Enhanced anti-cancer activities of a gold(III) pyrrolidinedithiocarbamato complex incorporated in a biodegradable metal-organic framework.

PubMed

Sun, Raymond Wai-Yin; Zhang, Ming; Li, Dan; Li, Mian; Wong, Alice Sze-Tsai

2016-10-01

An anti-cancer active gold(III) pyrrolidinedithiocarbamato complex [(PDTC)Au III Cl 2 ] (1) has been synthesized and characterized by means of X-ray crystallography. Compared to the pyrrolidinedithiocarbamate ligand itself, this gold(III) complex displays an up to 33-fold higher anti-cancer potency towards a panel of cancer cell lines including the cisplatin-resistant ovarian carcinoma cell line (A2780cis). As demonstrated by a set of Transwell® assay-based cytotoxicity experiments, incorporating this gold(III) complex in a zinc-based biodegradable metal-organic framework (MOF) displays a significant enhancement in anti-cancer activity towards A2780cis than the gold(III) complex alone. Copyright © 2016 Elsevier Inc. All rights reserved.

MCT1 promotes the cisplatin-resistance by antagonizing Fas in epithelial ovarian cancer

PubMed Central

Yan, Chunxiao; Yang, Fan; Zhou, Chunxia; Chen, Xuejun; Han, Xuechuan; Liu, Xueqin; Ma, Hongyun; Zheng, Wei

2015-01-01

This study was designed to investigate the role of MCT1 in the development of cisplatin-resistant ovarian cancer and its possible relationship with Fas. We found the expression of MCT1 was obviously increased both in cisplatin-resistant ovarian cancer tissue and A2780/CP cells compared with sensitive ovarian cancer tissue and cell lines A2780. And in A2780 cells treated with Cisplatin, the expression of MCT1 increased in a concentration-dependent manner, MCT1 knockdown attenuates cisplatin-induced cell viability. In A2780 and A2780/CP cells transfected with MCT1 siRNA, the activation of several downstream targets of Fas, including FasL and FAP-1 were largely prevented, whereas the expression of Caspase-3 was increased, accompanying with increased abundance of Fas. Coimmunoprecipitation and immunofluorescence showed that there is interaction between endogenous MCT1 with Fas in vivo and in vitro. In vivo, depletion of MCT1 by shRNA reverses cisplatin-resistance and the expression of Fas. This study showed that down regulation of MCT1 promote the sensibility to Cisplatin in ovarian cancer cell line. And this effect appeared to be mediated via antagonizing the effect of Fas. PMID:26045776

Functional activation of mutant p53V172F by platinum analogs in cisplatin-resistant human tumor cells is dependent on serine-20 phosphorylation

PubMed Central

Xie, Xiaolei; He, Guangan; Siddik, Zahid H.

2017-01-01

Dysfunctionality of the p53 tumor suppressor is a major cause of therapeutic drug resistance in cancer. Recently we reported that mutant, but otherwise functional, p53V172F was inactivated in cisplatin-resistant 2780CP/Cl-16 and 2780CP/Cl-24 human ovarian tumor cells by increased recruitment of the inhibitor MDM4. The current study demonstrates that, unlike cisplatin, platinum analogs oxaliplatin and DACH-diacetato-dichloro-Pt(IV) (DAP), strongly stabilize and activate p53V172F in resistant cells, as indicated by prolonged p53 half-life and transactivation of targets p21 (CDKN1A) and MDM2. This increase in MDM2 reduced MDM4 levels in cell lysates as well as the p53 immunocomplex and prevented reversion of p53 to the inactive p53-MDM2-MDM4 bound state. Phosphorylation of p53 at Ser15 was demonstrated by all three drugs in sensitive A2780 and corresponding resistant 2780CP/Cl-16 and 2780CP/Cl-24 cell lines. However, cisplatin induced Ser20 phosphorylation in A2780 cells only, but not in resistant cells; in contrast, both DAP and oxaliplatin induced this phosphorylation in all three cell lines. The inference that Ser20 phosphorylation is more important for p53 activation was confirmed by ectopic expression of a phosphomimetic (S20D) mutant p53 that displayed reduced binding, relative to wild-type p53, to both MDM2 and MDM4 in p53-knockout A2780 cells. In consonance, temporal studies demonstrated drug-induced Ser15 phosphorylation coincided with p53 stabilization, whereas Ser20 phosphorylation coincided with p53 transactivation. Implications Cisplatin fails to activate the pathway involved in phosphorylating mutant p53V172F at Ser20 in resistant cells, but this phosphorylation is restored by oxaliplatin and DAP that reactivates p53 function and circumvents cisplatin resistance. PMID:28031409

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells

PubMed Central

Alonezi, Sanad; Tusiimire, Jonans; Wallace, Jennifer; Dufton, Mark J.; Parkinson, John A.; Young, Louise C.; Clements, Carol J.; Park, Jin-Kyu; Jeon, Jong-Woon; Ferro, Valerie A.; Watson, David G.

2017-01-01

Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass spectrometry (MS) was applied to identify metabolic changes in A2780 (combination treatment 5 μg/mL melittin + 2 μg/mL cisplatin) and A2780CR (combination treatment 2 μg/mL melittin + 10 μg/mL cisplatin) cells. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) multivariate data analysis models were produced using SIMCA-P software. All models displayed good separation between experimental groups and high-quality goodness of fit (R2) and goodness of prediction (Q2), respectively. The combination treatment induced significant changes in both cell lines involving reduction in the levels of metabolites in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and pyrimidine metabolism, and the arginine/proline pathway. The combination of melittin with cisplatin that targets these pathways had a synergistic effect. The melittin-cisplatin combination had a stronger effect on the A2780 cell line in comparison with the A2780CR cell line. The metabolic effects of melittin and cisplatin in combination were very different from those of each agent alone. PMID:28420117

Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer

PubMed Central

Stefanou, Dimitra T.; Bamias, Aristotelis; Episkopou, Hara; Kyrtopoulos, Soterios A.; Likka, Maria; Kalampokas, Theodore; Photiou, Stylianos; Gavalas, Nikos; Sfikakis, Petros P.; Dimopoulos, Meletios A.; Souliotis, Vassilis L.

2015-01-01

Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that

22 CFR 127.10 - Civil penalty.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Civil penalty. (a) The Assistant Secretary of State for Political-Military Affairs is authorized to impose a civil penalty in an amount not to exceed that authorized by 22 U.S.C. 2778, 2779a and 2780 for each violation of 22 U.S.C. 2778, 2779a and 2780, or any regulation, order, license or approval issued...

Enhanced Cytotoxicity of Folic Acid-Targeted Liposomes Co-Loaded with C6 Ceramide and Doxorubicin: In Vitro Evaluation on HeLa, A2780-ADR, and H69-AR Cells.

PubMed

Sriraman, Shravan Kumar; Pan, Jiayi; Sarisozen, Can; Luther, Ed; Torchilin, Vladimir

2016-02-01

Current research in cancer therapy is beginning to shift toward the use of combinational drug treatment regimens. However, the efficient delivery of drug combinations is governed by a number of complex factors in the clinical setting. Therefore, the ability to synchronize the pharmacokinetics of the individual therapeutic agents present in combination not only to allow for simultaneous tumor accumulation but also to allow for a synergistic relationship at the intracellular level could prove to be advantageous. In this work, we report the development of a novel folic acid-targeted liposomal formulation simultaneously co-loaded with C6 ceramide and doxorubicin [FA-(C6+Dox)-LP]. In vitro cytotoxicity assays showed that the FA-(C6+Dox)-LP was able to significantly reduce the IC50 of Dox when compared to that after the treatment with the doxorubicin-loaded liposomes (Dox-LP) as well as the untargeted drug co-loaded (C6+Dox)-LP on HeLa, A2780-ADR, and H69-AR cells. The analysis of the cell cycle distribution showed that while the C6 liposomes (C6-LP) did not cause cell cycle arrest, all the Dox-containing liposomes mediated cell cycle arrest in HeLa cells in the G2 phase at Dox concentrations of 0.3 and 1 μM and in the S phase at the higher concentrations. It was also found that this arrest in the S phase precedes the progression of the cells to apoptosis. The targeted FA-(C6+Dox)-LP were able to significantly enhance the induction of apoptotic events in HeLa cell monolayers as compared to the other treatment groups. Next, using time-lapse phase holographic imaging microscopy, it was found that upon treatment with the FA-(C6+Dox)-LP, the HeLa cells underwent rapid progression to apoptosis after 21 h as evidenced by a drastic drop in the average area of the cells after loss of cell membrane integrity. Finally, upon evaluation in a HeLa spheroid cell model, treatment with the FA-(C6+Dox)-LP showed significantly higher levels of cell death compared to those with C6-LP and

Discovery of imidazo[1,2-a]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model.

PubMed

Han, Wooseok; Menezes, Daniel L; Xu, Yongjin; Knapp, Mark S; Elling, Robert; Burger, Matthew T; Ni, Zhi-Jie; Smith, Aaron; Lan, Jiong; Williams, Teresa E; Verhagen, Joelle; Huh, Kay; Merritt, Hanne; Chan, John; Kaufman, Susan; Voliva, Charles F; Pecchi, Sabina

2016-02-01

Alterations in PI3K/AKT signaling are known to be implicated with tumorigenesis. The PI3 kinases family of lipid kinases has been an attractive therapeutic target for cancer treatment. Imidazopyridine compound 1, a potent, selective, and orally available pan-PI3K inhibitor, identified by scaffold morphing of a benzothiazole hit, was further optimized in order to achieve efficacy in a PTEN-deleted A2780 ovarian cancer mouse xenograft model. With a hypothesis that a planar conformation between the core and the 6-heteroaryl ring will allow for the accommodation of larger 5'-substituents in a hydrophobic area under P-loop, SAR efforts focused on 5'-alkoxy heteroaryl rings at the 6-position of imidazopyridine and imidazopyridazine cores that have the same dihedral angle of zero degrees. 6'-Alkoxy 5'-aminopyrazines in the imidazopyridine series were identified as the most potent compounds in the A2780 cell line. Compound 14 with 1,1,1-trifluoroisopropoxy group at 6'-position demonstrated excellent potency and selectivity, good oral exposure in rats and in vivo efficacy in A2780 tumor-bearing mouse. Also, we disclose the X-ray co-crystal structure of one enantiomer of compound 14 in PI3Kα, confirming that the trifluoromethyl group fits nicely in the hydrophobic hot spot under P-loop. Copyright © 2016 Elsevier Ltd. All rights reserved.

Discovery of imidazo[1,2- a ]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model

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

Han, Wooseok; Menezes, Daniel L.; Xu, Yongjin

Alterations in PI3K/AKT signaling are known to be implicated with tumorigenesis. The PI3 kinases family of lipid kinases has been an attractive therapeutic target for cancer treatment. Imidazopyridine compound 1, a potent, selective, and orally available pan-PI3K inhibitor, identified by scaffold morphing of a benzothiazole hit, was further optimized in order to achieve efficacy in a PTEN-deleted A2780 ovarian cancer mouse xenograft model. With a hypothesis that a planar conformation between the core and the 6-heteroaryl ring will allow for the accommodation of larger 5'-substituents in a hydrophobic area under P-loop, SAR efforts focused on 5'-alkoxy heteroaryl rings at themore » 6-position of imidazopyridine and imidazopyridazine cores that have the same dihedral angle of zero degrees. 6'-Alkoxy 5'-aminopyrazines in the imidazopyridine series were identified as the most potent compounds in the A2780 cell line. Compound 14 with 1,1,1-trifluoroisopropoxy group at 6'-position demonstrated excellent potency and selectivity, good oral exposure in rats and in vivo efficacy in A2780 tumor-bearing mouse. Also, we disclose the X-ray co-crystal structure of one enantiomer of compound 14 in PI3Kα, confirming that the trifluoromethyl group fits nicely in the hydrophobic hot spot under P-loop.« less

Anti-proliferative ambuic acid derivatives from Hawaiian endophytic fungus Pestalotiopsis sp. FT172.

PubMed

Li, Chun-Shun; Yang, Bao-Jun; Turkson, James; Cao, Shugeng

2017-08-01

Five previously undescribed ambuic acid derivatives, pestallic acids A-E and three known analogs were isolated from the cultured broth of Pestalotiopsis sp. FT172. The structures of the pestallic acids A-E were determined through the analysis of HRMS and NMR spectroscopic data. The absolute configurations (ACs) of pestallic acids B-E were assigned by comparison of the experimental electric circular dichroism (ECD) spectra or the optical rotations with those in the literature. All compounds were tested against A2780 and cisplatin resistant A2780 (A2780CisR) cell lines. Pestallic acid E and (+)-ambuic acid showed potent activities with IC 50 values from 3.3 to 17.0 μM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer.

PubMed

Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J

2016-11-08

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer.

Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer

NASA Astrophysics Data System (ADS)

Gao, Xiang; Wang, Bilan; Wei, Xiawei; Men, Ke; Zheng, Fengjin; Zhou, Yingfeng; Zheng, Yu; Gou, Maling; Huang, Meijuan; Guo, Gang; Huang, Ning; Qian, Zhiyong; Wei, Yuquan

2012-10-01

Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

The role of topotecan for extending the platinum-free interval in recurrent ovarian cancer: an in vitro model.

PubMed

Horowitz, Neil S; Hua, Jun; Gibb, Randall K; Mutch, David G; Herzog, Thomas J

2004-07-01

Topotecan, a novel topoisomerase-I inhibitor, is an active agent of second-line chemotherapy for extending the platinum-free interval (PFI) and improving the chances of a response to platinum in recurrent ovarian cancer patients. The aim of this study was to understand the molecular mechanism of topotecan-based second-line chemotherapy through an in vitro cell culture model and to gain clinical insight into sequencing issues for second-line treatment with novel agents versus retreatment with platinum. The human ovarian cancer cell line A2780 and the cisplatin resistance cell line A2780-CR were separately seeded in 6-well cell culture plates and then exposed to multiple concentrations of cisplatin plus paclitaxel or topotecan for 7 days. Surviving cells were recovered and cultured in drug-free media for 3 weeks and then replated in a 96-well microtiter plate. The LD(50) for these cells was determined by a cytotoxic MTT assay after exposure to multiple clinically relevant concentrations of cisplatin or topotecan. Surviving cells were cultured in drug-free media for an additional 4 weeks at which time the LD(50) was reassessed for each cell population by a second MTT assay. Using RT-PCR and Northern blot hybridization to measure mRNA expression, the molecular profile of these cells in terms of resistance was evaluated for the multidrug-resistant gene (MDR-1), multidrug-resistant protein (MRP), Topoisomerase-I, and beta-Actin. The LD(50) to cisplatin was unchanged in A2780-CR cells treated by topotecan. Those A2780-CR cells originally exposed to higher concentrations of cisplatin became more resistant to cisplatin in the MTT assays, while those A2780-CR cell lines treated with a combination of lower cisplatin concentrations and paclitaxel became more sensitive to cisplatin in the MTT assay (P < 0.01). The second MTT assay demonstrated that the LD(50) for cisplatin in every cell line decreased significantly after a 4-week drug-free interval (P < 0.01). There was no

MicroRNA-133b targets glutathione S-transferase π expression to increase ovarian cancer cell sensitivity to chemotherapy drugs.

PubMed

Chen, Shuo; Jiao, Jin-Wen; Sun, Kai-Xuan; Zong, Zhi-Hong; Zhao, Yang

2015-01-01

Accumulating studies reveal that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. The aim of this study was to investigate the role of miR-133b in the development of drug resistance in ovarian cancer cells. We examined the levels of miR-133b expression in ovarian carcinoma tissues and the human ovarian carcinoma cell lines (A2780, A2780/DDP and A2780/Taxol, respectively). We determined the cell viability of these cell lines treated with cisplatin or paclitaxel in the presence or absence of miR-133b or anti-miR-133b transfection using the MTT assay. Reverse transcription polymerase chain reaction and Western blotting were used to assess the mRNA and protein expression levels of two drug-resistance-related genes: glutathione S-transferase (GST)-π and multidrug resistance protein 1 (MDR1). The dual-luciferase reporter assay was used to detect the promoter activity of GST-π in the presence and absence of miR-133b. The expression of miR-133b was significantly lower in primary resistant ovarian carcinomas than in the chemotherapy-sensitive carcinomas (P<0.05), and the same results were found in primary resistant ovarian cell lines (A2780/Taxol and A2780/DDP) compared to the chemotherapy-sensitive cell line (A2780; P<0.05). Following miR-133b transfection, four cell lines showed increased sensitivity to paclitaxel and cisplatin, while anti-miR-133b transfection reduced cell sensitivity to paclitaxel and cisplatin. Dual-luciferase reporter assay showed that miR-133b interacted with the 3'-untranslated region of GST-π. Compared to controls, the mRNA and protein levels of MDR1 and GST-π were downregulated after miR-133b transfection and upregulated after anti-miR-133b transfection. MicroRNA-133b may reduce ovarian cancer drug resistance by silencing the expression of the drug-resistance-related proteins, GST-π and MDR1. In future, the combination of miR-133b with

The LARSYS educational package: Instructor's notes. [instructional materials for training people to analyze remotely sensed data

NASA Technical Reports Server (NTRS)

Lindenlaub, J. C.; Davis, S. M.

1974-01-01

Materials are presented for assisting instructors in teaching the LARSYS Educational Package, which is a set of instructional materials to train people to analyze remotely sensed multispectral data. The seven units of the package are described. These units are: quantitative remote sensing, overview of the LARSYS software system, the 2780 remote terminal, demonstration of LARSYS on the 2780 remote terminal, exercises, guide to multispectral data analysis, and a case study using LARSYS for analysis of LANDSAT data.

Exosomes as mediators of platinum resistance in ovarian cancer

PubMed Central

Crow, Jennifer; Atay, Safinur; Banskota, Samagya; Artale, Brittany; Schmitt, Sarah; Godwin, Andrew K

2017-01-01

Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls. This coincided with increased epithelial to mesenchymal transition (EMT). DNA sequencing of EOC cell lines revealed previously unreported somatic mutations in the Mothers Against Decapentaplegic Homolog 4 (SMAD4) within platinum-resistant cells. A2780 cells engineered to exogenously express these SMAD4 mutations demonstrate up-regulation of EMT markers following carboplatin treatment, are more resistant to carboplatin, and release exosomes which impart a ~1.7-fold increase in resistance in naive A2780 recipient cells as compared to controls. These studies provide the first evidence that acquired SMAD4 mutations enhance the chemo-resistance profile of EOC and present a novel mechanism in which exchange of tumor-derived exosomes perpetuates an EMT phenotype, leading to the development of subpopulations of platinum-refractory cells. PMID:28060758

Exosomes as mediators of platinum resistance in ovarian cancer.

PubMed

Crow, Jennifer; Atay, Safinur; Banskota, Samagya; Artale, Brittany; Schmitt, Sarah; Godwin, Andrew K

2017-02-14

Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls. This coincided with increased epithelial to mesenchymal transition (EMT). DNA sequencing of EOC cell lines revealed previously unreported somatic mutations in the Mothers Against Decapentaplegic Homolog 4 (SMAD4) within platinum-resistant cells. A2780 cells engineered to exogenously express these SMAD4 mutations demonstrate up-regulation of EMT markers following carboplatin treatment, are more resistant to carboplatin, and release exosomes which impart a ~1.7-fold increase in resistance in naive A2780 recipient cells as compared to controls. These studies provide the first evidence that acquired SMAD4 mutations enhance the chemo-resistance profile of EOC and present a novel mechanism in which exchange of tumor-derived exosomes perpetuates an EMT phenotype, leading to the development of subpopulations of platinum-refractory cells.

Near East/South Asia Report, No. 2780.

DTIC Science & Technology

1983-07-08

Processing indicators such as [Text] or [Excerpt] in the first line of each item, or following the last line of a brief, indicate how the original... get his house, but that will also require that his wife keep work- ing to help pay for it. Home or Work? Dalila and Mustapha have been married for 7...playing on the stairs." Dalila plans to return to work. But she is a little apprehensive about doing so, because it will mean getting organized. Who

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

Piotrowska, Hanna; Myszkowski, Krzysztof; Ziółkowska, Alicja

In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC{sub 50} = 0.71 μM) and SKOV-3 (IC{sub 50} = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 andmore » p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.« less

Two new ortho benzoquinones from Uncaria rhynchophylla.

PubMed

Zhang, Qian; Chen, Lei; Hu, Le-Jian; Liu, Wen-Yuan; Feng, Feng; Qu, Wei

2016-03-01

The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH2Cl2 fraction by chromatography. Their structures were elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone (1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone (2), together with a known compound isorhynchophyllic acid (3) were isolated from U. rhynchophylla. These compounds were evaluated for their cytotoxicity against cancer cells A549, HepG2 and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak antiproliferative activities on A549, HepG2 and A2780 cells. Compound 3 significantly inhibited the proliferation of A549, HepG2 and A2780 cells with IC50 values being 5.8, 12.8 and 11.8 µmol·L(-1), respectively. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Synthesis, crystal structure and anticancer activity of tetrakis(N-isopropylimidazolidine-2-selenone)platinum(II) chloride

NASA Astrophysics Data System (ADS)

Ahmad, Saeed; Altoum, Ali Osman S.; Vančo, Ján; Křikavová, Radka; Trávníček, Zdeněk; Dvořák, Zdeněk; Altaf, Muhammad; Sohail, Manzar; Isab, Anvarhusein A.

2018-01-01

A Platinum(II) complex of N-isopropylimidazolidine-2-selenone (i-PrImSe), [Pt(i-PrImSe)4]Cl2 (1) was prepared and characterized by elemental analysis, IR and NMR (1H, 13C, 77Se &195Pt) spectroscopy, and X-ray crystallography. The structure of 1 consists of [Pt(i-PrImSe)4]2+ complex ion and chloride counter ions. The platinum(II) atom adopts a distorted square planar geometry. The in vitro antitumor activity of 1 as well as cisplatin, was evaluated by MTT assay against human; ovarian carcinoma A2780 and its cisplatin-resistant subline A2780R, prostate cancer 22Rv1 and breast cancer MCF-7 cell lines. The title complex displayed the activity against the A2780 cells (IC50 = 30.8 μM) at the level comparable to cisplatin (IC50 = 26.8 μM). The interaction studies with sulfur-containing biomolecules revealed its ability to form a variety of intermediates and oxidized species with L-cysteine and reduced glutathione.

Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology

PubMed Central

Alonezi, Sanad; Tusiimire, Jonans; Wallace, Jennifer; Dufton, Mark J.; Parkinson, John A.; Young, Louise C.; Clements, Carol J.; Park, Jin Kyu; Jeon, Jong Woon; Ferro, Valerie A.; Watson, David G.

2016-01-01

In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists. Principal component analysis (PCA) gave clear separation between the cisplatin-sensitive and resistant strains and their respective controls. The cisplatin-resistant cells were slightly more sensitive to melittin than the sensitive cells with IC50 values of 4.5 and 6.8 μg/mL respectively, although the latter cell line exhibited the greatest metabolic perturbation upon treatment. The changes induced by melittin in the cisplatin-sensitive cells led mostly to reduced levels of amino acids in the proline/glutamine/arginine pathway, as well as to decreased levels of carnitines, polyamines, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+). The effects on energy metabolism were supported by the data from the Biolog assays. The lipid compositions of the two cell lines were quite different with the A2780 cells having higher levels of several ether lipids than the A2780CR cells. Melittin also had some effect on the lipid composition of the cells. Overall, this study suggests that melittin might have some potential as an adjuvant therapy in cancer treatment. PMID:27754384

Ovarian cancer stem cells.

PubMed

Zeimet, A G; Reimer, D; Sopper, S; Boesch, M; Martowicz, A; Roessler, J; Wiedemair, A M; Rumpold, H; Untergasser, G; Concin, N; Hofstetter, G; Muller-Holzner, E; Fiegl, H; Marth, C; Wolf, D; Pesta, M; Hatina, J

2012-01-01

Because of its semi-solid character in dissemination and growth, advanced ovarian cancer with its hundreds of peritoneal tumor nodules and plaques appears to be an excellent in vivo model for studying the cancer stem cell hypothesis. The most important obstacle, however, is to adequately define and isolate these tumor-initiating cells endowed with the properties of anoikis-resistance and unlimited self-renewal. Until now, no universal single marker or marker constellation has been found to faithfully isolate (ovarian) cancer stem cells. As these multipotent cells are known to possess highly elaborated efflux systems for cytotoxic agents, these pump systems have been exploited to outline putative stem cells as a side-population (SP) via dye exclusion analysis. Furthermore, the cells in question have been isolated via flow cytometry on the basis of cell surface markers thought to be characteristic for stem cells.In the Vienna variant of the ovarian cancer cell line A2780 a proof-of-principle model with both a stable SP and a stable ALDH1A1+ cell population was established. Double staining clearly revealed that both cell fractions were not identical. Of note, A2780V cells were negative for expression of surface markers CD44 and CD117 (c-kit). When cultured on monolayers of healthy human mesothelial cells, green-fluorescence-protein (GFP)-transfected SP of A2780V exhibited spheroid-formation, whereas non-side-population (NSP) developed a spare monolayer growing over the healthy mesothelium. Furthermore, A2780V SP was found to be partially resistant to platinum. However, this resistance could not be explained by over-expression of the "excision repair cross-complementation group 1" (ERCC1) gene, which is essentially involved in the repair of platinated DNA damage. ERCC1 was, nonetheless, over-expressed in A2780V cells grown as spheres under stem cell-selective conditions as compared to adherent monolayers cultured under differentiating conditions. The same was true for

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

PubMed

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-02-24

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

PubMed Central

Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

2016-01-01

As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

21 CFR 870.2780 - Hydraulic, pneumatic, or photoelectric plethysmographs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices..., pneumatic, or photoelectric plethysmograph is a device used to estimate blood flow in a region of the body using hydraulic, pneumatic, or photoelectric measurement techniques. (b) Classification. Class II...

21 CFR 870.2780 - Hydraulic, pneumatic, or photoelectric plethysmographs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices..., pneumatic, or photoelectric plethysmograph is a device used to estimate blood flow in a region of the body using hydraulic, pneumatic, or photoelectric measurement techniques. (b) Classification. Class II...

21 CFR 870.2780 - Hydraulic, pneumatic, or photoelectric plethysmographs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices..., pneumatic, or photoelectric plethysmograph is a device used to estimate blood flow in a region of the body using hydraulic, pneumatic, or photoelectric measurement techniques. (b) Classification. Class II...

40 CFR 52.2780 - Control strategy for sulfur oxides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... maintenance of the national ambient air quality standards for sulfur oxides on the island of St. Croix. (b...) The entire regulation as it applies to the islands of St. Thomas and St. John. (2) The entire... island of St. Croix. (3) The entire regulation excluding subsection (a)(2) as it applies to the remaining...

12 CFR 627.2780 - Powers and duties of conservators.

Code of Federal Regulations, 2010 CFR

2010-01-01

... operations for the benefit of the creditors and stockholders of the institution. (b) The conservator may, with respect to Farm Credit institutions, exercise the powers that a receiver of an institution may exercise under any of the provisions of § 627.2725(b) of this part, except paragraphs § 627.2725 (b)(2) and...

40 CFR 52.2780 - Control strategy for sulfur oxides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Control strategy for sulfur oxides. 52... strategy for sulfur oxides. (a) The requirements of subpart G of this chapter are not met since there has... maintenance of the national ambient air quality standards for sulfur oxides on the island of St. Croix. (b...

40 CFR 52.2780 - Control strategy for sulfur oxides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Control strategy for sulfur oxides. 52... strategy for sulfur oxides. (a) The requirements of subpart G of this chapter are not met since there has... maintenance of the national ambient air quality standards for sulfur oxides on the island of St. Croix. (b...

40 CFR 52.2780 - Control strategy for sulfur oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Control strategy for sulfur oxides. 52... strategy for sulfur oxides. (a) The requirements of subpart G of this chapter are not met since there has... maintenance of the national ambient air quality standards for sulfur oxides on the island of St. Croix. (b...

40 CFR 52.2780 - Control strategy for sulfur oxides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Control strategy for sulfur oxides. 52... strategy for sulfur oxides. (a) The requirements of subpart G of this chapter are not met since there has... maintenance of the national ambient air quality standards for sulfur oxides on the island of St. Croix. (b...

Gold(I) Complexes of 9-Deazahypoxanthine as Selective Antitumor and Anti-Inflammatory Agents

PubMed Central

Vančo, Ján; Gáliková, Jana; Hošek, Jan; Dvořák, Zdeněk; Paráková, Lenka; Trávníček, Zdeněk

2014-01-01

The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1–5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1–5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1–5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1–5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds. PMID:25333949

Antiproliferative Cardenolide Glycosides of Elaeodendron alluaudianum from the Madagascar Rainforest1

PubMed Central

Hou, Yanpeng; Cao, Shugeng; Brodie, Peggy; Callmander, Martin; Ratovoson, Fidisoa; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.; Rakotonandrasana, Stephan; TenDyke, Karen; Suh, Edward M.; Kingston, David G. I.

2010-01-01

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of Elaeodendron alluaudianum led to the isolation of two new cardenolide glycosides (1 and 2). The 1H and 13C NMR spectra of both compounds were fully assigned using a combination of 2D NMR experiments, including 1H-1H COSY, HSQC, HMBC, and ROESY sequences. Both compounds 1 and 2 were tested against the A2780 human ovarian cancer cell line and the U937 human histiocytic lymphoma cell line assays, and showed significant antiproliferative activity with IC50 values of 0.12 and 0.07 μM against the A2780 human ovarian cancer cell line, and 0.15 and 0.08 μM against the U937 human histiocytic lymphoma cell line, respectively. PMID:19058971

ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells.

PubMed

Hinrichs, John W J; Klappe, Karin; Hummel, Ina; Kok, Jan W

2004-02-13

In this study we show that P-glycoprotein in multidrug-resistant 2780AD human ovarian carcinoma cells and multidrug resistance-associated protein 1 in multidrug-resistant HT29col human colon carcinoma cells are predominantly located in Lubrol-based detergent-insoluble glycosphingolipid-enriched membrane domains. This localization is independent of caveolae, since 2780AD cells do not express caveolin-1. Although HT29col cells do express caveolin-1, the ATP-binding cassette transporter and caveolin-1 were dissociated on the basis of differential solubility in Triton X-100 and absence of microscopical colocalization. While both the multidrug resistance-associated protein 1 and caveolin-1 are located in Lubrol-based membrane domains, they occupy different regions of these domains.

PG545 enhances anti-cancer activity of chemotherapy in ovarian models and increases surrogate biomarkers such as VEGF in preclinical and clinical plasma samples.

PubMed

Winterhoff, Boris; Freyer, Luisa; Hammond, Edward; Giri, Shailendra; Mondal, Susmita; Roy, Debarshi; Teoman, Attila; Mullany, Sally A; Hoffmann, Robert; von Bismarck, Antonia; Chien, Jeremy; Block, Matthew S; Millward, Michael; Bampton, Darryn; Dredge, Keith; Shridhar, Viji

2015-05-01

Despite the utility of antiangiogenic drugs in ovarian cancer, efficacy remains limited due to resistance linked to alternate angiogenic pathways and metastasis. Therefore, we investigated PG545, an anti-angiogenic and anti-metastatic agent which is currently in Phase I clinical trials, using preclinical models of ovarian cancer. PG545's anti-cancer activity was investigated in vitro and in vivo as a single agent, and in combination with paclitaxel, cisplatin or carboplatin using various ovarian cancer cell lines and tumour models. PG545, alone, or in combination with chemotherapeutics, inhibited proliferation of ovarian cancer cells, demonstrating synergy with paclitaxel in A2780 cells. PG545 inhibited growth factor-mediated cell migration and reduced HB-EGF-induced phosphorylation of ERK, AKT and EGFR in vitro and significantly reduced tumour burden which was enhanced when combined with paclitaxel in an A2780 model or carboplatin in a SKOV-3 model. Moreover, in the immunocompetent ID8 model, PG545 also significantly reduced ascites in vivo. In the A2780 maintenance model, PG545 initiated with, and following paclitaxel and cisplatin treatment, significantly improved overall survival. PG545 increased plasma VEGF levels (and other targets) in preclinical models and in a small cohort of advanced cancer patients which might represent a potential biomarker of response. Our results support clinical testing of PG545, particularly in combination with paclitaxel, as a novel therapeutic strategy for ovarian cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ribozyme-mediated cleavage of c-fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein.

PubMed Central

Scanlon, K J; Jiao, L; Funato, T; Wang, W; Tone, T; Rossi, J J; Kashani-Sabet, M

1991-01-01

The c-fos gene product Fos has been implicated in many cellular processes, including signal transduction, DNA synthesis, and resistance to antineoplastic agents. A fos ribozyme (catalytic RNA) was designed to evaluate the effects of suppressing Fos protein synthesis on expression of enzymes involved in DNA synthesis, DNA repair, and drug resistance. DNA encoding the fos ribozyme (fosRb) was cloned into the pMAMneo expression plasmid, and the resultant vector was transfected into A2780DDP cells resistant to the chemotherapeutic agent cisplatin. The parental drug-sensitive A2780S cells were transfected with the pMMV vector containing the c-fos gene. Morphological alterations were accompanied by significant changes in pharmacological sensitivity in both c-fos- and fosRb-transfected cells. pMAMneo fosRb transfectants revealed decreased c-fos gene expression, concomitant with reduced thymidylate (dTMP) synthase, DNA polymerase beta, topoisomerase I, and metallothionein IIA mRNAs. In contrast, c-myc expression was elevated after fos ribozyme action. Insertion of a mutant ribozyme, mainly capable of antisense activity, into A2780DDP cells resulted in smaller reductions in c-fos gene expression and in cisplatin resistance than the active ribozyme. These studies establish a role for c-fos in drug resistance and in mediating DNA synthesis and repair processes by modulating expression of genes such as dTMP synthase, DNA polymerase beta, and topoisomerase I. These studies also suggest the utility of ribozymes in the analysis of cellular gene expression. Images PMID:1660142

TET1 promotes cisplatin-resistance via demethylating the vimentin promoter in ovarian cancer.

PubMed

Han, Xi; Zhou, Yuanyuan; You, Yuanyi; Lu, Jiaojiao; Wang, Lijie; Hou, Huilian; Li, Jing; Chen, Wei; Zhao, Le; Li, Xu

2017-04-01

The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells. Ectopic expression of TET1 in A2780 cells promoted cisplatin resistance and decreased cytotoxicity induced by cisplatin, while inhibition of TET1 by siRNA transfection in CP70 cells attenuated cisplatin resistance and enhanced cytotoxicity of cisplatin. Increased TET1 induced re-expression of vimentin through active DNA demethylation, and cause partial epithelial-to-mesenchymal (EMT) in A2780 cells. Contrarily, knocking down of TET1 in CP70 cells reduced vimentin expression and reversed EMT process. Immunohistochemical analysis of TET1 in human ovarian cancer tissues revealed that TET1 existed in nucleus and cytoplasm in ovarian cancer tissues. And the expression of nuclear TET1 was positively correlated with residual tumor and chemotherapeutic response. Thus, TET1 expression causes resistance to cisplatin and one of the targets of TET1 action is vimentin in ovarian cancer. © 2017 International Federation for Cell Biology.

A New Typology for State-Sponsored International Terrorism

DTIC Science & Technology

2011-12-01

David C. Martin and John Walcott, Best Laid Plans: The inside Story of America’s War against Terrorism (New York: Simon and Schuster, 1988). 9...69 22 U.S.C. § 1691 70 22 U.S.C. § 2501 71 12 U.S.C. § 635 72 22 U.S.C. § 2780 73 Petra Minnerop, "Legal Status...D.C.: Congressional Research Service, 2010. Markey, Daniel. "A False Choice in Pakistan." Foreign Affairs 86, no. 4 (2007). Minnerop, Petra . "Legal

In Vitro Antitumor Active Gold(I) Triphenylphosphane Complexes Containing 7-Azaindoles

PubMed Central

Štarha, Pavel; Trávníček, Zdeněk; Drahoš, Bohuslav; Dvořák, Zdeněk

2016-01-01

A series of gold(I) complexes of the general composition [Au(naza)(PPh3)] (1–8) was prepared and thoroughly characterized (e.g., electrospray ionization (ESI) mass spectrometry and multinuclear nuclear magnetic resonance (NMR) spectroscopy). The N1-deprotonated anions of 7-azaindole or its derivatives (naza) are coordinated to the metal centre through the N1 atom of their pyrrole ring, as proved by a single crystal X-ray analysis of the complexes [Au(3I5Braza)(PPh3)] (7) and [Au(2Me4Claza)(PPh3)]·½H2O (8′). The in vitro cytotoxicity of the complexes 1–8 was studied against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the MRC-5 human normal fibroblast cell line. The complexes 4, 5, and 8, containing deprotonated 3-iodo-7-azaindole, 5-bromo-7-azaindole, and 2-methyl-4-chloro-7-azaindole (2Me4Claza), respectively, showed significantly higher potency (IC50 = 2.8–3.5 µM) than cisplatin (IC50 = 20.3 µM) against the A2780 cells and markedly lower effect towards the MRC-5 non-cancerous cells (IC50 = 26.0–29.2 µM), as compared with the mentioned A2780 cancer cells. The results of the flow cytometric studies of the A2780 cell cycle perturbations revealed a G2-cell cycle phase arrest of the cells treated by the representative complexes 1 and 5, which is indicative of a different mechanism of action from cisplatin (induced S-cell cycle phase arrest). The stability of the representative complex 8 in the water-containing solution as well as its ability to interact with the reduced glutathione, cysteine and bovine serum albumin was also studied using 1H and 31P-NMR spectroscopy (studied in the 50% DMF-d7/50% D2O mixture) and ESI+ mass spectrometry (studied in the 50% DMF/50% H2O mixture); DMF = dimethylformamide. The obtained results are indicative for the release of the N-donor azaindole-based ligand in the presence of the used biomolecules. PMID:27973440

Unsymmetric Mono- and Dinuclear Platinum(IV) Complexes Featuring an Ethylene Glycol Moiety: Synthesis, Characterization, and Biological Activity

PubMed Central

Pichler, Verena; Heffeter, Petra; Valiahdi, Seied M.; Kowol, Christian R.; Egger, Alexander; Berger, Walter; Jakupec, Michael A.; Galanski, Markus; Keppler, Bernhard K.

2014-01-01

Eight novel mononuclear and two dinuclear platinum(IV) complexes were synthesized and characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, mass spectrometry, and reversed-phase HPLC (log kw) and in one case by X-ray diffraction. Cytotoxicity of the compounds was studied in three human cancer cell lines (CH1, SW480, and A549) by means of the MTT assay, featuring IC50 values to the low micromolar range. Furthermore a selected set of compounds was investigated in additional cancer cell lines (P31 and P31/cis, A2780 and A2780/cis, SW1573, 2R120, and 2R160) with regard to their resistance patterns, offering a distinctly different scheme compared to cisplatin. To gain further insights into the mode of action, drug uptake, DNA synthesis inhibition, cell cycle effects, and induction of apoptosis were determined for two characteristic substances. PMID:23194425

MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells.

PubMed

Hu, Jianguo; Meng, Ying; Zhang, Zhanqin; Yan, Qiuting; Jiang, Xingwei; Lv, Zilan; Hu, Lina

2017-02-01

MARCH5 is a crucial regulator of mitochondrial fission. However, the expression and function of MARCH5 in ovarian cancer have not been determined. This study investigated the expression and function of MARCH5 in ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as its usefulness as an early diagnostic marker. We found that the expression of MARCH5 was substantially upregulated in ovarian cancer tissue in comparison with the normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas the ectopic expression of MARCH5 in A2780 cells had the opposite effect. Mechanistic investigations revealed that MARCH5 RNA may function as a competing endogenous RNA (ceRNA) to regulate the expression of SMAD2 and ATG5 by competing for MIR30A. Knocking down SMAD2 or ATG5 can block the effect of MARCH5 in A2780 cells. Also, silencing the expression of MARCH5 in SKOV3 cells can inhibit the TGFB1-SMAD2/3 pathway. In contrast, the ectopic expression of MARCH5 in A2780 cells can activate the TGFB1-SMAD2/3 pathway. In turn, the TGFB1-SMAD2/3 pathway can regulate MARCH5 and ATG5 through MIR30A. Overall, the results of this study identified MARCH5 as a candidate oncogene in ovarian cancer and a potential target for ovarian cancer therapy.

Four diterpenoid inhibitors of Cdc25B phosphatase from a marine anemone.

PubMed

Cao, Shugeng; Foster, Caleb; Lazo, John S; Kingston, David G I

2005-10-15

Three new diterpenoids and one known diterpenoid have been isolated from a sea anemone of the order Actiniara, and the structures of the new compounds, actiniarins A-C (1-3) were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. Compound 1 has a six-membered ring hemiacetal ring, and the equilibrium of this ring is discussed. All the isolates were evaluated for their inhibition of Cdc25B and for cytotoxicity against the A2780 ovarian cancer cell line.

Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles.

PubMed

Zou, Liang; Wang, Di; Hu, Yichen; Fu, Chaomei; Li, Wei; Dai, Liping; Yang, Lin; Zhang, Jinming

2017-09-01

Paclitaxel (PTX) is frequently suffered from multidrug resistance (MDR), resulting in lower chemotherapeutic efficacy and even chemotherapy failure. To combine the P-glycolprotein (P-gp) inhibitor would be a useful strategy to overcome MDR. However, what is needed now is an efficient vehicle to deliver multiple drugs into tumor simultaneously. In this study, PTX and Borneol (BNL), a natural compound with P-gp inhibition effect confirmed in intestinal absorption, were co-loaded in the fabricated PEG-PAMAM nanoparticle (NPs) by a one-step nano-precipitation method with high drug loading efficiency, narrow size distribution and low hemolysis rate. Based on P-gp inhibition activity of BNL, confirmed by drug efflux test and molecular docking model, the combination of PTX and BNL could improve intracellular concentration of PTX in A2780/PTX cells. Furthermore, compared to both free PTX and PTX+BNL, PB/NPs and P/NPs plus BNL exhibited higher cellular uptake and cytotoxicity in A2780/PTX cells, as well as the decreased MMP and enhanced apoptosis rate. More importantly, although PB/NPs and P/NPs+B showed similar tumor accumulation in tumor-bearing mice, PB/NPs could significantly decrease tumor growth of A2780/PTX tumor-bearing mice, in comparison to P/NPs+B. These results indicated the advantage of PTX and BNL co-delivery NPs for MDR reversal. These findings demonstrate that the co-delivery nano-sized system comprised by PEG-PAMAM polymer with PTX and BNL co-loaded would be a promising candidate for MDR treatment.

Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles

PubMed Central

Zou, Liang; Wang, Di; Hu, Yichen; Fu, Chaomei; Li, Wei; Dai, Liping; Yang, Lin; Zhang, Jinming

2017-01-01

Paclitaxel (PTX) is frequently suffered from multidrug resistance (MDR), resulting in lower chemotherapeutic efficacy and even chemotherapy failure. To combine the P-glycolprotein (P-gp) inhibitor would be a useful strategy to overcome MDR. However, what is needed now is an efficient vehicle to deliver multiple drugs into tumor simultaneously. In this study, PTX and Borneol (BNL), a natural compound with P-gp inhibition effect confirmed in intestinal absorption, were co-loaded in the fabricated PEG-PAMAM nanoparticle (NPs) by a one-step nano-precipitation method with high drug loading efficiency, narrow size distribution and low hemolysis rate. Based on P-gp inhibition activity of BNL, confirmed by drug efflux test and molecular docking model, the combination of PTX and BNL could improve intracellular concentration of PTX in A2780/PTX cells. Furthermore, compared to both free PTX and PTX+BNL, PB/NPs and P/NPs plus BNL exhibited higher cellular uptake and cytotoxicity in A2780/PTX cells, as well as the decreased MMP and enhanced apoptosis rate. More importantly, although PB/NPs and P/NPs+B showed similar tumor accumulation in tumor-bearing mice, PB/NPs could significantly decrease tumor growth of A2780/PTX tumor-bearing mice, in comparison to P/NPs+B. These results indicated the advantage of PTX and BNL co-delivery NPs for MDR reversal. These findings demonstrate that the co-delivery nano-sized system comprised by PEG-PAMAM polymer with PTX and BNL co-loaded would be a promising candidate for MDR treatment. PMID:28947984

Poly(alkylidenimine) Dendrimers Functionalized with the Organometallic Moiety [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ as Promising Drugs Against Cisplatin-Resistant Cancer Cells and Human Mesenchymal Stem Cells.

PubMed

Gouveia, Marisol; Figueira, João; Jardim, Manuel G; Castro, Rita; Tomás, Helena; Rissanen, Kari; Rodrigues, João

2018-06-17

Here and for the first time, we show that the organometallic compound [Ru(η⁵-C₅H₅)(PPh₃)₂Cl] (RuCp) has potential to be used as a metallodrug in anticancer therapy, and further present a new approach for the cellular delivery of the [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragment via coordination on the periphery of low-generation poly(alkylidenimine) dendrimers through nitrile terminal groups. Importantly, both the RuCp and the dendrimers functionalized with [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragments present remarkable toxicity towards a wide set of cancer cells (Caco-2, MCF-7, CAL-72, and A2780 cells), including cisplatin-resistant human ovarian carcinoma cell lines (A2780 cis R cells). Also, RuCp and the prepared metallodendrimers are active against human mesenchymal stem cells (hMSCs), which are often found in the tumor microenvironment where they seem to play a role in tumor progression and drug resistance.

Triphenyltin derivatives of sulfanylcarboxylic esters.

PubMed

Casas, José S; Couce, María D; Sánchez, Agustín; Seoane, Rafael; Sordo, José; Perez-Estévez, Antonio; Vázquez-López, Ezequiel

2018-03-01

The reaction of 3-(aryl)-2-sulfanylpropenoic acids [H 2 xspa; x: p=3-phenyl-, f=3-(2-furyl)-, t=3-(2-thienyl)-] with methanol or ethanol gave the corresponding methyl (Hxspme) or ethyl (Hxspee) esters. The reaction of these esters (HL) with triphenyltin(IV) hydroxide gave compounds of the type [SnPh 3 L], which were isolated and characterized as solids by elemental analysis, IR spectroscopy and mass spectrometry and in solution by multinuclear ( 1 H, 13 C and 119 Sn) NMR spectroscopy. The structures of [SnPh 3 (pspme)], [SnPh 3 (fspme)] and [SnPh 3 (fspee)] were determined by X-ray diffractometry and the antimicrobial activity against E. coli, S. aureus, B. subtilis, P. aeruginosa, Resistant P. aeruginosa (a strain resistant to 'carbapenem'), and C. albicans was tested and the in vitro cytotoxic activity against the HeLa-229, A2780 and A2780cis cell lines was determined for all compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Organometallic rhodium(III) and iridium(III) cyclopentadienyl complexes with curcumin and bisdemethoxycurcumin co-ligands.

PubMed

Pettinari, Riccardo; Marchetti, Fabio; Pettinari, Claudio; Condello, Francesca; Petrini, Agnese; Scopelliti, Rosario; Riedel, Tina; Dyson, Paul J

2015-12-21

A series of half-sandwich cyclopentadienyl rhodium(III) and iridium(III) complexes of the type [Cp*M(curc/bdcurc)Cl] and [Cp*M(curc/bdcurc)(PTA)][SO3CF3], in which Cp* = pentamethylcyclopentadienyl, curcH = curcumin and bdcurcH = bisdemethoxycurcumin as O^O-chelating ligands, and PTA = 1,3,5-triaza-7-phosphaadamantane, is described. The X-ray crystal structures of three of the complexes, i.e. [Cp*Rh(curc)(PTA)][SO3CF3] (5), [Cp*Rh(bdcurc)(PTA)][SO3CF3] (6) and [Cp*Ir(bdcurc)(PTA)][SO3CF3] (8), confirm the expected "piano-stool" geometry. With the exception of 5, the complexes are stable under pseudo-physiological conditions and are moderately cytotoxic to human ovarian carcinoma (A2780 and A2780cisR) cells and also to non-tumorigenic human embryonic kidney (HEK293) cells, but lack the cancer cell selectivity observed for related arene ruthenium(II) complexes.

Preclinical evaluation of olaparib and metformin combination in BRCA1 wildtype ovarian cancer.

PubMed

Hijaz, M; Chhina, J; Mert, I; Taylor, M; Dar, S; Al-Wahab, Z; Ali-Fehmi, R; Buekers, T; Munkarah, A R; Rattan, R

2016-08-01

BRCA mutated ovarian cancers show increased responsiveness to PARP inhibitors. PARP inhibitors target DNA repair and provide a second hit to BRCA mutated tumors, resulting in "synthetic lethality". We investigated a combination of metformin and olaparib to provide "synthetic lethality" in BRCA intact ovarian cancer cells. Ovarian cancer cell lines (UWB1.289, UWB1.289.BRCA, SKOV3, OVCAR5, A2780 and C200) were treated with a combination of metformin and olaparib. Cell viability was assessed by MTT and colony formation assays. Flow cytometry was used to detect cell cycle events. In vivo studies were performed in SKOV3 or A2780 xenografts in nude mice. Animals were treated with single agent, metformin or olaparib or combination. Molecular downstream effects were examined by immunohistochemistry. Compared to single drug treatment, combination of olaparib and metformin resulted in significant reduction of cell proliferation and colony formation (p<0.001) in ovarian cancer cells. This treatment was associated with a significant S-phase cell cycle arrest (p<0.05). Combination of olaparib and metformin significantly inhibited SKOV3 and A2780 ovarian tumor xenografts which were accompanied with decreased Ki-index (p<0.001). Metformin did not affect DNA damage signaling, while olaparib induced adenosine monophosphate activated kinase activation; that was further potentiated with metformin combination in vivo. Combining PARP inhibitors with metformin enhances its anti-proliferative activity in BRCA mutant ovarian cancer cells. Furthermore, the combination showed significant activity in BRCA intact cancer cells in vitro and in vivo. This is a promising treatment regimen for women with epithelial ovarian cancer irrespective of BRCA status. Copyright © 2016 Elsevier Inc. All rights reserved.

Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin: molecular mechanisms unveiled by gene expression profiling.

PubMed

Koch, Martin; Krieger, Michaela L; Stölting, Daniel; Brenner, Norbert; Beier, Manfred; Jaehde, Ulrich; Wiese, Michael; Royer, Hans-Dieter; Bendas, Gerd

2013-04-15

Previously we reported that liposomal cisplatin (CDDP) overcomes CDDP resistance of ovarian A2780cis cancer cells (Krieger et al., Int. J. Pharm. 389, 2010, 10-17). Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells. This suggests that the mode of action of liposomal CDDP is different from the free drug. To gain insight into mechanisms of liposomal CDDP activity, we performed a transcriptome analysis of untreated A2780cis cells, and A2780cis cells in response to exposure with IC50 values of free or liposomal CDDP. A process network analysis of upregulated genes showed that liposomal CDDP induced a highly different gene expression profile in comparison to the free drug. p53 was identified as a key player directing transcriptional responses to free or liposomal CDDP. The free drug induced expression of essential genes of the intrinsic (mitochondrial) apoptosis pathway (BAX, BID, CASP9) most likely through p38MAPK activation. In contrast, liposomal CDDP induced expression of genes from DNA damage pathways and several genes of the extrinsic pathway of apoptosis (TNFRSF10B-DR5, CD70-TNFSF7). It thus appears that liposomal CDDP overcomes CDDP resistance by inducing DNA damage and in consequence programmed cell death by the extrinsic pathway. Predictions from gene expression data with respect to apoptosis activation were confirmed at the protein level by an apoptosis antibody array. This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal CDDP as promising strategy for the treatment of CDDP resistant ovarian carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

PubMed

Pastorek, Michal; Simko, Veronika; Takacova, Martina; Barathova, Monika; Bartosova, Maria; Hunakova, Luba; Sedlakova, Olga; Hudecova, Sona; Krizanova, Olga; Dequiedt, Franck; Pastorekova, Silvia; Sedlak, Jan

2015-07-01

One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules.

Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

PubMed

Di Liddo, Rosa; Valente, Sergio; Taurone, Samanta; Zwergel, Clemens; Marrocco, Biagina; Turchetta, Rosaria; Conconi, Maria Teresa; Scarpa, Carlotta; Bertalot, Thomas; Schrenk, Sandra; Mai, Antonello; Artico, Marco

2016-01-20

Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy.

PubMed

Lee, F Y; Borzilleri, R; Fairchild, C R; Kim, S H; Long, B H; Reventos-Suarez, C; Vite, G D; Rose, W C; Kramer, R A

2001-05-01

BMS-247550, a novel epothilone derivative, is being developed by Bristol-Myers Squibb Company (BMS) as an anticancer agent for the treatment of patients with malignant tumors. BMS-247550 is a semisynthetic analogue of the natural product epothilone B and has a mode of action analogous to that of paclitaxel (i.e., microtubule stabilization). In vitro, it is twice as potent as paclitaxel in inducing tubulin polymerization. Like paclitaxel, BMS-247550 is a highly potent cytotoxic agent capable of killing cancer cells at low nanomolar concentrations. Importantly, BMS-247550 retains its antineoplastic activity against human cancers that are naturally insensitive to paclitaxel or that have developed resistance to paclitaxel, both in vitro and in vivo. Tumors for which BMS-247550 demonstrated significant antitumor activity encompass both paclitaxel-sensitive and -refractory categories, i.e., (a) paclitaxel-resistant: HCT116/VM46 colorectal (multidrug resistant), Pat-21 breast and Pat-7 ovarian carcinoma (clinical isolates; mechanisms of resistance not fully known), and A2780Tax ovarian carcinoma (tubulin mutation); (b) paclitaxel-insensitive: Pat-26 human pancreatic carcinoma (clinical isolate) and M5076 murine fibrosarcoma; and (c) paclitaxel sensitive: A2780 ovarian, LS174T, and HCT116 human colon carcinoma. In addition, BMS-247550 is p.o. efficacious against preclinical human tumor xenografts grown in immunocompromised mice or rats. Schedule optimization studies indicate that BMS-247550 is efficacious when administered frequently (every 2 days x 5) or intermittently (every 4 days x 3 or every 8 days x 2). These efficacy data demonstrate that BMS-247550 has the potential to surpass Taxol in both clinical efficacy and ease of use (i.e., less frequent treatment schedule and/or oral administration).

Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

PubMed

Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

2017-03-01

Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

77 FR 31345 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... electric reliability filings: Docket Numbers: RR12-9-000. Applicants: North American Electric Reliability Corp. Description: Petition of the North American Electric Reliability Corporation for Approval of... that the Commission received the following electric rate filings: Docket Numbers: ER11-2780-002...

75 FR 61747 - Union Leader Corporation; Supplemental Notice That Initial Market-Based Rate Filing Includes...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... of Union Leader Corporation's application for market-based rate authority, with an accompanying rate... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER10-2780-000] Union Leader Corporation; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket Section...

Dinuclear RuII(bipy)2 Derivatives: Structural, Biological, and in Vivo Zebrafish Toxicity Evaluation.

PubMed

Lenis-Rojas, Oscar A; Roma-Rodrigues, Catarina; Fernandes, Alexandra R; Marques, Fernanda; Pérez-Fernández, David; Guerra-Varela, Jorge; Sánchez, Laura; Vázquez-García, Digna; López-Torres, Margarita; Fernández, Alberto; Fernández, Jesús J

2017-06-19

Ruthenium-based drugs exhibit interesting properties as potential anticancer pharmaceuticals. We herein present the synthesis and characterization of a new family of ruthenium complexes with formulas [{Ru(bipy) 2 } 2 (μ-L)][CF 3 SO 3 ] 4 (L = bptz, 1a) and [{Ru(bipy) 2 } 2 (μ-L)][CF 3 SO 3 ] 2 (L = arphos, 2a; dppb, 3a; dppf, 4a), which were synthesized from the Ru(II) precursor compound cis-Ru(bipy) 2 Cl 2 . The complexes were characterized by elemental analysis, mass spectrometry, 1 H and 31 P{ 1 H} NMR, IR spectroscopy, and conductivity measurements. The molecular structures for three Ru(II) compounds were determined by single-crystal X-ray diffraction. The newly developed compounds interact with CT-DNA by intercalation, in particular, 2a, 3a, and 4a, which also seemed to induce some extent of DNA degradation. This effect seemed to be related with the formation of reactive oxygen species. The cytotoxic activity was evaluated against A2780, MCF7, and MDAMB231 human tumor cells. Compounds 2a and 4a were the most cytotoxic with activity compared to cisplatin (∼2 μM, 72 h) in the A2780 cisplatin sensitive cells. All the compounds induced A2780 cell death by apoptosis, however, to a lesser extent for compounds 4a and 2a. For these compounds, the mechanism of cell death in addition to apoptosis seemed to involve autophagy. In vivo toxicity was evaluated using the zebrafish embryo model. LC 50 estimates varied from 5.397 (3a) to 39.404 (1a) mg/L. Considering the in vivo toxicity in zebrafish embryos and the in vitro cytotoxicity in cancer cells, compound 1a seems to be the safest having no effect on dechirionation and presenting a good antiproliferative activity against ovarian carcinoma cells.

76 FR 70423 - Procurement List Proposed Additions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

..., Joint Base Andrews Naval Air Facility Washington, 1500 West Perimeter Road, Suite 2780, Joint Base Andrews, MD. NPA: Blind Industries & Services of Maryland, Baltimore, MD, Contracting Activity: Dept of the Air Force, FA2860 11 Cons Lgc, Andrews AFB, MD. Patricia Briscoe, Deputy Director, Business...

Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

PubMed

Xiao, Haijun; Wang, Lu

2015-01-01

To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

MT-4 suppresses resistant ovarian cancer growth through targeting tubulin and HSP27.

PubMed

Pai, Hui Chen; Kumar, Sunil; Shen, Chien-Chang; Liou, Jing Ping; Pan, Shiow Lin; Teng, Che Ming

2015-01-01

In this study, the anticancer mechanisms of MT-4 were examined in A2780 and multidrug-resistant NCI-ADR/res human ovarian cancer cell lines. To evaluate the activity of MT-4, we performed in vitro cell viability and cell cycle assays and in vivo xenograft assays. Immunoblotting analysis was carried out to evaluate the effect of MT-4 on ovarian cancer. Tubulin polymerization was determined using a tubulin binding assay. MT-4 (2-Methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-phenol), a derivative of moscatilin, can inhibit both sensitive A2780 and multidrug-resistant NCI-ADR/res cell growth and viability. MT-4 inhibited tubulin polymerization to induce G2/M arrest followed by caspase-mediated apoptosis. Further studies indicated that MT-4 is not a substrate of P-glycoprotein (p-gp). MT-4 also caused G2/M cell cycle arrest, accompanied by the upregulation of cyclin B, p-Thr161 Cdc2/p34, polo-like kinase 1 (PLK1), Aurora kinase B, and phospho-Ser10-histone H3 protein levels. In addition, we found that p38 MAPK pathway activation was involved in MT-4-induced apoptosis. Most importantly, MT-4 also decreased heat shock protein 27 expression and reduced its interaction with caspase-3, which inured cancer cells to chemotherapy resistance. Treatment of cells with SB203580 or overexpression of dominant negative (DN)-p38 or wild-type HSP27 reduced PARP cleavage caused by MT-4. MT-4 induced apoptosis through regulation of p38 and HSP27. Our xenograft models also show the in vivo efficacy of MT-4. MT-4 inhibited both A2780 and NCI-ADR/res cell growth in vitro and in vivo. These findings indicate that MT-4 could be a potential lead compound for the treatment of multidrug-resistant ovarian cancer.

Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells.

PubMed

Fan, Li; Ma, Yalin; Liu, Ying; Zheng, Dongping; Huang, Guangrong

2014-11-15

The polyphenolic flavonoid silymarin that is the milk thistle extract has been found to possess an anti-cancer effect against various human epithelial cancers. In this study, to explore the regulative effect of silymarin on human ovarian cancer line A2780s and PA-1 cells, 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay and flow cytometry were respectively used to determine the inhibitory effect of silymarin on the both cell lines, and to measure their cell cycle progression. Apoptosis induction and mitochondrial membrane potential damage were separately detected by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling assay and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide staining. Additionally, western blotting was applied to determine cytochrome C release and expression levels of p53, p21, p27, p16, CDK2, Bax, Bcl-2, procaspase-9, procaspase-3, cleaved caspase-9 and caspase-3 proteins. The activity of caspase-9 and caspase-3 was measured using Caspase-Glo-9 and Caspase-Glo-3 assay. The results indicated that silymarin effectively suppressed cell growth in a dose- and time-dependent manner, and arrested cell cycle progression at G1/S phase in A2780s and PA-1 cells via up-regulation of p53, p21, and p27 protein expression, and down-regulation of CDK2 protein expression. Additionally, silymarin treatment for 24h at 50 and 100µg/ml resulted in a reduction of mitochondrial membrane potential and cytochrome C release, and significantly induced apoptosis in A2780s and PA-1 cells by increasing Bax and decreasing Bcl-2 protein expression, and activation of caspase-9 and caspase-3. Therefore, silymarin is a possible potential candidate for the prevention and treatment of ovarian cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Bioactive compounds from Stuhlmannia moavi from the Madagascar dry forest.

PubMed

Liu, Yixi; Harinantenaina, Liva; Brodie, Peggy J; Bowman, Jessica D; Cassera, Maria B; Slebodnick, Carla; Callmander, Martin W; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Applequist, Wendy; Birkinshaw, Chris; Lewis, Gwilym P; Kingston, David G I

2013-12-15

Bioassay-directed fractionation of the leaf and root extracts of the antiproliferative Madagascar plant Stuhlmannia moavi afforded 6-acetyl-5,8-dihydroxy-2-methoxy-7-methyl-1,4-naphthoquinone (stuhlmoavin, 1) as the most active compound, with an IC50 value of 8.1 μM against the A2780 human ovarian cancer cell line, as well as the known homoisoflavonoid bonducellin (2) and the stilbenoids 3,4,5'-trihydroxy-3'-methoxy-trans-stilbene (3), piceatannol (4), resveratrol (5), rhapontigenin (6), and isorhapontigenin (7). The structure elucidation of all compounds was based on NMR and mass spectroscopic data, and the structure of 1 was confirmed by a single crystal X-ray analysis. Compounds 2-5 showed weak A2780 activities, with IC50 values of 10.6, 54.0, 41.0, and 74.0 μM, respectively. Compounds 1-3 also showed weak antimalarial activity against Plasmodium falciparum with IC50 values of 23, 26, and 27 μM, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

22 CFR 127.10 - Civil penalty.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Civil penalty. 127.10 Section 127.10 Foreign... Civil penalty. (a) The Assistant Secretary of State for Political-Military Affairs is authorized to impose a civil penalty in an amount not to exceed that authorized by 22 U.S.C. 2778, 2779a, and 2780 for...

22 CFR 127.10 - Civil penalty.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Civil penalty. 127.10 Section 127.10 Foreign... Civil penalty. (a) The Assistant Secretary of State for Political-Military Affairs is authorized to impose a civil penalty in an amount not to exceed that authorized by 22 U.S.C. 2778, 2779a and 2780 for...

22 CFR 127.10 - Civil penalty.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Civil penalty. 127.10 Section 127.10 Foreign... Civil penalty. (a) The Assistant Secretary of State for Political-Military Affairs is authorized to impose a civil penalty in an amount not to exceed that authorized by 22 U.S.C. 2778, 2779a and 2780 for...

22 CFR 127.10 - Civil penalty.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Civil penalty. 127.10 Section 127.10 Foreign... Civil penalty. (a) The Assistant Secretary of State for Political-Military Affairs is authorized to impose a civil penalty in an amount not to exceed that authorized by 22 U.S.C. 2778, 2779a, and 2780 for...

Giant gallstone: A case report

PubMed Central

Becerra, Pablo; Becerra, Valentina; Aguilar, Christian; Modragon, Itziar; Cooper, David K.C.

2011-01-01

Introduction There is a high incidence of gallstones in the Chilean population. Presentation of case We report on a 57-year-old man who complained of abdominal pain in the right upper quadrant. Abdominal ultrasound indicated acute cholecystitis and a single, extremely large pear-shaped gallstone (16.8 cm long, and 7.8 cm at its widest point and 4.1 cm at its narrowest point). Its fresh weight (at operation) was 278.0 g and, after 4 years, its dry weight was 259.5 g. Emergency classical cholecystectomy was carried out successfully. Discussion and Conclusion We have been unable to find a report of a larger gallstone in the English or Spanish language medical literature. PMID:22096735

Publications - GMC 124 | Alaska Division of Geological & Geophysical

Science.gov Websites

DGGS GMC 124 Publication Details Title: Total organic carbon, rock-eval pyrolysis, and vitrinite Reference Unknown, 1989, Total organic carbon, rock-eval pyrolysis, and vitrinite reflectance data from the Report Information gmc124.pdf (278.0 K) Keywords Pyrolysis; Rock-Eval Pyrolysis; Total Organic Carbon

Reduced graphene oxide-silver nanoparticle nanocomposite: a potential anticancer nanotherapy.

PubMed

Gurunathan, Sangiliyandi; Han, Jae Woong; Park, Jung Hyun; Kim, Eunsu; Choi, Yun-Jung; Kwon, Deug-Nam; Kim, Jin-Hoi

2015-01-01

Graphene and graphene-based nanocomposites are used in various research areas including sensing, energy storage, and catalysis. The mechanical, thermal, electrical, and biological properties render graphene-based nanocomposites of metallic nanoparticles useful for several biomedical applications. Epithelial ovarian carcinoma is the fifth most deadly cancer in women; most tumors initially respond to chemotherapy, but eventually acquire chemoresistance. Consequently, the development of novel molecules for cancer therapy is essential. This study was designed to develop a simple, non-toxic, environmentally friendly method for the synthesis of reduced graphene oxide-silver (rGO-Ag) nanoparticle nanocomposites using Tilia amurensis plant extracts as reducing and stabilizing agents. The anticancer properties of rGO-Ag were evaluated in ovarian cancer cells. The synthesized rGO-Ag nanocomposite was characterized using various analytical techniques. The anticancer properties of the rGO-Ag nanocomposite were evaluated using a series of assays such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, cellular levels of malonaldehyde and glutathione, caspase-3 activity, and DNA fragmentation in ovarian cancer cells (A2780). AgNPs with an average size of 20 nm were uniformly dispersed on graphene sheets. The data obtained from the biochemical assays indicate that the rGO-Ag nanocomposite significantly inhibited cell viability in A2780 ovarian cancer cells and increased lactate dehydrogenase leakage, reactive oxygen species generation, caspase-3 activity, and DNA fragmentation compared with other tested nanomaterials such as graphene oxide, rGO, and AgNPs. T. amurensis plant extract-mediated rGO-Ag nanocomposites could facilitate the large-scale production of graphene-based nanocomposites; rGO-Ag showed a significant inhibiting effect on cell viability compared to graphene oxide, rGO, and silver nanoparticles. The nanocomposites could be

Reduced graphene oxide–silver nanoparticle nanocomposite: a potential anticancer nanotherapy

PubMed Central

Gurunathan, Sangiliyandi; Han, Jae Woong; Park, Jung Hyun; Kim, Eunsu; Choi, Yun-Jung; Kwon, Deug-Nam; Kim, Jin-Hoi

2015-01-01

Background Graphene and graphene-based nanocomposites are used in various research areas including sensing, energy storage, and catalysis. The mechanical, thermal, electrical, and biological properties render graphene-based nanocomposites of metallic nanoparticles useful for several biomedical applications. Epithelial ovarian carcinoma is the fifth most deadly cancer in women; most tumors initially respond to chemotherapy, but eventually acquire chemoresistance. Consequently, the development of novel molecules for cancer therapy is essential. This study was designed to develop a simple, non-toxic, environmentally friendly method for the synthesis of reduced graphene oxide–silver (rGO–Ag) nanoparticle nanocomposites using Tilia amurensis plant extracts as reducing and stabilizing agents. The anticancer properties of rGO–Ag were evaluated in ovarian cancer cells. Methods The synthesized rGO–Ag nanocomposite was characterized using various analytical techniques. The anticancer properties of the rGO–Ag nanocomposite were evaluated using a series of assays such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, cellular levels of malonaldehyde and glutathione, caspase-3 activity, and DNA fragmentation in ovarian cancer cells (A2780). Results AgNPs with an average size of 20 nm were uniformly dispersed on graphene sheets. The data obtained from the biochemical assays indicate that the rGO–Ag nanocomposite significantly inhibited cell viability in A2780 ovarian cancer cells and increased lactate dehydrogenase leakage, reactive oxygen species generation, caspase-3 activity, and DNA fragmentation compared with other tested nanomaterials such as graphene oxide, rGO, and AgNPs. Conclusion T. amurensis plant extract-mediated rGO–Ag nanocomposites could facilitate the large-scale production of graphene-based nanocomposites; rGO–Ag showed a significant inhibiting effect on cell viability compared to graphene oxide, rGO, and

Quercetin induces the apoptosis of human ovarian carcinoma cells by upregulating the expression of microRNA-145.

PubMed

Zhou, Junbo; Gong, Jian; Ding, Chun; Chen, Guiqin

2015-08-01

Ovarian cancer is one of the most malignant types of cancer of the female human reproductive track, posing a severe threat to the health of the female population. Numerous previous studies have demonstrated that microRNA (miR)-145 is downregulated in ovarian cancer, and that quercetin can inhibit the growth of cancer cells via regulating the expression of miRs. Therefore, the present study investigated the effect of quercetin on the expression of miR-145 in SKOV-3 and A2780 human ovarian cancer cell lines. The results revealed that the expression levels of cleaved caspase-3 in the SKOV-3 and A2780 cells were significantly increased following treatment to induce overexpression of miR-145 compared with treatment with quercetin alone (P<0.01). However, the expression of cleaved caspase-3 in the anti-miR-145 (miR-145 inhibitor) group of cells was markedly decreased compared with that in the miR-145 overexpression group (P<0.01). Taken together, the results suggested that treatment with quercetin induced the apoptosis of human ovarian carcinoma cells through activation of the extrinsic death receptor mediated and intrinsic mitochondrial apoptotic pathways.

Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells

PubMed Central

2012-01-01

Introduction The taxanes paclitaxel and docetaxel are widely used in the treatment of breast, ovarian, and other cancers. Although their cytotoxicity has been attributed to cell-cycle arrest through stabilization of microtubules, the mechanisms by which tumor cells die remains unclear. Paclitaxel has been shown to induce soluble tumor necrosis factor alpha (sTNF-α) production in macrophages, but the involvement of TNF production in taxane cytotoxicity or resistance in tumor cells has not been established. Our study aimed to correlate alterations in the TNF pathway with taxane cytotoxicity and the acquisition of taxane resistance. Methods MCF-7 cells or isogenic drug-resistant variants (developed by selection for surviving cells in increasing concentrations of paclitaxel or docetaxel) were assessed for sTNF-α production in the absence or presence of taxanes by enzyme-linked immunosorbent assay (ELISA) and for sensitivity to docetaxel or sTNF-α by using a clonogenic assay (in the absence or presence of TNFR1 or TNFR2 neutralizing antibodies). Nuclear factor (NF)-κB activity was also measured with ELISA, whereas gene-expression changes associated with docetaxel resistance in MCF-7 and A2780 cells were determined with microarray analysis and quantitative reverse transcription polymerase chain reaction (RTqPCR). Results MCF-7 and A2780 cells increased production of sTNF-α in the presence of taxanes, whereas docetaxel-resistant variants of MCF-7 produced high levels of sTNF-α, although only within a particular drug-concentration threshold (between 3 and 45 nM). Increased production of sTNF-α was NF-κB dependent and correlated with decreased sensitivity to sTNF-α, decreased levels of TNFR1, and increased survival through TNFR2 and NF-κB activation. The NF-κB inhibitor SN-50 reestablished sensitivity to docetaxel in docetaxel-resistant MCF-7 cells. Gene-expression analysis of wild-type and docetaxel-resistant MCF-7, MDA-MB-231, and A2780 cells identified changes

Spectroscopy, electrochemistry and antiproliferative properties of Au(iii), Pt(ii) and Cu(ii) complexes bearing modified 2,2':6',2''-terpyridine ligands.

PubMed

Maroń, Anna; Czerwińska, Katarzyna; Machura, Barbara; Raposo, Luis; Roma-Rodrigues, Catarina; Fernandes, Alexandra R; Małecki, Jan G; Szlapa-Kula, Agata; Kula, Slawomir; Krompiec, Stanisław

2018-05-08

Structural, spectroscopic and electrochemical properties of six complexes [AuCl(L1)](PF6)2·CH3CN (1), [AuCl(L2)](PF6)2 (2), [PtCl(L1)](BPh4)·CH3CN (3), [PtCl(L2)](SO3CF3) (4), [CuCl2(L1)] (5) and [CuCl2(L2)]·CH3CN (6) with modified 2,2':6',2''-terpyridine ligands, 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (L1) and 4'-(4-methoxynaphthalen-1-yl)-2,2':6',2''-terpyridine (L2) were thoroughly investigated and a significant role of the substituent (4-methoxyphenyl or 4-methoxynaphthalen-1-yl) and the metal center was demonstrated. The naphthyl-based substituent was found to increase the emission quantum yield of the luminescent Au(iii) and Pt(ii) complexes. Furthermore, the antiproliferative potential of the reported complexes was examined towards human colorectal (HCT116) and ovarian (A2780) carcinoma cell lines as well as towards normal human fibroblasts. The Au(iii) complex 2 and Cu(ii) complex 5 were found to have a higher antiproliferative effect on HCT116 colorectal and A2780 ovarian carcinoma cells when compared with the Pt(ii) complex with the same ligand (4). The order of cytotoxicity in both cell lines is 2 > 6 > 1 > 3 > 4. Complex 2 seems to be more cytotoxic towards HCT116 and A2780 cancer cell lines with IC50 values 300× and 130× higher in normal human fibroblasts compared to the respective cancer cells. The viability loss induced by the complexes agrees with Hoechst 33258 staining and the typical morphological apoptotic characteristics like chromatin condensation and nuclear fragmentation and flow cytometry assay. The induction of apoptosis correlates with the induction of reactive oxygen species (ROS). Fluorescence microscopy analysis indicates that after 3 h of incubation, complexes 1-4 are localized inside HCT116 cells and the high levels of internalization correlate with their cytotoxicity.

Identifying gaps in the surgical training curriculum in Rwanda through evaluation of operative activity at a teaching hospital.

PubMed

Rickard, Jennifer L; Ntakiyiruta, Georges; Chu, Kathryn M

2015-01-01

To define the operations performed by surgical residents at a tertiary referral hospital in Rwanda to help guide development of the residency program. Cross-sectional study of all patients operated by surgical residents from October 2012 to September 2013. University Teaching Hospital of Kigali (Centre Hospitalier Universitaire de Kigali [CHUK]), a public, tertiary referral hospital in Kigali, Rwanda. All patient data were entered into the operative database by surgical residents at CHUK. A total of 2833 cases were entered into the surgical database. Of them, 53 cases were excluded from further analysis because no surgical resident was listed as the primary or assistant surgeon, leaving 2780 cases for analysis. There were 2780 operations involving surgical residents. Of them, 51% of procedures were classified under general surgery, 38% orthopedics, 7% neurosurgery, and 4% urology. Emergency operations accounted for 64% of the procedures, with 56% of those being general surgery and 35% orthopedic. Further, 50% of all operations were trauma, with 71% of those orthopedic and 21% general surgery. Surgical faculty were involved in 45% of operations as either the primary or the assistant surgeons, while the remainder of operations did not involve surgical faculty. Residents were primary surgeons in 68% of procedures and assistant surgeons in 84% of procedures. The operative experience of surgery residents at CHUK primarily involves emergency and trauma procedures. Although this likely reflects the demographics of surgical care within Rwanda, more focus should be placed on elective procedures to ensure that surgical residents are broadly trained. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Anti-inflammatory and antiproliferative activities of trifolirhizin, a flavonoid from Sophora flavescens roots

PubMed Central

Zhou, Huiping; Lutterodt, Herman; Cheng, Zhihong; Yu, Liangli (Lucy)

2009-01-01

Trifolirhizin, a pterocarpan flavonoid, was isolated from the roots of Sophora flavescens, and its chemical structure was confirmed by1H and 13C NMR and MS spectra. Its anti-inflammatory activity was examined in lipopolysaccharide (LPS)-stimulated mouse J774A.1 macrophages. Trifolirhizin not only dose-dependently inhibited LPS-induced expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but also inhibited lipopolysaccharide (LPS)-induced expression of cyclooxygenase-2 (COX-2). In addition, trifolirhizin showed in vitro inhibitory effects on the growth of human A2780 ovarian and H23 lung cancer cells. These results suggest that trifolirhizin possesses potential anti-inflammatory and anti-cancer activities. PMID:19402641

40 CFR 60.2780 - What must I include in the deviation report?

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Emissions Guidelines and Compliance Times for Commercial and Industrial Solid Waste Incineration Units Model Rule-Recordkeeping and...

40 CFR 60.2780 - What must I include in the deviation report?

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Emissions Guidelines and Compliance Times for Commercial and Industrial Solid Waste Incineration Units Model Rule-Recordkeeping and...

40 CFR 60.2780 - What must I include in the deviation report?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Compliance Times for Commercial and Industrial Solid Waste Incineration Units Model Rule-Recordkeeping and... downtime associated with zero, span, and other routine calibration checks). (f) Whether each deviation...

40 CFR 60.2780 - What must I include in the deviation report?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Compliance Times for Commercial and Industrial Solid Waste Incineration Units that Commenced Construction On... causes for monitoring downtime incidents (other than downtime associated with zero, span, and other...

40 CFR 60.2780 - What must I include in the deviation report?

Code of Federal Regulations, 2010 CFR

2010-07-01

... from the emission limitations or operating limit requirements. (b) The averaged and recorded data for those dates. (c) Duration and causes of each deviation from the emission limitations or operating limits... deviated from the emission limitations or operating limits specified in this subpart, include the six items...

¹⁸FDG a PET tumor diagnostic tracer is not a substrate of the ABC transporter P-glycoprotein.

PubMed

Krasznai, Zoárd T; Trencsényi, György; Krasznai, Zoltán; Mikecz, Pál; Nizsalóczki, Enikő; Szalóki, Gábor; Szabó, Judit P; Balkay, László; Márián, Teréz; Goda, Katalin

2014-11-20

2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) is a tumor diagnostic radiotracer of great importance in both diagnosing primary and metastatic tumors and in monitoring the efficacy of the treatment. P-glycoprotein (Pgp) is an active transporter that is often expressed in various malignancies either intrinsically or appears later upon disease progression or in response to chemotherapy. Several authors reported that the accumulation of (18)FDG in P-glycoprotein (Pgp) expressing cancer cells (Pgp(+)) and tumors is different from the accumulation of the tracer in Pgp nonexpressing (Pgp(-)) ones, therefore we investigated whether (18)FDG is a substrate or modulator of Pgp pump. Rhodamine 123 (R123) accumulation experiments and ATPase assay were used to detect whether (18)FDG is substrate for Pgp. The accumulation and efflux kinetics of (18)FDG were examined in two different human gynecologic (A2780/A2780AD and KB-3-1/KB-V1) and a mouse fibroblast (3T3 and 3T3MDR1) Pgp(+) and Pgp(-) cancer cell line pairs both in cell suspension and monolayer cultures. We found that (18)FDG and its derivatives did not affect either the R123 accumulation in Pgp(+) cells or the basal and the substrate stimulated ATPase activity of Pgp supporting that they are not substrates or modulators of the pump. Measuring the accumulation and efflux kinetics of (18)FDG in different Pgp(+) and Pgp(-) cell line pairs, we have found that the Pgp(+) cells exhibited significantly higher (p⩽0.01) (18)FDG accumulation and slightly faster (18)FDG efflux kinetics compared to their Pgp(-) counterparts. The above data support the idea that expression of Pgp may increase the energy demand of cells resulting in higher (18)FDG accumulation and faster efflux. We concluded that (18)FDG and its metabolites are not substrates of Pgp. Copyright © 2014 Elsevier B.V. All rights reserved.

An access to a library of novel triterpene derivatives with a promising pharmacological potential by Ugi and Passerini multicomponent reactions.

PubMed

Wiemann, Jana; Heller, Lucie; Csuk, René

2018-04-25

The promising combination of natural product leads and their derivatization by isocyanide-based multicomponent reactions (IMCRs) has gained interest in accessing diversity-oriented libraries with auspicious pharmacological potential. Therefore, a set of 34 Ugi and 3 Passerini products was successfully synthesized starting from naturally occurring triterpenoids, i.e. oleanolic acid (OA) and maslinic acid (MA), followed by a biological evaluation of the novel α-acylamino carboxamides and the α-acyloxy carboxamides in colorimetric SRB assays to determine their cytotoxic potential. Especially, the MA-Ugi products 6a, 6b and 7b showed a remarkable cytotoxicity for A2780 ovarian carcinoma cells in a low μM range. Compounds 6a and 7b induced programmed cell death in part through the apoptosis pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The effect of CA125 on metastasis of ovarian cancer: old marker new function.

PubMed

Yuan, Qin; Song, Jiayin; Yang, Weiwei; Wang, Hongyan; Huo, Qianyu; Yang, Jie; Yu, Xiaoxu; Liu, Yunde; Xu, Chen; Bao, Huijing

2017-07-25

CA125 has been used extensively to screen for neoplasms, especially in ovarian cancer. The serum CA125 level can be used as a better prognosis evaluation and it may dynamic monitoring the disease progression. We explored the effect of CA125 on ovarian cancer cell migration and its underlying mechanism. Transwell assays showed that exposure to 0.2 μg/ml or 0.4 μg/ml CA125 for 48 h increased migration of A2780 and OVCAR-3 ovarian cancer cells. This effect of CA125 was blocked addition of 200 ng/ml DKK-1, a Wnt pathway inhibitor. Conversely, addition of CA125 reversed the inhibitory effect of Wnt inhibition in A2780 cells pretreated with DKK-1. Examination of CA125 levels in serum from 97 ovarian cancer patients revealed no relationship between a patient's age or CA125 level currently used clinically for ovarian cancer diagnosis and metastasis. However, using receiver operating characteristic (ROC) curves, we identified a new cut-off value for the serum CA125 concentration (82.9 U/ml) that is predictive of metastasis. The area under the curve is 0.632. This new cut-off value has the potential to serve as a clinically useful indicator of metastasis in ovarian cancer patients.

The effect of CA125 on metastasis of ovarian cancer: old marker new function

PubMed Central

Yang, Weiwei; Wang, Hongyan; Huo, Qianyu; Yang, Jie; Yu, Xiaoxu; Liu, Yunde; Xu, Chen; Bao, Huijing

2017-01-01

CA125 has been used extensively to screen for neoplasms, especially in ovarian cancer. The serum CA125 level can be used as a better prognosis evaluation and it may dynamic monitoring the disease progression. We explored the effect of CA125 on ovarian cancer cell migration and its underlying mechanism. Transwell assays showed that exposure to 0.2 μg/ml or 0.4 μg/ml CA125 for 48 h increased migration of A2780 and OVCAR-3 ovarian cancer cells. This effect of CA125 was blocked addition of 200 ng/ml DKK-1, a Wnt pathway inhibitor. Conversely, addition of CA125 reversed the inhibitory effect of Wnt inhibition in A2780 cells pretreated with DKK-1. Examination of CA125 levels in serum from 97 ovarian cancer patients revealed no relationship between a patient's age or CA125 level currently used clinically for ovarian cancer diagnosis and metastasis. However, using receiver operating characteristic (ROC) curves, we identified a new cut-off value for the serum CA125 concentration (82.9 U/ml) that is predictive of metastasis. The area under the curve is 0.632. This new cut-off value has the potential to serve as a clinically useful indicator of metastasis in ovarian cancer patients. PMID:28637006

Synthesis and antitumor activity of some substituted indazole derivatives.

PubMed

Abbassi, Najat; Rakib, El Mostapha; Chicha, Hakima; Bouissane, Latifa; Hannioui, Abdellah; Aiello, Cinzia; Gangemi, Rosaria; Castagnola, Patrizio; Rosano, Camillo; Viale, Maurizio

2014-06-01

Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl]arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose-dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Implications of Virtual Machine Introspection for Digital Forensics on Nonquiescent Virtual Machines

DTIC Science & Technology

2011-06-01

metacity [ 2788] gnome-panel [ 2790] nautilus [ 2794] bonobo -activati [ 2797] gnome-vfs-daemo [ 2799] eggcups [ 2800] gnome-volume-ma [ 2809] bt...xrdb [ 2784] metacity [ 2788] gnome-panel [ 2790] nautilus [ 2794] bonobo -activati [ 2797] gnome-vfs-daemo [ 2799] eggcups [ 2800] gnome-volume...gnome-keyring-d [ 2764] gnome-settings- [ 2780] xrdb [ 2784] metacity [ 2788] gnome-panel [ 2790] nautilus [ 2794] bonobo -activati [ 2797] gnome

Assessment of DoD and Industry Networks for Computer Aided Logistics Support (CALS) Telecommunications.

DTIC Science & Technology

1987-06-01

International Business Machines ( IBM ) Corporation compatible synchronous terminals (2780/3780/327X), and the Federal Data Corporation (FDC) has developed...the interfaces for Burroughs look-alike asynchronous and synchronous terminals. Basically, this means that the IBM and Burroughs protocols are...and other vendor computers, such as IBM , UNIVAC, and Honeywell. The Navy has developed file transfer capabilities between Tandem and Burroughs. These

Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway.

PubMed

Arafa, El-Shaimaa A; Zhu, Qianzheng; Barakat, Bassant M; Wani, Gulzar; Zhao, Qun; El-Mahdy, Mohamed A; Wani, Altaf A

2009-12-01

Combination of innocuous dietary components with anticancer drugs is an emerging new strategy for cancer chemotherapy to increase antitumor responses. Tangeretin is a citrus flavonoid known to inhibit cancer cell proliferation. Here, we show an enhanced response of A2780/CP70 and 2008/C13 cisplatin-resistant human ovarian cancer cells to various combination treatments of cisplatin and tangeretin. Pretreatment of cells with tangeretin before cisplatin treatment synergistically inhibited cancer cell proliferation. This combination was effective in activating apoptosis via caspase cascade as well as arresting cell cycle at G(2)-M phase. Moreover, phospho-Akt and its downstream substrates, e.g., NF-kappaB, phospho-GSK-3beta, and phospho-BAD, were downregulated upon tangeretin-cisplatin treatment. The tangeretin-cisplatin-induced apoptosis in A2780/CP70 cells was increased by phosphoinositide-3 kinase (PI3K) inhibition and siRNA-mediated Akt silencing, but reduced by overexpression of constitutively activated Akt and GSK-3beta inhibition. The overall results indicated that tangeretin exposure preconditions cisplatin-resistant human ovarian cancer cells for a conventional response to low-dose cisplatin-induced cell death occurring through downregulation of PI3K/Akt signaling pathway. Thus, effectiveness of tangeretin combinations, as a promising modality in the treatment of resistant cancers, warrants systematic clinical studies.

A Self-Aligned InGaAs Quantum-Well Metal-Oxide-Semiconductor Field-Effect Transistor Fabricated through a Lift-Off-Free Front-End Process

NASA Astrophysics Data System (ADS)

Lin, Jianqiang; Kim, Tae-Woo; Antoniadis, Dimitri A.; del Alamo, Jesús A.

2012-06-01

We present a novel n-type InGaAs quantum-well metal-oxide-semiconductor field-effect transistor (QW-MOSFET) fabricated by a self-aligned gate-last process and investigate relevant Si-like manufacturing issues in future III-V MOSFETs. The device structure features a composite InP/Al2O3 gate barrier with a capacitance equivalent thickness (CET) of 3 nm and non alloyed Mo ohmic contacts. We have found that RIE introduces significant damage to the intrinsic device resulting in poor current drive and subthreshold swing. The effect is largely removed through a thermal annealing step. Thermally annealed QW-MOSFETs exhibit a subthreshold swing of 95 mV/dec, indicative of excellent interfacial characteristics. The peak mobility of the MOSFET is 2780 cm2 V-1 s-1.

miR-30a can inhibit DNA replication by targeting RPA1 thus slowing cancer cell proliferation.

PubMed

Zou, Zhenyou; Ni, Mengjie; Zhang, Jing; Chen, Yongfeng; Ma, Hongyu; Qian, Shihan; Tang, Longhua; Tang, Jiamei; Yao, Hailun; Zhao, Chengbin; Lu, Xiongwen; Sun, Hongyang; Qian, Jue; Mao, Xiaoting; Lu, Xulin; Liu, Qun; Zen, Juping; Wu, Hanbing; Bao, Zhaosheng; Lin, Shudan; Sheng, Hongyu; Li, Yunlong; Liang, Yong; Chen, Zhiqiang; Zong, Dan

2016-07-15

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Adenovirus‑mediated overexpression of cystic fibrosis transmembrane conductance regulator enhances invasiveness and motility of serous ovarian cancer cells.

PubMed

Xu, Jiao; Lin, Liangbo; Yong, Min; Dong, Xiaojing; Yu, Tinghe; Hu, Lina

2016-01-01

The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate‑binding cassette transporter family, members of which are involved in several types of cancer. Previous studies by our group reported that CFTR was highly expressed in serous ovarian cancer (SOC) tissues, and that knockdown of CFTR suppressed the proliferation of ovarian cancer in vitro and in vivo. Thus, the aim of the present study was to construct a recombinant adenoviral vector for the expression of the human CFTR gene in order to study the role of CFTR overexpression in the malignant invasion and migration of SOC cells in vitro. The present study then focused on the mechanisms of the role of CFTR in the migratory and invasive malignant properties of SOC cells. The CFTR gene was inserted into an adenoviral vector by using the AdEasy system in order to obtain the Ad‑CFTR overexpression vector, which was used to transfect the A2780 SOC cell line. Reverse-transcription polymerase chain reaction, western blot analysis and immunofluorescence were performed to detect the expression and localization of CFTR. Cell invasion and motility of the transfected cells compared with those of control cells were observed using Transwell and wound healing assays. A ~4,700 bp fragment of the CFTR gene was confirmed to be correctly cloned in the adenoviral vector and amplification of Ad‑CFTR was observed in HEK293 cells during package. After 48 h of transfection with Ad‑CFTR, ~90% of A2780 cells were red fluorescence protein‑positive. Immunofluorescence showed that following transfection, CFTR expression was increased and CFTR was located in the cell membrane and cytoplasm. CFTR overexpression was shown to enhance the invasion and motility of A2780 cells in vitro. Furthermore, the effects of CFTR overexpression on the activation c‑Src signaling were observed by western blot analysis. CFTR overexpressing cells showed the lowest activity of phospho‑Src (Tyr530

Choerosponins A and B, Two New Cytotoxic Bridged-Ring Ketones and the Determination of Their Absolute Configurations.

PubMed

Li, Chang-Wei; Han, Bing; Cai, Bing; Cui, Cheng-Bin

2017-03-27

Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A ( 1 ) and B ( 2 ), and their structures were elucidated by spectroscopic methods; their stereochemistry was determined by NOE difference experiments, CD spectra and the modified Mosher's method. Compound 1 has a rare dioxatricyclo skeleton. Flow cytometry and SRB methods were employed to evaluate the antitumor activity of the two compounds against tsFT210, HCT-15, HeLa, A2780 and MCF-7 cell lines, and both of them showed strong cytotoxicity. MTT and paper disc methods were also used to evaluate their anti-hypoxia and antibacterial activities, and both of them showed no apparent activities.

Quantitative Evaluation of Cisplatin Uptake in Sensitive and Resistant Individual Cells by Single-Cell ICP-MS (SC-ICP-MS).

PubMed

Corte Rodríguez, M; Álvarez-Fernández García, R; Blanco, E; Bettmer, J; Montes-Bayón, M

2017-11-07

One of the main limitations to the Pt-therapy in cancer is the development of associated drug resistance that can be associated with a significant reduction of the intracellular platinum concentration. Thus, intracellular Pt concentration could be considered as a biomarker of cisplatin resistance. In this work, an alternative method to address intracellular Pt concentration in individual cells is explored to permit the evaluation of different cell models and alternative therapies in a relatively fast way. For this aim, total Pt analysis in single cells has been implemented using a total consumption nebulizer coupled to inductively coupled plasma mass spectrometric detection (ICP-MS). The efficiency of the proposed device has been evaluated in combination with flow cytometry and turned out to be around 25% (cells entering the ICP-MS from the cells in suspension). Quantitative uptake studies of a nontoxic Tb-containing compound by individual cells were conducted and the results compared to those obtained by bulk analysis of the same cells. Both sets of data were statistically comparable. Thus, final application of the developed methodology to the comparative uptake of Pt-species in cisplatin resistant and sensitive cell lines (A2780cis and A2780) was conducted. The results obtained revealed the potential of this analytical strategy to differentiate between different cell lines of different sensitivity to the drug which might be of high medical interest.

Modification of meta-iodobenzylguanidine uptake in neuroblastoma cells by elevated temperature.

PubMed Central

Armour, A.; Mairs, R. J.; Gaze, M. N.; Wheldon, T. E.

1994-01-01

Successful imaging or treatment of neuroblastoma with 131I-meta-iodobenzylguanidine (131I-mIBG) depends on the selectivity of active (type 1) uptake of mIBG in neuroblastoma cells relative to passive (type 2) uptake present in most normal tissues. This study investigates the effects of moderately elevated temperature (39-41 degrees C) on the cellular uptake of 131I-mIBG in two neuroblastoma cell lines [SK-N-BE(2c) and IMR-32] and in a non-neuronal (ovarian carcinoma) cell line (A2780). In SK-N-BE(2c), a cell line with high active uptake capacity, the specific (type 1) uptake was reduced by 75% (P < 0.001) at 39 degrees C. Both IMR-32 and A2780 have a low capacity for accumulation of mIBG by active uptake. These cell lines demonstrated a statistically significant increase in accumulation at 39 degrees C, mainly as a result of increased non-specific transport. At 41 degrees C uptake of 131I-mIBG was reduced in all cell lines. Thus, the active component of mIBG uptake is more vulnerable to increased temperature than the passive component. It seems probable that moderately increased temperature will have an unfavourable effect on the therapeutic differential for targeted radiotherapy of neuroblastoma using radiolabelled mIBG. PMID:8080728

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

PubMed Central

Lin, Chao; Zhao, Xin-yu; Li, Lei; Liu, Huan-yi; Cao, Kang; Wan, Yang; Liu, Xin-yu; Nie, Chun-lai; Liu, Lei; Tong, Ai-ping; Deng, Hong-xin; Li, Jiong; Yuan, Zhu; Wei, Yu-quan

2012-01-01

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy. PMID:22590594

Development of EGFR Targeted Nanoemulsion for Imaging and Novel Platinum Therapy of Ovarian Cancer

PubMed Central

Ganta, Srinivas; Singh, Amit; Patel, Niravkumar R.; Cacaccio, Joseph; Rawal, Yashesh H.; Davis, Barbara J.; Amiji, Mansoor M.; Coleman, Timothy P.

2014-01-01

Purpose Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C6-ceramide, were designed to overcome these limitations. Methods The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780CP. Results The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist®. Conclusion The myrisplatin/C6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer. PMID:24643932

Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatin cytotoxicity in vivo.

PubMed

Rattan, Ramandeep; Graham, Rondell P; Maguire, Jacie L; Giri, Shailendra; Shridhar, Viji

2011-05-01

Ovarian cancer is the most lethal gynecologic cancer in women. Its high mortality rate (68%) reflects the fact that 75% of patients have extensive (>stage III) disease at diagnosis and also the limited efficacy of currently available therapies. Consequently, there is clearly a great need to develop improved upfront and salvage therapies for ovarian cancer. Here, we investigated the efficacy of metformin alone and in combination with cisplatin in vivo. A2780 ovarian cancer cells were injected intraperitoneally in nude mice; A2780-induced tumors in nude mice, when treated with metformin in drinking water, resulted in a significant reduction of tumor growth, accompanied by inhibition of tumor cell proliferation (as assessed by immunohistochemical staining of Ki-67, Cyclin D1) as well as decreased live tumor size and mitotic cell count. Metformin-induced activation of AMPK/mTOR pathway was accompanied by decreased microvessel density and vascular endothelial growth factor expression. More importantly, metformin treatment inhibited the growth of metastatic nodules in the lung and significantly potentiated cisplatin-induced cytotoxicity resulting in approximately 90% reduction in tumor growth compared with treatment by either of the drugs alone. Collectively, our data show for the first time that, in addition to inhibiting tumor cell proliferation, metformin treatment inhibits both angiogenesis and metastatic spread of ovarian cancer. Overall, our study provides a strong rationale for use of metformin in ovarian cancer treatment.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

PubMed

Hu, Ming; Zhao, Jixian; Ai, Xiangzhao; Budanovic, Maja; Mu, Jing; Webster, Richard D; Cao, Qian; Mao, Zongwan; Xing, Bengang

2016-09-13

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

Potential Anticancer Heterometallic Fe-Au and Fe-Pd Agents: Initial Mechanistic Insights

PubMed Central

Lease, Nicholas; Vasilevski, Vadim; Carreira, Monica; de Almeida, Andreia; Sanaú, Mercedes; Hirva, Pipsa; Casini, Angela; Contel, Maria

2013-01-01

A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenyl-phosphanes [{Cp-P(Ph2)=N-Ph}2Fe] (1), [{Cp-P(Ph2)=N-CH2-2-NC5H4}2Fe] (2) and [{Cp-P(Ph2)=N-CH2-2-NC5H4}Fe(Cp)] (3) have been synthesized and structurally characterized. Ligands 2 and 3 afford stable coordination complexes [AuCl2(3)]ClO4, [{AuCl2}2(2)](ClO4)2, [PdCl2(3)] and [{PdCl2}2(2)]. The complexes have been evaluated for their antripoliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M2Fe (M = Au, Pd) are more cytotoxic to cancer cells than their corresponding monometallic fragments. Moreover, these complexes were significantly more cytotoxic than cisplatin in the resistant A2780R and the MCF7 cell lines. Studies of the interactions of the trimetallic compounds with DNA and the zinc-finger protein PARP-1 indicate that they exert anticancer effects in vitro based on different mechanisms of actions with respect to cisplatin. PMID:23786413

Characterization and Targeting of the Aldehyde Dehydrogenase Subpopulation in Ovarian Cancer

DTIC Science & Technology

2013-07-01

from the A2780cp20 cell line . Task 2: Determine if ALDH1-positive cells survive chemotherapy in the tumor microenvironment. We have previously... lines . Anti- endoglin siRNAs were used to downregulate expression in ES2 and HeyA8MDR. In vitro, the effects of endoglin-knockdown individually and...ES2 or HeyA8MDR cell lines were administered chitosan-encapsulated anti- ENG siRNA or control siRNA with and without carboplatin. As described in the

Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.

PubMed

Chen, Tao; Li, Mian; Zhang, Ruiwen; Wang, Hui

2009-07-01

The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.

Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy

PubMed Central

Chen, Tao; Li, Mian; Zhang, Ruiwen; Wang, Hui

2009-01-01

The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR-3), and immortalized non-tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non-tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor- and, mitochondrion-mediated caspase-dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR-3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non-tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy. PMID:18466355

The varieties of religious development in adulthood: a longitudinal investigation of religion and rational choice.

