell carcinoma and adenocarcinomas explants studied. We found that SP induced the expression of IL-α in both normal and neoplastic cervical tissue explants. Employing HeLa (adenocarcinoma) cell line as a model system we identified PGE2 and EGF as possible ligands responsible for SP-mediated induction of IL-1α in these neoplastic cells. In addition, we showed that SP activates EP2/EGFR/PI3kinase-Akt signaling to induce IL-1α mRNA and protein expression. Furthermore, we demonstrate that in normal cervical tissue explants the induction of IL-1α by SP is via the activation of EP2/EGFR/PI3 kinase-Akt signaling. Conclusion SP-mediated induction of IL-1α in normal and neoplastic cervical epithelial cells suggests that SP may promote cervical inflammation as well as progression of cervical cancer in sexually active women. PMID:25237386

  7. Identification of non-random sequence properties in groups of signature peptides obtained in random sequence peptide microarray experiments.

    PubMed

    Kuznetsov, Igor B

    2016-05-01

    Immunosignaturing is an emerging experimental technique that uses random sequence peptide microarrays to detect antibodies produced by the immune system in response to a particular disease. Two important questions regarding immunosignaturing are "Do microarray peptides that exhibit a strong affinity to a given type of antibodies share common sequence properties?" and "If so, what are those properties?" In this work, three statistical tests designed to detect non-random patterns in the amino acid makeup of a group of microarray peptides are presented. One test detects patterns of significantly biased amino acid usage, whereas the other two detect patterns of significant bias in the biochemical properties. These tests do not require a large number of peptides per group. The tests were applied to analyze 19 groups of peptides identified in immunosignaturing experiments as being specific for antibodies produced in response to various types of cancer and other diseases. The positional distribution of the biochemical properties of the amino acids in these 19 peptide groups was also studied. Remarkably, despite the random nature of the sequence libraries used to design the microarrays, a unique group-specific non-random pattern was identified in the majority of the peptide groups studied. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 318-329, 2016. PMID:27037995

  8. Differential expression of immune-modulatory molecule HLA-E in non-neoplastic and neoplastic lesions of the thyroid.

    PubMed

    Zanetti, B R; Carvalho-Galano, D F; Feitosa, N L F; Hassumi-Fukasawa, M K; Miranda-Camargo, F A; Maciel, L M Z; Ribeiro-Silva, A; Soares, E G

    2013-01-01

    Human leukocyte antigen (HLA)–E is a non-classical molecule of the histocompatibility complex that functions as one of the main ligands of the Natural Killer (NK) cell inhibitory receptor CD94/NKG2A and inhibits its potent cytotoxic activity. Due to the important role of NK cells in combating neoplasm, we hypothesized that the differential expression of HLA-E could favor the progression of heterogeneous thyroid tumors.Using an immunohistochemistry technique in 143 biopsies of thyroid tumors, including benign and malignant neoplasms and goiters, we evaluated the expression of HLA-E among various tumor types and its association with the clinicopathological factors of diseases. We verified high HLA-E expression in all types of neoplastic tumors, although no significant differences between the groups were found. Low expression was observed in 95 percent of the goiter samples, showing significant differences between neoplastic and non-neoplastic lesions. Furthermore, a significant result was found with regard to the tumor size, with high HLA-E expression being related to smaller tumors. Therefore, our data suggest that an increase in HLA-E may be associated with the establishment of thyroid neoplasms, with either benign or malignant features. PMID:24355224

  9. Cell culture systems to study glial transformation

    SciTech Connect

    Bressler, J.P.; Cole, R.; de Vellis, J.

    1980-01-01

    The transformation of two different types of glial cells has been studied using an in vivo-/in vitro model and a complete in vitro model. The purpose of the study and to define in vitro model systems is to study the the neoplastic transformation of pure populations of glial cells. Data are presented to demonstrate that the transformed cells are glial and tumorigenic. (ACR)

  10. Immunohistochemical expression of SOX9 protein in immature, mature, and neoplastic canine Sertoli cells.

    PubMed

    Banco, Barbara; Palmieri, Chiara; Sironi, Giuseppe; Fantinato, Eleonora; Veronesi, Maria C; Groppetti, Debora; Giudice, Chiara; Martignoni, Benedetta; Grieco, Valeria

    2016-05-01

    Sex-determining region Y box9 gene (SOX9) protein plays a pivotal role in male sexual development. It regulates the transcription of the anti-Müllerian hormone gene promoting development of testis cords, multiplication, and maturation of Sertoli cells (SCs) and maintenance of spermatogenesis in adult testis. The immunohistochemical expression of SOX9 in normal testes has been reported in humans, mice, and rats. The present study aimed to investigate the expression of SOX9 in canine SCs during testicular maturation and neoplastic transformation. Canine testicular samples derived from three fetuses, four newborns, four prepubertal puppies, five adult dogs, 31 Sertoli cell tumors (SCTs) (one metastasizing), and five Leydig cell tumors (LCTs) were selected from departmental archive and tested immunohistochemically with a polyclonal antibody against SOX9 (1:150). All SCs from fetal, neonatal, and adult testes had a strong and exclusively nuclear labeling for SOX9. In SCs from prepubertal testes, SOX9 staining was highly variable with one negative sample (one of four), two samples with exclusively nuclear staining (two of four), and one with both nuclear and cytoplasmic labeling (one of four). Leydig cells (LCs) and LCTs were always negative. All 31 SCTs were positive for SOX9. The expression of SOX9 was nuclear, nuclear and cytoplasmic, and exclusively cytoplasmic in 18 of 31, 11 of 31, and two of 31 SCTs, respectively. This first report on the immunohistochemical expression of SOX9 in canine testes reports that in normal SCs from fetal, neonatal, and adult testes SOX9 labeled the nucleus, as in humans and laboratory animals. The cytoplasmic labeling observed in one prepubertal pairs of testes and in 11 SCTs could reflect SC immaturity or dedifferentiation, paralleling results observed in rat testes. The expression of SOX9 in SCs and SCTs and its absence in LCs and LCTs suggests that SOX9 is a reliable diagnostic marker for both normal and neoplastic SCs. PMID:26777558

  11. Methodological issues in observational studies and non-randomized controlled trials in oncology in the era of big data.

    PubMed

    Tanaka, Shiro; Tanaka, Sachiko; Kawakami, Koji

    2015-04-01

    Non-randomized controlled trials, cohort studies and database studies are appealing study designs when there are urgent needs for safety data, outcomes of interest are rare, generalizability is a matter of concern, or randomization is not feasible. This paper reviews four typical case studies from methodological viewpoints and clarifies how to minimize bias in observational studies in oncology. In summary, researchers planning observational studies should be cautious of selection of appropriate databases, validity of algorithms for identifying outcomes, comparison with incident users or self-control, rigorous collection of information on potential confounders and reporting details of subject selection. Further, a careful study protocol and statistical analysis plan are also necessary. PMID:25589456

  12. The Origin of Aging: Imperfectness-Driven Non-Random Damage Defines the Aging Process and Control of Lifespan

    PubMed Central

    Gladyshev, Vadim N.

    2013-01-01

    Physico-chemical properties preclude ideal biomolecules and perfect biological functions. This inherent imperfectness leads to the generation of damage by every biological process, at all levels, from small molecules to cells. The damage is too numerous to be repaired, is partially invisible to natural selection and manifests as aging. I propose that it is the inherent imperfectness of biological systems that is the true root of the aging process. As each biomolecule generates specific forms of damage, the cumulative damage is largely non-random and is indirectly encoded in the genome. I consider this concept in light of other proposed theories of aging and integrate these disparate ideas into a single model. I also discuss the evolutionary significance of damage accumulation and strategies for reducing damage. Finally, I suggest ways to test this integrated model of aging. PMID:23769208

  13. De-misty-fying the mesentery: an algorithmic approach to neoplastic and non-neoplastic mesenteric abnormalities.

    PubMed

    Taffel, Myles T; Khati, Nadia J; Hai, Nabila; Yaghmai, Vahid; Nikolaidis, Paul

    2014-08-01

    Mesenteric abnormalities are often incidentally discovered on cross-sectional imaging performed during daily clinical practice. Findings can range from the vague "misty mesentery" to solid masses, and the possible etiologic causes encompass a wide spectrum of underlying pathologies including infectious, inflammatory, and neoplastic processes. Unfortunately, the clinical and imaging findings are often non-specific and may overlap. This article discusses the various diseases that result in mesenteric abnormalities. It provides a framework to non-invasively differentiate these entities, when possible. PMID:24633598

  14. Multifunctional CD40L: pro- and anti-neoplastic activity.

    PubMed

    Korniluk, Aleksandra; Kemona, Halina; Dymicka-Piekarska, Violetta

    2014-10-01

    The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily. It is present not only on the surface of activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer (NK) cells but also on cancer cells. The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation. CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer. Although CD40L has a major contribution to anti-cancer activity, many reports point at its ambivalent nature. CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis. CD40L involvement in the inhibition of tumor progression has led to the emergence of not only therapy using recombinant forms of the ligand and vaccines in the treatment of cancer but also therapy consisting of inhibiting platelets-main source of CD40L. This article is a review of studies on the ambivalent role of CD40L in neoplastic diseases. PMID:25117071

  15. Cancer: The Transforming Power of Cell Competition.

    PubMed

    Gil, Jesus; Rodriguez, Tristan

    2016-02-22

    The tumour-host microenvironment plays key roles in cancer, but the mechanisms involved are not fully understood. Two new studies provide insight into this problem by showing that through cell competition, a fitness-sensing process that usually eliminates defective cells, pre-cancerous lesions signal the death of surrounding tissue that in turn promotes their neoplastic transformation. PMID:26906487

  16. Role of Peroxisome Proliferator-Activated Receptor γ and Its Ligands in Non-Neoplastic and Neoplastic Human Urothelial Cells

    PubMed Central

    Nakashiro, Koh-ichi; Hayashi, Yoshiki; Kita, Akiyo; Tamatani, Tetsuya; Chlenski, Alexandre; Usuda, Nobuteru; Hattori, Kazunori; Reddy, Janardan K.; Oyasu, Ryoichi

    2001-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPARγ reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPARγ in normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPARγ uniformly. All low-grade carcinomas were positive either diffusely or focally, whereas staining was primarily focal or absent in high-grade carcinomas. A nonneoplastic urothelial cell line (1T-1), a low-grade (RT4) carcinoma cell line, and two high-grade (T24 and 253J) carcinoma cell lines in culture expressed PPARγ mRNA and protein. Luciferase assay indicated that PPARγ was functional. PPARγ ligands (15-deoxy-Δ12,14-prostaglandin J2, troglitazone and pioglitazone) suppressed the growth of nonneoplastic and neoplastic urothelial cells in a dose-dependent manner. However, neoplastic cells were more resistant than were nonneoplastic cells. Failure to express PPARγ or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPARγ ligands. PMID:11485917

  17. Neoplastic cauda equina syndrome: a neuroimaging-based review.

    PubMed

    Bennett, Shelby J; Katzman, Gregory L; Roos, Raymond P; Mehta, Amar S; Ali, Saad

    2016-02-01

    Cauda equina syndrome refers to dysfunction of the cauda equina, the collection of ventral and dorsal lumbar, sacral and coccygeal nerve roots that surround the filum terminale. This most commonly occurs as a result of compression by a herniated lumbosacral disc. However, the syndrome may also complicate metastatic cancer or a primary neoplasm within or infiltrating the spinal canal. An accurate and timely diagnosis is critical to avoid irreversible loss of neurological function. The clinician and radiologist must therefore be aware of the many possible causes to guide timely management. Here we review the diverse neoplastic causes affecting the cauda equina nerve roots from a neuroimaging-based perspective. We divide them by location into intramedullary neoplasms at the conus (such as astrocytoma), intradural-extramedullary neoplasms (such as schwannoma and leptomeningeal metastases) and extradural neoplasms (such as spinal metastases from systemic neoplasms). We also discuss the clinical features associated with cauda equina tumours, with special focus on cauda equina syndrome. PMID:26442520

  18. Guidelines for genomic array analysis in acquired haematological neoplastic disorders.

    PubMed

    Schoumans, Jacqueline; Suela, Javier; Hastings, Ros; Muehlematter, Dominique; Rack, Katrina; van den Berg, Eva; Berna Beverloo, H; Stevens-Kroef, Marian

    2016-05-01

    Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism-detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc. PMID:26774012

  19. Risk factors for neoplastic progression in Barrett’s esophagus

    PubMed Central

    Wiseman, Elizabeth F; Ang, Yeng S

    2011-01-01

    Barrett’s esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a “metaplasia-dysplasia-carcinoma” (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clinical risk factors have been investigated, and associations with a variety of genetic, specific gastrointestinal and other modifiable factors have been proposed in the literature. This review summarizes the current understanding of the mechanisms involved in neoplastic progression of BE to EAC and critically appraises the relative roles and contributions of these putative risk factors from the published evidence currently available. PMID:21990948

  20. Nuclear Division Index may Predict Neoplastic Colorectal Lesions

    PubMed Central

    IONESCU, Mirela E.; CIOCIRLAN, Mihai; BECHEANU, Gabriel; NICOLAIE, Tudor; DITESCU, Cristina; TEIUSANU, Adriana G.; GOLOGAN, Serban I.; ARBANAS, Tudor; DICULESCU, Mircea M.

    2011-01-01

    ABSTRACT Background: Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. Methods: Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. Results: 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). Conclusion: NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker. PMID:22368693

  1. Non-random cation distribution in hexagonal Al 0.5Ga 0.5PO 4

    NASA Astrophysics Data System (ADS)

    Kulshreshtha, S. K.; Jayakumar, O. D.; Sudarsan, V.

    2010-05-01

    Based on powder X-ray diffraction and 31P Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) investigations of mixed phosphate Al 0.5Ga 0.5PO 4, prepared by co-precipitation method followed by annealing at 900 °C for 24 h, it is shown that Al 0.5Ga 0.5PO 4 phase crystallizes in hexagonal form with lattice parameter a=0.491(2) and c=1.106(4) nm. This hexagonal phase of Al 0.5Ga 0.5PO 4 is similar to that of pure GaPO 4. The 31P MAS NMR spectrum of the mixed phosphate sample consists of five peaks with systematic variation of their chemical shift values and is arising due to existence of P structural units having varying number of the Al 3+/Ga 3+ cations as the next nearest neighbors in the solid solution. Based on the intensity analysis of the component NMR spectra of Al 0.5Ga 0.5PO 4, it is inferred that the distribution of Al 3+ and Ga 3+ cations is non-random for the hexagonal Al 0.5Ga 0.5PO 4 sample although XRD patterns showed a well-defined solid solution formation.

  2. Co-occurrence analyses show that non-random community structure is disrupted by fire in two groups of soil arthropods (Isopoda Oniscidea and Collembola)

    NASA Astrophysics Data System (ADS)

    Pitzalis, Monica; Luiselli, Luca; Bologna, Marco A.

    2010-01-01

    In this paper, we tested the hypothesis that natural catastrophes may destroy non-random community structure in natural assemblages of organisms. As a study system, we selected fire as the catastrophic event, and two groups of soil arthropods (Collembola and Isopoda Oniscidea) as target organisms. By co-occurrence analyses and Monte Carlo simulations of niche overlap analysis (C-score, with fixed-equiprobable model; RA2 and RA3 algorithms) we evaluated whether the community structure of these two groups were random/non-random at three unburnt sites and at three neighbour burnt sites that were devastated by a large-scale fire in summer 2000. Both taxa experienced a remarkable reduction in the number of species sampled in burnt versus unburnt sites, but the difference among sites was not statistically significant for Oniscidea. We determined that community structure was clearly non-random at the unburnt sites for both Collembola (according to RA3 algorithm) and Isopoda Oniscidea (according to co-occurrence analysis) and that, as predicted by theory, the catastrophic event did deeply alter the community structure by removing the non-random organization of the species interactions. We also observed a shift from segregation to aggregation/randomness in soil arthropods communities affected by fire, a pattern that was similar to that observed in natural communities of organisms perturbed by the introduction of alien species, thus indicating that this pattern may be generalizable when alteration of communities may occur.

  3. Lectin histochemistry of normal and neoplastic peripheral nerve sheath. 2. Lectin binding patterns of schwannoma and neurofibroma.

    PubMed

    Matsumura, K; Nakasu, S; Nioka, H; Handa, J

    1993-01-01

    Lectin binding patterns of 31 schwannomas and 6 neurofibromas were examined using 12 lectins, and the results were compared with those of normal peripheral nerves. Tumors obtained from 10 cases of neurofibromatosis and 4 recurrent schwannomas were included. Changes of glycoconjugates were observed in association with a neoplastic transformation of Schwann cells; Arachis hypogaea (PNA) staining after neuraminidase treatment seen in normal Schwann cells was reduced in schwannoma of Antoni type A, and bindings with Glycine max (SBA) and Helix pomatia (HPA) after sialic acid removal, which were not seen in normal Schwann cells, appeared in schwannoma cells. Intensities of staining of tumor cells with each lectin were higher in Antoni type B than those in Antoni type A. No differences in lectin binding patterns were observed between schwannomas in patients with neurofibromatosis or recurrent schwannomas and ordinary, primary schwannomas in patients without stigmata of neurofibromatosis. Lectin binding patterns of Schwann cells and perineurial cells in neurofibroma were almost similar to those in normal peripheral nerves with an exception of faint stain of Schwann cells with HPA after neuraminidase pretreatment. This result suggests differences in extent of differentiation between schwannoma cells and neoplastic Schwann cells in neurofibroma. Specific PNA binding to perineurial cells in neurofibroma indicates the significance of this lectin as a marker of these cells. PMID:8310811

  4. Growth factors, their receptor expression and markers for proliferation of endothelial and neoplastic cells in human osteosarcoma.

    PubMed

    Bianchi, E; Artico, M; Di Cristofano, C; Leopizzi, M; Taurone, S; Pucci, M; Gobbi, P; Mignini, F; Petrozza, V; Pindinello, I; Conconi, M T; Della Rocca, C

    2013-01-01

    Osteosarcoma is the most common primary malignant tumour of the bone. Although new therapies continue to be reported, osteosarcoma-related morbidity and mortality remain high. Modern medicine has greatly increased knowledge of the physiopathology of this neoplasm. Novel targets for drug development may be identified through an understanding of the normal molecular processes that are deeply modified in pathological conditions. The aim of the present study is to investigate, by immunohistochemistry, the localisation of different growth factors and of the proliferative marker Ki-67 in order to determine whether these factors are involved in the transformation of osteogenic cells and in the development of human osteosarcoma. We observed a general positivity for NGF - TrKA - NT3 - TrKC - VEGF in the cytoplasm of neoplastic cells and a strong expression for NT4 in the nuclear compartment. TGF-beta was strongly expressed in the extracellular matrix and vascular endothelium. BDNF and TrKB showed a strong immunolabeling in the extracellular matrix. Ki-67/MIB-1 was moderately expressed in the nucleus of neoplastic cells. We believe that these growth factors may be considered potential therapeutic targets in the treatment of osteosarcoma, although proof of this hypothesis requires further investigation. PMID:24067459

  5. LDOC1 silenced by cigarette exposure and involved in oral neoplastic transformation

    PubMed Central

    Lee, Chia-Huei; Pan, Kao-Lu; Tang, Ya-Chu; Tsai, Ming-Hsien; Cheng, Ann-Joy; Shen, Mei-Ya; Cheng, Ying-Min; Huang, Tze-Ta; Lin, Pinpin

    2015-01-01

    Previously, we identified global epigenetic aberrations in smoking-associated oral squamous cell carcinoma (OSCC). We hypothesized that cigarette exposure triggers OSCC through alteration of the methylome of oral cells. Here we report that cigarette smoke condensate (CSC) significantly changes the genomic 5-methyldeoxycytidine content and nuclear accumulation of DNA methyltransferase 1 (DNMT1) and DNMT3A in human untransformed oral cells. By using integrated analysis of cDNA and methylation arrays of the smoking-associated dysplastic oral cell line and OSCC tumors, respectively, we identified four epigenetic targets—UCHL1, GPX3, LXN, and LDOC1—which may be silenced by cigarette. Results of quantitative methylation-specific PCR showed that among these four genes, LDOC1 promoter was the most sensitive to CSC. LDOC1 promoter hypermethylation and gene silencing followed 3 weeks of CSC treatment. LDOC1 knockdown led to a proliferative response and acquired clonogenicity of untransformed oral cells. Immunohistochemistry showed that LDOC1 was downregulated in 53.3% (8/15) and 57.1% (20/35) of premalignant oral tissues and early stage OSCCs, respectively, whereas 76.5% (13/17) of normal oral tissues showed high LDOC1 expression. Furthermore, the microarray data showed that LDOC1 expression had decreased in the lung tissues of current smokers compared with that in those of never smokers and had significantly decreased in the lung tumors of smokers compared with that in normal lung tissues. Our data suggest that CSC-induced promoter methylation may contribute to LDOC1 downregulation, thereby conferring oncogenic features to oral cells. These findings also imply a tumor suppressor role of LDOC1 in smoking-related malignancies such as OSCC and lung cancer. PMID:26317789

  6. ADAPTIVE RESPONSE AGAINST SPONTANEOUS NEOPLASTIC TRANSFORMATION IN VITRO INDUCED BY IONIZING RADIATION

    EPA Science Inventory

    The following paragraphs outline a project which addresses the area "Understanding biological responses to radiation and endogeneous damage". The proposed research addresses the following key question: (a) "How much do low doses of radiation protect against subsequent low doses ...

  7. ULTRAVIOLET RADIATION-INDUCED NEOPLASTIC TRANSFORMATION OF NORMAL HUMAN CELLS, IN VITRO

    EPA Science Inventory

    Human foreskin cell cultures in schedules DNA synthesis (S phase) of the cell cycle were exposed to UV irradiation at a dose of 10 J.sq. m. in the presence of insulin. These treated cell populations, when selectively passaged in a high amino acid supplemented complete growth medi...

  8. Complementary approaches to understanding the role of proteases and their natural inhibitors in neoplastic development: retrospect and prospect.

    PubMed

    Rubin, Harry

    2003-05-01

    A great deal of evidence has accumulated in recent years for an important but complex role for proteases in tumor development. However, attempts to treat cancer in humans with anti-proteases have been disappointing, and it has been suggested that more basic groundwork is needed before anti-proteases can be effectively applied. Considerable basic information comes from the recognition that earlier results on transformation of chicken embryo fibroblasts (CEF) by the Bryan strain of Rous sarcoma virus (B-RSV) can be explained in terms of proteases and their inhibitors. In particular, the full but reversible normalization of discrete transformed foci by appropriate concentrations of fetal bovine or of calf serum implies a causal role for multiple proteases in transformation, and the efficacy of treatment with a physiological balance of their natural inhibitors. Addition of certain proteases to contact-inhibited normal cultures was then found to stimulate their proliferation. The toxicity of medium produced by CEF heavily transformed with B-RSV suggests that cachexia and other systemic effects of human cancer may result from vascular dissemination of peptides from pericellular proteolysis within tumors. Comprehensive studies revealed significant increases of plasminogen activator and matrix metalloproteinases (MMPs) after infection of CEF with other strains of RSV, and correlation of the proteases with aspects of transformation. A similar role for proteases is indicated in the transformation of mammalian cells by chemical and physical agents. The information gained from functional experiments on cell transformation in culture is complementary to that obtained from the molecular identification of proteases and their inhibitors in all stages of tumor development. The speed, quantification and easy manipulation of the RSV-CEF transformation assay can be combined with current methods of characterizing proteases and anti-proteases to further enrich our basic knowledge of

  9. A school intervention for mental health literacy in adolescents: effects of a non-randomized cluster controlled trial

    PubMed Central

    2013-01-01

    Background “Mental health for everyone” is a school program for mental health literacy and prevention aimed at secondary schools (13–15 yrs). The main aim was to investigate whether mental health literacy, could be improved by a 3-days universal education programme by: a) improving naming of symptom profiles of mental disorder, b) reducing prejudiced beliefs, and c) improving knowledge about where to seek help for mental health problems. A secondary aim was to investigate whether adolescent sex and age influenced the above mentioned variables. A third aim was to investigate whether prejudiced beliefs influenced knowledge about available help. Method This non-randomized cluster controlled trial included 1070 adolescents (53.9% boys, M age14 yrs) from three schools in a Norwegian town. One school (n = 520) received the intervention, and two schools (n = 550) formed the control group. Pre-test and follow-up were three months apart. Linear mixed models and generalized estimating equations models were employed for analysis. Results Mental health literacy improved contingent on the intervention, and there was a shift towards suggesting primary health care as a place to seek help. Those with more prejudiced beleifs did not suggest places to seek help for mental health problems. Generally, girls and older adolescents recognized symptom profiles better and had lower levels of prejudiced beliefs. Conclusions A low cost general school program may improve mental health literacy in adolescents. Gender specific programs and attention to the age and maturity of the students should be considered when mental health literacy programmes are designed and tried out. Prejudice should be addressed before imparting information about mental health issues. PMID:24053381

  10. Telomere Disruption Results in Non-Random Formation of De Novo Dicentric Chromosomes Involving Acrocentric Human Chromosomes

    PubMed Central

    Stimpson, Kaitlin M.; Song, Ihn Young; Jauch, Anna; Holtgreve-Grez, Heidi; Hayden, Karen E.; Bridger, Joanna M.; Sullivan, Beth A.

    2010-01-01

    Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the α-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extra-chromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same α-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment. PMID:20711355

  11. Detecting neoplastic development in the hamster cheek pouch using Fourier domain low coherence interferometry

    NASA Astrophysics Data System (ADS)

    Graf, Robert N.; Robles, Francisco; Chen, Xiaoxin; Wax, Adam

    2009-02-01

    Fourier Domain Low Coherence Interferometry (fLCI) is an optical technique that recovers depth-resolved spectroscopic information about scatterers. The current fLCI system utilizes a white light Xe arc lamp source, a 4-f interferometer, and an imaging spectrometer at the detection plane to acquire spectra from 256 adjacent spatial points. This configuration permits the acquisition of ultrahigh depth resolution Fourier domain OCT images without the need for any beam scanning. fLCI has traditionally obtained depth-resolved spectral information by performing a short-time Fourier transform (STFT) on the detected spectra, similar to the processing techniques of spectroscopic OCT. We now employ a dual Gaussian window processing method which simultaneously obtains high spectral and temporal resolution, thus avoiding the resolution trade-off normally associated with the STFT. Wavelength dependent variations in scattering intensity are analyzed as a function of depth to obtain structural information about the probed scatterers. We now verify fLCI's ability to distinguish between normal and dysplastic epithelial tissue using the hamster cheek pouch model. Thirty hamsters will have one cheek pouch treated with the known carcinogen DMBA. At the conclusion of the 24 week treatment period the animals will be anesthetized and the cheek pouches will be extracted. We will use the fLCI optical system to measure the neoplastic transformation of the in situ subsurface tissue layers in both the normal and DMBA-treated cheek pouches. Traditional histological analysis will be used to verify the fLCI measurements. Our results will further establish fLCI as an effective method for distinguishing between normal and dysplastic epithelial tissues.

  12. Uroplakin Gene Expression by Normal and Neoplastic Human Urothelium

    PubMed Central

    Lobban, E. Dawn; Smith, Barbara A.; Hall, Geoffrey D.; Harnden, Patricia; Roberts, Paul; Selby, Peter J.; Trejdosiewicz, Ludwik K.; Southgate, Jennifer

    1998-01-01

    cDNA sequences for human uroplakins UPIa, UPIb, UPII, and UPIII were cloned and used to investigate uroplakin transcription by normal and neoplastic urothelial cells. Normal urothelium expressed mRNA for all four uroplakins, although UPIII could be detected only by ribonuclease protection assay. By in situ hybridization, UPIa and UPII were confined to superficial cells and UPIb was also expressed by intermediate cells. Cultured normal human urothelial cells showed a proliferative basal/intermediate cell phenotype and constitutive expression of UPIb only. Uroplakin expression by transitional cell carcinoma cell lines was related to their differentiated phenotype in vitro. RT4 cells expressed all uroplakins, VM-CUB-3 expressed three uroplakins, RT112 and HT1376 cells expressed only UPIb in high abundance, and COLO232, KK47, and EJ cells had no detectable expression. These results correlated with patterns of uroplakin expression in tumors. UPIa and UPII were detected superficially only in well differentiated transitional cell carcinoma papillae. UPIb was positive in seven of nine and overexpressed in five of nine noninvasive transitional cell carcinomas and was also present in four of eight invasive transitional cell carcinomas. Lymph node metastases retained the same pattern of UPIb expression as the primary tumor. Unlike the three differentiation-regulated uroplakins, UPIb may have an alternative role in urothelial cell/tissue processes. PMID:9846985

  13. Uroplakin gene expression by normal and neoplastic human urothelium.

    PubMed

    Lobban, E D; Smith, B A; Hall, G D; Harnden, P; Roberts, P; Selby, P J; Trejdosiewicz, L K; Southgate, J

    1998-12-01

    cDNA sequences for human uroplakins UPIa, UPIb, UPII, and UPIII were cloned and used to investigate uroplakin transcription by normal and neoplastic urothelial cells. Normal urothelium expressed mRNA for all four uroplakins, although UPIII could be detected only by ribonuclease protection assay. By in situ hybridization, UPIa and UPII were confined to superficial cells and UPIb was also expressed by intermediate cells. Cultured normal human urothelial cells showed a proliferative basal/intermediate cell phenotype and constitutive expression of UPIb only. Uroplakin expression by transitional cell carcinoma cell lines was related to their differentiated phenotype in vitro. RT4 cells expressed all uroplakins, VM-CUB-3 expressed three uroplakins, RT112 and HT1376 cells expressed only UPIb in high abundance, and COLO232, KK47, and EJ cells had no detectable expression. These results correlated with patterns of uroplakin expression in tumors. UPIa and UPII were detected superficially only in well differentiated transitional cell carcinoma papillae. UPIb was positive in seven of nine and overexpressed in five of nine noninvasive transitional cell carcinomas and was also present in four of eight invasive transitional cell carcinomas. Lymph node metastases retained the same pattern of UPIb expression as the primary tumor. Unlike the three differentiation-regulated uroplakins, UPIb may have an alternative role in urothelial cell/tissue processes. PMID:9846985

  14. Microfluorometric comparisons of heat-induced nuclear acridine orange metachromasia between normal cells and neoplastic cells from primary tumors of diverse origin.

    PubMed

    Alvarez, M R

    1975-01-01

    Nuclear fluorescence metachromasia of heated fixed cells subsequently stained with acridine orange was compared in smears and isolated nuclei of various types of primary tumors and normal cells from the tissues that gave rise to the tumors. The ratios of fluorescence emission at 590 and 530 nm reflect the thermal stability of chromatin in situ. The results show that the mean thermal stability of the chromatin in neoplastic cells was lower than the stability of their normal counterparts in all cases. This was found in both spontaneous and chemically induced tumors as divergent in type as a dog vaginal tumor and murine lymphocytic leukemia. These data, together with our previous observations in other neoplastic systems, indicate that reduced chromatin thermal stability may be a general characteristic of cells that have undergone neoplastic transformation and is not confined to rapidly growing tumors. The present investigation identifies the sources of variability encountered in measuring fluorescence metachromasia in slide preparations, and methods of minimizing this variability for potential cytodiagnostic application are discussed. PMID:45893

  15. Effectiveness of a 'Global Postural Reeducation' program for persistent Low Back Pain: a non-randomized controlled trial

    PubMed Central

    2010-01-01

    Background The aim of this non-randomized controlled trial was to evaluate the effectiveness of a Global Postural Reeducation (GPR) program as compared to a Stabilization Exercise (SE) program in subjects with persistent low back pain (LBP) at short- and mid-term follow-up (ie. 3 and 6 months). Methods According to inclusion and exclusion criteria, 100 patients with a primary complaint of persistent LBP were enrolled in the study: 50 were allocated to the GPR group and 50 to the SE group. Primary outcome measures were Roland and Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI). Secondary outcome measures were lumbar Visual Analogue Scale (VAS) and Fingertip-to-floor test (FFT). Data were collected at baseline and at 3/6 months by health care professionals unaware of the study. An intention to treat approach was used to analyze participants according to the group to which they were originally assigned. Results Of the 100 patients initially included in the study, 78 patients completed the study: 42 in the GPR group and 36 in the SE group. At baseline, the two groups did not differ significantly with respect to gender, age, BMI and outcome measures. Comparing the differences between groups at short- and mid-term follow-up, the GPR group revealed a significant reduction (from baseline) in all outcome measures with respect to the SE group. The ordered logistic regression model showed an increased likelihood of definitive improvement (reduction from baseline of at least 30% in RMDQ and VAS scores) for the GPR group compared to the SE group (OR 3.9, 95% CI 2.7 to 5.7). Conclusions Our findings suggest that a GPR intervention in subjects with persistent LBP induces a greater improvement on pain and disability as compared to a SE program. These results must be confirmed by further studies with higher methodological standards, including randomization, larger sample size, longer follow-up and subgrouping of the LBP subjects. Trial registration NCT

  16. Terminal deoxynucleotidyltransferase distribution in neoplastic and hematopoietic cells.

    PubMed

    Greenwood, M F; Coleman, M S; Hutton, J J; Lampkin, B; Krill, C; Bolium, F J; Holland, P

    1977-05-01

    In the present study, terminal deoxynucleotidyltransferase was examined in the peripheral blood and (or) bone marrow of 115 children with a variety of neoplastic, hematologic, and other unrelated disorders. Terminal deoxynucleotidyltransferase activity was present at 4.08+/-0.74 U/108 cells in 23 morphologicall normal bone marrow samples from childhood controls. Terminal transferase was present at greater than 23 U/108 nucleated cells and at greater than31 U/108 blasts in the bone marrow of all children with acute lymphoblastic leukemia studied at initial diagnosis and at disease relapse. Terminal deoxynucleotidyltransferase was detectable at low levels, less than 7.5 U/108 cells, in all remission marrow smaples. Bone marrow terminal transferase activity was markedly elevated in all untreated acute lymphoblastic leukemia patients, whereas low levels which were difficult to interpret were present in the peripheral blood samples of two patients at diagnosis and six patients at relapse who had low absolute lymphoblast counts. Because of greater variation in the lymphoblast content of peripheral blood, bone marrow assays are more reliable in detecting disease activity. Marrow terminal deoxynucleotidyltransferase values obtained during the active phase of acute lymphoblastic leukemia were significantly greater than those found in other types of leukemia, bone marrow malignancies, and hematologic disorders. Terminal transferase determinations in blast cells of two patients with leukemic conversion of non-Hodgkin's lymphoma and in tumor cells from one patient with Burkitt's lymphoma were within the control range. These dat further define the usefulness of terminal deoxynucleotidyltrnasferase assay in the differentiation and classication of hematologic malignancies. PMID:265945

  17. Immunohistochemical characterization of neoplastic cells of breast origin

    PubMed Central

    2012-01-01

    Background After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on Tissue Micro-Array. Methods Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. Results Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. Conclusions The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1366310812718988 PMID:22726568

  18. Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells

    PubMed Central

    Dingwall, Steve; Lee, Jung Bok; Guezguez, Borhane; Fiebig, Aline; McNicol, Jamie; Boreham, Douglas; Collins, Tony J.; Bhatia, Mick

    2015-01-01

    Studies have implicated that a small sub-population of cells within a tumour, termed cancer stem cells (CSCs), have an enhanced capacity for tumour formation in multiple cancers and may be responsible for recurrence of the disease after treatment, including radiation. Although comparisons have been made between CSCs and bulk-tumour, the more important comparison with respect to therapy is between tumour-sustaining CSC versus normal stem cells that maintain the healthy tissue. However, the absence of normal known counterparts for many CSCs has made it difficult to compare the radiation responses of CSCs with the normal stem cells required for post-radiotherapy tissue regeneration and the maintenance of tissue homeostasis. Here we demonstrate that transformed human embryonic stem cells (t-hESCs), showing features of neoplastic progression produce tumours resistant to radiation relative to their normal counterpart upon injection into immune compromised mice. We reveal that t-hESCs have a reduced capacity for radiation induced cell death via apoptosis and exhibit altered cell cycle arrest relative to hESCs in vitro. t-hESCs have an increased expression of BclXL in comparison to their normal counterparts and re-sensitization of t-hESCs to radiation upon addition of BH3-only mimetic ABT737, suggesting that overexpression of BclXL underpins t-hESC radiation insensitivity. Using this novel discovery platform to investigate radiation resistance in human CSCs, our study indicates that chemotherapy targeting Bcl2-family members may prove to be an adjuvant to radiotherapy capable of targeting CSCs. PMID:26082437

  19. Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; potential marker of disease recurrence

    PubMed Central

    2014-01-01

    Background Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry. Results Higher levels of methylation were associated with disease recurrence. In particular, MLH1, ATM and FHIT gene promoters were found to be significantly hypermethylated in recurring adenomas. Unconditional logistic regression analysis used to evaluate the relative risk (RR) of recurrence showed that FHIT and MLH1 were independent variables with an RR of 35.30 (95% CI 4.15-300.06, P = 0.001) and 17.68 (95% CI 1.91-163.54, P = 0.011), respectively. Conclusions Histopathological classification does not permit an accurate evaluation of the risk of recurrence of colorectal lesions. Conversely, results from our methylation analysis suggest that a classification based on molecular parameters could help to define the mechanisms involved in carcinogenesis and prove an effective method for identifying patients at high risk of recurrence. PMID:25091577

  20. Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression.

    PubMed Central

    Rieger, K. M.; Little, A. F.; Swart, J. M.; Kastrinakis, W. V.; Fitzgerald, J. M.; Hess, D. T.; Libertino, J. A.; Summerhayes, I. C.

    1995-01-01

    Analysis of human tumour-derived cell lines has previously resulted in the identification of novel transformation-related elements and provided a useful tool for functional studies of different genes. To establish the utility of such cell lines as indicators of change relevant to urothelial cancer, we have characterised the expression of five genes (p53, MDM2, Rb, E-cadherin, APC) within a panel of human bladder carcinoma cell lines. Using single-strand conformation polymorphism (SSCP) and direct sequencing, p53 mutations were identified in 7/15 (47%) cell lines reflecting events reported in bladder tumours. Immunohistochemical analysis of p53 in cultured cells and in paraffin-embedded sections of xenografts from the cell line panel revealed discordant results. An absence of p53 nuclear staining was associated with an exon 5 mutation in EJ and with multiple p53 mutations found in J82. Two cell lines positive for p53 staining in the absence of detectable mutation displayed overexpression of MDM2 (PSI, HT1197) in Western blot analysis. Loss or aberrant Rb expression was recorded in 5/15 (TCCSUP, SCaBER, 5637, HT1376, J82) cell lines. Absence of E-cadherin was recorded in 5/15 cell lines (TCCSUP, EJ, KK47, UM-UC-3, J82) with loss of alpha-catenin in immunoprecipitated E-cadherin complexes of CUBIII. Western blot analysis of APC revealed a truncated protein in 1/15 (CUBIII) cell lines. The characterisation of oncogenic events within this panel of human bladder carcinoma cell lines establishes a representation of change observed in bladder tumours and better defines the genotypic background in these experimental human cell models of neoplastic progression. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7669581

  1. Recovery of uncommon bacteria from blood: association with neoplastic disease.

    PubMed Central

    Beebe, J L; Koneman, E W

    1995-01-01

    bloodstream infections of Salmonella typhimurium and Capno-cytophaga canimorsus in Hodgkin's disease patients seems likely due to a particular mechanism which infection by these species is favored. The specific nature of these mechanisms remains to be determined. The recovery of any unusual bacterium from blood should warrant a careful consideration of the possibility of underlying disease, especially cancer. Microbiologists should advise clinicians of the unusual nature of the identified organism and provide the counsel that certain neoplastic processes, often accompanied by neutropenia, render the human host susceptible to invasion by almost any bacterium. The recovery of such organisms as C. septicum or S. bovis should prompt the clinician to aggressively seek to identify an occult neoplasm if one has not yet been diagnosed. PMID:7553569

  2. Cell surface oligosaccharide modulation during differentiation: VI. The effect of biomodulation on the senescent and neoplastic cell phenotype.

    PubMed

    Mann, P L; Busse, S C; Griffey, R H; Laubscher, K

    1992-01-01

    These investigations test the hypothesis developed previously, that there are biomolecules which control and integrate cellular differentiation. Our specific interest in cellular differentiation lies in the area of what we refer to as basal or primitive cellular differentiation mechanisms. These mechanisms are common to all cells, and are required for simple recognition and growth regulation. We have investigated two models, the IMR-90 human fetal lung fibroblast model as a representative of normal growth control, and the CG model, canine glioma cells, a transplantable growth transformed cell line. These two models represent normal, and aberrant cellular differentiation control. In previous studies we have shown that the arrangement of the cell surface oligosaccharide structure on these cell types are predictive of phenotypic transition. We have developed, and partially characterized a series of BIOMODULATORS (BM) which delay the onset of display of neoplastic cells. Three classes of BIOMODULATOR have been explored; (1) a large molecular weight natural product (25-35 kDa), PokeWeed Mitogen (PWM); (2) a small molecular weight natural product (500 Da) Cellular Activator and Differentiator (CAD) and a number of natural and synthetic analogs; and (3) an indolizidine alkaloid natural product, Swainsonine (Sw) which has a known cellular target (oligosaccharide biosynthesis). Preliminary data is presented which structurally links some of these BIOMODULATORS in terms of their effective stereochemistry. These BIOMODULATORS, when used before PDL 38, prevent the cell surface oligosaccharide display changes typical of morphological senescence and delay their onset to PDL 100 or more. These BIOMODULATORS also appear to have regulatory effects on the neoplastic cell models. This re-regulation results in increases in generation time and an increase in the ability of these cells to be recognized by cytotoxic lymphocytes. Proton NMR linewidth measurements of the fraction of 'bound

  3. Proliferating cell nuclear antigen (PCNA) activity in hepatocellular carcinoma, benign peri-neoplastic and normal liver.

    PubMed

    Mun, Kein-Seong; Cheah, Phaik-Leng; Baharudin, Nurul Bahiyah; Looi, Lai-Meng

    2006-12-01

    Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA

  4. The absorption of ultraviolet light by cell nuclei. A technique for identifying neoplastic change

    SciTech Connect

    Baisden, C.R.; Booker, D.; Wright, R.D. )

    1989-11-01

    A technique for measuring the absorption of 260-nm ultraviolet light by cell nuclei is described. The results of such measurements of normal thyroid epithelial cells and benign and malignant thyroid neoplastic cells demonstrate a progressive increase in absorbance that correlates with the histologic appearance of neoplasia. The possible theoretic basis for this phenomenon is explored. The increased nuclear absorbance observed in neoplastic cells is hypothesized to result from the disruption of hydrogen bonds between the DNA base pairs, which allows unwinding of the double helix and loss of the normal control of mitosis.

  5. Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis

    PubMed Central

    de Sá, V.K.; Rocha, T.P.; Moreira, AL.; Soares, F.A.; Takagaki, T.; Carvalho, L.; Nicholson, A.G.; Capelozzi, V.L.

    2015-01-01

    We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and −3, and hyaluronan synthases (HAS)-1, −2, and −3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and −3 and HAS-1, −2, and −3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic

  6. Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis.

    PubMed

    Sá, V K de; Rocha, T P; Moreira, Al; Soares, F A; Takagaki, T; Carvalho, L; Nicholson, A G; Capelozzi, V L

    2015-11-01

    We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and -3, and hyaluronan synthases (HAS)-1, -2, and -3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and -3 and HAS-1, -2, and -3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic procedure for

  7. 78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ...We propose to revise the criteria in parts A and B of the Listing of Impairments (listings) that we use to evaluate cases involving cancer (malignant neoplastic diseases) in adults and children under titles II and XVI of the Social Security Act (Act). These proposed revisions reflect our adjudicative experience, advances in medical knowledge, and recommendations from medical experts we......

  8. Interferons as Therapy for Viral and Neoplastic Diseases: From Panacea to Pariah to Paragon

    PubMed Central

    Friedman, Robert M.; Contente, Sara

    2009-01-01

    For more than 20 years after the excitement engendered by their discovery in 1957 as antiviral agents, there were no significant clinical uses of interferons; however, following their cloning they have been employed as effective treatment for several viral, autoimmune, and neoplastic diseases.

  9. Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis

    NASA Astrophysics Data System (ADS)

    Hellebust, Anne; Rosbach, Kelsey; Wu, Jessica Keren; Nguyen, Jennifer; Gillenwater, Ann; Vigneswaran, Nadarajah; Richards-Kortum, Rebecca

    2013-12-01

    In this longitudinal study, a mouse model of 4-nitroquinoline 1-oxide chemically induced tongue carcinogenesis was used to assess the ability of optical imaging with exogenous and endogenous contrast to detect neoplastic lesions in a heterogeneous mucosal surface. Widefield autofluorescence and fluorescence images of intact 2-NBDG-stained and proflavine-stained tissues were acquired at multiple time points in the carcinogenesis process. Confocal fluorescence images of transverse fresh tissue slices from the same specimens were acquired to investigate how changes in tissue microarchitecture affect widefield fluorescence images of intact tissue. Widefield images were analyzed to develop and evaluate an algorithm to delineate areas of dysplasia and cancer. A classification algorithm for the presence of neoplasia based on the mean fluorescence intensity of 2-NBDG staining and the standard deviation of the fluorescence intensity of proflavine staining was found to separate moderate dysplasia, severe dysplasia, and cancer from non-neoplastic regions of interest with 91% sensitivity and specificity. Results suggest this combination of noninvasive optical imaging modalities can be used in vivo to discriminate non-neoplastic from neoplastic tissue in this model with the potential to translate this technology to the clinic.

  10. EFFECTS OF PHOSGENE EXPOSURE ON BACTERIAL VIRAL AND NEOPLASTIC LUNG DISEASE SUSCEPTIBILITY IN MICE

    EPA Science Inventory

    The effects of phosgene inhalation exposure on host resistance models representative of bacterial, viral, and neoplastic lung diseases were assessed. ingle 4 h exposure to concentrations of phosgene of 0.025 ppm and above significantly enhanced mortality due to aerosol infection ...