PubMed

McCullough, Michael E; Enders, Craig K; Brion, Sharon L; Jain, Andrea R

2005-07-01

The authors used growth mixture models to study religious development during adulthood (ages 27-80) in a sample of individuals who were identified during childhood as intellectually gifted. The authors identified 3 discrete trajectories of religious development: (a) 40% of participants belonged to a trajectory class characterized by increases in religiousness until midlife and declines in later adulthood; (b) 41% of participants belonged to a trajectory class characterized by very low religiousness in early adulthood and age-related decline; and (c) 19% of participants belonged to a trajectory class characterized by high religiousness in early adulthood and age-related increases. Gender, strength of religious upbringing, number of children, marrying, and agreeableness predicted membership in the trajectory classes. Results were largely consistent with the rational choice theory of religious involvement.

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis.

PubMed

Lord, Rianne M; Allison, Simon J; Rafferty, Karen; Ghandhi, Laura; Pask, Christopher M; McGowan, Patrick C

2016-08-16

This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging atom, [{(p-cym)Ru(II)X(N,N)}{H(+)}{(N,N)XRu(II)(p-cym)}][PF6] (N,N = functionalised quinaldamide and X = Cl or Br). These complexes are formed by a reaction of [p-cymRu(μ-X)2]2 with a functionalised quinaldamide ligand. When filtered over NH4PF6, and under aerobic conditions the equilibrium of NH4PF6 ⇔ NH3 + HPF6 enables incorporation of HPF6 and the stabilisation of two monomeric ruthenium complexes by a bridging H(+), which are counter-balanced by a PF6 counterion. X-ray crystallographic analysis is presented for six new structures with OO distances of 2.420(4)-2.448(15) Å, which is significant for strong hydrogen bonds. Chemosensitivity studies against HCT116, A2780 and cisplatin-resistant A2780cis human cancer cells showed the ruthenium complexes with a bromide ancillary ligand to be more potent than those with a chloride ligand. The 4'-fluoro compounds show a reduction in potency for both chloride and bromide complexes against all cell lines, but an increase in selectivity towards cancer cells compared to non-cancer ARPE-19 cells, with a selectivity index >1. Mechanistic studies showed a clear correlation between IC50 values and induction of cell death by apoptosis.

Co-delivery of paclitaxel and tetrandrine via iRGD peptide conjugated lipid-polymer hybrid nanoparticles overcome multidrug resistance in cancer cells

PubMed Central

Zhang, Jinming; Wang, Lu; Fai Chan, Hon; Xie, Wei; Chen, Sheng; He, Chengwei; Wang, Yitao; Chen, Meiwan

2017-01-01

One of the promising strategies to overcome tumor multidrug resistance (MDR) is to deliver anticancer drug along with P-glycoprotein (P-gp) inhibitor simultaneously. To enhance the cancer cellular internalization and implement the controlled drug release, herein an iRGD peptide-modified lipid-polymer hybrid nanosystem (LPN) was fabricated to coload paclitaxel (PTX) and tetrandrine (TET) at a precise combination ratio. In this co-delivery system, PTX was covalently conjugated to poly (D,L-lactide-co-glycolide) polymeric core by redox-sensitive disulfide bond, while TET was physically capsulated spontaneously for the aim to suppress P-gp in advance by the earlier released TET in cancer cells. As a result, the PTX+TET/iRGD LPNs with a core-shell structure possessed high drug loading efficiency, stability and redox-sensitive drug release profiles. Owing to the enhanced cellular uptake and P-gp suppression mediated by TET, significantly more PTX accumulated in A2780/PTX cells treated with PTX+TET/iRGD LPNs than either free drugs or non-iRGD modified LPNs. As expected, PTX+TET/iRGD LPNs presented the highest cytotoxicity against A2780/PTX cells and effectively promoted ROS production, enhanced apoptosis and cell cycle arrests particularly. Taken together, the co-delivery system demonstrated great promise as potential treatment for MDR-related tumors based on the synergistic effects of P-gp inhibition, enhanced endocytosis and intracellular sequentially drug release. PMID:28470171

Antiproliferative Diterpenes from a Malleastrum sp. from the Madagascar dry forest[1

PubMed Central

Liu, Yixi; Wiedle, C. Houston; Brodie, Peggy J.; Callmander, Martin W.; Rakotondrajaona, R.; Rakotobe, Etienne; Rasamison, Vincent E.

2015-01-01

An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (−)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 μM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum. PMID:26594745

The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

PubMed

Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

2015-04-01

Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (p<0.05). Results illustrated that the brittle star extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (p<0.05). These finding revealed the anti-angiogenic effects of brittle star methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

PubMed

Brandhonneur, N; Hatahet, T; Amela-Cortes, M; Molard, Y; Cordier, S; Dollo, G

2018-04-01

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo 6 Br 14 cluster unit, (TBA) 2 Mo 6 Br 14 , presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA) 2 Mo 6 Br 14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA) 2 Mo 6 Br 14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Innovative T Cell-Targeted Therapy for Ovarian Cancer

DTIC Science & Technology

2012-10-01

from co-culture with EL4 -ROR1neg and EL4 -ROR1+ tumor targets. Ovarian cancer cell lines (A2780, EFO21, EFO27, IGROV1, OC314, and UPN251) were...profiled for ROR1 expression in normoxia (20% O2) and hypoxia (1% O2). Four-hour CRA was used to evaluate cytotoxicity against the OvCa and EL4 tumor...loaded aAPC for negative controls. EL4 is a murine T cell lymphoma cell line used to test specificity of CAR+ T cells with limited allo-reactivity

Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug.

PubMed

Rivard, Colleen; Geller, Melissa; Schnettler, Erica; Saluja, Manju; Vogel, Rachel Isaksson; Saluja, Ashok; Ramakrishnan, Sundaram

2014-11-01

Minnelide is a water-soluble pro-drug of triptolide, a natural product. The goal of this study was to evaluate the effectiveness of Minnelide on ovarian cancer growth in vitro and in vivo. The effect of Minnelide on ovarian cancer cell proliferation was determined by real time electrical impedance measurements. Multiple mouse models with C200 and A2780 epithelial ovarian cancer cell lines were used to assess the efficacy of Minnelide in inhibiting ovarian cancer growth. Minnelide decreased cell viability of both platinum sensitive and resistant epithelial ovarian cancer cells in vitro. Minnelide with carboplatin showed additive effects in vitro. Minnelide monotherapy increased the survival of mice bearing established ovarian tumors. Minnelide, in combination with carboplatin and paclitaxel, improved overall survival of mice. Minnelide is a promising pro-drug for the treatment of ovarian cancer, especially when combined with standard chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines.

PubMed

Sawers, L; Ferguson, M J; Ihrig, B R; Young, H C; Chakravarty, P; Wolf, C R; Smith, G

2014-09-09

Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT-PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC50, respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients.

C6 –C8 Bridged Epothilones: Consequences of Installing a Conformational Lock at the Edge of the Macrocycle

PubMed Central

Jiang, Yi; Banerjee, Abhijit; Brodie, Peggy J.; Bane, Susan; Kingston, David G. I.; Liotta, Dennis C.

2011-01-01

A series of conformationally restrained epothilone analogs with a short bridge between the methyl groups at C6 and C8 was designed to mimic the binding pose assigned to our recently reported EpoA-microtubule binding model. A versatile synthetic route to these bridged epothilone analogs has been successfully devised and implemented. Biological evaluation of the compounds against A2780 human ovarian cancer and PC3 prostate cancer cell lines suggested that the introduction of a bridge between C6-C8 reduced potency by 25–1000 fold in comparison with natural epothilone D. Tubulin assembly measurements indicate these bridged epothilone analogs to be mildly active, but without significant microtubule stabilization capacity. Molecular mechanics and DFT energy evaluations suggest the mild activity of the bridged epo-analogs may be due to internal conformational strain. PMID:22127984

Antiproliferative Cardenolides of an Elaeodendron sp. from the Madagascar Rain Forest

PubMed Central

Cao, Shugeng; Brodie, Peggy J.; Miller, James S.; Ratovoson, Fidy; Callmander, Martin W.; Randrianasolo, Sennen; Rakotobe, Etienne; Rasamison, Vincent E.; Suh, Edward M.; TenDyke, Karen; Kingston, David G. I.

2008-01-01

Bioassay-guided fractionation of an ethanol extract obtained from the Madagascar plant Elaeodendron sp. led to the isolation of two new cardenolides, elaeodendrosides T and U (1 and 2). The structures of the new compounds were elucidated using 1D and 2D NMR experiments, and mass spectrometry. Compounds 1, 3, 4, and 5 showed significant antiproliferative activity against A2780 human ovarian cancer cells with IC50 values of 0.085, 0.019, 0.19, and 0.10 µM, respectively, while compounds 2 and 6 were less active. PMID:17547460

FRET Imaging Trackable Long Circulating Biodegradable Nanomedicines for Ovarian Cancer Therapy

DTIC Science & Technology

2015-11-01

difference between treatment with 2P-EPI and P- EPI until day 35 when tumor started regrowth in P-EPI group , and four of the tumors grew back to ~1200...A2780 ovarian tumors were randomly assigned to four groups (n = 5 for each group ). P-EPI and 2P-EPIwere administered via tail veinwith dose 5mg/kg...and P-EPI until day 35 when tumor started re- growth in P-EPI group , and four of the tumors grew back to ~1200% at day 80 (p b 0.01) (Fig. 3). On the

Downregulation of LRRC8A protects human ovarian and alveolar carcinoma cells against Cisplatin-induced expression of p53, MDM2, p21Waf1/Cip1, and Caspase-9/-3 activation

PubMed Central

Sørensen, Belinda Halling; Nielsen, Dorthe; Thorsteinsdottir, Unnur Arna; Hoffmann, Else Kay

2016-01-01

The leucine-rich repeat containing 8A (LRRC8A) protein is an essential component of the volume-sensitive organic anion channel (VSOAC), and using pharmacological anion channel inhibitors (NS3728, DIDS) and LRRC8A siRNA we have investigated its role in development of Cisplatin resistance in human ovarian (A2780) and alveolar (A549) carcinoma cells. In Cisplatin-sensitive cells Cisplatin treatment increases p53-protein level as well as downstream signaling, e.g., expression of p21Waf1/Cip1, Bax, Noxa, MDM2, and activation of Caspase-9/-3. In contrast, Cisplatin-resistant cells do not enter apoptosis, i.e., their p53 and downstream signaling are reduced and caspase activity unaltered following Cisplatin exposure. Reduced LRRC8A expression and VSOAC activity are previously shown to correlate with Cisplatin resistance, and here we demonstrate that pharmacological inhibition and transient knockdown of LRRC8A reduce the protein level of p53, MDM2, and p21Waf1/Cip1 as well as Caspase-9/-3 activation in Cisplatin-sensitive cells. Cisplatin resistance is accompanied by reduction in total LRRC8A expression (A2780) or LRRC8A expression in the plasma membrane (A549). Activation of Caspase-3 dependent apoptosis by TNFα-exposure or hyperosmotic cell shrinkage is almost unaffected by pharmacological anion channel inhibition. Our data indicate 1) that expression/activity of LRRC8A is essential for Cisplatin-induced increase in p53 protein level and its downstream signaling, i.e., Caspase-9/-3 activation, expression of p21Waf1/Cip1 and MDM2; and 2) that downregulation of LRRC8A-dependent osmolyte transporters contributes to acquirement of Cisplatin resistance in ovarian and lung carcinoma cells. Activation of LRRC8A-containing channels is upstream to apoptotic volume decrease as hypertonic cell shrinkage induces apoptosis independent of the presence of LRRC8A. PMID:26984736

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

PubMed Central

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC50 values of 0.44 μM (0.14 μg/mL) and 0.045 μg/mL, respectively. A semisynthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. PMID:21480509

Human transport protein carrier for controlled photoactivation of antitumor prodrug and real-time intracellular tumor imaging.

PubMed

Li, Xi; Mu, Jing; Liu, Fang; Tan, Eddy Wei Ping; Khezri, Bahareh; Webster, Richard D; Yeow, Edwin Kok Lee; Xing, Bengang

2015-05-20

Current anticancer chemotherapy often suffers from poor tumor selectivity and serious drug resistance. Proper vectors for targeted delivery and controlled drug release play crucial roles in improving the therapeutic selectivity to tumor areas and also overcoming the resistance of cancer cells. In this work, we developed a novel human serum albumin (HSA) protein-based nanocarrier system, which combines the photoactivatable Pt(IV) antitumor prodrug for realizing the controlled release and fluorescent light-up probe for evaluations of drug action and efficacy. The constructed Pt(IV)-probe@HSA platform can be locally activated by light irradiation to release the active Pt species, which results in enhanced cell death at both drug-sensitive A2780 and cisplatin-resistant A2780cis cell lines when compared to the free prodrug molecules. Simultaneously, the cytotoxicity caused by light controlled drug release would further lead to the cellular apoptosis and trigger the activation of caspases 3, one crucial protease enzyme in apoptotic process, which could cleave the recognition peptide moiety (DEVD) with a flanking fluorescent resonance energy transfer (FRET) pair containing near-infrared (NIR) fluorophore Cy5 and quencher Qsy21 on the HSA nanocarrier surface. The turn-on fluorescence in response to caspase-3 could be assessed by fluorescence microscopy and flow cytometry analysis. Our results supported the hypothesis that such a unique design may present a successful platform for multiple roles: (i) a biocompatible protein-based nanocarrier for drug delivery, (ii) the controlled drug release with strengthened therapeutic effects, (iii) real-time monitoring of antitumor drug efficacy at the earlier stage.

Enhancement of the Effect of Methyl Pyropheophorbide-a-Mediated Photodynamic Therapy was Achieved by Increasing ROS through Inhibition of Nrf2-HO-1 or Nrf2-ABCG2 Signaling.

PubMed

Tian, Si; Yong, Min; Zhu, Jiang; Zhang, Li; Pan, Li; Chen, Qing; Li, Kai-Ting; Kong, Yu-Han; Jiang, Yuan; Yu, Ting-He; Yu, Le-Hua; Bai, Ding-Qun

2017-01-01

Emerging evidence indicates that the transcription factor nuclear factor-E2-related factor 2 (Nrf2) plays an essential role in cellular defense against oxidative stress; its activation has been related to cytoprotection. Here, we investigated the role of Nrf2 in improving the efficacy of methyl pyropheophorbide-amediated photodynamic therapy (Mppa-PDT) via the downregulation of Nrf2. Human ovarian cancer A2780 cells and SKOV3 cells were treated with Mppa-PDT and siRNA transfection was performed to inhibit Nrf2. After treated with siRNA and Mppa-PDT, the cell viability was examined with CCK-8 assay; cell apoptosis was detected tested by flow cytometry with Annexin V-FITC/PI; the celluar reactive oxygen species (ROS) and mitochondrial membrane potential were measured with DCFHDA and JC-1 staining; expression of protein was assessed by western blot analysis. We found that Nrf2 translocated from the cytoplasm to the nucleus in vitro and in vivo, and the expression of Nrf2 and P-Nrf2 increased through a possible mechanism regulated by mitogen-activated protein kinase (MAPK) after Mppa-PDT treatment. Furthermore, cytotoxicity and apoptosis induced by Mppa-PDT increased after Nrf2down-regulation. Nrf2 down -regulation increased reactive oxygen species (ROS) levels by attenuating antioxidants or pumping Mppa out of cells,which resulted from the inhibition of Nrf2-HO-1 or Nrf2- ABCG2 signaling. In addition, SKOV3 cells exhibited increased resistance to Mppa-PDT, and the expression levels of P-Nrf2 and ABCG2 were higher in SKOV3 cells than in A2780 cells, suggesting that Nrf2-ABCG2 signaling might be involved in the intrinsic resistanceto Mppa-PDT. These results provided evidence that Nrf2 down-regulation can enhance the effect of Mppa-PDT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biocompatible Lipid Nanoparticles as Carriers To Improve Curcumin Efficacy in Ovarian Cancer Treatment.

PubMed

Bondì, Maria Luisa; Emma, Maria Rita; Botto, Chiara; Augello, Giuseppa; Azzolina, Antonina; Di Gaudio, Francesca; Craparo, Emanuela Fabiola; Cavallaro, Gennara; Bachvarov, Dimcho; Cervello, Melchiorre

2017-02-22

Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin released after 24 h from Compritol-Captex, Compritol-Miglyol, and Compritol NLCs being, respectively, equal to 33, 28, and 18% w/w on the total entrapped curcumin. Considering the slower curcumin release profile, Compritol NLCs were chosen to perform successive in vitro studies on ovarian cancer cell lines. The results show that curcumin-loaded NLCs maintain anticancer activity, and reduce cell colony survival more effectively than free curcumin. As an example, the ability of A2780S cells to form colonies was decreased after treatment with 5 μM free curcumin by 50% ± 6, whereas, at the same concentration, the delivery of curcumin with NLC significantly (p < 0.05) inhibited colony formation to approximately 88% ± 1, therefore potentiating the activity of curcumin to inhibit A2780S cell growth. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases curcumin efficacy in vitro, indicating the potential use of NLCs as curcumin delivery systems.

Metformin, at concentrations corresponding to the treatment of diabetes, potentiates the cytotoxic effects of carboplatin in cultures of ovarian cancer cells.

PubMed

Erices, Rafaela; Bravo, Maria Loreto; Gonzalez, Pamela; Oliva, Bárbara; Racordon, Dusan; Garrido, Marcelo; Ibañez, Carolina; Kato, Sumie; Brañes, Jorge; Pizarro, Javier; Barriga, Maria Isabel; Barra, Alejandro; Bravo, Erasmo; Alonso, Catalina; Bustamente, Eva; Cuello, Mauricio A; Owen, Gareth I

2013-12-01

The use of the type 2 diabetics drug metformin has been correlated with enhanced progression-free survival in ovarian cancer. The literature has speculated that this enhancement is due to the high concentration of metformin directly causing cancer cell death. However, this explanation does not fit with clinical data reporting that the women exposed to constant micromolar concentrations of metformin, as present in the treatment of diabetes, respond better to chemotherapy. Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability. We demonstrate that previous exposure and maintenance of metformin in conjunction with carboplatin produces a synergistic enhancement in cytotoxicity of A2780 and SKOV3 cells (55% and 43%, respectively). Furthermore, in 5 (44%) of the 11 ovarian cancer primary cultures, micromolar metformin improved the cytotoxic response to carboplatin but not paclitaxel or doxorubicin. In conclusion, we present data that support the need for a clinical study to evaluate the adjuvant maintenance or prescription of currently approved doses of metformin during the chemotherapeutic treatment of ovarian cancer.

Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines

PubMed Central

Sawers, L; Ferguson, M J; Ihrig, B R; Young, H C; Chakravarty, P; Wolf, C R; Smith, G

2014-01-01

Background: Chemotherapy response in ovarian cancer patients is frequently compromised by drug resistance, possibly due to altered drug metabolism. Platinum drugs are metabolised by glutathione S-transferase P1 (GSTP1), which is abundantly, but variably expressed in ovarian tumours. We have created novel ovarian tumour cell line models to investigate the extent to which differential GSTP1 expression influences chemosensitivity. Methods: Glutathione S-transferase P1 was stably deleted in A2780 and expression significantly reduced in cisplatin-resistant A2780DPP cells using Mission shRNA constructs, and MTT assays used to compare chemosensitivity to chemotherapy drugs used to treat ovarian cancer. Differentially expressed genes in GSTP1 knockdown cells were identified by Illumina HT-12 expression arrays and qRT–PCR analysis, and altered pathways predicted by MetaCore (GeneGo) analysis. Cell cycle changes were assessed by FACS analysis of PI-labelled cells and invasion and migration compared in quantitative Boyden chamber-based assays. Results: Glutathione S-transferase P1 knockdown selectively influenced cisplatin and carboplatin chemosensitivity (2.3- and 4.83-fold change in IC50, respectively). Cell cycle progression was unaffected, but cell invasion and migration was significantly reduced. We identified several novel GSTP1 target genes and candidate platinum chemotherapy response biomarkers. Conclusions: Glutathione S-transferase P1 has an important role in cisplatin and carboplatin metabolism in ovarian cancer cells. Inter-tumour differences in GSTP1 expression may therefore influence response to platinum-based chemotherapy in ovarian cancer patients. PMID:25010864

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.

PubMed

Burger, Matthew T; Pecchi, Sabina; Wagman, Allan; Ni, Zhi-Jie; Knapp, Mark; Hendrickson, Thomas; Atallah, Gordana; Pfister, Keith; Zhang, Yanchen; Bartulis, Sarah; Frazier, Kelly; Ng, Simon; Smith, Aaron; Verhagen, Joelle; Haznedar, Joshua; Huh, Kay; Iwanowicz, Ed; Xin, Xiaohua; Menezes, Daniel; Merritt, Hanne; Lee, Isabelle; Wiesmann, Marion; Kaufman, Susan; Crawford, Kenneth; Chin, Michael; Bussiere, Dirksen; Shoemaker, Kevin; Zaror, Isabel; Maira, Sauveur-Michel; Voliva, Charles F

2011-10-13

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer

PubMed Central

2011-01-01

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer. PMID:24900266

Study of LH2 fueled subsonic passenger transport aircraft

NASA Technical Reports Server (NTRS)

Brewer, G. D.; Morris, R. E.

1976-01-01

The potential of using liquid hydrogen as fuel in subsonic transport aircraft was investigated to explore an expanded matrix of passenger aircraft sizes. Aircraft capable of carrying 130 passengers 2,780 km (1500 n.mi.); 200 passengers 5,560 km (3000 n.mi.); and 400 passengers on a 9,265 km (5000 n.mi.) radius mission, were designed parametrically. Both liquid hydrogen and conventionally fueled versions were generated for each payload/range in order that comparisons could be made. Aircraft in each mission category were compared on the basis of weight, size, cost, energy utilization, and noise.

A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062.

PubMed

Li, Chunshun; Sarotti, Ariel M; Yang, Baojun; Turkson, James; Cao, Shugeng

2017-07-12

A new N -methoxypyridone analog ( 1 ), together with four known compounds, was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was elucidated as 11 S -hydroxy-1-methoxyfusaricide ( 1 ) by extensive spectroscopic analysis and comparison with the literature. The absolute configuration of 1 was determined by comparison with the experimental and calculated ECD spectra. The absolute configuration of compound 3 was investigated and renamed as (+)-epipyridone by comparison of the optical rotation and CD spectrum with those of 1 . The other known compounds were identified as epicoccarine B ( 2 ), D8646-2-6 ( 4 ), and iso-D8646-2-6 ( 5 ). Compounds 4 and 5 showed modest inhibitory activity towards pathogenic fungi. Epicoccarine B ( 2 ) inhibited A2780 and TK-10 with an IC 50 value of 22 μM.

Biopanning and characterization of peptides with Fe3O4 nanoparticles-binding capability via phage display random peptide library technique.

PubMed

You, Fei; Yin, Guangfu; Pu, Ximing; Li, Yucan; Hu, Yang; Huang, Zhongbin; Liao, Xiaoming; Yao, Yadong; Chen, Xianchun

2016-05-01

Functionalization of inorganic nanoparticles (NPs) play an important role in biomedical applications. A proper functionalization of NPs can improve biocompatibility, avoid a loss of bioactivity, and further endow NPs with unique performances. Modification with vairous specific binding biomolecules from random biological libraries has been explored. In this work, two 7-mer peptides with sequences of HYIDFRW and TVNFKLY were selected from a phage display random peptide library by using ferromagnetic NPs as targets, and were verified to display strong binding affinity to Fe3O4 NPs. Fourier transform infrared spectrometry, fluorescence microscopy, thermal analysis and X-ray photoelectron spectroscopy confirmed the presence of peptides on the surface of Fe3O4 NPs. Sequence analyses revealed that the probable binding mechanism between the peptide and Fe3O4 NPs might be driven by Pearson hard acid-hard base specific interaction and hydrogen bonds, accompanied with hydrophilic interactions and non-specific electrostatic attractions. The cell viability assay indicated a good cytocompatibility of peptide-bound Fe3O4 NPs. Furthermore, TVNFKLY peptide and an ovarian tumor cell A2780 specific binding peptide (QQTNWSL) were conjugated to afford a liner 14-mer peptide (QQTNWSLTVNFKLY). The binding and targeting studies showed that 14-mer peptide was able to retain both the strong binding ability to Fe3O4 NPs and the specific binding ability to A2780 cells. The results suggested that the Fe3O4-binding peptides would be of great potential in the functionalization of Fe3O4 NPs for the tumor-targeted drug delivery and magnetic hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

Antiproliferative compounds of Cyphostemma greveana from a Madagascar dry forest.

PubMed

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

2011-04-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 μM (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

A new photoelectric ink based on nanocellulose/CdS quantum dots for screen-printing.

PubMed

Tang, Aimin; Liu, Yuan; Wang, Qinwen; Chen, Ruisong; Liu, Wangyu; Fang, Zhiqiang; Wang, Lishi

2016-09-05

CdS quantum dots with excellent photoelectrical properties embedded in nanocellulose could be exploited for use in photoelectrical ink. In this work, nanocellulose/CdS quantum dot composites were fabricated by controlling the carboxylate content of the nanocellulose and the molar ratio of Cd(2+)/-COOH. New photoelectric inks were prepared based on the composites, in which the CdS quantum dots acted as the pigment and the nanocellulose as the binder. The results of the photocurrent of the composites showed that the photocurrent could be tailored by the carboxylate content and the molar ratio of Cd(2+)/-COOH. And the photocurrent could be as high as 2μA. The surface tension of the photoelectric ink was 27.80±0.03mN/m and its viscosity was 30.3mPas. The photoelectric ink was stable with excellent fluidity and rheology, it could therefore be applied to screen-printing and three-dimensional (3D) printing. Copyright © 2016 Elsevier Ltd. All rights reserved.

The nerve growth factor alters calreticulin translocation from the endoplasmic reticulum to the cell surface and its signaling pathway in epithelial ovarian cancer cells.

PubMed

Vera, Carolina Andrea; Oróstica, Lorena; Gabler, Fernando; Ferreira, Arturo; Selman, Alberto; Vega, Margarita; Romero, Carmen Aurora

2017-04-01

Ovarian cancer is the seventh most common cancer among women worldwide, causing approximately 120,000 deaths every year. Immunotherapy, designed to boost the body's natural defenses against cancer, appears to be a promising option against ovarian cancer. Calreticulin (CRT) is an endoplasmic reticulum (ER) resident chaperone that, translocated to the cell membrane after ER stress, allows cancer cells to be recognized by the immune system. The nerve growth factor (NGF) is a pro-angiogenic molecule overexpressed in this cancer. In the present study, we aimed to determine weather NGF has an effect in CRT translocation induced by cytotoxic and ER stress. We treated A2780 ovarian cancer cells with NGF, thapsigargin (Tg), an ER stress inducer and mitoxantrone (Mtx), a chemotherapeutic drug; CRT subcellular localization was analyzed by immunofluorescence followed by confocal microscopy. In order to determine NGF effect on Mtx and Tg-induced CRT translocation from the ER to the cell membrane, cells were preincubated with NGF prior to Mtx or Tg treatment and CRT translocation to the cell surface was determined by flow cytometry. In addition, by western blot analyses, we evaluated proteins associated with the CRT translocation pathway, both in A2780 cells and human ovarian samples. We also measured NGF effect on cell apoptosis induced by Mtx. Our results indicate that Mtx and Tg, but not NGF, induce CRT translocation to the cell membrane. NGF, however, inhibited CRT translocation induced by Mtx, while it had no effect on Tg-induced CRT exposure. NGF also diminished cell death induced by Mtx. NGF effect on CRT translocation could have consequences in immunotherapy, potentially lessening the effectiveness of this type of treatment.

Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues.

PubMed

Sommerwerk, Sven; Heller, Lucie; Siewert, Bianka; Csuk, René

2015-09-01

We developed a synthetic scheme for the synthesis of naturally occurring (14R)-oenanthotoxin and several analogs. Key-steps of this synthesis were an efficient homo-coupling of alkynes and a chemoenzymatic resolution of racemic oenanthotoxin using novozyme 435 and vinyl acetate. The compounds were screened for their cytotoxic activity using a photometric sulforhodamine B assays and several human tumor cell lines. Oenanthotoxin and many derivatives thereof were cytotoxic to tumor cell lines as well as to non-malignant mouse fibroblasts. The highest activity was determined for human ovarian cancer cells A2780 with EC50 = 3.8 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synergistic efficacy in human ovarian cancer cells by histone deacetylase inhibitor TSA and proteasome inhibitor PS-341.

PubMed

Fang, Yong; Hu, Yi; Wu, Peng; Wang, Beibei; Tian, Yuan; Xia, Xi; Zhang, Qinghua; Chen, Tong; Jiang, Xuefeng; Ma, Quanfu; Xu, Gang; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding; Meng, Li

2011-05-01

Histone deacetylase inhibitors and proteasome inhibitor are all emerging as new classes of anticancer agents. We chose TSA and PS-341 to identify whether they have a synergistic efficacy on human ovarian cancer cells. After incubated with 500 nM TSA or/and 40 nM PS-341, we found that combined groups resulted in a striking increase of apoptosis and G2/M blocking rates, no matter in A2780, cisplatin-sensitive ovarian cancer cell line OV2008 or its resistant variant C13*. This demonstrated that TSA interacted synergistically with PS-341, which raised the possibility that combined the two drugs may represent a novel strategy in ovarian cancer.

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

Moradi, Hamid; Murugkar, Sangeeta; Ahmad, Abrar

Purpose: To improve classification by reducing batch effect in samples from the ovarian carcinoma cell lines A2780s (parental wild type) and A2780cp (cisplatin cross-radio-resistant), before, right after, and 24 hours after irradiation to 10Gy. Methods: Spectra were acquired with a home built confocal Raman microscope in 3 distinct runs of six samples: unirradiated s&cp (control pair), then 0h and 24h after irradiation. The Raman spectra were noise reduced, then background subtracted with SMIRF algorithm. ∼35 cell spectra were collected from each sample in 1024 channels from 700cm-1 to 1618cm-1. The spectra were analyzed by regularized multiclass LDA. For feature reductionmore » the spectra were grouped into 3 overlapping group pairs: s-cp, 0Gy–10Gy0h and 0Gy10–Gy24h. The three features, the three differences of the mean spectra were mapped to the analysis sub-space by the inverse regularized covariance matrix. The batch effect noticeably confounded the dose and time effect. Results: To remove the batch effect, the 2+2=4D subspace extended by the covariance matrix of the means of the 0Gy control groups was subtracted from the spectra of each sample. Repeating the analysis on the spectra with the control group variability removed, the batch effect was dramatically reduced in the dose and time directions enabling sharp linear discrimination. The cell type classification also improved. Conclusions: We identified a efficient batch effect removal technique crucial to the applicability of Raman microscopy to radiosensitivity studies both on cell cultures and potential clinical diagnostic applications.« less

Meroterpenoids and isoberkedienolactone from endophytic fungus Penicillium sp. associated with Dysosma versipellis.

PubMed

Li, Jun-Wei; Duan, Rui-Gang; Zou, Jian-Hua; Chen, Ri-Dao; Chen, Xiao-Guang; Dai, Jun-Gui

2014-06-01

Seven meroterpenoids and five small-molecular precursors were isolated from Penicillium sp., an endophytic fungus from Dysosma versipellis. The structures of new compounds, 11beta-acetoxyisoaustinone (1) and isoberkedienolactone (2) were elucidated based on analysis of the spectral data, and the absolute configuration of 2 was established by TDDFT ECD calculation with satisfactory match to its experimental ECD data. Meroterpenoids originated tetraketide and pentaketide precursors, resepectively, were found to be simultaneously produced in specific fungus of Penicillium species. These compounds showed weak cytotoxicity in vitro against HCT-116, HepG2, BGC-823, NCI-H1650, and A2780 cell lines with IC 50 > 10 micromol x L(-1).

Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy.

PubMed

Zhao, Jing; Xu, Youwei; Wang, Changyuan; Ding, Yanfang; Chen, Manyu; Wang, Yifei; Peng, Jinyong; Li, Lei; Lv, Li

2017-07-01

Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus ® copolymers entrapping the poorly soluble anticancer drug dioscin. In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus ® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus ® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus ® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein. The average size of the optimized mixed micelle was 67.15 nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration-time curve (AUC) than the free dioscin solution. Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.

Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752.

PubMed

Chen, XiuXiu; Gong, LiHua; Ou, RongYing; Zheng, ZhenZhen; Chen, JinYan; Xie, FengFeng; Huang, XiaoXiu; Qiu, JianGe; Zhang, WenJi; Jiang, QiWei; Yang, Yang; Zhu, Hua; Shi, Zhi; Yan, XiaoJian

2016-03-01

Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays.

PubMed

Raghavan, Shreya; Ward, Maria R; Rowley, Katelyn R; Wold, Rachel M; Takayama, Shuichi; Buckanovich, Ronald J; Mehta, Geeta

2015-07-01

Ovarian cancer grows and metastasizes from multicellular spheroidal aggregates within the ascites fluid. Multicellular tumor spheroids are therefore physiologically significant 3D in vitro models for ovarian cancer research. Conventional hanging drop cultures require high starting cell numbers, and are tedious for long-term maintenance. In this study, we generate stable, uniform multicellular spheroids using very small number of ovarian cancer cells in a novel 384 well hanging drop array platform. We used novel tumor spheroid platform and two ovarian cancer cell lines (A2780 and OVCAR3) to demonstrate the stable incorporation of as few as 10 cells into a single spheroid. Spheroids had uniform geometry, with projected areas (42.60×10(3)μm-475.22×10(3)μm(2) for A2780 spheroids and 37.24×10(3)μm(2)-281.01×10(3)μm(2) for OVCAR3 spheroids) that varied as a function of the initial cell seeding density. Phalloidin and nuclear stains indicated cells formed tightly packed spheroids with demarcated boundaries and cell-cell interaction within spheroids. Cells within spheroids demonstrated over 85% viability. 3D tumor spheroids demonstrated greater resistance (70-80% viability) to cisplatin chemotherapy compared to 2D cultures (30-50% viability). Ovarian cancer spheroids can be generated from limited cell numbers in high throughput 384 well plates with high viability. Spheroids demonstrate therapeutic resistance relative to cells in traditional 2D culture. Stable incorporation of low cell numbers is advantageous when translating this research to rare patient-derived cells. This system can be used to understand ovarian cancer spheroid biology, as well as carry out preclinical drug sensitivity assays. Copyright © 2015 Elsevier Inc. All rights reserved.

Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays

PubMed Central

Raghavan, Shreya; Ward, Maria R.; Rowley, Katelyn R.; Wold, Rachel M.; Takayama, Shuichi; Buckanovich, Ronald J.; Mehta, Geeta

2015-01-01

Background Ovarian cancer grows and metastasizes from multicellular spheroidal aggregates within the ascites fluid. Multicellular tumor spheroids are therefore physiologically significant3Din vitro models for ovarian cancer research. Conventional hanging drop cultures require high starting cell numbers, and are tedious for long-term maintenance. In this study, we generate stable, uniform multicellular spheroids using very small number of ovarian cancer cells in a novel 384 well hanging drop array platform. Methods We used novel tumor spheroid platform and two ovarian cancer cell lines (A2780 and OVCAR3) to demonstrate the stable incorporation of as few as 10 cells into a single spheroid. Results Spheroids had uniform geometry, with projected areas (42.60 × 103 μm–475.22 × 103 μm2 for A2780 spheroids and 37.24 × 103 μm2–281.01 × 103 μm2 for OVCAR3 spheroids) that varied as a function of the initial cell seeding density. Phalloidin and nuclear stains indicated cells formed tightly packed spheroids with demarcated boundaries and cell–cell interaction within spheroids. Cells within spheroids demonstrated over 85% viability. 3D tumor spheroids demonstrated greater resistance (70–80% viability) to cisplatin chemotherapy compared to 2D cultures (30–50% viability). Conclusions Ovarian cancer spheroids can be generated from limited cell numbers in high throughput 384 well plates with high viability. Spheroids demonstrate therapeutic resistance relative to cells in traditional 2D culture. Stable incorporation of low cell numbers is advantageous when translating this research to rare patient-derived cells. This system can be used to understand ovarian cancer spheroid biology, as well as carry out preclinical drug sensitivity assays. PMID:25913133

Photoactivated in Vitro Anticancer Activity of Rhenium(I) Tricarbonyl Complexes Bearing Water-Soluble Phosphines.

PubMed

Marker, Sierra C; MacMillan, Samantha N; Zipfel, Warren R; Li, Zhi; Ford, Peter C; Wilson, Justin J

2018-02-05

Fifteen water-soluble rhenium compounds of the general formula [Re(CO) 3 (NN)(PR 3 )] + , where NN is a diimine ligand and PR 3 is 1,3,5-triaza-7-phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (THP), or 1,4-diacetyl-1,3,7-triaza-5-phosphabicylco[3.3.1]nonane (DAPTA), were synthesized and characterized by multinuclear NMR spectroscopy, IR spectroscopy, and X-ray crystallography. The complexes bearing the THP and DAPTA ligands exhibit triplet-based luminescence in air-equilibrated aqueous solutions with quantum yields ranging from 3.4 to 11.5%. Furthermore, the THP and DAPTA complexes undergo photosubstitution of a CO ligand upon irradiation with 365 nm light with quantum yields ranging from 1.1 to 5.5% and sensitize the formation of 1 O 2 with quantum yields as high as 70%. In contrast, all of the complexes bearing the PTA ligand are nonemissive and do not undergo photosubstitution upon irradiation with 365 nm light. These compounds were evaluated as photoactivated anticancer agents in human cervical (HeLa), ovarian (A2780), and cisplatin-resistant ovarian (A2780CP70) cancer cell lines. All of the complexes bearing THP and DAPTA exhibited a cytotoxic response upon irradiation with minimal toxicity in the absence of light. Notably, the complex with DAPTA and 1,10-phenanthroline gave rise to an IC 50 value of 6 μM in HeLa cells upon irradiation, rendering it the most phototoxic compound in this library. The nature of the photoinduced cytotoxicity of this compound was explored in further detail. These data indicate that the phototoxic response may result from the release of both CO and the rhenium-containing photoproduct, as well as the production of 1 O 2 .

Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

PubMed Central

Křikavová, Radka; Hošek, Jan; Vančo, Ján; Hutyra, Jakub; Dvořák, Zdeněk; Trávníček, Zdeněk

2014-01-01

A series of gold(I) complexes involving triphenylphosphine (PPh3) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HLn) of the general composition [Au(Ln)(PPh3)] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC50 ≈ 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study. PMID:25226034

Anti-tumor effects of osthole on ovarian cancer cells in vitro.

PubMed

Jiang, Guoqiang; Liu, Jia; Ren, Baoyin; Tang, Yawei; Owusu, Lawrence; Li, Man; Zhang, Jing; Liu, Likun; Li, Weiling

2016-12-04

Cnidium monnieri (L.) Cusson is a commonly used traditional Chinese medicine to treat gynecological disease in some countries. Osthole, an active O-methylated coumadin isolated from Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-seizure and anti-inflammatory effects. However, the anti-tumor mechanism of osthole is not well known. Here, we show that osthole inhibited the proliferation and migration of two widely used ovarian cancer cell lines, A2780 and OV2008 cells, in a dose-dependent manner. The study investigated the molecular mechanisms underlying ovarian cancer cells proliferation, apoptosis, cell cycle arrest and migration triggered by osthole. Ovarian cancer cell lines A2780, OV2008 and normal ovarian cell line IOSE80 were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry assays were performed to confirm apoptosis and cell cycle. We employed wound healing and transwell assays to delineate invasive and migratory potential triggered by osthole. MTT assays indicated that cell viability significantly decreased in ovarian cancer cells treated with osthole without effect on normal ovarian cells. Flow cytometric analysis revealed that osthole suppressed cells proliferation by promoting G2/M arrest and inducing apoptosis. The underlying mechanisms involved were regulation of the relative apoptotic protein Bcl-2, Bax and Caspase 3/9. In addition, wound healing and transwell assays revealed that the migratory potential and activity of matrix metalloproteinase MMP-2 and MMP-9 were markedly inhibited when cells were exposed to osthole. Our findings suggested that osthole has the potential to be used in novel anti-cancer therapeutic formulations for ovarian cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner

PubMed Central

Rattan, R; Giri, S; Hartmann, LC; Shridhar, V

2011-01-01

Abstract Metformin, the most widely used drug for type 2 diabetes activates 59 adenosine monophosphate (AMP)-activated protein kinase (AMPK), which regulates cellular energy metabolism. Here, we report that ovarian cell lines VOSE, A2780, CP70, C200, OV202, OVCAR3, SKOV3ip, PE01 and PE04 predominantly express -α1, -β1, -γ1 and -γ2 isoforms of AMPK subunits. Our studies show that metformin treatment (1) significantly inhibited proliferation of diverse chemo-responsive and -resistant ovarian cancer cell lines (A2780, CP70, C200, OV202, OVCAR3, SKVO3ip, PE01 and PE04), (2) caused cell cycle arrest accompanied by decreased cyclin D1 and increased p21 protein expression, (3) activated AMPK in various ovarian cancer cell lines as evident from increased phosphorylation of AMPKα and its downstream substrate; acetyl co-carboxylase (ACC) and enhanced β-oxidation of fatty acid and (4) attenuated mTOR-S6RP phosphorylation, inhibited protein translational and lipid biosynthetic pathways, thus implicating metformin as a growth inhibitor of ovarian cancer cells. We also show that metformin-mediated effect on AMPK is dependent on liver kinase B1 (LKB1) as it failed to activate AMPK-ACC pathway and cell cycle arrest in LKB1 null mouse embryo fibroblasts (mefs). This observation was further supported by using siRNA approach to down-regulate LKB1 in ovarian cancer cells. In contrast, met formin inhibited cell proliferation in both wild-type and AMPKα1/2 null mefs as well as in AMPK silenced ovarian cancer cells. Collectively, these results provide evidence on the role of metformin as an anti-proliferative therapeutic that can act through both AMPK-dependent as well as AMPK-independent pathways. PMID:19874425

Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, Pestalotiopsis microspora.

PubMed

Liu, Shuai; Dai, Haofu; Makhloufi, Gamall; Heering, Christian; Janiak, Christoph; Hartmann, Rudolf; Mándi, Attila; Kurtán, Tibor; Müller, Werner E G; Kassack, Matthias U; Lin, Wenhan; Liu, Zhen; Proksch, Peter

2016-09-23

Seven new 14-membered macrolides, pestalotioprolides C (2), D-H (4-8), and 7-O-methylnigrosporolide (3), together with four known analogues, pestalotioprolide B (1), seiricuprolide (9), nigrosporolide (10), and 4,7-dihydroxy-13-tetradeca-2,5,8-trienolide (11), were isolated from the mangrove-derived endophytic fungus Pestalotiopsis microspora. Their structures were elucidated by analysis of NMR and MS data and by comparison with literature data. Single-crystal X-ray diffraction analysis was used to confirm the absolute configurations of 1, 2, and 10, while Mosher's method and the TDDFT-ECD approach were applied to determine the absolute configurations of 5 and 6. Compounds 3-6 showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC50 values of 0.7, 5.6, 3.4, and 3.9 μM, respectively, while compound 5 showed potent activity against the human ovarian cancer cell line A2780 with an IC50 value of 1.2 μM. Structure-activity relationships are discussed. Coculture of P. microspora with Streptomyces lividans caused a roughly 10-fold enhanced accumulation of compounds 5 and 6 compared to axenic fungal control.

Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway

PubMed Central

HUANG, HAIZHI; CHEN, ALLEN Y.; YE, XINGQIAN; LI, BINGYUN; ROJANASAKUL, YON; RANKIN, GARY O.; CHEN, YI CHARLIE

2015-01-01

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer cell lines, but did not induce apoptosis in the normal ovarian cell line. It induced both Bcl-2 family-dependent intrinsic and DR5 dependent extrinsic apoptosis in OVCAR-3 cells. P53, a multifunctional tumor suppressor, regulated apoptosis in OVCAR-3 cells through a Bcl-2 family protein-dependent pathway. Myricetin did not induce cell cycle arrest in either ovarian cancer cell line. Because of its potency and selectivity against cisplatin-resistant cancer cells, myricetin could potentially be used to overcome cancer chemoresistance against platinum-based therapy. PMID:26315556

Cytotoxic properties of a new organometallic platinum(II) complex and its gold(I) heterobimetallic derivatives.

PubMed

Serratrice, Maria; Maiore, Laura; Zucca, Antonio; Stoccoro, Sergio; Landini, Ida; Mini, Enrico; Massai, Lara; Ferraro, Giarita; Merlino, Antonello; Messori, Luigi; Cinellu, Maria Agostina

2016-01-14

A novel platinum(ii) organometallic complex, [Pt(pbi)(Me)(DMSO)], bearing the 2-(2'-pyridyl)-benzimidazole (pbiH) ligand, was synthesized and fully characterized. Interestingly, the reaction of this organometallic platinum(ii) complex with two distinct gold(i) phosphane compounds afforded the corresponding heterobimetallic derivatives with the pbi ligand bridging the two metal centers. The antiproliferative properties in vitro of [Pt(pbi)(Me)(DMSO)] and its gold(i) derivatives as well as those of the known coordination platinum(ii) and palladium(ii) complexes with the same ligand, of the general formula [MCl2(pbiH)], were comparatively evaluated against A2780 cancer cells, either sensitive or resistant to cisplatin. A superior biological activity of the organometallic compound clearly emerged compared to the corresponding platinum(ii) complex; the antiproliferative effects are further enhanced upon attaching the gold(i) triphenylphosphine moiety to the organometallic Pt compound. Remarkably, these novel metal species are able to overcome nearly complete resistance to cisplatin. Significant mechanistic insight into the study compounds was gained after investigating their reactions with a few representative biomolecules by electrospray mass spectrometry and X-ray crystallography. The obtained results are comprehensively discussed.

Design and synthesis of a series of bioavailable fatty acid synthase (FASN) KR domain inhibitors for cancer therapy.

PubMed

Lu, Tianbao; Schubert, Carsten; Cummings, Maxwell D; Bignan, Gilles; Connolly, Peter J; Smans, Karine; Ludovici, Donald; Parker, Michael H; Meyer, Christophe; Rocaboy, Christian; Alexander, Richard; Grasberger, Bruce; De Breucker, Sabine; Esser, Norbert; Fraiponts, Erwin; Gilissen, Ron; Janssens, Boudewijn; Peeters, Danielle; Van Nuffel, Luc; Vermeulen, Peter; Bischoff, James; Meerpoel, Lieven

2018-05-08

We designed and synthesized a new series of fatty acid synthase (FASN) inhibitors with potential utility for the treatment of cancer. Extensive SAR studies led to highly active FASN inhibitors with good cellular activity and oral bioavailability, exemplified by compound 34. Compound 34 is a potent inhibitor of human FASN (IC 50  = 28 nM) that effectively inhibits proliferation of A2780 ovarian cells (IC 50  = 13 nM) in lipid-reduced serum (LRS). This cellular activity can be rescued by addition of palmitate, consistent with an on-target effect. Compound 34 is also active in many other cell types, including PC3M (IC 50  = 25 nM) and LnCaP-Vancouver prostate cells (IC 50  = 66 nM), and is highly bioavailable (F 61%) with good exposure after oral administration. In a pharmacodynamics study in H460 lung xenograft-bearing mice, oral treatment with compound 34 results in elevated tumor levels of malonyl-CoA and decreased tumor levels of palmitate, fully consistent with the desired target engagement. Copyright © 2018 Elsevier Ltd. All rights reserved.

F14512, a polyamine-vectorized inhibitor of topoisomerase II, exhibits a marked anti-tumor activity in ovarian cancer.

PubMed

Thibault, Benoît; Clement, Emily; Zorza, Grégoire; Meignan, Samuel; Delord, Jean-Pierre; Couderc, Bettina; Bailly, Christian; Narducci, Fabrice; Vandenberghe, Isabelle; Kruczynski, Anna; Guilbaud, Nicolas; Ferré, Pierre; Annereau, Jean-Philippe

2016-01-01

Epithelial ovarian cancer is the fourth cause of death among cancer-bearing women and frequently associated with carboplatin resistance, underlining the need for more efficient and targeted therapies. F14512 is an epipodophylotoxin-core linked to a spermine chain which enters cells via the polyamine transport system (PTS). Here, we investigate this novel concept of vectorization in ovarian cancer. We compared the effects of etoposide and F14512 on a panel of five carboplatin-sensitive or resistant ovarian cancer models. We assessed the incorporation of F17073, a spermine-linked fluorescent probe, in these cells and in 18 clinical samples. We then showed that F14512 exhibits a high anti-proliferative and pro-apoptotic activity, particularly in cells with high levels of F17073 incorporation. Consistently, F14512 significantly inhibited tumor growth compared to etoposide, in a cisplatin-resistant A2780R subcutaneous model, at a dose of 1.25 mg/kg. In addition, ex vivo analysis indicated that 15 out of 18 patients presented a higher F17073 incorporation into tumor cells compared to normal cells. Overall, our data suggest that F14512, a targeted drug with a potent anti-tumor efficacy, constitutes a potential new therapy for highly PTS-positive and platinum-resistant ovarian cancer-bearing patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Structure-activity relationships in cytotoxic Au(I)/Au(III) complexes derived from 2-(2'-pyridyl)benzimidazole.

PubMed

Maiore, Laura; Aragoni, Maria Carla; Deiana, Carlo; Cinellu, Maria Agostina; Isaia, Francesco; Lippolis, Vito; Pintus, Anna; Serratrice, Maria; Arca, Massimiliano

2014-04-21

Gold(I) and gold(III) complexes derived from 2-(2'-pyridyl)benzimidazole (pbiH) were proven to be a promising class of in vitro antitumor agents against A2780 human ovarian cancer cells. In this paper, a comparative electrochemical, UV-vis absorption, and emission spectroscopic investigation is reported on pbiH, the two mononuclear Au(III) complexes [(pbi)AuX2] (X = Cl (1), AcO (2)), the four mononuclear Au(I) derivatives [(pbiH)AuCl] (3), [(pbiH)Au(PPh3)]PF6 ((4(+))(PF6(-))), [(pbi)Au(PPh3)] (5), and [(pbi)Au(TPA)] (6), the three mixed-valence Au(III)/Au(I) complexes [(μ-pbi)Au2Cl3] (7), [(Ph3P)Au(μ-pbi)AuX2]PF6 (X = Cl ((8(+))(PF6(-))), AcO ((9(+))(PF6(-)))), and the binuclear Au(I)-Au(I) compound [(μ-pbi)Au2(PPh3)2]PF6 ((10(+))(PF6(-))). All complexes feature irreversible reduction processes related to the Au(III)/Au(I) or Au(I)/Au(0) processes and peculiar luminescent emission at about 360-370 nm in CH2Cl2, with quantum yields that are remarkably lower ((0.7-14.5) × 10(-2)) in comparison to that determined for the free pbiH ligand (31.5 × 10(-2)) in the same solvent. The spectroscopic and electrochemical properties of all complexes were interpreted on the grounds of time-dependent PBE0/DFT calculations carried out both in the gas phase and in CH2Cl2 implicitly considered within the IEF-PCM SCRF approach. The electronic structure of the complexes, and in particular the energy and composition of the Kohn-Sham LUMOs, can be related to the antiproliferative properties against the A2780 ovarian carcinoma cell line, providing sound quantitative structure-activity relationships and shedding a light on the role played by the global charge and nature of ancillary ligands in the effectiveness of Au-based antitumor drugs.

Gold(III) complexes with 2-substituted pyridines as experimental anticancer agents: solution behavior, reactions with model proteins, antiproliferative properties.

PubMed

Maiore, Laura; Cinellu, Maria Agostina; Nobili, Stefania; Landini, Ida; Mini, Enrico; Gabbiani, Chiara; Messori, Luigi

2012-03-01

Gold(III) compounds form a family of promising cytotoxic and potentially anticancer agents that are currently undergoing intense preclinical investigations. Four recently synthesized and characterized gold(III) derivatives of 2-substituted pyridines are evaluated here for their biological and pharmacological behavior. These include two cationic adducts with 2-pyridinyl-oxazolines, [Au(pyox(R))Cl(2)][PF(6)], [pyox(R)=(S)-4-benzyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, I; (S)-4-iso-propyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, II] and two neutral complexes [Au(N,N'OH)Cl(2)], III, and [Au(N,N',O)Cl], IV, containing the deprotonated ligand N-(1-hydroxy-3-iso-propyl-2-yl)pyridine-2-carboxamide, N,N'H,OH, resulting from ring opening of bound pyox(R) ligand of complex II by hydroxide ions. The solution behavior of these compounds was analyzed. These behave as classical prodrugs: activation of the metal center typically takes place through release of the labile chloride ligands while the rest of the molecule is not altered; alternatively, activation may occur through gold(III) reduction. All compounds react eagerly with the model protein cyt c leading to extensive protein metalation. ESI MS experiments revealed details of gold-cyt c interactions and allowed us to establish the nature of protein bound metal containing fragments. The different behavior displayed by I and II compared to III and IV is highlighted. Remarkable cytotoxic properties, against the reference human ovarian carcinoma cell lines A2780/S and A2780/R were disclosed for all tested compounds with IC(50) values ranging from 1.43 to 6.18 μM in the sensitive cell line and from 1.59 to 10.86 μM in the resistant one. The common ability of these compounds to overcome cisplatin resistance is highlighted. The obtained results are thoroughly discussed in the frame of current knowledge on cytotoxic gold compounds. Copyright © 2011 Elsevier Inc. All rights reserved.

Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands.

PubMed

Allison, Simon J; Sadiq, Maria; Baronou, Efstathia; Cooper, Patricia A; Dunnill, Chris; Georgopoulos, Nikolaos T; Latif, Ayşe; Shepherd, Samantha; Shnyder, Steve D; Stratford, Ian J; Wheelhouse, Richard T; Willans, Charlotte E; Phillips, Roger M

2017-09-10

Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species. DNA damage induction was consistent with cytotoxicity observed against proliferating cells and Ag8 induced cell death by apoptosis. Ag8 also inhibited DNA repair enzyme PARP1, showed preferential activity against cisplatin resistant A2780 cells and potentiated the activity of temozolomide. Ag8 was substantially less active against non-proliferating non-cancer cells and selectively inhibited glycolysis in cancer cells. Ag8 also induced significant anti-tumour effects against cells implanted intraperitoneally in hollow fibres but lacked activity against hollow fibres implanted subcutaneously. Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional setting. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Role of Increased n-acetylaspartate Levels in Cancer

PubMed Central

Zand, Behrouz; Previs, Rebecca A.; Zacharias, Niki M.; Rupaimoole, Rajesha; Mitamura, Takashi; Nagaraja, Archana Sidalaghatta; Guindani, Michele; Dalton, Heather J.; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Hu, Wei; Pecot, Chad V.; Ivan, Cristina; Wu, Sherry Y.; McCullough, Christopher R.; Gharpure, Kshipra M.; Shoshan, Einav; Pradeep, Sunila; Mangala, Lingegowda S.; Rodriguez-Aguayo, Cristian; Wang, Ying; Nick, Alpa M.; Davies, Michael A.; Armaiz-Pena, Guillermo; Liu, Jinsong; Lutgendorf, Susan K.; Baggerly, Keith A.; Eli, Menashe Bar; Lopez-Berestein, Gabriel; Nagrath, Deepak; Bhattacharya, Pratip K.

2016-01-01

Background: The clinical and biological effects of metabolic alterations in cancer are not fully understood. Methods: In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across different cancer types, we analyzed the RNA expression of cancer types using RNASeqV2 data available from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/). Using NAT8L siRNA, molecular techniques and histological analysis, we determined cancer cell viability, proliferation, apoptosis, and tumor growth in in vitro and in vivo (n = 6–10 mice/group) settings. Data were analyzed with the Student’s t test and Kaplan-Meier analysis. Statistical tests were two-sided. Results: Patients with high levels of tumoral NAA and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), had worse overall survival than patients with low levels of NAA and NAT8L. The overall survival duration of patients with higher-than-median NAA levels (3.6 years) was lower than that of patients with lower-than-median NAA levels (5.1 years, P = .03). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) was associated with worse overall survival. NAT8L silencing reduced cancer cell viability (HEYA8: control siRNA 90.61%±2.53, NAT8L siRNA 39.43%±3.00, P < .001; A2780: control siRNA 90.59%±2.53, NAT8L siRNA 7.44%±1.71, P < .001) and proliferation (HEYA8: control siRNA 74.83%±0.92, NAT8L siRNA 55.70%±1.54, P < .001; A2780: control siRNA 50.17%±4.13, NAT8L siRNA 26.52%±3.70, P < .001), which was rescued by addition of NAA. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduced tumor growth statistically significantly (A2780: control siRNA 0.52 g±0.15, NAT8L siRNA 0.08 g±0.17, P < .001; HEYA8: control siRNA 0.79 g±0.42, NAT8L siRNA 0.24 g±0.18, P = .008, A

Polymer Micelles with Cross-Linked Polyanion Core for Delivery of a Cationic Drug Doxorubicin

PubMed Central

Kim, Jong Oh; Kabanov, Alexander V.; Bronich, Tatiana K.

2009-01-01

Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w %) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX. PMID:19386272

Making a commercial carbon fiber cloth having comparable capacitances to carbon nanotubes and graphene in supercapacitors through a "top-down" approach.

PubMed

Zhang, Tianchang; Kim, Christine H J; Cheng, Yingwen; Ma, Yanwen; Zhang, Hongbo; Liu, Jie

2015-02-21

A "top-down" and scalable approach for processing carbon fiber cloth (CFC) into flexible and all-carbon electrodes with remarkable areal capacity and cyclic stability was developed. CFC is commercially available in large quantities but its use as an electrode material in supercapacitors is not satisfactory. The approach demonstrated in this work is based on the sequential treatment of CFC with KOH activation and high temperature annealing that can effectively improve its specific surface area to a remarkable 2780 m(2) g(-1) while at the same time achieving a good electrical conductivity of 320 S m(-1) without sacrificing its intrinsic mechanical strength and flexibility. The processed CFC can be directly used as an electrode for supercapacitors without any binders, conductive additives and current collectors while avoiding elaborate electrode processing steps to deliver a specific capacitance of ∼0.5 F cm(-2) and ∼197 F g(-1) with remarkable rate performance and excellent cyclic stability. The properties of these processed CFCs are comparable or better than graphene and carbon nanotube based electrodes. We further demonstrate symmetric solid-state supercapacitors based on these processed CFCs with very good flexibility. This "top-down" and scalable approach can be readily applied to other types of commercially available carbon materials and therefore can have a substantial significance for high performance supercapacitor devices.

Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors.

PubMed

Burger, Matthew T; Knapp, Mark; Wagman, Allan; Ni, Zhi-Jie; Hendrickson, Thomas; Atallah, Gordana; Zhang, Yanchen; Frazier, Kelly; Verhagen, Joelle; Pfister, Keith; Ng, Simon; Smith, Aaron; Bartulis, Sarah; Merrit, Hanne; Weismann, Marion; Xin, Xiaohua; Haznedar, Joshua; Voliva, Charles F; Iwanowicz, Ed; Pecchi, Sabina

2011-01-13

Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided optimization of these pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties. A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered. Within this series a compound, 17, was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by in vivo inhibition of AKT(Ser473) phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model.

Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors

PubMed Central

2010-01-01

Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided optimization of these pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties. A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered. Within this series a compound, 17, was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic−efficacy relationship as determined by in vivo inhibition of AKTSer473 phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model. PMID:24900252

In vitro effects of Salvia officinalis L. essential oil on Candida albicans

PubMed Central

Sookto, Tularat; Srithavaj, Theerathavaj; Thaweboon, Sroisiri; Thaweboon, Boonyanit; Shrestha, Binit

2013-01-01

Objective To determine the anticandidal activities of Salvia officinalis L. (S. officinalis) essential oil against Candida albicans (C. albicans) and the inhibitory effects on the adhesion of C. albicans to polymethyl methacrylate (PMMA) resin surface. Methods Disc diffusion method was first used to test the anticandidal activities of the S. officinalis L. essential oil against the reference strain (ATCC 90028) and 2 clinical strains of C. albicans. Then the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were determined by modified membrane method. The adhesion of C. albicans to PMMA resin surface was assessed after immersion with S. officinalis L. essential oil at various concentrations of 1×MIC, 0.5×MIC and 0.25×MIC at room temperature for 30 min. One-way ANOVA was used to compare the Candida cell adhesion with the pretreatment agents and Tukey's test was used for multiple comparisons. Results S. officinalis L. essential oil exhibited anticandidal activity against all strains of C. albicans with inhibition zone ranging from 40.5 mm to 19.5 mm. The MIC and MLC of the oil were determined as 2.780 g/L against all test strains. According to the effects on C. albicans adhesion to PMMA resin surface, it was found that immersion in the essential oil at concentrations of 1×MIC (2.780 g/L), 0.5×MIC (1.390 g/L) and 0.25×MIC (0.695 g/L) for 30 min significantly reduced the adhesion of all 3 test strains to PMMA resin surface in a dose dependent manner (P<0.05). Conclusions S. officinalis L. essential oil exhibited anticandidal activities against C. albicans and had inhibitory effects on the adhesion of the cells to PMMA resin surface. With further testing and development, S. officinalis essential oil may be used as an antifungal denture cleanser to prevent candidal adhesion and thus reduce the risk of candida-associated denture stomatitis. PMID:23646301

Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport function.

PubMed

Feng, Sen-Ling; Yuan, Zhong-Wen; Yao, Xiao-Jun; Ma, Wen-Zhe; Liu, Liang; Liu, Zhong-Qiu; Xie, Ying

2016-08-01

Multidrug resistance (MDR) and tumor metastasis are the main causes of chemotherapeutic treatment failure and mortality in cancer patients. In this study, at achievable nontoxic plasma concentrations, citrus flavonoid tangeretin has been shown to reverse ABCB1-mediated cancer resistance to a variety of chemotherapeutic agents effectively. Co-treatment of cells with tangeretin and paclitaxel activated apoptosis as well as arrested cell cycle at G2/M-phase. Tangeretin profoundly inhibited the ABCB1 transporter activity since it significantly increased the intracellular accumulation of doxorubicin, and flutax-2 in A2780/T cells and decreased the efflux of ABCB1 substrates in Caco2 cells without altering the expression of ABCB1. Moreover, it stimulated the ATPase activity and inhibited verapamil-stimulated ATPase activity in a concentration-dependent manner, indicating a direct interaction with the transporter. The molecular docking results indicated a favorable binding of tangeretin with the transmemberane region site 1 of homology modeled ABCB1 transporter. The overall results demonstrated that tangeretin could sensitize ABCB1-overexpressing cancer cells to chemotherapeutical agents by directly inhibiting ABCB1 transporter function, which encouraged further animal and clinical studies in the treatment of resistant cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral focal fibrous hyperplasia and squamous cell papilloma treated with an erbium laser. Case presentation.

PubMed

Boj, J; Hernandez, M; Espasa, E; Espanya, A

2014-01-01

Mouth and oropharynx cancer constitute 5% of all malignancies; 95% of them are head and neck squamous cell carcinomas. Carcinogenesis is a multifactor process. Mutagenesis is also determined by the human papilloma virus which has recently been found to be etiologically associated with 20 to 25% of head and neck squamous cell carcinomas, mostly in the oropharinx. Focal fibrous hyperplasia of the connective tissue comes up as an answer to a chronic irritation in which a big amount of collagen can be found. As there exist certain clinical resemblance between squamous cell papilloma, fibrous focal hyperplasia and other mesenchimal tumors it is recommended to proceed, always, with removal and study. Two cases, one of an oral papilloma and another of a focal fibrous hyperplasia in pediatric patients, treated with an Er,Cr:YSGG laser wave length (mu) of 2780 nm are presented.

Potentiation by Tumor Necrosis Factor of Mitoxantrone Cytotoxicity to Human Ovarian Cancer Cell Lines

PubMed Central

Parodi, Silvio; Billi, Giovanna; Oliva, Cristina; Venturing, Marco; Noviello, Elvira; Conte, PierFranco

1992-01-01

The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PAD, while 3 cell lines (IGROV1, SKOV3, Mel80) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone. PMID:1517145

Main predictors for repetition of suicidal behaviour among women referred to a single public sector tertiary care hospital in Iran.

PubMed

Mostafazadeh, Babak; Farzaneh, Esmaeil

2017-09-01

To assess the main predictors for repetition of suicidal behaviour among women. This cross-sectional study was conducted at Loghman Hakim Hospital, Tehran, Iran, in 2014, and comprised women patients. The patients were divided into two groups, i.e. women repeating suicide and women without repeating suicide. Data was collected through a checklist and then analysed with SPSS 20. Of the 300 women, 121(40.3%) repeated suicide and 179(59.7%) did not. The overall mean age was 26.9±9.1 years (range: 14-80 years). High prevalence of psychological drug usage, alcohol use, history of self-mutilation (self-harm), psychotic disturbances, sexual relationships, as well as smoking and opium addition was revealed as major factors in repeated suicidal behaviour in women when compared with other women. The result of multivariate logistic regression model showed two factors of self-mutilation (odds ratio =2.692, p=0.002) and underlying psychotic disorders (odds ratio = 2.780, p<0.001) as main predictors of suicide in women. In this regard, demographic characteristics could not predict repeating suicidal attempts (p>0.05). The presence of underlying psychotic disorders and self-mutilation were main predictors for repetition of suicidal behaviour.

Risk assessment, spatial distribution, and source apportionment of heavy metals in Chinese surface soils from a typically tobacco cultivated area.

PubMed

Liu, Haiwei; Wang, Haiyun; Zhang, Yan; Yuan, Jumin; Peng, Yaodong; Li, Xiuchun; Shi, Yi; He, Kuanxin; Zhang, Qiming

2018-06-01

The heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the surface soils of tobacco (Nicotiana tabacum L.) fields in Jiangxi Province were analyzed, and the mean heavy metal concentrations were 3.55, 0.19, 25.89, 14.96, 0.25, 10.89, 27.80, and 44.00 mg/kg, respectively. Spatial distribution analysis showed that the highest concentrations were recorded in the north-western, south-western, and mid-eastern parts of the study area. The index of geo-accumulation and pollution index indicated modest enrichment with Cd and Hg, which were the only two metals posing a potentially high ecological risk to the local agricultural environment. The health risk assessment showed no considerable non-carcinogenic or carcinogenic risks for children and adults from these elements. The principal component analysis (PCA) and cluster analysis (CA) found that the variations in the Cr and Ni concentrations were largely on account of the soil parent rocks, but the As, Cd, Cu, and Hg variations in the soil were largely owing to agricultural practices of years. However, the main factor influencing Pb and Zn was atmospheric deposition.

Communitywide cryptosporidiosis outbreak associated with a surface water-supplied municipal water system--Baker City, Oregon, 2013.

PubMed

DeSilva, M B; Schafer, S; Kendall Scott, M; Robinson, B; Hills, A; Buser, G L; Salis, K; Gargano, J; Yoder, J; Hill, V; Xiao, L; Roellig, D; Hedberg, K

2016-01-01

Cryptosporidium, a parasite known to cause large drinking and recreational water outbreaks, is tolerant of chlorine concentrations used for drinking water treatment. Human laboratory-based surveillance for enteric pathogens detected a cryptosporidiosis outbreak in Baker City, Oregon during July 2013 associated with municipal drinking water. Objectives of the investigation were to confirm the outbreak source and assess outbreak extent. The watershed was inspected and city water was tested for contamination. To determine the community attack rate, a standardized questionnaire was administered to randomly sampled households. Weighted attack rates and confidence intervals (CIs) were calculated. Water samples tested positive for Cryptosporidium species; a Cryptosporidium parvum subtype common in cattle was detected in human stool specimens. Cattle were observed grazing along watershed borders; cattle faeces were observed within watershed barriers. The city water treatment facility chlorinated, but did not filter, water. The community attack rate was 28·3% (95% CI 22·1-33·6), sickening an estimated 2780 persons. Watershed contamination by cattle probably caused this outbreak; water treatments effective against Cryptosporidium were not in place. This outbreak highlights vulnerability of drinking water systems to pathogen contamination and underscores the need for communities to invest in system improvements to maintain multiple barriers to drinking water contamination.

An update on the LIM and SH3 domain protein 1 (LASP1): a versatile structural, signaling, and biomarker protein

PubMed Central

Orth, Martin F.; Cazes, Alex; Butt, Elke; Grunewald, Thomas G. P.

2015-01-01

The gene encoding the LIM and SH3 domain protein (LASP1) was cloned two decades ago from a cDNA library of breast cancer metastases. As the first protein of a class comprising one N-terminal LIM and one C-terminal SH3 domain, LASP1 founded a new LIM-protein subfamily of the nebulin group. Since its discovery LASP1 proved to be an extremely versatile protein because of its exceptional structure allowing interaction with various binding partners, its ubiquitous expression in normal tissues, albeit with distinct expression patterns, and its ability to transmit signals from the cytoplasm into the nucleus. As a result, LASP1 plays key roles in cell structure, physiological processes, and cell signaling. Furthermore, LASP1 overexpression contributes to cancer aggressiveness hinting to a potential value of LASP1 as a cancer biomarker. In this review we summarize published data on structure, regulation, function, and expression pattern of LASP1, with a focus on its role in human cancer and as a biomarker protein. In addition, we provide a comprehensive transcriptome analysis of published microarrays (n=2,780) that illustrates the expression profile of LASP1 in normal tissues and its overexpression in a broad range of human cancer entities. PMID:25622104

Quantitative estimation of itopride hydrochloride and rabeprazole sodium from capsule formulation.

PubMed

Pillai, S; Singhvi, I

2008-09-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C(18) column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies.

Measurement of nitrogen in the body using a commercial PGNAA system--phantom experiments.

PubMed

Chichester, D L; Empey, E

2004-01-01

An industrial prompt-gamma neutron activation analysis (PGNAA) system, originally designed for the real-time elemental analyses of bulk coal on a conveyor belt, has been studied to examine the feasibility of using such a system for body composition analysis. Experiments were conducted to measure nitrogen in a simple, tissue equivalent phantom comprised of 2.7 wt% of nitrogen. The neutron source for these experiments was 365 MBq (18.38 microg) of 252Cf located within an engineered low Z moderator and it yielded a dose rate in the measurement position of 3.91 mSv/h; data were collected using a 2780 cm(3) NaI(Tl) cylindrical detector with a digital signal processor and a 512 channel MCA. Source, moderator and detector geometries were unaltered from the system's standard configuration, where they have been optimized for considerations such as neutron thermalization, measurement sensitivity and uniformity, background radiation and external dose minimization. Based on net counts in the 10.8 MeV PGNAA nitrogen photopeak and its escape peaks the dose dependent nitrogen count rate was 11,600 counts/mSv with an uncertainty of 3.0% after 0.32 mSv (4.9 min), 2.0% after 0.74 mSv (11.4 min) and 1.0% after 3.02 mSv (46.4 min).

Cytotoxic cassaine diterpenoid-diterpenoid amide dimers and diterpenoid amides from the leaves of Erythrophleum fordii.

PubMed

Du, Dan; Qu, Jing; Wang, Jia-Ming; Yu, Shi-Shan; Chen, Xiao-Guang; Xu, Song; Ma, Shuang-Gang; Li, Yong; Ding, Guang-Zhi; Fang, Lei

2010-10-01

Detailed phytochemical investigation from the leaves of Erythrophleum fordii resulted in the isolation of 13 compounds, including three cassaine diterpenoid-diterpenoid amide dimers (1, 3 and 5), and seven cassaine diterpenoid amides (6 and 8-13), together with three previously reported ones, erythrophlesins D (2), C (4) and 3beta-hydroxynorerythrosuamide (7). Compounds 1, 3 and 5 are further additions to the small group of cassaine diterpenoid dimers represented by erythrophlesins A-D. Their structures were determined by analysis of extensive one- and two-dimensional NMR experiments and ESIMS methods. Cytotoxic activities of the isolated compounds were tested against HCT-8, Bel-7402, BGC-823, A549 and A2780 human cancer cell lines in the MTT test. Results showed that compounds 1 and 3-5 exhibited significantly selective cytotoxic activities (IC(50)<10 microM) against these cells, respectively. Copyright © 2010 Elsevier Ltd. All rights reserved.

Far-western blotting as a solution to the non-specificity of the anti-erythropoietin receptor antibody

PubMed Central

Fecková, Barbora; Kimáková, Patrícia; Ilkovičová, Lenka; Szentpéteriová, Erika; Debeljak, Nataša; Solárová, Zuzana; Sačková, Veronika; Šemeláková, Martina; Bhide, Mangesh; Solár, Peter

2016-01-01

The erythropoietin receptor (EpoR) is a member of the cytokine receptor family. The interaction between erythropoietin (Epo) and EpoR is important for the production and maturation of erythroid cells, resulting in the stimulation of hematopoiesis. The fact that EpoR was also detected in neoplastic cells has opened the question about the relevance of anemia treatment with recombinant Epo in cancer patients. Numerous studies have reported pro-stimulating and anti-apoptotic effects of Epo in cancer cells, thus demonstrating EpoR functionality in these cells. By contrast, a previous study claims the absence of EpoR in tumor cells. This apparent discrepancy is based, according to certain authors, on the use of non-specific anti-EpoR antibodies. With the aim of bypassing the direct detection of EpoR with an anti-EpoR antibody, the present authors propose a far-western blot methodology, which in addition, confirms the interaction of Epo with EpoR. Applying this technique, the presence of EpoR and its interaction with Epo in human ovarian adenocarcinoma A2780 and normal human umbilical vein endothelial cells was confirmed. Furthermore, modified immunoprecipitation of EpoR followed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis confirmed a 57 kDa protein as a human Epo-interacting protein in both cell lines. PMID:27446474

Quantitative Estimation of Itopride Hydrochloride and Rabeprazole Sodium from Capsule Formulation

PubMed Central

Pillai, S.; Singhvi, I.

2008-01-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C18 column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies. PMID:21394269

Welding, a risk factor of lung cancer: the ICARE study.

PubMed

Matrat, Mireille; Guida, Florence; Mattei, Francesca; Cénée, Sylvie; Cyr, Diane; Févotte, Joëlle; Sanchez, Marie; Menvielle, Gwenn; Radoï, Loredana; Schmaus, Annie; Woronoff, Anne-Sophie; Luce, Danièle; Stücker, Isabelle

2016-04-01

We investigated the relationship between lung cancer and occupational exposure to welding activity in ICARE, a population-based case-control study. Analyses were restricted to men (2276 cases, 2780 controls). Welding exposure was assessed through detailed questionnaires, including lifelong occupational history. ORs were computed using unconditional logistic regression, adjusted for lifelong cigarette smoking and occupational exposure to asbestos. Among the regular welders, welding was associated with a risk of lung cancer (OR=1.7, 95% CI 1.1 to 2.5), which increased with the duration (OR=2.0, 95% CI 1.0 to 3.9 when duration >10 years), and was maximum 10-20 years since last welding. The risk was more pronounced in case of gas welding (OR=2.0, 95% CI 1.2 to 3.3), when the workpiece was covered by paint, grease, or other substances (OR=2.0, 95% CI 1.2 to 3.4) and when it was cleaned with chemical substances before welding. No statistically significant increase in lung cancer risk was observed among occasional welders. Although these results should be confirmed, we showed that type of welding and mode of workpiece preparation are important determinants of the lung cancer risk in regular welders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Contributions of mobile, stationary and biogenic sources to air pollution in the Amazon rainforest: a numerical study with the WRF-Chem model

NASA Astrophysics Data System (ADS)

Abou Rafee, Sameh A.; Martins, Leila D.; Kawashima, Ana B.; Almeida, Daniela S.; Morais, Marcos V. B.; Souza, Rita V. A.; Oliveira, Maria B. L.; Souza, Rodrigo A. F.; Medeiros, Adan S. S.; Urbina, Viviana; Freitas, Edmilson D.; Martin, Scot T.; Martins, Jorge A.

2017-06-01

This paper evaluates the contributions of the emissions from mobile, stationary and biogenic sources on air pollution in the Amazon rainforest by using the Weather Research and Forecasting with Chemistry (WRF-Chem) model. The analyzed air pollutants were CO, NOx, SO2, O3, PM2. 5, PM10 and volatile organic compounds (VOCs). Five scenarios were defined in order to evaluate the emissions by biogenic, mobile and stationary sources, as well as a future scenario to assess the potential air quality impact of doubled anthropogenic emissions. The stationary sources explain the highest concentrations for all air pollutants evaluated, except for CO, for which the mobile sources are predominant. The anthropogenic sources considered resulted an increasing in the spatial peak-temporal average concentrations of pollutants in 3 to 2780 times in relation to those with only biogenic sources. The future scenario showed an increase in the range of 3 to 62 % in average concentrations and 45 to 109 % in peak concentrations depending on the pollutant. In addition, the spatial distributions of the scenarios has shown that the air pollution plume from the city of Manaus is predominantly transported west and southwest, and it can reach hundreds of kilometers in length.

Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

PubMed

Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

2010-04-12

Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

Evaluation of cell toxicity and DNA and protein binding of green synthesized silver nanoparticles.

PubMed

Ribeiro, A P C; Anbu, S; Alegria, E C B A; Fernandes, A R; Baptista, P V; Mendes, R; Matias, A S; Mendes, M; Guedes da Silva, M F C; Pombeiro, A J L

2018-05-01

Silver nanoparticles (AgNPs) were prepared by GREEN chemistry relying on the reduction of AgNO 3 by phytochemicals present in black tea extract. AgNPs were fully characterized by transmission electron microscopy (TEM), ultraviolet-visible spectroscopy ((UV-vis)), X-ray diffraction (XRD) and energy dispersive absorption spectroscopy (EDS). The synthesized AgNPs induced a decrease of the cell viability in a dose-dependent manner with a low IC 50 (0.5 ± 0.1 μM) for an ovarian carcinoma cell line (A2780) compared to primary human fibroblasts (IC 50 5.0 ± 0.1 μM). The DNA binding capability of CT (calf thymus) DNA was investigated using electronic absorption and fluorescence spectroscopies, circular dichroism and viscosity titration methods. Additionally, the AgNPs strongly quench the intrinsic fluorescence of BSA, as determined by synchronous fluorescence spectra. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

DOXIL when combined with Withaferin A (WFA) targets ALDH1 positive cancer stem cells in ovarian cancer.

PubMed

Kakar, Sham S; Worth, Christopher A; Wang, Zhenglong; Carter, Kelsey; Ratajczak, Mariusz; Gunjal, Pranesh

Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum-resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity. Resistance to chemotherapy and recurrence of cancer is primarily attributed to the presence of cancer stem cells (CSCs), a small population of cells present in cancer. Effect of DOXIL and withaferin A (WFA), both alone and in combination, was investigated on cell proliferation of ovarian cancer cell line A2780 and tumor growth in SCID mice bearing i.p. ovarian tumors. ALDH1 cells were isolated from A2780 using cell sorter, and effect of DOXIL and WFA both alone and in combination on tumorigenic function of ALDH1 was studied using spheroids formation assays in vitro. Western blots were performed to examine the expression of ALDH1 and Notch 1 genes. In our studies, we showed, for the first time, that DOXIL when combined with withaferin A (WFA) elicits synergistic effect on inhibition of cell proliferation of ovarian cancer cells and inhibits the expression of ALDH1 protein, a marker for ALDH1 positive cancer stem cells (CSCs), and Notch1, a signaling pathway gene required for self-renewal of CSCs. Inhibition of expression of both ALDH1 and Notch1 genes by WFA was found to be dose dependent, whereas DOXIL (200 nM) was found to be ineffective. SCID mice, bearing i.p. ovarian tumors, were treated with a small dose of DOXIL (2 mg/kg) in combination with a sub-optimal dose of WFA (2 mg/kg) which resulted in a highly significant (60% to 70%) reduction in tumor growth, and complete inhibition of metastasis

Three new labdane-type diterpene glycosides from fruits of Rubus chingii and their cytotoxic activities against five humor cell lines.

PubMed

Zhong, Ruijian; Guo, Qing; Zhou, Guoping; Fu, Huizheng; Wan, Kaihua

2015-04-01

Three new labdane-type diterpene glycosides, 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-7(8),13(14)-diene-3β,15,18-triol (1), 15,18-di-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (2), and 15-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranosyl-18-O-β-d-glucopyranosyl-13(E)-ent-labda-8(9),13(14)-diene-3β,15,18-triol (3), were isolated from the fruits of Rubus chingii. Their structures were elucidated on the basis of spectroscopic data and chemical methods. The cytotoxic activities of compounds 1-3 were evaluated against five human tumor cell lines (HCT-8, BGC-823, A549, and A2780). Compounds 3 showed cytotoxic activity against A549 with an IC50 value of 2.32μM. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

General Characteristics and Cytotoxic Effects of Nano-Poly (Butyl Cyanoacrylate) Containing Carboplatin on Ovarian Cancer Cells

PubMed Central

Kanaani, Leila; Far, Meysam Ebrahimi; Kazemi, S Maryam; Choupani, Edris; Tabrizi, Maral Mazloumi; Shahmabadi, Hasan Ebrahimi; Khiyavi, Azim Akbarzadeh

2017-01-01

The initial response to treatment and subsequent development of resistance to carboplatin are very important challenges. Use of nano drug delivery is a new method to replace standard chemotherapy. In this research, both non-PEGylated and PEGylated nanoparticles (NPs) were prepared by mini-emulsion polymerization of poly (butyl cyanoacrylate) (PBCA) NPs. Characteristics such as size, polydispersity index (PDI), zeta potential, drug release, and stability were examined. In addition, infrared spectroscopy was used for description of the produced NPs. Then, cytotoxicity effects of both formulations were studied on the A2780CIS ovarian cancer cell line with incubation for 24, 48, and 72h. Examination of characteristics of loaded carboplatin on the PBCA NPs under suitable laboratory conditions showed a positive effect of PEG on their properties. Cytotoxicity studies demonstrated greater toxicity with both formulations of nano-drugs than the free drug. The results indicated that PBCA NPs can be considered as suitable candidates for nano-drugs in chemotherapy. PMID:28240014

Eliciting the Intension of Drug Value Sets – Principles and Quality Assurance Applications

PubMed Central

Bahr, Nathan J.; Nelson, Scott D.; Winnenburg, Rainer; Bodenreider, Olivier

2018-01-01

Value sets (VSs) used in electronic clinical quality measures are lists of codes from standard terminologies (“extensional” VSs), whose purpose (“intension”) is not always explicitly stated. We elicited the intension for the 09/01/2014 release of extensional medication value sets by comparison to drug classes from the October 2014 release of RxClass. Value sets matched drug classes if they shared common ingredients, as evidenced by Jaccard similarity score. We elicited the intension of 80 extensional value sets. The average Jaccard similarity was 0.65 for single classes and 0.80 for combination classes, with 34% (27/80) of the value sets having high similarity scores. Manual review by a pharmacist indicated 51% (41/80) of the drug classes selected as the best mapping for a value set matched the intension reflected in that value set name. This approach has the potential for facilitating the development and maintenance of medication value sets. PMID:29295218

Phase change in CoTi2 induced by MeV electron irradiation

NASA Astrophysics Data System (ADS)

Zensho, Akihiro; Sato, Kazuhisa; Yasuda, Hidehiro; Mori, Hirotaro

2018-07-01

The phase change induced by MeV electron irradiation in the intermetallic compound E93-CoTi2 was investigated using high-voltage electron microscopy. Under MeV electron irradiation, CoTi2 was first transformed into an amorphous phase and, with continued irradiation, crystallite formation in the amorphous phase (i.e. formation of crystallites of a solid-solution phase within the amorphous phase) was induced. The critical temperature for amorphisation was around 250 K. The total dose (dpa) required for crystallite formation (i.e. that required for partial crystallisation) was high (i.e. 27-80 dpa) and, even after prolonged irradiation, the amorphous phase was retained in the irradiated sample. Such partial crystallisation behaviour of amorphous Co33Ti67 was clearly different from the crystallisation behaviour (i.e. amorphous-to-solid solution, polymorphous transformation) of amorphous Cr67Ti33 reported in the literature. A possible cause of the difference is discussed.

Bioactive ruthenium(II)-arene complexes containing modified 18β-glycyrrhetinic acid ligands.

PubMed

Kong, Yaqiong; Chen, Feng; Su, Zhi; Qian, Yong; Wang, Fang-Xin; Wang, Xiuxiu; Zhao, Jing; Mao, Zong-Wan; Liu, Hong-Ke

2018-05-01

Metal-arene complexes containing bioactive natural-product derived ligands can have new and unusual properties. We report the synthesis, characterization and antiproliferative activity of two new Ru(II) arene complexes with imidazole (dichlorido complex 1) or bipyridyl (chlorido complex 2) ligands conjugated to 18β-glycyrrhetinic acid, an active triterpenoid metabolite of Glycyrrhiza glabra. In general, the conjugated ligands and complexes showed only moderate activity against HeLa (cervical), MCF-7 (breast) and A2780 (ovarian) cancer cells, although the activity of complex 2 in the former two cell lines approached that of the drug cisplatin. Complex 2 (in contrast to complex 1) also exhibited significant activity towards both Gram-positive S. aureus and Gram-negative E. coil bacteria. Complex 2 can induce condensation of DNA and enhances the generation of intracellular reactive oxygen species (ROS). The conjugation of natural products to ligands in organometallic half-sandwich complexes provides a strategy to enhance their biological activities. Copyright © 2018 Elsevier Inc. All rights reserved.

New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities.

PubMed

Abd El-All, Amira S; Magd-El-Din, Asmaa A; Ragab, Fatma A F; ElHefnawi, Mahmoud; Abdalla, Mohamed M; Galal, Shadia A; El-Rashedy, Ahmed A

2015-07-01

A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A gargantuan acetaminophen level in an acidemic patient treated solely with intravenous N-acetylcysteine.

PubMed

Zell-Kanter, Michele; Coleman, Patrick; Whiteley, Patrick M; Leikin, Jerrold B

2013-01-01

The objective of this report is to describe an acidemic patient with one of the largest recorded acetaminophen ingestions in a patient with acidemia who was treated with supportive care and intravenous (IV) N-acetylcysteine. A 59-year-old female with a history of depression was found comatose. In the Emergency Department, she was obtunded with agonal respirations and immediately intubated. Activated charcoal was given through a nasogastric tube. An initial acetaminophen serum level was 1141 mg/L. The patient was started on IV N-acetylcysteine. The acetaminophen level peaked 2 hours later at 1193 mg/L. She was continued on the IV N-acetylcysteine protocol. The next day her aspartate aminotransferase was 3150 U/L, alanine aminotransferase was 2780 U/L, and creatinine phosphokinase was 16,197 U/L. There was no elevation in bilirubin or international normalized ratio (INR). Transaminase levels decreased on day 3 and normalized by day 4 when she was transferred to a psychiatric unit. Few cases have been reported of strikingly elevated acetaminophen levels in poisoned patients who did not receive hemodialysis. These patients did have increased lactate levels, and some had normal liver function tests. All of these patients received N-acetylcysteine and survived the poisoning without sequelae. This patient in this report was unique in that she had the highest reported serum acetaminophen level with acidosis and was treated successfully with only IV N-acetylcysteine and supportive care.

Antiproliferative and Antioxidant Properties of Anthocyanin Rich Extracts from Blueberry and Blackcurrant Juice

PubMed Central

Diaconeasa, Zoriţa; Leopold, Loredana; Rugină, Dumitriţa; Ayvaz, Huseyin; Socaciu, Carmen

2015-01-01

The present study was aimed at evaluating the antiproliferative potential of anthocyanin-rich fractions (ARFs) obtained from two commercially available juices (blueberry and blackcurrant juices) on three tumor cell lines; B16F10 (murine melanoma), A2780 (ovarian cancer) and HeLa (cervical cancer). Individual anthocyanin determination, identification and quantification were done using HPLC-MS. Antioxidant activity of the juices was determined through different mechanism methods such as DPPH and ORAC. For biological testing, the juices were purified through C18 cartridges in order to obtain fractions rich in anthocyanins. The major anthocyanins identified were glycosylated cyanidin derivatives. The antiproliferative activity of the fractions was tested using the MTT assay. The antiproliferative potential of ARF was found to be associated with those bioactive molecules, anthocyanins due to their antioxidant potential. The results obtained indicated that both blueberry and blackcurrants are rich sources of antioxidants including anthocyanins and therefore these fruits are highly recommended for daily consumption to prevent numerous degenerative diseases. PMID:25622252

Toxicological study of a new maintenance fluid, Veen 3G, in rats.

PubMed

Kamei, J; Onodera, K; Kawaguchi, M; Shibata, M; Kagawa, M; Wachi, M; Kojima, J

2002-10-01

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Crystal Structure of Mycobacterium tuberculosis H37Rv AldR (Rv2779c), a Regulator of the ald Gene

PubMed Central

Dey, Abhishek; Shree, Sonal; Pandey, Sarvesh Kumar; Tripathi, Rama Pati; Ramachandran, Ravishankar

2016-01-01

Here we report the crystal structure of M. tuberculosis AldR (Rv2779c) showing that the N-terminal DNA-binding domains are swapped, forming a dimer, and four dimers are assembled into an octamer through crystal symmetry. The C-terminal domain is involved in oligomeric interactions that stabilize the oligomer, and it contains the effector-binding sites. The latter sites are 30–60% larger compared with homologs like MtbFFRP (Rv3291c) and can consequently accommodate larger molecules. MtbAldR binds to the region upstream to the ald gene that is highly up-regulated in nutrient-starved tuberculosis models and codes for l-alanine dehydrogenase (MtbAld; Rv2780). Further, the MtbAldR-DNA complex is inhibited upon binding of Ala, Tyr, Trp and Asp to the protein. Studies involving a ligand-binding site G131T mutant show that the mutant forms a DNA complex that cannot be inhibited by adding the amino acids. Comparative studies suggest that binding of the amino acids changes the relative spatial disposition of the DNA-binding domains and thereby disrupt the protein-DNA complex. Finally, we identified small molecules, including a tetrahydroquinoline carbonitrile derivative (S010-0261), that inhibit the MtbAldR-DNA complex. The latter molecules represent the very first inhibitors of a feast/famine regulatory protein from any source and set the stage for exploring MtbAldR as a potential anti-tuberculosis target. PMID:27006398

Sesquiterpenes from Neurolaena lobata and their antiproliferative and anti-inflammatory activities.

PubMed

Lajter, Ildikó; Vasas, Andrea; Béni, Zoltán; Forgo, Peter; Binder, Markus; Bochkov, Valery; Zupkó, István; Krupitza, Georg; Frisch, Richard; Kopp, Brigitte; Hohmann, Judit

2014-03-28

Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5β-hydroxy-8β-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3β-acetoxy-8β-isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1-5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1-5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective.

Sesquiterpenes from Neurolaena lobata and Their Antiproliferative and Anti-inflammatory Activities

PubMed Central

2014-01-01

Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5β-hydroxy-8β-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3β-acetoxy-8β-isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1–5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1–5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective. PMID:24476550

Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate.

PubMed

Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B; Fuxe, Jonas; Shoshan, Maria

2012-12-01

Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC 50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations.

Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate

PubMed Central

Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B.; Fuxe, Jonas; Shoshan, Maria

2012-01-01

Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility, epithelial-mesenchymal transition (EMT) and expression of cancer stem cell markers CD117, CD44 and ALDH1. Accordingly, the cells formed self-renewing spheres in serum-free stem cell medium. Despite upregulation of mitochondrial mass and cytochrome c, and no upregulation of Bcl-2/Bcl-xL, SKOV-3-R were multiresistant to antineoplastic drugs. Cancer stem cells, or tumor-initiating cells (TICs) are highly chemoresistant and are believed to cause relapse into disseminated and resistant EOC. Our second aim was therefore to target resistance in these TIC-like cells. Resistance could be correlated with upregulation of hexokinase-II and VDAC, which are known to form a survival-promoting mitochondrial complex. The cells were thus sensitive to 3-bromopyruvate, which dissociates hexokinase-II from this complex, and were particularly sensitive to combination treatment with cisplatin at doses down to 0.1 x IC50. 3-bromopyruvate might thus be of use in targeting the especially aggressive TIC populations. PMID:22954696

Targeting mitochondria: Esters of rhodamine B with triterpenoids are mitocanic triggers of apoptosis.

PubMed

Wolfram, Ratna Kancana; Heller, Lucie; Csuk, René

2018-05-25

Triterpenoic acids, ursolic acid (1), oleanolic acid (2), glycyrrhetinic acid (3) and betulinic acid (4) were converted into their corresponding methyl 5-8 and benzyl esters 9-12 or benzyl amides 21-24. These derivatives served as starting materials for the synthesis of pink colored rhodamine B derivatives 25-36 which were screened for cytotoxicity in colorimetric SRB assays. All of the compounds were cytotoxic for a variety of human tumor cell lines. The activity of the benzyl ester derivatives 29-32 was lower than the cytotoxicity of the methyl esters 25-28. The benzyl amides 33-36 were the most cytotoxic compounds of this series. The most potential compound was a glycyrrhetinic acid rhodamine B benzyl amide 35. This compound showed activity against the different cancer cell lines in a two-digit to low three-digit nano-molar range. Staining experiments combined with fluorescence microscopy showed that this compound triggered apoptosis in A2780 ovarian carcinoma cells and acted as a mitocan. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

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

Chiang, Andrew; Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON; Zeng, Liang

Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesicmore » intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.« less

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells.

PubMed

Zhou, Yuanyuan; Zheng, Xia; Lu, Jiaojiao; Chen, Wei; Li, Xu; Zhao, Le

2018-01-01

The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host

Ultrasound-enhanced localized chemotherapy of drug-sensitive and multidrug resistant tumors

NASA Astrophysics Data System (ADS)

Rapoport, Natalya Y.; Gao, Zhonggao; Kamaev, Pavel; Christensen, Douglas A.

2006-05-01

A new modality of targeted tumor chemotherapy is based on the drug encapsulation in polymeric nanoparticles followed by a localized release at the tumor site triggered by focused ultrasound. Effect of 1 MHz and 3 MHz unfocused ultrasound applied locally to the tumor on the Doxorubicin (DOX) biodistribution and tumor growth rates was measured for ovarian carcinoma tumors in nu/nu mice. The bioeffects of ultrasound were investigated on the systemic and cellular levels. Growth rates of A2780 ovarian carcinoma tumors were substantially reduced by combining micellar drug delivery with tumor irradiation. Ultrasound effect was not thermal as manifested by intratumoral temperature measurements during sonication. Biodistribution studies showed that ultrasound did not enhance micelle extravasation. Main mechanisms of the ultrasound-enhanced chemotherapy included (i) passive targeting of drug-loaded micelles to the tumor interstitium; (ii) ultrasound-triggered localized drug release from micelles in the tumor volume; (iii) enhanced micelle and drug diffusion through the tumor interstitium; and (iv) ultrasound-triggered cell membrane damage resulting in the enhanced micelle and drug uptake by tumor cells.

Mosquitoes and Mosquito-Borne Arboviruses in the Qinghai-Tibet Plateau—Focused on the Qinghai Area, China

PubMed Central

Li, Wen-Juan; Wang, Jing-Lin; Li, Ming-Hua; Fu, Shi-Hong; Wang, Huan-Yu; Wang, Zhi-Yu; Jiang, Shuang-Ying; Wang, Xue-Wen; Guo, Peng; Zhao, Sheng-Cang; Shi, Yan; Lu, Nan-Nan; Nasci, Roger S.; Tang, Qing; Liang, Guo-Dong

2010-01-01

An investigation was conducted to identify the distribution of mosquitoes and mosquito-borne arboviruses in the Qinghai-Tibet Plateau, China from July to August in 2007. A total of 8,147 mosquitoes representing six species from three genera (Aedes, Culex, and Anopheles) were collected in three locations (Geermu city, altitude of 2,780 m; Xining city, 2,200 m; Minhe county, 1,700 m). Six virus isolates were obtained including Tahyna virus (TAHV), Liaoning virus, and Culex pipiens pallens Densovirus. A serosurvey showed immunoglobulin G antibodies by immunofluorescence assay (IFA) against TAHV in residents of all three locations. The IFA-positive human samples were confirmed by 90% plaque-reduction neutralization tests (PRNT90) against TAHV with titers ranging from 1:20 to 1:10,240. In addition, TAHV seropositive cows, sheep, and swine were found in these locations. This investigation represents the first isolation of TAHV from Ae. (Och.) detritus and the first evidence of TAHV infection in residents and livestock in the Qinghai-Tibet Plateau. PMID:20348523

UCHL1 Is a Putative Tumor Suppressor in Ovarian Cancer Cells and Contributes to Cisplatin Resistance

PubMed Central

Jin, Chengmeng; Yu, Wei; Lou, Xiaoyan; Zhou, Fan; Han, Xu; Zhao, Na; Lin, Biaoyang

2013-01-01

Ubiquitin carboxyl terminal hydrolase 1 (UCHL1) catalyzes the hydrolysis of COOH-terminal ubiquityl esters and amides. It has been reported as either an oncogene or a tumor suppressor in cancers. However, UCHL1's role in ovarian cancer is still unclear. Therefore, we conducted an analysis to understand the role of UCHL1 in ovarian cancer. Firstly, we detected UCHL1 promoter methylation status in 7 ovarian cancer cell lines. 4 of them with UCHL1 silencing showed heavy promoter methylation while the other 3 with relative high UCHL1 expression showed little promoter methylation. Then we reduced UCHL1 expression in ovarian cancer cell line A2780 and IGROV1 and found that inhibition of UCHL1 promoted cell proliferation by increasing cells in S phases of cell cycle. Knockdown of UCHL1 also reduced cell apoptosis and contributed to cisplatin resistance. Furthermore, the expression level of UCHL1 in several ovarian cancer cell lines correlated negatively with their cisplatin resistance levels. Microarray data revealed that UCHL1 related genes are enriched in apoptosis and cell death gene ontology (GO) terms. Several apoptosis related genes were increased after UCHL1 knockdown, including apoptosis regulator BCL2, BCL11A, AEN and XIAP. Furthermore, we identified up-regulation of Bcl-2 and pAKT as well as down-regulation of Bax in UCHL1 knockdown cells, while no significant alteration of p53 and AKT1 was found. This study provides a new and promising strategy to overcome cisplatin resistance in ovarian cancer via UCHL1 mediated pathways. PMID:24155778

Feasibility of the optical imaging of thrombus formation in a rotary blood pump by near-infrared light.

PubMed

Sakota, Daisuke; Murashige, Tomotaka; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

2014-09-01

Blood coagulation is one of the primary concerns when using mechanical circulatory support devices such as blood pumps. Noninvasive detection and imaging of thrombus formation is useful not only for the development of more hemocompatible devices but also for the management of blood coagulation to avoid risk of infarction. The objective of this study is to investigate the use of near-infrared light for imaging of thrombus formation in a rotary blood pump. The optical properties of a thrombus at wavelengths ranging from 600 to 750 nm were analyzed using a hyperspectral imaging (HSI) system. A specially designed hydrodynamically levitated centrifugal blood pump with a visible bottom area was used. In vitro antithrombogenic testing was conducted five times with the pump using bovine whole blood in which the activated blood clotting time was adjusted to 200 s prior to the experiment. Two halogen lights were used for the light sources. The forward scattering through the pump and backward scattering on the pump bottom area were imaged using the HSI system. HSI showed an increase in forward scattering at wavelengths ranging from 670 to 750 nm in the location of thrombus formation. The time at which the thrombus began to form in the impeller rotating at 2780 rpm could be detected. The spectral difference between the whole blood and the thrombus was utilized to image thrombus formation. The results indicate the feasibility of dynamically detecting and imaging thrombus formation in a rotary blood pump. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Practical considerations on frenectomy

NASA Astrophysics Data System (ADS)

Moldoveanu, Lucia; Badea, Florin Ciprian; Odor, Alin A.