  11. Cell cannibalism by malignant neoplastic cells: three cases in dogs and a literature review.

    PubMed

    Meléndez-Lazo, Antonio; Cazzini, Paola; Camus, Melinda; Doria-Torra, Georgina; Marco Valle, Alberto Jesús; Solano-Gallego, Laia; Pastor, Josep

    2015-06-01

    Cell cannibalism refers to the engulfment of cells by nonprofessional phagocytic cells. Studies in human medicine have demonstrated a relationship between the presence of cell cannibalism by neoplastic cells and a poor outcome, and have shown a positive correlation with the presence of metastasis at the time of diagnosis. The biologic significance of cell cannibalism is unknown, but it is proposed that it may represent a novel mechanism of tumor immune evasion as a survival strategy in cases of unfavorable microenvironmental conditions. This report describes clinical and morphologic features of 3 cases of dogs with malignant neoplasia in which the presence of cellular cannibalism was observed in cytologic and histologic specimens. In the 1(st) case, a dog with a primary tonsillar squamous cell carcinoma with metastasis to retropharyngeal lymph nodes had neoplastic epithelial cells engulfing neutrophils noted in cytologic examination of the lymph nodes. In the 2(nd) case, neoplastic epithelial cells were seen engulfing each other in fine-needle aspirates from a primary mammary carcinoma with lung metastasis. In the 3(rd) case, poorly differentiated neoplastic mast cells from a recurrent, metastatic grade III mast cell tumor were observed cannibalizing eosinophils. A brief review of the literature describing known cell-into-cell relationships and the possible biologic significance and mechanisms involved in this phenomenon is provided. The relationship between cell cannibalism and distant metastasis should be explored in further studies, as it may prove to be a criterion of malignancy, as it is proposed in human medicine. PMID:25688652

  12. Evaluation of NK and LAK cell activities in neoplastic patients during treatment with morphine.

    PubMed

    Provinciali, M; Di Stefano, G; Raffaeli, W; Pari, G; Desiderio, F; Fabris, N

    1991-07-01

    The cytotoxic activity of Natural Killer (NK) and Lymphokine Activated Killer (LAK) cells in neoplastic patients with or without antalgic treatment was studied. NK cell activity was found reduced in untreated neoplastic patients when compared to healthy subjects. The atalgic treatment with morphine (orally or intrathecally administered) was able to significantly reduce the mean values of NK cell activity found in cancer patients. In three patients the cytotoxicity of NK cells significantly decreased during transfer from oral to intrathecal administration of morphine. In contrast to the NK cell function, the development of LAK cell activity significantly increased in neoplastic patients when compared to healthy controls. Further increments were obtained during treatment with morphine. The oral treatment with morphine was able to determine a higher induction of LAK cells than the intrathecal administration of the drug. Besides providing new knowledge on the effect of morphine on immune system our findings suggest that, in order to include neoplastic patients in clinical trials of adoptive immunotherapy with LAK cells and interleukin-2 (IL-2), the antalgic therapy with oral administration of morphine may represent a better solution than the intrathecal administration of the drug. PMID:1774133

  13. CONCURRENT NEOPLASTIC AND PROTISTAN DISORDERS IN THE AMERICAN OYSTER (CRASSOSTREA VIRGINICA)

    EPA Science Inventory

    One of 373 oysters examined as part of a histological survey of oysters from Apalachicola Bay, Florida, USA, had a concurrent blood cell proliferative disorder and a protistan infection. The neoplastic blood cells (leukocytes) were found throughout the vesicular connective tissue...

  14. Liposomal cytarabine (DepoCyte) for the treatment of neoplastic meningitis.

    PubMed

    Rueda Domínguez, Antonio; Olmos Hidalgo, David; Viciana Garrido, Ruth; Torres Sánchez, Esperanza

    2005-07-01

    Neoplastic meningitis is a feared complication in cancer patients, the median survival ranging from some weeks to a few months. Management is palliative and aims to provide symptoms relief while delaying neurological deterioration. Intrathecal methotrexate and/or cytarabine is the most widely used treatment in such clinical situations. These drugs are administered 2 or 3 times a week--a circumstance that is both bothersome for the patient and time-costly for the medical personnel. Liposomal cytarabine is a sustained-release cytarabine formulation specifically developed for the treatment of neoplastic meningitis. Its administration on a twice-weekly basis ensures sustained cytotoxic drug concentrations in cerebrospinal fluid. Controlled clinical trials have shown liposomal cytarabine to be equally or more effective than the classical treatment for neoplastic meningitis. In lymphomatous meningitis, liposomal cytarabine offers superior response rates, improved patient quality of life, and a prolongation of the time to neurological progression. When the cause of meningitis is a solid tumor, liposomal cytarabine prolongs the time to neurological progression and improves quality of life. These observations indicate that DepoCyte is a convenient treatment for patients with neoplastic meningitis, due to its efficacy and easy of administration characteristics. PMID:16131445

  15. Generation and Quantitative Analysis of Pulsed Low Frequency Ultrasound to Determine the Sonic Sensitivity of Untreated and Treated Neoplastic Cells

    PubMed Central

    Trendowski, Matthew; Christen, Timothy D.; Zoino, Joseph N.; Acquafondata, Christopher; Fondy, Thomas P.

    2015-01-01

    Low frequency ultrasound in the 20 to 60 kHz range is a novel physical modality by which to induce selective cell lysis and death in neoplastic cells. In addition, this method can be used in combination with specialized agents known as sonosensitizers to increase the extent of preferential damage exerted by ultrasound against neoplastic cells, an approach referred to as sonodynamic therapy (SDT). The methodology for generating and applying low frequency ultrasound in a preclinical in vitro setting is presented to demonstrate that reproducible cell destruction can be attained in order to examine and compare the effects of sonication on neoplastic and normal cells. This offers a means by which to reliably sonicate neoplastic cells at a level of consistency required for preclinical therapeutic assessment. In addition, the effects of cholesterol-depleting and cytoskeletal-directed agents on potentiating ultrasonic sensitivity in neoplastic cells are discussed in order to elaborate on mechanisms of action conducive to sonochemotherapeutic approaches. PMID:26274053

  16. Galectin-1 is a useful marker for detecting neoplastic squamous cells in oral cytology smears.

    PubMed

    Noda, Yuri; Kondo, Yuko; Sakai, Manabu; Sato, Sunao; Kishino, Mitsunobu

    2016-06-01

    Cytologic diagnoses in the oral region are very difficult due to the small amount of cells in smears, which are also exposed to many stimulating factors and often show atypical changes. Galectin-1 (Gal1) is a β-galactoside binding protein that modulates tumor progression. Gal1 is very weakly expressed in normal cells, but is often overexpressed in neoplastic lesions. The aim of the present study was to determine whether it is possible to differentiate reactive changes from neoplastic changes in oral cytology smears based on the expression of Gal1. A total of 155 tissue biopsy specimens and 61 liquid-based cytology specimens were immunostained by an anti-Gal1 antibody, and Gal1 expression levels were subsequently evaluated. These samples consisted of oral squamous cell carcinomas, epithelial dysplasia, and oral mucosal diseases. The positive and negative expressions of Gal1 were examined in 37 specimens collected by scalpel and cytobrush biopsy. The sensitivity, specificity, and positive predictive value of Gal1 were also evaluated in smears. In tissue sections, the positive ratio of Gal1 in neoplastic lesions was high (72.3%). In cytology specimens, the positive ratio of Gal1 was higher in neoplastic lesions (79.0%) than in those negative for intraepithelial lesion or malignancy (22.2%). A correlation was found between immunocytochemical Gal1 expression and immunohistochemical Gal1 expression (P < .001). The sensitivity (75.0%), specificity (75.0%), and positive predictive value (91.3%) of Gal1 were also high in smears. In conclusion, Gal1 may be a useful marker for determining whether morphologic changes in cells are reactive or neoplastic. PMID:26980012

  17. Identifying Baseline Covariates for Use in Propensity Scores: A Novel Approach Illustrated for a Non-randomized Study of Recovery High Schools

    PubMed Central

    Tanner-Smith, Emily E.; Lipsey, Mark W.

    2014-01-01

    There are many situations where random assignment of participants to treatment and comparison conditions may be unethical or impractical. This article provides an overview of propensity score techniques that can be used for estimating treatment effects in non-randomized quasi-experimental studies. After reviewing the logic of propensity score methods, we call attention to the importance of the strong ignorability assumption and its implications. We then discuss the importance of identifying and measuring a sufficient set of baseline covariates upon which to base the propensity scores and illustrate approaches to that task in the design of a study of recovery high schools for adolescents treated for substance abuse. One novel approach for identifying important covariates that we suggest and demonstrate is to draw on the predictor-outcome correlations compiled in meta-analyses of prospective longitudinal correlations. PMID:25071297

  18. Expression of keratin and vimentin intermediate filaments in rabbit bladder epithelial cells at different stages of benzo(a)pyrene-induced neoplastic progression

    SciTech Connect

    Summerhayes, I.C.; Cheng, Y.S.E.; Sun, T.T.; Chen, L.B.

    1981-07-01

    Rabbit bladder epithelium, grown on collagen gels and exposed to the chemical carcinogen benzo(a)pyrene, produced nontumorigenic altered foci as well as tumorigenic epithelial cell lines during 120 to 180 d in culture. Immunofluorescence studies revealed extensive keratin filaments in both primary epithelial cells and benzo(a)pyrene-induced altered epithelial foci but showed no detectable vimentin filaments. The absence of vimentin expression in these cells was confirmed by two-dimensional gel electrophoresis. In contrast, immunofluorescence staining of the cloned benzo(a)pyrene-transformed rabbit bladder epithelial cell line, RBC-1, revealed a reduction in filamentous keratin concomitant with the expression of vimentin filaments. The epithelial nature of this cell line was established by the observation that cells injected into nude mice formed well-differentiated adenocarcinomas. Frozen sections of such tumors showed strong staining with antikeratins antibodies, but no detectable staining with antivimentin antibodies. These results demonstrated a differential expression of intermediate filament type in cells at different stages of neoplastic progression and in cells maintained in different growth environments. It is apparent that the expression of intermediate filaments throughout neoplastic progression is best studied by use of an in vivo model system in parallel with culture studies.

  19. In vitro and in vivo studies on potentiation of cytotoxic effects of anticancer drugs or cobalt 60 gamma ray by interferon on human neoplastic cells

    SciTech Connect

    Namba, M.; Yamamoto, S.; Tanaka, H.; Kanamori, T.; Nobuhara, M.; Kimoto, T.

    1984-11-15

    A possibility that interferon may potentiate the cytotoxic effects of anticancer drugs or /sup 60/Co gamma ray on human neoplastic cells was studied by in vitro and in vivo experimental procedures. The human neoplastic cells used were HeLa (uterine cervical cancer) and WI-38 CT-1 (embryonic lung fibroblasts transformed in culture by /sup 60/Co gamma ray) cells. As normal human cells, WI-38 cells were used. Interferon was a preparation of beta-type produced by human fibroblasts. The cytotoxicity was determined by colony formation for in vitro experiments and by tumor growth for animal experiments. Of 17 anticancer drugs, the cytotoxic effects of six drugs, namely, peplomycin, bleomycin, aclacinomycin, cisplatin, 5-fluorouracil (5-FU), and Adriamycin (doxorubicin) were potentiated by concomitant application of interferon. The cytolethal effects of /sup 60/Co gamma ray were also enhanced by interferon. The growth of tumor induced by transplantation of HeLa cells into a nude mouse was remarkably reduced by combination therapy of interferon and 5-FU. The current results indicate a possibility that combined therapy of certain types of anticancer drugs or /sup 60/Co gamma ray with interferon may be effective in treatment of cancer patients.

  20. A 4-Mb deletion in the region Xq27.3-q28 is associated with non-random inactivation of the non-mutant X chromosome

    SciTech Connect

    Clarke, J.T.R.; Han, L.P.; Michalickova, K.

    1994-09-01

    A girl with severe Hunter disease was found to have a submicroscopic deletion distrupting the IDS locus in the region Xq27.3-q28 together with non-random inactivation of the non-mutant X chromosome. Southern analysis of DNA from the parents and from hamster-patient somatic cell hybrids containing only the mutant X chromosome revealed that the deletion represented a de novo mutation involving the paternal X chromosome. Methylation-sensitive RFLP analysis of DNA from maternal fibroblasts and lymphocytes showed methylation patterns consistent with random X-inactivation, indicating that the non-random X-inactivation in the patient was not inherited and was likely a direct result of the Xq27.3-q28 deletion. A 15 kb EcoRI junction fragment, identified in patient DNA using IDS cDNA probes, was cloned from a size-selected patient DNA library. Clones containing the deletion junction were restriction mapped and fragments were subcloned and used to isolate normal sequence on either side of the deletion from normal X chromosome libraries. Comparison of the sequences from normal and mutant X chromosome clones straddling the deletion breakpoint showed that the mutation had occurred by recombination between Alu repeats. Screening of YAC contigs containing normal X chromosome sequence from the region of the mutation, using probes from either side of the deletion breakpoint, showed that the deletion was approximately 4 Mb in size. Probing of mutant DNA with 16 STSs distributed throughout the region of the deletion confirmed that the mutation is a simple deletion with no complex rearrangements of islands of retained DNA. A search for sequences at Xq27.3-q28 involved in X chromosome inactivation is in progress.

  1. Pivotal role of pervasive neoplastic and stromal cells reprogramming in circulating tumor cells dissemination and metastatic colonization.

    PubMed

    Meseure, Didier; Drak Alsibai, Kinan; Nicolas, Andre

    2014-12-01

    Reciprocal interactions between neoplastic cells and their microenvironment are crucial events in carcinogenesis and tumor progression. Pervasive stromal reprogramming and remodeling that transform a normal to a tumorigenic microenvironment modify numerous stromal cells functions, status redox, oxidative stress, pH, ECM stiffness and energy metabolism. These environmental factors allow selection of more aggressive cancer cells that develop important adaptive strategies. Subpopulations of cancer cells acquire new properties associating plasticity, stem-like phenotype, unfolded protein response, metabolic reprogramming and autophagy, production of exosomes, survival to anoikis, invasion, immunosuppression and therapeutic resistance. Moreover, by inducing vascular transdifferentiation of cancer cells and recruiting endothelial cells and pericytes, the tumorigenic microenvironment induces development of tumor-associated vessels that allow invasive cells to gain access to the tumor vessels and to intravasate. Circulating cancer cells can survive in the blood stream by interacting with the intravascular microenvironment, extravasate through the microvasculature and interact with the metastatic microenvironment of target organs. In this review, we will focus on many recent paradigms involved in the field of tumor progression. PMID:25523234

  2. P16(INK4a) expression as a potential prognostic marker in cervical pre-neoplastic and neoplastic lesions.

    PubMed

    Queiroz, Conceição; Silva, Tânia Correia; Alves, Venâncio A F; Villa, Luisa L; Costa, Maria Cecília; Travassos, Ana Gabriela; Filho, José Bouzas Araújo; Studart, Eduardo; Cheto, Tatiana; de Freitas, Luiz Antonio R

    2006-01-01

    An immunohistochemical analysis with monoclonal antibody p16(INK4a) was performed in formalin-fixed, paraffin-embedded samples of 60 cases. The aim was to investigate in biopsies the expression of p16(INK4a) of normal uterine cervical tissue, pre-cancerous and cancerous lesions, and their relation with human papilloma virus (HPV) and HIV status. Three parameters were evaluated: percentage of p16(INK4a) positive cells, reaction intensity, and cell staining pattern. All of these parameters were statistically different when compared among different histological groups. However, logistic regression model showed that the reaction intensity was the best indicator of the expression of p16(INK4a). This expression increases from normal to invasive squamous carcinoma. Sixty-six percent of the patients with CIN grade 1 (CIN1) expressed p16(INK4a) (all these cases were infected with high risk HPV). Our study supports the hypothesis that p16(INK4a) expression in pre-cancerous lesions and cancers can be used to identify HPV-transformed cells. Of great interest for routine diagnostic use is the fact that immunohistochemical testing for p16(INK4a) seems to be capable of identifying HPV-positive cells and potentially recognizing those lesions with an increased risk of progression to high-grade lesions. PMID:16376485

  3. Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

    PubMed Central

    Castro, Patrícia F.; Fantoni, Denise T.; Miranda, Bruna C.; Matera, Julia M.

    2016-01-01

    Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

  4. Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures.

    PubMed

    Castro, Patrícia F; Fantoni, Denise T; Miranda, Bruna C; Matera, Julia M

    2016-01-01

    Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

  5. Prognostic significance of neoplastic cell proliferation parameters in human haematological malignancies.

    PubMed

    Kotelnikov, V M

    1990-01-01

    High percentage of neoplastic cells in S, G2 and M phases of cell cycle is unfavourable prognostic sign in human haematological malignancies. In chronic leukaemias (CML and CLL) it is true for peripheral blood leukaemic cells, in non-Hodgkin lymphomas--for lymph node cells, in multiple myeloma--for bone marrow plasma cells. In acute leukaemia results are controversial: some authors found a correlation between proliferation parameters of bone marrow blast cells while others did not. These parameters correlate positively with the rate of complete remission and negatively with its duration. It is concluded that proliferation parameters of neoplastic cells may be used for individual prognosis in patients with haematological tumours especially in combination with other biological and clinical prognostic markers. PMID:1703108

  6. Immunohistological recognition of cyclin D1 expression by non-lymphoid cells among lymphoid neoplastic cells.

    PubMed

    Abdulla, Zainalabideen; Turley, Helen; Gatter, Kevin; Pezzella, Francesco

    2014-03-01

    Cyclin D1 immunostaining of non-neoplastic cells has been a source of diagnostic confusion especially in lymphoproliferative lesions. This study has reviewed these in two hundred and thirty-one haematopathological samples stained for cyclin D1. Most cases were formalin-fixed except for a few bone marrow trephines, which were B-5 fixed, and EDTA decalcified. Overall, 94% (216/231) of cases showed one or more types of non-neoplastic cells expressing Cyclin D1 of variable intensity. Endothelial cells and histiocytes were the most commonly identified Cyclin D1 positive cells being positive in 92% (214/231) of cases. Other normal cell types identified included fat cells, stromal fibroblasts, glial cells, spermatocytes, smooth muscle cells, osteoblasts and where present epithelial cells. Many normal cell types can express cyclinD1. Knowledge of these is useful to prevent misinterpretation of cyclin D1 positive tumours. PMID:23758159

  7. Temperature dependence of 1H NMR relaxation time, T2, for intact and neoplastic plant tissues

    NASA Astrophysics Data System (ADS)

    Lewa, Czesław J.; Lewa, Maria

    Temperature dependences of the spin-spin proton relaxation time, T2, have been shown for normal and tumorous tissues collected from kalus culture Nicotiana tabacum and from the plant Kalanchoe daigremontiana. For neoplastic plant tissues, time T2 was increased compared to that for intact plants, a finding similar to that for animal and human tissues. The temperature dependences obtained were compared to analogous relations observed with animal tissues.

  8. Neoplastic pericardial disease: Old and current strategies for diagnosis and management

    PubMed Central

    Lestuzzi, Chiara

    2010-01-01

    The prevalence of neoplastic pericardial diseases has changed over time and varies according to diagnostic methods. The diagnostic factor is usually the detection of neoplastic cells within the pericardial fluid or in specimens of pericardium, but the diagnosis may be difficult. Accurate sampling and cytopreparatory techniques, together with ancillary studies, including immunohistochemical tests and neoplastic marker dosage, are essential to obtain a reliable diagnosis. The goals of treatment may be simply to relieve symptoms (cardiac tamponade or dyspnea), to prevent recurrent effusion for a long-term symptomatic benefit, or to treat the local neoplastic disease with the aim of prolonging survival. Immediate relief of symptoms may be obtained with percutaneous drainage or with a surgical approach. For long term prevention of recurrences, various approaches have been proposed: extended drainage, pericardial window (surgical or percutaneous balloon pericardiostomy), sclerosing local therapy, local and/or systemic chemotherapy or radiation therapy (RT) (external or with intrapericardial radionuclides). The outcomes of various therapeutic approaches vary for different tumor types. Lymphoma and leukemias can be successfully treated with systemic chemotherapy; for solid tumors, percutaneous drainage and the use of systemic and/or local sclerosing and antineoplastic therapy seems to offer the best chance of success. The use of “pure” sclerosing agents has been replaced by agents with both sclerosing and antineoplastic activity (bleomycin or thiotepa), which seems to be quite effective in breast cancer, at least when associated with systemic chemotherapy. Local chemotherapy with platinum, mitoxantrone and other agents may lead to good local control of the disease, but the addition of systemic chemotherapy is probably relevant in order to prolong survival. The surgical approach (creation of a pericardial window, even with the mini-invasive method of balloon

  9. Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

    PubMed

    Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

    2014-01-01

    Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research. PMID:23828036

  10. Dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis

    PubMed Central

    2013-01-01

    Background Dialysis disequilibrium syndrome is characterized by neurological symptoms resulting from cerebral edema, which occurs as a consequence of hemodialysis. Dialysis disequilibrium syndrome most often occurs in patients who have just started hemodialysis, during hemodialysis, or soon after hemodialysis; although it may also occur in patients who are under maintenance hemodialysis with pre-existing neurological disease. Case presentation A 70-year-old woman, who had been receiving maintenance hemodialysis for one year, was diagnosed with ovarian cancer by ascites cytological examination. Two years later, she reported severe headache and nausea during hemodialysis and was diagnosed with dialysis disequilibrium syndrome. Although brain images revealed mild hydrocephalus without any mass lesions, poorly differentiated adenocarcinoma cells were detected in her cerebrospinal fluid. These findings indicated that DDS was induced by neoplastic meningitis due to ovarian cancer metastasis. Conclusion Neoplastic meningitis should be considered and excluded in hemodialysis patients with dialysis disequilibrium syndrome and malignancy by cytological examination of the cerebrospinal fluid even if cerebral imaging shows no obvious lesions. This is the first reported case of dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis. PMID:24238645

  11. Selected aspects of palliative care and quality of life at the terminal stage of neoplastic disease.

    PubMed

    Farbicka, Paulina; Nowicki, Andrzej

    2012-01-01

    Neoplastic diseases are among the most common causes of death. The quality of life in neoplastic disease depends on the type of neoplasm, level of progression, location, treatment possibilities and prognosis. Cancer reduces the quality of life at the advanced stage of disease. At this time patients feel pain and suffering. Palliative care is used in the terminal phase of neoplastic disease. It includes overall care of an incurable patient and her/his family. The main objective of palliative care is meeting somatic and psycho-social requirements. Recently, more and more physicians dealing with oncological patients are moving away from treatment of the patient like an object. They pay attention to a subjective approach to treatment outcomes that are felt by the patient. The model of medicine is becoming a holistic one and during examination physicians pay attention to the patient's physical and mental state, economic condition, social situation, feelings or lack of complaints more often. Research on quality of life is becoming a vital part of medical examination. PMID:23788936

  12. A comparative study of the major glycoprotein isolated from normal and neoplastic gastric mucosa.

    PubMed

    Schrager, J; Oates, M D

    1973-04-01

    The isolation and composition of glycoproteins from mucosae of normal stomachs, of stomachs with gastric ulcer, and of stomachs with carcinoma is described. The glycoproteins from the mucosae of normal stomachs and with gastric ulcer showed virtually the same carbohydrate and amino acid content as the principal gastric glycoprotein isolated from gastric aspirates. They all revealed a common basic carbohydrate composition: galactose, fucose, glucosamine, and galactosamine were present in approximate molar ratios of 4:3:3:1. THE RESULTS SUGGEST THAT THE GLYCOPROTEINS ISOLATED FROM GASTRIC ASPIRATES FROM NORMAL AND NEOPLASTIC GASTRIC MUCOSAE SHARE A NUMBER OF STRUCTURAL FEATURES: (1) a protein core with a characteristic amino acid composition; (2) the range of sugars forming the carbohydrate side chains; (3) galactosamine approximately equimolar with the sum of threonine and serine; (4) galactose approximately equimolar with the sum of glucosamine and galactosamine; (5) absence of mannose; (6) a high carbohydrate content (80-85%); and (7) blood group activity. The neoplastic glycoproteins differed from the normal glycoproteins in that the quantitative relationships of the carbohydrate components of the neoplastic glycoproteins showed variations dividing the extracts investigated into groups, each group with a distinctive and constant carbohydrate composition. The blood group specificity of 15 out of 24 cases investigated differed from that of the hosts' red cells. PMID:4706916

  13. [Use of BICAP by endoscopic route in the palliative treatment of neoplastic stenosis of the esophagus].

    PubMed

    Pantuso, G; Bottino, A; Cipolla, C; Gitto, C; Farro, G; Talarico, F; Latteri, M; Florena, M

    1990-12-01

    Over the years the palliative treatment of neoplastic stenosis of the esophagus in patients who cannot be operated has seen a variation of endoscopic methods which aimed to reopen the alimentary canal either using simple dilatation, or the insertion of endoprostheses, or sclerosing injection or antiblastic therapy, or lastly using disobstructive laser therapy. In particular, the use of Neodymium YAG laser in endoscopic therapy for the deobstruction of neoplastic esophageal stenosis is currently widely used. More recently deobstruction of the stenosis may also be achieved using bipolar diathermocoagulation with BICAP following esophageal dilatation. Recent comparative studies of the use of BICAP and laser therapy in the treatment of neoplastic esophageal stenosis have tended to reveal the complementary characteristics of the two techniques. The present paper reports the Authors' experience in this respect which has been satisfactory with regard to both methods, in line with the findings of other studies. In the study of two groups of 8 patients treated with BICAP and laser therapy respectively, recanalisation was obtained in 100% of cases with good functional results in 75% of patients treated with BICAP and 87.5% of those receiving laser therapy. The time interval between one treatment session and the next in relation to the efficacy of the therapy was similar in both methods and ranged from a minimum of 4 weeks to a maximum of 12 weeks. Complications were scarce in both groups. PMID:1708116

  14. Neoplastic lesions in CADASIL syndrome: report of an autopsied Japanese case

    PubMed Central

    Hassan, Wael Abdo; Udaka, Naoka; Ueda, Akihiko; Ando, Yukio; Ito, Takaaki

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is one of the most common heritable causes of stroke and dementia in adults. The gene involved in the pathogenesis of CADASIL is Notch3; in which mutations affect the number of cysteine residues in its extracellular domain, causing its accumulation in small arteries and arterioles of the affected individuals. Besides the usual neurological and vascular findings that have been well-documented in CADASIL patients, this paper additionally reports multiple neoplastic lesions that were observed in an autopsy case of CADASIL patient; that could be related to Notch3 mutation. The patient was a 62 years old male, presented with a past history of neurological manifestations, including gait disturbance and frequent convulsive attacks. He was diagnosed as CADASIL syndrome with Notch3 Arg133Cys mutation. He eventually developed hemiplegia and died of systemic convulsions. Autopsy examination revealed-besides the vascular and neurological lesions characteristic of CADASIL- multiple neoplastic lesions in the body; carcinoid tumorlet and diffuse idiopathic pulmonary neuro-endocrine cell hyperplasia (DIPNECH) in the lungs, renal cell carcinoma (RCC), prostatic adenocarcinoma (ADC) and adenomatoid tumor of the epididymis. This report describes a spectrum of neoplastic lesions that were found in a case of CADASIL patient that could be related to Notch3 gene mutations. PMID:26261665

  15. Targeting neoplastic B cells and harnessing microenvironment: the "double face" of ibrutinib and idelalisib.

    PubMed

    Maffei, Rossana; Fiorcari, Stefania; Martinelli, Silvia; Potenza, Leonardo; Luppi, Mario; Marasca, Roberto

    2015-01-01

    Tyrosine kinase inhibitors (TKIs) targeting signaling molecules downstream B cell receptor (BCR) are powerfully spreading in the therapeutic landscape of B cell lymphoproliferative disease, due to a manageable toxicity profile and encouraging clinical effectiveness. In particular, ibrutinib, previously called PCI-32765, is a potent inhibitor of Bruton tyrosine kinase (Btk), recently approved for the treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). Moreover, idelalisib (formerly GS-1101 and CAL-101) is a selective reversible inhibitor of the p110δ isoform of phosphoinositol 3 kinase (PI3K) approved for the treatment of patients with relapsed follicular lymphoma (FL) and CLL. These agents directly affect the neoplastic clone, disrupting the supportive platform provided by BCR signaling cascade and by other microenvironmental mutualistic interactions, and also interfering with chemokine gradients and adhesive properties of neoplastic B cells. In the present review, we describe the clinical efficacy of ibrutinib and idelalisib in CLL and B cell non-Hodgkin lymphoma (B-NHL), then focusing on the mode of action (MOA) of these TKIs towards the neoplastic B cell compartment. At last, the review would further expand the view on potential additional targets of ibrutinib and idelalisib belonging to other microenvironmental cellular elements. PMID:26022368

  16. Selected aspects of palliative care and quality of life at the terminal stage of neoplastic disease

    PubMed Central

    Farbicka, Paulina

    2013-01-01

    Neoplastic diseases are among the most common causes of death. The quality of life in neoplastic disease depends on the type of neoplasm, level of progression, location, treatment possibilities and prognosis. Cancer reduces the quality of life at the advanced stage of disease. At this time patients feel pain and suffering. Palliative care is used in the terminal phase of neoplastic disease. It includes overall care of an incurable patient and her/his family. The main objective of palliative care is meeting somatic and psycho-social requirements. Recently, more and more physicians dealing with oncological patients are moving away from treatment of the patient like an object. They pay attention to a subjective approach to treatment outcomes that are felt by the patient. The model of medicine is becoming a holistic one and during examination physicians pay attention to the patient's physical and mental state, economic condition, social situation, feelings or lack of complaints more often. Research on quality of life is becoming a vital part of medical examination. PMID:23788936

  17. Human colon tissue in organ culture: preservation of normal and neoplastic characteristics

    PubMed Central

    Bhagavathula, Narasimharao; Mankey, Cohra; DaSilva, Marissa; Paruchuri, Tejaswi; Aslam, Muhammad Nadeem; Varani, James

    2009-01-01

    Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the presence of elongated crypts with small, densely packed cells at the crypt base and mucin-containing goblet cells in the upper portion. Ki67 staining, for proliferating cells, was confined to the lower third of the crypt, while expression of extracellular calcium-sensing receptor was seen in the upper third and surface epithelium. E-cadherin and β-catenin were expressed throughout the epithelium and confined to the cell surface. In tumor tissue, the same disorganized, abnormal glandular structures seen at time zero were present after 2 d. The majority of cells in these structures were mucin-poor, but occasional goblet cells were seen and mucin staining was present. Ki67 staining was seen throughout the abnormal epithelium and calcium-sensing receptor expression was weak and variable. E-cadherin was seen at the cell surface (similar to normal tissue), but in some places, there was diffuse cytoplasmic staining. Finally, intense cytoplasmic and nuclear β-catenin staining was observed in cultured neoplastic tissue. PMID:19915935

  18. Multiphoton microscopy and microspectroscopy for diagnostics of inflammatory and neoplastic lung

    NASA Astrophysics Data System (ADS)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Flanders, James; Southard, Teresa L.; Weiss, Robert S.; Webb, Watt W.

    2012-03-01

    Limitations of current medical procedures for detecting early lung cancers inspire the need for new diagnostic imaging modalities for the direct microscopic visualization of lung nodules. Multiphoton microscopy (MPM) provides for subcellular resolution imaging of intrinsic fluorescence from unprocessed tissue with minimal optical attenuation and photodamage. We demonstrate that MPM detects morphological and spectral features of lung tissue and differentiates between normal, inflammatory and neoplastic lung. Ex vivo MPM imaging of intrinsic two-photon excited fluorescence was performed on mouse and canine neoplastic, inflammatory and tumor-free lung sites. Results showed that MPM detected microanatomical differences between tumor-free and neoplastic lung tissue similar to standard histopathology but without the need for tissue processing. Furthermore, inflammatory sites displayed a distinct red-shifted fluorescence compared to neoplasms in both mouse and canine lung, and adenocarcinomas displayed a less pronounced fluorescence emission in the 500 to 550 nm region compared to adenomas in mouse models of lung cancer. These spectral distinctions were also confirmed by two-photon excited fluorescence microspectroscopy. We demonstrate the feasibility of applying MPM imaging of intrinsic fluorescence for the differentiation of lung neoplasms, inflammatory and tumor-free lung, which motivates the application of multiphoton endoscopy for the in situ imaging of lung nodules.

  19. Estimating fitness consequences of dispersal: a road to 'know-where'? Non-random dispersal and the underestimation of dispersers' fitness.

    PubMed

    Doligez, Blandine; Pärt, Tomas

    2008-11-01

    philopatric and dispersing individuals, others, based on adult and juvenile survival, are open to the alternative explanation of biased fitness estimates. 6. We list three potential ways of reducing the risk of making wrong inferences on biased fitness estimates due to such non-random dispersal behaviour between dispersing and philopatric individuals: (a) diagnosing effects of non-random dispersal, (b) reducing the effects of spatially limited study area and (c) performing controlled experiments. PMID:18808435

  20. Immunohistochemical detection of Ca antigen in normal, dysplastic and neoplastic squamous epithelia of the human uterine cervix.

    PubMed Central

    Lloyd, J M; O'Dowd, T; Driver, M; Tee, D E

    1984-01-01

    Immunohistochemical staining was performed on biopsies and cytological samples from normal, dysplastic and neoplastic squamous epithelia using the monoclonal Ca 1 antibody. The results of staining 92 biopsies and 20 cytological samples are described and it is reported that positive staining with Ca 1 antibody was detected in normal, dysplastic and neoplastic epithelia. The role of the Ca 1 antibody in the study of cervical cancer is discussed. Images PMID:6368596

  1. Radiogenic cell transformation and carcinogenesis

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Mei, M.; Durante, M.; Craise, L. M.

    1995-01-01

    Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic

  2. Novel gene arrangement in the mitochondrial genome of Bothus myriaster (Pleuronectiformes: Bothidae): evidence for the Dimer-Mitogenome and Non-random Loss model.

    PubMed

    Gong, Li; Shi, Wei; Yang, Min; Li, Donghe; Kong, Xiaoyu

    2016-09-01

    In the present study, the complete mitochondrial genome of the oval flounder Bothus myriaster was determined and a novel gene rearrangement was discovered. A striking finding was that eight genes encoded by the L-strand (ND6 and tRNA-Q, A, C, Y, S1, E, and P genes) were translocated to a position between tRNA-T and tRNA-F. Simultaneously, the original order of the rearranged genes Q-A-C-Y-S1-ND6-E-P was maintained. Thus, the genes with identical transcriptional polarities were clustered in the genome with one exception that tRNA-N gene is located in the original position. The other rearrangement was the H-strand-encoded tRNA-D that translocated from its typical location between COI and COII to a position between S1 and ND6. The Dimer-Mitogenome and Non-random Loss model (DMNL)was adopted to account for the novel rearrangement in B. myriaster mitogenome, which provides evidence to support the hypothesis of the DMNL model. PMID:25629499

  3. Design and Baseline Findings of a Multi-site Non-randomized Evaluation of the Effect of a Health Programme on Microfinance Clients in India

    PubMed Central

    Saha, Somen

    2014-01-01

    Microfinance is the provision of financial services for the poor. Health program through microfinance has the potential to address several access barriers to health. We report the design and baseline findings of a multi-site non-randomized evaluation of the effect of a health program on the members of two microfinance organizations from Karnataka and Gujarat states of India. Villages identified for roll-out of health services with microfinance were pair-matched with microfinance only villages. A quantitative survey at inception and twelve months post health intervention compare the primary outcome (incidence of childhood diarrhea), and secondary outcome (place of last delivery, toilet at home, and out-of-pocket expenditure on treatment). At baseline, the intervention and comparison communities were similar except for out-of-pocket expenditure on health. Low reported use of toilet at home indicates the areas are heading towards a sanitation crisis. This should be an area of program priority for the microfinance organizations. While respondents primarily rely on their savings for meeting treatment expenditure, borrowing from friends, relatives, and money-lenders remains other important source of meeting treatment expenditure in the community. Programs need to prioritize steps to ensure awareness about national health insurance schemes, entitlement to increase service utilization, and developing additional health financing safety nets for financing outpatient care, that are responsible for majority of health-debt. Finally we discuss implications of such programs for national policy makers. PMID:24373263

  4. Feasibility and effectiveness of a combined individual and psychoeducational group intervention in psychiatric residential facilities: A controlled, non-randomized study.

    PubMed

    Magliano, Lorenza; Puviani, Marta; Rega, Sonia; Marchesini, Nadia; Rossetti, Marisa; Starace, Fabrizio

    2016-01-30

    This controlled, non-randomized study explored the feasibility of introducing a Combined Individual and Group Intervention (CIGI) for users with mental disorders in residential facilities, and tested whether users who received the CIGI had better functioning than users who received the Treatment-As-Usual (TAU), at two-year follow up. In the CIGI, a structured cognitivebehavioral approach called VADO (in English, Skills Assessment and Definition of Goals) was used to set specific goals with each user, while Falloon's psychoeducational treatment was applied with the users as a group. Thirty-one professionals attended a training course in CIGI, open to users' voluntary participation, and applied it for two years with all users living in 8 residential facilities of the Mental Health Department of Modena, Italy. In the same department, 5 other residential facilities providing TAU were used as controls. ANOVA for repeated measures showed a significant interaction effect between users' functioning at baseline and follow up assessments, and the intervention. In particular, change in global functioning was higher in the 55 CIGI users than in the 44 TAU users. These results suggest that CIGI can be successfully introduced in residential facilities and may be useful to improve functioning in users with severe mental disorders. PMID:26723137

  5. Links between fear of humans, stress and survival support a non-random distribution of birds among urban and rural habitats

    PubMed Central

    Rebolo-Ifrán, Natalia; Carrete, Martina; Sanz-Aguilar, Ana; Rodríguez-Martínez, Sol; Cabezas, Sonia; Marchant, Tracy A.; Bortolotti, Gary R.; Tella, José L.

    2015-01-01

    Urban endocrine ecology aims to understand how organisms cope with new sources of stress and maintain allostatic load to thrive in an increasingly urbanized world. Recent research efforts have yielded controversial results based on short-term measures of stress, without exploring its fitness effects. We measured feather corticosterone (CORTf, reflecting the duration and amplitude of glucocorticoid secretion over several weeks) and subsequent annual survival in urban and rural burrowing owls. This species shows high individual consistency in fear of humans (i.e., flight initiation distance, FID), allowing us to hypothesize that individuals distribute among habitats according to their tolerance to human disturbance. FIDs were shorter in urban than in rural birds, but CORTf levels did not differ, nor were correlated to FIDs. Survival was twice as high in urban as in rural birds and links with CORTf varied between habitats: while a quadratic relationship supports stabilizing selection in urban birds, high predation rates may have masked CORTf-survival relationship in rural ones. These results evidence that urban life does not constitute an additional source of stress for urban individuals, as shown by their near identical CORTf values compared with rural conspecifics supporting the non-random distribution of individuals among habitats according to their behavioural phenotypes. PMID:26348294

  6. Links between fear of humans, stress and survival support a non-random distribution of birds among urban and rural habitats.

    PubMed

    Rebolo-Ifrán, Natalia; Carrete, Martina; Sanz-Aguilar, Ana; Rodríguez-Martínez, Sol; Cabezas, Sonia; Marchant, Tracy A; Bortolotti, Gary R; Tella, José L

    2015-01-01

    Urban endocrine ecology aims to understand how organisms cope with new sources of stress and maintain allostatic load to thrive in an increasingly urbanized world. Recent research efforts have yielded controversial results based on short-term measures of stress, without exploring its fitness effects. We measured feather corticosterone (CORTf, reflecting the duration and amplitude of glucocorticoid secretion over several weeks) and subsequent annual survival in urban and rural burrowing owls. This species shows high individual consistency in fear of humans (i.e., flight initiation distance, FID), allowing us to hypothesize that individuals distribute among habitats according to their tolerance to human disturbance. FIDs were shorter in urban than in rural birds, but CORTf levels did not differ, nor were correlated to FIDs. Survival was twice as high in urban as in rural birds and links with CORTf varied between habitats: while a quadratic relationship supports stabilizing selection in urban birds, high predation rates may have masked CORTf-survival relationship in rural ones. These results evidence that urban life does not constitute an additional source of stress for urban individuals, as shown by their near identical CORTf values compared with rural conspecifics supporting the non-random distribution of individuals among habitats according to their behavioural phenotypes. PMID:26348294

  7. A non-randomized confirmatory study regarding selection of fertility-sparing surgery for patients with epithelial ovarian cancer: Japan Clinical Oncology Group Study (JCOG1203).

    PubMed

    Satoh, Toyomi; Tsuda, Hitoshi; Kanato, Keisuke; Nakamura, Kenichi; Shibata, Taro; Takano, Masashi; Baba, Tsukasa; Ishikawa, Mitsuya; Ushijima, Kimio; Yaegashi, Nobuo; Yoshikawa, Hiroyuki

    2015-06-01

    Fertility-sparing treatment has been accepted as a standard treatment for epithelial ovarian cancer in stage IA non-clear cell histology grade 1/grade 2. In order to expand an indication of fertility-sparing treatment, we have started a non-randomized confirmatory trial for stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The protocol-defined fertility-sparing surgery is optimal staging laparotomy including unilateral salpingo-oophorectomy, omentectomy, peritoneal cytology and pelvic and para-aortic lymph node dissection or biopsy. After fertility-sparing surgery, four to six cycles of adjuvant chemotherapy with paclitaxel and carboplatin are administered. We plan to enroll 250 patients with an indication of fertility-sparing surgery, and then the primary analysis is to be conducted for 63 operated patients with pathologically confirmed stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The primary endpoint is 5-year overall survival. Secondary endpoints are other survival endpoints and factors related to reproduction. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000013380. PMID:26059697

  8. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues.

    PubMed

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-07-01

    The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II(+) FRCs/CD35(+) FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas. PMID:26700650

  9. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues

    PubMed Central

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-01-01

    Abstract The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II+ FRCs/CD35+ FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas. PMID:26700650

  10. Involvement of epigenetics and EMT related miRNA in arsenic induced neoplastic transformation and their potential clinical use

    PubMed Central

    Michailidi, Christina; Hayashi, Masamichi; Datta, Sayantan; Sen, Tanusree; Zenner, Kaitlyn; Oladeru, Oluwadamilola; Brait, Mariana; Izumchenko, Evgeny; Baras, Alexander; VandenBussche, Christopher; Argos, Maria; Bivalacqua, Trinity J; Ahsan, Habibul; Hahn, Noah M.; Netto, George J.; Sidransky, David; Hoque, Mohammad O.

    2015-01-01

    Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject’s risk of developing urothelial carcinoma (UC). To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic exposed subjects, UC patients and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time dependent manner after arsenic treatment and cellular morphology was changed. In soft agar assay, colonies were observed only in arsenic treated cells and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in invasion assay were observed only in arsenic treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were down-regulated in arsenic exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P=0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC=0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early UC detection. PMID:25586904

  11. Role of Vitamin D receptor gene in radiation-induced neoplastic transformation of human breast epithelial cell.

    PubMed

    Roy, Debasish; Calaf, Gloria; Hei, Tom K

    2003-09-01

    1 Alpha,25-(OH)(2)-Vitamin D(3), the physiologically active metabolite of Vitamin D is known for its pro-differentiating and antiproliferative activity on various cancer cell lines. It exerts its growth-regulatory effects through binding to the Vitamin D recepter (VDR), a member of the steroid/thyroid/retinoic acid receptor family, which functions as a ligand-dependent transcription factor. There is accumulating evidence that Vitamin D may be an important determinant of both the occurrence and progression of breast cancer. Since radiation is an important etiological factor for breast cancer progression, it is important to study the role of VDR gene in radiation-induced breast carcinogenesis. This study is focused on a human breast tumor model developed by irradiating the spontaneously immortalized MCF-10F cell line with graded doses of high-linear energy transfer (LET) radiation followed by treatment with estrogen. Study of VDR gene by restriction digestion with ApaI, BsmI and TaqI detected no polymorphism but direct sequencing analyses identified few single-base mutations within intron 8 and exon 9 of the gene. Over-expression of the VDR gene was noticed in irradiated and tumorigenic cell lines compared with control. Likewise, immunohistochemical data indicated a significant increase in VDR intensity in irradiated and tumorigenic cell lines. Considering all these evidence, it is likely that VDR can be used as a prognostic marker of tumor progression in radiation- and estrogen-induced breast carcinogenesis. PMID:12957667

  12. Low plasma selenium concentration is associated with elevated risk to neoplastic polyps of the colon

    SciTech Connect

    Clark, L.C.; Hixson, L.G.; Sampliner, R.E. ); Combs, G.F. Jr. )

    1991-03-11

    A cross-sectional study was conducted to examine the relationship of selenium (Se) status and polyps incidence in a sequential series of 100 patients undergoing outpatient colonoscopies at the Tucson VA Hospital. Se was measured in plasma samples by electrothermal atomic absorption spectrophotometry with Zeeman background correction using a reduced palladium matrix modified. The activities of the Se-dependent enzyme glutathione peroxidase (SeGSHpx) were measured using H{sub 2}O{sub 2} as substrate in all plasma samples and in colonic mucosal biopsies obtained from some patients. The mean plasma Se concentration of patients without polyps was 134 ng/ml. Mean plasma Se levels of patients with only diminutive or large polyps were 127 ng/ml and 125 ng/ml; while patients with polyps of both sizes had a mean plasma Se level of 121 ng/ml. Patients with no reported history of cancer, neoplastic polyps or prior colonoscopy, showed an inverse association of plasma Se level and risk of benign colonic neoplasms. The age-adjusted odds ratio for neoplastic polyps was 3.8 for patients with plasma Se levels below vs. above the median value. This association was stronger for patients under 68 yrs of age than for older patients. Activities of SeGSHpx in plasma or colonic mucosa were not related to plasma Se level; however, smokers showed greater SeGSHpx activities than non-smokers. This study is the first to detect an association of Se status and risk to neoplastic polyps of the colon.

  13. Evaluation of the Efficacy and Safety of Short-Course Deep Sedation Therapy for the Treatment of Intracerebral Hemorrhage After Surgery: A Non-Randomized Control Study.