2014-01-01

Besides surgically classical frenectomy, modern dentistry currently allows its approach by dental laser. Materials and Method: We proposed clinical observation of the results obtained by frenectomy with/without frenoplasty made by laser Er,Cr:YSGG 2780 nm. Results: The patients reported no pain, bleeding, swelling or major discomfort during the postoperative control of the following day. In terms of psycho-emotional reactions, both patients well behave well, the calm being given by no pain, bleeding, suture or edema. Discussions: The accuracy of this method, as well as the use of additional means of healing, allow satisfactory results both for patient and physician. Working parameters depend on the type of laser that is used, in our case Biolase Waterlase MD Turbo, regularly used in Toldimed Clinic in Constanta. Conclusions: Our study reveals that the possibilities regarding the surgical modeling of the lower lip frenulum are higher due to laser than the classical surgical approach. Moreover, a major role in the prevention of relapse by inappropriate healing is represented by the approach of frenectomy accompanied by frenuloplasty.

Precipitation chemistry along an inland transect on the Olympic Peninsula, Washington

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

Blew, R.D.; Edmonds, R.L.

1995-03-01

The objective of this study was to examine oceanic influences, seasonal variation, and effect of distance from the ocean on the chemistry of bulk precipitation falling on the Pacific coast of Washington State. Bulk precipitation was collected at Sites 4, 13, 24, and 31 km inland from the Pacific Ocean. Mean electrical conductivity of precipitation ranged from 0.47 to 1.02 mS m{sup -1} and mean pH ranged from 5.3 to 5.6. Annual precipitation increased from 2780 mm at 4 km to approximately 3500 mm at 13 km from the coast and remained constant through 31 km inland. Precipitation was highestmore » in the late fall and winter months and lowest during the summer. Rates of ion deposition had a similar seasonal pattern to that of precipitation. Concentrations of Cl, SO{sub 4}, Mg, Na, and excess Ca (Ca in excess of expected sea salt levels) were highest nearest to the coast and were reflected in higher electrical conductivity in precipitation falling closets to the coast.« less

Re-Os ages for Archean molybdenite and pyrite, Kuittila-Kivisuo, Finland and Proterozoic molybdenite, Kabeliai, Lithuania: Testing the chronometer in a metamorphic and metasomatic setting

USGS Publications Warehouse

Stein, H.J.; Sundblad, K.; Markey, R.J.; Morgan, J.W.; Motuza, G.

1998-01-01

that the Re-Os isotopic system in pyrite has been reset on the millimeter scale and that the 21 ppt 187Os intercept reflects the in situ decay of 187Re during the ~160 to 170 m.y. interval from ~2778 Ma (time of molybdenite ± pyrite deposition) to ~2607 Ma (time of pyrite resetting). When the Re-Os data for molybdenites from the nearby Kivisuo prospect are plotted together with the Kuittila molybdenite and pyrite data, a well-constrained five-point isochron with an age of 2780 ± 8 Ma and a 187Os intercept (-2.4 ± 3.8 ppt) of essentially zero results (MSWD = 1.5). We suggest that the pyrite isochron age records a regional metamorphic and/or hydrothermal event, possibly the time of Au mineralization. A proposed Re-Os age of ~2607 Ma for Au mineralization is in good agreement with radiometric ages by other methods that address the timing of Archean Au mineralization in deposits worldwide (so-called 'late Au model'). Molybdenite, in contrast, provides a robust Re-Os chronometer, retaining its original formation age of ~2780 Ma, despite subsequent metamorphic disturbances in Archean and Proterozoic time.

A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity.

PubMed

Ude, Ziga; Romero-Canelón, Isolda; Twamley, Brendan; Fitzgerald Hughes, Deirdre; Sadler, Peter J; Marmion, Celine J

2016-07-01

7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Hubble Space Telescope Extragalactic Distance Scale Key Project. 1: The discovery of Cepheids and a new distance to M81

NASA Technical Reports Server (NTRS)

Freedman, Wendy L.; Hughes, Shaun M.; Madore, Barry F.; Mould, Jeremy R.; Lee, Myung Gyoon; Stetson, Peter; Kennicutt, Robert C.; Turner, Anne; Ferrarese, Laura; Ford, Holland

1994-01-01

We report on the discovery of 30 new Cepheids in the nearby galaxy M81 based on observations using the Hubble Space Telescope (HST). The periods of these Cepheids lie in the range of 10-55 days, based on 18 independent epochs using the HST wide-band F555W filter. The HST F555W and F785LP data have been transformed to the Cousins standard V and I magnitude system using a ground-based calibration. Apparent period-luminosity relations at V and I were constructed, from which apparent distance moduli were measured with respect to assumed values of mu(sub 0) = 18.50 mag and E(B - V) = 0.10 mag for the Large Magellanic Cloud. The difference in the apparent V and I moduli yields a measure of the difference in the total mean extinction between the M81 and the LMC Cepheid samples. A low total mean extinction to the M81 sample of E(B - V) = 0.03 +/- 0.05 mag is obtained. The true distance modulus to M81 is determined to be 27.80 +/- 0.20 mag, corresponding to a distance of 3.63 +/- 0.34 Mpc. These data illustrate that with an optimal (power-law) sampling strategy, the HST provides a powerful tool for the discovery of extragalactic Cepheids and their application to the distance scale. M81 is the first calibrating galaxy in the target sample of the HST Key Project on the Extragalactic Distance Scale, the ultimate aim of which is to provide a value of the Hubble constant to 10% accuracy.

The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

PubMed

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

PubMed Central

Jae, Hwan Jun; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

Objective The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. Materials and Methods This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. Results The tumor necrosis rate was significantly higher in the high dose group (93% ± 7.6 [mean ± SD]) than that in the control group (48% ± 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% ± 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% ± 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Conclusion Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method. PMID:19885316

Implant bone integration importance in forensic identification.

PubMed

De Angelis, Danilo; Cattaneo, Cristina

2015-03-01

Odontological identification consists of the comparison of antemortem dental information regarding a missing person with postmortem data from an unidentified corpse or human remains. Usually, the comparison concerns morphologic features that the operator chooses among all the visible characteristics because of inter-individual uniqueness; for this reason, implants can be of enormous assistance. A case concerning the recovery of a burnt oral implant, connected to a bone fragment, among 2780 charred bone fragments, suspected to have belonged to a victim of homicide, is presented to demonstrate that dental implants and their site of bone integration represent a very precious element for personal forensic identification. Because of their morphological invariability in time and because of their morphologic uniqueness, they were used as evidence to associate unidentified human charred remains to a missing person where DNA analysis failed to do so. The case illustrates the fundamental contribution, not yet described in literature, given by the clinical aspects of tooth replacement with dental implants to a forensic discipline. Clinical practitioners should therefore be aware of the great importance of their work and of dental records in a forensic identification scenario. © 2014 American Academy of Forensic Sciences.

Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles.

PubMed

Dufes, Christine; Muller, Jean-Marc; Couet, William; Olivier, Jean-Christophe; Uchegbu, Ijeoma F; Schätzlein, Andreas G

2004-01-01

The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug.

Ensemble Modeling of the July 23, 2012 CME Event

NASA Astrophysics Data System (ADS)

Cash, M. D.; Biesecker, D. A.; Millward, G.; Arge, C. N.; Henney, C. J.

2013-12-01

On July 23, 2012 a large and very fast coronal mass ejection (CME) was observed by STEREO A. This CME was unusual in that the estimates of the speed of the CME ranged from 2125 km/s to 2780 km/s based on dividing the distance of STEREO A from the Sun by the transit time of the CME. Modeling of this CME event with the WSA-Enlil model has also suggested that a very fast speed is required in order to obtain the correct arrival time at 1 AU. We present a systematic study of parameter space for the July 23, 2012 CME event through an ensemble study using the WSA-Enlil model to predict the arrival time of the CME at STEREO A. We investigate how variations in the initial speed, angular width, and direction affect the predicted arrival time. We also explore how variations in the background solar wind influence CME arrival time by using varying ADAPT maps within our ensemble study. Factors involved in the fast transit time of this large CME are discussed and the optimal CME parameters are presented.

Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κB/MMP-2/-9 pathway.

PubMed

Li, Xiaozhao; Bao, Chunyu; Ma, Zhinan; Xu, Boqun; Liu, Xiaoqiu; Ying, Xiaoyan; Zhang, Xuesen

2018-05-09

As widely used in consumer products, perfluorooctanoic acid (PFOA) has become a common environmental pollutant, which has been detected in human serum and associated with cancers. Our previous study showed that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Here, we showed that PFOA (≥100 nM) treatment also stimulated A2780 ovarian cancer cell invasion and migration, which correlated with increased matrix metalloproteinases MMP-2/-9 expression, important proteases associated with tumor invasion and migration. Notably, PFOA treatment induced activation of ERK1/2/ NF-κB signaling. Pre-treatment with U0126, an ERK1/2inhibitor；or JSH-23, a NF-kB inhibitor, can reverse the PFOA-induced cell migration and invasion. Consistent with these results, inhibiting ERK1/2 or NF-κB signaling abolished PFOA-induced up-regulation of MMP-2/-9 expression. These results indicate that PFOA can stimulate ovarian cancer cell migration, invasion and MMP-2/-9 expression by up-regulating ERK/NF-κB pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigation of Parametric Influence on the Properties of Al6061-SiCp Composite

NASA Astrophysics Data System (ADS)

Adebisi, A. A.; Maleque, M. A.; Bello, K. A.

2017-03-01

The influence of process parameter in stir casting play a major role on the development of aluminium reinforced silicon carbide particle (Al-SiCp) composite. This study aims to investigate the influence of process parameters on wear and density properties of Al-SiCp composite using stir casting technique. Experimental data are generated based on a four-factors-five-level central composite design of response surface methodology. Analysis of variance is utilized to confirm the adequacy and validity of developed models considering the significant model terms. Optimization of the process parameters adequately predicts the Al-SiCp composite properties with stirring speed as the most influencing factor. The aim of optimization process is to minimize wear and maximum density. The multiple objective optimization (MOO) achieved an optimal value of 14 wt% reinforcement fraction (RF), 460 rpm stirring speed (SS), 820 °C processing temperature (PTemp) and 150 secs processing time (PT). Considering the optimum parametric combination, wear mass loss achieved a minimum of 1 x 10-3 g and maximum density value of 2.780g/mm3 with a confidence and desirability level of 95.5%.

Toxicity of silver nanoparticles to Arabidopsis: Inhibition of root gravitropism by interfering with auxin pathway.

PubMed

Sun, Juzhi; Wang, Likai; Li, Shuang; Yin, Liyan; Huang, Jin; Chen, Chunli

2017-10-01

Impacts of polyvinylpyrrolidine-coated silver nanoparticles (AgNPs) on root gravitropism in Arabidopsis thaliana were investigated at the physiological, cellular, and molecular levels. Our results showed that AgNPs were taken up by the root and primarily localized at the cell wall and intercellular spaces. Root gravitropism was inhibited by exposure to AgNPs, and the inhibition in root gravitropism caused by exposure to AgNPs exhibited a dose-response relationship. Auxin accumulation was reduced in the root tips because of exposure to AgNPs. However, increased indole-3-acetic acid level could not rescue the inhibition of root gravitropism. Real-time polymerase chain reaction showed significant downregulation of expression of auxin receptor-related genes, which is the TIR1/AFB family of F-box proteins including AFB1, AFB2, AFB3, AFB5, and TIR1. Therefore, the present study suggests that AgNPs have toxicity to the model plant A. thaliana as shown by inhibition of root gravitropism along with a reduction in auxin accumulation and expression of auxin receptors. Environ Toxicol Chem 2017;36:2773-2780. © 2017 SETAC. © 2017 SETAC.

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

NASA Astrophysics Data System (ADS)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-09-01

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase ( p < 0.05) in expression of apoptotic genes ( Bcl2, Bax, p53) and 13.2- to 27.1-fold increase ( p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

Crystal Structure of Mycobacterium tuberculosis H37Rv AldR (Rv2779c), a Regulator of the ald Gene: DNA BINDING AND IDENTIFICATION OF SMALL MOLECULE INHIBITORS.

PubMed

Dey, Abhishek; Shree, Sonal; Pandey, Sarvesh Kumar; Tripathi, Rama Pati; Ramachandran, Ravishankar

2016-06-03

Here we report the crystal structure of M. tuberculosis AldR (Rv2779c) showing that the N-terminal DNA-binding domains are swapped, forming a dimer, and four dimers are assembled into an octamer through crystal symmetry. The C-terminal domain is involved in oligomeric interactions that stabilize the oligomer, and it contains the effector-binding sites. The latter sites are 30-60% larger compared with homologs like MtbFFRP (Rv3291c) and can consequently accommodate larger molecules. MtbAldR binds to the region upstream to the ald gene that is highly up-regulated in nutrient-starved tuberculosis models and codes for l-alanine dehydrogenase (MtbAld; Rv2780). Further, the MtbAldR-DNA complex is inhibited upon binding of Ala, Tyr, Trp and Asp to the protein. Studies involving a ligand-binding site G131T mutant show that the mutant forms a DNA complex that cannot be inhibited by adding the amino acids. Comparative studies suggest that binding of the amino acids changes the relative spatial disposition of the DNA-binding domains and thereby disrupt the protein-DNA complex. Finally, we identified small molecules, including a tetrahydroquinoline carbonitrile derivative (S010-0261), that inhibit the MtbAldR-DNA complex. The latter molecules represent the very first inhibitors of a feast/famine regulatory protein from any source and set the stage for exploring MtbAldR as a potential anti-tuberculosis target. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Grazing alters net ecosystem C fluxes and the global warming potential of a subtropical pasture.

PubMed

Gomez-Casanovas, Nuria; DeLucia, Nicholas J; Bernacchi, Carl J; Boughton, Elizabeth H; Sparks, Jed P; Chamberlain, Samuel D; DeLucia, Evan H

2018-03-01

The impact of grazing on C fluxes from pastures in subtropical and tropical regions and on the environment is uncertain, although these systems account for a substantial portion of global C storage. We investigated how cattle grazing influences net ecosystem CO 2 and CH 4 exchange in subtropical pastures using the eddy covariance technique. Measurements were made over several wet-dry seasonal cycles in a grazed pasture, and in an adjacent pasture during the first three years of grazer exclusion. Grazing increased soil wetness but did not affect soil temperature. By removing aboveground biomass, grazing decreased ecosystem respiration (R eco ) and gross primary productivity (GPP). As the decrease in R eco was larger than the reduction in GPP, grazing consistently increased the net CO 2 sink strength of subtropical pastures (55, 219 and 187 more C/m 2 in 2013, 2014, and 2015). Enteric ruminant fermentation and increased soil wetness due to grazers, increased total net ecosystem CH 4 emissions in grazed relative to ungrazed pasture (27-80%). Unlike temperate, arid, and semiarid pastures, where differences in CH 4 emissions between grazed and ungrazed pastures are mainly driven by enteric ruminant fermentation, our results showed that the effect of grazing on soil CH 4 emissions can be greater than CH 4 produced by cattle. Thus, our results suggest that the interactions between grazers and soil hydrology affecting soil CH 4 emissions play an important role in determining the environmental impacts of this management practice in a subtropical pasture. Although grazing increased total net ecosystem CH 4 emissions and removed aboveground biomass, it increased the net storage of C and decreased the global warming potential associated with C fluxes of pasture by increasing its net CO 2 sink strength. © 2017 by the Ecological Society of America.

Ecological and health risk-based characterization of agricultural soils contaminated with polycyclic aromatic hydrocarbons in the vicinity of a chemical plant in China.

PubMed

Liu, Geng; Niu, Junjie; Guo, Wenjiong; An, Xiangsheng; Zhao, Long

2016-11-01

Polycyclic aromatic hydrocarbons (PAHs) from chemical plants can cause serious pollution of surrounding agricultural soils. A comprehensive study of agricultural soils was conducted in the vicinity of a chemical plant in China to characterize the soil PAH concentration, as well as their composition and sources. Human health and a screening-level ecological risk assessment were conducted for PAH contamination in agricultural soils. The results showed that the total concentrations of 16 priority PAHs ranged from 250.49 to 9387.26 ng g(-1), with an average of 2780.42 ng g(-1). High molecular weight PAHs (four to six rings) were the dominant component, accounting for more than 60% of all PAHs. Principal component analysis (PCA) and positive matrix factorization model (PMF) suggested that diesel emissions, coal combustion, coke ovens, and fuel combustion and gasoline emissions were the main sources of PAHs in agricultural soils. The ecological risk assessment results based on the effects range-low (ERL), the effects range-median (ERM), and the ecological screening levels (ESL) indicated that the exposure to ∑PAH16 was >ERL, >ERM, and ≥ERL and ESL at 78.1% of the soil sampling stations, and could induce biological effects in mammals. The Bapeq concentrations posed a potential carcinogenic risk to humans. Further risk management and control of soil PAHs in these agricultural soils is required to ensure the safety of the biocoenosis and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human Leukocyte Antigen-Presented Macrophage Migration Inhibitory Factor is a Surface Biomarker and Potential Therapeutic Target for Ovarian Cancer

PubMed Central

Patterson, Andrea M; Kaabinejadian, Saghar; McMurtrey, Curtis P; Bardet, Wilfried; Jackson, Ken W; Zuna, Rosemary E; Husain, Sanam; Adams, Gregory P; MacDonald, Glen; Dillon, Rachelle L.; Ames, Harold; Buchli, Rico; Hawkins, Oriana E; Weidanz, Jon A; Hildebrand, William H

2015-01-01

T cells recognize cancer cells via human leukocyte antigen (HLA)/peptide complexes and, when disease overtakes these immune mechanisms, immunotherapy can exogenously target these same HLA/peptide surface markers. We previously identified an HLA-A2-presented peptide derived from macrophage migration inhibitory factor (MIF) and generated antibody RL21A against this HLA-A2/MIF complex. The objective of the current study was to assess the potential for targeting the HLA-A2/MIF complex in ovarian cancer. First, MIF peptide FLSELTQQL was eluted from the HLA-A2 of the human cancerous ovarian cell lines SKOV3, A2780, OV90, and FHIOSE118hi and detected by mass spectrometry. By flow cytometry, RL21A was shown to specifically stain these four cell lines in the context of HLA-A2. Next, partially matched HLA-A*02:01+ ovarian cancer (n=27) and normal fallopian tube (n=24) tissues were stained with RL21A by immunohistochemistry to assess differential HLA-A2/MIF complex expression. Ovarian tumor tissues revealed significantly increased RL21A staining compared to normal fallopian tube epithelium (p<0.0001), with minimal staining of normal stroma and blood vessels (p<0.0001 and p<0.001 compared to tumor cells) suggesting a therapeutic window. We then demonstrated the anti-cancer activity of toxin-bound RL21A via the dose-dependent killing of ovarian cancer cells. In summary, MIF-derived peptide FLSELTQQL is HLA-A2-presented and recognized by RL21A on ovarian cancer cell lines and patient tumor tissues, and targeting of this HLA-A2/MIF complex with toxin-bound RL21A can induce ovarian cancer cell death. These results suggest that the HLA-A2/MIF complex should be further explored as a cell-surface target for ovarian cancer immunotherapy. PMID:26719579

Adenovirus 36 antibodies associated with clinical diagnosis of overweight/obesity but not BMI gain: a military cohort study.

PubMed

Voss, Jameson D; Burnett, Daniel G; Olsen, Cara H; Haverkos, Harry W; Atkinson, Richard L

2014-09-01

Obesity is a public health priority, which also threatens national security. Adenovirus 36 (Adv36) increases adiposity in animals and Adv36 antibody status is associated with human obesity, but it is unknown whether infection predicts the development of human adiposity. The objective of the study was to assess infection status and subsequent weight gain. The study had a retrospective cohort design. The study was conducted at Air Force fitness testing and clinical encounters. PARTICIPANTS included Air Force male enlistees, aged 18-22 years, with a baseline body mass index (BMI) of 20-30 kg/m(2) followed up from enlistment (beginning in 1995) until 2012 or separation from the Air Force. EXPOSURE included Adv36 infection status at the time of entry. Follow-up BMI, the primary outcome, and diagnosis of overweight/obesity by the International Classification of Diseases, ninth revision V85.25+ and 278.0* series (secondary outcome) were recorded. The last recorded follow-up BMI was similar among infected and uninfected, 26.4 and 27.2 kg/m(2), respectively (P > .05). However, infected individuals had a higher hazard of a medical provider's diagnosis of overweight/obese over time (hazard ratio 1.8, 95% confidence interval 1.0-3.1, P = .04), adjusted for baseline BMI. Additionally, infected individuals who were lean at baseline (BMI of 22.5 kg/m(2)) had a 3.9 times greater hazard of developing an overweight/obese clinical diagnosis (95% confidence interval 1.5-9.7, P = .004) compared with uninfected lean individuals after adjusting for interaction (P = .03) between infection and baseline BMI. The presence of Adv36 antibodies was not associated with higher BMI at baseline or follow-up within this military population. However, being infected was associated with developing a clinical diagnosis of overweight/obesity, especially among those lean at baseline.

Short-term Effects of a Physical Activity Intervention on Obesity and Aerobic Fitness of Adolescent Girls.

PubMed

Kelishadi, Roya; Minasian, Vazgen; Marandi, Sayed Mohammad; Farajzadegan, Ziba; Khalighinejad, Pooyan; Shirdavani, Soheila; Omidi, Razieh

2014-12-01

In the past two decades, physical activity has decreased during both childhood and adolescence, and particularly adolescence. It seems that schools are attractive settings in which to implement interventions designed in order to promote physical activity in children; but in Iranian students, few studies have evaluated the effects of such interventions on overweight and obese children. The aim of this study was to evaluate the effects of a short-term school-based physical activity on obesity and aerobic fitness in 12-14 years aged girls. This is a study with single group pretest and posttest design, in which 129 middle school girls in city of Isfahan were assessed based on preventive plan of inactivity in children at the Provincial Health Office. Variables, including weight, height, body mass index (BMI), waist-hip ratio (WHR), body fat percentage and aerobic power of subjects were measured using valid tests. This study showed that subjects' body fat percentage changed about 3.6% (37.74% pretest vs. 36.39% posttest), VO2 max changed 7.43% (29.72 pretest vs. 31.93 posttest), WHR changed 1.12% (0.89 pretest vs. 0.88 posttest), whereas BMI was changed 1.65% (27.80 pretest vs. 27.34 posttest). Findings also revealed that there were significant differences between fat percent, (P = 0.001) and VO2 max (P = 0.001) of subjects, but there was no difference between BMI of them in pre- and post-tests (P = 0.361). These results suggest that even a short-term exercise intervention may lead to positive changes in body fat percentage, WHR and aerobic fitness of overweight children. Therefore, school-based physical activity interventions can be an effective preventive strategy to control obesity and overweight in students.

lH-Pyrazolo[3,4-b]quinolin-3-amine derivatives inhibit growth of colon cancer cells via apoptosis and sub G1 cell cycle arrest.

PubMed

Karthikeyan, Chandrabose; Amawi, Haneen; Viana, Arabela Guedes; Sanglard, Leticia; Hussein, Noor; Saddler, Maria; Ashby, Charles R; Moorthy, N S Hari Narayana; Trivedi, Piyush; Tiwari, Amit K

2018-07-15

A series of lH-pyrazolo[3,4-b]quinolin-3-amine derivatives were synthesized and evaluated for anticancer efficacy in a panel of ten cancer cell lines, including breast (MDAMB-231 and MCF-7), colon (HCT-116, HCT-15, HT-29 and LOVO), prostate (DU-145 and PC3), brain (LN-229), ovarian (A2780), and human embryonic kidney (HEK293) cells, a non-cancerous cell line. Among the eight derivatives screened, compound QTZ05 had the most potent and selective antitumor efficacy in the four colon cancer cell lines, with IC 50 values ranging from 2.3 to 10.2 µM. Furthermore, QTZ05 inhibited colony formation in HCT-116 cells in a concentration-dependent manner. Cell cycle analysis data indicated that QTZ05 caused an arrest in the sub G1 cell cycle in HCT-116 cells. QTZ05 induced apoptosis in HCT-116 cells in a concentration-dependent manner that was characterized by chromatin condensation and increase in the fluorescence of fluorochrome-conjugated Annexin V. The findings from our study suggest that QTZ05 may be a valuable prototype for the development of chemotherapeutics targeting apoptotic pathways in colorectal cancer cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Solid lipid nanoparticles for the delivery of 1,3,5-triaza-7-phosphaadamantane (PTA) platinum (II) carboxylates.

PubMed

Sguizzato, Maddalena; Cortesi, Rita; Gallerani, Eleonora; Drechsler, Markus; Marvelli, Lorenza; Mariani, Paolo; Carducci, Federica; Gavioli, Riccardo; Esposito, Elisabetta; Bergamini, Paola

2017-05-01

The use of solid lipid nanoparticles (SLN) is a promising route for the delivery of platinum complexes aimed to anticancer activity. This paper describes the production and characterization of SLN suitable for the loading of Pt complexes containing the biocompatible phosphine 1,3,5-triaza-7-phosphaadamantane (PTA) as neutral ligand. After a screening of several lipidic phases, stearic acid-based SLN were identified as the most appropriate for the purpose. They were produced by emulsion-dilution method and then characterized in terms of dimension, polydispersity, time stability, pH balance and morphological aspect. Stearic acid SLN are designed as a system able to coordinate to platinum, acting as anionic carboxylic ligands, replacing the base carbonate of the Pt synthon [PtCO 3 (DMSO) 2 ], where also DMSO can subsequently be substituted by phosphinic ligands, namely PTA. SLN functionalised with Pt-PTA were produced and characterized by this synthetic route. The toxicity of plain SLN and the antiproliferative effect of SLN functionalised with Pt-PTA were evaluated on two human cancer cell lines K562 and A2780. The results indicate that SLN can be exploited as a delivery system for Pt complexes with potential anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Cobalt nanoparticles for biomedical applications: Facile synthesis, physiochemical characterization, cytotoxicity behavior and biocompatibility

NASA Astrophysics Data System (ADS)

Ansari, S. M.; Bhor, R. D.; Pai, K. R.; Sen, D.; Mazumder, S.; Ghosh, Kartik; Kolekar, Y. D.; Ramana, C. V.

2017-08-01

Cobalt (Co) nanoparticles (NPs) were produced by a simple, one step hydrothermal method with the capping of oleic acid. Intrinsic structural, physiochemical and magnetic properties of Co NPs were investigated and demonstrated their applicability in biomedicine. X-ray diffraction, Raman spectroscopy and infrared (IR) spectroscopic studies confirm the single phase Co NPs with a high structural quality. The IR data revealed the capping of oleic acid via monodentate interaction. Small angle scattering studies suggest the existence of sticky hard sphere type of interaction among the Co NPs because of magnetic interaction which is further evidenced by electron microscopy imaging analyses. The Co NPs exhibit a ferromagnetic character over a wide range of temperature (20-300 K). The temperature dependence of magnetic parameters namely, saturation magnetization, remanent magnetization, coercivity and reduced remanent magnetization were determined and correlated with structure of Co NPs. The Cytotoxicity studies demonstrate that these Co NPs exhibit the mild anti-proliferative character against the cancer cells (cisplatin resistant ovarian cancer (A2780/CP70)) and safe nature towards the normal cells. Haemolytic behavior of human red blood cells (RBC) revealed (<5%) haemolysis signifying the compatibility of Co NPs with human RBC which is an essential feature in vivo biomedical applications without creating any harmful effects in the human blood stream.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression.

PubMed

Strekalova, Elena; Malin, Dmitry; Good, David M; Cryns, Vincent L

2015-06-15

Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination. Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780-91. ©2015 AACR. ©2015 American Association for Cancer

Detection of chemical changes in bone after irradiation with Er,Cr:YSGG laser

NASA Astrophysics Data System (ADS)

Benetti, Carolina; Santos, Moises O.; Rabelo, Jose S.; Ana, Patrícia A.; Correa, Paulo R.; Zezell, Denise M.

2011-03-01

The use of laser for bone cutting can be more advantageous than the use of drill. However, for a safe clinical application, it is necessary to know the effects of laser irradiation on bone tissues. In this study, the Fourier Transform Infrared spectroscopy (FTIR) was used to verify the molecular and compositional changes promoted by laser irradiation on bone tissue. Bone slabs were obtained from rabbit's tibia and analyzed using ATR-FTIR. After the initial analysis, the samples were irradiated using a pulsed Er,Cr:YSGG laser (2780nm), and analyzed one more time. In order to verify changes due to laser irradiation, the area under phosphate (1300-900cm-1), amides (1680-1200cm-1), water (3600-2400cm-1), and carbonate (around 870cm-1 and between 1600-1300cm-1) bands were calculated, and normalized by phosphate band area (1300-900cm-1). It was observed that Er,Cr:YSGG irradiation promoted a significant decrease in the content of water and amides I and III at irradiated bone, evidencing that laser procedure caused an evaporation of the organic content and changed the collagen structure, suggesting that these changes may interfere with the healing process. In this way, these changes should be considered in a clinical application of laser irradiation in surgeries.

Preclinical activity of melflufen (J1) in ovarian cancer

PubMed Central

Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P.; Gullbo, Joachim

2016-01-01

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration. PMID:27528037

Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

PubMed

Alvarez-Berríos, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

2014-01-01

The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

Preclinical activity of melflufen (J1) in ovarian cancer.

PubMed

Carlier, Charlotte; Strese, Sara; Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P; Gullbo, Joachim

2016-09-13

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics.

PubMed

Santos, Gilberto Monteiro dos; Montrezol, Fábio Tanil; Pauli, Luciana Santos Souza; Sartori-Cintra, Angélica Rossi; Colantonio, Emilson; Gomes, Ricardo José; Marinho, Rodolfo; Moura, Leandro Pereira de; Pauli, José Rodrigo

2014-01-01

To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training's equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

PubMed

Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

In situ Localization of the Human Multidrug‐resistance Gene mRNA Using Thymine‐Thymine Dimerized Single‐stranded cDNA

PubMed Central

Koji, Takehiko; Ueda, Kazumitsu; Pastan, Ira; Gottesman, Michael M.; Nakane, Paul K.; Mori, Shigeo

1990-01-01

In order to detect the mRNA transcribed from the multidrug‐resistance gene (MDR1), thymine‐thymine (T‐T) dimerized single‐stranded DNA probes have been utilized for hybridization with mRNA either on nitrocellulose filters or in cells and tissues. S1 nuclease digestion rather than sonication was used to obtain short T‐T dimerized single‐stranded DNA (300–400 bases) so that they could penetrate well into the cytoplasm. The hybridized T‐T DNA was detected immunohisto‐chemically using rabbit anti‐T‐T DNA antibody (Ab) and peroxidase‐labeled goat anti‐rabbit IgG Ab. Employing this system, MDR1 mRNA could be localized clearly in the human multidrug‐resistant cell lines K562/ADM, CEM/VLB, 2780ad, and KBC4 cells as well as in human fetal kidney and gastric carcinoma. Furthermore, our system successfully detected the expression of MDR1 mRNA in cell lines of increasing resistance. These results paralleled results obtained at the protein level by immunohistochemistry. The analysis of MDR1 RNA expression by this in situ hybridization technique should be useful in the study of normal human tissues and tumor samples expressing the MDR1 gene. PMID:1977730

Expected lifetime numbers, risks, and burden of osteoporotic fractures for 50-year old Chinese women: a discrete event simulation incorporating FRAX.

PubMed

Jiang, Yawen; Ni, Weiyi

2016-11-01

This work was undertaken to provide an estimation of expected lifetime numbers, risks, and burden of fractures for 50-year-old Chinese women. A discrete event simulation model was developed to simulate the lifetime fractures of 50-year-old Chinese women at average risk of osteoporotic fracture. Main events in the model included hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture. Fracture risks were calculated using the FRAX ® tool. Simulations of 50-year-old Chinese women without fracture risks were also carried out as a comparison to determine the burden of fractures. A 50-year-old Chinese woman at average risk of fracture is expected to experience 0.135 (95 % CI: 0.134-0.137) hip fractures, 0.120 (95 % CI: 0.119-0.122) clinical vertebral fractures, 0.095 (95 % CI: 0.094-0.096) wrist fractures, 0.079 (95 % CI: 0.078-0.080) humerus fractures, and 0.407 (95 % CI: 0.404-0.410) other fractures over the remainder of her life. The residual lifetime risk of any fracture, hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture for a 50-year-old Chinese woman is 37.36, 11.77, 10.47, 8.61, 7.30, and 27.80 %, respectively. The fracture-attributable excess quality-adjusted life year (QALY) loss and lifetime costs are estimated at 0.11 QALYs (95 % CI: 0.00-0.22 QALYs) and US $714.61 (95 % CI: US $709.20-720.02), totaling a net monetary benefit loss of US $1,104.43 (95 % CI: US $904.09-1,304.78). Chinese women 50 years of age are at high risk of osteoporotic fracture, and the expected economic and quality-of-life burden attributable to osteoporotic fractures among Chinese women is substantial.

Study of in vitro antimicrobial and antiproliferative activities of selected Saharan plants.

PubMed

Palici, Ionut F; Liktor-Busa, Erika; Zupkó, István; Touzard, Blaise; Chaieb, Mohamed; Urbán, Edit; Hohmann, Judit

2015-12-01

The aim of the present study was the evaluation of the antimicrobial and antiproliferative activities of selected Saharan species, which are applied in the traditional medicine but not studied thoroughly from chemical and pharmacological point of view. The studied plants, namely Anthyllis henoniana, Centropodia forskalii, Cornulaca monacantha, Ephedra alata var. alenda, Euphorbia guyoniana, Helianthemum confertum, Henophyton deserti, Moltkiopsis ciliata and Spartidium saharae were collected from remote areas of North Africa, especially from the Tunisian region of Sahara. After drying and applying the appropriate extraction methods, the plant extracts were tested in antimicrobial screening assay, performed on 19 Gram-positive and -negative strains of microbes. The inhibition zones produced by plant extracts were determined by disc-diffusion method. Remarkable antibacterial activities were exhibited by extracts of Ephedra alata var. alenda and Helianthemum confertum against B. subtilis, M. catarrhalis and methicillin-resistant and non-resistant S. aureus. Minimum inhibitory concentrations of these two species were also determined. Antiproliferative effects of the extracts were evaluated against 4 human adherent cell lines (HeLa, A431, A2780 and MCF7). Notable cell growth inhibition was found for extract of Helianthemum confertum and Euphorbia guyoniana. Our results provided data for selection of some plant species for further detailed pharmacological and phytochemical examinations.

Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated Macrophages.

PubMed

Lee, Kijun; Ahn, Ji-Hye; Lee, Kyung-Tae; Jang, Dae Sik; Choi, Jung-Hye

2018-01-15

Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to have various biological activities such as antioxidant, hepatoprotective, and antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are poorly characterized. In the present study, we investigated the anti-cancer effect of deoxyschizandrin on human ovarian cancer cell lines and tumour-associated macrophages (TAMs). Deoxyschizandrin induced G₀/G₁ phase cell cycle arrest and inhibited cyclin E expression in human ovarian cancer cells. Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced cell growth inhibition. Interestingly, increased production of reactive oxygen species and decreased activation of Akt were observed in A2780 cells treated with deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced cell growth inhibition was markedly suppressed by Akt overexpression. In addition, deoxyschizandrin was found to inhibit the expression of the M2 phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian cancer cells. Moreover, expression and production of the tumour-promoting factors MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly suppressed by deoxyschizandrin treatment. Taken together, these data suggest that deoxyschizandrin exerts anti-cancer effects by inducing G₀/G₁ cell cycle arrest in ovarian cancer cells and reducing the protumoural phenotype of TAMs.

New Abietane and Kaurane Type Diterpenoids from the Stems of Tripterygium regelii

PubMed Central

Fan, Dongsheng; Zhou, Shuangyan; Zheng, Zhiyuan; Zhu, Guo-Yuan; Yao, Xiaojun; Yang, Ming-Rong; Jiang, Zhi-Hong; Bai, Li-Ping

2017-01-01

Eleven new abietane type (1‒11), and one new kaurane (12), diterpenes, together with eleven known compounds (13–23), were isolated and identified from the stems of Tripterygium regelii, which has been used as a traditional folk Chinese medicine for the treatment of rheumatoid arthritis in China. The structures of new compounds were characterized by means of the interpretation of high-resolution electrospray ionization mass spectrometry (HRESIMS), extensive nuclear magnetic resonance (NMR) spectroscopic data and comparisons of their experimental CD spectra with calculated electronic circular dichroism (ECD) spectra. Compound 1 is the first abietane type diterpene with an 18→1 lactone ring. Compound 19 was isolated from the plants of the Tripterygium genus for the first time, and compounds 14–17 were isolated from T. regelii for the first time. Triregelin I (9) showed significant cytotoxicity against A2780 and HepG2 with IC50 values of 5.88 and 11.74 µM, respectively. It was found that this compound was inactive against MCF-7 cells. The discovery of these twelve new diterpenes not only provided information on chemical substances of T. regelii, but also contributed to the chemical diversity of natural terpenoids. PMID:28098763

Molecular survey of Bartonella henselae and Bartonella clarridgeiae in pet cats across Japan by species-specific nested-PCR.

PubMed

Sato, S; Kabeya, H; Negishi, A; Tsujimoto, H; Nishigaki, K; Endo, Y; Maruyama, S

2017-10-01

Cats are known to be the main reservoir for Bartonella henselae and Bartonella clarridgeiae, which are the agents of 'cat-scratch disease' in humans. In the present study, we investigated the prevalence of the two Bartonella species on 1754 cat bloods collected from all prefectures in Japan during 2007-2008 by a nested-polymerase chain reaction (PCR) targeting the 16S-23S rRNA internal transcribed spacer region. Overall, Bartonella DNA was detected in 4·6% (80/1754) of the cats examined. The nested-PCR showed that 48·8% (39/80) of the positive cats were infected with B. henselae mono-infection, 33·8% (27/80) with B. clarridgeiae mono-infection and 17·5% (14/80) were infected with both species. The prevalence (5·9%; 65/1103) of Bartonella infection in the western part of Japan was significantly higher than that (2·3%; 15/651) of eastern Japan (P < 0·001). Statistical analysis of the cats examined suggested a significant association between Bartonella infection and FeLV infection (OR = 1·9; 95% CI = 1·1-3·4), but not with FIV infection (OR = 1·6; 95% CI = 1·0-2·6).

A new generation of ferrociphenols leads to a great diversity of reactive metabolites, and exhibits remarkable antiproliferative properties† †Electronic supplementary information (ESI) available: Experimental procedures for syntheses and biological evaluation, supplementary Fig. 1–8 and Tables 1–6, X-ray crystallographic data, cif file. CCDC 1527404. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04213b

PubMed Central

Wang, Yong; Dansette, Patrick M.; Pigeon, Pascal; McGlinchey, Michael J.

2017-01-01

Organometallic compounds bearing the redox motif [ferrocenyl-ene-phenol] have very promising antiproliferative properties which have been further improved by incorporating pertinent substituents able to engender new mechanisms. Here we show that novel ferrociphenols bearing a hydroxypropyl chain exhibit strong antiproliferative effects, in most cases much better than those of cisplatin, tamoxifen, or of previously described ferrociphenols devoid of this terminal OH. This is illustrated, in the case of one of these compounds, by its IC50 values of 110 nM for MDA-MB-231 triple negative breast cancer cells and of 300 nM for cisplatin-resistant A2780cisR human ovarian cancer cells, and by its GI50 values lower than 100 nM towards a series of melanoma and renal cancer cell lines of the NCI-60 panel. Interestingly, oxidative metabolism of these hydroxypropyl-ferrociphenols yields two kinds of quinone methides (QMs) that readily react with various nucleophiles, such as glutathione, to give 1,6- and 1,8-adducts. Protonation of these quinone methides generates numerous reactive metabolites leading eventually to many rearrangement and cleavage products. This unprecedented and fully characterized metabolic profile involving a wide range of electrophilic metabolites that should react with cell macromolecules may be linked to the remarkable profile of antiproliferative activities of this new series. Indeed, the great diversity of unexpected reactive metabolites found upon oxidation will allow them to adapt to various situations present in the cancer cell. These data initiate a novel strategy for the rational design of anticancer molecules, thus opening the way to new organometallic potent anticancer drug candidates for the treatment of chemoresistant cancers. PMID:29629075

Diosgenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranoside obtained as a new anticancer agent from Dioscorea futschauensis induces apoptosis on human colon carcinoma HCT-15 cells via mitochondria-controlled apoptotic pathway.

PubMed

Wang, San-Long; Cai, Bing; Cui, Cheng-Bin; Liu, Hong-Wei; Wu, Chun-Fu; Yao, Xin-Sheng

2004-06-01

Diosgenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranoside (DRG) is a well-known pentacyclic triterpene glycoside newly isolated from the rhizomes of Dioscorea futschauensis R. Kunth (Dioscoreaceae) by our group. In the present work, the inhibitory effect of DRG on the cell proliferation of human cancer cell lines was examined to reveal for the first time that DRG shows stronger anticancer activity than that of the positive control cisplatin. DRG inhibited the proliferation of human cancer cells, A431, A2780, A549, K562, and HCT-15, with IC50 (micromol L(-1)) values of 9.33 +/- 0.22, 18.7 +/- 0.16, 9.98 +/- 0.38, 6.44 +/- 0.10, and 5.86 +/- 0.14 respectively. It was then found, by morphological observation, "DNA ladder" detection and flow cytometric analysis, that DRG exerts its anticancer effect through inducing apoptosis on HCT-15 cells. Furthermore, it has been demonstrated that DRG triggers a mitochondria-controlled apoptotic pathway to induce apoptosis on HCT-15 cells, which involves the reduction of the mitochondrial potential (deltapsim), the release of cytochrome c from mitochondria into the cytosol, and the down-regulation of the ratio of Bcl-2/Bax expression level. The present results reasonably suggest that regulating the balance of Bcl-2/Bax expression level plays a key role in the DRG-induced apoptosis. Such findings provide novel knowledge to elucidate the biological properties of DRG, even though DRG was discovered early in the late 1960s. These results suggest that DRG may be a good candidate as a chemotherapeutic agent to treat human colon carcinoma.

DSM-IV Axis II personality disorders and suicide and attempted suicide in China.

PubMed

Tong, Yongsheng; Phillips, Michael R; Conner, Kenneth R

2016-10-01

There are meagre data on Axis II personality disorders and suicidal behaviour in China. To describe the prevalence of Axis II personality disorders in suicides and suicide attempts in China and to estimate risk for these outcomes associated with personality disorders. People who died by suicide (n = 151), people who attempted suicide (n = 118) and living community controls (n = 140) were randomly sampled from four Chinese counties and studied using the Structured Clinical Interviews for DSM-IV-TR Axis I Disorders (SCID-I) and Axis II Personality Disorders (SCID-II). We also determined the prevalence of subthreshold versions of ten DSM-IV personality disorders. Axis II personality disorders were present in 7% of the suicide group, 6% of the suicide attempt group and 1% of the control group. Threshold and subthreshold personality disorders had adjusted odds ratios (point estimates) in the range of 2.7-8.0 for suicide and for suicide attempts. Axis II personality disorders may confer increased risk for suicidal behaviour in China, but their low prevalence in the community and among people with suicidal behaviour suggests that other personality constructs such as select dimensional traits may be a more fruitful avenue for understanding and preventing suicide in China. © The Royal College of Psychiatrists 2016.

Association of Natural Intake of Dietary Plant Sterols with Carotid Intima–Media Thickness and Blood Lipids in Chinese Adults: A Cross-Section Study

PubMed Central

Wang, Ping; Chen, Yu-ming; He, Li-ping; Chen, Chao-gang; Zhang, Bo; Xue, Wen-qiong; Su, Yi-xiang

2012-01-01

Background Many studies showed a moderate cholesterol-lowering effect of plant sterols (PS), but increased circulating PS might be atherogenic. We evaluated the associations between natural dietary intake of PS and carotid intima–media thickness (IMT) and serum lipids. Methodology/Principal Findings This community-based cross-sectional study included 1160 men and 2780 women aged 31–75 years. Dietary intakes were assessed using a food-frequency questionnaire. The IMTs at the common, bifurcation and internal carotid artery segments, and fasting serum total (TC), LDL (LDLc) and HDL (HDLc) cholesterol, and triglycerides (TG) were determined. After adjusting for potential covariates, multivariate analysis showed a dose-dependent inverse association of total PS intake with serum TC, LDLc, non-HDLc in women (P<0.001) and in men (P<0.05). As compared to the lowest quartile of PS intake (<206 mg/d), the multivariate-adjusted means of TC, LDLc and non-HDLc in the highest quartile of PS intake (447 mg/d) decreased by 5.0%, 6.2% and 6.5% in women (P<0.005), and by 6.4%, 7.1% and 6.7% (P>0.05) in men. Although the IMTs tended to be lower with greater intake of dietary PS, only small differences in the left internal IMT between the highest and lowest groups were observed among men (−7.6%) and women (−5.1%) (P<0.05). The multivariate analysis showed no significant mean differences among the PS groups in HDLc, TG and IMTs at other studied sites among men and women (all P>0.05). Conclusions Greater PS consumption from natural diets is associated with lower serum total, LDL, non-HDL cholesterol and with thinner left internal IMT in women and men. PMID:22412917

Spatial and temporal corroboration of a fire-scar-based fire history in a frequently burned ponderosa pine forest.

PubMed

Farris, Calvin A; Baisan, Christopher H; Falk, Donald A; Yool, Stephen R; Swetnam, Thomas W

2010-09-01

Fire scars are used widely to reconstruct historical fire regime parameters in forests around the world. Because fire scars provide incomplete records of past fire occurrence at discrete points in space, inferences must be made to reconstruct fire frequency and extent across landscapes using spatial networks of fire-scar samples. Assessing the relative accuracy of fire-scar fire history reconstructions has been hampered due to a lack of empirical comparisons with independent fire history data sources. We carried out such a comparison in a 2780-ha ponderosa pine forest on Mica Mountain in southern Arizona (USA) for the time period 1937-2000. Using documentary records of fire perimeter maps and ignition locations, we compared reconstructions of key spatial and temporal fire regime parameters developed from documentary fire maps and independently collected fire-scar data (n = 60 plots). We found that fire-scar data provided spatially representative and complete inventories of all major fire years (> 100 ha) in the study area but failed to detect most small fires. There was a strong linear relationship between the percentage of samples recording fire scars in a given year (i.e., fire-scar synchrony) and total area burned for that year (y = 0.0003x + 0.0087, r2 = 0.96). There was also strong spatial coherence between cumulative fire frequency maps interpolated from fire-scar data and ground-mapped fire perimeters. Widely reported fire frequency summary statistics varied little between fire history data sets: fire-scar natural fire rotations (NFR) differed by < 3 yr from documentary records (29.6 yr); mean fire return intervals (MFI) for large-fire years (i.e., > or = 25% of study area burned) were identical between data sets (25.5 yr); fire-scar MFIs for all fire years differed by 1.2 yr from documentary records. The known seasonal timing of past fires based on documentary records was furthermore reconstructed accurately by observing intra-annual ring position of fire

Cholecystectomy using a novel Single-Site(®) robotic platform: early experience from 45 consecutive cases.

PubMed

Konstantinidis, Konstantinos M; Hirides, Petros; Hirides, Savas; Chrysocheris, Pericles; Georgiou, Michael

2012-09-01

The aim of this work was to study the feasibility, safety, and efficacy of single-incision robotic cholecystectomy using a novel platform from Intuitive Surgical. All operations were performed by the same surgeon. Parameters assessed included patient history, indication for surgery, operation time, complication rate, conversion rate, robot-related issues, length of hospital stay, postoperative pain, and time to return to work. All patients were followed for a 2-month period postoperatively. Forty-five patients (22 women, 23 men) underwent single-incision robotic cholecystectomy from March 1 to July 15, 2011. There were no conversions to either conventional laparoscopy or laparotomy, although in three cases a second trocar was used. There were no major complications apart from a single case of postoperative hemorrhage. Average patient age was 47 ± 12 years (range = 27-80 years) and average BMI was 30 kg/m(2) (mean = 28.8 ± 4 kg/m(2), range = 18.4-46.7 kg/m(2)). The primary indication for surgery was gallstones. The mean operation time (skin-to-skin) was 84.5 ± 25.5 min (range = 51-175 min), docking time was 5.8 ± 1.5 min (range = 4-11 min), and console time (net surgical time) was 43 ± 21.9 min (range = 21-121 min). Intraoperative blood loss was negligible. There were no collisions between the robotic arms and no other robot-related problems. Average postoperative length of stay was less than 24 h. The mean Visual Analog Pain Scale Score 6 h after the operation was 2.2 ± 1.51 (range = 0-6) and patients returned to normal activities in 4.48 ± 2.3 days (range = 1-9 days). Single-Site(®) is a new platform offering a potentially more stable and reliable environment to perform single-port cholecystectomy. Both simple and complicated cholecystectomies can be performed with safety. The technique is possible in patients with a high BMI. The induction of pneumoperitoneum using the new port and the docking process require additional training.

Effects of graphene quantum dots on linear and nonlinear optical behavior of malignant ovarian cells

NASA Astrophysics Data System (ADS)

Mohajer, Salman; Ara, Mohammad Hossein Majles; Serahatjoo, Leila

2016-07-01

We investigate linear and nonlinear optical properties of standard human ovarian cancer cells (cell line: A2780cp) in vitro. Cells were treated by graphene quantum dots (GQDs) with two special concentrations. Nontoxicity of GQDs was examined in standard biological viability tests. Cancerous cells were fixed on a glass slide; then, interaction of light with biofilms was studied in linear and nonlinear regimes. Absorption spectra of untreated biofilms and biofilms with two different concentrations of GQDs was studied by UV-visible spectrophotometer. Optical behavior of biofilms in a linear regime of intensity (with low-intensity laser exposure) was reported using a simple optical setup. After that, we compared the attenuation of light in biofilm of cancerous cells with and without GQDs. Nonlinear behavior of these biofilms was investigated by a Z-scan setup using a continued wave He-Ne laser. Results showed that GQDs decreased the extinction coefficient and changed the sign and exact value of the nonlinear refractive index of malignant ovarian cells noticeably. The nonlinear refractive index of studied cells with no GQDs treatment was in the order of 10-8 (cm2/w) with a positive sign. This quantity changed to the same order of magnitude with a negative sign after GQDs treatment. Thus, GQDs can be used for cancer diagnosis under laser irradiation.

Characteristics and porcelain bond strength of (Ti,Al)N coating on dental alloys.

PubMed

Chung, Kwok-Hung; Duh, Jeng-Gong; Shin, Daehwan; Cagna, David R; Cronin, Robert J

2002-01-01

The effect of a novel titanium-aluminum nitride film, or (Ti,Al)N film, on the bond strength between a dental porcelain and two nickel-based dental alloy substrates was investigated. A thin layer of (Ti,Al)N film was deposited on flat metal samples using a reactive radio-frequency sputtering method. A uniform thickness of porcelain was applied to the film- coated metal samples. Metal-ceramic specimens were subjected to three-point bending, and failure loads were recorded. Bond strengths between the porcelain and (Ti,Al)N-coated metal alloys ranged from 159.0 +/- 11.7 N to 278.0 +/- 12.3 N. These values were significantly greater (p< 0.05) than bond strengths recorded for control samples that did not incorporate the (Ti,Al)N film. An electron probe microanalyzer with a line profile mode was used to characterize the interface between the (Ti,Al)N film and the porcelain. Results of this investigation suggest that the (Ti,Al)N film (1) increases the flexural bond strength between dental porcelain and nickel-based alloy substrates by permitting elemental diffusion, (2) interferes with the surface oxide formation that characteristically originates from the nickel-based metal alloy substrate, and (3) provides an appropriate oxide layer for porcelain application. Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 516-521, 2002

Elevated high-sensitive troponin T in negative stress test individuals.

PubMed

Brzezinski, Rafael Y; Fisher, Eyal; Ehrenwald, Michal; Shefer, Gabi; Stern, Naftali; Shapira, Itzhak; Zeltser, David; Berliner, Shlomo; Shenhar-Tsarfaty, Shani; Milwidsky, Assi; Rogowski, Ori

2018-06-01

The exercise ECG stress test (EST) is still the first step of work-up in intermediate risk patients in many clinical scenarios. High-sensitive cardiac troponin T (hs-cTnT) elevation is related to future cardiovascular events in the general population and in patients with ischaemic heart disease. The relation between these 2 tests is not well described. A total of 2780 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 49 years, 79% men) were analysed. Multiple physiologic and metabolic parameters including hs-cTnT were collected. All participants completed an EST manually reviewed by a cardiologist. A positive EST was documented in 224 subjects (8%). The majority (91%) of participants with hs-cTnT levels of 5-14 ng/L had a negative EST as well as 89.3% of subjects with levels >14 ng/L. The proportion of subjects with a positive EST and detectable hs-cTnT levels (>5 ng/L) was not significantly greater compared to those with a negative EST (53.1% vs 46.2%, respectively, P = .09). Among subjects referred for EST as part of an annual health survey, we found no significant association between EST results to hs-cTnT detection. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Gallic acid sensitizes paclitaxel-resistant human ovarian carcinoma cells through an increase in reactive oxygen species and subsequent downregulation of ERK activation.

PubMed

Sánchez-Carranza, Jessica Nayelli; Díaz, J Fernando; Redondo-Horcajo, Mariano; Barasoain, Isabel; Alvarez, Laura; Lastres, Pedro; Romero-Estrada, Antonio; Aller, Patricio; González-Maya, Leticia

2018-06-01

Paclitaxel (PTX) is currently used as a front-line chemotherapeutic agent for several types of cancer, including ovarian carcinoma; however, PTX-resistance frequently arises through multiple mechanisms. The development of new strategies using natural compounds and PTX in combination has been the aim of several prior studies, in order to enhance the efficacy of chemotherapy. In this study, we found the following: (i) gallic acid (GA), a phenolic compound, potentiated the capacity of PTX to decrease proliferation and to cause G2/M cycle arrest in the PTX-resistant A2780AD ovarian cancer cell line; (ii) GA exerted a pro-oxidant action by increasing the production of reactive oxygen species (ROS), and co-treatment with the antioxidant agent N‑acetyl-L‑cysteine (NAC) prevented GA+PTX-induced cell proliferation inhibition and G2/M phase arrest; (iii) PTX stimulated ERK phosphorylation/activation, and co-treatment with the MEK/ERK inhibitor PD98049 potentiated the proliferation inhibition and G2/M phase arrest; (iv) and finally, GA abrogated the PTX-induced stimulation of ERK phosphorylation, a response that was prevented by co-treatment with NAC. Taken together, these results indicate that GA sensitizes PTX-resistant ovarian carcinoma cells via the ROS‑mediated inactivation of ERK, and suggest that GA could represent a useful co-adjuvant to PTX in ovarian carcinoma treatment.

Cytotoxic steroids from Monascus purpureus-fermented rice.

PubMed

Shang, Xiao-Ya; Li, Jin-Jie; Liu, Ming-Tao; Li, Shuai; Liu, Ying; Wang, Ye-Feng; Huang, Xiao; Jin, Zong-Lian

2011-01-01

Bioassay-guided fractionation of an EtOH extract of Monascus purpureus-fermented rice led to the isolation of two new steroids (22S, 23R, 24S)-20β,23α,25α-trihydroxy-16,22-epoxy-4,6,8(14)-trienergosta-3-one (1), the first example of a steroid possessing both a conjugated triene ketone system and a fused 4H-furan ring side chain within one molecule, and (22E, 24R)-3β,5α-dihydroxyergosta-23-methyl-7,22-dien-6-one (2), as well as two known compounds (22E, 24R)-3β,5α-dihydroxyergosta-7,22-dien-6-one (3) and (22E, 24R)-6β-methoxy-ergosta-7,22-diene-3β,5α-diol (4). Their structures were assigned by detailed interpretation of HRESIMS, 1D and 2D NMR spectroscopic data. The absolute stereochemistry of 1 was determined by single-crystal X-ray crystallography while the absolute stereochemistry of 2 was established by CD. Compounds 1-4 showed cytotoxic activity against the lung adenocarcinoma (A549) with IC(50) values of 0.08, 0.94, 12.6 and 13.5 μM, respectively. In addition, compounds 1 and 2 exhibited moderate activities against human ovarian cancer (A2780), with IC(50) values of 2.8 and 5.1 μM. Copyright © 2011 Elsevier Inc. All rights reserved.

Modeling and optimization of poly(3hydroxybutyrate-co-3hydroxyvalerate) production from cane molasses by Azohydromonas lata MTCC 2311 in a stirred-tank reactor: effect of agitation and aeration regimes.

PubMed

Zafar, Mohd; Kumar, Shashi; Kumar, Surendra; Dhiman, Amit K

2012-07-01

The effects of agitation and aeration rates on copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] production by Azohydromonas lata MTCC 2311 using cane molasses supplemented with propionic acid in a bioreactor were investigated. The experiments were conducted in a three-level factorial design by varying the impeller (150-500 rev min(-1)) and aeration (0.5-1.5 vvm) rates. Further, the data were fitted to mathematical models [quadratic polynomial equation and artificial neural network (ANN)] and process variables were optimized by genetic algorithm-coupled models. ANN and hybrid ANN-GA were found superior for modeling and optimization of process variables, respectively. The maximum copolymer concentration of 7.45 g l(-1) with 21.50 mol% of 3HV was predicted at process variables: agitation speed, 287 rev min(-1); and aeration rate, 0.85 vvm, which upon validation gave 7.20 g l(-1) of P(3HB-co-3HV) with 21 mol% of 3HV with the prediction error (%) of 3.38 and 2.32, respectively. Agitation speed established a relative high importance of 72.19% than of aeration rate (27.80%) for copolymer accumulation. The volumetric gas-liquid mass transfer coefficient (k (L) a) was strongly affected by agitation and aeration rates. The highest P(3HB-co-3HV) productivity of 0.163 g l(-1) h(-1) was achieved at 0.17 s(-1) of k (L) a value. During the early phase of copolymer production process, 3HB monomers were accumulated, which were shifted to 3HV units (9-21%) during the cultivation period of 24-42 h. The enhancement of 7.5 and 34% were reported for P(3HB-co-3HV) production and 3HV content, respectively, by hybrid ANN-GA paradigm, which revealed the significant utilization of cane molasses for improved copolymer production.

Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles.

PubMed

Gurunathan, Sangiliyandi; Kim, EunSu; Han, Jae Woong; Park, Jung Hyun; Kim, Jin-Hoi

2015-12-15

The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs) using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis) spectroscopy was used to monitor the conversion of Pd(II) ions to Pd(0)NPs. X-ray diffraction (XRD) revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR) further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH), increased reactive oxygen species (ROS) generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP), enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy.

Dietary Intake, Food Processing, and Cooking Methods Among Amish and Non-Amish Adults Living in Ohio Appalachia: Relevance to Nutritional Risk Factors for Cancer

PubMed Central

Cuyun Carter, Gebra B.; Katz, Mira L.; Ferketich, Amy K.; Clinton, Steven K.; Grainger, Elizabeth M.; Paskett, Electra D.; Bloomfield, Clara D.

2013-01-01

This study’s purpose was to examine the source, storage, preparation, and intake of food among Amish and non-Amish adults to understand dietary practices as a potential contributing factor to lower cancer incidence rates. Interviews were conducted with a random sample of 134 Amish and 154 non-Amish adults including questions about dietary practices and a 24-h dietary recall. Amish compared to non-Amish adults reported (1) less refrigeration in homes (85% vs. 100%, P < .01); (2) rarely/never obtaining food from restaurants and grocery stores (P < .01); (3) consuming less alcohol (P < .01); (4) consuming fewer daily servings of vegetables (males: 1.2 vs. 1.9 servings/day, P < .01; females: 1.0 vs. 2.1 servings/day, P < .01); and (5) a greater percentage of energy from saturated fat (males: 16.7% vs. 12.6%, P < .01; females: 16.3% vs. 12.0%, P < .01). Amish males reported greater amount of energy intake (2780 kcal vs. 2298 kcal, P = .03) compared to non-Amish males. Amish and non-Amish dietary patterns show some differences that may impact cancer although neither group achieves current diet and cancer prevention guidelines. Lifestyle factors, screening, and healthcare access may be contributing to the lower cancer incidence rates among the Amish and these results suggest areas of intervention to reduce the cancer burden. PMID:22026912

Dietary intake, food processing, and cooking methods among Amish and non-Amish adults living in Ohio Appalachia: relevance to nutritional risk factors for cancer.

PubMed

Cuyun Carter, Gebra B; Katz, Mira L; Ferketich, Amy K; Clinton, Steven K; Grainger, Elizabeth M; Paskett, Electra D; Bloomfield, Clara D

2011-11-01

This study's purpose was to examine the source, storage, preparation, and intake of food among Amish and non-Amish adults to understand dietary practices as a potential contributing factor to lower cancer incidence rates. Interviews were conducted with a random sample of 134 Amish and 154 non-Amish adults including questions about dietary practices and a 24-h dietary recall. Amish compared to non-Amish adults reported (1) less refrigeration in homes (85% vs. 100%, P < .01); (2) rarely/never obtaining food from restaurants and grocery stores (P < .01); (3) consuming less alcohol (P < .01); (4) consuming fewer daily servings of vegetables (males: 1.2 vs. 1.9 servings/day, P < .01; females: 1.0 vs. 2.1 servings/day, P < .01); and (5) a greater percentage of energy from saturated fat (males: 16.7% vs. 12.6%, P < .01; females: 16.3% vs. 12.0%, P < .01). Amish males reported greater amount of energy intake (2780 kcal vs. 2298 kcal, P = .03) compared to non-Amish males. Amish and non-Amish dietary patterns show some differences that may impact cancer although neither group achieves current diet and cancer prevention guidelines. Lifestyle factors, screening, and healthcare access may be contributing to the lower cancer incidence rates among the Amish and these results suggest areas of intervention to reduce the cancer burden.

Treatment and disposal of refinery sludges: Indian scenario.

PubMed

Bhattacharyya, J K; Shekdar, A V

2003-06-01

Crude oil is a major source of energy and feedstock for petrochemicals. Oily sludge, bio-sludge and chemical sludge are the major sludges generated from the processes and effluent treatment plants of the refineries engaged in crude oil refining operations. Refineries in India generate about 28,220 tons of sludge per annum. Various types of pollutants like phenols, heavy metals, etc. are present in the sludges and they are treated as hazardous waste. Oily sludge, which is generated in much higher amount compared to other sludges, contains phenol (90-100 mg/kg), nickel (17-25 mg/kg), chromium (27-80 mg/kg), zinc (7-80 mg/kg), manganese (19-24 mg/kg), cadmium (0.8-2 mg/kg), copper (32-120 mg/kg) and lead (0.001-0.12 mg/ kg). Uncontrolled disposal practices of sludges in India cause degradation of environmental and depreciation of aesthetic quality. Environmental impact due to improper sludge management has also been identified. Salient features of various treatment and disposal practices have been discussed. Findings of a case study undertaken by the authors for Numaligarh Refinery in India have been presented. Various system alternatives have been identified for waste management in Numaligarh Refinery. A ranking exercise has been carried out to evaluate the alternatives and select the appropriate one. A detailed design of the selected waste management system has been presented.

Therapeutic effect of Chinese herbal medicines for post stroke recovery: A traditional and network meta-analysis.

PubMed

Han, Shi-You; Hong, Zhi-You; Xie, Yu-Hua; Zhao, Yong; Xu, Xiao

2017-12-01

Stroke is a condition with high morbidity and mortality, and 75% of stroke survivors lose their ability to work. Stroke is a burden to the family and society. The purpose of this study was to evaluate the effectiveness of Chinese herbal patent medicines in the treatment of patients after the acute phase of a stroke. We searched the following databases through August 2016: PubMed, Embase, Cochrane library, China Knowledge Resource Integrated Database (CNKI), China Science Periodical Database (CSPD), and China Biology Medicine disc (CBMdisc) for studies that evaluated Chinese herbal patent medicines for post stroke recovery. A random-effect model was used to pool therapeutic effects of Chinese herbal patent medicines on stroke recovery. Network meta-analysis was used to rank the treatment for each Chinese herbal patent medicine. In our meta-analysis, we evaluated 28 trials that included 2780 patients. Chinese herbal patent medicines were effective in promoting recovery after stroke (OR, 3.03; 95% CI: 2.53-3.64; P < .001). Chinese herbal patent medicines significantly improved neurological function defect scores when compared with the controls (standard mean difference [SMD], -0.89; 95% CI, -1.44 to -0.35; P = .001). Chinese herbal patent medicines significantly improved the Barthel index (SMD, 0.73; 95% CI, 0.53-0.94; P < .001) and the Fugl-Meyer assessment scores (SMD, 0.60; 95% CI, 0.34-0.86; P < .001). In the network analysis, MLC601, Shuxuetong, and BuchangNaoxintong were most likely to improve stroke recovery in patients without acupuncture. Additionally, Mailuoning, Xuesaitong, BuchangNaoxintong were the patented Chinese herbal medicines most likely to improve stroke recovery when combined with acupuncture. Our research suggests that the Chinese herbal patent medicines were effective for stroke recovery. The most effective treatments for stroke recovery were MLC601, Shuxuetong, and BuchangNaoxintong. However, to clarify the specific effective

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway

PubMed Central

Lu, Jingjing; Xu, Ying; Wei, Xuan; Zhao, Zhe; Xue, Jing

2016-01-01

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β, β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway. PMID:28097141

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway.

PubMed

Lu, Jingjing; Xu, Ying; Wei, Xuan; Zhao, Zhe; Xue, Jing; Liu, Peishu

2016-01-01

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3 β , β -catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3 β , could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3 β /Slug signaling pathway.

Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics

PubMed Central

dos Santos, Gilberto Monteiro; Montrezol, Fábio Tanil; Pauli, Luciana Santos Souza; Sartori-Cintra, Angélica Rossi; Colantonio, Emilson; Gomes, Ricardo José; Marinho, Rodolfo; de Moura, Leandro Pereira; Pauli, José Rodrigo

2014-01-01

Objective To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. Methods The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training’s equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. Results The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Conclusion Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals. PMID:25628192

Transfer Hydrogenation and Antiproliferative Activity of Tethered Half-Sandwich Organoruthenium Catalysts

PubMed Central

2018-01-01

We report the synthesis and characterization of four neutral organometallic tethered complexes, [Ru(η6-Ph(CH2)3-ethylenediamine-N-R)Cl], where R = methanesulfonyl (Ms, 1), toluenesulfonyl (Ts, 2), 4-trifluoromethylbenzenesulfonyl (Tf, 3), and 4-nitrobenzenesulfonyl (Nb, 4), including their X-ray crystal structures. These complexes exhibit moderate antiproliferative activity toward human ovarian, lung, hepatocellular, and breast cancer cell lines. Complex 2 in particular exhibits a low cross-resistance with cisplatin. The complexes show potent catalytic activity in the transfer hydrogenation of NAD+ to NADH with formate as hydride donor in aqueous solution (310 K, pH 7). Substituents on the chelated ligand decreased the turnover frequency in the order Nb > Tf > Ts > Ms. An enhancement of antiproliferative activity (up to 22%) was observed on coadministration with nontoxic concentrations of sodium formate (0.5–2 mM). Complex 2 binds to nucleobase guanine (9-EtG), but DNA appears not to be the target, as little binding to calf thymus DNA or bacterial plasmid DNA was observed. In addition, complex 2 reacts rapidly with glutathione (GSH), which might hamper transfer hydrogenation reactions in cells. Complex 2 induced a dose-dependent G1 cell cycle arrest after 24 h exposure in A2780 human ovarian cancer cells while promoting an increase in reactive oxygen species (ROS), which is likely to contribute to its antiproliferative activity.

Fatigue and In Vivo Validation of a Peritoneum-Lined Self-Expanding Nitinol Stent-Graft

PubMed Central

Bastijanic, Jennifer M.; Etscheidt, Jordan; Sattiraju, Mallika; Bonsignore, Craig; Kopchok, George; White, Rodney; Sarac, Timur P.

2014-01-01

Purpose To assess the fatigue and in vivo performance of a new stent-graft incorporating bovine peritoneum lining that is designed for application in peripheral vascular occlusive disease. Methods Bovine peritoneum-lined stent-grafts were subjected to accelerated in vitro pulsatile fatigue and axial/torsional fatigue testing designed to simulate 10 years of physiological strain on the devices. At specified times the devices were evaluated for stent fracture, suture failure, or tissue tearing. Seven dogs underwent bilateral common iliac artery (CIA) balloon angioplasty injury with unilateral placement of the peritoneum-lined stent-graft. Angiography and intravascular ultrasound were performed prior to treatment, after treatment, and prior to sacrifice at 30 days. Vessels were perfusion fixed and histologically evaluated at 5 regions: above stent, proximal stent, mid stent, distal stent, and below stent. Results No evidence of stent, suture, or tissue failure was present during or after pulsatile and axial/torsional fatigue testing. At 30±0.3 days after implantation, all vessels were patent. The average lumen area at explantation across stented vessels was 25.45 mm2. Lumen areas tended to be reduced above (23.57 mm2) and below (24.17 mm2) the stent. Lumen areas were consistent across stented regions at explantation (proximal stent 27.80 mm2, mid stent 25.88 mm2, and distal stent 25.81 mm2). The mean neointimal area in peritoneum-lined stents was 2.02±1.52 mm2, with a neointima:media ratio of 1.03±0.50. These values were significantly lower in the above and below stent areas than in the stented regions, but there was no difference in either measure within the proximal, mid, or distal stent. Conclusion The custom-designed peritoneum-lined stent-graft is promising for clinical peripheral applications due to its ability to resist relevant long-term physiological stresses and outstanding short-term patency rates in canine implantations. PMID:25290804

Exploring the potential of phyllosilicate minerals as potassium fertilizers using sodium tetraphenylboron and intensive cropping with perennial ryegrass

PubMed Central

Li, Ting; Wang, Huoyan; Wang, Jing; Zhou, Zijun; Zhou, Jianmin

2015-01-01

In response to addressing potassium (K) deficiency in soil and decreasing agricultural production costs, the potential of K-bearing phyllosilicate minerals that can be directly used as an alternative K source has been investigated using sodium tetraphenylboron (NaTPB) extraction and an intensive cropping experiment. The results showed that the critical value of K-release rate and leaf K concentration was 3.30 g kg−1 h−1 and 30.64 g (kg dry matter)−1, respectively under the experimental conditions. According to this critical value, the maximum amount of released K that could be utilized by a plant with no K deficiency symptoms was from biotite (27.80 g kg−1) and vermiculite (5.58 g kg−1), followed by illite, smectite and muscovite with 2.76, 0.88 and 0.49 g kg−1, respectively. Ryegrass grown on phlogopite showed K deficiency symptoms during the overall growth period. It is concluded that biotite and vermiculite can be directly applied as a promising and sustainable alternative to the use of classical K fertilizers, illite can be utilized in combination with soluble K fertilizers, whereas muscovite, phlogopite and smectite may not be suitable for plant growth. Further field experiments are needed to assess the use of these phyllosilicate minerals as sources of K fertilizer. PMID:25782771

Periconceptional Over-the-Counter Nonsteroidal Anti-inflammatory Drug Exposure and Risk for Spontaneous Abortion

PubMed Central

Velez Edwards, Digna R.; Aldridge, Tiara; Baird, Donna D.; Funk, Michele Jonsson; Savitz, David A.; Hartmann, Katherine E.

2012-01-01

Objective To estimate the association between over-the-counter nonsteroidal anti-inflammatory drug (NSAID) exposure during the early first-trimester and risk for spontaneous abortion (gestation prior to 20 weeks) in a prospective cohort. Methods Women were enrolled in the Right from the Start study (2004–2010). Exposure data regarding over-the-counter NSAID use from the last menstrual period through the 6th week of pregnancy were obtained from intake and first-trimester interviews. Pregnancy outcomes were self-reported and verified by medical records. Gestational age was determined from last menstrual period. Stage of development prior to loss was determined from study ultrasound. Cox proportional hazards regression models were used to estimate the association between NSAID exposure and pregnancy outcome, taking into account candidate confounders. Results Among 2,780 pregnancies, 367 women (13%) experienced an spontaneous abortion. NSAID exposure was reported by 1,185 (43%) women. NSAID exposure was not associated with spontaneous abortion risk in unadjusted models (hazard ratio [HR] = 1.01, 95% confidence interval [CI] 0.82, 1.24) or models adjusted for maternal age (adjusted [aHR] = 1.00, 95% CI 0.81, 1.23). Conclusions Our findings suggest that use of non-prescription over-the-counter NSAIDs in early pregnancy does not put women at increased risk of spontaneous abortion. PMID:22914399

On-line double isotope dilution laser ablation inductively coupled plasma mass spectrometry for the quantitative analysis of solid materials.

PubMed

Fernández, Beatriz; Rodríguez-González, Pablo; García Alonso, J Ignacio; Malherbe, Julien; García-Fonseca, Sergio; Pereiro, Rosario; Sanz-Medel, Alfredo

2014-12-03

We report on the determination of trace elements in solid samples by the combination of on-line double isotope dilution and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The proposed method requires the sequential analysis of the sample and a certified natural abundance standard by on-line IDMS using the same isotopically-enriched spike solution. In this way, the mass fraction of the analyte in the sample can be directly referred to the certified standard so the previous characterization of the spike solution is not required. To validate the procedure, Sr, Rb and Pb were determined in certified reference materials with different matrices, including silicate glasses (SRM 610, 612 and 614) and powdered samples (PACS-2, SRM 2710a, SRM 1944, SRM 2702 and SRM 2780). The analysis of powdered samples was carried out both by the preparation of pressed pellets and by lithium borate fusion. Experimental results for the analysis of powdered samples were in agreement with the certified values for all materials. Relative standard deviations in the range of 6-21% for pressed pellets and 3-21% for fused solids were obtained from n=3 independent measurements. Minimal sample preparation, data treatment and consumption of the isotopically-enriched isotopes are the main advantages of the method over previously reported approaches. Copyright © 2014 Elsevier B.V. All rights reserved.

Contributions to a shallow aquifer study by reprocessed seismic sections from petroleum exploration surveys, eastern Abu Dhabi, United Arab Emirates

USGS Publications Warehouse

Woodward, D.

1994-01-01

The US Geological Survey, in cooperation with the National Drilling Company of Abu Dhabi, is conducting a 4-year study of the fresh and slightly saline groundwater resources of the eastern Abu Dhabi Emirate. Most of this water occurs in a shallow aquifer, generally less than 150 m deep, in the Al Ain area. A critical part of the Al Ain area coincides with a former petroleum concession area where about 2780 km of vibroseis data were collected along 94 seismic lines during 1981-1983. Field methods, acquistion parameters, and section processing were originally designed to enhance reflections expected at depths ranging from 5000 to 6000 m, and subsurface features directly associated with the shallow aquifer system were deleted from the original seismic sections. The original field tapes from the vibroseis survey were reprocessed in an attempt to extract shallow subsurface information (depths less than 550 m) for investigating the shallow aquifer. A unique sequence of reproccessing parameters was established after reviewing the results from many experimental tests. Many enhancements to the resolution of shallow seismic reflections resulted from: (1) application of a 20-Hz, low-cut filter; (2) recomputation of static corrections to a datum nearer the land surface; (3) intensive velocity analyses; and (4) near-trace muting analyses. The number, resolution, and lateral continuity of shallow reflections were greatly enhanced on the reprocessed sections, as was the delineation of shallow, major faults. Reflections on a synthetic seismogram, created from a borehole drilled to a depth of 786 m on seismic line IQS-11, matcheddprecisely with shallow reflections on the reprocessed section. The 33 reprocessed sections were instrumental in preparing a map showing the major structural features that affect the shallow aquifer system. Analysis of the map provides a better understanding of the effect of these shallow features on the regional occurrence, movement, and quality of

Milk composition in free-ranging polar bears (Ursus maritimus) as a model for captive rearing milk formula.

PubMed

Hedberg, Gail E; Derocher, Andrew E; Andersen, Magnus; Rogers, Quinton R; DePeters, Edward J; Lönnerdal, Bo; Mazzaro, Lisa; Chesney, Russell W; Hollis, Bruce

2011-01-01

The goals of this study were to have an improved understanding of milk composition and to help create a suitable milk formula for cubs raised in captivity. Milk samples were evaluated for fat, fatty acids, carbohydrate, vitamin D(3), 25(OH)D(3), vitamin A (retinol), vitamin E (α-tocopherol), protein, and amino acids. Total lipids in milk did not differ for cubs (mean ± SEM = 26.60 ± 1.88 g/100 ml vs. yearlings 27.80 ± 2.20 g/100 ml). Milk lipids were of 23.6% saturated fatty acid for cubs and 22.4% for yearlings. Milk consumed by cubs and yearlings contained 43.8 and 42.0% mono-unsaturated fatty acids and 23.4 and 21.9% polyunsaturated fatty acids, respectively. Carbohydrate content was higher in milk for cubs (4.60 ± 0.64 g/100 ml) than for yearlings (2.60 ± 0.40 g/100 ml). Vitamin D(3) concentration of milk was 18.40 ± 5.00 ng/ml in early lactation compared with 7.60 ± 2.00 ng/ml for mid-lactation. 25(OH)D(3) was lower in milk consumed by cubs (162.00 ± 6.70 pg/ml) than in milk consumed by yearlings (205.00 ± 45.70 pg/ml). Vitamin A concentrations were 0.06 ± 0.01 and 0.03 ± 0.01 µg/ml for cubs and yearlings, respectively. Vitamin E was higher in milk consumed by cubs (20.16 ± 4.46 µg/ml) than by yearlings (7.30 ± 1.50 µg/ml). Protein content did not differ in milk available to cubs (11.40 ± 0.80 g/100 ml compared with milk for yearlings 11.80 ± 0.40 g/100 ml). Taurine was the most abundant free amino acid at 3,165.90 ± 192.90 nmol/ml (0.04% as fed basis). © 2011 Wiley Periodicals, Inc.

Pharmaceuticals and personal care products (PPCPs) in urban and suburban rivers of Beijing, China: occurrence, source apportionment and potential ecological risk.

PubMed

Dai, Guohua; Wang, Bin; Fu, Chaochen; Dong, Rui; Huang, Jun; Deng, Shubo; Wang, Yujue; Yu, Gang

2016-04-01

This study analyzed 15 pharmaceuticals and personal care products (PPCPs) in two rivers with different urbanization levels in the surrounding watershed (urban and suburb) in Beijing, China. Along the rivers, effluent samples from wastewater treatment plants (WWTPs) and wastewater samples from direct discharge outlets were also collected to reveal their possible contribution to the occurrence of PPCPs in these two rivers. Among the 15 PPCPs, 14 compounds were detected with caffeine (maximum 11,900 ng L(-1)) being the dominant compound. The total concentration of the detected PPCPs in direct discharge outlets (median 4706 ng L(-1)) was much higher than that in river waters (2780 ng L(-1)) and WWTP effluents (1971 ng L(-1)). The suburban-influenced Liangshui River had significantly higher PPCP concentrations compared to the urban-influenced Qing River due to more input of untreated wastewater from direct discharge outlets. Source apportionment showed that approximately 55% of the total PPCPs were contributed by untreated wastewater in the suburban-influenced river. Finally, ecological risk assessment has been regarded as a necessary part of general research. According to the environmental risk assessment results, caffeine, trimethoprim and metoprolol were found to be the most critical compounds, due to their high risk quotient values. The results of the present study can provide useful information for future PPCP pollution control and sustainable water management in Beijing, China.

Effectiveness of functional electrical stimulation on walking speed, functional walking category, and clinically meaningful changes for people with multiple sclerosis.

PubMed

Street, Tamsyn; Taylor, Paul; Swain, Ian

2015-04-01

To determine the effectiveness of functional electrical stimulation (FES) on drop foot in patients with multiple sclerosis (MS), using data from standard clinical practice. Case series with a consecutive sample of FES users collected between 2008 and 2013. Specialist FES center at a district general hospital. Patients with MS who have drop foot (N=187) (117 women, 70 men; mean age, 55y [range, 27-80y]; mean duration since diagnosis, 11.7y [range, 1-56y]). A total of 166 patients were still using FES after 20 weeks, with 153 patients completing the follow-up measures. FES of the common peroneal nerve (178 unilateral, 9 bilateral FES users). Clinically meaningful changes (ie, >.05m/s and >0.1m/s) and functional walking category derived from 10-m walking speed. An increase in walking speed was found to be highly significant (P<.001), both initially where a minimum clinically meaningful change was observed (.07m/s) and after 20 weeks with a substantial clinically meaningful change (.11m/s). After 20 weeks, treatment responders displayed a 27% average improvement in their walking speed. No significant training effect was found. Overall functional walking category was maintained or improved in 95% of treatment responders. FES of the dorsiflexors is a well-accepted intervention that enables clinically meaningful changes in walking speed, leading to a preserved or an increased functional walking category. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis

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

Qiu, Jun-jun; Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011

HOX transcript antisense RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in serous ovarian cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 andmore » OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression. - Highlights: • HOTAIR overexpression correlates with an aggressive tumour phenotype and a poor prognosis in SOC. • HOTAIR promotes SOC cell proliferation both in vitro and in vivo. • The proliferative role of HOTAIR is associated with regulation of the cell cycle and apoptosis.« less

Meta-analysis of mobile phone use and intracranial tumors.

PubMed

Lahkola, Anna; Tokola, Kari; Auvinen, Anssi

2006-06-01

A summary of epidemiologic evidence regarding the effect of mobile phone use on intracranial tumor risk was obtained by means of a meta-analysis. Reports of published studies on mobile phone use and intracranial tumors were sought. Altogether 12 relevant publications were identified from the PubMed database and reference lists of articles. Fixed or random effects analysis was carried out depending on the presence of heterogeneity between studies. Risk estimates were obtained for people who had used mobile phones for the longest periods of time (>5 years in most reports). A pooled estimate was calculated for all intracranial tumors combined and also separately for different histological tumor types. Separate analyses were conducted also based on the tumor location and type of mobile telephone network (NMT or GSM). Twelve studies with 2780 cases gave a pooled odds ratio (OR) of 0.98 [95% confidence interval (95% CI) 0.83-1.16] for all intracranial tumors related to mobile phone use. For gliomas, the pooled OR was 0.96 (95% CI 0.78-1.18), for meningiomas it was 0.87 (95% CI 0.72-1.05), and for acoustic neuromas it was 1.07 (95% CI 0.89-1.30). Little indication was found for increased risks of analogue or digital phone use or temporal or occipital tumors. The totality of evidence does not indicate a substantially increased risk of intracranial tumors from mobile phone use for a period of at least 5 years.

Transcatheter arterial embolization for upper gastrointestinal tract bleeding

PubMed Central

Širvinskas, Audrius; Smolskas, Edgaras; Brimienė, Vilma; Brimas, Gintautas

2017-01-01

Introduction Transcatheter arterial embolization is a possible treatment for patients with recurrent bleeding from the upper gastrointestinal tract after failed endoscopic management and is also an alternative to surgical treatment. Aim To analyze the outcomes of transcatheter arterial embolization and identify the clinical and technical factors that influenced the rates of morbidity and mortality. Material and methods A retrospective analysis was carried out, based on the data of 36 patients who underwent transcatheter arterial embolization for acute nonvariceal upper gastrointestinal bleeding in 2013 to 2015 in our center. An analysis was performed between early rebleeding rates, mortality and the following factors: patient sex, age, number of units of packed red blood cells and packed plasma administered to the patients, length of hospital stay, therapeutic or prophylactic embolization. Results The technical success rate of the embolization procedure was 100%. There were 15 (41.70%) therapeutic embolizations and 21 (58.3%) prophylactic embolizations. There was a 77.8% clinical success rate. Following embolization, 10 (27.80%) patients had repeated bleeding and 9 (25.0%) patients died. Significant associations were found between rebleeding and prophylactic embolization (OR = 10.53; p = 0.04) and between mortality and prophylactic embolization (OR = 10.53; p = 0.04) and units of packed red blood cells (OR = 1.25; p < 0.01). Conclusions In our experience, transcatheter arterial embolization is a safe treatment method for acute nonvariceal upper gastrointestinal bleeding and a possible alternative to surgery for high-risk patients. PMID:29362654

Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study

PubMed Central

Mattei, Francesca; Liverani, Silvia; Guida, Florence; Matrat, Mireille; Cenée, Sylvie; Azizi, Lamiae; Menvielle, Gwenn; Sanchez, Marie; Pilorget, Corinne; Lapôtre-Ledoux, Bénédicte; Luce, Danièle; Richardson, Sylvia; Stücker, Isabelle

2016-01-01

Background The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. Objectives The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. Methods We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case–control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. Results After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. Conclusions Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk. PMID:26911986

Problematic Internet Use in University Students: associated factors and differences of gender.

PubMed

Fernández-Villa, Tania; Alguacil Ojeda, Juan; Almaraz Gómez, Ana; Cancela Carral, José María; Delgado-Rodríguez, Miguel; García-Martín, Miguel; Jiménez-Mejías, Eladio; Llorca, Javier; Molina, Antonio José; Ortíz Moncada, Rocío; Valero-Juan, Luiz Félix; Martín, Vicente

2015-12-15

The aim of this paper is to make a descriptive analysis of Problematic Internet Use in college students, evaluating the possible association with health problems and addictive behaviors, as well as gender differences in user types. A total of 2,780 students participated in the study between 2011 and 2014, 29% of them being males (age 20.8 ± 5.1 years) and 71% females (age 20.3 ± 4.4 years). The prevalence of Problematic Internet Use (PIU) assessed by the Internet Addiction Test was 6.08%. Being under 21 years of age and studying for degrees in subjects other than the health sciences were associated factors with a higher frequency of this problem, no differences by gender or type of address were found. The results show a significant association with some health problems (migraines, back pain, excess weight or obesity, insufficient rest), psychological aspects (risk of eating disorders, risk of mental disorder, depression), family problems and discrimination; with no associations with substance use (alcohol, cannabis or tobacco) being found. Concerning the time of Internet use, weekly hours were significantly higher in women than in men, both the total time as for leisure. The analysis of the profile use in problematic users revealed that males are related to aspects of entertainment such as games or shopping online and females are related to aspects of socialization, such as chats and social networks.

Visualising the procedures in the influence of water on the ablation of dental hard tissue with erbium:yttrium-aluminium-garnet and erbium, chromium:yttrium-scandium-gallium-garnet laser pulses.

PubMed

Mir, Maziar; Gutknecht, Norbert; Poprawe, Reinhart; Vanweersch, Leon; Lampert, Friedrich

2009-05-01

The exact mechanism of the ablation of tooth hard tissue with most common wavelengths, which are 2,940 nm and 2,780 nm, is not yet clear. There are several different theories, but none of them has yet been established. Concepts and methods of looking at these mechanisms have been based on heat formation and transformation, and mathematical calculations evaluating the outcome of ablation, such as looking at the shape of cuts. This study provides a new concept, which is the monitoring of the direct interactions between laser light, water and enamel, with a high-speed camera. For this purpose, both the above-mentioned wavelengths were examined. Bovine anterior teeth were prepared as thin slices. Each imaged slice had a thickness close to that of the beam diameter so that the ablation effect could be shown in two dimensional pictures. The single images were extracted from the video-clips and then were animated. The following steps, explaining the ablation procedures during each pulse, were seen and reported: (1) low-output energy intensity in the first pulses that did not lead to an ablative effect; (2) bubble formation with higher output energy density; (3) the tooth surface during the pulse was covered with the plume of vapour (comparable with a cloud), and the margins of ablation on the tooth were not clear; (4) when the vapour bubble (cloud) was collapsing, an additional ablative process at the surface could be seen.

Multi-functional Magnetic Nanoparticles for Magnetic Resonance Imaging and Cancer Therapy

PubMed Central

Yallapu, Murali M.; Othman, Shadi F.; Curtis, Evan T.; Gupta, Brij K.; Jaggi, Meena; Chauhan, Subhash C.

2010-01-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapuetic agent for cancer therapy. PMID:21167595

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Yallapu, Murali M; Othman, Shadi F; Curtis, Evan T; Gupta, Brij K; Jaggi, Meena; Chauhan, Subhash C

2011-03-01

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

PubMed

Keleştimur, F; Aksu, A

1996-01-01

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Outcome of opening wedge high tibial osteotomy augmented with a Biosorb® wedge and fixed with a plate and screws in 124 patients with a mean of ten years follow-up.

PubMed

Saragaglia, Dominique; Blaysat, Marc; Inman, Dominic; Mercier, Numa

2011-08-01

The objective of this work was firstly to evaluate the long-term results of medial opening wedge high tibial osteotomy (HTO) and secondly to evaluate the tolerance and integration of a Biosorb® wedge (β Tricalcium Phosphate, SBM Company, Lourdes, France). The series consisted of 124 knees in 110 patients, 74 men and 36 women, with mean age of 53.23±10.68 years (range 32-74) and treated between June 1995 and November 2000 for medial compartment knee osteoarthritis by the senior author. The mean preoperative Lysholm and Tegner functional score was 65.44±13.32 (range 27-80) and the preoperative HKA angle was 172.51°±3.8° (range 162-179°). According to the modified Ahlbäck classification there were 27 stage I, 42 stage II, 44 stage III and 11 stage IV knees. All patients were reviewed clinically and radiologically with a mean follow-up of 10.39±1.98 years (range 8-14 years). Immediate postoperative complications consisted of nine undisplaced lateral tibial plateau fractures of no clinical significance, two deep vein thromboses and three pulmonary emboli which resolved with appropriate treatment. At a later stage, there were seven delayed unions without development of pseudarthrosis, and three screw breakages when the AO T-plate was used, leading to a secondary angulation in one case, requiring revision by femoral osteotomy. Postoperative mean weightbearing HKA angle was 182°±1.8° (range 178-186°) and 73.4% of axes were 184°±2°. Fifteen knees (12.1%) underwent total knee arthroplasty (TKA) after a mean delay of 8.87±3.04 years and were excluded from the final analysis. Concerning the long-term results (n = 107 knees), the mean Lysholm-Tegner score was 88±12.7 points (51-100) and the KOOS score was 86±14.6 points (25-100) with 94 patients satisfied or very satisfied (87.85%). In terms of the HTO survivorship curve, with failure consisting of revision to TKA or another operation, survival was 88.8% at five years and 74% at ten years. Concerning

Determination of caffeine, myosmine, and nicotine in chocolate by headspace solid-phase microextraction coupled with gas chromatography-tandem mass spectrometry.

PubMed

Müller, Christoph; Vetter, Florian; Richter, Elmar; Bracher, Franz

2014-02-01

The occurrence of the bioactive components caffeine (xanthine alkaloid), myosmine and nicotine (pyridine alkaloids) in different edibles and plants is well known, but the content of myosmine and nicotine is still ambiguous in milk/dark chocolate. Therefore, a sensitive method for determination of these components was established, a simple separation of the dissolved analytes from the matrix, followed by headspace solid-phase microextraction coupled with gas chromatography-tandem mass spectrometry (HS-SPME-GC-MS/MS). This is the first approach for simultaneous determination of caffeine, myosmine, and nicotine with a convenient SPME technique. Calibration curves were linear for the xanthine alkaloid (250 to 3000 mg/kg) and the pyridine alkaloids (0.000125 to 0.003000 mg/kg). Residuals of the calibration curves were lower than 15%, hence the limits of detection were set as the lowest points of the calibration curves. The limits of detection calculated from linearity data were for caffeine 216 mg/kg, for myosmine 0.000110 mg/kg, and for nicotine 0.000120 mg/kg. Thirty samples of 5 chocolate brands with varying cocoa contents (30% to 99%) were analyzed in triplicate. Caffeine and nicotine were detected in all samples of chocolate, whereas myosmine was not present in any sample. The caffeine content ranged from 420 to 2780 mg/kg (relative standard deviation 0.1 to 11.5%) and nicotine from 0.000230 to 0.001590 mg/kg (RSD 2.0 to 22.1%). © 2014 Institute of Food Technologists®

Risk assessment of genotoxic and carcinogenic alkenylbenzenes in botanical containing products present on the Chinese market.

PubMed

Ning, Jia; Cui, XinYue; Kong, XiangNan; Tang, YiFei; Wulandari, Riana; Chen, Lu; Wesseling, Sebas; Rietjens, Ivonne M C M

2018-05-01

In the present study, a risk assessment of plant food supplements (PFS), traditional Chinese medicines (TCM) and herbal teas containing alkenylbenzenes was performed using the Margin of Exposure (MOE) approach. The levels of alkenylbenzenes in botanical preparations collected on the Chinese market were quantified and the combined estimated daily intake (EDI) was determined using dose additivity. The combined EDI values obtained assuming equal potency of all alkenylbenzenes detected in the PFS, TCM and herbal teas were 0.3 to 14.3, 0.05 to 539.4 and 0.04 to 42.5 μg/kg bw/day, respectively. Calculating combined EDI values taking into account the toxic equivalency (TEQ) approach, the values for PFS, TCM and herbal teas were 0.3 to 7.7, 0.05 to 278.0 and 0.02 to 16.5 μg estragole equivalents/kg bw/day, respectively. The MOE values resulting from consumption of these PFS, TCM and one cup of herbal tea per day during life-time were generally lower than 10 000, suggesting a potential priority for risk management. For short-term exposure such as two weeks consumption, applying Haber's rule, only one TCM 6 () still had an MOE value below 10 000. It is concluded that selected consumption of Chinese botanical preparations raise a concern because of exposure to alkenylbenzenes, especially when exposure is for longer periods of time. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Outcomes of functional weight-bearing rehabilitation of Achilles tendon ruptures.

PubMed

Jackson, Gillian; Sinclair, Victoria F; McLaughlin, Charles; Barrie, James

2013-08-01

The introduction of functional rehabilitation for patients with Achilles tendon rupture has dramatically changed treatment programs for this condition. The authors introduced a functional weight-bearing protocol for patients with an acute Achilles tendon rupture treated operatively and nonoperatively in 2002. They hypothesized that no significant differences would exist in the rerupture rates and functional outcomes between the groups. Between 2002 and 2008, the authors collected data on 80 consecutive patients treated with a weight-bearing functional orthosis for complete Achilles tendon rupture. Following evidence-based counseling, 51 patients chose nonoperative treatment and 29 chose operative treatment. Outcome measures included rerupture rates, other complications, and functional scoring. The nonoperative group was a decade older (median age, 47 years [range, 27-80 years]) than the operative group (median age, 37 years [range, 24-55 years]). Rerupture was noted in 2 (4%) patients in the nonoperative treatment group and 1 (3%) patient in the operative group. Two (7%) patients in the operative group developed superficial wound infections and reported no nerve injuries. Median Achilles Tendon Total Rupture Score was 82 points in the nonoperative group and 94 in the operative group. Median Victorian Institute of Sports Assessment-Achilles tendinopathy questionnaire scores were 60 and 91 for the nonoperative and operative groups, respectively. Both groups had low rerupture rates. Functional scores, using the newly validated Achilles Tendon Total Rupture Score, were lower in the nonoperative group. Copyright 2013, SLACK Incorporated.

Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study.

PubMed

Barul, Christine; Carton, Matthieu; Radoï, Loredana; Menvielle, Gwenn; Pilorget, Corinne; Bara, Simona; Stücker, Isabelle; Luce, Danièle

2018-04-05

To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer. ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models. No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (OR = 1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (OR = 2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively). This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk.

The ablation threshold of Er;Cr:YSGG laser radiation in bone tissue

NASA Astrophysics Data System (ADS)

Benetti, Carolina; Zezell, Denise Maria

2015-06-01

In laser cut clinical applications, the use of energy densities lower than the ablation threshold causes increase of temperature of the irradiated tissue, which might result in an irreversible thermal damage. Hence, knowing the ablation threshold is crucial for insuring the safety of these procedures. The aim of this study was to determine the ablation threshold of the Er,Cr:YSGG laser in bone tissue. Bone pieces from jaws of New Zealand rabbits were cut as blocks of 5 mm × 8 mm and polished with sandpaper. The Er,Cr:YSGG laser used in this study had wavelength of 2780 nm, 20 Hz of frequency, and the irradiation condition was chosen so as to simulate the irradiation during a surgical procedure. The laser irradiation was performed with 12 different values of laser energy densities, between 3 J/cm2 and 42 J/cm2, during 3 seconds, resulting in the overlap of 60 pulses. This process was repeated in each sample, for all laser energy densities. After irradiation, the samples were analyzed by scanning electron microscope (SEM), and it was measured the crater diameter for each energy density. By fitting a curve that related the ablation threshold with the energy density and the corresponding diameter of ablation crater, it was possible to determine the ablation threshold. The results showed that the ablation threshold of the Er,Cr:YSGG in bone tissue was 1.95+/-0.42 J/cm2.

Tunable microwave absorbing nano-material for X-band applications

NASA Astrophysics Data System (ADS)

Sadiq, Imran; Naseem, Shahzad; Ashiq, Muhammad Naeem; Khan, M. A.; Niaz, Shanawer; Rana, M. U.

2016-03-01

The effect of rare earth elements substitution in Sr1.96RE0.04Co2Fe27.80Mn0.2O46 (RE=Ce, Gd, Nd, La and Sm) X-type hexagonal ferrites prepared by using sol gel autocombustion method was studied. The XRD and FTIR analysis show the single phase of the prepared material. The lattice constants a (Å) and c (Å) varies with the additives. The particle size measured by Scherer formula for all the samples varies in the range of 54-100 nm and confirmed by the TEM analysis. The average grain size measured by SEM analysis lies in the range of 0.672-1.01 μm for all the samples. The Gd-substituted ferrite has higher value of coercivity (526.06 G) among all the samples which could be a good material for longitudinal recording media. The results also indicate that the Gd-substituted sample has maximum reflection loss of -25.2 dB at 11.878 GHz, can exhibit the best microwave absorption properties among all the substituted samples. Furthermore, the minimum value of reflection loss shifts towards the lower and higher frequencies with the substitution of rare earth elements which confirms that the microwave absorption properties can be tuned with the substitution of rare earth elements in pure ferrites. The peak value of attenuation constant at higher frequency agrees well the reflection loss data.

Causes of death in critically ill multiple sclerosis patients.

PubMed

Karamyan, A; Brandtner, H; Grinzinger, S; Chroust, V; Bacher, C; Otto, F; Reisp, M; Hauer, L; Sellner, J

2017-10-01

Patients with multiple sclerosis (MS) experience higher mortality rates as compared to the general population. While the risk of intensive care unit (ICU) admission is also reported to be higher, little is known about causes of death CoD in critically ill MS patients. To study the causes of death (CoD) in the series of critically ill patients with MS verified by autopsy. We reviewed hospital electronic charts of MS patients treated at the neurological ICU of a tertiary care hospital between 2000 and 2015. We compared clinical and pathological CoD for those who were autopsied. Overall, 10 patients were identified (seven female; median age at death 65 years, range 27-80), and six of them were autopsied. The median MS duration prior to ICU admission was 27.5 years (range 1-50), and the median EDSS score at the time of ICU admission was 9 (range 5-9.5). The median length of ICU stay was 3 days (range 2-213). All the individuals in our series had experienced respiratory insufficiency during their ICU stay. The autopsy examination of brain tissue did not reveal evidences of MS lesions in one patient. In another patient, Lewy bodies were found on brain immunohistochemistry. Mortality in critically ill MS patients is largely driven by respiratory complications. Sporadic disparities between clinical and pathological findings can be expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Polyphenolic Compounds and Antioxidant Activity of Cold-Pressed Seed Oil from Finola Cultivar of Cannabis sativa L.