    PubMed

    Hou, Dapeng; Liu, Beibei; Zhang, Juan; Wang, Qiushi; Zheng, Wei

    2016-01-01

    BACKGROUND While mild and moderate sedation have been widely used to reduce sudden agitation in intracerebral hemorrhage (ICH) patients after surgery, agitation is still a frequent problem, which may cause postoperative blood pressure fluctuation. The present study aimed to evaluate the efficacy and safety of short-course deep sedation for the treatment of ICH after surgery. MATERIAL AND METHODS A total of 41 ICH patients who received surgery, including traditional craniotomy hematoma removal and decompressive craniectomy, were including in this non-randomized control study. Patients in the deep sedation group received continuous postoperative sedation with a target course for ≤12 hours and reached SAS scores of 1~2. Patients in the traditional sedition group received continuous light sedation and reached SAS scores of 3~4. Additional therapeutic interventions included antihypertensive treatment, mechanical ventilation, tracheotomy, and re-operation. RESULTS Patients in the deep sedation group had deeper sedation degree, and lower systolic blood pressure (SBP) and diastolic blood pressure (DBP). Residual hematoma after surgery in patients in the deep sedation group were smaller on the second, seventh, and fourteenth day after surgery (p=0.023, 0.003, 0.004, respectively). The 3-month mortality and quality of life of patients in the deep sedation group were lower and better than that of patients in the traditional sedation group, respectively (p=0.044, p<0.01). No significant difference in the incidence of ventilator-associated pneumonia (VAP) and ICU days were observed between the two groups. CONCLUSIONS Short-course deep sedation therapy in ICH patients after surgery is efficient in controlling postoperative blood pressure, reducing re-bleeding, and improving clinical prognosis. PMID:27466863

  14. Effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda: results from a non-randomized controlled trial

    PubMed Central

    2012-01-01

    Background While the HIV epidemic is levelling off in sub-Saharan Africa, it remains at an unacceptably high level. Young people aged 15-24 years remain particularly vulnerable, resulting in a regional HIV prevalence of 1.4% in young men and 3.3% in young women. This study assesses the effectiveness of a peer-led HIV prevention intervention in secondary schools in Rwanda on young people’s sexual behavior, HIV knowledge and attitudes. Methods In a non-randomized longitudinal controlled trial, fourteen schools were selected in two neighboring districts in Rwanda Bugesera (intervention) and Rwamagana (control). Students (n = 1950) in eight intervention and six control schools participated in three surveys (baseline, six and twelve months in the intervention). Analysis was done using linear and logistic regression using generalized estimation equations adjusted for propensity score. Results The overall retention rate was 72%. Time trends in sexual risk behavior (being sexually active, sex in last six months, condom use at last sex) were not significantly different in students from intervention and control schools, nor was the intervention associated with increased knowledge, perceived severity or perceived susceptibility. It did significantly reduce reported stigma. Conclusions Analyzing this and other interventions, we identified several reasons for the observed limited effectiveness of peer education: 1) intervention activities (spreading information) are not tuned to objectives (changing behavior); 2) young people prefer receiving HIV information from other sources than peers; 3) outcome indicators are not adequate and the context of the relationship in which sex occurs and the context in which sex occurs is ignored. Effectiveness of peer education may increase through integration in holistic interventions and redefining peer educators’ role as focal points for sensitization and referral to experts and services. Finally, we argue that a narrow focus on

  15. Rock magnetic evidence of non-random raw material selection criteria in Cerro Toledo Obsidian Artifacts from Valles Caldera, New Mexico

    NASA Astrophysics Data System (ADS)

    Gregovich, A.; Feinberg, J. M.; Steffen, A.; Sternberg, R. S.

    2014-12-01

    Stone tools are one of the most enduring forms of ancient human behavior available to anthropologists. The geologic materials that comprise stone tools are a reflection of the rocks that were available locally or through trade, as are the intended use of the tools and the knapping technology needed to produce them. Investigation of the rock magnetic and geochemical characteristics of the artifacts and the geological source materials provides a baseline to explore these past behaviors. This study uses rock magnetic properties to explore the raw material selection criteria involved in the production of obsidian tools in the region around Valles Caldera in northern New Mexico. Obsidian is locally abundant and was traded by tribes across the central United States. Here we compare the rock magnetic properties of a sample of obsidian projectile points (N =25) that have been geochemically sourced to the Cerro Toledo obsidian flow with geological samples collected from four sites within the same flow (N =135). This collection of archaeological artifacts, albeit small, contains representatives of at least 8 different point styles that were used over 6000 years from the Archaic into the Late Prehistoric. Bulk rock hysteresis parameters (Mr, Ms, Bc, and Bcr) and low-field susceptibility (Χ) measurements show that the projectile points generally contain a lower concentration of magnetic minerals than the geologic samples. For example, the artifacts' median Ms value is 2.9 x 10-3 Am2kg-1, while that of the geological samples is 6.5 x 10-3 Am2kg-1. The concentration of magnetic minerals in obsidian is a proxy for the concentration of microlites in general, and this relationship suggests that although obsidian was locally abundant, toolmakers employed non-random selection criteria resulting in generally lower concentrations of microlites in their obsidian tools.

  16. Evaluation of the Efficacy and Safety of Short-Course Deep Sedation Therapy for the Treatment of Intracerebral Hemorrhage After Surgery: A Non-Randomized Control Study

    PubMed Central

    Hou, Dapeng; Liu, Beibei; Zhang, Juan; Wang, Qiushi; Zheng, Wei

    2016-01-01

    Background While mild and moderate sedation have been widely used to reduce sudden agitation in intracerebral hemorrhage (ICH) patients after surgery, agitation is still a frequent problem, which may cause postoperative blood pressure fluctuation. The present study aimed to evaluate the efficacy and safety of short-course deep sedation for the treatment of ICH after surgery. Material/Methods A total of 41 ICH patients who received surgery, including traditional craniotomy hematoma removal and decompressive craniectomy, were including in this non-randomized control study. Patients in the deep sedation group received continuous postoperative sedation with a target course for ≤12 hours and reached SAS scores of 1~2. Patients in the traditional sedition group received continuous light sedation and reached SAS scores of 3~4. Additional therapeutic interventions included antihypertensive treatment, mechanical ventilation, tracheotomy, and re-operation. Results Patients in the deep sedation group had deeper sedation degree, and lower systolic blood pressure (SBP) and diastolic blood pressure (DBP). Residual hematoma after surgery in patients in the deep sedation group were smaller on the second, seventh, and fourteenth day after surgery (p=0.023, 0.003, 0.004, respectively). The 3-month mortality and quality of life of patients in the deep sedation group were lower and better than that of patients in the traditional sedation group, respectively (p=0.044, p<0.01). No significant difference in the incidence of ventilator-associated pneumonia (VAP) and ICU days were observed between the two groups. Conclusions Short-course deep sedation therapy in ICH patients after surgery is efficient in controlling postoperative blood pressure, reducing re-bleeding, and improving clinical prognosis. PMID:27466863

  17. Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V.

    PubMed

    Gleixner, Karoline V; Peter, Barbara; Blatt, Katharina; Suppan, Verena; Reiter, Andreas; Radia, Deepti; Hadzijusufovic, Emir; Valent, Peter

    2013-09-01

    Patients with advanced systemic mastocytosis, including mast cell leukemia, have a poor prognosis. In these patients, neoplastic mast cells usually harbor the KIT mutant D816V that confers resistance against tyrosine kinase inhibitors. We examined the effects of the multi-kinase blocker ponatinib on neoplastic mast cells and investigated whether ponatinib acts synergistically with other antineoplastic drugs. Ponatinib was found to inhibit the kinase activity of KIT G560V and KIT D816V in the human mast cell leukemia cell line HMC-1. In addition, ponatinib was found to block Lyn- and STAT5 activity in neoplastic mast cells. Ponatinib induced growth inhibition and apoptosis in HMC-1.1 cells (KIT G560V(+)) and HMC-1.2 cells (KIT G560V(+)/KIT D816V(+)) as well as in primary neoplastic mast cells. The effects of ponatinib were dose-dependent, but higher IC50-values were obtained in HMC-1 cells harboring KIT D816V than in those lacking KIT D816V. In drug combination experiments, ponatinib was found to synergize with midostaurin in producing growth inhibition and apoptosis in HMC-1 cells and primary neoplastic mast cells. The ponatinib+midostaurin combination induced substantial inhibition of KIT-, Lyn-, and STAT5 activity, but did not suppress Btk. We then applied a Btk short interfering RNA and found that Btk knockdown sensitizes HMC-1 cells against ponatinib. Finally, we were able to show that ponatinib synergizes with the Btk-targeting drug dasatinib to produce growth inhibition in HMC-1 cells. In conclusion, ponatinib exerts major growth-inhibitory effects on neoplastic mast cells in advanced systemic mastocytosis and synergizes with midostaurin and dasatinib in inducing growth arrest in neoplastic mast cells. PMID:23539538

  18. Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V

    PubMed Central

    Gleixner, Karoline V.; Peter, Barbara; Blatt, Katharina; Suppan, Verena; Reiter, Andreas; Radia, Deepti; Hadzijusufovic, Emir; Valent, Peter

    2013-01-01

    Patients with advanced systemic mastocytosis, including mast cell leukemia, have a poor prognosis. In these patients, neoplastic mast cells usually harbor the KIT mutant D816V that confers resistance against tyrosine kinase inhibitors. We examined the effects of the multi-kinase blocker ponatinib on neoplastic mast cells and investigated whether ponatinib acts synergistically with other antineoplastic drugs. Ponatinib was found to inhibit the kinase activity of KIT G560V and KIT D816V in the human mast cell leukemia cell line HMC-1. In addition, ponatinib was found to block Lyn- and STAT5 activity in neoplastic mast cells. Ponatinib induced growth inhibition and apoptosis in HMC-1.1 cells (KIT G560V+) and HMC-1.2 cells (KIT G560V+/KIT D816V+) as well as in primary neoplastic mast cells. The effects of ponatinib were dose-dependent, but higher IC50-values were obtained in HMC-1 cells harboring KIT D816V than in those lacking KIT D816V. In drug combination experiments, ponatinib was found to synergize with midostaurin in producing growth inhibition and apoptosis in HMC-1 cells and primary neoplastic mast cells. The ponatinib+midostaurin combination induced substantial inhibition of KIT-, Lyn-, and STAT5 activity, but did not suppress Btk. We then applied a Btk short interfering RNA and found that Btk knockdown sensitizes HMC-1 cells against ponatinib. Finally, we were able to show that ponatinib synergizes with the Btk-targeting drug dasatinib to produce growth inhibition in HMC-1 cells. In conclusion, ponatinib exerts major growth-inhibitory effects on neoplastic mast cells in advanced systemic mastocytosis and synergizes with midostaurin and dasatinib in inducing growth arrest in neoplastic mast cells. PMID:23539538

  19. Mediastinal sarcoidosis mimicking lymph malignancy recurrence after anti-neoplastic therapy.

    PubMed

    El Hammoumi, Massine; El Marjany, Mohamed; Moussaoui, Driss; Doudouh, Aberahim; Mansouri, Hamid; Kabiri, El Hassane

    2015-07-01

    The aim of our work is to promote the awareness about the development of sarcoidosis after antineoplastic therapy in order to avoid diagnostic errors with FDG-PET/CT findings. We report the observation of three women with breast, cervix and stomach treated cancers who developed a sarcoidosis after the end of anti-neoplastic therapy. The utility of FDG-PET/CT is in pinpointing the organs candidates for diagnostic biopsy and not distinguishing between the malignancy and granulomatous or inflammatory diseases. PMID:25294405

  20. Uptake and distribution of fluorescently labeled cobalamin in neoplastic and healthy breast tissue

    NASA Astrophysics Data System (ADS)

    Cannon, Michelle J.; McGreevy, James M.; Holden, Joseph A.; West, Frederick G.; Grissom, Charles B.

    2000-05-01

    Fluorescent analogs of cobalamin (vitamin B12) have been developed as diagnostic markers of cancer cells. These compounds are recognized by transcobalamin, a cobalamin transport protein, with high affinity, as shown by surface plasmon resonance. The cellular sequestration and gross distribution of fluorescent cobalamin bioconjugates in breast tissue is being examined by epifluorescence microscopy. The distribution of each compound is being evaluated in proliferative and non-proliferative tissue, i.e. normal tissue and breast carcinoma. The results of preliminary studies suggest that fluorescent analogs of cobalamin may be a useful tool in therapeutic breast operations to define tumor margins and to distinguish neoplastic breast tissue from healthy breast tissue.

  1. MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer.

    PubMed

    Mao, Jenny T; Xue, Bingye; Smoake, Jane; Lu, Qing-Yi; Park, Heesung; Henning, Susanne M; Burns, Windie; Bernabei, Alvise; Elashoff, David; Serio, Kenneth J; Massie, Larry

    2016-08-01

    Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 μg/mL) in vitro was much higher than the IC50 (0.032-0.13 μg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer. PMID:27289489

  2. Hypercobalaminaemia is associated with hepatic and neoplastic disease in cats: a cross sectional study

    PubMed Central

    2014-01-01

    Background When increased serum cobalamin concentrations are encountered clinically they are usually attributed to parenteral supplementation, dietary factors, or otherwise ignored. However, recently, hypercobalaminaemia has been associated with numerous diseases in humans, most notably neoplastic and hepatic disorders. The aim of this retrospective, observational, cross-sectional study was to determine the significance of increased cobalamin in cats. Results In total, 237 records were retrieved and 174 cats, of various ages and sexes met the inclusion criteria. A total of 42 cats had increased serum cobalamin concentration, and had not received prior supplementation. Multiple logistic regression analysis revealed that increased serum cobalamin concentration was positively related to pedigree breed (pedigree breeds more likely to have increased cobalamin concentration, odds ratio [OR] 4.24, 95% CI 1.78-10.15, P = 0.001), to having liver disease (OR 9.91, 95% CI 3.54-27.68), and to having a solid neoplasm (OR 8.54, 95% CI 1.10-66.45). Conclusions The results of the current study suggest that increased serum cobalamin concentrations should not be ignored in cats with no history of supplementation, and investigation for underlying hepatic or neoplastic disease is warranted. PMID:25103858

  3. Evaluation of impact of immunocytochemical techniques in cytological diagnosis of neoplastic effusions.

    PubMed Central

    Linari, A; Bussolati, G

    1989-01-01

    A prospective study (1984-87) on the immunocytochemical identification of cancer cells in effusions using HMFG2 monoclonal antibody, and in addition, monoclonal anti-CEA and B72.3 antibodies in cases of suspected mesothelioma, was undertaken. On the basis of cytology alone, of a total of 2362 pleural, peritoneal, and pericardial effusions, 525 cases were diagnosed as positive and 1485 as negative for neoplastic cells, while in 352 (15%) specimens from 307 patients the diagnosis was doubtful. Sections of the embedded sediment of doubtful cases were tested with HMFG2 antibody and proved positive in 215 cases, negative in 108, and inconclusive in 29. The results were checked by following the clinical outcome of the cases. The method was specific in identifying cancer cells in cases at best diagnosed as suspicious on the basis of cytology alone; this represents a clear diagnostic gain. Sensitivity of the test, however, was relatively low (41%). Combined cytological and immunocytochemical characteristics (CEA negative and only some of the neoplastic cells positive with HMFG2 and B72.3 monoclonal antibodies) permitted diagnosis on the effusions of most cases of mesothelioma. The impact of the diagnosis on the progress of the disease was not appreciable as no difference in outcome was noted, irrespective of whether cancer cells had been recognised. The occurrence of an effusion remains an ominous sign in most patients treated for cancer. Images PMID:2685053

  4. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

    PubMed

    Granger, D L; Lehninger, A L

    1982-11-01

    Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed. PMID:6292238

  5. Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell lines.

    PubMed

    Walters, Denise K; Muff, Roman; Langsam, Bettina; Gruber, Philipp; Born, Walter; Fuchs, Bruno

    2007-08-01

    Taurolidine, the active agent of Taurolin, is a broad spectrum anti-biotic that has been used for over 15 years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agent. PMID:17458504

  6. Interobserver agreement for the spine instability neoplastic score varies according to the experience of the evaluator

    PubMed Central

    Teixeira, William Gemio Jacobsen; de Mesquita Coutinho, Pedro Ricardo; Marchese, Luiz Delboni; Narazaki, Douglas Kenji; Cristante, Alexandre Fogaça; Teixeira, Manoel Jacobsen; de Barros Filho, Tarcísio Eloy Pessoa; de Camargo, Olavo Pires

    2013-01-01

    OBJECTIVES: To evaluate the interobserver agreement for the Neoplastic Spine Instability Score (SINS) among spine surgeons with or without experience in vertebral metastasis treatment and physicians in other specialties. METHODS: Case descriptions were produced based on the medical records of 40 patients with vertebral metastases. The descriptions were then published online. Physicians were invited to evaluate the descriptions by answering questions according to the Neoplastic Spine Instability Score (SINS). The agreement among physicians was calculated using the kappa coefficient. RESULTS: Seventeen physicians agreed to participate: three highly experienced spine surgeons, seven less-experienced spine surgeons, three surgeons of other specialties, and four general practitioners (n = 17). The agreement for the final SINS score among all participants was fair, and it varied according to the SINS component. The agreement was substantial for the spine location only. The agreement was higher among experienced surgeons. The agreement was nearly perfect for spinal location among the spine surgeons who were highly experienced in vertebral metastases. CONCLUSIONS: This study demonstrates that the experience of the evaluator has an impact on SINS scale classification. The interobserver agreement was only fair among physicians who were not spine surgeons and among spine surgeons who were not experienced in the treatment of vertebral metastases, which may limit the use of the SINS scale for the screening of unstable lesions by less-experienced evaluators. PMID:23525318

  7. A core of kinase-regulated interactomes defines the neoplastic MDSC lineage

    PubMed Central

    Zudaire, Isabel; Liechtenstein, Therese; Arasanz, Hugo; Lozano, Teresa; Casares, Noelia; Chaikuad, Apirat; Knapp, Stefan; Guerrero-Setas, David; Escors, David; Kochan, Grazyna; Santamaría, Enrique

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) differentiate from bone marrow precursors, expand in cancer-bearing hosts and accelerate tumor progression. MDSCs have become attractive therapeutic targets, as their elimination strongly enhances anti-neoplastic treatments. Here, immature myeloid dendritic cells (DCs), MDSCs modeling tumor-infiltrating subsets or modeling non-cancerous (NC)-MDSCs were compared by in-depth quantitative proteomics. We found that neoplastic MDSCs differentially expressed a core of kinases which controlled lineage-specific (PI3K-AKT and SRC kinases) and cancer-induced (ERK and PKC kinases) protein interaction networks (interactomes). These kinases contributed to some extent to myeloid differentiation. However, only AKT and ERK specifically drove MDSC differentiation from myeloid precursors. Interfering with AKT and ERK with selective small molecule inhibitors or shRNAs selectively hampered MDSC differentiation and viability. Thus, we provide compelling evidence that MDSCs constitute a distinct myeloid lineage distinguished by a “kinase signature” and well-defined interactomes. Our results define new opportunities for the development of anti-cancer treatments targeting these tumor-promoting immune cells. PMID:26320174

  8. Neoplastic meningitis resulting from hematological malignancies: pharmacokinetic considerations and maximizing outcome

    PubMed Central

    Grewal, Jai; Saria, Marlon; Grewal, Harpreet K; Kesari, Santosh

    2012-01-01

    Neoplastic meningitis, also known as leptomeningeal metastases, is a complication of various types of cancer that occurs when tumor cells enter the cerebrospinal fluid (CSF), travel along CSF pathways and grow. Treatment options include drug delivery directly into the CNS or systemic administration for targeted action in the CNS. CNS drug delivery is limited by the blood–brain barrier and the blood–CSF barrier. It may be possible to partially overcome this by using high-dose systemic therapy; however, this is done at the possible expense of increased systemic toxicity. Intra-CSF drug delivery bypasses the blood–brain barrier and allows direct access of the chemotherapeutic agent to the CSF. Because neoplastic meningitis occurs in an increasingly large percentage of all cancer patients, it is imperative to optimize drug delivery to the CSF and meninges. Both the pharmacokinetic profile of the chemotherapeutic agent and the site of administration influence therapeutic efficacy. Achieving prolonged therapeutic cytotoxic drug concentrations and even distribution in the CSF will improve efficacy. In this article we summarize data on the efficacy, safety and outcome of high-dose systemic and intra-CSF treatments. PMID:22396850

  9. The treatment of snoring by radiofrequency-assisted uvulopalatoplasty and results after one-session protocol: a prospective, longitudinal, non-randomized study.

    PubMed

    Chiesa Estomba, Carlos Miguel; Rivera Schmitz, Teresa; Ossa Echeverri, Carla Cristina; Betances Reinoso, Frank Alberto; Fariña Conde, José; Alonso Parraga, Dionisio

    2015-10-01

    Snoring is usually caused by the vibration of walls of the soft palate at the pharyngeal level. Its worldwide prevalence is estimated to range between 2 and 85% depending on age, gender or population group. The aim of this study is to determine the degree of improvement that can be subjectively evident in patients treated by snoring with radiofrequency-assisted uvulopalatoplasty based on a one-session protocol. This is a prospective, longitudinal, non-randomized study. Patients of both sexes, aged 18 years, who attended to the ENT consultation in a tertiary hospital with snoring during the period of July 2012-July 2013 were included. Age, body mass index, Epworth sleepiness scale were calculated. The volume of snoring of each subject was assessed using a visual analog scale. A total of 27 patients were included in the study; the average age of the sample was 49 years (±8.7; min 36/max 74); of these 22 (81.5%) were male and 5 (18.5%) females. The average BMI was 27.07 ± 2.5 (min 23.15/max 29.39) before the test and after 1 year was 26.75 ± 2.32 (min 23.11/max 29.56) with no statistically significant differences in BMI before and after surgery (p = 0.407). Preoperative snoring intensity was 8.10 ± 0.93 according to VAS. We found a statistically significant difference in the post-operative intensity at 3 months of 3.93 ± 0.88 (p ≤ 0.05) at 6 months of 4.41 ± 1.08 (p ≤ 0.05), and after 1 year 4.90 ± 0.77 (p ≤ 0.05). The average rate of ESS was significantly higher preoperatively than post-operative, being 8.76 ± 3.1 preoperative and 6.93 ± 1.68 post-operative (p ≤ 0.05). We conclude that the use of radiofrequency in simple snorers with an apnea/hypopnea index <15 events per hour and a BMI < 30 kg/m(2) in whom clinically proven that the source of snoring is the soft palate, can be treated by one-session protocol, being possible to obtain an improvement of snoring up to 70% of cases by a short follow-up period. PMID:25837987

  10. Non-randomized studies as a source of complementary, sequential or replacement evidence for randomized controlled trials in systematic reviews on the effects of interventions.

    PubMed

    Schünemann, Holger J; Tugwell, Peter; Reeves, Barnaby C; Akl, Elie A; Santesso, Nancy; Spencer, Frederick A; Shea, Beverley; Wells, George; Helfand, Mark

    2013-03-01

    The terms applicability, generalizability, external validity and transferability are related, sometimes used interchangeably and have in common that they lack a clear and consistent definition in the classic epidemiological literature. However, all of these terms generally describe one overarching theme: whether or not available research evidence can be directly utilized to answer the healthcare questions at hand, ideally supported by a judgment about the degree of confidence for this utilization. This concept has been called directness. The objectives of this paper were to delineate how non-randomized studies (NRS) inform judgments in relation to directness and the concepts that it encompasses in the context of systematic reviews. We will briefly review what is known and describe the theoretical and practical issues as well as offer guidance to those tackling the challenges of judging directness and using research evidence to answer healthcare questions with evidence from NRS. In particular, we suggest a framework in which authors can use NRS as a complement, sequence or replacement for randomized controlled trials (RCTs) by focusing on judgments about the population, intervention, comparison and outcomes. Authors of systematic reviews will use NRS to complement judgments about the inconsistencies, the rationale and credibility of subgroup analysis, the baseline risk estimates for the determination of absolute benefits and downsides, and the directness of surrogate outcomes. This evidence includes contextual or supplementary evidence. Authors of systematic review and other summaries of the evidence use NRS as sequential evidence to provide evidence when insufficient evidence is available for an outcome from RCTs, but NRS evidence is available (e.g., long-term harms). Use of evidence from NRS may also serve to replace RCT evidence when NRS provide equivalent (or potentially higher) confidence in the evidence (i.e. quality) compared to indirect evidence from RCTs

  11. The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important?

    PubMed

    Bonsib, Stephen M; Pei, Ying

    2010-07-01

    Surgical nephrectomy is a procedure that has been performed for nearly 100 years. In the presence of a normal contralateral kidney, such as in a renal transplant donor or child with Wilms tumor, it is a benign procedure without deleterious consequences on the remaining kidney. However, many adults and some children postnephrectomy will develop chronic kidney disease. The non-neoplastic kidney in tumor resections may harbor a large number of developmental and acquired diseases predictive of this outcome or that convey other medically significant information. Examination of the non-neoplastic kidney is a fertile opportunity to identify these unsuspected conditions that may ultimately dictate the subsequent clinical course and influence the medical care provided. This review discusses the consequences of unilateral and partial nephrectomy, and illustrates many conditions that may be encountered in the non-neoplastic cortex with a discussion of their clinical implications. PMID:20574169

  12. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

    SciTech Connect

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

  13. Noninvasive monitoring of photodynamic therapy on skin neoplastic lesions using the optical attenuation coefficient measured by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Goulart, Viviane P.; dos Santos, Moisés O.; Latrive, Anne; Freitas, Anderson Z.; Correa, Luciana; Zezell, Denise M.

    2015-05-01

    Photodynamic therapy (PDT) has become a promising alternative for treatment of skin lesions such as squamous cell carcinoma. We propose a method to monitor the effects of PDT in a noninvasive way by using the optical attenuation coefficient (OAC) calculated from optical coherence tomography (OCT) images. We conducted a study on mice with chemically induced neoplastic lesions and performed PDT on these lesions using homemade photosensitizers. The response of neoplastic lesions to therapy was monitored using, at the same time, macroscopic clinical visualization, histopathological analysis, OCT imaging, and OCT-based attenuation coefficient measurement. Results with all four modalities demonstrated a positive response to treatment. The attenuation coefficient was found to be 1.4 higher in skin lesions than in healthy tissue and it decreased after therapy. This study shows that the OAC is a potential tool to noninvasively assess the evolution of skin neoplastic lesions with time after treatment.

  14. Transformation linked decrease of pyruvate dehydrogenase complex in human epidermis.

    PubMed

    Eboli, M L; Pasquini, A

    1994-10-14

    Epidermis exhibits glycolytic features peculiar to cancer cells. The activity of pyruvate dehydrogenase complex, both active (PDHa) and total (PDHt) forms, has been investigated and compared in epidermis and epidermal carcinomas from human source. Low or undetectable PDHa is found in either normal and neoplastic tissue. PDHt is unchanged in human epidermis between the second and seventh decades of life but is dramatically decreased following neoplastic transformation (0.107 and 0.026 units/g fresh tissue for epidermis and epidermal carcinoma, respectively). As PDH plays a key role in mitochondrial carbohydrate metabolism, the decrease of total enzymic capacity found in tumors suggest that different mechanisms regulate PDH expression and, in turn, glycolytic mechanisms of epidermis and cancer cells. PMID:7954343

  15. Validation of coded aperture coherent scatter spectral imaging for normal and neoplastic breast tissues via surgical pathology

    NASA Astrophysics Data System (ADS)

    Morris, R. E.; Albanese, K. E.; Lakshmanan, M. N.; McCall, S. J.; Greenberg, J. A.; Kapadia, A. J.

    2016-03-01

    This study intends to validate the sensitivity and specificity of coded aperture coherent scatter spectral imaging (CACSSI) by comparison to standard histological preparation and pathologic analysis methods used to differentiate normal and neoplastic breast tissues. A composite overlay of the CACSSI rendered image and pathologist interpreted stained sections validate the ability of CACSSI to differentiate normal and neoplastic breast structures ex-vivo. Via comparison to pathologist annotated slides, the CACSSI system may be further optimized to maximize sensitivity and specificity for differentiation of breast carcinomas.

  16. Immunohistochemical analysis of Mcl-1 and Bcl-2 proteins in normal and neoplastic lymph nodes.

    PubMed Central

    Krajewski, S.; Bodrug, S.; Gascoyne, R.; Berean, K.; Krajewska, M.; Reed, J. C.

    1994-01-01

    The Bcl-2 protein blocks programmed cell death and becomes overproduced in many follicular non-Hodgkin's lymphomas as the result of t(14; 18) translocations involving the Bcl-2 gene. Mcl-1 is a recently discovered gene whose encoded protein has significant homology with Bcl-2 but whose function remains unknown. In this study, we compared the in vivo patterns of Bcl-2 and Mcl-1 protein production in normal and neoplastic lymph node biopsies by immunohistochemical means using specific polyclonal antisera. Intracellular Mcl-1 immunoreactivity was located primarily in the cytosol in a punctate pattern and was also seen in association with the nuclear envelope in many cases, similar to the results obtained for Bcl-2, which resides in the outer mitochondrial membrane, nuclear envelope, and endoplasmic reticulum. In 4 of 4 reactive tonsils and 28 of 28 nodes with reactive follicular hyperplasia, reciprocal patterns of Bcl-2 and Mcl-1 protein expression were observed. Bcl-2 immunostaining was highest in mantle zone lymphocytes and absent from most germinal center cells, whereas Mcl-1 immunoreactivity was highest in germinal center lymphocytes and absent from mantle zone lymphocytes. Mcl-1 was also expressed in some interfollicular lymphocytes, particularly those that had the appearance of activated lymphocytes. Similar to the patterns of Bcl-2 and mcl-1 expression seen in reactive nodes, Mcl-1 protein was largely absent from the malignant cells in 2 of 2 mantle cell lymphomas, whereas strong Bcl-2 immunostaining was found in these cells. In contrast to normal nodes, however, the neoplastic follicles of t(14;18) containing follicular non-Hodgkin's lymphomas immunostained positively for both Bcl-2 and Mcl-1 in 24 of 27 cases. Intense immunostaining for Mcl-1 was also observed in Reed-Sternberg cells in 2 of 2 cases of Hodgkin's disease but Bcl-2 immunoreactivity was present at much lower levels. These findings demonstrate that the levels of Mcl-1 and Bcl-2 proteins are

  17. Endoscopic submucosal dissection for the treatment of neoplastic lesions in the gastrointestinal tract

    PubMed Central

    Białek, Andrzej; Wiechowska-Kozłowska, Anna; Pertkiewicz, Jan; Karpińska, Katarzyna; Marlicz, Wojciech; Milkiewicz, Piotr; Starzyńska, Teresa

    2013-01-01

    AIM: To investigate the indications, resection rate, and safety of endoscopic submucosal dissection (ESD) for neoplastic lesions in the gastrointestinal tract at a European referral center. METHODS: We carried out a retrospective analysis of the ESD procedures performed in our center for mucosal neoplastic and submucosal lesions of the gastrointestinal tract. The duration of the procedure, en bloc and complete (R0) resection rates, and complication rates were evaluated. Variables were reported as mean ± SD or simple proportions. Univariate analysis and comparisons of procedure times and resection rates were performed using Mann-Whitney U tests, or χ2 tests for dichotomous variables. RESULTS: Between 2007 and 2011, ESD was performed in a total of 103 patients (46.7% male, mean age 64.0 ± 12.7 years). The indications for the procedure were epithelial tumor (n = 54), submucosal tumor (n = 42), or other (n = 7). The total en bloc resection rate was 90.3% (93/103) and R0 resection rate 80.6% (83/103). The median speed of the procedure was 15.0 min/cm2. The complete resection rate was lower for submucosal tumors arising from the muscle layer (68%, 15/22, P < 0.05). Resection speed was quicker for submucosal tumors localized in the submucosal layer than for lesions arising from the muscularis propria layer (8.1 min/cm2 vs 17.9 min/cm2, P < 0.05). The R0 resection rate and speed were better in the last 24 mo (90.1%, 49/54 and 15.3 min/cm2) compared to the first 3 years of treatment (73.5%, 36/49, P < 0.05 and 22.0 min/cm2, P < 0.05). Complications occurred in 14.6% (n = 15) of patients, including perforation in 5.8% (n = 6), pneumoperitoneum in 3.9% (n = 4), delayed bleeding in 1.9% (n = 2), and other in 2.9% (n = 3). Only one patient with delayed perforation required surgical treatment. During the mean follow-up of 26 ± 15.3 mo, among patients with R0 resection, recurrence occurred in one patient (1.2%). CONCLUSION: ESD is an effective and safe method for resection of

  18. A Critical Evaluation of microRNA Biomarkers in Non-Neoplastic Disease

    PubMed Central

    Haider, Baqer A.; Baras, Alexander S.; McCall, Matthew N.; Hertel, Joshua A.; Cornish, Toby C.; Halushka, Marc K.

    2014-01-01

    Background MicroRNAs (miRNAs) are small (∼22-nt), stable RNAs that critically modulate post-transcriptional gene regulation. MicroRNAs can be found in the blood as components of serum, plasma and peripheral blood mononuclear cells (PBMCs). Many microRNAs have been reported to be specific biomarkers in a variety of non-neoplastic diseases. To date, no one has globally evaluated these proposed clinical biomarkers for general quality or disease specificity. We hypothesized that the cellular source of circulating microRNAs should correlate with cells involved in specific non-neoplastic disease processes. Appropriate cell expression data would inform on the quality and usefulness of each microRNA as a biomarker for specific diseases. We further hypothesized a useful clinical microRNA biomarker would have specificity to a single disease. Methods and Findings We identified 416 microRNA biomarkers, of which 192 were unique, in 104 publications covering 57 diseases. One hundred and thirty-nine microRNAs (33%) represented biologically plausible biomarkers, corresponding to non-ubiquitous microRNAs expressed in disease-appropriate cell types. However, at a global level, many of these microRNAs were reported as “specific” biomarkers for two or more unrelated diseases with 6 microRNAs (miR-21, miR-16, miR-146a, miR-155, miR-126 and miR-223) being reported as biomarkers for 9 or more distinct diseases. Other biomarkers corresponded to common patterns of cellular injury, such as the liver-specific microRNA, miR-122, which was elevated in a disparate set of diseases that injure the liver primarily or secondarily including hepatitis B, hepatitis C, sepsis, and myocardial infarction. Conclusions Only a subset of reported blood-based microRNA biomarkers have specificity for a particular disease. The remainder of the reported non-neoplastic biomarkers are either biologically implausible, non-specific, or uninterpretable due to limitations of our current understanding of micro

  19. Reading Transformation

    ERIC Educational Resources Information Center

    Reeves, Melinda

    2006-01-01

    The parents of students who attend Decatur High School thought that there was little hope of their kids going on to college. After a year or so in Decatur's reading program, their sons and daughters were both transformed and college bound. In this article, the author describes how Decatur was able to successfully transform their students. Seven…

  20. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

    PubMed Central

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    ABSTRACT Objective To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Methods Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. Results The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). Conclusion The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues. PMID:26761548

  1. Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

    PubMed

    Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T; Field, Alison E; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L

    2016-07-01

    Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public

  2. DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome: a unique constellation of neoplastic conditions

    PubMed Central

    Yang, Jiandong; Doros, Leslie; Williams, Gretchen M.; Harris, Anne; Stewart, Douglas R.; Messinger, Yoav; Field, Amanda; Dehner, Louis P.; Hill, D Ashley

    2014-01-01

    Germline mutations in DICER1 are associated with increased risk for a wide variety of neoplastic conditions, including pleuropulmonary blastoma (PPB), cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, botryoid embryonal rhabdomyosarcoma of the uterine cervix, ciliary body medulloepithelioma, pineoblastoma, pituitary blastoma and nodular thyroid hyperplasia or thyroid carcinoma. These tumors may be seen in isolation or in constellation with other characteristic tumor types in individuals or family members. Here we describe the medical history of a child with a heterozygous, loss of function germline DICER1 mutation and multiple tumors associated with the syndrome.. Although germline mutations in DICER1 are rare, tumors of these types will be seen by practicing pathologists and should prompt consideration of an underlying DICER1 mutation. PMID:25356068

  3. Antioxidant strategies in genetic syndromes with high neoplastic risk in infant age.

    PubMed

    Anichini, Cecilia; Lotti, Federica; Longini, Mariangela; Felici, Cosetta; Proietti, Fabrizio; Buonocore, Giuseppe

    2014-01-01

    Oxidative stress plays a key role in carcinogenesis. Oxidative damage to cell components can lead to the initiation, promotion and progression of cancer. Oxidative stress is also a distinctive sign in several genetic disorders characterized by a cancer predisposition such as ataxia-telangiectasia, Fanconi anemia, Down syndrome, Beckwith-Wiedemann syndrome and Costello syndrome. Taking into account the link between oxidative stress and cancer, the capacity of antioxidant agents to prevent or delay neoplastic development has been tested in various studies, both in vitro and in vivo, with interesting and promising results. In recent years, research has been conducted into the molecular mechanisms linking oxidative stress to the pathogenesis of the genetic syndromes we consider in this review, with the resulting identification of possible new therapeutic targets. The aim of this review is to focus on the oxidative mechanisms intervening in carcinogenesis in cancer-prone genetic disorders and to analyze the current status and future prospects of antioxidants. PMID:25688491

  4. Pre-neoplastic epigenetic disruption of transcriptional enhancers in chronic inflammation

    PubMed Central

    Kron, Ken J.; Bailey, Swneke D.; Roulois, David; Lupien, Mathieu; Line, Sérgio R. Peres; de Souza, Ana Paula; De Carvalho, Daniel D.

    2016-01-01

    Chronic periodontitis (CP) is a chronic inflammatory disease independently associated with higher incidence of oral cavity squamous cell carcinoma (OSCC). However, the molecular mechanism responsible for this increased incidence is unknown. Here we profiled the DNA methylome of CP patients and healthy controls and compared to a large set of OSCC samples from TCGA. We observed a significant overlap between the altered DNA methylation patterns in CP and in OSCC, suggesting an emergence of a pre-neoplastic epigenome in CP. Remarkably, the hypermethylated CpGs in CP were significantly enriched for enhancer elements. This aberrant enhancer methylation is functional and able to disrupt enhancer activity by preventing the binding of chromatin looping factors. This study provides new insights on the molecular mechanisms linking chronic inflammation and tumor predisposition, highlighting the role of epigenetic disruption of transcriptional enhancers. PMID:26908456

  5. The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the Mist

    SciTech Connect

    Goldenring, James R.; Nam, Ki Taek; Mills, Jason C.

    2011-11-15

    The digestive-enzyme secreting, gastric epithelial chief (zymogenic) cell is remarkable and underappreciated. Here, we discuss how all available evidence suggests that mature chief cells in the adult, mammalian stomach are postmitotic, slowly turning over cells that arise via a relatively long-lived progenitor, the mucous neck cell, The differentiation of chief cells from neck cells does not involve cell division, and the neck cell has its own distinct pattern of gene expression and putative physiological function. Thus, the ontogeny of the normal chief cell lineage exemplifies transdifferentiation. Furthermore, under pathophysiogical loss of acid-secreting parietal cell, the chief cell lineage can itself trasndifferentiate into a mucous cell metaplasia designated Spasmolytic Polypeptide Expressing Metaplasia (SPEM). Especially in the presence of inflammation, this metaplastic lineage can regain proliferative capacity and, in humans may also further differentiate into intestinal metaplasia. The results indicate that gastric fundic lineages display remarkable plasticity in both physiological ontogeny and pathophysiological pre-neoplastic metaplasia.

  6. Regulation of Notch signaling and endocytosis by the Lgl neoplastic tumor suppressor

    PubMed Central

    Portela, Marta; Parsons, Linda M; Grzeschik, Nicola A; Richardson, Helena E

    2015-01-01

    The evolutionarily conserved neoplastic tumor suppressor protein, Lethal (2) giant larvae (Lgl), plays roles in cell polarity and tissue growth via regulation of the Hippo pathway. In our recent study, we showed that in the developing Drosophila eye epithelium, depletion of Lgl leads to increased ligand-dependent Notch signaling. lgl mutant tissue also exhibits an accumulation of early endosomes, recycling endosomes, early-multivesicular body markers and acidic vesicles. We showed that elevated Notch signaling in lgl− tissue can be rescued by feeding larvae the vesicle de-acidifying drug chloroquine, revealing that Lgl attenuates Notch signaling by limiting vesicle acidification. Strikingly, chloroquine also rescued the lgl− overgrowth phenotype, suggesting that the Hippo pathway defects were also rescued. In this extraview, we provide additional data on the regulation of Notch signaling and endocytosis by Lgl, and discuss possible mechanisms by which Lgl depletion contributes to signaling pathway defects and tumorigenesis. PMID:25789785

  7. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata.

    PubMed

    Sima, Peter; Vetvicka, Vaclav

    2011-11-10

    An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come. PMID:22087433

  8. Expression of splice variants of mts1 gene in normal and neoplastic human tissues

    SciTech Connect

    Ambartsumyan, N.S. |; Grigorian, M.S.; Lukanidin, E.M.

    1995-09-01

    Data on cloning of cDNA corresponding to human mts1 gene transcripts are presented. By comparing nucleotide sequences of the genomic DNA clone and cDNA of mts1, it was shown that human osteosarcoma OHS cells contain two alternative splice variants of mts1 transcripts. Alternative splicing occurs in the 5{prime}-untranslated region of the mts1 pre-mRNA. Both splice variants, hu-mts1 and hu-mts1(var), demonstrate similar stability in the cells, and each contains one open reading frame for the MTS1 protein. However, the two types of transcripts are translated with different effectiveness. The level of transcription of mts1 splice variants in different normal and neoplastic tissues and cell lines varies significantly. The role of alternative splicing as the mechanism responsible for posttranscriptional regulation of mts1 gene expression is discussed. 31 refs., 5 figs.

  9. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata

    PubMed Central

    Sima, Peter; Vetvicka, Vaclav

    2011-01-01

    An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come. PMID:22087433

  10. Scanning acoustic microscopy for characterization of neoplastic and inflammatory lesions of lymph nodes.

    PubMed

    Miura, Katsutoshi; Nasu, Hatsuko; Yamamoto, Seiji

    2013-01-01

    A scanning acoustic microscope (SAM) imaging system calculates and color codes speed of sound (SOS). We evaluated the SAM results for lymph node imaging and compared these results with those of light microscopy (LM). SAM showed normal structures and localized/diffuse lesions of the lymph node. Our results revealed that as a rule, soft areas such as cystic necrosis presented less SOS while harder areas such as coagulative necrosis, granulomas, and fibrosis exhibited greater SOS. SOS increased according to stromal desmoplastic reactions and cellular concentration. In neoplastic lesions, statistically significant differences in SOS were observed among scirrhous carcinomas, lymphomas, and medullary carcinomas. SAM provided the following benefits over LM: (1) images reflected the tissue elasticity of each lesion, (2) digitized SOS data could be statistically comparable, (3) images were acquired in a few minutes without special staining, (4) SAM images and echographic images were comparable for clinical ultrasound imaging study. PMID:23409246

  11. Neoplastic meningitis from breast carcinoma with complete response to liposomal cytarabine: case report.

    PubMed

    Gaviani, Paola; Silvani, A; Corsini, E; Erbetta, A; Salmaggi, A

    2009-06-01

    Neoplastic meningitis from breast cancer often leads to a progressive neurologic deterioration followed by fatal outcome. The therapy is based on the administration of high dose systemic chemotherapy with drugs able to pass through the blood-brain barrier, such as methotrexate (MTX) and cytarabine, cranial or craniospinal irradiation, and intrathecal (IT) administration of MTX and/or cytarabine. However, these approaches only have modest efficacy and are associated with side effects for the patients. A depot formulation of liposomal cytarabine (DepoCyte) has proven to be useful in clinical trials. We describe the case of a woman with a diagnosis of leptomeningeal carcinomatosis from breast carcinoma who presented cerebrospinal fluid normalization and prolonged complete MRI response to intrathecal chemotherapy with liposomal cytarabine (DepoCyte). PMID:19259616

  12. NON-RANDOM CELL KILLING IN CRYOPRESERVATION: IMPLICATIONS FOR PERFORMANCE OF THE BATTERY OF LEUKOCYTE TESTS (BLT) - I. TOXIC AND IMMUNOTOXIC EFFECTS

    EPA Science Inventory

    To eliminate between-tests error in longitudinal studies, for specimen sharing, convenient scheduling, etc., it is necessary to freeze freshly separated leukocytes as well as non-transformed, continuous T lymphocyte (CTL) lines. o test the efficacy of a programmable reezer (tempe...

  13. Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes.

    PubMed

    Suliman, Salwa; Mustafa, Kamal; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Osdal, Tereza; Hamza, Amani O; Sun, Yang; Parajuli, Himalaya; Waag, Thilo; Nickel, Joachim; Johannessen, Anne Christine; McCormack, Emmet; Costea, Daniela Elena

    2016-07-01

    This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK(Luc)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK(Luc) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK(Luc) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK(Luc) both in vitro in 3D-OT and in vivo in xenografts formed by DOK(Luc) alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK(Luc) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK(Luc), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities. PMID:27108402

  14. Gene Signature Distinguishes Patients with Chronic Ulcerative Colitis Harboring Remote Neoplastic Lesions

    PubMed Central

    Pekow, Joel; Dougherty, Urszula; Huang, Yong; Gometz, Edward; Nathanson, Jeff; Cohen, Greg; Levy, Shawn; Kocherginsky, Masha; Venu, Nanda; Westerhoff, Maria; Hart, John; Noffsinger, Amy E.; Hanauer, Stephen B; Hurst, Roger D.; Fichera, Alessandro; Joseph, Loren J; Liu, Qiang; Bissonnette, Marc

    2013-01-01

    Background Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in non-dysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions. Methods Gene expression was analyzed by cDNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly up-regulated from controls, to UC without neoplasia, to UC with remote neoplasia were evaluated by real time PCR. Several gene products were also examined by immunohistochemistry. Results 468 genes were significantly up-regulated and 541 genes were significantly down-regulated in UC patints with neoplasia compared to UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly up-regulated from controls to non-dysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in non-dysplastic tissue from UC patients harboring remote neoplasia, compared to UC patients without neoplasia and controls. Conclusions Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease. PMID:23388545

  15. Effect of carcinogen dose on the dynamics of neoplastic development in rat tracheal epithelium

    SciTech Connect

    Terzaghi, M.; Nettesheim, P.; Riester, L.