PubMed

Smeriglio, Antonella; Galati, Enza M; Monforte, Maria T; Lanuzza, Francesco; D'Angelo, Valeria; Circosta, Clara

2016-08-01

The aim of this study was to characterize the polyphenolic compounds and antioxidant activity of cold-pressed seed oil from Finola cultivar of industrial hemp (Cannabis sativa L.). Several methodologies have been employed to evaluate the in vitro antioxidant activity of Finola hempseed oil (FHSO) and both lipophilic (LF) and hydrophilic fractions (HF). The qualitative and quantitative composition of the phenolic fraction of FHSO was performed by HPLC analyses. From the results is evident that FHSO has high antioxidative activity, as measured by DPPH radical (146.76 mmol of TE/100 g oil), inhibited β-carotene bleaching, quenched a chemically generated peroxyl radical in vitro and showed high ferrous ion chelating activity. Reactivity towards 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation and ferric-reducing antioxidant power values were 695.2 µmol of TE/100g oil and 3690.6 µmol of TE/100 g oil respectively. FHSO contains a significant amount of phenolic compounds of which 2780.4 mg of quercetin equivalent/100 g of total flavonoids. The whole oil showed higher antioxidant activity compared with LF and HF. Our findings indicate that the significant antioxidant properties shown from Finola seed oil might generally depend on the phenolic compounds, especially flavonoids, such as flavanones, flavonols, flavanols and isoflavones. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Risk indicator for agricultural inputs of trace elements to Canadian soils.

PubMed

Sheppard, S C; Grant, C A; Sheppard, M I; de Jong, R; Long, J

2009-01-01

Trace elements (TEs) are universally present in environmental media, including soil, but agriculture uses some materials that have increased TE concentrations. Some TEs (e.g., Cu, Se, and Zn) are added to animal feeds to ensure animal health. Similarly, TEs are present in micronutrient fertilizers. In the case of phosphate fertilizers, some TEs (e.g., Cd) may be inadvertently elevated because of the source rock used in the manufacturing. The key question for agriculture is "After decades of use, could these TE additions result in the deterioration of soil quality?" An early warning would allow the development of best management practices to slow or reverse this trend. This paper discusses a model that estimates future TE concentrations for the 2780 land area polygons composing essentially all of the agricultural land in Canada. The development of the model is discussed, as are various metrics to express the risk related to TE accumulation. The elements As, Cd, Cu, Pb, Se, and Zn are considered, with inputs from the atmosphere, fertilizers, manures, and municipal biosolids. In many cases, steady-state concentrations could be toxic, but steady state is far in the future. In 100 yr, the soil concentrations (Century soil concentrations) are estimated to be up to threefold higher than present background, an impact even if not a problematic impact. The geographic distribution reflects agricultural intensity. Contributions from micronutrient fertilizers are perhaps the most uncertain due to the limited data available on their use.

Methionine+cystine requirement of broiler chickens fed low-density diets under tropical conditions.

PubMed

Aftab, Usama; Ashraf, Muhammad

2009-03-01

Two experiments were conducted to determine the M+C requirement of straight-run broiler chickens (Hubbard x Hubbard) during the period 4-21 (Exp. 1) and 21-40 (Exp. 2) days of age. Experiments were conducted during summer months (July-August) in open-sided houses, thus exposing chicks to chronic heat stress. Daily min-max temperature averaged 26-37C (Exp. 1) and 23-36C (Exp. 2). M+C deficient basal diets were formulated to contain low-nutrient-density, i.e., 2750 kcal per kg ME, 20.1% CP (Exp. 1), and 2780 kcal per kg ME, 17.0% CP (Exp. 2). Diets were supplemented with DL-methionine to provide total M+C level ranging from 0.64 to 0.89 % (six increments) and 0.54 to 0.79% (six increments), respectively in experiment 1 and 2. Requirements (0.95 of the maximum quadratic response) were found to be 0.77 and 0.75% total M+C, respectively for gain and feed efficiency, during 4-21 days; and 0.67% total M+C for both gain and feed efficiency during 21-40 days of age. Calculated on the digestible M+C basis, the estimates were 0.67 and 0.65% respectively for gain and feed efficiency during 4-21 days of age; and 0.60% for gain and feed efficiency during 21-40 days of age.

Adherence to secondary prophylaxis for rheumatic heart disease is underestimated by register data

PubMed Central

de Dassel, Jessica Langloh; Fittock, Marea Therese; Wilks, Sagen Cheyenne; Poole, Jane Elizabeth; Carapetis, Jonathan Rhys; Ralph, Anna P.

2017-01-01

Objective In high-burden Australian states and territories, registers of patients with acute rheumatic fever and rheumatic heart disease are maintained for patient management, monitoring of system performance and research. Data validation was undertaken for the Australian Northern Territory Rheumatic Heart Disease Register to determine quality and impact of data cleaning on reporting against key performance indicators: overall adherence, and proportion of patients receiving ≥80% of scheduled penicillin doses for secondary prophylaxis. Methods Register data were compared with data from health centres. Inconsistencies were identified and corrected; adherence was calculated before and after cleaning. Results 2780 penicillin doses were validated; 426 inconsistencies were identified, including 102 incorrect dose dates. After cleaning, mean adherence increased (63.5% to 67.3%, p<0.001) and proportion of patients receiving ≥80% of doses increased (34.2% to 42.1%, p = 0.06). Conclusions The Northern Territory Rheumatic Heart Disease Register underestimates adherence, although the key performance indicator of ≥80% adherence was not significantly affected. Program performance is better than hitherto appreciated. However some errors could affect patient management, as well as accuracy of longitudinal or inter-jurisdictional comparisons. Adequate resources are needed for maintenance of data quality in acute rheumatic fever/rheumatic heart disease registers to ensure provision of evidence-based care and accurate assessment of program impact. PMID:28562621

IND2, a pyrimido[1”,2”:1,5]pyrazolo[3,4-b]quinoline derivative, circumvents multi-drug resistance and causes apoptosis in colon cancer cells

PubMed Central

Karthikeyan, Chandrabose; Lee, Crystal; Moore, Joshua; Mittal, Roopali; Suswam, Esther A.; Abbott, Kodye L; Pondugula, Satyanarayana R.; Manne, Upender; Narayanan, Narayanan K.; Trivedi, Piyush; Tiwari, Amit K.

2014-01-01

Naturally occurring condensed quinolines have anticancer properties. In efforts to find active analogues, we designed and synthesized eight polycyclic heterocycles with a pyrimido[1”,2”:1,5]pyrazolo[3,4-b]quinoline framework (IND series). The compounds were evaluated for activity against colon (HCT-116 and S1-MI-80), prostate (PC3 and DU-145), breast (MCF-7 and MDAMB-231), ovarian (ov2008 and A2780), and hepatocellular (HepG2) cancer cells and against non-cancerous Madin Darby canine kidney (MDCK), mouse embryonic fibroblast (NIH/3T3), and human embryonic kidney cells (HEK293). IND-2, a 4-chloro-2-methyl pyrimido[1”,2”:1,5]pyrazolo[3,4-b]quinoline, exhibited more than tenfold selectivity and potent cytotoxic activity against colon cancer cells relative to the other cancer and non-cancer cells. With five additional colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo), IND-2 had similar cytotoxicity and selectivity, and submicromolar concentrations caused changes in the morphology of HCT-116 and HCT-15 cells. IND-2 did not activate the transactivating function of the pregnane X receptor (PXR), indicating that it does not induce PXR-regulated ABCB1 or ABCG2 transporters. Indeed, IND-2 was not a substrate of ABCB1 or ABCG2, and it induced cytotoxicity in HEK293 cells overexpressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. IND-2 was cytotoxic to resistant colon carcinoma S1-MI-80 cells, approximately three- and fivefold more than SN-38 and topotecan, respectively. In HCT-116 colon cancer cells, IND-2 produced concentration-dependent changes in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation. These findings suggest that, by increasing apoptosis, IND-2 has potential therapeutic efficacy for colorectal cancer. PMID:25537531

Selective inhibition of tumor cell associated Vacuolar-ATPase 'a2' isoform overcomes cisplatin resistance in ovarian cancer cells.

PubMed

Kulshrestha, Arpita; Katara, Gajendra K; Ginter, Jordyn; Pamarthy, Sahithi; Ibrahim, Safaa A; Jaiswal, Mukesh K; Sandulescu, Corina; Periakaruppan, Ramayee; Dolan, James; Gilman-Sachs, Alice; Beaman, Kenneth D

2016-06-01

Development of resistance to platinum compounds significantly hinders successful ovarian cancer (OVCA) treatment. In tumor cells, dysregulated pH gradient across cell membranes is a key physiological mechanism of metastasis/chemo-resistance. These pH alterations are mediated by aberrant activation of key multi-subunit proton pumps, Vacuolar-ATPases (V-ATPases). In tumor cells, its 'a2' isoform (V-ATPase-V0a2) is a component of functional plasma-membrane complex and promotes tumor invasion through tumor-acidification and immuno-modulation. Its involvement in chemo-resistance has not been studied. Here, we show that V-ATPase-V0a2 is over-expressed in acquired-cisplatin resistant OVCA cells (cis-A2780/cis-TOV112D). Of all the 'a' subunit isoforms, V-ATPase-V0a2 exhibited an elevated expression on plasma membrane of cisplatin-resistant cells compared to sensitive counterparts. Immuno-histochemistry revealed V-ATPase-V0a2 expression in both low grade (highly drug-resistant) and high grade (highly recurrent) human OVCA tissues indicating its role in a centralized mechanism of tumor resistance. In cisplatin resistant cells, shRNA mediated inhibition of V-ATPase-V0a2 enhanced sensitivity towards both cisplatin and carboplatin. This improved cytotoxicity was mediated by enhanced cisplatin-DNA-adduct formation and suppressed DNA-repair pathway, leading to enhanced apoptosis. Suppression of V0a2 activity strongly reduced cytosolic pH in resistant tumor cells, which is known to enhance platinum-associated DNA-damage. As an indicator of reduced metastasis and chemo-resistance, in contrast to plasma membrane localization, a diffused cytoplasmic localization of acidic vacuoles was observed in V0a2-knockdown resistant cells. Interestingly, pre-treatment with monoclonal V0a2-inhibitory antibody enhanced cisplatin cytotoxicity in resistant cells. Taken together, our findings suggest that the isoform specific inhibition of V-ATPase-V0a2 could serve as a therapeutic strategy for chemo

Sodium consumption among hypertensive adults advised to reduce their intake: national health and nutrition examination survey, 1999-2004.

PubMed

Ayala, Carma; Gillespie, Cathleen; Cogswell, Molly; Keenan, Nora L; Merritt, Robert

2012-07-01

The authors estimated the prevalence of taking action to reduce intake related to actual sodium consumption among 2970 nonpregnant US adults 18 years and older with self-reported hypertension by using data from the National Health and Nutrition Examination Survey 1999-2004. Adjusted multiple linear regression assessed differences in mean sodium intake by action status. A total of 60.5% of hypertensive adults received advice to reduce sodium intake. Of this group, 83.7% took action to reduce sodium. Action to reduce sodium intake differed significantly by age, race/ethnicity, and use of an antihypertensive. The mean (±standard error) sodium intake among hypertensive adults was 3341±37 mg and differed by sex, age, race/ethnicity, education, and body mass index (P<.05), with the lowest intake among adults aged 65 years and older (2780±48 mg). Mean intake did not differ significantly by action status either overall or by subgroup except for one age category: among patients 65 years and older, mean intake was significantly lower among those who took action (2715±63 mg) than among those who did not (3401±206 mg; P=.0124). Regardless of action, mean intake was well above 1999-2004 recommendations for daily sodium intake and about twice as high as the current recommendation for hypertensive adults (1500 mg). © 2012 Wiley Periodicals, Inc.

Metabolomics Analysis of Metabolic Effects of Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibition on Human Cancer Cells

PubMed Central

Tolstikov, Vladimir; Nikolayev, Alexander; Dong, Sucai; Zhao, Genshi; Kuo, Ming-Shang

2014-01-01

Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide–consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry–based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer) and HCT-116 (colorectal cancer) cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA), and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC)-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level. PMID:25486521

Regulation of human MutYH DNA glycosylase by the E3 ubiquitin ligase mule.

PubMed

Dorn, Julia; Ferrari, Elena; Imhof, Ralph; Ziegler, Nathalie; Hübscher, Ulrich

2014-03-07

Oxidation of DNA is a frequent and constantly occurring event. One of the best characterized oxidative DNA lesions is 7,8-dihydro-8-oxoguanine (8-oxo-G). It instructs most DNA polymerases to preferentially insert an adenine (A) opposite 8-oxo-G instead of the appropriate cytosine (C) thus showing miscoding potential. The MutY DNA glycosylase homologue (MutYH) recognizes A:8-oxo-G mispairs and removes the mispaired A giving way to the canonical base excision repair that ultimately restores undamaged guanine (G). Here we characterize for the first time in detail a posttranslational modification of the human MutYH DNA glycosylase. We show that MutYH is ubiquitinated in vitro and in vivo by the E3 ligase Mule between amino acids 475 and 535. Mutation of five lysine residues in this region significantly stabilizes MutYH, suggesting that these are the target sites for ubiquitination. The endogenous MutYH protein levels depend on the amount of expressed Mule. Furthermore, MutYH and Mule physically interact. We found that a ubiquitination-deficient MutYH mutant shows enhanced binding to chromatin. The mutation frequency of the ovarian cancer cell line A2780, analyzed at the HPRT locus can be increased upon oxidative stress and depends on the MutYH levels that are regulated by Mule. This reflects the importance of tightly regulated MutYH levels in the cell. In summary our data show that ubiquitination is an important regulatory mechanism for the essential MutYH DNA glycosylase in human cells.

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS.

PubMed

Almeida, Gilberto S; Bawn, Carlo M; Galler, Martin; Wilson, Ian; Thomas, Huw D; Kyle, Suzanne; Curtin, Nicola J; Newell, David R; Maxwell, Ross J

2017-09-01

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ( 1 H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD + ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild-type (WT) and PARP1 knock-out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. 1 H-MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD + levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD + levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD + levels in the temozolomide-treated group. The combination of rucaparib and temozolomide did not prevent the NAD + depletion caused by temozolomide treatment. The 1 H-MRS results show that NAD + levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD + would be valuable. Copyright © 2017 John Wiley & Sons, Ltd.

High temperature radiance spectroscopy measurements of solid and liquid uranium and plutonium carbides

NASA Astrophysics Data System (ADS)

Manara, D.; De Bruycker, F.; Boboridis, K.; Tougait, O.; Eloirdi, R.; Malki, M.

2012-07-01

In this work, an experimental study of the radiance of liquid and solid uranium and plutonium carbides at wavelengths 550 nm ⩽ λ ⩽ 920 nm is reported. A fast multi-channel spectro-pyrometer has been employed for the radiance measurements of samples heated up to and beyond their melting point by laser irradiation. The melting temperature of uranium monocarbide, soundly established at 2780 K, has been taken as a radiance reference. Based on it, a wavelength-dependence has been obtained for the high-temperature spectral emissivity of some uranium carbides (1 ⩽ C/U ⩽ 2). Similarly, the peritectic temperature of plutonium monocarbide (1900 K) has been used as a reference for plutonium monocarbide and sesquicarbide. The present spectral emissivities of solid uranium and plutonium carbides are close to 0.5 at 650 nm, in agreement with previous literature values. However, their high temperature behaviour, values in the liquid, and carbon-content and wavelength dependencies in the visible-near infrared range have been determined here for the first time. Liquid uranium carbide seems to interact with electromagnetic radiation in a more metallic way than does the solid, whereas a similar effect has not been observed for plutonium carbides. The current emissivity values have also been used to convert the measured radiance spectra into real temperature, and thus perform a thermal analysis of the laser heated samples. Some high-temperature phase boundaries in the systems U-C and Pu-C are shortly discussed on the basis of the current results.

Triterpenoidal saponins from the fruits of Gleditsia caspica with proapoptotic properties.

PubMed

Shaheen, Usama; Ragab, Ehab A; Abdalla, Ashraf N; Bader, Ammar

2018-01-01

Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, 1 H- 13 C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showed that caspicaosides M, N and L, respectively, exhibited high cytotoxic activity with IC 50  ≤ 10 μM (72 h) at least against one of the three used cancer cell lines, MCF 7, A2780 and HT 29; and were 2-34 folds selective against the normal fibroblasts (MRC 5). All compounds also induced apoptosis and caused G 2 /M arrest in MCF 7 cells (24 h); thus showing pro-apoptotic properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

PubMed

Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

Modified filter-aided sample preparation (FASP) method increases peptide and protein identifications for shotgun proteomics.

PubMed

Ni, Mao-Wei; Wang, Lu; Chen, Wei; Mou, Han-Zhou; Zhou, Jie; Zheng, Zhi-Guo

2017-01-30

Mass spectrometry (MS)-based protein identification depends mainly on protein extraction and digestion. Although sodium dodecyl sulfate (SDS) can preclude enzymatic digestion and interfere with MS analysis, it is still the most widely used surfactant in these steps. To overcome these disadvantages, a SDS-compatible proteomic technique for SDS removal prior to MS-based analyses was developed, namely filter-aided sample preparation (FASP). Herein, based on the effectiveness of sodium deoxycholate and a detergent removal spin column, we developed a modified FASP (mFASP) method and compared its overall performance, total number of peptides and proteins identified for shotgun proteomic experiments with that of the FASP method. Identification of 4570 ± 392 and 9139 ± 317 peptides and description of 862 ± 46 and 1377 ± 33 protein groups with two or more peptides from the ovarian cancer cell line A2780 was accomplished by FASP and mFASP methods, respectively. The mFASP method (21.2 ± 0.2%) had higher average peptide to protein coverage than FASP method (13.2 ± 0.5%). More hydrophobic peptides were identified by mFASP than by FASP, as indicated by the GRAVY score distribution. The reported method enables reliable and efficient identification of proteins and peptides in whole-cell extracts containing SDS. The new approach allows for higher throughput (the simultaneous identification of more proteins), a more comprehensive investigation of proteins, and potentially the discovery of new biomarkers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of Noncovalent Platinum Drug–Protein Interactions on Drug Efficacy: Use of Fluorescent Conjugates as Probes for Drug Metabolism

PubMed Central

Benedetti, Brad T.; Peterson, Erica J.; Kabolizadeh, Peyman; Martínez, Alberto; Kipping, Ralph; Farrell, Nicholas P.

2012-01-01

The overall efficacy of platinum based drugs is limited by metabolic deactivation through covalent drug–protein binding. In this study the factors affecting cytotoxicity in the presence of glutathione, human serum albumin (HSA) and whole serum binding with cisplatin, BBR3464, and TriplatinNC, a “noncovalent” derivative of BBR3464, were investigated. Upon treatment with buthionine sulfoximine (BSO), to reduce cellular glutathione levels, cisplatin and BBR3464-induced apoptosis was augmented whereas TriplatinNC-induced cytotoxicity was unaltered. Treatment of A2780 ovarian carcinoma cells with HSA-bound cisplatin (cisplatin/HSA) and cisplatin preincubated with whole serum showed dramatic decreases in cytotoxicity, cellular accumulation, and DNA adduct formation compared to treatment with cisplatin alone. Similar effects are seen with BBR3464. In contrast, TriplatinNC, the HSAbound derivative (TriplatinNC/HSA), and TriplatinNC pretreated with whole serum retained identical cytotoxic profiles and equal levels of cellular accumulation at all time points. Confocal microscopy of both TriplatinNC-NBD, a fluorescent derivative of TriplatinNC, and TriplatinNC-NBD/HSA showed nuclear/nucleolar localization patterns, distinctly different from the lysosomal localization pattern seen with HSA. Cisplatin-NBD, a fluorescent derivative of cisplatin, was shown to accumulate in the nucleus and throughout the cytoplasmwhile the localization of cisplatin-NBD/HSA was limited to lysosomal regions of the cytoplasm. The results suggest that TriplatinNCcan avoid high levels of metabolic deactivation currently seen with clinical platinum chemotherapeutics, and therefore retain a unique cytotoxic profile after cellular administration. PMID:21548575

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

PubMed

Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

Er,Cr:YSGG laser-assisted surgical treatment of peri-implantitis with 1-year reentry and 18-month follow-up.

PubMed

Azzeh, Manal M

2008-10-01

Peri-implantitis may occur because of biologic or mechanical factors. It can be treated by a variety of methods. In the present case report, treatment was attempted by regenerative osseous surgery associated with an erbium, chromium-doped:yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser. A 28-year-old, non-smoking male complained of gum recession around an implant in the area of upper left central incisor. After clinical examination and radiographs, it was found that there was 2 mm recession, a probing depth of 7 mm, mobility grade one, and bone mesially and distally. Regenerative osseous surgery was performed using an Er,Cr:YSGG laser (2,780 nm) at different settings to open the flap, remove the granulation tissues, perforate the bone, and clean the implant surface. A bone graft and a bioabsorbable membrane were used for bone regeneration. The patient was reevaluated at 3, 6, 12 (with reentry), and 18 months postoperatively. At 3, 6, and 12 months postoperatively, there were no reported complications, with probing depths of 3 to 5 mm, <1 mm recession, no bleeding or implant mobility, and good bone formation. Slight pus discharge was present at 12 months. At 18 months postoperatively, probing depth was 2 mm, recession was <1 mm, there was no bleeding, implant mobility, or discharge, and there was better bone formation. The results were satisfactory to the patient and the clinician. The Er,Cr:YSGG laser enabled regenerative osseous surgery around an implant with no complications and with high patient and clinician satisfaction and confidence.

The burden of headache disorders in Pakistan: methodology of a population-based nationwide study, and questionnaire validation

PubMed Central

2013-01-01

Background Large geographical gaps in our knowledge of the prevalence and burden of headache disorders include Pakistan, a country with major problems of poverty, illiteracy and security. We report implementation in this country of standard methods developed by Lifting The Burden (LTB) for population-based burden-of-headache studies. Methods We surveyed six locations from the four provinces: Lahore and Multan (Punjab), Karachi and Sukkur (Sindh), Abbottabad (Khyber Pakhtunkhwa) and Gwadar (Baluchistan). We randomly selected rural and urban households in each, which were visited by trained non-medical interviewers from the same locations. One randomly selected adult member (18–65 years) of each household was interviewed using LTB’s structured questionnaire translated into Urdu, the national language. Validation was performed among patients and accompanying attendants in three (urban and rural) medical facilities. After responding to the questionnaire, these participants were re-interviewed and diagnosed by a neurologist (gold standard). Results The survey was completed by 4,223 respondents (1,957 [46.3%] male, 2,266 [53.7%] female, 1,443 [34.2%] urban, 2,780 [65.8%] rural, mean age 34.4 ± 11.0 years). The participation rate was 89.5%. There were 180 participants (46.1% male, 53.9% female, 41.7% urban, 58.3% rural, mean age 39.4 ± 14.2 years) in the validation sample, of whom 147 (81.7%) reported headache in the last year. The questionnaire was 100% sensitive in screening for headache and for headache on ≥15 days/month, and showed good agreement with the gold-standard diagnoses (kappa = 0.77). It was relatively insensitive for TTH. The questionnaire’s default diagnosis of probable MOH when medication overuse accompanied headache on ≥15 days/month was not supported by evidence of causation in most cases seen by the neurologist. In public-health terms, precise diagnosis in these cases matters less than reliably detecting the coexistence of

Survey of aflatoxin concentrations in wild bird seed purchased in Texas.

PubMed

Henke, S E; Gallardo, V C; Martinez, B; Balley, R

2001-10-01

The use of backyard feeders to attract avian wildlife is a common practice throughout the United States. However, feeding wildlife may create a problem due to aflatoxin, a harmful fungal metabolite, which can affect wildlife that are fed contaminated grain. Our study was initiated to determine if songbirds were being exposed to aflatoxin-contaminated feed throughout Texas. Bags of wild bird seed (n = 142) were purchased from grain cooperatives, grocery stores, and pet shops located in the panhandle, central, south, east, and west regions of Texas during spring and summer 1999. Aflatoxin concentrations in bird seed ranged from non-detectable to 2,780 micrograms/kg. Overall, 17% of samples had aflatoxin concentrations greater than 100 micrograms/kg, of which 83% contained corn as an ingredient. Retail establishment effects were noted in the southern and western regions of Texas, with average concentrations of aflatoxin greater from bags of bird seed purchased from grain cooperatives, followed by pet shops, then grocery stores. Regional differences in aflatoxin levels were not apparent from bags of seed purchased at pet shops: however, regional differences were noted in aflatoxin levels from seeds obtained at grocery stores and grain cooperatives. Average aflatoxin concentration from seed purchased at grocery stores was greatest in the panhandle region, followed by the remaining regions. Within grain cooperatives, the panhandle, south, and west regions of Texas exhibited higher levels of aflatoxin-contaminated bird seed than cooperatives within the east and central regions of Texas. Granivorous songbirds in Texas are exposed to aflatoxins at backyard feeders, which may be a significant morbidity and mortality factor.

[Changes in knowledge, attitudes, and smoking behavior among young people in Germany. Results of repeated, representative surveys by the BZgA].

PubMed

Orth, B; Töppich, J

2010-02-01

Following an increase in tobacco consumption among 12 to 17 year olds between 1993 and 1997, a policy mix comprising various structural and behavioral prevention measures was implemented in Germany. One element of this policy mix is the "rauchfrei" ("smoke-free") youth campaign of the BZgA (Federal Centre for Health Education), a combination of media that reaches a large number of youth, personal communication, and setting-based interventions. The aim is to prevent young people from starting to smoke and to promote the cessation of smoking at an early stage. Based on a multistage intervention model, wide coverage of the measures should be achieved among young people, as well as changes in knowledge, attitudes, social norms, and behavioral intentions. Based on the intervention model, repeated, representative cross-sectional surveys were conducted to examine the development of these indicators and of tobacco consumption. Five studies were conducted during the period from 2003 to 2008, each comprising between 1,220 and 2,780 computer-assisted telephone interviews with randomly selected young people between the ages of 12 and 17. The percentage of young people reached by information offered on the subject of not smoking rose between 2003 and 2008. Participation in school-based prevention measures also rose. There was an increase in knowledge regarding the harmful substances contained in cigarette smoke, and in the percentage of young people who rated active and passive smoking as being harmful to health. In addition, the attitude towards smoking of young people who have never smoked became more critical, as did that perceived in the social environment. The proportion of young people who smoke declined substantially, from 27.5% (2001) to 15.4% (2008), and there was been a major rise in the number who have never smoked, from 40.5% (2001) to 60.6% (2008). The change in knowledge-based risk assessments, attitudes, and social norms should be further promoted by mass media

Recruiting Human Microbiome Shotgun Data to Site-Specific Reference Genomes

PubMed Central

Xie, Gary; Lo, Chien-Chi; Scholz, Matthew; Chain, Patrick S. G.

2014-01-01

The human body consists of innumerable multifaceted environments that predispose colonization by a number of distinct microbial communities, which play fundamental roles in human health and disease. In addition to community surveys and shotgun metagenomes that seek to explore the composition and diversity of these microbiomes, there are significant efforts to sequence reference microbial genomes from many body sites of healthy adults. To illustrate the utility of reference genomes when studying more complex metagenomes, we present a reference-based analysis of sequence reads generated from 55 shotgun metagenomes, selected from 5 major body sites, including 16 sub-sites. Interestingly, between 13% and 92% (62.3% average) of these shotgun reads were aligned to a then-complete list of 2780 reference genomes, including 1583 references for the human microbiome. However, no reference genome was universally found in all body sites. For any given metagenome, the body site-specific reference genomes, derived from the same body site as the sample, accounted for an average of 58.8% of the mapped reads. While different body sites did differ in abundant genera, proximal or symmetrical body sites were found to be most similar to one another. The extent of variation observed, both between individuals sampled within the same microenvironment, or at the same site within the same individual over time, calls into question comparative studies across individuals even if sampled at the same body site. This study illustrates the high utility of reference genomes and the need for further site-specific reference microbial genome sequencing, even within the already well-sampled human microbiome. PMID:24454771

MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1.

PubMed

Wu, Di-di; Li, Xue-Song; Meng, Xiao-Na; Yan, Jing; Zong, Zhi-Hong

2016-08-01

Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3'-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

Geothermal Power Potential in the Tatun Volcano Group, Taiwan

NASA Astrophysics Data System (ADS)

Tseng, H. H.; Song, S.

2013-12-01

Recent energy issues have concentrated the attention on finding alternative ones. National demands for renewable and sustainable energy increase rapidly, especially the geothermal power production, which is viewed as the most potential opportunity. This study attempts to estimate the geothermal powers in the Tatung Volcano Group (TVG), Taiwan and evaluate the possibility to develop the Enhanced Geothermal System. Tatung Volcano Group is located at the northwest part of Taiwan. It has violent volcanism during 0.8-0.20Ma, and is still active with many thermal manifestations. The young volcanic activity provides the TVG with high geothermal gradient and is well suitable for exploiting geothermal resources. Many explorations on geothermal energy have been accomplished in this area during1966-1973. They included resistivity survey, magnetic prospecting, gravity method, seismic prospecting and etc. In this study, we base on previous data and apply the probabilistic volumetric method proposed by Geotherm EX Inc., modified from the approach introduced by the USGS to evaluate the geothermal power potential in TVG. Meanwhile, use a Monte Carlo simulation technique to calculate the probability distribution of potentially recoverable energy reserves. The results show that the mean value is 270Mw, and P50 is 254Mw for 30 years, separately. Furthermore, the power potential of enhanced geothermal system in TVG is also estimated by the quantitative model proposed by Massachusetts Institute of Technology (MIT 2006). The results suggest that the mean value is 3,000 MW and P50 is 2,780 MW for 30 years, separately.

Use of the erbium, chromium:yttrium-scandium-gallium-garnet laser on human enamel tissues. Influence of the air-water spray on the laser-tissue interaction: scanning electron microscope evaluations.

PubMed

Olivi, Giovanni; Angiero, Francesca; Benedicenti, Stefano; Iaria, Giuseppe; Signore, Antonio; Kaitsas, Vassilios

2010-11-01

The study investigated the influence of varying amounts of air/water spray and the energy used by an erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) 2,780 nm laser when treating dental tissues. The morphological effects produced by the laser interaction on healthy human enamel were evaluated by scanning electron microscopy (SEM). The vestibular and lingual surfaces of ten molars were treated with laser at different power settings; each surface was subdivided into cervical, median, and occlusal parts and treated with different proportions of water spray; the series contained 60 tooth portions. Treatment differed in terms of power setting and air/water percentage. All specimens were then subjected to dehydration and metallisation. At SEM evaluation, the classic aspect of laser-treated enamel was visible: grooves, flakes, shelves and sharp edges, indicative of micro-explosion rather than melting. Vaporisation of the tissue created a clear delimitation from surrounding healthy tissue, with partial respect to the prismatic structure of the treated enamel. The aspect of the enamel was rarely type 1 Silverstone but more frequently type 2 or 3, with prismatic structure not respected and/or completely disordered. These morphological differences appeared to be correlated with the inclination of the laser beam aimed at the enamel prisms and with the percentage of air/water used. The laser system analysed showed itself to be effective at removing human dental enamel. The results appeared to be closely correlated with the variation of the percentage of the laser's water-air spray.

Asphalt-derived high surface area activated porous carbons for carbon dioxide capture.

PubMed

Jalilov, Almaz S; Ruan, Gedeng; Hwang, Chih-Chau; Schipper, Desmond E; Tour, Josiah J; Li, Yilun; Fei, Huilong; Samuel, Errol L G; Tour, James M

2015-01-21

Research activity toward the development of new sorbents for carbon dioxide (CO2) capture have been increasing quickly. Despite the variety of existing materials with high surface areas and high CO2 uptake performances, the cost of the materials remains a dominant factor in slowing their industrial applications. Here we report preparation and CO2 uptake performance of microporous carbon materials synthesized from asphalt, a very inexpensive carbon source. Carbonization of asphalt with potassium hydroxide (KOH) at high temperatures (>600 °C) yields porous carbon materials (A-PC) with high surface areas of up to 2780 m(2) g(-1) and high CO2 uptake performance of 21 mmol g(-1) or 93 wt % at 30 bar and 25 °C. Furthermore, nitrogen doping and reduction with hydrogen yields active N-doped materials (A-NPC and A-rNPC) containing up to 9.3% nitrogen, making them nucleophilic porous carbons with further increase in the Brunauer-Emmett-Teller (BET) surface areas up to 2860 m(2) g(-1) for A-NPC and CO2 uptake to 26 mmol g(-1) or 114 wt % at 30 bar and 25 °C for A-rNPC. This is the highest reported CO2 uptake among the family of the activated porous carbonaceous materials. Thus, the porous carbon materials from asphalt have excellent properties for reversibly capturing CO2 at the well-head during the extraction of natural gas, a naturally occurring high pressure source of CO2. Through a pressure swing sorption process, when the asphalt-derived material is returned to 1 bar, the CO2 is released, thereby rendering a reversible capture medium that is highly efficient yet very inexpensive.

Mixed copper-platinum complex formation could explain synergistic antiproliferative effect exhibited by binary mixtures of cisplatin and copper-1,10-phenanthroline compounds: An ESI-MS study.

PubMed

Pivetta, Tiziana; Lallai, Viola; Valletta, Elisa; Trudu, Federica; Isaia, Francesco; Perra, Daniela; Pinna, Elisabetta; Pani, Alessandra

2015-10-01

Cisplatin, cis-diammineplatinum(II) dichloride, is a metal complex used in clinical practice for the treatment of cancer. Despite its great efficacy, it causes adverse reactions and most patients develop a resistance to cisplatin. To overcome these issues, a multi-drug therapy was introduced as a modern approach to exploit the drug synergy. A synergistic effect had been previously found when testing binary combinations of cisplatin and three copper complexes in vitro, namely, Cu(phen)(OH2)2(OClO3)2, [Cu(phen)2(OH2)](ClO4)2 and [Cu(phen)2(H2dit)](ClO4)2,(phen=1,10-phenanthroline, H2dit=imidazolidine-2-thione), against the human acute T-lymphoblastic leukaemia cell line (CCRF-CEM). In this work [Cu(phen)2(OH2)](ClO4)2 was also tested in combination with cisplatin against cisplatin-resistant sublines of CCRF-CEM (CCRF-CEM-res) and ovarian (A2780-res) cancer cell lines. The tested combinations show a synergistic effect against both the types of resistant cells. The possibility that this effect was caused by the formation of new adducts was considered and mass spectra of solutions containing cisplatin and one of the three copper complexes at a time were measured using electrospray ionisation at atmospheric-pressure mass spectrometry (ESI-MS). A mixed complex was detected and its stoichiometry was assessed on the basis of the isotopic pattern and the results of tandem mass spectrometry experiments. The formed complex was found to be [Cu(phen)(OH)μ-(Cl)2Pt(NH3)(H2O)](+). Copyright © 2015 Elsevier Inc. All rights reserved.

The limits of informed consent.

PubMed Central

1975-01-01

The patient, a 59-year-old man, was referred to a psychiatric hospital with what appeared initially to be the signs and symptoms of mental disorder. In hospital a lesion of the brain was diagnosed and surgery was proposed to relieve the condition. The patient, however, during this and subsequent admissions to hospital, refused operation. His refusal to consent was regarded as valid as he seemed to have good insight into his condition. Finally, under section 26 of the Mental Health Act, he was treated surgically. Unfortunately the patient died six weeks later of intracranial haemorrhage. Three comments are made on this case - two by psychiatrists, Dr K Davison and Dr Ashley Robin, the other by a professor of Christian ethics, Professor F C Blackie. Both psychiatrists argue that when a patient's mind is affected by mental or organic illness to the degree that 'he cannot bring a rational and conscious mind' to the question of his treatment then the doctor, in consultation with the relatives, making clear to them the likely course of events if an operation is not performed, must take whatever is the proper course of action, in this case surgery. In this view, such an operation performed immediately the diagnosis was confirmed might not have been so complicated. Professor Blackie, commending 'the attempt to regard the patient as a responsible human being' with a 'moral right to be consulted on all aspects of treatment', questions in this patient the limits to which the appeal to reason was carried. He concludes that 'in this situation the advice and consent of the family must weigh more heavily than the statements of the patient'. PMID:2780

The association of falls and various physical activities in Chinese nonagenarians/centenarians.

PubMed

Hao, Qiukui; Yang, Ming; Luo, Li; Hai, Shan; Ding, Xiang; Dong, Birong

2015-01-01

Little is known about the relationship between falls and various physical activities in the oldest old people. This study was conducted to observe the association of fall with various exercise habits and farm work in very old people. In this cross-sectional study of a Chinese cohort of men and women aged 90-108 years, we observed the association of fall with habitual (current and former) farm work and exercise in very old people. The population included 805 unrelated Chinese nonagenarians and centenarians (68.94% of the subjects were women, with a mean age of 93.70 years). In the women, the subjects with a continuing exercise habit had a significantly lower prevalence of fall than those without an exercise habit; the subjects who had never exercised had a significantly higher prevalence of fall than those who exercised. In men, there was no significant difference in the prevalence of these habits between the subjects with and without fall. After adjusting for age, gender, body mass index, educational levels, life styles, vision levels and temperament, we found that current habitual farm work (OR=1.755 95% CI (1.107, 2.780)) and exercise OR=0.666 95% CI (0.445, 0.997) had a significant odds ratio for fall; among the females, continuing exercise (vs. having never exercised) had a significant odds ratio for fall (OR=0.620 95% CI (0.395, 0.973)). Habitual farm work might be positively associated with fall; however, habitual exercise might be negatively associated with fall in Chinese long-lived old people. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Aspergillus nodules; another presentation of Chronic Pulmonary Aspergillosis.

PubMed

Muldoon, Eavan G; Sharman, Anna; Page, Iain; Bishop, Paul; Denning, David W

2016-08-18

There are a number of different manifestations of pulmonary aspergillosis. This study aims to review the radiology, presentation, and histological features of lung nodules caused by Aspergillus spp. Patients were identified from a cohort attending our specialist Chronic Pulmonary Aspergillosis clinic. Patients with cavitating lung lesions, with or without fibrosis and those with aspergillomas or a diagnosis of invasive aspergillosis were excluded. Demographic, laboratory, and clinical data and radiologic findings were recorded. Thirty-three patients with pulmonary nodules and diagnostic features of aspergillosis (histology and/or laboratory findings) were identified. Eighteen (54.5 %) were male, mean age 58 years (range 27-80 years). 19 (57.6 %) were former or current smokers. The median Charleston co-morbidity index was 3 (range 0-7). All complained of a least one of; dyspnoea, cough, haemoptysis, or weight loss. None reported fever. Ten patients (31 %) did not have an elevated Aspergillus IgG, and only 4 patients had elevated Aspergillus precipitins. Twelve patients (36 %) had a single nodule, six patients (18 %) had between 2 and 5 nodules, 2 (6 %) between 6 and 10 nodules and 13 (39 %) had more than 10 nodules. The mean size of the nodules was 21 mm, with a maximum size ranging between 5-50 mm. No nodules had cavitation radiographically. The upper lobes were most commonly involved. Histology was available for 18 patients and showed evidence of granulation tissue, fibrosis, and visualisation of fungal hyphae. Pulmonary nodules are a less common manifestation of aspergillosis in immunocompetent patients. Distinguishing these nodules from other lung pathology may be difficult on CT findings alone.

Increase in soil stable carbon isotope ratio relates to loss of organic carbon: results from five long-term bare fallow experiments.

PubMed

Menichetti, Lorenzo; Houot, Sabine; van Oort, Folkert; Kätterer, Thomas; Christensen, Bent T; Chenu, Claire; Barré, Pierre; Vasilyeva, Nadezda A; Ekblad, Alf

2015-03-01

Changes in the (12)C/(13)C ratio (expressed as δ(13)C) of soil organic C (SOC) has been observed over long time scales and with depth in soil profiles. The changes are ascribed to the different reaction kinetics of (12)C and (13)C isotopes and the different isotopic composition of various SOC pool components. However, experimental verification of the subtle isotopic shifts associated with SOC turnover under field conditions is scarce. We determined δ(13)C and SOC in soil sampled during 1929-2009 in the Ap-horizon of five European long-term bare fallow experiments kept without C inputs for 27-80 years and covering a latitudinal range of 11°. The bare fallow soils lost 33-65% of their initial SOC content and showed a mean annual δ(13)C increase of 0.008-0.024‰. The (13)C enrichment could be related empirically to SOC losses by a Rayleigh distillation equation. A more complex mechanistic relationship was also examined. The overall estimate of the fractionation coefficient (ε) was -1.2 ± 0.3‰. This coefficient represents an important input to studies of long-term SOC dynamics in agricultural soils that are based on variations in (13)C natural abundance. The variance of ε may be ascribed to site characteristics not disclosed in our study, but the very similar kinetics measured across our five experimental sites suggest that overall site-specific factors (including climate) had a marginal influence and that it may be possible to isolate a general mechanism causing the enrichment, although pre-fallow land use may have some impact on isotope abundance and fractionation.

Bypassing multidrug resistant ovarian cancer using ultrasound responsive doxorubicin/curcumin co-deliver alginate nanodroplets.

PubMed

Baghbani, Fatemeh; Moztarzadeh, Fathollah

2017-05-01

Ultrasound-responsive perfluorocarbon nanoemulsions are a class of new multifunctional smart nanocarriers which combine diagnostic properties with therapeutic properties and release their drug payload in a controlled manner in response to ultrasound. Therefore, combination therapy using chemotherapeutic and chemosensitizing agents co-entrapped in these nanocarriers seems beneficial for cancer treatment. In the present study, multifunctional smart alginate/perfluorohexane nanodroplets were developed for co-delivery of doxorubicin and curcumin (a strong chemosensitizer). The nanodroplets with the average particle size of 55.1nm were synthesized via nanoemulsion process. The entrapment efficiency of doxorubicin was 92.3%. To improve curcumin entrapment into the alginate shell, Span 60 was added to the formulation as a co-surfactant and finally curcumin entrapment of about 40% was achieved. Ultrasound-mediated drug release kinetic was evaluated at two different frequencies of 28kHz (low frequency) and 1MHz (high frequency). Low frequency ultrasound resulted in higher triggered drug release from nanodroplets. The nanodroplets showed strong ultrasound contrast via droplet to bubble transition as confirmed via B-mode ultrasound imaging. Enhanced cytotoxicity in adriamycin-resistant A2780 ovarian cancer cells was observed for Dox-Cur-NDs compared to Dox-NDs because of the synergistic effects of doxorubicin and curcumin. However, ultrasound irradiation significantly increased the cytotoxicity of Dox-Cur-NDs. Finally, in vivo ovarian cancer treatment using Dox/Cur-NDs combined with ultrasound irradiation resulted in efficient tumor regression. According to the present study, nanotherapy of multidrug resistant human ovarian cancer using ultrasound responsive doxorubicin/curcumin co-loaded alginate-shelled nanodroplets combined with ultrasound irradiation could be a promising modality for the future of cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Rational design of dicarboxylato platinum(II) complexes with purine-mimetic ligands as novel anticancer agents.

PubMed

Hoffmann, Kamil; Wiśniewska, Joanna; Wojtczak, Andrzej; Sitkowski, Jerzy; Denslow, Agnieszka; Wietrzyk, Joanna; Jakubowski, Mateusz; Łakomska, Iwona

2017-07-01

Six novel platinum(II) complexes containing purine-mimetic ligands (5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp), 7-isobutyl-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp)) and dicarboxylato ligands (glutarato (glut) or cyclobutane-1,1-dicarboxylato (CBDC)) have been prepared and characterized with multinuclear magnetic resonance ( 1 H, 13 C, 15 N, 195 Pt) NMR, infrared (IR) and X-ray crystallography. Spectroscopic data in solid state and in solution unambiguously confirm the square-planar geometry of Pt(II) with two monodentate N3-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine ligands and one O-chelating dicarboxylato ligand. Next, the effect of all the platinum(II) compounds on the viability of normal or cancer cells and their putative mechanisms of action have been investigated. Of the studied platinum(II) complexes, two ([Pt(glut)(dbtp) 2 ] and [Pt(CBDC)(dbtp) 2 ]) overcame the cisplatin resistance in human ovarian tumor cells (A2780cis or OVCAR-3) and arrested the cell cycle at S phase in mice mammary gland cancer cells (4T1), which indicates a mechanism of action different from that of cisplatin. Interestingly, preliminary in vivo toxicity assays revealed that both compounds tested in mice ([Pt(glut)(dbtp) 2 ] 3 and [Pt(CBDC)(dbtp) 2 ] 6) were less toxic in vivo than cisplatin or oxaliplatin. Additionally, compound 6 did not cause myelosuppression and showed over fivefold less accumulation in the liver than its glutarato analog 3. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term outcome of elderly patients requiring intensive care admission for abdominal pathologies: survival and quality of life.

PubMed

Merlani, P; Chenaud, C; Mariotti, N; Ricou, B

2007-05-01

Medical developments have allowed the management of patients aged over 70 years with severe abdominal pathologies requiring intensive care unit (ICU) admission. These patients require enhanced life support and present a high ICU mortality. We investigated the outcome and quality of life (QOL) of elderly patients 2 years after their ICU stay for abdominal pathologies. Patients aged 70 years or over with abdominal pathologies, admitted to our ICU over a period of 2 years, were included. Two years following their ICU stay, a letter informed the patients about the present study. Consent to participate was obtained by telephone. QOL was assessed by the Euro-QOL and Short Form-36 questionnaires. Other patient-centered outcomes were evaluated. Overall, 2780 patients were admitted to the ICU during the study period; 141 (5%) patients were eligible; 112 of the 141 (79%) survived their ICU stay, 95 (67%) survived their hospital stay and 52 (37%) were alive 2 years after their ICU stay; 36 of the 52 survivors (69%) answered the questionnaire. Their QOL 2 years after their ICU stay was decreased in comparison with an age-matched population. Eighty-one per cent of patients lived at home and 57% were totally independent. They perceived their ICU stay as positive and 75% stated that they would agree to go through intensive care again. Factors associated with 2-year survival were the absence of co-morbidity, absence of malignancy and a lower Simplified Acute Physiology II score on ICU admission. A high mortality rate and a decrease in QOL were observed in elderly patients with severe abdominal pathologies. Nonetheless, these patients were able to adapt well to their physical disabilities.

Anti-tumor and Anti-angiogenic Effects of Aspirin-PC in Ovarian Cancer

PubMed Central

Huang, Yan; Lichtenberger, Lenard M.; Taylor, Morgan; Bottsford-Miller, Justin N.; Haemmerle, Monika; Wagner, Michael J.; Lyons, Yasmin; Pradeep, Sunila; Hu, Wei; Previs, Rebecca A.; Hansen, Jean M.; Fang, Dexing; Dorniak, Piotr L.; Filant, Justyna; Dial, Elizabeth J.; Shen, Fangrong; Hatakeyama, Hiroto; Sood, Anil K.

2016-01-01

To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC vs. aspirin on 3 human (A2780, SKOV3ip1, HeyA8), and a mouse (ID8) ovarian cancer cell line over an 8-day culture period. In the in vivo studies, the aspirin test drugs were studied alone and in the presence of a VEGF-A inhibitor (bevacizumab or B20), due to an emerging role for platelets in tumor growth following anti-angiogenic therapy, and we examined their underlying mechanisms. Aspirin-PC was more potent (vs. aspirin) in blocking the growth of both human and mouse ovarian cancer cells in monolayer culture. Using in vivo model systems of ovarian cancer, we found that aspirin-PC significantly reduced ovarian cancer growth by 50–90% (depending on the ovarian cell line/density). The efficacy was further enhanced in combination with Bevacizumab or B20. The growth-inhibitory effect on ovarian tumor mass and number of tumor nodules was evident, but less pronounced for aspirin and the VEGF inhibitors alone. There was no detectable gastrointestinal toxicity. Both aspirin and aspirin-PC also inhibited cell proliferation, angiogenesis and increased apoptosis of ovarian cancer cells. In conclusion, PC-associated aspirin markedly inhibits the growth of ovarian cancer cells, which exceeds that of the parent drug, in both cell culture and in mouse model systems. We also found that both aspirin-PC and aspirin have robust anti-neoplastic action in the presence of VEGF blocking drugs. PMID:27638860

CARS microscopy for the monitoring of lipid storage in C. elegans

NASA Astrophysics Data System (ADS)

Enejder, Annika; Brackmann, Christian; Axäng, Claes; Åkeson, Madeleine; Pilon, Marc

2008-02-01

After several years of proof-of-principle measurements and focus on technological development, it is timely to make full use of the capabilities of CARS microscopy within the biosciences. We have here identified an urgent biological problem, to which CARS microscopy provides unique insights and consequently may become a widely accepted experimental procedure. In order to improve present understanding of mechanisms underlying dysfunctional metabolism regulation reported for many of our most wide-spread diseases (obesity, diabetes, cardio-vascular diseases etc.), we have monitored genetic and environmental impacts on cellular lipid storage in the model organism C. elegans in vivo in a full-scale biological study. Important advantages of CARS microscopy could be demonstrated compared to present technology, i.e. fluorescence microscopy of labelled lipid stores. The fluorescence signal varies not only with the presence of lipids, but also with the systemic distribution of the fluorophore and the chemical properties of the surrounding medium. By instead probing high-density regions of CH bonds naturally occurring in the sample, the CARS process was shown to provide a consistent representation of the lipid stores. The increased accumulation of lipid stores in mutants with deficiencies in the insulin and transforming growth factor signalling pathways could hereby be visualized and quantified. Furthermore, spectral CARS microscopy measurements in the C-H bond region of 2780-2930 cm -1 provided the interesting observation that this accumulation comes with a shift in the ordering of the lipids from gel- to liquid phase. The present study illustrates that CARS microscopy has a strong potential to become an important instrument for systemic studies of lipid storage mechanisms in living organisms, providing new insights into the phenomena underlying metabolic disorders.