    1982-11-01

    The aim was to analyze carcinogen dose effects on the development of carcinogen-altered preneoplastic epithelial cell populations following exposure to 7,12-dimethylbenz(a)anthracene (DMBA). Upon exposure to carcinogen, cells appear in the tracheal epithelium which are distinguishable by an enhanced in vitro growth capacity. Cultures established from carcinogen-exposed cells form expanding epithelial foci (EF). Designated EF-forming units (EFFU), these clonogenic units often escape senescence permanently and may become neoplastic after repeated subculturing. Clonogenic units give rise to subculturable progeny (EFFU/sub s/) and to progeny which became anchorage independent (EFFU/sub s,ag/sup +//). In the tracheal cell culture system, anchorage-independent growth is highly correlated with oncogenicity in vivo. Tracheas were exposed in vivo for 4 weeks to DMBA in doses ranging from 5 to 335 ..mu..g. Exposure to DMBA resulted in a 100- to 500-fold increase in frequency of EFFU, but no definitive carcinogen dose-response effect was detected on the number of clonogenic cells forming EF or subculturable EF, although there was some indication that the latter might be increasing with increasing dose. There was a marked carcinogen dose effect on the frequency and rate of appearance of EFFU/sub s,ag/sup +//. The data suggest that the carcinogen dose affects either the rate of growth of EFFU/sub x,ag/sup +//, the cell compartment with neoplastic potential, or the conversion rate of EFFU/sub s/ to EFFU/sub s,ag/sup +//.

  16. Lightweight transformer

    SciTech Connect

    Swallom, D.W.; Enos, G.

    1990-05-01

    The technical effort described in this report relates to the program that was performed to design, fabricate, and test a lightweight transformer for Strategic Defense Initiative Organization (SDIO) mission requirements. The objectives of this program were two-fold: (1) design and fabricate a lightweight transformer using liquid hydrogen as the coolant; and (2) test the completed transformer assembly with a low voltage, dc power source. Although the full power testing with liquid helium was not completed, the program demonstrated the viability of the design approach. The lightweight transformer was designed and fabricated, and low and moderate power testing was completed. The transformer is a liquid hydrogen cooled air core transformer that uses thin copper for its primary and secondary windings. The winding mass was approximately 12 kg, or 0.03 kg/kW. Further refinements of the design to a partial air core transformer could potentially reduce the winding mass to as low as 4 or 5 kg, or 0.0125 kg/kW. No attempt was made on this program to reduce the mass of the related structural components or cryogenic container. 8 refs., 39 figs., 2 tabs.

  17. mSin3A corepressor regulates diverse transcriptional networks governing normal and neoplastic growth and survival

    PubMed Central

    Dannenberg, Jan-Hermen; David, Gregory; Zhong, Sheng; van der Torre, Jaco; Wong, Wing H.; DePinho, Ronald A.

    2005-01-01

    mSin3A is a core component of a large multiprotein corepressor complex with associated histone deacetylase (HDAC) enzymatic activity. Physical interactions of mSin3A with many sequence-specific transcription factors has linked the mSin3A corepressor complex to the regulation of diverse signaling pathways and associated biological processes. To dissect the complex nature of mSin3A's actions, we monitored the impact of conditional mSin3A deletion on the developmental, cell biological, and transcriptional levels. mSin3A was shown to play an essential role in early embryonic development and in the proliferation and survival of primary, immortalized, and transformed cells. Genetic and biochemical analyses established a role for mSin3A/HDAC in p53 deacetylation and activation, although genetic deletion of p53 was not sufficient to attenuate the mSin3A null cell lethal phenotype. Consistent with mSin3A's broad biological activities beyond regulation of the p53 pathway, time-course gene expression profiling following mSin3A deletion revealed deregulation of genes involved in cell cycle regulation, DNA replication, DNA repair, apoptosis, chromatin modifications, and mitochondrial metabolism. Computational analysis of the mSin3A transcriptome using a knowledge-based database revealed several nodal points through which mSin3A influences gene expression, including the Myc-Mad, E2F, and p53 transcriptional networks. Further validation of these nodes derived from in silico promoter analysis showing enrichment for Myc-Mad, E2F, and p53 cis-regulatory elements in regulatory regions of up-regulated genes following mSin3A depletion. Significantly, in silico promoter analyses also revealed specific cis-regulatory elements binding the transcriptional activator Stat and the ISWI ATP-dependent nucleosome remodeling factor Falz, thereby expanding further the mSin3A network of regulatory factors. Together, these integrated genetic, biochemical, and computational studies demonstrate the

  18. Quantitative evaluation of DNA methylation patterns for ALVEs and TVB genes in a neoplastic disease susceptible and resistant chicken model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chicken endogenous virus, ALVE (Avian Leukosis Virus subgroup E), is inherited as LTR (long terminal repeat) retrotransposons, which is negatively correlated with fitness and disease resistance, and any changes in DNA methylation pattern may thus contribute to the susceptibility to neoplastic diseas...

  19. Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: morphologic and immunohistochemical findings and differential diagnosis.

    PubMed

    Huang, Pei-Wen; Chang, Kuo-Ming

    2015-01-01

    Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms' tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result. PMID:25885143

  20. Triple transformation

    NASA Astrophysics Data System (ADS)

    Khan, Farrukh I.; Schinn, Dustin S.

    2013-08-01

    A new business plan that enables policy transformation and resource mobilization at the national and international level, while improving access to resources, will allow the Green Climate Fund to integrate development goals and action on climate change.

  1. Covariant Transform

    NASA Astrophysics Data System (ADS)

    Kisil, Vladimir V.

    2011-03-01

    Dedicated to the memory of Cora Sadosky The paper develops theory of covariant transform, which is inspired by the wavelet construction. It was observed that many interesting types of wavelets (or coherent states) arise from group representations which are not square integrable or vacuum vectors which are not admissible. Covariant transform extends an applicability of the popular wavelets construction to classic examples like the Hardy space H2, Banach spaces, covariant functional calculus and many others.

  2. Hexon Modification to Improve the Activity of Oncolytic Adenovirus Vectors against Neoplastic and Stromal Cells in Pancreatic Cancer

    PubMed Central

    Lucas, Tanja; Benihoud, Karim; Vigant, Frédéric; Schmidt, Christoph Q. Andreas; Simmet, Thomas; Kochanek, Stefan

    2015-01-01

    Primary pancreatic carcinoma has an unfavourable prognosis and standard treatment strategies mostly fail in advanced cases. Virotherapy might overcome this resistance to current treatment modalities. However, data from clinical studies with oncolytic viruses, including replicating adenoviral (Ad) vectors, have shown only limited activity against pancreatic cancer and other carcinomas. Since pancreatic carcinomas have a complex tumor architecture and frequently a strong stromal compartment consisting of non-neoplastic cell types (mainly pancreatic stellate cells = hPSCs) and extracellular matrix, it is not surprising that Ad vectors replicating in neoplastic cells will likely fail to eradicate this aggressive tumor type. Because the TGFβ receptor (TGFBR) is expressed on both neoplastic cells and hPSCs we inserted the TGFBR targeting peptide CKS17 into the hypervariable region 5 (HVR5) of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. We demonstrated increased transduction of both pancreatic cancer cell lines and of hPSCs and enhanced cytotoxicity in co-cultures of both cell types. Surface plasmon resonance analysis demonstrated decreased binding of coagulation factor X to CKS17-modified Ad particles and in vivo biodistribution studies performed in mice indicated decreased transduction of hepatocytes. Thus, to increase activity of replicating Ad vectors we propose to relax tumor cell selectivity by genetic hexon-mediated targeting to the TGFBR (or other receptors present on both neoplastic and non-neoplastic cells within the tumor) to enable replication also in the stromal cell compartment of tumors, while abolishing hepatocyte transduction, and thereby increasing safety. PMID:25692292

  3. Synthesis, characterization, and in vitro anti-neoplastic activity of novel vic-dioximes bearing thiosemicarbazone side groups and their mononuclear complexes.

    PubMed

    Babahan, İlknur; Özmen, Ali; Orhan, Nil; Kazar, Didem; Değirmenci, Esin Hafize

    2014-04-01

    Two novel vicinal dioxime ligands containing thiosemicarbazone units, (2E)-2-[4-(diethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]hydrazine carbothioamide (L(1)H2) and (2E)-2-[4-(dimethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]hydrazinecarbothioamide (L(2)H2), were synthesized. Using the HL-60 human leukemia cell line, the in vitro anti-neoplastic activity of these thiosemicarbazone-oxime derivatives was evaluated. Mononuclear nickel(II), copper(II), and cobalt(II) complexes with a metal:ligand ratio of 1:2 for both the L(1)H2 and L(2)H2 ligands were also synthesized. To characterize these compounds, Fourier transform-infrared spectroscopy (FT-IR), mass spectrometry (MS), magnetic susceptibility measurements, (1)H and (13)C nuclear magnetic resonance (NMR), ultraviolet-visible (UV-Vis) absorption spectroscopy, heteronuclear multiple-bond correlation (HMQC), and elemental analysis were performed. For L(1)H2, L(2)H2, and each of their derivatives, antiproliferative effects against HL-60 cells were exhibited and the associated IpC50 values ranged from 5μM to 20μM. Furthermore, L(1)H2 and its derivatives inhibited the proliferation of HL-60 cells more effectively than L(2)H2, and 5μM [Cu(L(1)H)2] exhibited the strongest antiproliferative activity. PMID:24651042

  4. Chromosomal changes in cultured human epithelial cells transformed by low- and high-let radiation

    NASA Astrophysics Data System (ADS)

    Chui-Hsu Yang, Tracy; Craise, Laurie M.; Prioleau, John C.; Stampfer, Martha R.; Rhim, Johng S.

    1992-07-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude mice. Neoplastic transformation was achieved by irradiating cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level.

  5. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    NASA Technical Reports Server (NTRS)

    Craise, L. M.; Prioleau, J. C.; Stampfer, M. R.; Rhim, J. S.; Yang, TC-H (Principal Investigator)

    1992-01-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude mice. Neoplastic transformation was achieved by irradiating cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level.

  6. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    SciTech Connect

    Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

    1990-11-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs.

  7. SHARP transformation

    NASA Astrophysics Data System (ADS)

    Wyatt, Stephan

    2004-08-01

    The U.S. Navy"s SHAred Reconnaissance Pod (SHARP) employs the Recon/Optical, Inc. (ROI) CA-279 dual spectral band (visible/IR) digital cameras operating from an F-18E/F aircraft to perform low-to-high altitude reconnaissance missions. SHARP has proven itself combat worthy, with a rapid transition from development to operational deployment culminating in a highly reliable and effective reconnaissance capability for joint forces operating in Operation Iraqi Freedom (OIF). The U.S. Navy"s intelligence, surveillance and reconnaissance (ISR) roadmap transforms the SHARP system from being solely an independent reconnaissance sensor to a node in the growing Joint ISR network. ROI and the U.S. Navy have combined their resources to ensure the system"s transformation continues to follow the ISR road map. Pre-planned product improvements (P3I) for the CA-270 camera systems will lead the way in that transformation.

  8. Differential Roles of ERα and ERβ in Normal and Neoplastic Development in the Mouse Mammary Gland

    PubMed Central

    Mehta, Rajendra G.; Hawthorne, Michael; Mehta, Rajeshwari R.; Torres, Karen E. O.; Peng, Xinjian; McCormick, David L.; Kopelovich, Levy

    2014-01-01

    The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ. PMID:25405629

  9. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

    PubMed

    Aggarwal, Abhishek; Höbaus, Julia; Tennakoon, Samawansha; Prinz-Wohlgenannt, Maximilian; Graça, João; Price, Sally A; Heffeter, Petra; Berger, Walter; Baumgartner-Parzer, Sabina; Kállay, Enikö

    2016-01-01

    Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R-568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced differentiation and apoptosis only in cells with a functional CaSR, which were further enhanced in the presence of NPS R-568, a positive allosteric modulator of CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3 suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part, mediated by the CaSR. Taken together, our data provides molecular evidence to support the epidemiological observation that both, vitamin D and calcium are needed for protection against malignant transformation of the colon and that their effect is modulated by the presence of a functional CaSR. This article is part of a Special Issue

  10. Transformation Time

    ERIC Educational Resources Information Center

    Berry, John N., III

    2007-01-01

    The program for the march by librarians on America's capital for the American Library Association (ALA) conference is predictably loaded with lobbying, legislation, and DC tours. It also abounds with professional opportunity and reflects the impact of Leslie Burger, one of the most activist ALA presidents in recent history. Her "Transformation"…

  11. Transformation & Metamorphosis

    ERIC Educational Resources Information Center

    Lott, Debra

    2009-01-01

    The sculptures of Canadian artist Brian Jungen are a great inspiration for a lesson on creating new forms. Jungen transforms found objects into unique creations without fully concealing their original form or purpose. Frank Stella's sculpture series, including "K.132,2007" made of stainless steel and spray paint, is another great example of…

  12. Transforming Schools.

    ERIC Educational Resources Information Center

    Cookson, Peter W., Jr., Ed.; Schneider, Barbara, Ed.

    The authors in this book address the issues that relate to the crisis in American education and review some of the proposed solutions. To transform education, schools must be examined as social systems that are interrelated with families, communities, and the world of work. Following the introduction, section 1, "Conditions for Educational…

  13. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    SciTech Connect

    Price, Paul S. Keenan, Russell E.; Swartout, Jeffrey C.

    2008-11-15

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals.

  14. Photodynamic therapy and the treatment of neoplastic diseases of the head and neck: an update

    NASA Astrophysics Data System (ADS)

    Biel, Merrill A.

    1994-07-01

    Forty-nine patients with neoplastic diseases of the larynx, oral cavity, pharynx and tracheobronchial tree have been treated with photodynamic therapy with follow-up to 40 months. Those patients with primary recurrent leukoplakia, carcinoma-in-situ, and T1 carcinomas obtained a complete response after one photodynamic therapy (PDT) treatment and remain free of disease. Eight patients with T2 and T3 carcinomas treated with PDT obtained a complete or partial response, but in all cases, the carcinomas recurred locally, many times with overlying normal mucosa. This is due to the inability to adequately deliver laser light to the depths of the tumor bed, despite aggressive use of interstitial implantation. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. Further development of devices to measure and deliver light into the depths of a tumor bed are required prior to the use of PDT to effectively treat larger solid tumors of the head and neck.

  15. Expression of neural cell adhesion molecule in normal and neoplastic human neuroendocrine tissues.

    PubMed Central

    Jin, L.; Hemperly, J. J.; Lloyd, R. V.

    1991-01-01

    The neural cell adhesion molecule (N-CAM) is a group of cell surface glycoproteins involved in direct cell--cell adhesion. N-CAM expression in normal and neoplastic tissues was examined with specific antibodies and oligonucleotide probes by immunohistochemistry and in situ hybridization. Most neuroendocrine cells and tumors with secretory granules expressed N-CAM protein and mRNA. Parathyroid adenomas (4) were somewhat unusual, because N-CAM mRNA, but not protein, was detected in some of these benign neoplasms. Most non-neuroendocrine cells and tumors did not express N-CAM, although uterine smooth muscle and an adrenal cortical carcinoma were both positive. Western blots disclosed proteins of 180, 140, and 120 kd in normal adult brain, whereas two pheochromocytomas, a null cell adenoma, and a gastrinoma had proteins of approximately 180 and 140 kd. These results indicate that N-CAM protein and mRNA are widely expressed in neuroendocrine cells and neoplasms. N-CAM oligonucleotide probes as well as antibodies against N-CAM can be used as broad-spectrum neuroendocrine markers. In addition, these molecular probes can be used to examine the role of N-CAM in the development and regulation of neuroendocrine tissues. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2012179

  16. Malignant lymphoma presenting with neoplastic angioendotheliosis of the central nervous system.

    PubMed

    Yamamura, Y; Akamizu, H; Hirata, T; Kito, S; Hamada, T

    1983-01-01

    In this paper we report a case of malignant lymphoma with neoplastic angioendotheliosis in the brain. A 44-year-old man with transient episodes of deafness, hypersomnia, and anorexia over a 5-month period acutely deteriorated. He presented with low grade fever, dementia, frontal lobe signs, general hyperreflexia, muscle weakness of the extremities, and ataxia. He did not have hepatosplenomegaly, lymph node swelling, or skin eruptions. On the 15th day after admission to the hospital he developed convulsions and died. Post-mortem examination revealed multiple infarcts in the central nervous system, especially in the bilateral cerebral white matter and basal ganglia, where mononuclear tumor cells were widespread within the lumens of small blood vessels, accompanied by lymphocytic infiltration and degenerative and occulsive changes of the vessels. Intravascularly in many visceral organs and in the adrenal glands, both intra- and extravascularly, proliferation of tumor cells was observed. Furthermore, a small nest of malignant lymphoma of diffuse mixed cell type was found in a para-aortic lymph node, and the lymphoma cells were identical to tumor cells observed in the brain and other organs. PMID:6851298

  17. Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium

    PubMed Central

    Bartosch, Carla; Monteiro-Reis, Sara; Almeida-Rios, Diogo; Vieira, Renata; Castro, Armando; Moutinho, Manuel; Rodrigues, Marta; Graça, Inês

    2016-01-01

    Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models. PMID:26701732

  18. Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications.

    PubMed

    Helsten, Teresa; Schwaederle, Maria; Kurzrock, Razelle

    2015-09-01

    Fibroblast growth factors (FGFs) and their receptors (FGFRs) are transmembrane growth factor receptors with wide tissue distribution. FGF/FGFR signaling is involved in neoplastic behavior and also development, differentiation, growth, and survival. FGFR germline mutations (activating) can cause skeletal disorders, primarily dwarfism (generally mutations in FGFR3), and craniofacial malformation syndromes (usually mutations in FGFR1 and FGFR2); intriguingly, some of these activating FGFR mutations are also seen in human cancers. FGF/FGFR aberrations reported in cancers are mainly thought to be gain-of-function changes, and several cancers have high frequencies of FGFR alterations, including breast, bladder, or squamous cell carcinomas (lung and head and neck). FGF ligand aberrations (predominantly gene amplifications) are also frequently seen in cancers, in contrast to hereditary syndromes. There are several pharmacologic agents that have been or are being developed for inhibition of FGFR/FGF signaling. These include both highly selective inhibitors as well as multi-kinase inhibitors. Of note, only four agents (ponatinib, pazopanib, regorafenib, and recently lenvatinib) are FDA-approved for use in cancer, although the approval was not based on their activity against FGFR. Perturbations in the FGFR/FGF signaling are present in both inherited and malignant diseases. The development of potent inhibitors targeting FGF/FGFR may provide new tools against disorders caused by FGF/FGFR alterations. PMID:26224133

  19. Is there a relationship between spinal instability in neoplastic disease and Tokuhashi scoring system?

    PubMed

    de Oliveira, Matheus Fernandes; Rotta, Jose Marcus; Botelho, Ricardo Vieira

    2016-07-01

    Spinal instability neoplastic score (SINS) classification evaluates spinal stability by adding together six radiographic and clinical components. The objective of this study was to verify the association between SINS and Tokuhashi scoring system (TSS) score. Fifty-eight patients with vertebral metastases were admitted from 2010 to 2014 at Hospital do Servidor Público Estadual de São Paulo. They were evaluated according to their SINS and Tokuhashi SS score. Fourteen patients (24.13 %) scored from 0 to 6 points (stable spine), 37 (63.79 %) scored from 7 to 12 (potentially unstable), and 7 (12.06 %) scored from 13 to 18 (unstable). In stable spine patients according to SINS, the mean TSS score was 9.2. In potentially unstable spine patients, the mean TSS score was 8.24. In unstable spine patients, mean TSS score was 6.28. There was a statistically significant difference of the TSS score between stable and unstable patients. After evaluating TSS score in each patient, the worse the SINS, the worse was also the TSS score. PMID:26860530

  20. Effect of Pomegranate Hull Extract on Liver Neoplastic Changes in Rats: More than an Antioxidant.

    PubMed

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Abd El-Fattah, Eslam E

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. The current work was designed to elucidate the molecular mechanisms underlying the antitumorigenic effect of pomegranate hull extract (PHE) in livers of rats exposed to the hepatocarcinogen diethyl nitrosamine (DENA) with emphasis on oxidative stress, proliferation, and apoptosis. Male albino rats were divided into three groups: normal control, DENA group, and PHE group. PHE was given to rats orally 3 times weekly for 10 wk, 4 wk before and 6 wk after DENA (200 mg/kg, single i.p. dose). The results indicated a prophylactic effect of PHE against neoplastic changes in the liver, which was evidenced by the decrease of tumor size, liver index, and the anti-apoptotic protein Bcl-2; and the increase of glutathione. PHE group also showed decreased expression of liver cyclin D1 and β-catenin genes compared with DENA group. It is proved that PHE has antitumorigenic effect and could be a candidate for anticancer drugs. PMID:27383944

  1. Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues.

    PubMed

    Millanta, F; Calandrella, M; Bari, G; Niccolini, M; Vannozzi, I; Poli, A

    2005-12-01

    Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours. PMID:16054892

  2. Ultrasonographic Differentiation Between Nodular Hyperplasia and Neoplastic Follicular-Patterned Lesions of the Thyroid Gland.

    PubMed

    Song, Yong Sub; Kim, Ji-Hoon; Na, Dong Gyu; Min, Hye Sook; Won, Jae-Kyung; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho

    2016-08-01

    We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs. PMID:27166018

  3. Human papillomavirus infection in non-neoplastic uterine cervical disease in Hong Kong.

    PubMed

    Lee, C N; Cavanagh, H M; Lo, S T; Ng, C S

    2001-01-01

    The polymerase chain reaction (PCR) was used to detect and identify human papillomavirus (HPV) in 108 cases of formalin-fixed, paraffin-embedded, non-neoplastic uterine cervical biopsy tissue retrieved from the surgical pathology archives of the Department of Pathology, Caritas Medical Centre, Hong Kong. After DNA extraction, HPV L1 gene primers were used to detect the presence of HPV, and type-specific primers (to HPV types 6, 11, 16, 18, 31 and 33) were used to identify the specific HPV type on HPV L1-positive cases. PCR amplification of the beta-globin gene was used to ensure the quality of amplifiable DNA extracted. Of 94 cases that yielded sufficient good-quality DNA for PCR analysis, three (one endocervical polyp, one chronic inflammation with erosion, and a normal biopsy) had detectable HPV infection. Two of these had high-risk HPV type 16; the other had an uncommon HPV type. In view of the low incidence of HPV found in these patients, large-scale population screening of clinical samples using PCR to detect the presence of HPV and identify high-risk asymptomatic patients would not be cost-effective. PMID:11440211

  4. [Experience in the use of Broviac catheters in children with hematologic neoplastic diseases].

    PubMed

    Swiatkiewicz, V; Molski, S; Wysocki, M; Jundziłł, W; Hryncewicz, W; Pilecki, O

    1996-08-01

    Between 1990 and 1994, 61 Broviac catheters were implanted in 53 children with haematological neoplastic diseases. The mean duration of catheter function was 206 days (range 14-615 days). The total observation time was 12544 days, during which 84 catheter-related complications were recorded, i.e. 6.7 per 1000 catheter use days. Infections occurred with a frequency of 3.8 episodes/1000 cath, days, the majority of which were bacteriemias (2.6/1000 cath, days). Gram-positive and Gram-negative strains were the isolated etiologic agents with equal frequency. Most of infectious episodes (85%) responded well to initial empiric antibiotics treatment without removal of the catheters. Mechanica complications (occlusion, displacement or catheter leakage) occurred significant less frequently and were managed by repairing or replacing the device or clearing the block. No deaths were related to catheter complications. In conclusion indwelling Broviac catheters offer a safe and effective method of long-term venous access. Infections are the most frequent catheter-related complications. PMID:8927470

  5. Expression pattern of FCRL (FREB, FcRX) in normal and neoplastic human B cells.

    PubMed

    Masir, Noraidah; Jones, Margaret; Pozzobon, Michela; Marafioti, Teresa; Volkova, Olga Y; Mechetina, Ludmila V; Hansmann, Martin-Leo; Natkunam, Yasodha; Taranin, Alexander V; Mason, David Y

    2004-11-01

    FCRL (also known as FREB and FcRX) is a recently described member of the family of Fc receptors for immunoglobulin G (IgG). In the present study we analysed its expression in normal and neoplastic lymphoid tissue using immunohistochemical techniques. FCRL was preferentially expressed in a proportion of germinal centre cells and, more weakly, in mantle zone B cells. In addition, strong labelling was observed in marginal zone B cells in the spleen, representing one of the few markers for this cell type. The majority of cases of small B-cell lymphoma, diffuse large B-cell lymphoma and lymphocyte predominance Hodgkin's disease were positive for FCRL. However, the number of positive cells varied widely, and in consequence we could not define a cut-off that distinguished subsets of diffuse large B-cell lymphoma. Our results also showed that FCRL tended to be negative in T-cell-rich B-cell lymphoma and in classical Hodgkin's disease. FCRL may therefore represent a novel marker for normal B cells (e.g. splenic marginal zone cells) and may also be useful as a potential marker of B-cell neoplasms. PMID:15491296

  6. High-fidelity DNA histograms in neoplastic progression in Barrett's esophagus.

    PubMed

    Yu, Chenggong; Zhang, Xiaoqi; Huang, Qin; Klein, Michael; Goyal, Raj K

    2007-05-01

    This study describes the high-fidelity DNA histograms in different stages of neoplastic progression to Barrett's adenocarcinoma (BAC). High-fidelity DNA histograms were obtained with image cytometry on sections, and were classified based on DNA index values of the peaks into diploid, mild aneuploid, moderate aneuploid and severe aneuploid. Heterogeneity index (HI) representing cells with different DNA content and the 5N exceeding cell fraction were determined. One hundred and eighty-seven cases, including 34 normal gastrointestinal mucosa (control), 66 Barrett's-specialized intestinal metaplasia (SIM), 22 low-grade dysplasia (LGD), 22 high-grade dysplasia (HGD) and 43 BAC were investigated. Controls showed sharp diploid peaks with HI values less than 13, and no 5N exceeding nuclei. SIM showed a spectrum of histograms including diploid, mild aneuploid and moderate aneuploid histograms. The frequency and severity of aneuploidy increased with worsening histological grades of dysplasia. All BAC cases were aneuploid, with moderate or severe aneuploidy. Marked elevated HI values (>20) and 5N exceeding fractions (>5%) were found in 5%, 32%, 50% and 88% of cases with SIM, LGD, HGD and BAC, respectively. The high-fidelity DNA histograms suggest that (1) Barrett's SIM may already be dysplastic in nature, and all BAC may be markedly aneuploid; and (2) elevated cellular DNA heterogeneity and 5N fractions may be markers of progressive chromosomal changes and 'unstable aneuploidy' that identifies progressive lesions. PMID:17310216

  7. Immunotherapy with CpG-ODN in neoplastic meningitis: A phase I trial.

    PubMed

    Ursu, Renata; Taillibert, Sophie; Banissi, Claire; Vicaut, Eric; Bailon, Olivier; Le Rhun, Emilie; Guillamo, Jean-Sebastien; Psimaras, Dimitri; Tibi, Annick; Sacko, Adama; Marantidou, Athina; Belin, Catherine; Carpentier, Antoine F

    2015-09-01

    TLR-9 agonists are immunostimulating agents that have antitumor effects in animal models. A phase I trial was conducted to define the safety profile of subcutaneous injections, combined with intrathecally administration of CpG-28, a TRL 9 agonist, in patients with neoplastic meningitis (NM). Cohorts of 3-6 patients with NM were treated for 5 weeks with escalating doses of CpG-28. The primary endpoint was tolerance. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Twenty-nine patients were treated with CpG-28. The primary cancers were malignant glioma, lung carcinoma, breast cancer, melanoma or melanocytoma, ependymoma, and colorectal cancer. The median age was 56 years and median Karnovsky Performance status (KPS) was 70%. The treatment was well tolerated. Adverse effects that were possibly or probably related to the studied drug were grade 2 lymphopenia, anemia and neutropenia, local erythema at injection sites, fever and seizure. There were five serious adverse events: two confusions, two infections of ventricular devices and one grade 4 thrombopenia and neutropenia. The median PFS was 7 weeks and median OS was 15 weeks. Interestingly, the median survival was slightly (but not significantly) higher in the eight patients who were concomitantly treated with bevacizumab (19 weeks vs 15 weeks; P = 0.11). CpG-28 was well tolerated at doses up to 0.3 mg/kg subcutaneously and 18 mg intrathecally. Additional trials are warranted. PMID:26094710

  8. Automatic segmentation of histological structures in normal and neoplastic mammary gland tissue sections

    SciTech Connect

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravi; Ortiz de Solorzano, Carlos

    2003-01-18

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a ''phantom.'' Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  9. Automatic segementation of histological structures in normal and neoplastic mammary gland tissue sections

    NASA Astrophysics Data System (ADS)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam; Malladi, Ravikanth; Ortiz de Solorzano, Carlos

    2003-07-01

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a "phantom." Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  10. Evidence for clonal origin of neoplastic neuronal and glial cells in gangliogliomas.

    PubMed Central

    Zhu, J. J.; Leon, S. P.; Folkerth, R. D.; Guo, S. Z.; Wu, J. K.; Black, P. M.

    1997-01-01

    Gangliogliomas are rare tumors of the central nervous system that account for approximately 1% of all brain tumors. Histologically, gangliogliomas are composed of intimately admixed glial and neuronal components, the pathological origins of which remain to be characterized. Clonal analysis through examination of the pattern of the X chromosome inactivation allows one to distinguish monoclonal differentiation of a genetically abnormal progenitor cell from parallel, but independent, clonal expansion of two different cell types during tumorigenesis in biphasic neoplasms, such as gangliogliomas. In the present study, we investigated the clonality of eight gangliogliomas from female patients using both methylation- and transcription-based clonality assays at the androgen receptor locus (HUMARA) on the X chromosome. Among tumors from seven patients who were heterozygous at the HUMARA locus, five were identified as monoclonal with the methylation-based clonality assay, and the results were confirmed by the transcription-based method, whereas two were shown to be polyclonal by the methylation-based clonality assay but monoclonal by transcription-based clonality analysis. We conclude that the predominant cell types in most gangliogliomas are monoclonal in origin and derive from a common precursor cell that subsequently differentiates to form neoplastic glial and neuronal elements. Images Figure 2 Figure 3 PMID:9250169

  11. Liposomal cytarabine in neoplastic meningitis from primary brain tumors: a single institutional experience.

    PubMed

    Gaviani, P; Corsini, E; Salmaggi, A; Lamperti, E; Botturi, A; Erbetta, A; Milanesi, I; Legnani, F; Pollo, B; Silvani, A

    2013-12-01

    Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte(®). In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte(®) regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte(®) (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte(®) cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte(®), and the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %). PMID:23525755

  12. [The value of fine needle aspiration cytology in suspected neoplastic salivary gland enlargement].

    PubMed

    Schoengen, A; Binder, T; Krause, H R; Stussak, G; Zeelen, U

    1995-04-01

    Imaging offers little support in the management of salivary gland masses suggestive of a neoplastic lesion. There are also contraindications for a surgical biopsy in many cases. Fine-needle aspiration cytology (FNAC) is not yet widely recognized as a diagnostic tool. To date, 206 FNAC were carried out from 1986 through 1993 on 181 consecutive patients and were reviewed in the present study. Histological confirmation was possible in 174 tests, while 32 were confirmed on clinical follow-up. In sum, 192 samples were sufficient for interpretation, 10 were questionable by our standards and 4 were non-diagnostic. One hundred-seventy-one samples were true-negative, 27 true-positive, 4 false-negative and 4 false-positive. Sensitivity was 87.1% and specificity 97.7%. Out of 141 primary diagnostic procedures in which a final histologic diagnosis was available, FNAC was able to determine histogenesis in 113/124 benign lesions and 9/17 malignant masses. These included 65/67 pleomorphic adenomas and 21/22 adenolymphomas. In 8 cases a diagnosis of "adenoma" was made. Difficulties in interpretation were found in lesions that were mucoepidermoid carcinomas and, in part, adenoid cystic carcinomas. No complications occurred. Provided that there was sufficient experience in performing the aspiration technique and in cytologic interpretation, FNAC was found to be a quick, reliable, low-cost, easy-to-perform method with low risk in the management of nearly all benign and most malignant salivary gland lesions. PMID:7790235

  13. Autophagy in malignant transformation and cancer progression

    PubMed Central

    Galluzzi, Lorenzo; Pietrocola, Federico; Bravo-San Pedro, José Manuel; Amaravadi, Ravi K; Baehrecke, Eric H; Cecconi, Francesco; Codogno, Patrice; Debnath, Jayanta; Gewirtz, David A; Karantza, Vassiliki; Kimmelman, Alec; Kumar, Sharad; Levine, Beth; Maiuri, Maria Chiara; Martin, Seamus J; Penninger, Josef; Piacentini, Mauro; Rubinsztein, David C; Simon, Hans-Uwe; Simonsen, Anne; Thorburn, Andrew M; Velasco, Guillermo; Ryan, Kevin M; Kroemer, Guido

    2015-01-01

    Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy. PMID:25712477

  14. The genetic/metabolic transformation concept of carcinogenesis

    PubMed Central

    Franklin, Renty B.

    2014-01-01

    The carcinogenesis process is poorly understood and subject to varying concepts and views. A rejuvenated interest has arisen regarding the role of altered cellular intermediary metabolism in the development and progression of cancer. As a result, differing views of the implications of altered metabolism in the development of cancer exist. None of the concepts recognize and incorporate the principles of cell metabolism to cell activity, which are applicable to all cells including the carcinogenesis process. This presentation incorporates a novel concept of carcinogenesis that includes a “genetic/metabolic” transformation that encompasses these principles of cell metabolism to cell activity. The intermediary metabolism transformation is essential to provide the bioenergetic/ synthetic, growth/proliferation, and migration/invasive events of malignancy. The concept invokes an “oncogenetic transformation” for the development of neoplastic cells from their precursor normal cells; and a required “genetic/metabolic” transformation for facilitation of the development of the neoplastic cells to malignant cells with the manifestation of the malignant process. Such a concept reveals stages and events of carcinogenesis that provide approaches for the identification of biomarkers and for development of therapeutic agents. The presentation discusses the contemporary application of genetics and proteomics to altered cellular metabolism in cancer; and underscores the importance of proper integration of genetics and proteomics with biochemical and metabolic studies, and the consequences of inappropriate studies. PMID:22109079

  15. Cell-block procedure in endoscopic ultrasound-guided-fine-needle-aspiration of gastrointestinal solid neoplastic lesions

    PubMed Central

    Ieni, Antonio; Barresi, Valeria; Todaro, Paolo; Caruso, Rosario Alberto; Tuccari, Giovanni

    2015-01-01

    In the present review we have analyzed the clinical applications of endoscopic ultrasound-guided-fine-needle-aspiration (EUS-FNA) and the methodological aspects obtained by cell-block procedure (CBP) in the diagnostic approach to the gastrointestinal neoplastic pathology. CBP showed numerous advantages in comparison to the cytologic routine smears; in particular, better preservation of cell architecture, achievement of routine haematoxylin-eosin staining equivalent to histological slides and possibility to perform immunohistochemistry or molecular analyses represented the most evident reasons to choose this method. Moreover, by this approach, the differential diagnosis of solid gastrointestinal neoplasias may be more easily achieved and the background of contaminant non-neoplastic gastrointestinal avoided. Finally, biological samples collected by EUS-FNA CBP-assisted should be investigated in order to identify and quantify further potential molecular markers. PMID:26322154

  16. Clinical value of pathologic examination of non-neoplastic kidney in patients with upper urinary tract malignancies

    PubMed Central

    Wee, Jee Wan; Kang, Hye Ran; Kwon, Soon Hyo; Jeon, Jin Seok; Han, Dong Cheol; Jin, So-Young; Yang, Won Jae; Noh, Hyunjin

    2016-01-01

    Background/Aims: While surgical resection remains the standard of care in the treatment of upper urinary tract malignancies, nephrectomy is a risk factor for the development of chronic kidney disease (CKD). The aim of this study was to determine whether histologic evaluation of non-neoplastic kidney could enable early identification of unrecognized kidney disease and could be of prognostic value in predicting postoperative renal outcomes. Methods: We retrospectively analyzed 51 patients with upper urinary tract malignancies who received uninephrectomy or uninephroureterectomy. A thorough pathologic evaluation of non-neoplastic kidney including special stains, immunofluorescence, and electron microscopic studies was performed. The degree of parenchymal changes was graded from 0 to 15. Results: Of 51 patients, only 13 showed normal kidney pathology. Fifteen patients showed glomerular abnormalities, 14 showed diabetic nephropathy, and 11 showed vascular nephropathy. There was one case each of reflux nephropathy and chronic pyelonephritis. The median histologic score was 5 points. Only 25.4% of patients had ≤ 3 points. Score more than 5 was observed in 47.1% of patients. Postoperative estimated glomerular filtration rate (eGFR) at 3 to 36 months were obtained from 90.2% of patients, and of those, 34.8% had de novo CKD. Since no one had CKD in partial nephrectomized patients, we determined risk factors for CKD in radical nephrectomized patients. Cox regression analysis revealed that postoperative AKI, preoperative eGFR, and histologic score of non-neoplastic kidney were the independent predictors for CKD. Conclusions: We conclude that routine pathologic evaluation of non-neoplastic kidney provides valuable diagnostic and prognostic information. PMID:27237301

  17. Therapeutic and toxicologic evaluation of anti-lipogenic agents in cancer cells compared with non-neoplastic cells.

    PubMed

    Deepa, Perinkulam Ravi; Vandhana, Suryanarayanan; Jayanthi, Udayakumar; Krishnakumar, Subramanian

    2012-06-01

    Fatty acid synthase (FASN), a multi-enzyme complex, is involved in lipid biosynthesis. FASN is over-expressed in different types of cancers and is being widely investigated for its role in cancer progression, diagnosis and therapy. Here, three inhibitors targeting different domains of FASN--cerulenin, triclosan and orlistat--were evaluated for their anti-proliferative efficacy in ocular cancer, retinoblastoma (RB) cells and their toxicity (if any) in normal cells. FASN inhibitors were tested in cultured retinoblastoma Y79 cells, normal fibroblast (3T3) and Müller glial (MIOM1) cells. Cell viability was determined by MTT-based assay, and IC(50) (50% inhibitory concentration) of the FASN inhibitors was calculated in neoplastic and non-neoplastic cells. The IC(50) after 48 and 96 hr of incubation with the three anti-FASN agents showed that cerulenin, triclosan and orlistat inhibited retinoblastoma cell proliferation in a dose- and time-dependent manner. The cancer cells exhibited differential dose- and time-dependent response/sensitivities to cerulenin, triclosan and orlistat. The 48-hr neoplastic IC(50) dosages were, however, not toxic to the normal cells. These findings were confirmed by phase-contrast microscopic assessment of cell morphology. Therapeutic index (TI) was calculated as a ratio of the IC(50) normal cells, to the IC(50) neoplastic cells. Relative to normal MIOM1 cells, TI was 9.18 for cerulenin, while 5.32 for triclosan and 1.72 for orlistat. The TI computed relative to 3T3 cells was 28.64, 7.10 and 2.58 for cerulenin, triclosan and orlistat, respectively. DNA fragmentation analysis suggests that FASN inhibitors induced apoptotic DNA damage in retinoblastoma cells. Thus, FASN inhibition can be an effective strategy in retinoblastoma therapy. PMID:22151915

  18. A Fuzzy-C-Means-Clustering Approach: Quantifying Chromatin Pattern of Non-Neoplastic Cervical Squamous Cells

    PubMed Central

    Tang, Jing Rui; Mat Isa, Nor Ashidi; Ch’ng, Ewe Seng

    2015-01-01

    Despite the effectiveness of Pap-smear test in reducing the mortality rate due to cervical cancer, the criteria of the reporting standard of the Pap-smear test are mostly qualitative in nature. This study addresses the issue on how to define the criteria in a more quantitative and definite term. A negative Pap-smear test result, i.e. negative for intraepithelial lesion or malignancy (NILM), is qualitatively defined to have evenly distributed, finely granular chromatin in the nuclei of cervical squamous cells. To quantify this chromatin pattern, this study employed Fuzzy C-Means clustering as the segmentation technique, enabling different degrees of chromatin segmentation to be performed on sample images of non-neoplastic squamous cells. From the simulation results, a model representing the chromatin distribution of non-neoplastic cervical squamous cell is constructed with the following quantitative characteristics: at the best representative sensitivity level 4 based on statistical analysis and human experts’ feedbacks, a nucleus of non-neoplastic squamous cell has an average of 67 chromatins with a total area of 10.827μm2; the average distance between the nearest chromatin pair is 0.508μm and the average eccentricity of the chromatin is 0.47. PMID:26560331

  19. Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Zhang, Weiying; Nandakumar, Nivedita; Shi, Yuhao; Manzano, Mark; Smith, Alias; Graham, Garrett; Gupta, Swati; Vietsch, Eveline E.; Laughlin, Sean Z.; Wadhwa, Mandheer; Chetram, Mahandranauth; Joshi, Mrinmayi; Wang, Fen; Kallakury, Bhaskar; Toretsky, Jeffrey; Wellstein, Anton; Yi, Chunling

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, KRAS has thus far not been a viable therapeutic target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), a protein regulated by the Hippo pathway during tissue development and homeostasis, was increased in human PDAC tissue compared with that in normal pancreatic epithelia. In genetically engineered KrasG12D and KrasG12D: Trp53R172H mouse models, pancreas-specific deletion of Yap halted the progression of early neoplastic lesions to PDAC without affecting normal pancreatic development and endocrine function. Although Yap was dispensable for acinar to ductal metaplasia (ADM), an initial step in the progression to PDAC, Yap was critically required for the proliferation of mutant Kras or Kras:Trp53 neoplastic pancreatic ductal cells in culture and for their growth and progression to invasive PDAC in mice. Yap functioned as a critical transcriptional switch downstream of the oncogenic KRAS–mitogen-activated protein kinase (MAPK) pathway, promoting the expression of genes encoding secretory factors that cumulatively sustained neoplastic proliferation, a tumorigenic stromal response in the tumor microenvironment, and PDAC progression in Kras and Kras: Trp53 mutant pancreas tissue. Together, our findings identified Yap as a critical oncogenic KRAS effector and a promising therapeutic target for PDAC and possibly other types of KRAS-mutant cancers. PMID:24803537

  20. Antigen expression in normal and neoplastic canine tissues defined by a monoclonal antibody generated against canine mesothelioma cells.

    PubMed

    Liu, K X; Bird, A E; Lenz, S D; McDonough, S P; Wolfe, L G

    1994-11-01

    Monoclonal antibody (MAb) 3B5 generated against canine mesothelioma cells was applied to canine tumors and normal tissues via immunohistochemical and immunoblotting techniques to evaluate antigen binding. By use of an avidin-biotin immunoperoxidase complex (ABC) method, immunoreactivity was noted in reactive mesothelial cells and in normal tissues was observed primarily in mesothelial cell linings, endothelial cells, and smooth muscle of blood vessels and soft tissues; the reactivity was nearly equivalent in frozen or formalin-fixed, paraffin-embedded tissue sections. Use of the ABC method on formalin-fixed, paraffin-embedded tumors yielded moderate to strong cytoplasmic immunostaining of neoplastic cells in 10/11 (91%) mesotheliomas, 18/23 (78%) hemangiosarcomas, 4/10 (40%) intestinal and lung carcinomas, and < or = 20% of hemangiomas, leiomyosarcomas, leiomyomas, mammary carcinomas, and squamous cell carcinomas. No immunostaining of tumor cells was observed in fibrosarcomas, hemangiopericytomas, perianal gland carcinomas, and melanomas. Immunoblotting was performed on samples that demonstrated strong immunoreactivity with MAb 3B5 by the ABC method: mesothelioma, hemangiosarcoma, urinary bladder (smooth muscle), and lung (alveolar capillaries). These analyses showed that MAb 3B5 bound a major antigen of 78 kilodaltons (kd) and minor antigens at 56 and 54 kd in normal and neoplastic tissues. The preliminary immunohistochemical results suggest that MAb 3B5 may possess utility in diagnosis of mesotheliomas and hemangiosarcomas, discrimination of cell types in proliferative serosal lesions, and demonstration of vascularity or angiogenesis in neoplastic and inflammatory lesions. PMID:7863582

  1. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer

    PubMed Central

    Antonio, Nicole; Bønnelykke-Behrndtz, Marie Louise; Ward, Laura Chloe; Collin, John; Christensen, Ib Jarle; Steiniche, Torben; Schmidt, Henrik; Feng, Yi; Martin, Paul

    2015-01-01

    There is a long-standing association between wound healing and cancer, with cancer often described as a “wound that does not heal”. However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of RasG12V-driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre-neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre-neoplastic cells and these interactions lead to increased proliferation of the pre-neoplastic cells. One of the wound-inflammation-induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome. PMID:26136213

  2. The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer.

    PubMed

    Antonio, Nicole; Bønnelykke-Behrndtz, Marie Louise; Ward, Laura Chloe; Collin, John; Christensen, Ib Jarle; Steiniche, Torben; Schmidt, Henrik; Feng, Yi; Martin, Paul

    2015-09-01

    There is a long-standing association between wound healing and cancer, with cancer often described as a "wound that does not heal". However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of Ras(G12V)-driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre-neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre-neoplastic cells and these interactions lead to increased proliferation of the pre-neoplastic cells. One of the wound-inflammation-induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome. PMID:26136213

  3. Effect of carcinogen release rate on the incidence of preneoplastic and neoplastic lesions of the respiratory tract epithelium in rats

    SciTech Connect

    Shiba, M.; Klein-Szanto, A.J.P.; Marchok, A.C.; Pal, B.C.; Nettesheim, P.

    1982-11-01

    Inbred F344 rat tracheal transplants were exposed to 7,12-dimethylbenz(a)anthracene (DMBA) delivered at different release rates from intraluminal pellets made of various matrices to study the effect of carcinogen dose rate on the induction of lesions in the epithelium. These matrices were beeswax, beeswax-stearyl alcohol, and beeswax-cholesterol. In addition, DMBA adsorbed onto carbon particles was dispersed in beeswax-stearyl alcohol. The fastest release was obtained from beeswax pellets from which 99% of the carcinogen (198 ..mu..g) was released in 4 weeks, and the slowest release was from DMBA adsorbed on carbon at a ratio of 1:9 from which only 56% (113 ..mu..g) was released in 16 weeks. Morphometry of histologic sections showed marked differences in the percentage of luminal surface covered by dysplastic-neoplastic epithelium (i.e., 7.5% in the tracheas exposed to the fastest releasing pellets and 46.3% in the tracheas exposed to the slowest releasing pellets). An inverse linear correlation was found between the cumulative amount of DMBA release from the different pellet matrices at 2 weeks and the incidence of dysplastic plus neoplastic lesions of tracheal epithelium at 16 weeks. The results indicated that lower doses of carcinogen delivered slowly are more effective in producing dysplastic plus neoplastic lesions than higher doses delivered rapidly.

  4. Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm

    PubMed Central

    Kajdos, Magdalena; Janas, Łukasz; Kolasa-Zwierzchowska, Dorota; Wilczyński, Jacek R.

    2015-01-01

    Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs’ release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients’ serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease. PMID:26848301

  5. RF transformer

    DOEpatents

    Smith, James L.; Helenberg, Harold W.; Kilsdonk, Dennis J.

    1979-01-01

    There is provided an improved RF transformer having a single-turn secondary of cylindrical shape and a coiled encapsulated primary contained within the secondary. The coil is tapered so that the narrowest separation between the primary and the secondary is at one end of the coil. The encapsulated primary is removable from the secondary so that a variety of different capacity primaries can be utilized with one secondary.

  6. A novel autoantibody test for the detection of pre-neoplastic lung lesions

    PubMed Central

    2014-01-01

    Background Atypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung. Accurate diagnosis of AAH and SCD could facilitate earlier clinical intervention and provide useful information for assessing lung cancer risk in human populations. Detection of AAH and SCD has been achieved by imaging and bronchoscopy clinically, but sensitivity and specificity remain less than satisfactory. We utilized the ability of the immune system to identify lesion specific proteins for detection of AAH and SCD. Methods AAH and SCD tissue was surgically removed from six patients of Chinese descent (3 AAH and 3 SCD) with corresponding serum samples. Total RNA was extracted from the tissues and a cDNA library was generated and incorporated into a T7 bacteriophage vector. Following enrichment to remove "normal" reactive phages, a total of 200 AAH related and 200 SCD related phage clones were chosen for statistical classifier development and incorporation into a microarray. Microarray slides were tested with an independent double-blinded population consisting of 100 AAH subjects, 100 SCD subjects and 200 healthy control subjects. Results Sensitivity of 82% and specificity of 70% were achieved in the detection of AAH using a combination of 9 autoantibody biomarkers. Likewise, 86% sensitivity and 78% specificity were achieved in the detection of SCD using a combination of 13 SCD-associated markers. Sequencing analysis identified that most of these 22 autoantibody biomarkers had known malignant associations. Conclusions Both diagnostic values showed promising sensitivity and specificity in detection of pre-neoplastic lung lesions. Hence, this technology could be a useful non-invasive tool to assess lung cancer risk in human populations. PMID:24708840

  7. Immunotherapy with CpG-ODN in neoplastic meningitis: A phase I trial

    PubMed Central

    Ursu, Renata; Taillibert, Sophie; Banissi, Claire; Vicaut, Eric; Bailon, Olivier; Le Rhun, Emilie; Guillamo, Jean-Sebastien; Psimaras, Dimitri; Tibi, Annick; Sacko, Adama; Marantidou, Athina; Belin, Catherine; Carpentier, Antoine F

    2015-01-01

    TLR-9 agonists are immunostimulating agents that have antitumor effects in animal models. A phase I trial was conducted to define the safety profile of subcutaneous injections, combined with intrathecally administration of CpG-28, a TRL 9 agonist, in patients with neoplastic meningitis (NM). Cohorts of 3–6 patients with NM were treated for 5 weeks with escalating doses of CpG-28. The primary endpoint was tolerance. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Twenty-nine patients were treated with CpG-28. The primary cancers were malignant glioma, lung carcinoma, breast cancer, melanoma or melanocytoma, ependymoma, and colorectal cancer. The median age was 56 years and median Karnovsky Performance status (KPS) was 70%. The treatment was well tolerated. Adverse effects that were possibly or probably related to the studied drug were grade 2 lymphopenia, anemia and neutropenia, local erythema at injection sites, fever and seizure. There were five serious adverse events: two confusions, two infections of ventricular devices and one grade 4 thrombopenia and neutropenia. The median PFS was 7 weeks and median OS was 15 weeks. Interestingly, the median survival was slightly (but not significantly) higher in the eight patients who were concomitantly treated with bevacizumab (19 weeks vs 15 weeks; P = 0.11). CpG-28 was well tolerated at doses up to 0.3 mg/kg subcutaneously and 18 mg intrathecally. Additional trials are warranted. PMID:26094710

  8. Promotional effects of CO2 laser on neoplastic lesions in hamsters

    NASA Astrophysics Data System (ADS)

    Kingsbury, Jeffrey S.; Margarone, Joseph E., III; Satchidanand, S.; Liebow, Charles

    1991-06-01

    Surgical incision may have promotional effects on neoplastic lesions, possibly through release of tissue growth factors (e.g., EGF, FGF(beta) , IGF, TGF(alpha) ). The CO2 laser may precipitate altered release of these factors. To test this, .5 cm laser, and scalpel incisions were made into fields treated by application of .5% DMBA in acetone, 3 times a week for 6 weeks (group 1) and 12 weeks (group 2). DMBA is a complete carcinogen (initiator and promoter). At 6 weeks, chemically, but not histologically, definable premalignant lesions are seen. Treatment for 12 weeks causes histologic neoplasia which can be graded with T-N-M classification. For both groups, the surgical sites were examined clinically and histologically 4 weeks post-op in a blind fashion. Standard criteria were utilized for defining neoplasia. For group 1, 3 out of 6 laser treated animals developed large exophytic squamous cell carcinomas, but no lesions developed in 12 contralateral, 3 control and 3 scalpel treated pouches. For group 2, 12 of 16 laser treated animals developed tumor with mean grade of 1.75 and mean size of 7.4 mm, 5 of 6 scalpel treated animals developed tumor with mean grade of 1.83 and mean size of 3.6 mm and 3 of 6 control animals developed tumor with mean grade of 1.00 and mean size of 1.5 mm. By the Student 't' test on the binomial distribution lasers cause significant promotion (p < .01). These results suggest that laser surgery may have earlier and more profound promotional effects than scalpel on initiated cells relative to tumor size in the vicinity of the wound site by increased release of growth factors.

  9. Expression of p53 in preneoplastic and early neoplastic bronchial lesions.

    PubMed

    Martin, B; Verdebout, J-M; Mascaux, C; Paesmans, M; Rouas, G; Verhest, A; Ninane, V; Sculier, J-P

    2002-01-01

    p53 alteration has been reported to be an early event in bronchial carcinogenesis. Our study purpose was to determine the rate of p53 expression in the various preneoplastic and early neoplastic bronchial lesions obtained by biopsy during fluorescence bronchoscopy and to analyse its association with patients characteristics. Various stages of preneoplastic lesions as well as radio-occult lung cancer were studied in biopsies obtained by fluorescence bronchoscopy. We assessed the expression of p53 by immunohistochemistry using monoclonal antibody clone DO7. The p53 expression was considered as positive if > or = 1% of cells were positive and the level of positivity was expressed in percentage of positive cells. Fourteen patients were included in each category of preneoplastic lesions. At the threshold of 1% of positive cells p53 expression was observed in 28.5% of the patients with a histologically normal epithelium. This number of positive patients increased with the severity of preneoplastic lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia, carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4, 9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant correlation between p53 expression and patient characteristics such as sex, age, smoking habits and indication for fluorescence bronchoscopy. The alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics. PMID:11836584

  10. Detection of aryl hydrocarbon hydroxylase activity in normal and neoplastic human breast epithelium

    SciTech Connect

    Greiner, J.W.; Malan-Shibley, L.B.; Janss, D.H.

    1980-01-28

    Studies were conducted to determine whether normal and/or neoplastic (MCF-7) human breast epithelial cells contain the microsomal aryl hydrocarbon hydroxylase (AHH) which catalyses the conversion of polycyclic aromatic hydrocarbons (PAH) to carcinogenic intermediates. Low constitutive levels of AHH activity were found in homogenates of both normal human breast epithelial and MCF-7 cells. The addition of 7,12-dimethylbenz(a)anthracene (DMBA) to the culture medium of either cell type significantly increased AHH activity. Peak induction of hydroxylase activity occurred following the in vitro addition of 10 ..mu..M DMBA. A time course of DMBA-induced AHH activity in both normal human breast epithelium and MCF-7 cells revealed maximal induction 16 hr after 10 ..mu..M DMBA was added to the culture medium. Benzo(a)pyrene (BP), 3-methylcholanthrene (MCA) and benz(a)anthracene (BA) also induced AHH activity in normal and MCF-7 cells. For example, the addition of 10 ..mu..M BP to the culture medium of either normal human breast epithelial or MCF-7 cells for 16 hr increased AHH activity 13.8 and 65.3-fold, respectively. For all PAH, the magnitude of AHH induction was substantially greater in MCF-7 than normal breast epithelial cells. Finally, ..cap alpha..-naphthoflavone inhibited BA-induced AHH activity in MCF-7 cells. The study demonstrates the presence of a PAH-inducible AHH enzyme(s) in normal human breast epithelial cells grown in primary culture and in the human breast tumor cell line, MCF-7.

  11. MS-22NEOPLASTIC MENINGITIS FROM EPENDYMOMAS OF THE ADULT: A RETROSPECTIVE ANALYSIS

    PubMed Central

    Rudà, Roberta; Magistrello, Michela; Bertero, Luca; Bosa, Chiara; Pellerino, Alessia; Nicolotto, Elisa; Moretto, Francesco; Garbossa, Diego; Soffietti, Riccardo

    2014-01-01

    BACKGROUND: There is lack of information regarding the natural history and treatment outcome of neoplastic meningitis (NM) from ependymomas of the adult. AIM OF THE STUDY: To retrospectively analyze all patients with biopsy proven adult ependymomas with NM, who were diagnosed and treated at a single neuro-oncological Institution over the last decade. PATIENTS AND METHODS: We collected from the database and follow-up visits 15 evaluable patients (12 males, 3 females) with a median age of 45 (range 20-72). Histological diagnosis was as follows: 6 grade III (40%), 4 grade II (27%) and 5 grade I (myxopapillary) (33%) ependymomas. Overall, median time to NM was 2 years (range: 0-24). NM occurred at diagnosis in 5/15 (33%) and during follow-up in 10/15 (67%): among these latter the primary tumor was under control in 6/10 (60%) and progressive in 4/10 (40%). All but 4 patients were symptomatic and MRI of the whole CNS was available in all patients. The diagnosis of NM was CSF-based in 7/15 (47%) and radiologically-based in 8/15 (53%). RT to the bulky disease was applied in 7/15 (47%) and surgery in 2/15 (13%). Medical therapies consisted variably in intrathecal Depocyte, temozolomide, nitrosourea-based regimens and bevacizumab. Four out of 12 symptomatic patients had a significant clinico-radiological response. Median survival was 20 months (range: 1 month-7 years), and 7/15 patients are still alive. CONCLUSIONS: NM from ependymomas in the adult is more indolent compared with other NM types, with longer survivals after multimodality treatment. Prospective studies are warranted.

  12. Hamlet's Transformation.

    NASA Astrophysics Data System (ADS)

    Usher, P. D.

    1997-12-01

    William Shakespeare's Hamlet has much evidence to suggest that the Bard was aware of the cosmological models of his time, specifically the geocentric bounded Ptolemaic and Tychonic models, and the infinite Diggesian. Moreover, Shakespeare describes how the Ptolemaic model is to be transformed to the Diggesian. Hamlet's "transformation" is the reason that Claudius, who personifies the Ptolemaic model, summons Rosencrantz and Guildenstern, who personify the Tychonic. Pantometria, written by Leonard Digges and his son Thomas in 1571, contains the first technical use of the word "transformation." At age thirty, Thomas Digges went on to propose his Perfit Description, as alluded to in Act Five where Hamlet's age is given as thirty. In Act Five as well, the words "bore" and "arms" refer to Thomas' vocation as muster-master and his scientific interest in ballistics. England's leading astronomer was also the father of the poet whose encomium introduced the First Folio of 1623. His oldest child Dudley became a member of the Virginia Company and facilitated the writing of The Tempest. Taken as a whole, such manifold connections to Thomas Digges support Hotson's contention that Shakespeare knew the Digges family. Rosencrantz and Guildenstern in Hamlet bear Danish names because they personify the Danish model, while the king's name is latinized like that of Claudius Ptolemaeus. The reason Shakespeare anglicized "Amleth" to "Hamlet" was because he saw a parallel between Book Three of Saxo Grammaticus and the eventual triumph of the Diggesian model. But Shakespeare eschewed Book Four, creating this particular ending from an infinity of other possibilities because it "suited his purpose," viz. to celebrate the concept of a boundless universe of stars like the Sun.

  13. TRANSFORMER APPARATUS

    DOEpatents

    Wolfgang, F.; Nicol, J.

    1962-11-01

    Transformer apparatus is designed for measuring the amount of a paramagnetic substance dissolved or suspended in a diamagnetic liquid. The apparatus consists of a cluster of tubes, some of which are closed and have sealed within the diamagnetic substance without any of the paramagnetic material. The remaining tubes are open to flow of the mix- ture. Primary and secondary conductors are wrapped around the tubes in such a way as to cancel noise components and also to produce a differential signal on the secondaries based upon variations of the content of the paramagnetic material. (AEC)

  14. Rotary Transformer

    NASA Technical Reports Server (NTRS)

    McLyman, Colonel Wm. T.

    1996-01-01

    None given. From first Par: Many spacecraft (S/C) and surface rovers require the transfer of signals and power across rotating interfaces. Science instruments, antennas and solar arrays are elements needing rotary power transfer for certain (S/C) configurations. Delivery of signal and power has mainly been done by using the simplest means, the slip ring approach. This approach, although simple, leaves debris generating noise over a period of time...The rotary transformer is a good alternative to slip rings for signal and power transfer.

  15. Corn transformed

    SciTech Connect

    Moffat, A.S.

    1990-08-10

    Researchers have produced fertile corn transformed with a foreign gene that makes the plants resistant to the herbicide bialaphos. This achievement, is the first report of fertile transgenic corn in the reviewed literature, and it is the capstone of almost a decade's efforts to genetically engineer this country's most important crop. The only other major crop to be so manipulated is rice. The ability produce transgenic corn gives biologists a valuable tool to probe the whys and hows of gene expression and regulation. It may also give plant breeders a way to develop new corn varieties with a speed and predictability that would be impossible with classical breeding techniques.

  16. Transformational leadership.

    PubMed

    Marlow, D L

    1996-01-01

    In these uncertain times in the healthcare industry, administrators are asked to do more with less time and resources. Because of the extended roles they are playing in today's organizations, radiology administrators are looked upon as agents of change. What leadership skills do they need in this turbulent and uncertain healthcare environment? What are the trait's of tomorrow's leaders? The transformational leader is the one who will guide us through this changing healthcare environment. Several behavioral patterns emerge as important traits for tomorrow's leaders to have-individual consideration, intellectual stimulation and charisma. Tomorrow's leader must view each person as an individual, showing genuine concern and belief in each person's ability to perform. Transformational leaders stimulate others by encouraging them to be curious and try new ideas. The final characteristic, charisma, is the ability to inspire others. Luckily, leaders are made, not born: today's leaders can learn to be responsive, to draw out new ideas from employees, and to communicate self-esteem, energy and enthusiasm. PMID:10163135

  17. Morphological transformation of an established Syrian hamster dermal cell with the anti-tussive agent noscapine.

    PubMed

    Porter, R; Parry, E M; Parry, J M

    1992-05-01

    Following exposure to the alkaloid noscapine hydrochloride over a concentration range of 10-120 micrograms/ml immortal cultures of Syrian hamster dermal fibroblasts were shown to undergo morphological transformation. The resultant transformed foci produced cultures which were anchorage independent as confirmed by soft agar tests. Karyotype analysis of a noscapine transformed colony demonstrated an increase in chromosome number compared to the immortal culture and the non-random duplication of a translocated chromosome 9 previously identified in the immortal culture. These data indicate that noscapine, which has previously been shown to be a spindle inhibitor and inducer of polyploidy in cultured cells, is capable of inducing in vitro cell transformation. Such data indicate a carcinogenic potential for this widely used cough suppressant. PMID:1602976

  18. Lactoperoxidase-catalyzed iodination of membrane proteins in normal and neoplastic epidermal cells

    SciTech Connect

    Brysk, M.M.; Snider, J.M.

    1982-01-01

    Cell surface proteins of normal human, mouse, and rat cells in primary culture, of human basal cell carcinoma, and of carcinogen-transformed cell lines were examined by lactoperoxidase-catalyzed iodination. Autoradiography was used to record the distribution of label in the polypeptide subunits separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. There was no significant difference in the results for normal cells of human, mouse, and rat. On the other hand, carcinogen-transformed mouse cells had many more labeled polypeptide bands of widely distributed molecular weights. The iodination profiles from human basal cell carcinoma cells were much more akin to those from normal cells than to those from carcinogen-transformed cells. Treatment of iodinated cells with proteolytic enzymes visibly altered the polypeptide bands.

  19. Non-Randomized Confirmatory Trial of Laparoscopy-Assisted Total Gastrectomy and Proximal Gastrectomy with Nodal Dissection for Clinical Stage I Gastric Cancer: Japan Clinical Oncology Group Study JCOG1401.

    PubMed

    Kataoka, Kozo; Katai, Hitoshi; Mizusawa, Junki; Katayama, Hiroshi; Nakamura, Kenichi; Morita, Shinji; Yoshikawa, Takaki; Ito, Seiji; Kinoshita, Takahiro; Fukagawa, Takeo; Sasako, Mitsuru

    2016-06-01

    Several prospective studies on laparoscopy-assisted distal gastrectomy for early gastric cancer have been initiated, but no prospective study evaluating laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy has been completed to date. A non-randomized confirmatory trial was commenced in April 2015 to evaluate the safety of laparoscopy-assisted total gastrectomy and laparoscopy-assisted proximal gastrectomy for clinical stage I gastric cancer. A total of 245 patients will be accrued from 42 Japanese institutions over 3 years. The primary endpoint is the proportion of patients with anastomotic leakage. The secondary endpoints are overall survival, relapse-free survival, proportion of patients with completed laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy, proportion of patients with conversion to open surgery, adverse events, and short-term clinical outcomes. The UMIN Clinical Trials Registry number is UMIN000017155. PMID:27433394

  20. Risk of Bias in Systematic Reviews of Non-Randomized Studies of Adverse Cardiovascular Effects of Thiazolidinediones and Cyclooxygenase-2 Inhibitors: Application of a New Cochrane Risk of Bias Tool

    PubMed Central

    Bilandzic, Anja; Fitzpatrick, Tiffany; Rosella, Laura; Henry, David

    2016-01-01

    Background Systematic reviews of the effects of healthcare interventions frequently include non-randomized studies. These are subject to confounding and a range of other biases that are seldom considered in detail when synthesizing and interpreting the results. Our aims were to assess the reliability and usability of a new Cochrane risk of bias (RoB) tool for non-randomized studies of interventions and to determine whether restricting analysis to studies with low or moderate RoB made a material difference to the results of the reviews. Methods and Findings We selected two systematic reviews of population-based, controlled non-randomized studies of the relationship between the use of thiazolidinediones (TZDs) and cyclooxygenase-2 (COX-2) inhibitors and major cardiovascular events. Two epidemiologists applied the Cochrane RoB tool and made assessments across the seven specified domains of bias for each of 37 component studies. Inter-rater agreement was measured using the weighted Kappa statistic. We grouped studies according to overall RoB and performed statistical pooling for (a) all studies and (b) only studies with low or moderate RoB. Kappa scores across the seven bias domains ranged from 0.50 to 1.0. In the COX-2 inhibitor review, two studies had low overall RoB, 14 had moderate RoB, and five had serious RoB. In the TZD review, six studies had low RoB, four had moderate RoB, four had serious RoB, and two had critical RoB. The pooled odds ratios for myocardial infarction, heart failure, and death for rosiglitazone versus pioglitazone remained significantly elevated when analyses were confined to studies with low or moderate RoB. However, the estimate for myocardial infarction declined from 1.14 (95% CI 1.07–1.24) to 1.06 (95% CI 0.99–1.13) when analysis was confined to studies with low RoB. Estimates of pooled relative risks of cardiovascular events with COX-2 inhibitors compared with no nonsteroidal anti-inflammatory drug changed little when analyses were

  1. Non-Randomized Confirmatory Trial of Laparoscopy-Assisted Total Gastrectomy and Proximal Gastrectomy with Nodal Dissection for Clinical Stage I Gastric Cancer: Japan Clinical Oncology Group Study JCOG1401

    PubMed Central

    Kataoka, Kozo; Mizusawa, Junki; Katayama, Hiroshi; Nakamura, Kenichi; Morita, Shinji; Yoshikawa, Takaki; Ito, Seiji; Kinoshita, Takahiro; Fukagawa, Takeo; Sasako, Mitsuru

    2016-01-01

    Several prospective studies on laparoscopy-assisted distal gastrectomy for early gastric cancer have been initiated, but no prospective study evaluating laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy has been completed to date. A non-randomized confirmatory trial was commenced in April 2015 to evaluate the safety of laparoscopy-assisted total gastrectomy and laparoscopy-assisted proximal gastrectomy for clinical stage I gastric cancer. A total of 245 patients will be accrued from 42 Japanese institutions over 3 years. The primary endpoint is the proportion of patients with anastomotic leakage. The secondary endpoints are overall survival, relapse-free survival, proportion of patients with completed laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy, proportion of patients with conversion to open surgery, adverse events, and short-term clinical outcomes. The UMIN Clinical Trials Registry number is UMIN000017155. PMID:27433394

  2. Potentiation of cytotoxicity by 3-aminobenzamide in DNA repair-deficient human tumor cell lines following exposure to methylating agents or anti-neoplastic drugs.

    PubMed

    Babich, M A; Day, R S

    1988-04-01

    We studied the potentiation by 3-aminobenzamide (3AB) of killing of nine human cell lines exposed to alkylating agents. Cell lines included normal, transformed and DNA repair-proficient and -deficient phenotypes. 3AB potentiated cell killing by the methylating agents methylmethanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in all lines tested. The degree of potentiation ranged from 1.7- to 3.8-fold, based on the LD99. The average potentiation observed with MMS (2.7-fold) was greater than with MNNG (2.2-fold). On average the potentiation of MMS and MNNG killing of repair-deficient Mer- lines (2.4-fold) was similar to that of repair-proficient Mer+ lines. The degree of 3AB potentiation of MNNG killing (2.0-fold) was similar in Mer+ Rem- lines and in Mer+ Rem+ lines. Mer+ Rem+, Mer+ Rem-, Mer- Rem+, and Mer- Rem- strains all appeared proficient in a 3AB-sensitive DNA repair pathway. Within experimental error, 20 mM 3AB did not inhibit the removal of the MNNG-induced methylpurines 7-methylguanine, O6-methylguanine and 3-methyladenine from the DNA of repair-proficient Mer+ Rem+ HT29 cells, consistent with evidence that 3AB inhibits the ligation step of excision repair. 3AB potentiated cell killing by the bifunctional alkylating agents 1-(2-chlorethyl)-1-nitrosourea or busulfan, two anti-neoplastic drugs, by only 0.9- to 1.5-fold. These drugs therefore produce DNA damage which is not efficiently repaired by the pathways that repair methylated bases. PMID:3356063

  3. eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor cells

    PubMed Central

    Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R.; Beadnell, Thomas C.; Schwertfeger, Kathryn L.; Benyumov, Alexey O.; Manivel, J. Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B.; Polunovsky, Vitaly A.

    2015-01-01

    Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biological outputs remains unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased cell self-renewal, triggered DNA replication stress, and induced formation of pre-malignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands, and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its pro-neoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. PMID:25524901

  4. Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

    PubMed Central

    2013-01-01

    could aid the spermatogonial cells to be part of a pro-survival pathway that helps to evade the toxic effects of endogenous oxidants and contributes to testicular neoplastic growth. PMID:24059746

  5. Responsiveness of neoplastic and hyperplastic parathyroid tissues to calcium in vitro.

    PubMed Central

    Habener, J F

    1978-01-01

    Secretory and biosynthetic responses of adenomatous, carcinomatous, and hyperplastic parathyroid tissues to variable concentrations of extracellular calcium were assessed in vitro. Tissues, obtained at the time of parathyroidectomy, were incubated for 4 h in media containing radioactive amino acids and varying (0.5-5.0 mM) concentrations of calcium. Amounts of newly synthesized and total parathyroid hormone and proparathyroid hormone in extracts of tissues and media were measured by polyacrylamide gel electrophoresis and by radioimmunoassay, respectively. All tissues studied (six adenomas, two specimens of chief-cell hyperplasia, one carcinoma, and normal bovine and human glands) responded to changes in calcium concentrations; decreasing concentrations of calcium stimulated release and decreased tissue storage of hormone. Six of the abnormal tissues required greater than normal concentrations of calcium (1.8-2.4 mM for 50% of effect) to elicit secretory responses comparable with those of normal glands (1.4 mM). Maximum effects of calcium on release of hormone varied from 2- to 10-fold among different tissues. Release of some hormone persisted even in concentrations of calcium as high as 5.0 mM. Relative amounts of hormone released from and retained in the tissues varied greatly among the tissues, as did the absolute amounts of hormone produced; newly synthesized, labeled hormone ranged between 0.6 and 12% of total labeled protein, and immunoreactive hormone ranged between 0.015 and 0.9% of total tissue protein. Effects of calcium on hormone biosynthesis, as determined by analyses of amounts of proparathyroid hormone in the tissues, were variable among tissues and in many cases were negligible. These results indicate that neoplastic and hyperplastic parathyroid tissues retain secretory responsiveness to changes in extracellular concentrations of calcium. Responses, however, are highly variable among different tissues, and in many instances are abnormal, inasmuch as

  6. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

    PubMed Central

    Lucey, D R; Clerici, M; Shearer, G M

    1996-01-01

    In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for

  7. Short-term intake of a Japanese-style healthy lunch menu contributes to prevention and/or improvement in metabolic syndrome among middle-aged men: a non-randomized controlled trial

    PubMed Central

    2014-01-01

    Background Metabolic syndrome is now widely appreciated as a cluster of metabolic abnormalities such as visceral obesity, hypertension, hyperglycemia and dyslipidemia. To date, incidence of metabolic syndrome is continuously increasing worldwide. In addition, low vegetable consumption has recently become a serious issue in Japan. Furthermore, Japan is facing a shortfall in places offering food that can help prevent metabolic syndrome in the first place. Our study is designed to influence these developments. We conducted a non-randomized controlled trial by offering a Japanese-style healthy lunch menu to middle-aged men in a workplace cafeteria. This menu was designed to prevent and reduce metabolic syndrome. Methods This intervention study took the form of a non-randomized controlled trial. Participants chose the control or intervention group. The control group consumed their habitual lunches without restriction and only nutrient contents were assessed. The intervention group received a Japanese-style healthy lunch at a workplace cafeteria for 3 months. The participants worked in offices at a city hall and mostly had low levels of physical activity. Data of 35 males (control group: 7 males, intervention group: 28 males, mean age: 47.2 ± 7.9 years) were collected and analyzed. Results We obtained an effective outcome by demonstrating that ongoing intake of a Japanese-style healthy lunch decreased blood pressure and serum lipids and increased plasma ghrelin levels. The results grew more pronounced as intake of Japanese-style healthy lunches increased in frequency. Conclusions This study presents new empirical data as a result of an original intervention program undertaken in Japan. A Japanese-style healthy lunch menu containing many vegetables consumed can help prevent and/or improve metabolic syndrome. PMID:24673894

  8. Herbicide Transformation

    PubMed Central

    Lanzilotta, R. P.; Pramer, David

    1970-01-01

    A strain of Fusarium solani isolated from soil by enrichment techniques used propanil (3′, 4′-dichloropropionanilide) as a sole source of organic carbon and energy for growth in pure culture. The primary product of the transformation of propanil by F. solani was isolated and identified as 3,4-dichloroaniline (DCA). This compound accumulated in the medium to a level (80 μg/ml) which stopped further herbicide utilization. Herbicide utilization by F. solani was influenced by various environmental and nutritional factors. It was more sensitive to acid than alkaline pH. Added glucose and yeast extract increased the rate of propanil decomposition, and the reduced aeration retarded growth of the fungus and herbicide utilization. The growth of F. solani on propionate was inhibited by added DCA. Images PMID:5437305

  9. Discrimination of Benign and Neoplastic Mucosa with a High-Resolution Microendoscope (HRME) in Head and Neck Cancer

    PubMed Central

    Vila, Peter M.; Park, Chan W.; Pierce, Mark C.; Goldstein, Gregg H.; Levy, Lauren; Gurudutt, Vivek V.; Polydorides, Alexandras D.; Godbold, James H.; Teng, Marita S.; Genden, Eric M.; Miles, Brett A.; Anandasabapathy, Sharmila; Gillenwater, Ann M.; Richards-Kortum, Rebecca; Sikora, Andrew G.

    2012-01-01

    Background The efficacy of ablative surgery for head and neck squamous cell carcinoma (HNSCC) depends critically on obtaining negative margins. While intraoperative "frozen section" analysis of margins is a valuable adjunct, it is expensive, time-consuming, and highly dependent on pathologist expertise. Optical imaging has potential to improve the accuracy of margins by identifying cancerous tissue in real time. Our aim was to determine the accuracy and inter-rater reliability of head and neck cancer specialists using high-resolution microendoscopic (HRME) images to discriminate between cancerous and benign mucosa. Methods Thirty-eight patients diagnosed with HNSCC were enrolled in this single-center study. HRME was used to image each specimen after application of proflavine, with concurrent standard histopathologic analysis. Images were evaluated for quality control, and a training set containing representative images of benign and neoplastic tissue was assembled. After viewing training images, seven head and neck cancer specialists with no prior HRME experience reviewed 37 test images and were asked to classify each. Results The mean accuracy of all reviewers in correctly diagnosing neoplastic mucosa was 97 percent (95% Cl = 94–99%). The mean sensitivity and specificity were 98 percent (97–100%) and 92 percent (87–98%), respectively. The Fleiss kappa statistic for inter-rater reliability was 0.84 (0.77–0.91). Conclusions Medical professionals can be quickly trained to use HRME to discriminate between benign and neoplastic mucosa in the head and neck. With further development, the HRME shows promise as a method of real-time margin determination at the point of care. PMID:22492225

  10. Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC

    PubMed Central

    Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo

    2016-01-01

    Background Promoter hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. Results The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Methods Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Conclusions Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance. PMID:26862732

  11. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine.

    PubMed

    Jaeckle, K A; Phuphanich, S; Bent, M J; Aiken, R; Batchelor, T; Campbell, T; Fulton, D; Gilbert, M; Heros, D; Rogers, L; O'Day, S J; Akerley, W; Allen, J; Baidas, S; Gertler, S Z; Greenberg, H S; LaFollette, S; Lesser, G; Mason, W; Recht, L; Wong, E; Chamberlain, M C; Cohn, A; Glantz, M J; Gutheil, J C; Maria, B; Moots, P; New, P; Russell, C; Shapiro, W; Swinnen, L; Howell, S B

    2001-01-01

    DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. PMID:11161370

  12. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

    PubMed Central

    Jaeckle, K A; Phuphanich, S; Bent, M J van den; Aiken, R; Batchelor, T; Campbell, T; Fulton, D; Gilbert, M; Heros, D; Rogers, L; O'Day, S J; Akerley, W; Allen, J; Baidas, S; Gertler, S Z; Greenberg, H S; LaFollette, S; Lesser, G; Mason, W; Recht, L; Wong, E; Chamberlain, M C; Cohn, A; Glantz, M J; Gutheil, J C; Maria, B; Moots, P; New, P; Russell, C; Shapiro, W; Swinnen, L; Howell, S B

    2001-01-01

    DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515+); median survival was 88 days (range 1–515+), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161370

  13. Heparin-Binding Epidermal Growth Factor-like Growth Factor/Diphtheria Toxin Receptor in Normal and Neoplastic Hematopoiesis

    PubMed Central

    Vinante, Fabrizio; Rigo, Antonella

    2013-01-01

    Heparin-binding EGF-like growth factor (HB-EGF) belongs to the EGF family of growth factors. It is biologically active either as a molecule anchored to the membrane or as a soluble form released by proteolytic cleavage of the extracellular domain. HB-EGF is involved in relevant physiological and pathological processes spanning from proliferation and apoptosis to morphogenesis. We outline here the main activities of HB-EGF in connection with normal or neoplastic differentiative or proliferative events taking place primitively in the hematopoietic microenvironment. PMID:23888518

  14. In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells.

    PubMed

    Yamamoto, Yusuke; Ning, Gang; Howitt, Brooke E; Mehra, Karishma; Wu, Lingyan; Wang, Xia; Hong, Yue; Kern, Florian; Wei, Tay Seok; Zhang, Ting; Nagarajan, Niranjan; Basuli, Debargha; Torti, Suzy; Brewer, Molly; Choolani, Mahesh; McKeon, Frank; Crum, Christopher P; Xian, Wa

    2016-03-01

    High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre-metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed 'serous tubal intraepithelial carcinoma' or STIC. Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall short of STIC but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high-grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of FTSCs were capable of multipotent differentiation and that the tumours derived from transformed FTSCs shared the histological and molecular features of HGSC. We also demonstrated that altered expression of some biomarkers seen in transformed FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and transformed FTSCs showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen in vivo. Biomarkers unique to STIC relative to normal tubal epithelium provide a basis for novel detection approaches to early HGSC, but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed FTSCs may provide unique early targets for prevention strategies. Central to these efforts has been the ability to clone

  15. In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells

    PubMed Central

    Howitt, Brooke E; Mehra, Karishma; Wu, Lingyan; Wang, Xia; Hong, Yue; Kern, Florian; Wei, Tay Seok; Zhang, Ting; Nagarajan, Niranjan; Basuli, Debargha; Torti, Suzy; Brewer, Molly; Choolani, Mahesh; McKeon, Frank; Crum, Christopher P; Xian, Wa

    2016-01-01

    High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre-metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed ‘serous tubal intraepithelial carcinoma’ or STIC. Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall short of STIC but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high-grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of FTSCs were capable of multipotent differentiation and that the tumours derived from transformed FTSCs shared the histological and molecular features of HGSC. We also demonstrated that altered expression of some biomarkers seen in transformed FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and transformed FTSCs showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen in vivo. Biomarkers unique to STIC relative to normal tubal epithelium provide a basis for novel detection approaches to early HGSC, but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed FTSCs may provide unique early targets for prevention strategies. Central to these efforts has been the ability to

  16. Mitochondrial alteration in malignantly transformed human small airway epithelial cells induced by alpha particles

    PubMed Central

    Zhang, Suping; Wen, Gengyun; Huang, Sarah XL; Wang, Jianrong; Tong, Jian; Hei, Tom K.

    2012-01-01

    Human small airway epithelial cells (SAECs) immortalized with human telomerase reverse transcriptase (h-TERT) were exposed to either a single or multiple doses of α particles. Irradiated cells showed a dose-dependent cytotoxicity and progressive neoplastic transformation phenotype. These included an increase in saturation density of growth, a greater resistance to PALA, faster anchorage-independent growth, reinforced cell invasion and c-Myc expression. In addition, the transformed cells formed progressively growing tumors upon inoculation into athymic nude mice. Specifically, α-irradiation induced damage to both mitochondrial DNA (mtDNA) and mitochondrial functions in transformed cells as evidenced by increased mtDNA copy number and common deletion, decreased oxidative phosphorylation (OXPHOS) activity as measured by cytochrome C oxidase (COX) activity and oxygen consumption. There was a linear correlation between mtDNA copy number, common deletion, COX activity and cellular transformation represented by soft agar colony formation and c-Myc expression. These results suggest that mitochondria are associated with neoplastic transformation of SAEC cells induced by α particles, and that the oncogenesis process may depend not only on the genomes inside the nucleus, but also on the mitochondrial DNA outside the nucleus. PMID:22644783

  17. Rodent cell transformation assays-a brief historical perspective.

    PubMed

    Schechtman, Leonard M

    2012-04-11

    In vitro cell transformation is a process characterized by a series of progressive distinctive events that often emulate manifestations occurring in vivo and which are associated with neoplasia. Attendant cellular and sub-cellular alterations include, among others: cellular immortality, phenotypic changes, aneuploidy, genetic variability, cellular disarray, anchorage-independent growth, and tumorigenicity in vivo. Early chemically induced neoplastic transformation studies involved the use of normal diploid (Syrian) hamster embryo (SHE) cells and monitored the formation of morphologically altered colonies. Later investigations employed primarily two established mouse cell lines, i.e. the BALB/c 3T3 A31 cell line and the C3H 10T 1/2 cell line, and monitored the induction of morphologically aberrant foci. In either case, such transformed cellular clusters (colonies and foci) could induce tumors upon inoculation in vivo. Some subsequent noteworthy advancements using these systems included pH adjustments, metabolic supplementation, amplification of expression of formerly latent transformed foci, concurrent detection of mutagenesis and transformation, and use of a Bhas 42 cell line (v-Ha-ras transfected BALB/c 3T3 cells) to detect both tumor initiators and promoters. Over time, such transformation assay systems have been found useful in academic, industry and regulatory laboratories, generally for research purposes, but also occasionally as screening tools for potential chemical carcinogens. Nevertheless, to date, use of these assays for decision-making purposes in the regulatory arena remains elusive and will require comprehensive validation to gain universal acceptance. PMID:22230428

  18. A novel stem cell associated marker identified by monoclonal antibody HESC5:3 differentiates between neoplastic lesions in follicular thyroid neoplasms.

    PubMed

    Heikkilä, Annukka; Fermér, Christian; Hagström, Jaana; Louhimo, Johanna; Mäenpää, Hanna; Siironen, Päivi; Heiskanen, Ilkka; Nilsson, Olle; Arola, Johanna; Haglund, Caj

    2015-07-01

    Follicular thyroid lesions are the bane of cytopathology. Differentiation between adenoma and carcinoma is impossible, and often these neoplasms are indistinguishable even from uninodular goitre. In other cancers as well, a theory of stem cells as the origin of cancer has been discussed in thyroid carcinogenesis. We aimed to examine a novel stem cell associated marker identified by monoclonal antibody HESC5:3 in follicular lesions in an attempt to find a marker for differential diagnosis in thyroid cytopathology. HESC5:3 was raised against and is specific for undifferentiated human embryonic stem cells. The epitope of this novel antibody is to be defined. Immunohistochemical expression of HESC5:3 was examined in clinical material comprised of follicular neoplasms (83 adenomas, 43 carcinomas) and non-neoplastic lesions (41 goitrous, 22 hyperplastic, 23 normal tissue specimens). Staining differed significantly between neoplastic and non-neoplastic lesions. Nuclear staining was increased in non-neoplastic cells, whereas in neoplastic cells expression was mainly cytoplasmic. There was no difference between benign and malignant lesions, suggesting a role in early tumourigenesis. In conclusion, the HESC5:3 epitope may be of benefit as a neoplasia marker in distinguishing between uninodular goitre and neoplasia. Characterization of the epitope would increase the interest in this promising new stem cell associated marker. PMID:25960045

  19. Extra-prostatic Transgene-associated Neoplastic Lesions in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) Mice

    PubMed Central

    Berman-Booty, Lisa D.; Thomas-Ahner, Jennifer M.; Bolon, Brad; Oglesbee, Michael J.; Clinton, Steven K.; Kulp, Samuel K.; Chen, Ching-Shih; La Perle, Krista

    2014-01-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of pre-neoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubulo-acinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here we describe the histologic and immunohistochemical features of two novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain, and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice as well as in male TRAMP mice without histologically apparent prostate tumors. In this paper we also calculate the incidences of the urethral carcinomas and renal tubulo-acinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

  20. Electrotransfer of gene encoding endostatin into normal and neoplastic mouse tissues: inhibition of primary tumor growth and metastatic spread.

    PubMed

    Cichoń, Tomasz; Jamrozy, Laura; Glogowska, Joanna; Missol-Kolka, Ewa; Szala, Stanisław

    2002-09-01

    Electroporation-mediated gene transfer relies upon direct delivery of plasmids into cells permeabilized by electric fields, a method more efficient than transfer using nonviral vectors, although neither approaches the transfer efficiency of viral vectors. Here we studied electrotransfer of a gene encoding an angiogenesis inhibitor (endostatin) into primary tumors and muscle tissues, which would serve as a site of synthesis and secretion into the bloodstream of a therapeutic antimetastatic protein with systemic effects. Optimum electroporation conditions (voltage, number and duration of impulses, separation of caliper electrodes) were first established to maximize expression of a reporter gene transferred into murine Renca kidney carcinoma, B16(F10) melanoma, or skeletal muscle tissues. In neoplastic tissues, electrotransfer of plasmid DNA was far more efficient than electroporation with lipoplexes, but no differences between naked DNA and lipoplexes were found in case of electroporated muscles. We then studied the electrotransfer of plasmid DNA carrying the endostatin gene into pre-established experimental Renca tumors. A significant inhibition of tumor growth was observed in animals electroporated with this construct. Electrotransfer of the endostatin gene into muscle tissues resulted in reduced numbers of experimental B16(F10) metastases in the lungs. This study clearly shows that electroporation may be used to efficiently transfer antiangiogenic genes into both normal and neoplastic tissues. PMID:12189527

  1. Optic Neuritis as Isolated Manifestation of Leptomeningeal Carcinomatosis: A Case Report and Systematic Review of Ocular Manifestations of Neoplastic Meningitis

    PubMed Central

    Basilico, Paola; Trezzi, Ilaria; Borellini, Linda; Franco, Giulia; Civelli, Vittorio; Bresolin, Nereo; Baron, Pierluigi

    2013-01-01

    Introduction. Leptomeningeal carcinomatosis occurs in about 5% of cancer patients. Ocular involvement is a common clinical manifestation and often the presenting clinical feature. Materials and Methods. We report the case of a 52-year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis. Ocular symptoms were the presenting clinical feature in 34 patients (83%) out of 41 included in our review, the unique manifestation of meningeal carcinomatosis in 3 patients (7%). Visual loss was the presenting clinical manifestation in 17 patients (50%) and was the most common ocular symptom (70%). Other ocular signs were diplopia, ptosis, papilledema, anisocoria, exophthalmos, orbital pain, scotomas, hemianopsia, and nystagmus. Associated clinical symptoms were headache, altered consciousness, meningism, limb weakness, ataxia, dizziness, seizures, and other cranial nerves involvement. All patients except five underwent CSF examination which was normal in 1 patient, pleocytosis was found in 11 patients, increased protein levels were observed in 16 patients, and decreased glucose levels were found in 8 patients. Cytology was positive in 29 patients (76%). Conclusion. Meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms. PMID:24223306

  2. Optic neuritis as isolated manifestation of leptomeningeal carcinomatosis: a case report and systematic review of ocular manifestations of neoplastic meningitis.

    PubMed

    Lanfranconi, Silvia; Basilico, Paola; Trezzi, Ilaria; Borellini, Linda; Franco, Giulia; Civelli, Vittorio; Pallotti, Francesco; Bresolin, Nereo; Baron, Pierluigi

    2013-01-01

    Introduction. Leptomeningeal carcinomatosis occurs in about 5% of cancer patients. Ocular involvement is a common clinical manifestation and often the presenting clinical feature. Materials and Methods. We report the case of a 52-year old lady with optic neuritis as isolated manifestation of neoplastic meningitis and a review of ocular involvement in neoplastic meningitis. Ocular symptoms were the presenting clinical feature in 34 patients (83%) out of 41 included in our review, the unique manifestation of meningeal carcinomatosis in 3 patients (7%). Visual loss was the presenting clinical manifestation in 17 patients (50%) and was the most common ocular symptom (70%). Other ocular signs were diplopia, ptosis, papilledema, anisocoria, exophthalmos, orbital pain, scotomas, hemianopsia, and nystagmus. Associated clinical symptoms were headache, altered consciousness, meningism, limb weakness, ataxia, dizziness, seizures, and other cranial nerves involvement. All patients except five underwent CSF examination which was normal in 1 patient, pleocytosis was found in 11 patients, increased protein levels were observed in 16 patients, and decreased glucose levels were found in 8 patients. Cytology was positive in 29 patients (76%). Conclusion. Meningeal carcinomatosis should be considered in patients with ocular symptoms even in the absence of other suggestive clinical symptoms. PMID:24223306

  3. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    PubMed

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome. PMID:25175810

  4. Hepatocyte expressions in hepatocellular carcinomas, gastrointestinal neoplasms, and non-neoplastic gastrointestinal mucosa: its role as a diagnostic marker.

    PubMed Central

    Lee, Hye Seung; Kim, Woo Ho; Kang, Gyeong Hoon

    2003-01-01

    We performed immunohistochemical staining against Hepatocyte (Hep) and CD10 antibodies in 75 hepatocellular carcinoma (HCC), 50 cholangiocarcinomas, 49 colorectal adenocarcinomas, and 308 gastric adenocarcinomas by tissue array method. We also evaluated the various non-neoplastic adult tissues and fetal digestive organs. Hep was expressed in 80% of HCCs, and HCCs without Hep expression were more likely to have a higher Edmondson & Steiner grade than HCCs with Hep expression (p=0.004). In non-HCCs, 16% of cholangiocarcinomas, 8.2% of colorectal carcinomas, and 44.2% of gastric carcinomas expressed Hep. Gastric carcinomas with Hep expression were significantly associated with early gastric carcinomas (p<0.001). In non-neoplastic tissues, Hep was found expressed in normal hepatocytes, small intestinal mucosa, and intestinal metaplasia of the stomach. Fetal hepatocytes expressed Hep after 19 weeks of gestation. CD10 was detected in 46.7% (35/75) of HCCs, and canalicular staining pattern was predominant in HCCs. In conclusion, the expression of Hep and CD10 may help to distinguish HCCs from non-HCCs. PMID:14676441

  5. Non-random sharing of Plantae genes.

    PubMed

    Chan, Cheong Xin; Bhattacharya, Debashish

    2011-05-01

    The power of eukaryote genomics relies strongly on taxon sampling. This point was underlined in a recent analysis of red algal genome evolution in which we tested the Plantae hypothesis that posits the monophyly of red, green (including plants) and glaucophyte algae. The inclusion of novel genome data from two mesophilic red algae enabled us to robustly demonstrate the sisterhood of red and green algae in the tree of life. Perhaps more exciting was the finding that >1,800 putative genes in the unicellular red alga Porphyridium cruentum showed evidence of gene-sharing with diverse lineages of eukaryotes and prokaryotes. Here we assessed the correlation between the putative functions of these shared genes and their susceptibility to transfer. It turns out that genes involved in complex interactive networks such as biological regulation and transcription/translation are less susceptible to endosymbiotic or horizontal gene transfer, when compared to genes with metabolic and transporter functions. PMID:21980581

  6. Interventions for physical activity promotion applied to the primary healthcare settings for people living in regions of low socioeconomic level: study protocol for a non-randomized controlled trial

    PubMed Central

    2014-01-01

    Background Regular physical activity practice has been widely recommended for promoting health, but the physical activity levels remain low in the population. Therefore, the study of interventions to promote physical activity is essential. Objective: To present the methodology of two physical activity interventions from the “Ambiente Ativo” (“Active Environment”) project. Methods 12-month non-randomized controlled intervention trial. 157 healthy and physically inactive individuals were selected: health education (n = 54) supervised exercise (n = 54) and control (n = 49). Intervention based on health education: a multidisciplinary team of health professionals organized the intervention in group discussions, phone calls, SMS and educational material. Intervention based on supervised exercise program: consisted of offering an exercise program in groups supervised by physical education professionals involving strength, endurance and flexibility exercises. The physical activity level was assessed by the International Physical Activity Questionnaire (long version), physical activities recalls, pedometers and accelerometers over a seven-day period. Result This study described two different proposals for promoting physical activity that were applied to adults attended through the public healthcare settings. The participants were living in a region of low socioeconomic level, while respecting the characteristics and organization of the system and its professionals, and also adapting the interventions to the realities of the individuals attended. Conclusion Both interventions are applicable in regions of low socioeconomic level, while respecting the social and economic characteristics of each region. Trial registration ClinicalTrials.gov NCT01852981 PMID:24624930

  7. Effectiveness of Kenya's Community Health Strategy in delivering community-based maternal and newborn health care in Busia County, Kenya: non-randomized pre-test post test study

    PubMed Central

    Wangalwa, Gilbert; Cudjoe, Bennett; Wamalwa, David; Machira, Yvonne; Ofware, Peter; Ndirangu, Meshack; Ilako, Festus

    2012-01-01

    Background Maternal mortality ratio and neonatal mortality rate trends in Kenya have remained unacceptably high in a decade. In 2007, the Ministry of Public Health and Sanitation adopted a community health strategy to reverse the poor health outcomes in order to meet Millennium Development Goals 4 and 5. It aims at strengthening community participation and its ability to take action towards health. The study aimed at evaluating the effectiveness of the strategy in improving maternal and neonatal health outcomes in Kenya. Methods Between 2008 and 2010, the African Medical and Research Foundation implemented a community-based maternal and newborn care intervention package in Busia County using the community health strategy approach. An interventional, non-randomized pre-test post test study design was used to evaluate change in essential maternal and neonatal care practices among mothers with children aged 0 - 23 months. Results There was statistically significant (p < 0.05) increase in attendance of at least four antenatal care visits (39% to 62%), deliveries by skilled birth attendants (31% to 57%), receiving intermittent preventive treatment (23% to 57%), testing for HIV during pregnancy (73% to 90%) and exclusive breastfeeding (20% to 52%). Conclusion The significant increase in essential maternal and neonatal care practices demonstrates that, community health strategy is an appropriate platform to deliver community based interventions. The findings will be used by actors in the child survival community to improve current approaches, policies and practice in maternal and neonatal care. PMID:23467438

  8. RANDOMNESS of Numbers DEFINITION(QUERY:WHAT? V HOW?) ONLY Via MAXWELL-BOLTZMANN CLASSICAL-Statistics(MBCS) Hot-Plasma VS. Digits-Clumping Log-Law NON-Randomness Inversion ONLY BOSE-EINSTEIN QUANTUM-Statistics(BEQS) .

    NASA Astrophysics Data System (ADS)

    Siegel, Z.; Siegel, Edward Carl-Ludwig

    2011-03-01

    RANDOMNESS of Numbers cognitive-semantics DEFINITION VIA Cognition QUERY: WHAT???, NOT HOW?) VS. computer-``science" mindLESS number-crunching (Harrel-Sipser-...) algorithmics Goldreich "PSEUDO-randomness"[Not.AMS(02)] mea-culpa is ONLY via MAXWELL-BOLTZMANN CLASSICAL-STATISTICS(NOT FDQS!!!) "hot-plasma" REPULSION VERSUS Newcomb(1881)-Weyl(1914;1916)-Benford(1938) "NeWBe" logarithmic-law digit-CLUMPING/ CLUSTERING NON-Randomness simple Siegel[AMS Joint.Mtg.(02)-Abs. # 973-60-124] algebraic-inversion to THE QUANTUM and ONLY BEQS preferentially SEQUENTIALLY lower-DIGITS CLUMPING/CLUSTERING with d = 0 BEC, is ONLY VIA Siegel-Baez FUZZYICS=CATEGORYICS (SON OF TRIZ)/"Category-Semantics"(C-S), latter intersection/union of Lawvere(1964)-Siegel(1964)] category-theory (matrix: MORPHISMS V FUNCTORS) "+" cognitive-semantics'' (matrix: ANTONYMS V SYNONYMS) yields Siegel-Baez FUZZYICS=CATEGORYICS/C-S tabular list-format matrix truth-table analytics: MBCS RANDOMNESS TRUTH/EMET!!!

  9. Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression

    SciTech Connect

    Nelson, Celeste M.; Inman, Jamie L.; Bissell, Mina J.

    2008-02-13

    Here we describe a simple micromolding method to construct three-dimensional arrays of organotypic epithelial tissue structures that approximate in vivo histology. An elastomeric stamp containing an array of posts of defined geometry and spacing is used to mold microscale cavities into the surface of type I collagen gels. Epithelial cells are seeded into the cavities and covered with a second layer of collagen. The cells reorganize into hollow tissues corresponding to the geometry of the cavities. Patterned tissue arrays can be produced in 3-4 h and will undergo morphogenesis over the following one to three days. The protocol can easily be adapted to study a variety of tissues and aspects of normal and neoplastic development.

  10. Endoscopic therapy with curative intent for neoplastic epithelial lesions: indications rewiew and the role of "water-jet" technology.

    PubMed

    Ciocîrlan, M; Lupu, A; Ciora, C; Fanică, Dana; Ispas, Maria; Preda, Carmen; Mănuc, M; Diculescu, M

    2013-01-01

    Neoplastic lesions of the gastrointestinal tract have a large prevalence worldwide and in Romania. Their therapy is tailored to their TNM stage, which can be estimated using non invasive or minimally invasive imaging studies. Precursor lesions and superficial carcinomas are amenable to endoscopic therapy, providing that their endoscopic and/or endoscopic ultrasound aspect suggest a maximal extension to the submucosal layer. Polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are ablative techniques used for their curative intent treatment. Large superficial carcinomas are to be removed by ESD as "en bloc" resection is essential to post procedure histological appraisal of the curative oncology nature of their resection. ESD complications rates and duration are nowadays reduced with the aid of "water-jet" technology, by combining submucosal fluid jet injection and electro-resection in a single knife. PMID:24502069

  11. Histopathological Features of Non-Neoplastic Breast Parenchyma Do Not Predict BRCA Mutation Status of Patients with Invasive Breast Cancer

    PubMed Central

    Bayraktar, Soley; Qiu, Hongming; Liu, Diane; Shen, Yu; Gutierrez-Barrera, Angelica M; Arun, Banu K; Sahin, Aysegul A

    2015-01-01

    BACKGROUND Several studies have evaluated histologic features of non-neoplastic breast parenchyma in patients with BRCA1/2 mutations, but the results are conflicting. The limited data suggest a much higher prevalence of high-risk precursor lesions in BRCA carriers. Therefore, we designed this study to compare the clinicopathological characteristics of peritumoral benign breast tissue in patients with and without deleterious BRCA mutations. METHODS Women with breast cancer (BC) who were referred for genetic counseling and underwent BRCA genetic testing in 2010 and 2011 were included in the study. RESULTS Of the six benign histological features analyzed in this study, only stromal fibrosis grade 2/3 was found to be statistically different, with more BRCA noncarriers having stromal fibrosis grade 2/3 than BRCA1/2 carriers (P = 0.04). CONCLUSION There is no significant association between mutation risk and the presence of benign histologic features of peritumoral breast parenchyma. PMID:26327783

  12. Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation.

    PubMed

    Takeuchi, Masao; Higashino, Atsunori; Takeuchi, Kikuko; Hori, Yutaro; Koshiba-Takeuchi, Kazuko; Makino, Hatsune; Monobe, Yoko; Kishida, Marina; Adachi, Jun; Takeuchi, Jun; Tomonaga, Takeshi; Umezawa, Akihiro; Kameoka, Yosuke; Akagi, Ken-Ichi

    2015-01-01

    Comprehensive analysis of alterations in gene expression along with neoplastic transformation in human cells provides valuable information about the molecular mechanisms underlying transformation. To further address these questions, we performed whole transcriptome analysis to the human mesenchymal stem cell line, UE6E7T-3, which was immortalized with hTERT and human papillomavirus type 16 E6/E7 genes, in association with progress of transformation in these cells. At early stages of culture, UE6E7T-3 cells preferentially lost one copy of chromosome 13, as previously described; in addition, tumor suppressor genes, DNA repair genes, and apoptosis-activating genes were overexpressed. After the loss of chromosome 13, additional aneuploidy and genetic alterations that drove progressive transformation, were observed. At this stage, the cell line expressed oncogenes as well as genes related to anti-apoptotic functions, cell-cycle progression, and chromosome instability (CIN); these pro-tumorigenic changes were concomitant with a decrease in tumor suppressor gene expression. At later stages after prolong culture, the cells exhibited chromosome translocations, acquired anchorage-independent growth and tumorigenicity in nude mice, (sarcoma) and exhibited increased expression of genes encoding growth factor and DNA repair genes, and decreased expression of adhesion genes. In particular, glypican-5 (GPC5), which encodes a cell-surface proteoglycan that might be a biomarker for sarcoma, was expressed at high levels in association with transformation. Patched (Ptc1), the cell surface receptor for hedgehog (Hh) signaling, was also significantly overexpressed and co-localized with GPC5. Knockdown of GPC5 expression decreased cell proliferation, suggesting that it plays a key role in growth in U3-DT cells (transformants derived from UE6E7T-3 cells) through the Hh signaling pathway. Thus, the UE6E7T-3 cell culture model is a useful tool for assessing the functional contribution of

  13. Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation

    PubMed Central

    Hori, Yutaro; Koshiba-Takeuchi, Kazuko; Makino, Hatsune; Monobe, Yoko; Kishida, Marina; Adachi, Jun; Takeuchi, Jun; Tomonaga, Takeshi; Umezawa, Akihiro; Kameoka, Yosuke; Akagi, Ken-ichi

    2015-01-01

    Comprehensive analysis of alterations in gene expression along with neoplastic transformation in human cells provides valuable information about the molecular mechanisms underlying transformation. To further address these questions, we performed whole transcriptome analysis to the human mesenchymal stem cell line, UE6E7T-3, which was immortalized with hTERT and human papillomavirus type 16 E6/E7 genes, in association with progress of transformation in these cells. At early stages of culture, UE6E7T-3 cells preferentially lost one copy of chromosome 13, as previously described; in addition, tumor suppressor genes, DNA repair genes, and apoptosis-activating genes were overexpressed. After the loss of chromosome 13, additional aneuploidy and genetic alterations that drove progressive transformation, were observed. At this stage, the cell line expressed oncogenes as well as genes related to anti-apoptotic functions, cell-cycle progression, and chromosome instability (CIN); these pro-tumorigenic changes were concomitant with a decrease in tumor suppressor gene expression. At later stages after prolong culture, the cells exhibited chromosome translocations, acquired anchorage-independent growth and tumorigenicity in nude mice, (sarcoma) and exhibited increased expression of genes encoding growth factor and DNA repair genes, and decreased expression of adhesion genes. In particular, glypican-5 (GPC5), which encodes a cell-surface proteoglycan that might be a biomarker for sarcoma, was expressed at high levels in association with transformation. Patched (Ptc1), the cell surface receptor for hedgehog (Hh) signaling, was also significantly overexpressed and co-localized with GPC5. Knockdown of GPC5 expression decreased cell proliferation, suggesting that it plays a key role in growth in U3-DT cells (transformants derived from UE6E7T-3 cells) through the Hh signaling pathway. Thus, the UE6E7T-3 cell culture model is a useful tool for assessing the functional contribution of

  14. Reliability of the Spinal Instability Neoplastic Score (SINS) among radiation oncologists: an assessment of instability secondary to spinal metastases

    PubMed Central

    2014-01-01

    Background The Spinal Instability Neoplastic Score (SINS) categorizes tumor related spinal instability. It has the potential to streamline the referral of patients with established or potential spinal instability to a spine surgeon. This study aims to define the inter- and intra-observer reliability and validity of SINS among radiation oncologists. Methods Thirty-three radiation oncologists, across ten international sites, rated 30 neoplastic spinal disease cases. For each case, the total SINS (0-18 points), three clinical categories (stable: 0-6 points, potentially unstable: 7-12 points, and unstable: 13-18 points), and a binary scale (‘stable’: 0-6 points and ‘current or possible instability’; surgical consultation recommended: 7-18 points) were recorded. Evaluation was repeated 6-8 weeks later. Inter-observer agreement and intra-observer reproducibility were calculated by means of the kappa statistic and translated into levels of agreement (slight, fair, moderate, substantial, and excellent). Validity was determined by comparing the ratings against a spinal surgeon’s consensus standard. Results Radiation oncologists demonstrated substantial (κ = 0.76) inter-observer and excellent (κ = 0.80) intra-observer reliability when using the SINS binary scale (‘stable’ versus ‘current or possible instability’). Validity of the binary scale was also excellent (κ = 0.85) compared with the gold standard. None of the unstable cases was rated as stable by the radiation oncologists ensuring all were appropriately recommended for surgical consultation. Conclusions Among radiation oncologists SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumor related spinal disease: Is the spine ‘stable’ or is there ‘current or possible instability’ that warrants surgical assessment? PMID:24594004

  15. The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues.

    PubMed Central

    Turley, H.; Comley, M.; Houlbrook, S.; Nozaki, N.; Kikuchi, A.; Hickson, I. D.; Gatter, K.; Harris, A. L.

    1997-01-01

    In mammalian cells, there are two isoforms of DNA topoisomerase II, designated alpha (170-kDa form) and beta (180-kDa form). Previous studies using cell lines have shown that the topoisomerase IIalpha and beta isoforms are differentially regulated during the cell cycle and in response to changes in growth state. Moreover, both isoforms can act as targets for a range of anti-tumour drugs. Here, we have analysed the normal tissue distribution in humans of topoisomerase IIalpha and beta using isoform-specific antibodies. In addition, we have studied expression of these isoforms in 69 primary tumour biopsies, representative either of tumours that are responsive to topoisomerase II-targeting drugs (breast, lung, lymphoma and seminoma) or of those that show de novo drug resistance (colon). Topoisomerase IIalpha was expressed exclusively in the proliferating compartments of all normal tissues, and was detectable in both the cell nucleus and cytoplasm. In biologically aggressive or rapidly proliferating tumours (e.g. high-grade lymphomas and seminomas), there was a high level of topoisomerase IIalpha, although expression was still detectable in colon tumours, indicating that expression of this isoform is not sufficient to explain the intrinsic drug resistance of colon tumours. Topoisomerase IIbeta was expressed ubiquitously in vivo and was localized in both the nucleoli and the nucleoplasm. This isoform was present in quiescent cell populations, but was expressed at a generally higher level in all tumours and proliferating cells than in normal quiescent tissues. We conclude that topoisomerase IIalpha is a strict proliferation marker in normal and neoplastic cells in vivo, but that topoisomerase IIbeta has a much more general cell and tissue distribution than has topoisomerase IIalpha. The apparent up-regulation of topoisomerase IIbeta in neoplastic cells has implications for the response of patients to anti-tumour therapies that include topoisomerase II-targeting drugs

  16. Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans.

    PubMed Central

    Ward, J. M.; Stevens, J. L.; Konishi, N.; Kurata, Y.; Uno, H.; Diwan, B. A.; Ohmori, T.

    1992-01-01

    Vimentin expression was studied immunohistochemically in renal cortical tubules of untreated male rats of various ages, rats exposed to toxins (barbital sodium, folic acid) and carcinogens (streptozotocin, N-bis(2-hydroxypropyl)nitrosamine, barbital sodium, and in humans of various ages with or without renal epithelial tumors. Fetal, neonatal, and young adult rats did not express vimentin in renal cortical tubules. Regenerative renal tubular lesions from rats with aging nephropathy and from rats with toxic nephropathy both expressed vimentin. Mitogenic lesions induced by folic acid at 24 hours, however, were not immunoreactive for vimentin. Carcinogen-induced preneoplastic renal cortical tubular lesions in rats were most often focally immunoreactive whereas strong vimentin expression was found in almost all induced renal tumors. In kidneys of three children (younger than 2 years of age), vimentin was not found in renal cortical tubular cells except in rare individual cells in one case. Vimentin was abundant in basophilic regenerative tubules in kidneys of aged individuals, however. Most (7/10) human renal carcinomas and latent preneoplastic or neoplastic renal tubular lesions found incidentally at autopsy (2/4) showed vimentin expression. The authors suggest that the switching to vimentin expression in phenotypically normal renal cortical tubular cells in rats and humans, which do not usually express the intermediate filament protein vimentin, should be considered vimentin metaplasia. Vimentin expression is dissociated from increased cell proliferation in hyperplastic and neoplastic lesions, however. Instead the degree of dedifferentiation of the tubule cells and changes in phenotype were associated with vimentin expression. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:1415487

  17. A HUMAN BRONCHIAL EPITHELIAL CELL STRAIN WITH UNUSUAL IN VITRO GROWTH POTENTIAL WHICH UNDERGOES NEOPLASTIC TRANSFORMATION AFTER SV40 T ANTIGEN GENE TRANSFECTION

    EPA Science Inventory

    Bronchial epithelial cells were cultured from an individual with no evidence of malignant disease. hese cells, designated HB56B, had greatly extended in vitro life-span, being able to undergo 50 passages and 200 population doubling in contrast to the usual 3 to 4 passages and 20 ...

  18. Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.

    PubMed

    Michailidi, Christina; Hayashi, Masamichi; Datta, Sayantan; Sen, Tanusree; Zenner, Kaitlyn; Oladeru, Oluwadamilola; Brait, Mariana; Izumchenko, Evgeny; Baras, Alexander; VandenBussche, Christopher; Argos, Maria; Bivalacqua, Trinity J; Ahsan, Habibul; Hahn, Noah M; Netto, George J; Sidransky, David; Hoque, Mohammad Obaidul

    2015-03-01

    Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection. PMID:25586904

  19. Exposure to airborne PM2.5 suppresses microRNA expression and deregulates target oncogenes that cause neoplastic transformation in NIH3T3 cells

    PubMed Central

    Cheng, Xinxin; Shao, Mingming; Wu, Chen; Wang, Suhan; Li, Hongmin; Wei, Lixuan; Gao, Yanning; Tan, Wen; Cheng, Shujun; Wu, Tangchun; Yu, Dianke; Lin, Dongxin

    2015-01-01

    Long-term exposure to airborne PM2.5 is associated with increased lung cancer risk but the underlying mechanism remains unclear. We characterized global microRNA and mRNA expression in human bronchial epithelial cells exposed to PM2.5 organic extract and integrally analyzed microRNA-mRNA interactions. Foci formation and xenograft tumorigenesis in mice with NIH3T3 cells expressing genes targeted by microRNAs were performed to explore the oncogenic potential of these genes. We also detected plasma levels of candidate microRNAs in subjects exposed to different levels of air PM2.5 and examined the aberrant expression of genes targeted by these microRNAs in human lung cancer. Under our experimental conditions, treatment of cells with PM2.5 extract resulted in downregulation of 138 microRNAs and aberrant expression of 13 mRNAs (11 upregulation and 2 downregulation). In silico and biochemical analyses suggested SLC30A1, SERPINB2 and AKR1C1, among the upregulated genes, as target for miR-182 and miR-185, respectively. Ectopic expression of each of these genes significantly enhanced foci formation in NIH3T3 cells. Following subcutaneous injection of these cells into nude mice, fibrosarcoma were formed from SLC30A1- or SERPINB2-expressing cells. Reduced plasma levels of miR-182 were detected in subjects exposed to high level of PM2.5 than in those exposed to low level of PM2.5 (P = 0.043). Similar results were seen for miR-185 although the difference was not statistically significant (P = 0.328). Increased expressions of SLC30A1, SERPINB2 and AKR1C1 were detected in human lung cancer. These results suggest that modulation of miR-182 and miR-185 and their target genes may contribute to lung carcinogenesis attributable to PM2.5 exposure. PMID:26338969

  20. Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

    PubMed Central

    Perlino, E.; Loverro, G.; Maiorano, E.; Giannini, T.; Cazzolla, A.; Napoli, A.; Fiore, M. G.; Ricco, R.; Marra, E.; Selvaggi, L.

    1998-01-01

    Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma. Images Figure 1 Figure 5 Figure 6 Figure 8 PMID:9579831

  1. Down-regulated expression of transforming growth factor beta 1 mRNA in endometrial carcinoma.

    PubMed

    Perlino, E; Loverro, G; Maiorano, E; Giannini, T; Cazzolla, A; Napoli, A; Fiore, M G; Ricco, R; Marra, E; Selvaggi, L

    1998-04-01

    Transforming growth factor beta1 (TGF-beta1) is a potent modulator of cell proliferation in vitro, and recent studies have demonstrated its overexpression in several different tumours; nevertheless, the molecular mechanisms of TGF-beta1 action on cell growth and differentiation have not been fully elucidated. To clarify the role of TGF-beta and its receptor in human endometrial proliferation and differentiation, TGF-beta1 expression at both the mRNA and protein levels has been evaluated by using Northern blotting and immunohistochemistry, in both normal (atrophic, proliferative and secretory) and neoplastic (adenocarcinoma) endometrial samples. This study demonstrates that TGF-beta1 mRNA expression is dramatically reduced in endometrial carcinomas with respect to non-neoplastic tissues, whereas the immunohistochemical expression of TGF-beta1 is enhanced in the epithelial component of endometrial carcinomas compared with non-neoplastic tissues. These data suggest that TGF-beta1 acts as a paracrine regulator of endometrial cell proliferation and that it may contribute to the carcinogenic mechanisms of endometrial carcinoma. PMID:9579831

  2. Pathology neoplastic and non-neoplastic.

    PubMed

    Graeme-Cook, F

    1996-07-01

    Polyps of the gastrointestinal tract are common and often hard to diagnose by endoscopic or gross examination. Biopsy or polypectomy enables diagnosis and prognostication. This article is by no means encyclopedic, but attempts to discuss the pathology of the more common intestinal polyps. PMID:8829315

  3. Endoscopic Papillectomy into the Treatment of Neoplastic Lesions of Vater Papilla

    PubMed Central

    Ghidirim, G.; Mişin, I.; Istrate, V.; Cazacu, S.

    2009-01-01

    Adenomas of the duodenal papilla are rare. The frequency of malignant adenomas is 15-30%. Villous adenoma is a premalignant lesion with the highest rate of transformation. Options for surgical treatment include endoscopic and ablation resection, transduodenal ampullectomy, duodeno-pancreatectomy. Aim: Evaluation of the efficacy and safety of endoscopic papillectomy for ampullary adenomas. Material and method: 12 patients were selected (F:M, 5:7, age range 37 - 68 years) with ampullary adenoma, treated by endoscopic papillectomy. Biliary sphincterotomy was performed in 6 cases; and pancreatic sphincterotomy was performed in 3 cases. Biliary stenting was performed in 2 cases; pancreatic stent was placed in 11 cases. Results: En bloc resection was performed in 8 cases, and piecemeal resection in 4 cases. Complete resection R0 was noted in 10 cases. Pathology examination has show: tubulo-villous adenoma (5 patients); villous adenoma (4 patients), tubular adenoma (2 cases), adenocarcinoma (one case). Complications were immediate: bleeding (2 cases) and pancreatitis (1 case). Follow-up endoscopy reveals no ductal stenosis or recurrence. Conclusion: Endoscopic papillectomy is a safe and well-tolerated alternative to surgical treatment of ampullary adenoma. PMID:24778815

  4. Impact of a Multifaceted and Clinically Integrated Training Program in Evidence-Based Practice on Knowledge, Skills, Beliefs and Behaviour among Clinical Instructors in Physiotherapy: A Non-Randomized Controlled Study

    PubMed Central

    Olsen, Nina Rydland; Bradley, Peter; Espehaug, Birgitte; Nortvedt, Monica Wammen; Lygren, Hildegunn; Frisk, Bente; Bjordal, Jan Magnus

    2015-01-01

    Background and Purpose Physiotherapists practicing at clinical placement sites assigned the role as clinical instructors (CIs), are responsible for supervising physiotherapy students. For CIs to role model evidence-based practice (EBP) they need EBP competence. The aim of this study was to assess the short and long term impact of a six-month multifaceted and clinically integrated training program in EBP on the knowledge, skills, beliefs and behaviour of CIs supervising physiotherapy students. Methods We invited 37 CIs to participate in this non-randomized controlled study. Three self-administered questionnaires were used pre- and post-intervention, and at six-month follow-up: 1) The Adapted Fresno test (AFT), 2) the EBP Belief Scale and 3) the EBP Implementation Scale. The analysis approach was linear regression modeling using Generalized Estimating Equations. Results In total, 29 CIs agreed to participate in the study: 14 were invited to participate in the intervention group and 15 were invited to participate in the control group. One in the intervention group and five in the control group were lost to follow-up. At follow-up, the group difference was statistically significant for the AFT (mean difference = 37, 95% CI (15.9 -58.1), p<0.001) and the EBP Beliefs scale (mean difference = 8.1, 95% CI (3.1 -13.2), p = 0.002), but not for the EBP Implementation scale (mean difference = 1.8. 95% CI (-4.5-8.1), p = 0.574). Comparing measurements over time, we found a statistically significant increase in mean scores related to all outcome measures for the intervention group only. Conclusions A multifaceted and clinically integrated training program in EBP was successful in improving EBP knowledge, skills and beliefs among CIs. Future studies need to ensure long-term EBP behaviour change, in addition to assessing CIs’ abilities to apply EBP knowledge and skills when supervising students. PMID:25894559

  5. The pan-Bcl-2 blocker obatoclax promotes the expression of Puma, Noxa, and Bim mRNA and induces apoptosis in neoplastic mast cells.

    PubMed

    Peter, Barbara; Cerny-Reiterer, Sabine; Hadzijusufovic, Emir; Schuch, Karina; Stefanzl, Gabriele; Eisenwort, Gregor; Gleixner, Karoline V; Hoermann, Gregor; Mayerhofer, Matthias; Kundi, Michael; Baumgartner, Sigrid; Sperr, Wolfgang R; Pickl, Winfried F; Willmann, Michael; Valent, Peter

    2014-01-01

    Advanced SM is an incurable neoplasm with short survival time. So far, no effective therapy is available for these patients. We and others have shown recently that neoplastic MC in ASM and MCL express antiapoptotic Mcl-1, Bcl-2, and Bcl-xL. In this study, we examined the effects of the pan-Bcl-2 family blocker obatoclax (GX015-070) on primary neoplastic MC, the human MC leukemia cell line HMC-1, and the canine mastocytoma cell line C2. Obatoclax was found to inhibit proliferation in primary human neoplastic MC (IC₅₀: 0.057 μM), in HMC-1.2 cells expressing KIT D816V (IC₅₀: 0.72 μM), and in HMC-1.1 cells lacking KIT D816V (IC₅₀: 0.09 μM), as well as in C2 cells (IC₅₀: 0.74 μM). The growth-inhibitory effects of obatoclax in HMC-1 cells were accompanied by an increase in expression of Puma, Noxa, and Bim mRNA, as well as by apoptosis, as evidenced by microscopy, TUNEL assay, and caspase cleavage. Viral-mediated overexpression of Mcl-1, Bcl-xL, or Bcl-2 in HMC-1 cells was found to introduce partial resistance against apoptosis-inducing effects of obatoclax. We were also able to show that obatoclax synergizes with several other antineoplastic drugs, including dasatinib, midostaurin, and bortezomib, in producing apoptosis and/or growth arrest in neoplastic MC. Together, obatoclax exerts major growth-inhibitory effects on neoplastic MC and potentiates the antineoplastic activity of other targeted drugs. Whether these drug effects can be translated to application in patients with advanced SM remains to be determined. PMID:24052572

  6. The use of transformed IMR90 cell model to identify the potential extra-telomeric effects of hTERT in cell migration and DNA damage response

    PubMed Central

    2014-01-01

    Background Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomesase, is responsible for telomere maintenance and its reactivation is implicated in almost 90% human cancers. Recent evidences show that hTERT is essential for neoplastic transformation independent of its canonical function. However, the roles of hTERT in the process remain elusive. In the current work, we explore the extra-telomeric role of hTERT in the neoplastic transformation of fibroblast IMR90. Results Here we established transformed IMR90 cells by co-expression of three oncogenic factors, namely, H-Ras, SV40 Large-T antigen and hTERT (RSH). The RSH-transformed cells acquired hallmarks of cancer, such as they can grow under anchorage independent conditions; self-sufficient in growth signals; attenuated response to apoptosis; and possessed recurrent chromosomal abnormalities. Furthermore, the RSH-transformed cells showed enhanced migration capability which was also observed in IMR90 cells expressing hTERT alone, indicating that hTERT plays a role in cell migration, and thus possibly contribute to their metastatic potential during tumor transformation. This notion was further supported by our microarray analysis. In addition, we found that Ku70 were exclusively upregulated in both RSH-transformed IMR90 cells and hTERT-overexpressing IMR90 cells, suggesting the potential role of hTERT in DNA damage response (DDR). Conclusions Collectively, our study revealed the extra-telomeric effects of hTERT in cell migration and DDR during neoplastic transformation. PMID:25098897

  7. Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor.

    PubMed Central

    Mellon, J. K.; Cook, S.; Chambers, P.; Neal, D. E.

    1996-01-01

    We have examined levels of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in neoplastic and non-neoplastic bladder tissue using a standard radioimmunoassay technique. Tumour samples had much higher TGF-alpha levels compared with EGF and TGF-alpha levels in malignant tissue were significantly higher than in benign bladder samples. There was, in addition, a difference in mean EGF levels from 'normal' bladder samples from non-tumour bearing areas of bladder in patients with bladder cancer compared with 'normal' bladder tissue obtained at the time of organ retrieval surgery. Levels of EGF and TGF-alpha did not correlate with levels of EGF receptor (EGFR) as determined by a radioligand binding method but levels of TGF-alpha > 10 ng gm-1 of tumour tissue did correlate with EGFR positivity defined using immunohistochemistry. These data suggest that TGF-alpha is the likely ligand for EGFR in bladder tumours. PMID:8605103

  8. Loss of p53 protein during radiation transformation of primary human mammary epithelial cells

    SciTech Connect

    Wazer, D.E.; Chu, Qiuming; Liu, Xiao Long; Gao, Qingshen; Safaii, H.; Band, V. )

    1994-04-01

    The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated [gamma]-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G[sub 1] arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells. 44 refs., 8 figs., 1 tab.

  9. Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens

    SciTech Connect

    Ohanian, S.H.; McCabe, R.P.; Evans, C.H.

    1981-12-01

    The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo(a)pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

  10. Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens

    SciTech Connect

    Ohanian, S.H.; McCabe, R.P.; Evans, C.H.

    1981-12-01

    The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo(a)pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit anitsera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other cultured cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

  11. Transforming the Way We Teach Function Transformations

    ERIC Educational Resources Information Center

    Faulkenberry, Eileen Durand; Faulkenberry, Thomas J.

    2010-01-01

    In this article, the authors discuss "function," a well-defined rule that relates inputs to outputs. They have found that by using the input-output definition of "function," they can examine transformations of functions simply by looking at changes to input or output and the respective changes to the graph. Applying transformations to the input…

  12. Quantitative Evaluation of DNA Methylation Patterns for ALVE and TVB Genes in a Neoplastic Disease Susceptible and Resistant Chicken Model

    PubMed Central

    Yu, Ying; Zhang, Huanmin; Tian, Fei; Bacon, Larry; Zhang, Yuan; Zhang, Wensheng; Song, Jiuzhou

    2008-01-01

    Chicken endogenous viruses, ALVE (Avian Leukosis Virus subgroup E), are inherited as LTR (long terminal repeat) retrotransposons, which are negatively correlated with disease resistance, and any changes in DNA methylation may contribute to the susceptibility to neoplastic disease. The relationship between ALVE methylation status and neoplastic disease in the chicken is undefined. White Leghorn inbred lines 72 and 63 at the ADOL have been respectively selected for resistance and susceptibility to tumors that are induced by avian viruses. In this study, the DNA methylation patterns of 3∼6 CpG sites of four conserved regions in ALVE, including one unique region in ALVE1, the promoter region in the TVB (tumor virus receptor of ALV subgroup B, D and E) locus, were analyzed in the two lines using pyrosequencing methods in four tissues, i.e., liver, spleen, blood and hypothalamus. A significant CpG hypermethylation level was seen in line 72 in all four tissues, e.g., 91.86±1.63% for ALVE region2 in blood, whereas the same region was hemimethylated (46.16±2.56%) in line 63. CpG methylation contents of the ALVE regions were significantly lower in line 63 than in line 72 in all tissues (P<0.01) except the ALVE region 3/4 in liver. RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in line 63 than in line 72 (P<0.01). The methylation levels of six recombinant congenic strains (RCSs) closely resembled to the background line 63 in ALVE-region 2, which imply the methylation pattern of ALVE-region 2 may be a biomarker in resistant disease breeding. The methylation level of the promoter region in the TVB was significantly different in blood (P<0.05) and hypothalamus (P<0.0001), respectively. Our data disclosed a hypermethylation pattern of ALVE that may be relevant for resistance against ALV induced tumors in chickens. PMID:18320050

  13. Neuregulin-1 Administration Protocols Sufficient for Stimulating Cardiac Regeneration in Young Mice Do Not Induce Somatic, Organ, or Neoplastic Growth

    PubMed Central

    Ganapathy, Balakrishnan; Nandhagopal, Nikitha; Polizzotti, Brian D.; Bennett, David; Asan, Alparslan; Wu, Yijen; Kühn, Bernhard

    2016-01-01

    Background We previously developed and validated a strategy for stimulating heart regeneration by administration of recombinant neuregulin (rNRG1), a growth factor, in mice. rNRG1 stimulated proliferation of heart muscle cells, cardiomyocytes, and was most effective when administration began during the neonatal period. Our results suggested the use of rNRG1 to treat pediatric patients with heart failure. However, administration in this age group may stimulate growth outside of the heart. Methods NRG1 and ErbB receptor expression was determined by RT-PCR. rNRG1 concentrations in serum were quantified by ELISA. Mice that received protocols of recombinant neuregulin1-β1 administration (rNRG1, 100 ng/g body weight, daily subcutaneous injection for the first month of life), previously shown to induce cardiac regeneration, were examined at pre-determined intervals. Somatic growth was quantified by weighing. Organ growth was quantified by MRI and by weighing. Neoplastic growth was examined by MRI, visual inspection, and histopathological analyses. Phospho-ERK1/2 and S6 kinase were analyzed with Western blot and ELISA, respectively. Results Lung, spleen, liver, kidney, brain, and breast gland exhibited variable expression of the NRG1 receptors ErbB2, ErbB3, ErbB4, and NRG1. Body weight and tibia length were not altered in mice receiving rNRG1. MRI showed that administration of rNRG1 did not alter the volume of the lungs, liver, kidneys, brain, or spinal cord. Administration of rNRG1 did not alter the weight of the lungs, spleen, liver, kidneys, or brain. MRI, visual inspection, and histopathological analyses showed no neoplastic growth. Follow-up for 6 months showed no alteration of somatic or organ growth. rNRG1 treatment increased the levels of phospho-ERK1/2, but not phospho-S6 kinase. Conclusions Administration protocols of rNRG1 for stimulating cardiac regeneration in mice during the first month of life did not induce unwanted growth effects. Further studies may be

  14. Symplectic wavelet transformation.

    PubMed

    Fan, Hong-Yi; Lu, Hai-Liang

    2006-12-01

    Usually a wavelet transform is based on dilated-translated wavelets. We propose a symplectic-transformed-translated wavelet family psi(*)(r,s)(z-kappa) (r,s are the symplectic transform parameters, |s|(2)-|r|(2)=1, kappa is a translation parameter) generated from the mother wavelet psi and the corresponding wavelet transformation W(psi)f(r,s;kappa)=integral(infinity)(-infinity)(d(2)z/pi)f(z)psi(*)(r,s)(z-kappa). This new transform possesses well-behaved properties and is related to the optical Fresnel transform in quantum mechanical version. PMID:17099740

  15. Oncogenic Transformation of Dendritic Cells and Their Precursors Leads to Rapid Cancer Development in Mice

    PubMed Central

    Böttcher, Jan P.; Zelenay, Santiago; Rogers, Neil C.; Helft, Julie; Schraml, Barbara U.

    2015-01-01

    Dendritic cells (DCs) are powerful APCs that can induce Ag-specific adaptive immune responses and are increasingly recognized as important players in innate immunity to both infection and malignancy. Interestingly, although there are multiple described hematological malignancies, DC cancers are rarely observed in humans. Whether this is linked to the immunogenic potential of DCs, which might render them uniquely susceptible to immune control upon neoplastic transformation, has not been fully investigated. To address the issue, we generated a genetically engineered mouse model in which expression of Cre recombinase driven by the C-type lectin domain family 9, member a (Clec9a) locus causes expression of the Kirsten rat sarcoma viral oncogene homolog (Kras)G12D oncogenic driver and deletion of the tumor suppressor p53 within developing and differentiated DCs. We show that these Clec9aKras-G12D mice rapidly succumb from disease and display massive accumulation of transformed DCs in multiple organs. In bone marrow chimeras, the development of DC cancer could be induced by a small number of transformed cells and was not prevented by the presence of untransformed DCs. Notably, activation of transformed DCs did not happen spontaneously but could be induced upon stimulation. Although Clec9aKras-G12D mice showed altered thymic T cell development, peripheral T cells were largely unaffected during DC cancer development. Interestingly, transformed DCs were rejected upon adoptive transfer into wild-type but not lymphocyte-deficient mice, indicating that immunological control of DC cancer is in principle possible but does not occur during spontaneous generation in Clec9aKras-G12D mice. Our findings suggest that neoplastic transformation of DCs does not by default induce anti-cancer immunity and can develop unhindered by immunological barriers. PMID:26459350

  16. Oncogenic Transformation of Dendritic Cells and Their Precursors Leads to Rapid Cancer Development in Mice.

    PubMed

    Böttcher, Jan P; Zelenay, Santiago; Rogers, Neil C; Helft, Julie; Schraml, Barbara U; Reis e Sousa, Caetano

    2015-11-15

    Dendritic cells (DCs) are powerful APCs that can induce Ag-specific adaptive immune responses and are increasingly recognized as important players in innate immunity to both infection and malignancy. Interestingly, although there are multiple described hematological malignancies, DC cancers are rarely observed in humans. Whether this is linked to the immunogenic potential of DCs, which might render them uniquely susceptible to immune control upon neoplastic transformation, has not been fully investigated. To address the issue, we generated a genetically engineered mouse model in which expression of Cre recombinase driven by the C-type lectin domain family 9, member a (Clec9a) locus causes expression of the Kirsten rat sarcoma viral oncogene homolog (Kras)(G12D) oncogenic driver and deletion of the tumor suppressor p53 within developing and differentiated DCs. We show that these Clec9a(Kras-G12D) mice rapidly succumb from disease and display massive accumulation of transformed DCs in multiple organs. In bone marrow chimeras, the development of DC cancer could be induced by a small number of transformed cells and was not prevented by the presence of untransformed DCs. Notably, activation of transformed DCs did not happen spontaneously but could be induced upon stimulation. Although Clec9a(Kras-G12D) mice showed altered thymic T cell development, peripheral T cells were largely unaffected during DC cancer development. Interestingly, transformed DCs were rejected upon adoptive transfer into wild-type but not lymphocyte-deficient mice, indicating that immunological control of DC cancer is in principle possible but does not occur during spontaneous generation in Clec9a(Kras-G12D) mice. Our findings suggest that neoplastic transformation of DCs does not by default induce anti-cancer immunity and can develop unhindered by immunological barriers. PMID:26459350

  17. Does school-based physical activity decrease overweight and obesity in children aged 6–9 years? A two-year non-randomized longitudinal intervention study in the Czech Republic

    PubMed Central

    2012-01-01

    Background Globally, efforts aimed at the prevention of childhood obesity have led to the implementation of a range of school-based interventions. This study assessed whether augmenting physical activity (PA) within the school setting resulted in increased daily PA and decreased overweight/obesity levels in 6-9-year-old children. Methods Across the first to third primary school years, PA of 84 girls and 92 boys was objectively monitored five times (each for seven successive days) using Yamax pedometer (step counts) and Caltrac accelerometer (activity energy expenditure AEE - kcal/kg per day). Four schools were selected to participate in the research (2 intervention, 2 controls), comprising intervention (43 girls, 45 boys) and control children (41 girls, 47 boys). The study was non-randomized and the intervention schools were selected on the basis of existing PA-conducive environment. Analyses of variance (ANOVA) for repeated measures examined the PA programme and gender effects on the step counts and AEE. Logistic regression (Enter method) determined the obesity and overweight occurrence prospect over the course of implementation of the PA intervention. Results There was a significant increase of school-based PA during schooldays in intervention children (from ≈ 1718 to ≈ 3247 steps per day; and from 2.1 to ≈ 3.6 Kcal/Kg per day) in comparison with the control children. Increased school-based PA of intervention children during schooldays contributed to them achieving >10,500 steps and >10.5 Kcal/Kg per school day across the 2 years of the study, and resulted in a stop of the decline in PA levels that is known to be associated with the increasing age of children. Increased school-based PA had also positive impact on leisure time PA of schooldays and on PA at weekends of intervention children. One year after the start of the PA intervention, the odds of being overweight or obese in the intervention children was almost three times lower than that of

  18. A phloem-limited fijivirus induces the formation of neoplastic phloem tissues that house virus multiplication in the host plant.

    PubMed

    Shen, Jiangfeng; Chen, Xian; Chen, Jianping; Sun, Liying

    2016-01-01

    A number of phloem-limited viruses induce the development of tumours (enations) in the veins of host plants, but the relevance of tumour induction to the life cycle of those viruses is unclear. In this study, we performed molecular and structural analyses of tumours induced by rice black-streaked dwarf virus (RBSDV, genus Fijivirus) infection in maize plants. The transcript level of the maize cdc2 gene, which regulates the cell cycle, was highly elevated in tumour tissues. Two-dimensional electrophoresis identified 25 cellular proteins with altered accumulation in the tumour tissues. These proteins are involved in various metabolic pathways, including photosynthesis, redox, energy pathways and amino acid synthesis. Histological analysis indicated that the tumours predominantly originated from hyperplastic growth of phloem, but those neoplastic tissues have irregular structures and cell arrangements. Immunodetection assays and electron microscopy observations indicated that in the shoots, RBSDV is confined to phloem and tumour regions and that virus multiplication actively occurs in the tumour tissue, as indicated by the high accumulation of non-structural proteins and formation of viroplasms in the tumour cells. Thus, the induction of tumours by RBSDV infection provides a larger environment that is favourable for virus propagation in the host plant. PMID:27432466

  19. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    SciTech Connect

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-10-22

    Highlights: {yields} ConA induces cancer cell death targeting apoptosis and autophagy. {yields} ConA inhibits cancer cell angiogenesis. {yields} ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca{sup 2+}/Mn{sup 2+}-dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-{kappa}B-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  20. Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

    PubMed

    Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D

    2015-02-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

  1. Loss of mesenchymal bone morphogenetic protein signaling leads to development of reactive stroma and initiation of the gastric neoplastic cascade.

    PubMed

    Roy, Sébastien A B; Allaire, Joannie M; Ouellet, Camille; Maloum-Rami, Faiza; Pomerleau, Véronique; Lemieux, Étienne; Babeu, Jean-Philippe; Rousseau, Jasmin; Paquet, Marilène; Garde-Granger, Perrine; Boudreau, François; Perreault, Nathalie

    2016-01-01

    Bmps are morphogens involved in various gastric cellular functions. Studies in genetically-modified mice have shown that Bmp disruption in gastric epithelial and stromal cell compartments leads to the development of tumorigenesis. Our studies have demonstrated that abrogation of gastric epithelial Bmp signaling alone was not sufficient to recapitulate the neoplastic features associated with total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not appear to be a key player in gastric tumorigenesis initiation. These observations suggest a greater role for stromal Bmp signaling in gastric polyposis initiation. In order to identify the specific roles played by mesenchymal Bmp signaling in gastric homeostasis, we generated a mouse model with abrogation of Bmp signaling exclusively in the gastro-intestinal mesenchyme (Bmpr1a(ΔMES)). We were able to expose an unsuspected role for Bmp loss of signaling in leading normal gastric mesenchyme to adapt into reactive mesenchyme. An increase in the population of activated-fibroblasts, suggesting mesenchymal transdifferentiation, was observed in mutant stomach. Bmpr1a(ΔMES) stomachs exhibited spontaneous benign polyps with presence of both intestinal metaplasia and spasmolytic-polypeptide-expressing metaplasia as early as 90 days postnatal. These results support the novel concept that loss of mesenchymal Bmp signaling cascade acts as a trigger in gastric polyposis initiation. PMID:27609464

  2. Cingulin, a specific protein component of tight junctions, is expressed in normal and neoplastic human epithelial tissues.

    PubMed Central

    Citi, S.; Amorosi, A.; Franconi, F.; Giotti, A.; Zampi, G.

    1991-01-01

    Cingulin is a 140-kd protein localized on the cytoplasmic face of avian tight junctions. The expression of cingulin in human normal and neoplastic colonic tissue has been investigated with an antiserum against chicken cingulin. Human cingulin shares its apparent molecular mass and localization with avian cingulin. In normal colonic epithelium, villous adenomas, and differentiated adenocarcinomas, cingulin staining is observed in the junctional region of the polarized cells lining the surface, the crypts, and the glandular lumina. In poorly differentiated adenocarcinomas, labeling also is observed at the interface between cancer tissue and stroma, or in clumps of malignant cells, forming a pattern that highlights the presence of small, compressed lumina. The cingulin content of four adenocarcinomas, estimated by immunoblotting and densitometry, was higher than that of the normal tissue (150% to 230%). Cingulin was detected in a metastasis from a colon adenocarcinoma but not in nonepithelial tissues and neoplasias, suggesting that cingulin may be a useful marker in the characterization of colonic and probably other epithelial neoplasias. Images Figure 1 Figure 2 Figure 3 PMID:2012170

  3. Histopathological and Immunohistochemical Characterization of Methyl Eugenol-induced Nonneoplastic and Neoplastic Neuroendocrine Cell Lesions in Glandular Stomach of Rats.

    PubMed

    Janardhan, Kyathanahalli S; Rebolloso, Yvette; Hurlburt, Geoffrey; Olson, David; Lyght, Otis; Clayton, Natasha P; Gruebbel, Margarita; Picut, Catherine; Shackelford, Cynthia; Herbert, Ronald A

    2015-07-01

    Methyl eugenol induces neuroendocrine (NE) cell hyperplasia and tumors in F344/N rat stomach. Detailed histopathological and immunohistochemical (IHC) characterization of these tumors has not been previously reported. The objective of this study was to fill that data gap. Archived slides and paraffin blocks were retrieved from the National Toxicology Program Archives. NE hyperplasias and tumors were stained with chromogranin A, synaptophysin, amylase, gastrin, H(+)/K(+) adenosine triphosphatase (ATPase), pepsinogen, somatostatin, and cytokeratin 18 (CK18) antibodies. Many of the rats had gastric mucosal atrophy, due to loss of chief and parietal cells. The hyperplasias and tumors were confined to fundic stomach, and females were more affected than the males. Hyperplasia of NE cells was not observed in the pyloric region. Approximately one-third of the females with malignant NE tumors had areas of pancreatic acinar differentiation. The rate of metastasis was 21%, with liver being the most common site of metastasis. Immunohistochemically, the hyperplasias and tumors stained consistently with chromogranin A and synaptophysin. Neoplastic cells were also positive for amylase and CK18 and negative for gastrin, somatostatin, H(+)/K(+) ATPase, and pepsinogen. Metastatic neoplasms histologically similar to the primary neoplasm stained positively for chromogranin A and synaptophysin. Based on the histopathological and IHC features, the neoplasms appear to arise from enterochromaffin-like cells. PMID:25452433

  4. Appraisals of Bangladeshi Medicinal Plants Used by Folk Medicine Practitioners in the Prevention and Management of Malignant Neoplastic Diseases

    PubMed Central

    Kabidul Azam, Md. Nur; Rahman, Md. Mizanur; Biswas, Samanta

    2016-01-01

    Cancer is a group of diseases which is categorized to differentiate into diverse cell types and move around in the body to sites of organogenesis that is key to the process of tumor genesis. All types of cancer fall into the group of malignant neoplastic diseases. In Bangladesh, cancer is now one of the foremost killer diseases and its personal, social, and economic bearing are huge. Plant-derived natural compounds (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan) are useful for the treatment of cancer. Since there is no extensive ethnobotanical research study in Bangladesh regarding the traditional uses of medicinal plants against neoplasms, therefore, a randomized ethnopharmacological surveys were carried out in 3 districts of Bangladesh to learn more about the usage of anticancer medicinal plants and their chemical constituents having antineoplastic activity. Comprehensive interviews were conducted to the folk medicine practitioners and medicinal plants as pointed out by them were photographed, collected, deposited, and identified at the Bangladesh National Herbarium. The various plant parts have been used by the healers which included whole plant, leaves, fruits, barks, roots, and seeds. This study evaluated considerable potential for discovery of novel compounds with less side effects in the management and prevention of malignancy in cancer. PMID:27382642

  5. Relationship between receptors for epidermal growth factor and steroid hormones in normal, dysplastic and neoplastic canine mammary tissues.

    PubMed

    Donnay, I; Devleeschouwer, N; Wouters-Ballman, P; Leclercq, G; Verstegen, J

    1996-05-01

    The concentrations of receptors for epidermal growth factor (EGF-R), oestrogen (ER) and progesterone (PR) were measured in 108 samples from canine mammary tumours and 132 samples of normal mammary tissue removed surgically from 84 bitches. The history and clinical signs were also recorded. Binding sites of high affinity were detected in 70 per cent of both types of tissue and no significant variations in EGF-R concentrations or positivity were observed with the histology, location, size or number of mammary tumours or the age of the animal. A significant direct correlation (P = 0.002) was observed between the concentrations of ER and EGF-R only in malignant tumours. The concentrations of EGF-R were significantly correlated (P = 0.04) in normal mammary tissues adjacent to and distant from the lesions, but not between normal tissue and tumour tissue. No significant differences were observed in the expression of EGF-R in normal and neoplastic tissues from the same bitches. The direct correlation between the concentrations of EGF-R and ER in malignant tumours could be related to an oestrogen-dependent expression of EGF-R or to a similar pattern of regulation of the receptors. PMID:8735517

  6. Appraisals of Bangladeshi Medicinal Plants Used by Folk Medicine Practitioners in the Prevention and Management of Malignant Neoplastic Diseases.

    PubMed

    Kabidul Azam, Md Nur; Rahman, Md Mizanur; Biswas, Samanta; Ahmed, Md Nasir

    2016-01-01

    Cancer is a group of diseases which is categorized to differentiate into diverse cell types and move around in the body to sites of organogenesis that is key to the process of tumor genesis. All types of cancer fall into the group of malignant neoplastic diseases. In Bangladesh, cancer is now one of the foremost killer diseases and its personal, social, and economic bearing are huge. Plant-derived natural compounds (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan) are useful for the treatment of cancer. Since there is no extensive ethnobotanical research study in Bangladesh regarding the traditional uses of medicinal plants against neoplasms, therefore, a randomized ethnopharmacological surveys were carried out in 3 districts of Bangladesh to learn more about the usage of anticancer medicinal plants and their chemical constituents having antineoplastic activity. Comprehensive interviews were conducted to the folk medicine practitioners and medicinal plants as pointed out by them were photographed, collected, deposited, and identified at the Bangladesh National Herbarium. The various plant parts have been used by the healers which included whole plant, leaves, fruits, barks, roots, and seeds. This study evaluated considerable potential for discovery of novel compounds with less side effects in the management and prevention of malignancy in cancer. PMID:27382642

  7. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    PubMed Central

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  8. Identification of circulating microRNAs during the liver neoplastic process in a murine model of hereditary tyrosinemia type 1.

    PubMed

    Angileri, Francesca; Morrow, Geneviève; Scoazec, Jean-Yves; Gadot, Nicolas; Roy, Vincent; Huang, Suli; Wu, Tangchun; Tanguay, Robert M

    2016-01-01

    Hereditary tyrosinemia type 1 (HT1) is a severe inborn error of metabolism, impacting the tyrosine catabolic pathway with a high incidence of hepatocellular carcinoma (HCC). Using a HT1 murine model, we investigated the changes in profiles of circulating and hepatic miRNAs. The aim was to determine if plasma miRNAs could be used as non-invasive markers of liver damage in HT1 progression. Plasma and liver miRNAome was determined by deep sequencing after HT1 phenotype was induced. Sequencing analysis revealed deregulation of several miRNAs including let-7/miR-98 family, miR-21 and miR-148a, during manifestation of liver pathology. Three miRNAs (miR-98, miR-200b, miR-409) presenting the highest plasmatic variations among miRNAs found in both plasma and liver and with >1000 reads in at least one plasma sample, were further validated by RT-qPCR. Two of these miRNAs have protein targets involved in HT1 and significant changes in their circulating levels are detectable prior an increase in protein expression of alpha-fetoprotein, the current biomarker for HCC diagnosis. Future assessment of these miRNAs in HT1 patients and their association with liver neoplastic lesions might designate these molecules as potential biomarkers for monitoring HT1 damage progression, improving diagnosis for early HCC detection and the design of novel therapeutic targets. PMID:27282650

  9. Loss of mesenchymal bone morphogenetic protein signaling leads to development of reactive stroma and initiation of the gastric neoplastic cascade

    PubMed Central

    Roy, Sébastien A. B.; Allaire, Joannie M.; Ouellet, Camille; Maloum-Rami, Faiza; Pomerleau, Véronique; Lemieux, Étienne; Babeu, Jean-Philippe; Rousseau, Jasmin; Paquet, Marilène; Garde-Granger, Perrine; Boudreau, François; Perreault, Nathalie

    2016-01-01

    Bmps are morphogens involved in various gastric cellular functions. Studies in genetically-modified mice have shown that Bmp disruption in gastric epithelial and stromal cell compartments leads to the development of tumorigenesis. Our studies have demonstrated that abrogation of gastric epithelial Bmp signaling alone was not sufficient to recapitulate the neoplastic features associated with total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not appear to be a key player in gastric tumorigenesis initiation. These observations suggest a greater role for stromal Bmp signaling in gastric polyposis initiation. In order to identify the specific roles played by mesenchymal Bmp signaling in gastric homeostasis, we generated a mouse model with abrogation of Bmp signaling exclusively in the gastro-intestinal mesenchyme (Bmpr1aΔMES). We were able to expose an unsuspected role for Bmp loss of signaling in leading normal gastric mesenchyme to adapt into reactive mesenchyme. An increase in the population of activated-fibroblasts, suggesting mesenchymal transdifferentiation, was observed in mutant stomach. Bmpr1aΔMES stomachs exhibited spontaneous benign polyps with presence of both intestinal metaplasia and spasmolytic-polypeptide-expressing metaplasia as early as 90 days postnatal. These results support the novel concept that loss of mesenchymal Bmp signaling cascade acts as a trigger in gastric polyposis initiation. PMID:27609464

  10. Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

    PubMed Central

    Peter, Barbara; Winter, Georg E.; Blatt, Katharina; Bennett, Keiryn L.; Stefanzl, Gabriele; Rix, Uwe; Eisenwort, Gregor; Hadzijusufovic, Emir; Gridling, Manuela; Dutreix, Catherine; Hoermann, Gregor; Schwaab, Juliana; Radia, Deepti; Roesel, Johannes; Manley, Paul W.; Reiter, Andreas; Superti-Furga, Giulio; Valent, Peter

    2016-01-01

    Proteomic-based drug testing is an emerging approach to establish the clinical value and anti-neoplastic potential of multi-kinase inhibitors. The multikinase inhibitor midostaurin (PKC412) is a promising new agent used to treat patients with advanced systemic mastocytosis (SM). We examined the target interaction-profiles and the mast cell (MC)-targeting effects of two pharmacologically relevant midostaurin metabolites, CGP52421 and CGP62221. All three compounds, midostaurin and the two metabolites, suppressed IgE-dependent histamine secretion in basophils and MC with reasonable IC50 values. Midostaurin and CGP62221 also produced growth-inhibition and dephosphorylation of KIT in the MC leukemia cell line HMC-1.2, whereas the second metabolite, CGP52421, that accumulates in vivo, showed no substantial effects. Chemical proteomic profiling and drug-competition experiments revealed that midostaurin interacts with KIT and several additional kinase-targets. The key downstream-regulator FES was recognized by midostaurin and CGP62221, but not by CGP52421 in MC lysates, whereas the IgE-receptor-downstream target SYK was recognized by both metabolites. Together, our data show that the clinically relevant midostaurin metabolite CGP52421 inhibits IgE-dependent histamine release, but is a weak inhibitor of MC proliferation which may have clinical implications and may explain why mediator-related symptoms improve in SM patients even when disease progression occurs. PMID:26349526

  11. A phloem-limited fijivirus induces the formation of neoplastic phloem tissues that house virus multiplication in the host plant

    PubMed Central

    Shen, Jiangfeng; Chen, Xian; Chen, Jianping; Sun, Liying

    2016-01-01

    A number of phloem-limited viruses induce the development of tumours (enations) in the veins of host plants, but the relevance of tumour induction to the life cycle of those viruses is unclear. In this study, we performed molecular and structural analyses of tumours induced by rice black-streaked dwarf virus (RBSDV, genus Fijivirus) infection in maize plants. The transcript level of the maize cdc2 gene, which regulates the cell cycle, was highly elevated in tumour tissues. Two-dimensional electrophoresis identified 25 cellular proteins with altered accumulation in the tumour tissues. These proteins are involved in various metabolic pathways, including photosynthesis, redox, energy pathways and amino acid synthesis. Histological analysis indicated that the tumours predominantly originated from hyperplastic growth of phloem, but those neoplastic tissues have irregular structures and cell arrangements. Immunodetection assays and electron microscopy observations indicated that in the shoots, RBSDV is confined to phloem and tumour regions and that virus multiplication actively occurs in the tumour tissue, as indicated by the high accumulation of non-structural proteins and formation of viroplasms in the tumour cells. Thus, the induction of tumours by RBSDV infection provides a larger environment that is favourable for virus propagation in the host plant. PMID:27432466

  12. Identification of circulating microRNAs during the liver neoplastic process in a murine model of hereditary tyrosinemia type 1

    PubMed Central

    Angileri, Francesca; Morrow, Geneviève; Scoazec, Jean-Yves; Gadot, Nicolas; Roy, Vincent; Huang, Suli; Wu, Tangchun; Tanguay, Robert M.

    2016-01-01

    Hereditary tyrosinemia type 1 (HT1) is a severe inborn error of metabolism, impacting the tyrosine catabolic pathway with a high incidence of hepatocellular carcinoma (HCC). Using a HT1 murine model, we investigated the changes in profiles of circulating and hepatic miRNAs. The aim was to determine if plasma miRNAs could be used as non-invasive markers of liver damage in HT1 progression. Plasma and liver miRNAome was determined by deep sequencing after HT1 phenotype was induced. Sequencing analysis revealed deregulation of several miRNAs including let-7/miR-98 family, miR-21 and miR-148a, during manifestation of liver pathology. Three miRNAs (miR-98, miR-200b, miR-409) presenting the highest plasmatic variations among miRNAs found in both plasma and liver and with >1000 reads in at least one plasma sample, were further validated by RT-qPCR. Two of these miRNAs have protein targets involved in HT1 and significant changes in their circulating levels are detectable prior an increase in protein expression of alpha-fetoprotein, the current biomarker for HCC diagnosis. Future assessment of these miRNAs in HT1 patients and their association with liver neoplastic lesions might designate these molecules as potential biomarkers for monitoring HT1 damage progression, improving diagnosis for early HCC detection and the design of novel therapeutic targets. PMID:27282650

  13. Diet and tumor LKB1 expression interact to determine sensitivity to anti-neoplastic effects of metformin in vivo.

    PubMed

    Algire, C; Amrein, L; Bazile, M; David, S; Zakikhani, M; Pollak, M

    2011-03-10

    Hypothesis-generating epidemiological research has suggested that cancer burden is reduced in diabetics treated with metformin and experimental work has raised questions regarding the role of direct adenosine monophosphate-activated protein kinase (AMPK)-mediated anti-neoplastic effects of metformin as compared with indirect effects attributable to reductions in circulating insulin levels in the host. We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression. In the absence of hyperinsulinemia, metformin inhibited only the growth of tumors transfected with short hairpin RNA against LKB1, a finding attributable neither to an effect on host insulin level nor to activation of AMPK within the tumor. Further investigation in vitro showed that cells with reduced LKB1 expression are more sensitive to metformin-induced adenosine triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent energy-conservation mechanisms. Thus, loss of function of LKB1 can accelerate proliferation in contexts where it functions as a tumor suppressor, but can also sensitize cells to metformin. These findings predict that any clinical utility of metformin or similar compounds in oncology will be restricted to subpopulations defined by host insulin levels and/or loss of function of LKB1. PMID:21102522

  14. Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype.

    PubMed

    Sato, Shingo; Tang, Yuning J; Wei, Qingxia; Hirata, Makoto; Weng, Angela; Han, Ilkyu; Okawa, Atsushi; Takeda, Shu; Whetstone, Heather; Nadesan, Puvindran; Kirsch, David G; Wunder, Jay S; Alman, Benjamin A

    2016-07-26

    The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype. PMID:27425618

  15. Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth.

    PubMed

    Peter, B; Winter, G E; Blatt, K; Bennett, K L; Stefanzl, G; Rix, U; Eisenwort, G; Hadzijusufovic, E; Gridling, M; Dutreix, C; Hoermann, G; Schwaab, J; Radia, D; Roesel, J; Manley, P W; Reiter, A; Superti-Furga, G; Valent, P

    2016-02-01

    Proteomic-based drug testing is an emerging approach to establish the clinical value and anti-neoplastic potential of multikinase inhibitors. The multikinase inhibitor midostaurin (PKC412) is a promising new agent used to treat patients with advanced systemic mastocytosis (SM). We examined the target interaction profiles and the mast cell (MC)-targeting effects of two pharmacologically relevant midostaurin metabolites, CGP52421 and CGP62221. All three compounds, midostaurin and the two metabolites, suppressed IgE-dependent histamine secretion in basophils and MC with reasonable IC(50) values. Midostaurin and CGP62221 also produced growth inhibition and dephosphorylation of KIT in the MC leukemia cell line HMC-1.2, whereas the second metabolite, CGP52421, which accumulates in vivo, showed no substantial effects. Chemical proteomic profiling and drug competition experiments revealed that midostaurin interacts with KIT and several additional kinase targets. The key downstream regulator FES was recognized by midostaurin and CGP62221, but not by CGP52421 in MC lysates, whereas the IgE receptor downstream target SYK was recognized by both metabolites. Together, our data show that the clinically relevant midostaurin metabolite CGP52421 inhibits IgE-dependent histamine release, but is a weak inhibitor of MC proliferation, which may have clinical implications and may explain why mediator-related symptoms improve in SM patients even when disease progression occurs. PMID:26349526

  16. Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast.

    PubMed Central

    Bussolati, G.; Cassoni, P.; Ghisolfi, G.; Negro, F.; Sapino, A.

    1996-01-01

    Recent evidence indicates that oxytocin (OT), in addition to the induction of myometrial and myoepithelial cell contraction, can influence proliferation and differentiation in developing mammary glands and in breast cancer cells, hence the interest in detecting and locating OT receptors (OTRs). We produced rabbit antisera and a monoclonal antibody against a synthetic peptide corresponding to the carboxy terminus of the predicted OTR sequence. We tested their specificity in immunoblasts and immunocytochemical tests. All of the antibodies specifically stained myometrium (at term of pregnancy). In the human breast, OTRs were detected in myoepithelial cells along ducts of normal lobules and in sclerosing adenosis. Intraductal cells in benign hyperplastic lesions were also positive. OTRs were demonstrated in cases of primary and metastatic carcinomas of the breast. In the same tissues, OTR gene expression was shown by reverse transcriptase polymerase chain reaction procedures detecting the specific mRNA. These results suggest that the interaction between OT and its receptors might play a role in the origin and evolution of non-neoplastic lesions and carcinomas of the breast. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:8669475

  17. The efficacy of high-intensity, focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva.

    PubMed

    Zhou, W; Zhu, L; Zhou, H; Shen, K; Lang, J; Cui, Q; Shi, H

    2016-01-01

    Non-neoplastic epithelial disorders of the vulva (NNEDV) are common types of vulval lesions. Although corticosteroids represent a first-line treatment for NNEDV, concerns exist about the safety associated with long-term topical corticosteroid use. Recently, several clinical trials have identified high-intensity focused ultrasound (HIFU) as a promising treatment modality for NNEDV. The aim of this multi-center, randomized, controlled clinical trial was to investigate the efficacy of HIFU therapy in women with NNEDV based on histological alterations. We enrolled patients who were clinically diagnosed with NNEDV. They were randomized into 2 treatment groups: 1) halcinonide for 3 months or 2) HIFU once. A total of 123 patients were biopsied both prior to and after the therapy, and 62 and 61 patients were assigned to the HIFU and halcinonide groups, respectively. The histological changes were then analyzed. After the treatments, the therapeutic effects were observed in both groups. Comparing the diagnosis and alterations in lichenoid and sclerotic patterns and in chronic inflammation, we found statistically significant differences. Furthermore, when compared with the halcinonide group, the HIFU group exhibited enhanced curative effects that were statistically significant (P = 0.039). Based on the histological evidence from this randomized, controlled trial, HIFU represents an effective method for the treatment of NNEDV. PMID:27188744

  18. 28-Channel rotary transformer

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1981-01-01

    Transformer transmits power and digital data across rotating interface. Array has many parallel data channels, each with potential l megabaud data rate. Ferrite-cored transformers are spaced along rotor; airgap between them reduces crosstalk.

  19. Equations For Rotary Transformers

    NASA Technical Reports Server (NTRS)

    Salomon, Phil M.; Wiktor, Peter J.; Marchetto, Carl A.

    1988-01-01

    Equations derived for input impedance, input power, and ratio of secondary current to primary current of rotary transformer. Used for quick analysis of transformer designs. Circuit model commonly used in textbooks on theory of ac circuits.

  20. Chemical Transformation Simulator

    EPA Science Inventory

    The Chemical Transformation Simulator (CTS) is a web-based, high-throughput screening tool that automates the calculation and collection of physicochemical properties for an organic chemical of interest and its predicted products resulting from transformations in environmental sy...

  1. Transformation of Pasteurella novicida

    PubMed Central

    Tyeryar, Franklin J.; Lawton, William D.

    1969-01-01

    Deoxyribonucleic acid from a streptomycin-resistant mutant of Pasteurella novicida transformed portions of P. novicida streptomycin-sensitive populations to streptomycin-resistant. Similarly, mutants auxotrophic for tryptophan or purine biosynthesis were also transformed to nutritional independence. PMID:5359612

  2. Shiftable multiscale transforms

    NASA Technical Reports Server (NTRS)

    Simoncelli, Eero P.; Freeman, William T.; Adelson, Edward H.; Heeger, David J.

    1992-01-01

    A type of translational invariance, referred to as shiftability, is defined for wavelet transforms. The property of shiftability is first discussed with respect to individual parameters: spatial position, orientation, and scale. The discussion then focuses on transformations that are simultaneously shiftable with respect to subsets of these parameters. It is shown that the critical sampling condition on the wavelet transforms must be relaxed to achieve shiftability. Two example transforms are implemented and applied to several signal and image processing problems.

  3. Achieving Perspective Transformation.

    ERIC Educational Resources Information Center

    Nowak, Jens

    Perspective transformation is a consciously achieved state in which the individual's perspective on life is transformed. The new perspective serves as a vantage point for life's actions and interactions, affecting the way life is lived. Three conditions are basic to achieving perspective transformation: (1) "feeling" experience, i.e., getting in…

  4. Identification of a non-specific inhibitor of (methyl/sup 3/H)thymidine incorporation into DNA of normal and pre-neoplastic cells

    SciTech Connect

    Overbye, L.J.

    1989-01-01

    Growth in mammalian cells is controlled by a variety of factors, both stimulatory and inhibitory. Bullough et al. (2) first proposed the idea that endogenous mitotic inhibitors may play a role in controlling cellular proliferation. Inhibitors may be tissue-specific (9) or non-specific (for review see Lozzio et al. (5)). Although many inhibitors are proteins of high molecular weights, several low molecular weight inhibitors of (/sup 3/H) thymidine incorporation (and therefore DNA synthesis) have been identified (1,3,6). Unlabelled thymidine has also been noted to be inhibitory (4). This paper describes a non-specific, unstable inhibitor that is found in media conditioned by neoplastic epithelial cells and some normal fibroblasts and inhibits (/sup 3/H) thymidine incorporation into normal and pre-neoplastic cells. The inhibitory activity has not been isolated and could consists of more than one compound. 9 refs., 1 tab.

  5. Prognostic Impact of Reduced Connexin43 Expression and Gap Junction Coupling of Neoplastic Stromal Cells in Giant Cell Tumor of Bone

    PubMed Central

    Balla, Peter; Maros, Mate Elod; Barna, Gabor; Antal, Imre; Papp, Gergo; Sapi, Zoltan; Athanasou, Nicholas Anthony; Benassi, Maria Serena; Picci, Pierro; Krenacs, Tibor

    2015-01-01

    Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in α-smooth muscle actin positive than α-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in

  6. Three-Dimensional Printing as an Interdisciplinary Communication Tool: Preparing for Removal of a Giant Renal Tumor and Atrium Neoplastic Mass.

    PubMed

    Golab, Adam; Slojewski, Marcin; Brykczynski, Miroslaw; Lukowiak, Magdalena; Boehlke, Marek; Matias, Daniel; Smektala, Tomasz

    2016-01-01

    Three-dimensional (3D) printing involves preparing 3D objects from a digital model. These models can be used to plan and practice surgery. We used 3D printing to plan for a rare complicated surgery involving the removal of a renal tumor and neoplastic mass, which reached the heart atrium. A printed kidney model was an essential element of communication for physicians with different specializations. PMID:27585198

  7. Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer

    PubMed Central

    Hyland, Paula B.; Kinsella, B. Therese

    2015-01-01

    The prostanoid thromboxane (TX) A2 is increasingly implicated in neoplastic progression, including prostate cancer (PCa). Mechanistically, we recently identified protein kinase C-related kinase (PRK) 1 as a functional interactant of both the TPα and TPβ isoforms of the human T prostanoid receptor (TP). The interaction with PRK1 was not only essential for TPα/TPβ-induced PCa cell migration but also enabled the TXA2-TP axis to induce phosphorylation of histone H3 at Thr11 (H3Thr11), an epigenetic marker both essential for and previously exclusively associated with androgen-induced chromatin remodelling and transcriptional activation. PRK1 is a member of a subfamily of three structurally related kinases comprising PRK1/PKNα, PRK2/PKNγ and PRK3/PKNβ that are widely yet differentially implicated in various cancers. Hence, focusing on the setting of prostate cancer, this study investigated whether TPα and/or TPβ might also complex with PRK2 and PRK3 to regulate their activity and neoplastic responses. While TPα and TPβ were found in immune complexes with PRK1, PRK2 and PRK3 to regulate their activation and signalling, they do so differentially and in a TP agonist-regulated manner dependent on the T-loop activation status of the PRKs but independent of their kinase activity. Furthermore, TXA2-mediated neoplastic responses in prostate adenocarcinoma PC-3 cells, including histone H3Thr11 phosphorylation, was found to occur through a PRK1- and PRK2-, but not PRK3-, dependent mechanism. Collectively, these data suggest that TXA2 acts as both a neoplastic and epigenetic regulator and provides a mechanistic explanation, at least in part, for the prophylactic benefits of Aspirin in reducing the risk of certain cancers. PMID:26296974

  8. Note: Tesla transformer damping

    NASA Astrophysics Data System (ADS)

    Reed, J. L.

    2012-07-01

    Unexpected heavy damping in the two winding Tesla pulse transformer is shown to be due to small primary inductances. A small primary inductance is a necessary condition of operability, but is also a refractory inefficiency. A 30% performance loss is demonstrated using a typical "spiral strip" transformer. The loss is investigated by examining damping terms added to the transformer's governing equations. A significant alteration of the transformer's architecture is suggested to mitigate these losses. Experimental and simulated data comparing the 2 and 3 winding transformers are cited to support the suggestion.

  9. N- and C-terminal isoforms of Arg quantified by real-time PCR are specifically expressed in human normal and neoplastic cells, in neoplastic cell lines, and in HL-60 cell differentiation.

    PubMed

    Perego, Roberto A; Corizzato, Matteo; Bianchi, Cristina; Eroini, Barbara; Bosari, Silvano

    2005-04-01

    The human ABL2 (or ARG) gene codes for a nonreceptor tyrosine kinase is involved in translocation with the ETV6 gene in human leukemia and has an altered expression in several human carcinomas. Two isoforms of Arg with different N-termini (1A and 1B) have been described. The C-terminal domain of Arg contains two F-actin-binding sequences that perform a number of actions related to cell morphology and motility by interacting with actin filaments. We have identified different-sized specific cDNAs in hematopoietic, epithelial, nervous, and fibroblastic cells by means of the reverse transcription (RT)-polymerase chain reaction (PCR) analysis of human Arg mRNA. Some of these cDNAs showed an adjunctive alternative splice event involving the 63 bp sequence of exon II, thus leading to four cDNA types with different N-termini: 1A long and short, and 1B long and short. Other cDNAs lacked a 309 bp sequence in the last exon involving one of the C-terminal F-actin binding domains, thus giving rise to two cDNA types: C-termini long and short. Quantified by real-time PCR-quantitative RT-PCR-these Arg transcript isoforms have specific expression patterns not only in different normal and tumor cell types, but also during cell differentiation and growth arrest. These isoforms maintained the open reading frames, and eight putative proteins were predicted. The different C-termini isoforms seem to retain the same quantitative reciprocal ratio of their respective transcripts. The Arg protein isoforms with different C-terminal actin-binding domains and different N-termini might have specific cellular localizations/concentrations, and differently regulated catalytic activity with different implications in normal and neoplastic cells. PMID:15765532

  10. Cross-Analysis of Gene and miRNA Genome-Wide Expression Profiles in Human Fibroblasts at Different Stages of Transformation

    PubMed Central

    Ostano, Paola; Bione, Silvia; Belgiovine, Cristina; Chiodi, Ilaria; Ghimenti, Chiara; Scovassi, A. Ivana; Chiorino, Giovanna

    2012-01-01

    Abstract We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non-transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c-Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis. PMID:22321013

  11. Transformation pathways of liposomes.

    PubMed

    Hotani, H

    1984-09-01

    Liposomes undergoing transformation were observed by dark-field light microscopy in order to study the role of lipid in morphogenesis of biological vesicular structures. Liposomes were found to transform sequentially in a well-defined manner through one of several transformation pathways. A circular biconcave form was an initial shape in all the pathways and it transformed into a stable thin flexible filament or small spheres via a variety of regularly shaped vesicles which possessed geometrical symmetry. The transformation was reversible up to a certain point in each pathway. Osmotic pressure was found to be the driving force for the transformations. Biological membrane vesicles such as trypsinized red cell ghosts also transformed by similar pathways. PMID:6548263

  12. Establishment of 3D Co-Culture Models from Different Stages of Human Tongue Tumorigenesis: Utility in Understanding Neoplastic Progression

    PubMed Central

    Sawant, Sharada; Dongre, Harsh; Singh, Archana Kumari; Joshi, Shriya; Costea, Daniela Elena; Mahadik, Snehal; Ahire, Chetan; Makani, Vidhi; Dange, Prerana; Sharma, Shilpi; Chaukar, Devendra; Vaidya, Milind

    2016-01-01

    To study multistep tumorigenesis process, there is a need of in-vitro 3D model simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue models comprising various stages of neoplastic progression of tongue tumorigenesis and to evaluate the utility of these models to investigate the role of stromal fibroblasts in maintenance of desmosomal anchoring junctions using transmission electron microscopy. We reconstituted in-vitro models representing normal, dysplastic, and malignant tissues by seeding primary keratinocytes on either fibroblast embedded in collagen matrix or plain collagen matrix in growth factor-free medium. The findings of histomorphometry, immunohistochemistry, and electron microscopy analyses of the three types of 3D cultures showed that the stratified growth, cell proliferation, and differentiation were comparable between co-cultures and their respective native tissues; however, they largely differed in cultures grown without fibroblasts. The immunostaining intensity of proteins, viz., desmoplakin, desmoglein, and plakoglobin, was reduced as the disease stage increased in all co-cultures as observed in respective native tissues. Desmosome-like structures were identified using immunogold labeling in these cultures. Moreover, electron microscopic observations revealed that the desmosome number and their length were significantly reduced and intercellular spaces were increased in cultures grown without fibroblasts when compared with their co-culture counterparts. Our results showed that the major steps of tongue tumorigenesis can be reproduced in-vitro. Stromal fibroblasts play a role in regulation of epithelial thickness, cell proliferation, differentiation, and maintenance of desmosomalanchoring junctions in in-vitro grown tissues. The reconstituted co-culture models could help to answer various biological questions especially related to tongue tumorigenesis. PMID:27501241

  13. Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2

    PubMed Central

    Parkinson, Eric Kenneth

    2013-01-01

    The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

  14. In vitro cytotoxicity of Selol-loaded magnetic nanocapsules against neoplastic cell lines under AC magnetic field activation

    NASA Astrophysics Data System (ADS)

    Falqueiro, A. M.; Siqueira-Moura, M. P.; Jardim, D. R.; Primo, F. L.; Morais, P. C.; Mosiniewicz-Szablewska, E.; Suchocki, P.; Tedesco, A. C.

    2012-04-01

    The goals of this study are to evaluate invitro compatibility of magnetic nanomaterials and their therapeutic potential against cancer cells. Highly stable ionic magnetic fluid sample (maghemite, γ-Fe2O3) and Selol were incorporated into polymeric nanocapsules by nanoprecipitation method. The cytotoxic effect of Selol-loaded magnetic nanocapsules was assessed on murine melanoma (B16-F10) and oral squamous cell carcinoma (OSCC) cell lines following AC magnetic field application. The influence of different nanocapsules on cell viability was investigated by colorimetric MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the absence of AC magnetic field Selol-loaded magnetic nanocapsules, containing 100 µg/mL Selol plus 5 × 1012 particle/mL, showed antitumoral activity of about 50% on B16-F10 melanoma cells while OSCC carcinoma cells demonstrated drug resistance at all concentrations of Selol and magnetic fluid (range of 100-500 µg/mL Selol and 5 × 1012-2.5 × 1013 particle/mL). On the other hand, under AC applied fields (1 MHz and 40 Oe amplitude) B16-F10 cell viability was reduced down to 40.5% (±3.33) at the highest concentration of nanoencapsulated Selol. The major effect, however, was observed on OSCC cells since the cell viability drops down to about 33.3% (±0.38) under application of AC magnetic field. These findings clearly indicate that the Selol-loaded magnetic nanocapsules present different toxic effects on neoplastic cell lines. Further, the cytotoxic effect was maximized under AC magnetic field application on OSCC, which emphasizes the effectiveness of the magnetohyperthermia approach.

  15. Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium.

    PubMed

    Fu, Xiao Wen; Song, Ping Fang; Spindel, Eliot R

    2015-11-01

    The ly-6 proteins are a large family of proteins that resemble the snake three finger alpha toxins such as α-bungarotoxin and are defined by their multiple cysteine residues. Multiple members of the ly-6 protein family can modulate nicotinic signaling including lynx1, lynx2, slurp-1, slurp-2 and prostate stem cell antigen (PSCA). Consistent with the expression of multiple nicotinic receptors in bronchial epithelium, multiple members of the nicotinic-modulatory ly-6 proteins are expressed in lung including lynx1 and lynx2. We studied the role of lynx1 as an exemplar of the role of ly-6 proteins in lung. Our data demonstrates that lynx1 acts as a negative modulator of nicotinic signaling in normal and neoplastic lung. In normal lung lynx1 serves to limit the ability of chronic nicotine exposure to increase levels of nicotinic receptors and also serves to limit the ability of nicotine to upregulate levels of GABAA receptors in lung. In turn this allows lynx1 to limit the ability of nicotine to upregulate levels of mucin which is mediated by GABAergic signaling. This suggests that lynx1-mimetics may have potential for treatment of asthma and COPD. In that most lung cancer cells also express nicotinic receptor and lynx1 we examined the role of lynx-1 in lung cancer. Lynx1 levels are decreased in lung cancers compared to adjacent normal lung. Knockdown of lynx1 by siRNAs increased growth of lung cancer cells while expression of lynx1 in lung cancer cell decreased cell proliferation. This suggests that lynx1 is an endogenous regulator of lung cancer growth. Given that multiple small molecule negative and positive allosteric modulators of nicotinic receptors have already been developed, this suggests that lynx1 is a highly druggable target both for development of drugs that may limit lung cancer growth as well as for drugs that may be effective for asthma or COPD treatment. PMID:26025503

  16. Hepatotoxin N-nitrosomorpholine-induced carcinogenesis in rat liver: ex vivo exploration of preneoplastic and neoplastic hepatocytes.

    PubMed

    Jeong, Jin Sook; Lee, Sang Hyeung; Jung, Kap Joong; Choi, Yong C; Park, Woong Yang; Kim, In Hoo; Kim, Sang Soon

    2003-02-01

    N-nitrosomorpholine (NNM) is a hepatotoxic and hepatocarcinogenic agent. This agent was administered in the form of drinking water which contained 200 mg of NNM/liter. Its time-dependent intake profile showed four phases over 20 weeks, followed by a fifth phase where only water was supplied. Most frequently, hepatocellular carcinoma appeared between the end of phase IV and the beginning of phase V. At 5 weeks of NNM administration, foci of altered hepatocytes (FAH) containing 100-1000 hepatocytes could be isolated together with free hepatocytes by the collagenase perfusion method. When these foci were grown on the William's Medium E containing hormonally defined medium, they were able to survive approximately twice as long as normal hepatocytes At 10 weeks of NNM administration, few FAH were isolated together with free hepatocytes. The hepatocytes which had been placed under extended chemical stress showed increased heat tolerance (7 to 8 h) at 43 degrees C, while normal hepatocytes could survive 3 to 4 h. At the neoplastic phase spanning the end of the 20 weeks of the NNM administration and water phase, the rats bearing hepatocellular carcinoma entered the terminal stage, where observable tumor masses could be isolated from the tumor bearing liver and tested for ex vivo growth in tissue culture. After stabilization of the isolated primary hepatoma cells through 10 passages of propagation on William's Medium E or minimal Eagle's medium containing 10% FBS, their gene expression profile was analyzed by DNA microarray and compared with the profile of normal hepatocytes. The comparison revealed that upregulation involved ribosome-dependent protein synthesis, including 40S ribosomal proteins (S4, S7, S18, S20), 60S ribosomal proteins (L6, L21, L32, L37, P1), initiation factor 4A, and elongation factor 1alpha. PMID:12645635

  17. Evolutionary malignant resistance of cells to damaging factors as common biological defence mechanism in neoplastic development. Review of conception.

    PubMed

    Monceviciute-Eringiene, E

    2000-09-01

    Cells have some inborn resistance to harmful factors, which could be called physiological or natural resistance. The mechanisms of multixenobiotic resistance (MXR) and multidrug resistance (MDR) have common features in the formation of acquired resistance in microorganisms, carcinogenesis, tumour metastases and chemotherapy or irradiation. ATP-dependent membrane P-glycoprotein, as an MDR efflux pump, glutathione S-transferases and other products of evolutionary resistance-related genes arised for exportation and detoxification of cytotoxic xenobiotics and drugs are transmitted from bacteria to man. On the one hand, this evolutionary MXR as a common biological defence mechanism is a "driving" power to conserve homeostasis of cells, tissues and organs. On the other hand, mutation, selection and simplification of properties are the causes of functional and morphological changes in tumour cells which regress to a more primitive mode of existence (atavism) for adaptation to survival. In the present work are presented data on the forms of E. coli resistant to antibiotics and of sarcoma 45 resistant to alkylic preparations. They may be helpful in revealing the causes of resistance and acquired accelerated growth of cells. The development of tumours as fibromas 14-15 years following injection of a vital dye trypan blue into human skin supports our conception that neoplastic growth is a particular case of the evolutionary resistance of cells adapted to the damaging factors. So, tumour cells adopting the enhancement mechanisms of general biological persistent resistance, i. e. undergoing repeated cycles of malignancy enhancement, adapt themselves to survive under the changed unfavourable conditions. PMID:11144527

  18. MCT-1 expression and PTEN deficiency synergistically promote neoplastic multinucleation through the Src/p190B signaling activation.

    PubMed

    Wu, M-H; Chen, Y-A; Chen, H-H; Chang, K-W; Chang, I-S; Wang, L-H; Hsu, H-L

    2014-10-23

    Multinucleation is associated with malignant neoplasms; however, the molecular mechanism underlying the nuclear abnormality remains unclear. Loss or mutation of PTEN promotes the development of malignant tumors. We now demonstrate that increased expression of the oncogene MCT-1 (multiple copies in T-cell malignancy 1) antagonizes PTEN gene presentation, PTEN protein stability and PTEN functional activity, thereby further promoting phosphoinositide 3 kinase/AKT signaling, survival rate and malignancies of the PTEN-deficient cells. In the PTEN-null cancer cells, MCT-1 interacts with p190B and Src in vivo, supporting that they are in proximity of the signaling complexes. MCT-1 overexpression and PTEN loss synergistically augments the Src/p190B signaling function that leads to inhibition of RhoA activity. Under such a condition, the incidence of mitotic catastrophes including spindle multipolarity and cytokinesis failure is enhanced, driving an Src/p190B/RhoA-dependent neoplastic multinucleation. Targeting MCT-1 by the short hairpin RNA markedly represses the Src/p190B function, improves nuclear structures and suppresses xenograft tumorigenicity of the PTEN-null breast cancer cells. Consistent with the oncogenic effects in vitro, clinical evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene promotion and PTEN gene suppression in human breast cancer. Accordingly, MCT-1 gene induction is recognized as a potential biomarker of breast tumor development. Abrogating MCT-1 function may be a promising stratagem for management of breast cancer involving Src hyperactivation and/or PTEN dysfunction. PMID:24858043

  19. Evaluating the Effectiveness of an Antimicrobial Stewardship Program on Reducing the Incidence Rate of Healthcare-Associated Clostridium difficile Infection: A Non-Randomized, Stepped Wedge, Single-Site, Observational Study

    PubMed Central

    McArthur, Leslie

    2016-01-01

    Background The incidence rate of healthcare-associated Clostridium difficile infection (HA-CDI) is estimated at 1 in 100 patients. Antibiotic exposure is the most consistently reported risk factor for HA-CDI. Strategies to reduce the risk of HA-CDI have focused on reducing antibiotic utilization. Prospective audit and feedback is a commonly used antimicrobial stewardship intervention (ASi). The impact of this ASi on risk of HA-CDI is equivocal. This study examines the effectiveness of a prospective audit and feedback ASi on reducing the risk of HA-CDI. Methods Single-site, 339 bed community-hospital in Barrie, Ontario, Canada. Primary outcome is HA-CDI incidence rate. Daily prospective and audit ASi is the exposure variable. ASi implemented across 6 wards in a non-randomized, stepped wedge design. Criteria for ASi; any intravenous antibiotic use for ≥ 48 hrs, any oral fluoroquinolone or oral second generation cephalosporin use for ≥ 48 hrs, or any antimicrobial use for ≥ 5 days. HA-CDI cases and model covariates were aggregated by ward, year and month starting September 2008 and ending February 2016. Multi-level mixed effect negative binomial regression analysis was used to model the primary outcome, with intercept and slope coefficients for ward-level random effects estimated. Other covariates tested for inclusion in the final model were derived from previously published risk factors. Deviance residuals were used to assess the model’s goodness-of-fit. Findings The dataset included 486 observation periods, of which 350 were control periods and 136 were intervention periods. After accounting for all other model covariates, the estimated overall ASi incidence rate ratio (IRR) was 0.48 (95% 0.30, 0.79). The ASi effect was independent of antimicrobial utilization. The ASi did not seem to reduce the risk of Clostridium difficile infection on the surgery wards (IRR 0.87, 95% CI 0.45, 1.69) compared to the medicine wards (IRR 0.42, 95% CI 0.28, 0.63). The ward

  20. Impact of tissue type and content of neoplastic cells of samples on the quality of epidermal growth factor receptor mutation analysis among patients with lung adenocarcinoma

    PubMed Central

    PALIOGIANNIS, PANAGIOTIS; ATTENE, FEDERICO; COSSU, ANTONIO; DEFRAIA, EFISIO; PORCU, GIUSEPPE; CARTA, ANNAMARIA; SOTGIU, MARIA IGNAZIA; PAZZOLA, ANTONIO; CORDERO, LORENZO; CAPELLI, FRANCESCA; FADDA, GIOVANNI MARIA; ORTU, SALVATORE; SOTGIU, GIOVANNI; PALOMBA, GRAZIA; SINI, MARIA CRISTINA; PALMIERI, GIUSEPPE; COLOMBINO, MARIA

    2015-01-01

    Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. A total of 515 patients with histologically-confirmed disease were included in the present study. Formalin-fixed paraffin embedded tissue samples were used for the mutation analysis and the content of the neoplastic cells was evaluated using light microscopy. Genomic DNA was isolated using a standard protocol. The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. The mean age of the patients examined was 64.9 years and 357 (69.3%) were male. A total of 429 tissue samples (83.3%) were obtained by biopsy and the remaining samples were obtained by surgery. A total of 456 samples (88.5%) were observed from primary lung adenocarcinomas, while 59 (11.5%) were from metastatic lesions. EGFR mutations occurred in 59 cases (11.5%); exon 18 mutations were detected in one case (1.7%), whereas exon 19 and 21 mutations were detected in 30 (51%) and 28 (47.3%) cases, respectively. EGFR mutations were more frequent in females and patients that had never smoked. The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. However, a statistically significant difference in the number of mutations detected was found between samples with at least 50% of neoplastic cells (450 cases-57 mutations; 12.7%) and those with <50% of neoplastic

  1. Catalytic coherence transformations

    NASA Astrophysics Data System (ADS)

    Bu, Kaifeng; Singh, Uttam; Wu, Junde

    2016-04-01

    Catalytic coherence transformations allow the otherwise impossible state transformations using only incoherent operations with the aid of an auxiliary system with finite coherence that is not being consumed in any way. Here we find the necessary and sufficient conditions for the deterministic and stochastic catalytic coherence transformations between a pair of pure quantum states. In particular, we show that the simultaneous decrease of a family of Rényi entropies of the diagonal parts of the states under consideration is a necessary and sufficient condition for the deterministic catalytic coherence transformations. Similarly, for stochastic catalytic coherence transformations we find the necessary and sufficient conditions for achieving a higher optimal probability of conversion. We thus completely characterize the coherence transformations among pure quantum states under incoherent operations. We give numerous examples to elaborate our results. We also explore the possibility of the same system acting as a catalyst for itself and find that indeed self-catalysis is possible. Further, for the cases where no catalytic coherence transformation is possible we provide entanglement-assisted coherence transformations and find the necessary and sufficient conditions for such transformations.

  2. Magnetically Controlled Variable Transformer

    NASA Technical Reports Server (NTRS)

    Kleiner, Charles T.

    1994-01-01

    Improved variable-transformer circuit, output voltage and current of which controlled by use of relatively small current supplied at relatively low power to control windings on its magnetic cores. Transformer circuits of this type called "magnetic amplifiers" because ratio between controlled output power and power driving control current of such circuit large. This ratio - power gain - can be as large as 100 in present circuit. Variable-transformer circuit offers advantages of efficiency, safety, and controllability over some prior variable-transformer circuits.

  3. Arsenicals produce stable progressive changes in DNA methylation patterns that are linked to malignant transformation of immortalized urothelial cells

    SciTech Connect

    Jensen, Taylor J.; Novak, Petr; Wnek, Shawn M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2009-12-01

    Aberrant DNA methylation participates in carcinogenesis and is a molecular hallmark of a tumor cell. Tumor cells generally exhibit a redistribution of DNA methylation resulting in global hypomethylation with regional hypermethylation; however, the speed in which these changes emerge has not been fully elucidated and may depend on the temporal location of the cell in the path from normal, finite lifespan to malignant transformation. We used a model of arsenical-induced malignant transformation of immortalized human urothelial cells and DNA methylation microarrays to examine the extent and temporal nature of changes in DNA methylation that occur during the transition from immortal to malignantly transformed. Our data presented herein suggest that during arsenical-induced malignant transformation, aberrant DNA methylation occurs non-randomly, progresses gradually at hundreds of gene promoters, and alters expression of the associated gene, and these changes are coincident with the acquisition of malignant properties, such as anchorage independent growth and tumor formation in immunocompromised mice. The DNA methylation changes appear stable, since malignantly transformed cells removed from the transforming arsenical exhibited no reversion in DNA methylation levels, associated gene expression, or malignant phenotype. These data suggest that arsenicals act as epimutagens and directly link their ability to induce malignant transformation to their actions on the epigenome.

  4. Clonal evolution of B cells in transformation from low- to high-grade lymphoma

    PubMed Central

    Matolcsy, András; Schattner, Elaine J.; Knowles, Daniel M.; Casali, Paolo

    2015-01-01

    An outcome of low-grade B cell non-Hodgkins's lymphomas is the transformation to high-grade diffuse large B cell lymphomas (DLBL). To investigate the mechanisms of clonal evolution in the transformation to DLBL, we performed longitudinal molecular analyses of immunoglobulin (Ig), VHDJH gene sequences expressed in cases of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma (FL) that transformed to DLBL. Among the neoplastic CLL and SLL cells and their respective high-grade transformants, there was no evidence for a clonotypic shift or acquired mutations in the expressed Ig VHDJH gene segments, as further confirmed by a specific and sensitive PCR-single strand polymorphism analysis. In contrast, among the FL cells there was a high degree of intraclonal diversification with highly divergent VHDJH gene sequences. Despite this intraclonal heterogeneity, the related DLBL expressed a collinear but unique VHDJH gene sequence. The intraclonal genealogical tree for the FL case demonstrated that the DLBL emerged in association with unique VHDJH gene mutational events. Among the intraclonal FL and related DLBL transformants, the nature and distribution of the Ig VHDJH gene mutations were consistent with antigenic selection. Thus, clonal evolution in the transformation from low- to high-grade B cell lymphoma may involve distinct pathways which vary according to the cellular origin and the type of the progenitor B cell tumor. PMID:10229093

  5. Transformer design tradeoffs

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1977-01-01

    Technical memorandum includes transformer area product numbers, which are used to summarize dimensional and electrical properties of C-cores, pot cores, lamination, powder cores, and tape-wound cores. To aid in core selection, comparison of five common core materials is presented to indicate their influence on overall transformer efficiency and weight.

  6. Biochemical transformation of coals

    DOEpatents

    Lin, M.S.; Premuzic, E.T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed. 7 figs.

  7. Fourier Transform Spectrometer

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Understanding the global atmospheric changes is difficult with today's current technology. However, with high resolution and nearly continuous observations from a satellite, it's possible to transform our understanding of the atmosphere. To enable the next generation of atmospheric science, a new class of orbiting atmospheric sensors is being developed. The foundation of this advanced concept is the Fourier Transform Spectrometer, or FTS.

  8. Deployment & Market Transformation (Brochure)

    SciTech Connect

    Not Available

    2012-04-01

    NREL's deployment and market transformation (D and MT) activities encompass the laboratory's full range of technologies, which span the energy efficiency and renewable energy spectrum. NREL staff educates partners on how they can advance sustainable energy applications and also provides clients with best practices for reducing barriers to innovation and market transformation.

  9. Genetic Transformation of Bacteria.

    ERIC Educational Resources Information Center

    Moss, Robert.

    1991-01-01

    An activity in which students transform an ampicillin-sensitive strain of E. coli with a plasmid containing a gene for ampicillin resistance is described. The procedure for the preparation of competent cells and the transformation of competent E. coli is provided. (KR)

  10. Support Principals, Transform Schools

    ERIC Educational Resources Information Center

    Aguilar, Elena; Goldwasser, Davina; Tank-Crestetto, Kristina

    2011-01-01

    The Transformational Coaching Team in Oakland Unified School District provides differentiated, sustained, job-embedded support to the district's school leaders. In this article, members of the team describe how they work with principals to transform the culture of schools. Student achievement data show above-average improvement in schools in which…

  11. Two Different Squeeze Transformations

    NASA Technical Reports Server (NTRS)

    Han, D. (Editor); Kim, Y. S.

    1996-01-01

    Lorentz boosts are squeeze transformations. While these transformations are similar to those in squeezed states of light, they are fundamentally different from both physical and mathematical points of view. The difference is illustrated in terms of two coupled harmonic oscillators, and in terms of the covariant harmonic oscillator formalism.

  12. A Transformation Called "Twist"

    ERIC Educational Resources Information Center

    Hwang, Daniel

    2010-01-01

    The transformations found in secondary mathematics curriculum are typically limited to stretches and translations (e.g., ACARA, 2010). Advanced students may find the transformation, twist, to be of further interest. As most available resources are written for professional-level readers, this article is intended to be an introduction accessible to…

  13. Disc piezoelectric ceramic transformers.

    PubMed

    Erhart, Jirií; Půlpán, Petr; Doleček, Roman; Psota, Pavel; Lédl, Vít

    2013-08-01

    In this contribution, we present our study on disc-shaped and homogeneously poled piezoelectric ceramic transformers working in planar-extensional vibration modes. Transformers are designed with electrodes divided into wedge, axisymmetrical ring-dot, moonie, smile, or yin-yang segments. Transformation ratio, efficiency, and input and output impedances were measured for low-power signals. Transformer efficiency and transformation ratio were measured as a function of frequency and impedance load in the secondary circuit. Optimum impedance for the maximum efficiency has been found. Maximum efficiency and no-load transformation ratio can reach almost 100% and 52 for the fundamental resonance of ring-dot transformers and 98% and 67 for the second resonance of 2-segment wedge transformers. Maximum efficiency was reached at optimum impedance, which is in the range from 500 Ω to 10 kΩ, depending on the electrode pattern and size. Fundamental vibration mode and its overtones were further studied using frequency-modulated digital holographic interferometry and by the finite element method. Complementary information has been obtained by the infrared camera visualization of surface temperature profiles at higher driving power. PMID:25004532

  14. Transformative Learning and Identity

    ERIC Educational Resources Information Center

    Illeris, Knud

    2014-01-01

    Transformative learning has usually been defined as transformations of meaning perspectives, frames of reference, and habits of mind--as proposed initially by Jack Mezirow. However, several authors have found this definition too narrow and too cognitively oriented, and Mezirow has later emphasized that emotional and social conditions are also…

  15. Adaptive Wavelet Transforms

    SciTech Connect

    Szu, H.; Hsu, C.

    1996-12-31

    Human sensors systems (HSS) may be approximately described as an adaptive or self-learning version of the Wavelet Transforms (WT) that are capable to learn from several input-output associative pairs of suitable transform mother wavelets. Such an Adaptive WT (AWT) is a redundant combination of mother wavelets to either represent or classify inputs.

  16. Direct current transformer

    NASA Technical Reports Server (NTRS)

    Khanna, S. M.; Urban, E. W. (Inventor)

    1979-01-01

    A direct current transformer in which the primary consists of an elongated strip of superconductive material, across the ends of which is direct current potential is described. Parallel and closely spaced to the primary is positioned a transformer secondary consisting of a thin strip of magnetoresistive material.

  17. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

    PubMed Central

    Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

    2007-01-01

    Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Results EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH

  18. Systematic review of the relation between smokeless tobacco and non-neoplastic oral diseases in Europe and the United States

    PubMed Central

    Kallischnigg, Gerd; Weitkunat, Rolf; Lee, Peter N

    2008-01-01

    Background How smokeless tobacco contributes to non-neoplastic oral diseases is unclear. It certainly increases risk of oral mucosal lesions, but reviewers disagree as to other conditions. In some areas, especially South-East Asia, risk is difficult to quantify due to the many products, compositions (including non-tobacco ingredients), and usage practices involved. This review considers studies from Europe (in practice mainly Scandinavia) and from the USA. Methods Experimental and epidemiological studies published in 1963–2007 were identified that related risk of oral lesions to smokeless tobacco use. Data were assessed separately for oral mucosal lesions, periodontal and gingival diseases, dental caries and tooth loss, and oral pain. Results Oral mucosal lesions: Thirty-three epidemiological studies consistently show a strong dose-related effect of current snuff on oral mucosal lesion prevalence. In Scandinavia, users have a near 100% prevalence of a characteristic "snuff-induced lesion", but prevalence of the varied lesions reported in the USA is lower. Associations with chewing tobacco are weaker. The lack of clear association with former use suggests reversibility following cessation, consistent with experimental studies showing rapid lesion regression on quitting. Periodontal and gingival diseases: Two of four studies report a significant association of snuff with attachment loss and four out of eight with gingival recession. Snuff is not clearly related to gingivitis or periodontal diseases. Limited evidence suggests chewing tobacco is unrelated to periodontal or gingival diseases. Tooth loss: Swedish studies show no association with snuff, but one US study reported an association with snuff, and another with chewing tobacco. Dental caries: Evidence from nine studies suggests a possible relationship with use of smokeless tobacco, particularly chewing tobacco, and the risk of dental caries. Oral pain: Limited evidence precludes any clear conclusion

  19. Serpine2/PN-1 Is Required for Proliferative Expansion of Pre-Neoplastic Lesions and Malignant Progression to Medulloblastoma

    PubMed Central

    Vaillant, Catherine; Kool, Marcel; Schwarzentruber-Schauerte, Alexandra; Méreau, Hélène; Cabuy, Erik; Lobrinus, Johannes A.; Pfister, Stefan; Zuniga, Aimée; Frank, Stephan; Zeller, Rolf

    2015-01-01

    Background Medulloblastomas are malignant childhood brain tumors that arise due to the aberrant activity of developmental pathways during postnatal cerebellar development and in adult humans. Transcriptome analysis has identified four major medulloblastoma subgroups. One of them, the Sonic hedgehog (SHH) subgroup, is caused by aberrant Hedgehog signal transduction due to mutations in the Patched1 (PTCH1) receptor or downstream effectors. Mice carrying a Patched-1 null allele (Ptch1∆/+) are a good model to study the alterations underlying medulloblastoma development as a consequence of aberrant Hedgehog pathway activity. Results Transcriptome analysis of human medulloblastomas shows that SERPINE2, also called Protease Nexin-1 (PN-1) is overexpressed in most medulloblastomas, in particular in the SHH and WNT subgroups. As siRNA-mediated lowering of SERPINE2/PN-1 in human medulloblastoma DAOY cells reduces cell proliferation, we analyzed its potential involvement in medulloblastoma development using the Ptch1∆/+ mouse model. In Ptch1∆/+ mice, medulloblastomas arise as a consequence of aberrant Hedgehog pathway activity. Genetic reduction of Serpine2/Pn-1 interferes with medulloblastoma development in Ptch1∆/+ mice, as ~60% of the pre-neoplastic lesions (PNLs) fail to develop into medulloblastomas and remain as small cerebellar nodules. In particular the transcription factor Atoh1, whose expression is essential for development of SHH subgroup medulloblastomas is lost. Comparative molecular analysis reveals the distinct nature of the PNLs in young Ptch1∆/+Pn-1Δ/+ mice. The remaining wild-type Ptch1 allele escapes transcriptional silencing in most cases and the aberrant Hedgehog pathway activity is normalized. Furthermore, cell proliferation and the expression of the cell-cycle regulators Mycn and Cdk6 are significantly reduced in PNLs of Ptch1∆/+Pn-1Δ/+ mice. Conclusions Our analysis provides genetic evidence that aberrant Serpine2/Pn-1 is required for

  20. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

    SciTech Connect

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25

    Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

  1. Understanding the Role of Keratins 8 and 18 in Neoplastic Potential of Breast Cancer Derived Cell Lines

    PubMed Central

    Iyer, Sapna V.; Dange, Prerana P.; Alam, Hunain; Sawant, Sharada S.; Ingle, Arvind D.; Borges, Anita M.; Shirsat, Neelam V.; Dalal, Sorab N.; Vaidya, Milind M.

    2013-01-01

    Background Breast cancer is a complex disease which cannot be defined merely by clinical parameters like lymph node involvement and histological grade, or by routinely used biomarkers like estrogen receptor (ER), progesterone receptor (PGR) and epidermal growth factor receptor 2 (HER2) in diagnosis and prognosis. Breast cancer originates from the epithelial cells. Keratins (K) are cytoplasmic intermediate filament proteins of epithelial cells and changes in the expression pattern of keratins have been seen during malignant transformation in the breast. Expression of the K8/18 pair is seen in the luminal cells of the breast epithelium, and its role in prognostication of breast cancer is not well understood. Methodology/Principal Findings In this study, we have modulated K8 expression to understand the role of the K8/18 pair in three different breast epithelium derived cell lines: non-transformed MCF10A, transformed but poorly invasive MDA MB 468 and highly invasive MDA MB 435. The up-regulation of K8 in the invasive MDA MB 435 cell line resulted in a significant decrease in proliferation, motility, in-vitro invasion, tumor volume and lung metastasis. The down-regulation of K8 in MDA MB 468 resulted in a significant increase in transformation potential, motility and invasion in-vitro, while MCF10A did not show any changes in cell transformation assays. Conclusions/Significance These results indicate the role of K8/18 in modulating invasion in breast cancer -its presence correlating with less invasive phenotype and absence correlating with highly invasive, dedifferentiated phenotype. These data may have important implications for prognostication of breast cancer. PMID:23341946

  2. Transformer design tradeoffs

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1976-01-01

    Material was presented to assist transformer designers in the transition from long-used English units to the less familiar metric equivalents. A coordination between the area product numbers ap (product of window and core cross-section areas) and current density J was developed for a given regulation and temperature rise. Straight-line relationships for Ap and Volume, Ap and surface area At and, Ap and weight were developed. These relationships can now be used as new tools to simplify and standardize the process of transformer design. They also made it possible to design transformers of small bulk and volume or to optimize efficiency.

  3. Optical sine transformation.

    PubMed

    Yang, G; Zhang, J; Gong, J; Chen, J; Ho, Y

    1987-10-15

    The phase mask distribution of optical sine transformation (OST) has been calculated according to the optical general transformation theory. To avoid the diffraction loss of the phase mask, the optical waveguide method is used. Computation shows that the optical sine transformation is possible with only one phase mask, i.e., one-half of a cylindrical lens in the 1-D case and one-quarter of a spherical lens in the 2-D case. Experimental results agree with the theoretical prediction. Image compression by OST is also given. PMID:20523380

  4. Advances in the Natural transform

    NASA Astrophysics Data System (ADS)

    Belgacem, F. B. M.; Silambarasan, R.

    2012-11-01

    The literature review of the Natural transform and the existing definitions and connections to the Laplace and Sumudu transforms are discussed in this communication. Along with the complex inverse Natural transform and Heaviside's expansion formula, the relation of Bessel's function to Natural transform (and hence Laplace and Sumudu transforms) are defined.

  5. A discrete fractional random transform

    NASA Astrophysics Data System (ADS)

    Liu, Zhengjun; Zhao, Haifa; Liu, Shutian

    2005-11-01

    We propose a discrete fractional random transform based on a generalization of the discrete fractional Fourier transform with an intrinsic randomness. Such discrete fractional random transform inheres excellent mathematical properties of the fractional Fourier transform along with some fantastic features of its own. As a primary application, the discrete fractional random transform has been used for image encryption and decryption.

  6. A Classical Science Transformed.

    ERIC Educational Resources Information Center

    Kovalevsky, Jean

    1979-01-01

    Describes how satellites and other tools of space technology have transformed classical geodesy into the science of space geodynamics. The establishment and the activities of the French Center for Geodynamic and Astronomical Research Studies (CERGA) are also included. (HM)

  7. Transformer design tradeoffs

    NASA Technical Reports Server (NTRS)

    Mclyman, W. T.

    1977-01-01

    In space, power system transformer components are frequently the heaviest and bulkiest items in the power conversion circuit. They also have a significant effect upon the overall performance and efficiency of the system. Accordingly, the design of such transformers has an important effect on overall system weight, power-inversion efficiency, and cost. Relationships were between the parameters used by transformer designers that can be used as new tools to standardize and simplify transformer design. They can be used to optimize the design either for small size and weight or efficiency. The metric system of units, rather than the familiar English units, is used; however, material is presented to assist the reader in the transition from one system to the other.

  8. Imaging Fourier transform spectrometer

    SciTech Connect

    Bennett, C.L.

    1993-09-13

    This invention is comprised of an imaging Fourier transform spectrometer having a Fourier transform infrared spectrometer providing a series of images to a focal plane array camera. The focal plane array camera is clocked to a multiple of zero crossing occurrences as caused by a moving mirror of the Fourier transform infrared spectrometer and as detected by a laser detector such that the frame capture rate of the focal plane array camera corresponds to a multiple of the zero crossing rate of the Fourier transform infrared spectrometer. The images are transmitted to a computer for processing such that representations of the images as viewed in the light of an arbitrary spectral ``fingerprint`` pattern can be displayed on a monitor or otherwise stored and manipulated by the computer.

  9. Fourier Transform Mass Spectrometry

    PubMed Central

    Scigelova, Michaela; Hornshaw, Martin; Giannakopulos, Anastassios; Makarov, Alexander

    2011-01-01

    This article provides an introduction to Fourier transform-based mass spectrometry. The key performance characteristics of Fourier transform-based mass spectrometry, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of Fourier transform-based mass spectrometry technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for an application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook. PMID:21742802

  10. Fractals and Transformations.

    ERIC Educational Resources Information Center

    Bannon, Thomas J.

    1991-01-01

    Discussed are several different transformations based on the generation of fractals including self-similar designs, the chaos game, the koch curve, and the Sierpinski Triangle. Three computer programs which illustrate these concepts are provided. (CW)

  11. Proof in Transformation Geometry

    ERIC Educational Resources Information Center

    Bell, A. W.

    1971-01-01

    The first of three articles showing how inductively-obtained results in transformation geometry may be organized into a deductive system. This article discusses two approaches to enlargement (dilatation), one using coordinates and the other using synthetic methods. (MM)

  12. Nontensorial Transformation Optics

    NASA Astrophysics Data System (ADS)

    García-Meca, C.; Barceló, C.

    2016-06-01

    We present an alternative version of transformation optics that allows us to mold the flow of light without rotating or scaling the electromagnetic fields. The resulting media experience unusual force densities, are nonreciprocal, and exhibit loss or gain. Because of these singular features, a variety of effects and devices unreachable by standard transformation optics can be achieved, including reflectionless light compression, optical modes with arbitrary in-plane polarization, and special isolators.

  13. Series Transmission Line Transformer

    DOEpatents

    Buckles, Robert A.; Booth, Rex; Yen, Boris T.

    2004-06-29

    A series transmission line transformer is set forth which includes two or more of impedance matched sets of at least two transmissions lines such as shielded cables, connected in parallel at one end ans series at the other in a cascading fashion. The cables are wound about a magnetic core. The series transmission line transformer (STLT) which can provide for higher impedance ratios and bandwidths, which is scalable, and which is of simpler design and construction.

  14. 25. VIEW, LOOKING SOUTHWEST INSIDE TRANSFORMER ROOM, SHOWING TRANSFORMERS AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. VIEW, LOOKING SOUTHWEST INSIDE TRANSFORMER ROOM, SHOWING TRANSFORMERS AND KNIFE SWITCHES - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  15. Floral Transformation of Wheat

    NASA Astrophysics Data System (ADS)

    Agarwal, Sujata; Loar, Star; Steber, Camille; Zale, Janice

    A method is described for the floral transformation of wheat using a protocol similar to the floral dip of Arabidopsis. This method does not employ tissue culture of dissected embryos, but instead pre-anthesis spikes with clipped florets at the early, mid to late uninucleate microspore stage are dipped in Agrobacterium infiltration media harboring a vector carrying anthocyanin reporters and the NPTII selectable marker. T1 seeds are examined for color changes induced in the embryo by the anthocyanin reporters. Putatively transformed seeds are germinated and the seedlings are screened for the presence of the NPTII gene based on resistance to paromomycin spray and assayed with NPTII ELISAs. Genomic DNA of putative transformants is digested and analyzed on Southern blots for copy number to determine whether the T-DNA has integrated into the nucleus and to show the number of insertions. The non-optimized transformation efficiencies range from 0.3 to 0.6% (number of transformants/number of florets dipped) but the efficiencies are higher in terms of the number of transformants produced/number of seeds set ranging from 0.9 to 10%. Research is underway to maximize seed set and optimize the protocol by testing different Agrobacterium strains, visual reporters, vectors, and surfactants.

  16. Protease-sensitive prion species in neoplastic spleens of prion-infected mice with uncoupling of PrP(Sc) and prion infectivity.

    PubMed

    Krasemann, Susanne; Neumann, Melanie; Szalay, Beata; Stocking, Carol; Glatzel, Markus

    2013-02-01

    Prion diseases are fatal neurodegenerative disorders. An important step in disease pathophysiology is the conversion of cellular prion protein (PrP(C)) to disease-associated misfolded conformers (PrP(Sc)). These misfolded PrP variants are a common component of prion infectivity and are detectable in diseased brain and lymphoreticular organs such as spleen. In the latter, PrP(Sc) is thought to replicate mainly in follicular dendritic cells within spleen follicles. Although the presence of PrP(Sc) is a hallmark for prion disease and serves as a main diagnostic criterion, in certain instances the amount of PrP(Sc) does not correlate well with neurotoxicity or prion infectivity. Therefore, it has been proposed that prions might be a mixture of different conformers and aggregates with differing properties. This study investigated the impact of disruption of spleen architecture by neoplasia on the abundance of different PrP species in spleens of prion-infected mice. Although follicular integrity was completely disturbed, titres of prion infectivity in neoplastic spleens were not significantly altered, yet no protease-resistant PrP(Sc) was detectable. Instead, unique protease-sensitive prion species could be detected in neoplastic spleens. These results indicate the dissociation of PrP(Sc) and prion infectivity and showed the presence of non-PrP(Sc) PrP species in spleen with divergent biochemical properties that become apparent after tissue architecture disruption. PMID:23136363

  17. Experimental Evidence of ω-3 Polyunsaturated Fatty Acid Modulation of Inflammatory Cytokines and Bioactive Lipid Mediators: Their Potential Role in Inflammatory, Neurodegenerative, and Neoplastic Diseases

    PubMed Central

    Calviello, Gabriella; Su, Hui-Min; Weylandt, Karsten H.; Fasano, Elena; Serini, Simona; Cittadini, Achille

    2013-01-01

    A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action of ω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others' laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects of ω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects of ω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases. PMID:23691510

  18. Complementary use of optical coherence tomography and 5-aminolevulinic acid induced fluorescent spectroscopy for diagnosis of neoplastic processes in cervix and vulva

    NASA Astrophysics Data System (ADS)

    Sapozhnikova, Veronika V.; Shakhova, Natalia M.; Kamensky, Vladislav A.; Kuranov, Roman V.; Loshenov, Victor B.; Petrova, Svetlana A.

    2003-07-01

    A new approach to improving the diagnostic value of optical methods is suggested, which is based on a complementary investigation of different optical parameters of biotissues. The aim of this paper is comparative study of the feasibility of two optical methods - fluorescence spectroscopy and optical coherence tomography - for visualization of borders of neoplastic processes in the uterine cervix and vulva. Fluorescence spectroscopy is based on the detection of biochemical and optical coherence tomography on backscattering properties in norm and pathological changes of tissues. By means of these optical methods changes in biochemical and morphological properties of tissues were investigated. A parallel analysis of these two optical methods and histology from the center of tumors and their optical borders was made. Thirteen female patients with neoplastic changes in uterine cervix and vulva were enrolled in this study. The borders of the tumor determined by optical methods (fluorescence spectroscopy and optical coherence tomography) are coinciding with the biopsy proved ones. In addition, OCT and fluorescence borders of tumor in the uterine cervix and vulva exceeds colposcopically detectable borders, the averaging difference 2 mm. In future optical methods would considerably enhance diagnostic accuracy of conventional methods used in oncogynecology.

  19. Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin-10 in cervical neoplastic lesions.

    PubMed

    Prata, Thiago Theodoro Martins; Bonin, Camila Mareti; Ferreira, Alda Maria Teixeira; Padovani, Cacilda Tezelli Junqueira; Fernandes, Carlos Eurico dos Santos; Machado, Ana Paula; Tozetti, Inês Aparecida

    2015-09-01

    A specific immune response to human papillomavirus (HPV) in the cervical microenvironment plays a key role in eradicating infection and eliminating mutated cells. However, high-risk HPVs modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (IL-10). This production of IL-10, in conjunction with HPV infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the IL-10-producing cellular phenotype, and investigate the influence of host and HPV factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in IL-10 production by keratinocytes, macrophages and Langerhans cells in high-grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30 years, and was also correlated with high viral load, and infection with a single HPV type, particularly high-risk HPVs. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different IL-10-producing cellular phenotypes in cervical cancer samples, and samples classified as high-grade cervical lesions (cervical intraepithelial neoplasia stages II and III). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression. PMID:26059395

  20. Relativistic Transformation of Solid Angle.

    ERIC Educational Resources Information Center

    McKinley, John M.

    1980-01-01

    Rederives the relativistic transformations of light intensity from compact sources (stars) to show where and how the transformation of a solid angle contributes. Discusses astrophysical and other applications of the transformations. (Author/CS)

  1. Role of growth factors in the growth of normal and transformed cells

    SciTech Connect

    Lokeshwar, V.B.

    1989-01-01

    Growth factors play an important role in the growth of normal cells. However, their untimely and/or excess production leads to neoplastic transformation. The role of growth factors in the growth of normal cells was studied by investigating the mechanism of transmodulation of the cell surface EGF receptor number by protamine. Protamine increased the EGF stimulated mitogenic response in Swiss mouse 3T3 cells and A431 cells by increasing the number of functionally active EGF receptors. Protamine also increased EGF receptor number in plasma membranes and solubilized membranes. This was evidenced by an increase in both {sup 125}I-EGF-EGF-receptor complex and EGF stimulated phosphorylation of the EGF receptor. The solubilized EGF receptor was retained on a protamine-agarose gel indicating that protamine might increase EGF receptor number by directly activating cryptic EGF receptors in the plasma membranes. The role of growth factors in neoplastic transformation was studied by investigating the role of the oncogene v-sis in the growth of Simian sarcoma virus (SSV) transformed cells. The product of the oncogene v-sis is 94% homologous to the B chain of PDGF. This study found that (i) v-sis gene product is synthesized as a 32 kDa unglycosylated monomer which is glycosylated, dimerized and proteolytically processed into p36, p72, p68, p58, p44 and p27 mol. wt. species respectively. (ii) p36, p72, p68 and p58 are very likely formed in the endoplasmic reticulum and/or Golgi complex. A fraction of newly synthesized p72, p68 and p58 is degraded intracellularly at a fast rate. (iii) p44 is a secretory product which remains tightly associated with the cell surface. p44 is recaptured by the cells through interaction with cell surface PDGF receptors and degraded into p27. (iv) During long term cultures p44 is extracellularly cleaved into a 27 kDa product.

  2. Alterations in cellular differentiation, mitogenesis, cytoskeleton and growth characteristics during Syrian hamster embryo cell multistep in vitro transformation.

    PubMed

    Isfort, R J; Cody, D B; Doersen, C J; Kerckaert, G A; Leboeuf, R A

    1994-10-01

    In vitro Syrian hamster embryo (SHE) cell transformation is a neoplastic process that proceeds through several identifiable consecutive stages including in vitro morphological transformation (mt), acquisition of immortality (I+), acquisition of tumorigenicity (T+) and tumor-derived cells (I'TD). Eight transformed lineages consisting of cells at the mt, I+, T+ and I'TD stages were assayed for alterations in general markers of cell differentiation, mitogenic signaling pathways, cytoskeleton and cellular growth in 3D matrix. Alterations in cellular differentiation markers included a decrease in H19 gene expression and placental alkaline phosphatase enzymatic activity at the mt stage in all lineages examined with a complete absence of H19 gene expression and placental alkaline phosphatase enzymatic activity by the I'TD stage in a majority of transformed lineages. Changes in mitogenic signaling pathways included the production of autocrine growth factors and alterations in growth factor-induced immediate early gene expression by the I'TD stage of transformation in the majority of transformed lineages investigated. By the I'TD stage of transformation in most lineages, changes in both the cytoskeleton (including a decrease in tropomyosin-I gene expression) and the Matrigel growth characteristics of SHE cells were observed. PMID:7927892

  3. Improvement of the BALB/c-3T3 cell transformation assay: a tool for investigating cancer mechanisms and therapies.

    PubMed

    Poburski, Doerte; Thierbach, René

    2016-01-01

    The identification of cancer preventive or therapeutic substances as well as carcinogenic risk assessment of chemicals is nowadays mostly dependent on animal studies. In vitro cell transformation assays mimic different stages of the in vivo neoplastic process and represent an excellent alternative to study carcinogenesis and therapeutic options. In the BALB/c-3T3 two-stage transformation assay cells are chemically transformed by treatment with MCA and TPA, along with the final Giemsa staining of morphological aberrant foci. In addition to the standard method we can show, that it is possible to apply other chemicals in parallel to identify potential preventive or therapeutic substances during the transformation process. Furthermore, we successfully combined the BALB/c cell transformation assay with several endpoint applications for protein analysis (immunoblot, subcellular fractionation and immunofluorescence) or energy parameter measurements (glucose and oxygen consumption) to elucidate cancer mechanisms in more detail. In our opinion the BALB/c cell transformation assay proves to be an excellent model to investigate alterations in key proteins or energy parameters during the different stages of transformation as well as therapeutic substances and their mode of action. PMID:27611302

  4. Improvement of the BALB/c-3T3 cell transformation assay: a tool for investigating cancer mechanisms and therapies

    PubMed Central

    Poburski, Doerte; Thierbach, René

    2016-01-01

    The identification of cancer preventive or therapeutic substances as well as carcinogenic risk assessment of chemicals is nowadays mostly dependent on animal studies. In vitro cell transformation assays mimic different stages of the in vivo neoplastic process and represent an excellent alternative to study carcinogenesis and therapeutic options. In the BALB/c-3T3 two-stage transformation assay cells are chemically transformed by treatment with MCA and TPA, along with the final Giemsa staining of morphological aberrant foci. In addition to the standard method we can show, that it is possible to apply other chemicals in parallel to identify potential preventive or therapeutic substances during the transformation process. Furthermore, we successfully combined the BALB/c cell transformation assay with several endpoint applications for protein analysis (immunoblot, subcellular fractionation and immunofluorescence) or energy parameter measurements (glucose and oxygen consumption) to elucidate cancer mechanisms in more detail. In our opinion the BALB/c cell transformation assay proves to be an excellent model to investigate alterations in key proteins or energy parameters during the different stages of transformation as well as therapeutic substances and their mode of action. PMID:27611302

  5. Transforming Potential of the Adenovirus Type 5 E4orf3 Protein

    PubMed Central

    Nevels, Michael; Täuber, Birgitt; Kremmer, Elisabeth; Spruss, Thilo; Wolf, Hans; Dobner, Thomas

    1999-01-01

    Previous observations that the adenovirus type 5 (Ad5) E4orf6 and E4orf3 gene products have redundant effects in viral lytic infection together with the recent findings that E4orf6 possesses transforming potential prompted us to investigate the effect of E4orf3 expression on the transformation of primary rat cells in combination with adenovirus E1 oncogene products. Our results demonstrate for the first time that E4orf3 can cooperate with adenovirus E1A and E1A plus E1B proteins to transform primary baby rat kidney cells, acting synergistically with E4orf6 in the presence of E1B gene products. Transformed rat cells expressing E4orf3 exhibit morphological alterations, higher growth rates and saturation densities, and increased tumorigenicity compared with transformants expressing E1 proteins only. Consistent with previous results for adenovirus-infected cells, the E4orf3 protein is immunologically restricted to discrete nuclear structures known as PML oncogenic domains (PODs) in transformed rat cells. As opposed to E4orf6, the ability of E4orf3 to promote oncogenic cell growth is probably not linked to a modulation of p53 functions and stability. Instead, our results indicate that the transforming activities of E4orf3 are due to combinatorial effects that involve the binding to the adenovirus 55-kDa E1B protein and the colocalization with PODs independent from interactions with the PML gene product. These data fit well with a model in which the reorganization of PODs may trigger a cascade of processes that cause uncontrolled cell proliferation and neoplastic growth. In sum, our results provide strong evidence for the idea that interactions with PODs by viral proteins are linked to oncogenic transformation. PMID:9882365

  6. Martensitic transformation in zirconia

    SciTech Connect

    Deville, Sylvain . E-mail: sylvain.deville@insa-lyon.fr; Guenin, Gerard; Chevalier, Jerome

    2004-11-08

    We investigate by atomic force microscopy (AFM) the surface relief resulting from martensitic tetragonal to monoclinic phase transformation induced by low temperature autoclave aging in ceria-stabilized zirconia. AFM appears as a very powerful tool to investigate martensite relief quantitatively and with a great precision. The crystallographic phenomenological theory is used to predict the expected relief induced by the transformation, for the particular case of lattice correspondence ABC1, where tetragonal c axis becomes the monoclinic c axis. A model for variants spatial arrangement for this lattice correspondence is proposed and validated by the experimental observations. An excellent agreement is found between the quantitative calculations outputs and the experimental measurements at nanometer scale yielded by AFM. All the observed features are explained fully quantitatively by the calculations, with discrepancies between calculations and quantitative experimental measurements within the measurements and calculations precision range. In particular, the crystallographic orientation of the transformed grains is determined from the local characteristics of transformation induced relief. It is finally demonstrated that the strain energy is the controlling factor of the surface transformation induced by low temperature autoclave treatments in this material.

  7. On spinors transformations

    NASA Astrophysics Data System (ADS)

    Budinich, Marco

    2016-07-01

    We begin showing that for even dimensional vector spaces V all automorphisms of their Clifford algebras are inner. So all orthogonal transformations of V are restrictions to V of inner automorphisms of the algebra. Thus under orthogonal transformations P and T—space and time reversal—all algebra elements, including vectors v and spinors φ, transform as v → xvx-1 and φ → xφx-1 for some algebra element x. We show that while under combined PT spinor φ → xφx-1 remains in its spinor space, under P or T separately φ goes to a different spinor space and may have opposite chirality. We conclude with a preliminary characterization of inner automorphisms with respect to their property to change, or not, spinor spaces.

  8. Translating and Transforming Care

    PubMed Central

    Gillespie, Alex; Moore, Helen

    2015-01-01

    This article examines how the Disability Living Allowance claim form, used in the United Kingdom to allocate £13 billion of disability benefits, translates and transforms disability and care. Twenty-two people with acquired brain injury and their main informal caregivers (n = 44) were video-recorded filling in the disability claim form. Participants disagreed on 26% of the questions, revealing two types of problems. Translation problems arose as participants struggled to provide categorical responses to ambiguous questions and were unable to report contextual variability in care needs or divergences of perception. Transformation problems arose as participants resisted the way in which the form positioned them, forcing them to conceptualize their relationship in terms of dependency and burden. The disability claim form co-opts claimants to translate care and disability into bureaucratically predefined categories, and it transforms the care relationship that it purports to document. PMID:25792487

  9. Transformational plasmon optics.

    PubMed

    Liu, Yongmin; Zentgraf, Thomas; Bartal, Guy; Zhang, Xiang

    2010-06-01

    We propose and demonstrate efficiently molding surface plasmon polaritons (SPPs) based on transformation optics. SPPs are surface modes of electromagnetic waves tightly bound at metal-dielectric interfaces, which allow us to scale optics beyond the diffraction limit. Taking advantage of transformation optics, here we show that the propagation of SPPs can be manipulated in a prescribed manner by careful control of the dielectric material properties adjacent to a metal. Since the metal properties are completely unaltered, this methodology provides a practical way for routing light at very small scales. For instance, our approach enables SPPs to travel at uneven and curved surfaces over a broad wavelength range, where SPPs would normally suffer significant scattering losses. In addition, a plasmonic 180 degrees waveguide bend and a plasmonic Luneburg lens with simple designs are presented. The unique design flexibility of the transformational plasmon optics introduced here may open a new door to nano optics and downscaling of photonic circuits. PMID:20465268

  10. Transformation based endorsement systems

    NASA Technical Reports Server (NTRS)

    Sudkamp, Thomas

    1988-01-01

    Evidential reasoning techniques classically represent support for a hypothesis by a numeric value or an evidential interval. The combination of support is performed by an arithmetic rule which often requires restrictions to be placed on the set of possibilities. These assumptions usually require the hypotheses to be exhausitive and mutually exclusive. Endorsement based classification systems represent support for the alternatives symbolically rather than numerically. A framework for constructing endorsement systems is presented in which transformations are defined to generate and update the knowledge base. The interaction of the knowledge base and transformations produces a non-monotonic reasoning system. Two endorsement based reasoning systems are presented to demonstrate the flexibility of the transformational approach for reasoning with ambiguous and inconsistent information.

  11. Plastid transformation in soybean.

    PubMed

    Dubald, Manuel; Tissot, Ghislaine; Pelissier, Bernard

    2014-01-01

    The biotechnological potential of plastid genetic engineering has been illustrated in a limited number of higher plant species. We have developed a reproducible method to generate plastid transformants in soybean (Glycine max), a crop of major agronomic importance. The transformation vectors are delivered to embryogenic cultures by the particle gun method and selection performed using the aadA antibiotic resistance gene. Homoplasmy is established rapidly in the selected events without the need for further selection or regeneration cycles, and genes of interest can be expressed at a high level in green tissues. This is a significant step toward the commercial application of this technology. PMID:24599865

  12. Successful Transformational Radiology Leaders.

    PubMed

    Douget, Karen

    2015-01-01

    Transformational radiology leaders elevate subordinates, expand self-awareness, develop lasting relationships, strive to exceed expectations, and uphold the vision and goals of the organization. In order for radiology leaders to become more transformational in their leadership style there are four fundamental elements they must learn: idealized influence, individualized consideration, inspirational motivation, and intellectual stimulation. Leaders can utilize personality and self-assessments to learn more about themselves, identify areas of strengths and weaknesses, and learn to be more effective when leading employees. PMID:26710553

  13. High Expression of the DNA Methyltransferase Gene Characterizes Human Neoplastic Cells and Progression Stages of Colon Cancer

    NASA Astrophysics Data System (ADS)

    El-Deiry, Wafik S.; Nelkin, Barry D.; Celano, Paul; Chiu Yen, Ray-Whay; Falco, Joseph P.; Hamilton, Stanley R.; Baylin, Stephen B.

    1991-04-01

    DNA methylation abnormalities occur consistently in human neoplasia including widespread hypomethylation and more recently recognized local increases in DNA methylation that hold potential for gene inactivation events. To study this imbalance further, we have cloned and localized to chromosome 19 a portion of the human DNA methyltransferase gene that codes for the enzyme catalyzing DNA methylation. Expression of this gene is low in normal human cells, significantly increased (30- to 50-fold by PCR analysis) in virally transformed cells, and strikingly elevated in human cancer cells (several hundredfold). In comparison to colon mucosa from patients without neoplasia, median levels of DNA methyltransferase transcripts are 15-fold increased in histologically normal mucosa from patients with cancers or the benign polyps that can precede cancers, 60-fold increased in the premalignant polyps, and >200-fold increased in the cancers. Thus, increases in DNA methyltransferase gene expression precede development of colonic neoplasia and continue during progression of colonic neoplasms. These increases may play a role in the genetic instability of cancer and mark early events in cell transformation.

  14. A modified method for the culture of naturally HPV-infected high-grade cervical intraepithelial neoplasia keratinocytes from human neoplastic cervical biopsies

    PubMed Central

    LIU, YU-ZHEN; WANG, TIAN-TIAN; ZHANG, YOU-ZHONG

    2016-01-01

    Few studies on cervical intraepithelial neoplasia (CIN) keratinocyte cultures are available due to the numerous technical and methodological problems associated with the in vitro cultivation of these cells. The present study investigated an applicable and effective method for the in vitro cultivation of high-grade CIN keratinocytes from human neoplastic cervical biopsies. Human neoplastic cervical tissue sections were obtained and digested using type I collagen in order to dissociate the cells. The cells were seeded in tissue culture plastic plates that were coated with rat tail collagen type I and contained modified keratinocyte serum-free medium (K-SFM) supplemented with 5% fetal bovine serum. The medium was replaced with K-SFM on days 3, 5 and 7, respectively. The unattached cells were recovered and the cell viability was determined accurately using the Trypan Blue exclusion method. The expression of keratin 14 (K14), keratin 19 (K19), keratin 17 (K17) and P63 was assayed using immunofluorescence in order to identify the presence of CIN keratinocytes. The present results indicated that the attachment rate of CIN keratinocytes significantly increased between 56.75±1.76% on day 3 and 77.09±3.55% on day 5, and became relatively stable between days 5 and 7. The cell viability significantly decreased between 83.00±0.50% on day 5 and 68.17±1.04% on day 7. The passaged CIN keratinocytes maintained the original unequally sized, abnormally shaped morphology and did not undergo differentiation. In addition, the passaged CIN keratinocytes exhibited the same human papilloma virus (HPV) genotype that was detected in the original primary cells. K14 and K19 were expressed in the majority of the normal and CIN keratinocytes, whereas K17 and P63 were expressed only in high-grade CIN keratinocytes. The present study proposes a simple and practical method for rapidly obtaining highly purified naturally HPV-infected high-grade CIN keratinocytes from small neoplastic cervical

  15. Quantitative analysis of the anti-proliferative activity of combinations of selected iron-chelating agents and clinically used anti-neoplastic drugs.

    PubMed

    Potuckova, Eliska; Jansova, Hana; Machacek, Miloslav; Vavrova, Anna; Haskova, Pavlina; Tichotova, Lucie; Richardson, Vera; Kalinowski, Danuta S; Richardson, Des R; Simunek, Tomas

    2014-01-01

    Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7 breast cancer cells, we explored the combined anti-proliferative potential of four iron chelators, namely: desferrioxamine (DFO), salicylaldehyde isonicotinoyl hydrazone (SIH), (E)-N'-[1-(2-hydroxy-5-nitrophenyl)ethyliden] isonicotinoyl hydrazone (NHAPI), and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), plus six selected anti-neoplastic drugs. These six agents are used for breast cancer treatment and include: paclitaxel, 5-fluorouracil, doxorubicin, methotrexate, tamoxifen and 4-hydroperoxycyclophosphamide (an active metabolite of cyclophosphamide). Our quantitative chelator-drug analyses were designed according to the Chou-Talalay method for drug combination assessment. All combinations of these agents yielded concentration-dependent, anti-proliferative effects. The hydrophilic siderophore, DFO, imposed antagonism when used in combination with all six anti-tumor agents and this antagonistic effect increased with increasing dose. Conversely, synergistic interactions were observed with combinations of the lipophilic chelators, NHAPI or Dp44mT, with doxorubicin and also the combinations of SIH, NHAPI or Dp44mT with tamoxifen. The combination of Dp44mT with anti-neoplastic agents was further enhanced following formation of its redox-active iron and especially copper complexes. The most potent combinations of Dp44mT and NHAPI with tamoxifen were confirmed as synergistic using another estrogen receptor-expressing breast cancer cell line, T47D, but not estrogen receptor-negative MDA

  16. Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA

    SciTech Connect

    Franklin, Jeffrey L.; Rankin, Carl R.; Levy, Shawn; Snoddy, Jay R.; Zhang, Bing; Washington, Mary Kay; Thomson, J. Michael; Whitehead, Robert H.; Coffey, Robert J.

    2013-10-11

    Highlights: •Non-coding RNAs are found in the colonic crypt progenitor compartment. •Colonocytes transformed by ncNRFR are highly invasive and metastatic. •ncNRFR has a region similar to the miRNA, let-7 family. •ncNRFR expression alters let-7 activity as measured by reporter construct. •ncNRFR expression upregulates let-7b targets. -- Abstract: Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation.

  17. Focus On: Transforming Relationships.

    ERIC Educational Resources Information Center

    Karal, Pearl; And Others

    1985-01-01

    Karal describes the psychodynamics by which children learn to fear and distrust long-term commitments. Vaines proposes a conceptualization of the home economist as transforming actor. LeBow addresses methods of treating obese youth. Fewster and Kuhonta offer insights on communicating with Third World rural women. (SK)