Cytotoxicity and cellular response mechanisms of water-soluble platinum(II) complexes of lidocaine and phenylcyanamide derivatives.

PubMed

Tabrizi, Leila; Chiniforoshan, Hossein

2017-02-01

Three new platinum(II) complexes of lidocaine and phenylcyanamide derivative ligands of formula K[Pt(3,5-(NO 2 ) 2 pcyd) 2 (LC)], 1, K[Pt(3,5-(CF 3 ) 2 pcyd) 2 (LC)], 2, K[Pt(3,5-Cl 2 pcyd) 2 (LC)], 3 (LC: lidocaine, 3,5-(NO 2 ) 2 pcyd: 3,5-dinitro phenylcyanamide, 3,5-(CF 3 ) 2 pcyd: 3,5-bis(trifluoromethyl) phenylcyanamide, 3,5-Cl 2 pcyd: 3,5-dichloro phenylcyanamide) have been synthesized and fully characterized. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. The complexes 1-3 revealed a significant in vitro antiproliferative activity against human ovarian carcinoma (A2780), colorectal adenocarcinoma (HT29), breast (MCF-7), liver hepatocellular carcinoma (HepG-2) and lung adenocarcinoma (A549) cancer cell lines. All the complexes are more active than cisplatin and follow the trend 1 > 2 > 3. Mechanistic studies showed that the trend in cytotoxicity of the Pt(II) complexes is mainly consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which consequently results in the loss of mitochondrial membrane potential and apoptosis induction. The complex 1 caused to approximately 80-fold higher DNA platination level with respect to cisplatin. The complexes 1-3 can considerably stimulate the production of hydrogen peroxide in a time-dependent manner. Also, the complexes 1-3 induced an increase in reactive oxygen species (ROS) production that was superior to that induced by antimycin. The complex 1 had the most effect on ROS production in comparison with other complexes.

Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa

PubMed Central

Kosack, Cara S.; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng'ang'a, Anne; Bita, André; Zahinda, Jean-Paul B. N.; Fransen, Katrien

2017-01-01

ABSTRACT Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable. PMID:28747371

Characteristics and Outcomes of Patients with Ewing Sarcoma Over 40 Years of Age at Diagnosis

PubMed Central

Karski, Erin E.; Matthay, Katherine K.; Neuhaus, John M.; Goldsby, Robert E.; DuBois, Steven G.

2012-01-01

Background The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥ 40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. Methods This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥ 40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Results Patients ≥ 40 years of age were more likely to have extra-skeletal tumors (66.1% v 31.7%; p<0.001), axial tumors (64.0% v 57.2%; p=0.01), and metastatic disease at diagnosis (35.5% v 30.0%; p=0.04) compared to younger patients. Five-year survival for those age ≥ 40 and age < 40 were 40.6% and 54.3%, respectively (p<0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63 - 2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Conclusion Patients ≥ 40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. PMID:22959474

Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis.

PubMed

Karski, Erin E; Matthay, Katherine K; Neuhaus, John M; Goldsby, Robert E; Dubois, Steven G

2013-02-01

The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p < 0.001), axial tumors (64.0% vs. 57.2%; p = 0.01), and metastatic disease at diagnosis (35.5% vs. 30.0%; p = 0.04) compared to younger patients. Five-year survival for those age ≥40 and age <40 were 40.6% and 54.3%, respectively (p < 0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63-2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Patients ≥40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improving cancer care for American Indians with cervical cancer in the Indian Health Service (IHS) system - Navigation may not be enough.

PubMed

Dockery, Lauren E; Motwani, Anita; Ding, Kai; Doescher, Mark; Dvorak, Justin D; Moore, Kathleen N; Holman, Laura L

2018-04-01

Patient navigation programs have been shown to positively impact cancer outcomes for minority populations. Little is known regarding the effects of these programs on American Indian (AI) populations. The purpose of this study is to characterize the impact of a patient navigation program on AI cervical cancer patients at a tertiary care center. A retrospective review of all AI cervical cancer patients receiving navigation services and a cohort of AI patients treated prior to navigation services was performed. Additional comparisons were made between those with and without Indian Health Service (IHS) funding. Summary statistics were used to describe demographic, clinical characteristics, treatment, and survivorship across groups. Of 55 patients identified, 34 received navigation and 21 did not. In navigated patients, median age was 46years (27-80years) compared with 42years (17-68years) in pre-navigation patients (p=0.53). There was no difference between stage at diagnosis (p=0.73). No difference was noted in treatment received between groups (p=0.48). Distance traveled for treatment between groups did not differ (p=0.46). Median time to initiation of treatment was not different between groups, 30.5days vs. 27.5days (p=0.18). Among patients with IHS funding, navigation services did not alter time to initiation of treatment (p=0.57), and there was no difference in completion of prescribed therapy between groups (92% navigated vs 100% pre-navigation). Navigation services for AI cervical cancer patients did not alter initiation or completion of treatment. Navigation programs may provide less tangible benefits to AI cervical cancer patients and further study is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunotherapy targeting folate receptor induces cell death associated with autophagy in ovarian cancer

PubMed Central

Wen, Yunfei; Graybill, Whitney S.; Previs, Rebecca A.; Hu, Wei; Ivan, Cristina; Mangala, Lingegowda S.; Zand, Behrouz; Nick, Alpa M.; Jennings, Nicholas B.; Dalton, Heather J.; Sehgal, Vasudha; Ram, Prahlad; Lee, Ju-Seog; Vivas-Mejia, Pablo E.; Coleman, Robert L.; Sood, Anil K.

2014-01-01

Purpose Cancer cells are highly dependent on folate metabolism, making them susceptible to drugs that inhibit folate receptor activities. Targeting overexpressed folate receptor alpha (FRα) in cancer cells offers a therapeutic opportunity. We investigated the functional mechanisms of MORAB-003 (farletuzumab), a humanized monoclonal antibody against FRα, in ovarian cancer models. Experimental Design We first examined FRα expression in an array of human ovarian cancer cell lines and then assessed the in vivo effect of MORAB-003 on tumor growth and progression in several orthotopic mouse models of ovarian cancer derived from these cell lines. Molecular mechanisms of tumor cell death induced by MORAB-003 were investigated by cDNA and protein expression profiling analysis. Mechanistic studies were performed to determine the role of autophagy in MORAB-003–induced cell death. Results MORAB-003 significantly decreased tumor growth in the high-FRα IGROV1 and SKOV3ip1 models but not in the low-FRα A2780 model. MORAB-003 reduced proliferation but had no significant effect on apoptosis. Protein expression and cDNA microarray analyses showed that MORAB-003 regulated an array of autophagy-related genes. It also significantly increased expression of LC3 isoform II and enriched autophagic vacuolization. Blocking autophagy with hydroxychloroquine or bafilomycin A1 reversed the growth inhibition induced by MORAB-003. In add, alteration of FOLR1 gene copy number significantly correlated with shorter disease-free survival in patients with ovarian serous cystadenocarcinoma. Conclusions MORAB-003 displays prominent antitumor activity in ovarian cancer models expressing FRα at high levels. Blockade of folate receptor by MORAB-003 induced sustained autophagy and suppressed cell proliferation. PMID:25416196

Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity

PubMed Central

Gooden, M J M; Wiersma, V R; Boerma, A; Leffers, N; Boezen, H M; ten Hoor, K A; Hollema, H; Walenkamp, A M E; Daemen, T; Nijman, H W; Bremer, E

2014-01-01

Background: In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). Methods: CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. Results: sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29–4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. Conclusions: High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours. PMID:24518602

The impact of pediatric obesity on hospitalized children with lower respiratory tract infections in the United States.

PubMed

Okubo, Yusuke; Nochioka, Kotaro; Testa, Marcia A

2018-04-01

Obesity is the most common public health problem and is a clinically complicating risk factor among hospitalized children. The impact of pediatric obesity on the severity and morbidity of lower respiratory tract infections remains unclear. We conducted a retrospective cohort study of bronchitis and pneumonia among children aged 2-20 years using hospital discharge records. The data were obtained from the Kid's Inpatient Database in 2003, 2006, 2009, and 2012, and were weighted to estimate the number of hospitalizations in the United States. We used the International Classification of Diseases, Ninth Revision, Clinical Modification code (278.0×) to classify whether the patient was obese or not. We investigated the associations between pediatric obesity and use of mechanical ventilation using multivariable logistic regression model. In addition, we ascertained the relationships between pediatric obesity, comorbid blood stream infections, mean healthcare cost, and length of hospital stay. We estimated a total of 133 602 hospitalizations with pneumonia and bronchitis among children aged between 2 and 20 years. Obesity was significantly associated with use of mechanical ventilation (adjusted OR 2.90, 95% CI 2.15-3.90), comorbid bacteremia or septicemia (adjusted OR 1.58, 95% CI 1.03-2.44), elevated healthcare costs (adjusted difference $383, 95%CI $276-$476), and prolonged length of hospital stay (difference 0.32 days, 95%CI 0.23-0.40 days), after adjusting for patient and hospital characteristics using multivariable logistic regression models. Pediatric obesity is an independent risk factor for severity and morbidity among pediatric patients with lower respiratory tract infections. These findings suggest the importance of obesity prevention for pediatric populations. © 2017 John Wiley & Sons Ltd.

Integrated modeling of the dynamic meteorological and sea surface conditions during the passage of Typhoon Morakot

NASA Astrophysics Data System (ADS)

Lee, Han Soo; Yamashita, Takao; Hsu, John R.-C.; Ding, Fei

2013-01-01

In August 2009, Typhoon Morakot caused massive flooding and devastating mudslides in the southern Taiwan triggered by extremely heavy rainfall (2777 mm in 4 days) which occurred during its passage. It was one of the deadliest typhoons that have ever attacked Taiwan in recent years. In this study, numerical simulations are performed for the storm surge and ocean surface waves, together with dynamic meteorological fields such as wind, pressure and precipitation induced by Typhoon Morakot, using an atmosphere-waves-ocean integrated modelling system. The wave-induced dissipation stress from breaking waves, whitecapping and depth-induced wave breaking, is parameterized and included in the wave-current interaction process, in addition to its influence on the storm surge level in shallow water along the coast of Taiwan. The simulated wind and pressure field captures the characteristics of the observed meteorological field. The spatial distribution of the accumulated rainfall within 4 days, from 00:00 UTC 6 August to 00:00 UTC 10 August 2009, shows similar patterns as the observed values. The 4-day accumulated rainfall of 2777 mm at the A-Li Shan mountain weather station for the same period depicted a high correlation with the observed value of 2780 mm/4 days. The effects of wave-induced dissipation stress in the wave-current interaction resulted in increased surge heights on the relatively shallow western coast of Taiwan, where the bottom slope of the bathymetry ranges from mild to moderate. The results also show that wave-breaking has to be considered for accurate storm surge prediction along the east coast of Taiwan over the narrow bank of surf zone with a high horizontal resolution of the model domain.

Can differences in physical activity by socio-economic status in European adolescents be explained by differences in psychosocial correlates? A mediation analysis within the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study.

PubMed

De Cocker, Katrien; Artero, Enrique G; De Henauw, Stefaan; Dietrich, Sabine; Gottrand, Frédéric; Béghin, Laurent; Hagströmer, Maria; Sjöström, Michael; Plada, Maria; Manios, Yannis; Mauro, Beatrice; Molnár, Dénes; Moreno, Luis A; Ottevaere, Charlene; Valtueña, Jara; Maes, Lea; De Bourdeaudhuij, Ilse

2012-11-01

Socio-economic status (SES) has been positively associated with physical activity (PA) levels in adolescents. In order to tackle these social inequalities, information is needed about the underlying mechanisms of this association. The present study aimed to investigate the potential mediating role of psychosocial correlates of PA on the relationship between SES and PA in European adolescents. Cross-sectional study testing the mediating role of psychosocial correlates in the SES-PA association using the product-of-coefficients test of MacKinnon. Ten European cities in nine different countries, the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Adolescents (n 2780) aged 12·5-17·49 years self-reported on PA (moderate-to-vigorous intensity PA and total PA), SES indicators (education of the mother and Family Affluence Scale) and psychosocial correlates of PA (stage of change, attitudes, awareness, modelling, social support, self-efficacy, benefits, barriers and environmental correlates). SES (Family Affluence Scale) was significantly associated with moderate-to-vigorous intensity PA. According to single-mediator models, this association was significantly mediated by stage of change (t = 3·6, P ≤ 0·001), awareness (t = 2·7, 0·001 < P ≤ 0·01), modelling (t = 4·8, P ≤ 0·001), self-efficacy (t = 2·5, 0·01

Study of the interaction of 1,4-dihydropyridine derivatives with glucocorticoid hormone receptors from the rat liver.

PubMed

Vaitkuviene, Aida; Ulinskaite, Audrone; Meskys, Rolandas; Duburs, Gunars; Klusa, Vija; Liutkevicius, Evaldas

2006-01-01

Seventeen derivatives of 1,4-dihydropyridine (DHP) series were tested in vitro for their ability to inhibit [1,2,4-(3)H]-dexamethasone binding to glucocorticoid receptor from the rat liver cytosol. Depending on structural features and inhibiting activities, the compounds can be divided into three groups. The first group (nifedipine, foridone, J-6-163, OSI-4164 and OSI-7724) had the highest activity: they inhibited specific ligand-receptor binding by 70-80% at concentrations of 10(-5) M and 10(-4) M, with apparent IC(50)values of 1.5-6.0 muM. The second group (cerebrocrast, diethone, OSI-1211 and OSI-7265) was active at concentration of 10(-4) M, and their IC(50) values were 23-45 muM; compound OSI-5003 was almost inactive. Both groups are compounds with scarce water solubility, more or less lipophilic. The third group of compounds comprises ionogenic compounds (organic cations or anions with corresponding inorganic counterions): most of them are water-soluble (glutapyrone, carbatone, gammapyrone, OSI-2780, OSI-1580, OSI-2140) or liposome-forming (A-74). They lack the above-mentioned activity. Among the first two groups, compounds possessing more bulky substituents in positions 3 and 5 are less active. The aromatic ring in the position 4 is essential for the optimal activity. It seems that there is a bell-shaped dependence of activity upon lipophilicity. In general, the compounds of the first group are strong Ca-antagonists, while the second group includes moderate Ca-antagonists, but each group comprises also compounds which lack Ca antagonistic activity. All compounds of the third group lack Ca antagonistic properties.

Monepantel induces autophagy in human ovarian cancer cells through disruption of the mTOR/p70S6K signalling pathway

PubMed Central

Bahrami, Farnaz; Pourgholami, Mohammad H; Mekkawy, Ahmed H; Rufener, Lucien; Morris, David L

2014-01-01

We have recently shown that the novel anthelmintic drug monepantel (MPL) inhibits growth, proliferation and colony formation, arrests the cell cycle and induces cleavage of PARP-1 in ovarian cancer cell lines. Here we report on the mechanism behind the anticancer properties of MPL. The cytotoxic effect of MPL on ovarian cancer cells (OVCAR-3 and A2780) was investigated employing a panel of tests used for the detection of apoptosis and autophagy. Apoptosis and autophagy were defined by caspase activity, DNA-laddering, Annexin-V and acridine orange (AO) staining. Autophagy markers such as LC3B, SQSTM1/p62 and mammalian target of rapamycin (mTOR) pathway related proteins were assessed by western blotting and ELISA techniques. MPL did not activate caspases 3 or 8, nor did it alter the percentage of Annexin V positive stained cells. Failure to cause DNA laddering and the inability of z-VAD-fmk to block the MPL antiproliferative effects led to the ruling out of apoptosis as the mechanism behind MPL-induced cell death. On the other hand, accumulation of acidic vacuoles with distinct chromatin morphology and an increase in punctuate localization of green fluorescent protein-LC3B, and MPL-induced changes in the expression of SQSTM1/p62 were all indicative of MPL-induced autophagy. Consistent with this, we found inhibition of mTOR phosphorylation leading to suppression of the mTOR/p70S6K signalling pathway. Our findings provide the first evidence to show that MPL triggers autophagy through the deactivation of mTOR/p70S6K signalling pathway. PMID:25232497

Human umbilical blood mononuclear cell-derived mesenchymal stem cells serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice.

PubMed

Hu, Weihua; Wang, Jing; He, Xiangfeng; Zhang, Hongyi; Yu, Fangliu; Jiang, Longwei; Chen, Dengyu; Chen, Junsong; Dou, Jun

2011-01-01

Ovarian cancer causes more deaths than any other cancer of the female reproductive system, and its overall cure rate remains low. The present study investigated human umbilical blood mononuclear cell (UBMC)-derived mesenchymal stem cells (UBMC-MSCs) as interleukin-21 (IL-21) gene delivery vehicles for ovarian cancer therapy in nude mice. MSCs were isolated from UBMCs and the expanded cells were phenotyped by flow cytometry. Cultured UBMCs were differentiated into osteocytes and adipocytes using appropriate media and then the UBMC-MSCs were transfected with recombinant pIRES2-IL-21-enhancement green fluorescent protein. UBMC-MSCs expressing IL-21 were named as UBMC-MSC-IL-21. Mice with A2780 ovarian cancer were treated with UBMC-MSC-IL-21 intravenously, and the therapeutic efficacy was evaluated by the tumor volume and mouse survival. To address the mechanism of UBMC-MSC-IL-21 against ovarian cancer, the expression of IL-21, natural killer glucoprotein 2 domain and major histocompatibility complex class I chain-related molecules A/B were detected in UBMC-MSC-IL-21 and in the tumor sites. Interferon-γ-secreting splenocyte numbers and natural killer cytotoxicity were significantly increased in the UBMC-MSC-IL-21-treated mice as compared with the UBMC-MSCs or the UBMC-MSC-mock plasmid-treated mice. Most notably, tumor growth was delayed and survival was prolonged in ovarian-cancer-bearing mice treated with UBMC-MSC-IL-21. Our data provide important evidence that UBMC-MSCs can serve as vehicles for IL-21 gene delivery and inhibit the established tumor. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Chemosensitizing effects of metformin on cisplatin- and paclitaxel-resistant ovarian cancer cell lines.

PubMed

Dos Santos Guimarães, Isabella; Ladislau-Magescky, Taciane; Tessarollo, Nayara Gusmão; Dos Santos, Diandra Zipinotti; Gimba, Etel Rodrigues Pereira; Sternberg, Cinthya; Silva, Ian Victor; Rangel, Leticia Batista Azevedo

2017-11-21

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. Primary cytoreductive surgery with adjuvant taxane-platinum chemotherapy is the standard treatment to fight ovarian cancer, however, their side effects are severe, and chemoresistance emerges at high rates. Therefore, EOC clinic urges for novel treatment strategies to reverse chemoresistance and to improve the survival rates. Metformin has been shown to act in synergy with certain anti-cancer agents, overcoming chemoresistance in various types of tumors. This paper aims to investigate the use of metformin as a new treatment option for cisplatin- and paclitaxel-resistant ovarian cancer. The effects of metformin alone or in combination with conventional drugs on resistant EOC cell lines were investigated using the MTT assay for cell proliferation; Flow Cytometry analysis for cell cycle and the mRNA expression was analyzed using the real-time PCR technique. We found that metformin exhibited antiproliferative effects in paclitaxel-resistant A2780-PR, and in cisplatin-resistant ACRP cell lines. The combined therapy containing conventional drugs and metformin improved the effect of the treatment in cell proliferation rate, especially in the resistant cells. We found that metformin, in clinical relevant doses, could significantly reduce the mRNA expression of inflammatory cytokines and NF-κB signaling pathway. Taken together, our observations suggest that metformin inhibits the inflammatory pathway induced by paclitaxel and cisplatin treatment. Furthermore, metformin in combination with paclitaxel or cisplatin improved the sensitivity in drug-resistant ovarian cancer cells. Therefore, metformin may be beneficial treatment strategy, particularly in patients with tumors refractory to platinum and taxanes. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Laser assisted periodontal treatment: from bactericidal effect to local modification of the host response

NASA Astrophysics Data System (ADS)

Ciurescu, Codruţa.; Teslaru, Silvia; Zetu, Liviu; Ciurescu, Daniel

2016-03-01

The aim of the present short-term study is to investigate efficiency of laser therapy as adjunct to conventional periodontal therapy in patients with chronic periodontitis. Methods. The study protocol included 44 patients (20 males, 24 females; age 45-60) with moderate and advanced chronic periodontitis, recruited in Private Clinic Krondent (Brasov, Romania). The patients were randomly assigned in two groups, one group (test-sites group, 22 patients) treated by ultrasonic scaling and root planning followed by laser therapy (940 nm diode laser and 2780 nm Er:Cr:YAG laser) and second group (control-sites group, 22 patients) treated only by ultrasonic scaling and root planning. All patients were submitted to initial evaluation, recording of bleeding on probing (BOP) and probing of pockets depth (PPD), oral hygiene instruction and motivation. Indices BOP and PPD for the assessed periodontal sites were also recorded at 8 weeks, 16 weeks and 24 weeks after treatment. Results. Periodontal inflammatory parameters PPD (PPD>=4mm) were significantly lower in test-sites group as compared with control-sites group at 2 months (82% vs. 90%), 4 months (42% vs. 62%), and 6 months (11% vs. 30%).Periodontal parameters BOP were lower among patients in control-sites group and test-sites group at 2 months (38% vs. 32%), and significantly lower in test-sites group at 4 months (42% vs.26%), and 6 months (44% vs. 24%). Conclusions. The additional use of laser therapy increases significantly the efficiency of periodontal treatment comparing with conventional periodontal therapy.

Challenges in microarray class discovery: a comprehensive examination of normalization, gene selection and clustering

PubMed Central

2010-01-01

Background Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre-processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization. Result We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered), missing value imputation (2), standardization of data (2), gene selection (19) or clustering method (11). The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that background correction is

ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19.

PubMed

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V; Dion, Patrick A; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A; Williams, Kelly L; Blair, Ian P; Nicholson, Garth A; Gonzalez-Perez, Paloma; Brown, Robert H; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-11-07

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19

PubMed Central

Takahashi, Yuji; Fukuda, Yoko; Yoshimura, Jun; Toyoda, Atsushi; Kurppa, Kari; Moritoyo, Hiroyoko; Belzil, Veronique V.; Dion, Patrick A.; Higasa, Koichiro; Doi, Koichiro; Ishiura, Hiroyuki; Mitsui, Jun; Date, Hidetoshi; Ahsan, Budrul; Matsukawa, Takashi; Ichikawa, Yaeko; Moritoyo, Takashi; Ikoma, Mayumi; Hashimoto, Tsukasa; Kimura, Fumiharu; Murayama, Shigeo; Onodera, Osamu; Nishizawa, Masatoyo; Yoshida, Mari; Atsuta, Naoki; Sobue, Gen; Fifita, Jennifer A.; Williams, Kelly L.; Blair, Ian P.; Nicholson, Garth A.; Gonzalez-Perez, Paloma; Brown, Robert H.; Nomoto, Masahiro; Elenius, Klaus; Rouleau, Guy A.; Fujiyama, Asao; Morishita, Shinichi; Goto, Jun; Tsuji, Shoji

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3–5 years from onset. Familial ALS (FALS) comprises 5%–10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions. PMID:24119685

Physicochemical, Antioxidant, and Cytotoxic Properties of Xao Tam Phan (Paramignya trimera) Root Extract and Its Fractions.

PubMed

Nguyen, Van Tang; Sakoff, Jennette A; Scarlett, Christopher J

2017-04-01

Xao tam phan (Paramignya trimera (Oliv.) Guillaum) has been used as a medicinal plant for cancer prevention and treatment in recent years. The objective of this study was to determine the physicochemical, antioxidant, and cytotoxic properties of crude P. trimera root (PTR) extract and its fractions using MeOH as a solvent and microwave-assisted extraction as an advanced technique for preparation of the PTR extract. The results showed that the PTR extract had high contents of saponins, phenolics, flavonoids, and proanthocyanidins (7731.05 mg escin equiv. (EE), 238.13 mg gallic acid equiv. (GAE), 81.49 mg rutin equiv., and 58.08 mg catechin equiv. (CE)/g dried extract, resp.). Antioxidant activity of PTR extract was significantly higher (P < 0.05) than those of four its fractions and ostruthin, a key bioactive compound in the P. trimera, while potent cytotoxic capacity of PTR extract on various cancer cell lines in terms of MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed with GI 50 values ranging from 15 to 32 μg/ml. Cytotoxic potential on pancreatic cancer cells of PTR extract (100 - 200 μg/ml) was significantly higher (P < 0.05) than those of its four fractions (50 μg/ml), ostruthin (20 μg/ml) and gemcitabine (50 nm), and being comparable to a saponin-enriched extract from quillajia bark, a commercial product. Based on the results achieved, we can conclude that the PTR extract is a potential source for application of in the nutraceutical, medical, and pharmaceutical industries. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Physicochemical Properties, Antioxidant and Cytotoxic Activities of Crude Extracts and Fractions from Phyllanthus amarus

PubMed Central

Nguyen, Van Tang; Sakoff, Jennette A.; Scarlett, Christopher J.

2017-01-01

Background: Phyllanthus amarus (P. amarus) has been used as a medicinal plant for the prevention and treatment of chronic ailments such as diabetes, hepatitis, and cancer. Methods: The physicochemical properties, antioxidant and cytotoxic activities of crude extracts and fractions from P. amarus were determined using spectrophotometric method. Results: The P. amarus methanol (PAM) extract had lower levels of residual moisture (7.40%) and water activity (0.24) and higher contents of saponins, phenolics, flavonoids, and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents per g dried extract, respectively) than those of the P. amarus water (PAW) extract. The antioxidant activity of PAM extract was significantly higher (p < 0.05) than that of the PAW extract, PAM fractions, and phyllanthin (known as a major compound in the P. amarus). Higher cytotoxic activity of PAM extract based on MTT assay on different cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed in comparison to the PAW extract and PAM fractions. The cytotoxic potential of the PAW extract (200 μg/mL), based on the CCK-8 assay on a pancreatic cancer cell line (MiaCaPa2) was significantly lower (p < 0.05) than those of gemcitabine (50 nM) and a saponin-enriched extract from quillajia bark at 200 μg/mL (a commercial product), but was significantly higher than that of phyllanthin at 2 μg/mL. Conclusions: The results achieved from this study reveal that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs. PMID:28930257

A novel reactor for the simulation of gas and ash interactions in volcanic eruption plumes

NASA Astrophysics Data System (ADS)

Ayris, Paul M.; Cimarelli, Corrado; Delmelle, Pierre; Dingwell, Donald B.

2014-05-01

on aggregation processes. Large quantities of material can be processed in the AGAR. We invite discussions regarding collaboration with 'downstream' projects that would benefit from use of such materials, or from access to and further development of, the advanced gas-ash reactor. References Ayris, P. M., Lee, A. F., Wilson, K., Kueppers, U., Dingwell, D. B., & Delmelle, P. (2013a). SO2 sequestration in large volcanic eruptions: high-temperature scavenging by tephra. Geochimica et Cosmochimica Acta. Ayris, P. M., Delmelle, P., Maters, E., & Dingwell, D. B. (2013b). Quantifying HCl and SO2 adsorption by tephra in volcanic eruptions. In EGU General Assembly Conference Abstracts (Vol. 15, p. 2780). Rose, W. I. (1977). Scavenging of volcanic aerosol by ash: atmospheric and volcanologic implications. Geology, 5(10), 621-624.

Population genetic structure of rare and endangered plants using molecular markers

USGS Publications Warehouse

Raji, Jennifer; Atkinson, Carter T.

2013-01-01

This study was initiated to assess the levels of genetic diversity and differentiation in the remaining populations of Phyllostegia stachyoides and Melicope zahlbruckneri in Hawai`i Volcanoes National Park and determine the extent of gene flow to identify genetically distinct individuals or groups for conservation purposes. Thirty-six Amplified Fragment Length Polymorphic (AFLP) primer combinations generated a total of 3,242 polymorphic deoxyribonucleic acid (DNA) fragments in the P. stachyoides population with a percentage of polymorphic bands (PPB) ranging from 39.3 to 65.7% and 2,780 for the M. zahlbruckneri population with a PPB of 18.8 to 64.6%. Population differentiation (Fst) of AFLP loci between subpopulations of P. stachyoides was low (0.043) across populations. Analysis of molecular variance of P. stachyoides showed that 4% of the observed genetic differentiation occurred between populations in different kīpuka and 96% when individuals were pooled from all kīpuka. Moderate genetic diversity was detected within the M. zahlbruckneri population. Bayesian and multivariate analyses both classified the P. stachyoides and M. zahlbruckneri populations into genetic groups with considerable sub-structuring detected in the P. stachyoides population. The proportion of genetic differentiation among populations explained by geographical distance was estimated by Mantel tests. No spatial correlation was found between genetic and geographic distances in both populations. Finally, a moderate but significant gene flow that could be attributed to insect or bird-mediated dispersal of pollen across the different kīpuka was observed. The results of this study highlight the utility of a multi-allelic DNA-based marker in screening a large number of polymorphic loci in small and closely related endangered populations and revealed the presence of genetically unique groups of individuals in both M. zahlbruckneri and P. stachyoides populations. Based on these findings

Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia.

PubMed

Mkulama, Mtawa A P; Chishimba, Sandra; Sikalima, Jay; Rouse, Petrica; Thuma, Philip E; Mharakurwa, Sungano

2008-05-21

In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less than 5 kg and also in expectant mothers. SP is also the choice drug for intermittent preventive therapy in pregnancy and serves as stand-by treatment during ACT stock outs. The current study assessed the status of Plasmodium falciparum point mutations associated with antifolate drug resistance in the area around Macha. A representative sample of 2,780 residents from the vicinity of Macha was screened for malaria by microscopy. At the same time, blood was collected onto filter paper and dried for subsequent P. falciparum DNA analysis. From 188 (6.8%) individuals that were thick film-positive, a simple random sub-set of 95 P. falciparum infections were genotyped for DHFR and DHPS antifolate resistance mutations, using nested PCR and allele-specific restriction enzyme digestion. Plasmodium falciparum field samples exhibited a high prevalence of antifolate resistance mutations, including the DHFR triple (Asn-108 + Arg-59 + Ile-51) mutant (41.3%) and DHPS double (Gly-437 + Glu-540) mutant (16%). The quintuple (DHFR triple + DHPS double) mutant was found in 4 (6.5%) of the samples. Levels of mutated parasites showed a dramatic escalation, relative to previous surveys since 1988. However, neither of the Val-16 and Thr-108 mutations, which jointly confer resistance to cycloguanil, was detectable among the human infections. The Leu-164 mutation, associated with high grade resistance to both pyrimethamine and cycloguanil, as a multiple mutant with Asn-108, Arg-59 and (or) Ile-51, was also absent. This study points to escalating levels of P. falciparum antifolate resistance in the vicinity of Macha. Continued monitoring is recommended to ensure timely policy revisions before widespread resistance exacts

Parental History of Anxiety and Alcohol-Use Disorders and Alcohol Expectancies as Predictors of Alcohol-Related Problems*

PubMed Central

Morean, Meghan E.; Corbin, William R.; Sinha, Rajita; O'Malley, Stephanie S.

2009-01-01

Objective: Research has consistently identified a family history of alcoholism as a risk factor for alcohol-related problems, and global positive expectancies have been found to moderate this association. High rates of comorbidity between alcohol use and anxiety disorders suggest that a family history of anxiety disorders may also increase risk. Further, expectations of negative reinforcement (e.g., tension reduction) have been found to moderate the influence of anxiety-related traits. The current study sought to extend previous research by examining the influence of parental history of alcoholism, anxiety disorders, and the combination, as predictors of alcohol-related problems. Expectancies of global positive changes and tension reduction were hypothesized to moderate the influence of parental history of alcoholism and anxiety, respectively. Method: Direct interviews with parents assessed their history of alcoholism and anxiety for 144 offspring (ages 18-32; 53.5% male) creating four groups: those with a parental history of alcoholism (27.80%), anxiety (22.20%), both alcoholism and anxiety (33.30%), and no history of psychopathology (16.70%). Established measures assessed the offsprings'alcohol expectancies, alcohol use, and alcohol-related problems. Results: Although expected interactions between parental alcoholism and global positive expectancies and between parental anxiety and tension-reduction expectancies were not found, global positive expectancies were associated with alcohol-related problems among the group with parental history of both alcoholism and anxiety. Conclusions: The results suggest that the relation between parental history of alcoholism and global positive expectancies observed in previous studies may be strongest among individuals with a comorbid parental history of alcohol and anxiety disorders. Incorporating expectancies into interventions targeting individuals with a comorbid parental history of alcohol and anxiety disorders may have

Economic Burden in Chinese Patients with Diabetes Mellitus Using Electronic Insurance Claims Data

PubMed Central

Vemer, Pepijn; Zhu, Jingjing; Postma, Maarten J.; Chen, Wen

2016-01-01

Background There is a paucity of studies that focus on the economic burden in daily care in China using electronic health data. The aim of this study is to describe the development of the economic burden of diabetic patients in a sample city in China from 2009 to 2011 using electronic data of patients’ claims records. Methods This study is a retrospective, longitudinal study in an open cohort of Chinese patients with diabetes. The patient population consisted of people living in a provincial capital city in east China, covered by the provincial urban employee basic medical insurance (UEBMI). We included any patient who had at least one explicit diabetes diagnosis or received blood glucose lowering medication in at least one registered outpatient visit or hospitalization during a calendar year in the years 2009–2011. Cross-sectional descriptions of different types of costs, prevalence of diabetic complications and related diseases, medication use were performed for each year separately and differences between three years were compared using a chi-square test or the non-parametric Kruskal-Wallis H test. Results Our results showed an increasing trend in total medical cost (from 2,383 to 2,780 USD, p = 0.032) and diabetes related cost (from 1,655 to 1,857 USD) for those diabetic patients during the study period. The diabetes related economic burden was significantly related to the prevalence of complications and related diseases (p<0.001). The overall medication cost during diabetes related visits also increased (from 1,335 to 1,383 USD, p = 0.021). But the use pattern and cost of diabetes-related medication did not show significant changes during the study period. Conclusion The economic burden of diabetes increased significantly in urban China. It is important to improve the prevention and treatment of diabetes to contribute to the sustainability of the Chinese health-care system. PMID:27570976

Everolimus-eluting bioresorbable vascular scaffolds implanted in coronary bifurcation lesions: Impact of polymeric wide struts on side-branch impairment.

PubMed

De Paolis, Marcella; Felix, Cordula; van Ditzhuijzen, Nienke; Fam, Jiang Ming; Karanasos, Antonis; de Boer, Sanneke; van Mieghem, Nicolas M; Daemen, Joost; Costa, Francesco; Bergoli, Luis Carlos; Ligthart, Jurgen M R; Regar, Evelyn; de Jaegere, Peter P; Zijlstra, Felix; van Geuns, Robert Jan; Diletti, Roberto

2016-10-15

Limited data are available on bioresorbable vascular scaffolds (BVS) performance in bifurcations lesions and on the impact of BVS wider struts on side-branch impairment. Patients with at least one coronary bifurcation lesion involving a side-branch ≥2mm in diameter and treated with at least one BVS were examined. Procedural and angiographic data were collected and a dedicated methodology for off-line quantitative coronary angiography (QCA) in bifurcation was applied (eleven-segment model), to assess side-branch impairment occurring any time during the procedure. Two- and three-dimensional QCA were used. Optical coherence tomography (OCT) analysis was performed in a subgroup of patients and long-term clinical outcomes reported. A total of 102 patients with 107 lesions, were evaluated. Device- and procedural-successes were 99.1% and 94.3%, respectively. Side-branch impairment occurring any time during the procedure was reported in 13 bifurcations (12.1%) and at the end of the procedure in 6.5%. Side-branch minimal lumen diameter (Pre: 1.45±0.41mm vs Final: 1.48±0.42mm, p=0.587) %diameter-stenosis (Pre: 26.93±16.89% vs Final: 27.80±15.57%, p=0.904) and minimal lumen area (Pre: 1.97±0.89mm(2) vs Final: 2.17±1.09mm(2), p=0.334), were not significantly affected by BVS implantation. Mean malapposed struts at the bifurcation polygon-of-confluence were 0.63±1.11. The results of the present investigation suggest feasibility and relative safety of BVS implantation in coronary bifurcations. BVS wide struts have a low impact on side-branch impairment when considering bifurcations with side-branch diameter≥2mm. Copyright © 2016. Published by Elsevier Ireland Ltd.

Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth

PubMed Central

Lin, Yvonne G.; Immaneni, Anand; Merritt, William M.; Mangala, Lingegowda S.; Kim, SeungWook; Shahzad, Mian M.K.; Tsang, Yvonne T.M.; Armaiz-Pena, Guillermo N.; Lu, Chunhua; Kamat, Aparna A.; Han, Liz Y.; Spannuth, WhitneyA.; Nick, Alpa M.; Landen, Charles N.; Wong, Kwong K.; Gray, Michael J.; Coleman, Robert L.; Bodurka, Diane C.; Brinkley, William R.; Sood, Anil K.

2009-01-01

Purpose The Aurora kinase family plays pivotal roles in mitotic integrity and cell cycle.We sought to determine the effects of inhibiting Aurora kinase on ovarian cancer growth in an orthotopic mouse model using a small molecule pan-Aurora kinase inhibitor, MK-0457. Experimental Design We examined cell cycle regulatory effects and ascertained the therapeutic efficacy of Aurora kinase inhibition both alone and combined with docetaxel using both in vitro and in vivo ovarian cancer models. Results In vitro cytotoxicity assays with HeyA8 and SKOV3ip1 cells revealed >10-fold greater docetaxel cytotoxicity in combination with MK-0457. After in vivo dose kinetics were determined using phospho-histone H3 status, therapy experiments with the chemosensitive HeyA8 and SKOV3ip1as well as the chemoresistant HeyA8-MDR and A2780-CP20 models showed that Aurora kinase inhibition alone significantly reduced tumor burden compared with controls (P values < 0.01). Combination treatment with docetaxel resulted in significantly improved reduction in tumor growth beyond that afforded by docetaxel alone (P ≤ 0.03). Proliferating cell nuclear antigen immunohistochemistry revealed that MK-0457 alone and in combination with docetaxel significantly reduced cellular proliferation (P values < 0.001). Compared with controls, treatment with MK-0457 alone and in combination with docetaxel also significantly increased tumor cell apoptosis by ∼3-fold (P < 0.01). Remarkably, compared with docetaxel monotherapy, MK-0457 combined with docetaxel resulted in significantly increased tumor cell apoptosis. Conclusions Aurora kinase inhibition significantly reduces tumor burden and cell proliferation and increases tumor cell apoptosis in this preclinical orthotopic model of ovarian cancer. The role of Aurora kinase inhibition in ovarian cancer merits further investigation in clinical trials. PMID:18765535

Participatory mapping of sex trade and enumeration of sex workers using capture-recapture methodology in Diego-Suarez, Madagascar.

PubMed

Kruse, Natalie; Behets, Frieda M-T F; Vaovola, Georgine; Burkhardt, Gillian; Barivelo, Texina; Amida, X; Dallabetta, Gina

2003-08-01

Capture-recapture methodology has been employed to estimate the size of hidden or difficult-to-reach human populations such as sex workers, homeless persons, and intravenous drug users. This study took place in the context of efforts to improve the quality of curative and preventive services for sexually transmitted infections offered to sex workers in Diego-Suarez, Madagascar in partnership with sex workers. The goal of this study was to better understand sex-trading practices, map out sex work sites, and estimate the size of a mobile sex-worker population in Diego-Suarez, Madagascar using methods that can be reproduced in other resource-poor settings. Forty sex workers were trained to function as field researchers. Key informants in designated neighborhoods were identified and interviewed. Basic maps of sex-trade sites were designed by hand. The number of sex workers in Diego-Suarez was estimated using capture-recapture methodology. An educational brochure was used to "capture" sex workers during a first phase, and "recapture" 2 weeks later. Most sex trade was street based and mobile. Capture-recapture methods estimated a total of 2684 sex workers (95% CI: 2588-2780) in Diego-Suarez, or approximately 12% of the 15- to 49-year-old female population in the city. Geographic mapping and capture-recapture proved to be low-cost and relatively easy to use techniques for counting a hard-to-reach population, such as female street-based sex workers. Sex workers can be capable fieldworkers, and their active participation in research concerning sex work should be considered whenever possible. A high proportion of women of reproductive age were found to engage in sex work, indicating that there is an urgent need to scale up sexually transmitted infection and HIV prevention activities targeting sex workers, their sexual partners, and the general population.

Disease evolution in late-onset and early-onset systemic lupus erythematosus.

PubMed

Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

2017-10-01

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Ascites interferes with the activity of lurbinectedin and trabectedin: Potential role of their binding to alpha 1-acid glycoprotein.

PubMed

Erba, E; Romano, M; Gobbi, M; Zucchetti, M; Ferrari, M; Matteo, C; Panini, N; Colmegna, B; Caratti, G; Porcu, L; Fruscio, R; Perlangeli, M V; Mezzanzanica, D; Lorusso, D; Raspagliesi, F; D'Incalci, M

2017-11-15

Trabectedin and its analogue lurbinectedin are effective drugs used in the treatment of ovarian cancer. Since the presence of ascites is a frequent event in advanced ovarian cancer we asked the question whether ascites could modify the activity of these compounds against ovarian cancer cells. The cytotoxicity induced by trabectedin or lurbinectedin against A2780, OVCAR-5 cell lines or primary culture of human ovarian cancer cells was compared by performing treatment in regular medium or in ascites taken from either nude mice or ovarian cancer patients. Ascites completely abolished the activity of lurbinectedin at up to 10nM (in regular medium corresponds to the IC90), strongly reduced that of trabectedin, inhibited the cellular uptake of lurbinectedin and, to a lesser extent, that of trabectedin. Since α1-acid glycoprotein (AGP) is present in ascites at relatively high concentrations, we tested if the binding of the drugs to this protein could be responsible for the reduction of their activity. Adding AGP to the medium at concentration range of those found in ascites, we reproduced the anticytotoxic effect of ascites. Erythromycin partially restored the activity of the drugs, presumably by displacing them from AGP. Equilibrium dialysis experiments showed that both drugs bind AGP, but the affinity of binding of lurbinectedin was much greater than that of trabectedin. KD values are 8±1.7 and 87±14nM for lurbinectedin and trabectedin, respectively. The studies intimate the possibility that AGP present in ascites might reduce the activity of lurbinectedin and to a lesser extent of trabectedin against ovarian cancer cells present in ascites. AGP plasma levels could influence the distribution of these drugs and thus they should be monitored in patients receiving these compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Significance of VEGFR-2 on Ovarian Cancer Cells

PubMed Central

Spannuth, Whitney A.; Nick, Alpa M.; Jennings, Nicholas B.; Armaiz-Pena, Guillermo N.; Mangala, Lingegowda S.; Danes, Christopher G.; Lin, Yvonne G.; Merritt, William M.; Thaker, Premal H.; Kamat, Aparna A.; Han, Liz Y.; Tonra, James R.; Coleman, Robert L.; Ellis, Lee M.; Sood, Anil K.

2009-01-01

Vascular endothelial growth factor receptor (VEGFR) has recently been discovered on ovarian cancer cells, but its functional significance is unknown and is the focus of the current study. By protein analysis, A2780-par and HeyA8 ovarian cancer cell lines expressed VEGFR-1 and HeyA8 and SKOV3ip1 expressed VEGFR-2. By in situ hybridization (ISH), 85% of human ovarian cancer specimens showed moderate to high VEGFR-2 expression while only 15% showed moderate to high VEGFR-1 expression. By immunofluorescence, little or no VEGFR-2 was detected in normal ovarian surface epithelial cells, whereas expression was detected in 75% of invasive ovarian cancer specimens. To differentiate between the effects of tumor versus host expression of VEGFR, nude mice were injected with SKOV3ip1 cells and treated with either human VEGFR-2 specific antibody (1121B), murine VEGFR-2 specific antibody (DC101), or the combination. Treatment with 1121B reduced SKOV3ip1 cell migration by 68% (p < 0.01) and invasion by 72% (p < 0.01), but exposure to VEGFR-1 antibody had no effect. Treatment with 1121B effectively blocked VEGF-induced phosphorylation of p130Cas. In vivo, treatment with either DC101 or 1121B significantly reduced tumor growth alone and in combination in the SKOV3ip1 and A2774 models. Decreased tumor burden after treatment with DC101 or 1121B correlated with increased tumor cell apoptosis, decreased proliferative index, and decreased microvessel density. These effects were significantly greater in the combination group (p<0.001). We show functionally active VEGFR-2 is present on most ovarian cancer cells. The observed anti-tumor activity of VEGF-targeted therapies may be mediated by both anti-angiogenic and direct anti-tumor effects. PMID:19058181

Asteroid spin-rate studies using large sky-field surveys

NASA Astrophysics Data System (ADS)

Chang, Chan-Kao; Lin, Hsing-Wen; Ip, Wing-Huen; Prince, Thomas A.; Kulkarni, Shrinivas R.; Levitan, David; Laher, Russ; Surace, Jason

2017-12-01

Eight campaigns to survey asteroid rotation periods have been carried out using the intermediate Palomar Transient Factory in the past 3 years. 2780 reliable rotation periods were obtained, from which we identified two new super-fast rotators (SFRs), (335433) 2005 UW163 and (40511) 1999 RE88, and 23 candidate SFRs. Along with other three known super-fast rotators, there are five known SFRs so far. Contrary to the case of rubble-pile asteroids (i.e., bounded aggregations by gravity only), an internal cohesion, ranging from 100 to 1000 Pa, is required to prevent these five SFRs from flying apart because of their super-fast rotations. This cohesion range is comparable with that of lunar regolith. However, some candidates of several kilometers in size require unusually high cohesion (i.e., a few thousands of Pa). Therefore, the confirmation of these kilometer-sized candidates can provide important information about asteroid interior structure. From the rotation periods we collected, we also found that the spin-rate limit of C-type asteroids, which has a lower bulk density, is lower than for S-type asteroids. This result is in agreement with the general picture of rubble-pile asteroids (i.e., lower bulk density, lower spin-rate limit). Moreover, the spin-rate distributions of asteroids of 3< D < 15 km in size show a steady decrease along frequency for f > 5 rev/day, regardless of the location in the main belt. The YORP effect is indicated to be less efficient in altering asteroid spin rates from our results when compared with the flat distribution found by Pravec et al. (Icarus 197:497-504, 2008. doi: 10.1016/j.icarus.2008.05.012). We also found a significant number drop at f = 5 rev/day in the spin-rate distributions of asteroids of D < 3 km.

Half-sandwich rhodium(III) transfer hydrogenation catalysts: Reduction of NAD(+) and pyruvate, and antiproliferative activity.

PubMed

Soldevila-Barreda, Joan J; Habtemariam, Abraha; Romero-Canelón, Isolda; Sadler, Peter J

2015-12-01

Organometallic complexes have the potential to behave as catalytic drugs. We investigate here Rh(III) complexes of general formula [(Cp(x))Rh(N,N')(Cl)], where N,N' is ethylenediamine (en), 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen) or N-(2-aminoethyl)-4-(trifluoromethyl)benzenesulfonamide (TfEn), and Cp(x) is pentamethylcyclopentadienyl (Cp*), 1-phenyl-2,3,4,5-tetramethylcyclopentadienyl (Cp(xPh)) or 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl (Cp(xPhPh)). These complexes can reduce NAD(+) to NADH using formate as a hydride source under biologically-relevant conditions. The catalytic activity decreased in the order of N,N-chelated ligand bpy > phen > en with Cp* as the η(5)-donor. The en complexes (1-3) became more active with extension to the Cp(X) ring, whereas the activity of the phen (7-9) and bpy (4-6) compounds decreased. [Cp*Rh(bpy)Cl](+) (4) showed the highest catalytic activity, with a TOF of 37.4±2h(-1). Fast hydrolysis of the chlorido complexes 1-10 was observed by (1)H NMR (<10min at 310K). The pKa* values for the aqua adducts were determined to be ca. 8-10. Complexes 1-9 also catalysed the reduction of pyruvate to lactate using formate as the hydride donor. The efficiency of the transfer hydrogenation reactions was highly dependent on the nature of the chelating ligand and the Cp(x) ring. Competition reactions between NAD(+) and pyruvate for reduction by formate catalysed by 4 showed a preference for reduction of NAD(+). The antiproliferative activity of complex 3 towards A2780 human ovarian cancer cells increased by up to 50% when administered in combination with non-toxic doses of formate, suggesting that transfer hydrogenation can induce reductive stress in cancer cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Burden of Obesity on Pediatric Inpatients with Acute Asthma Exacerbation in the United States.

PubMed

Okubo, Yusuke; Nochioka, Kotaro; Hataya, Hiroshi; Sakakibara, Hiroshi; Terakawa, Toshiro; Testa, Marcia

Obesity and asthma are common health problems in the United States. The objective of this study was to evaluate the clinical and economic burdens of obesity on hospitalized children with acute asthma exacerbation in 2012. Hospital discharge records of patients aged 2 to 18 years with a diagnosis of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data were compiled by the Agency for Healthcare Research and Quality. The discharge records were weighted to estimate the number of hospitalizations because of asthma exacerbations in the United States. To classify whether the patient was obese or not, we used the International Classification of Diseases, Ninth Revision, Clinical Modification code 278.0x. We compared the odds of using noninvasive or invasive mechanical ventilation, mean total charges for inpatient service, and length of hospital stay between obese and nonobese patients. A total of 74,338 patient discharges were extracted. Of these, 3,494 discharges were excluded because of chronic medical conditions. Using discharge weight variables, we estimated a total of 100,157 hospitalizations with asthma exacerbations among children aged between 2 and 18 years in 2012. Obesity was significantly associated with higher odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared with nonobesity. These findings suggest that obesity is a significant risk factor of severe asthma exacerbation that requires mechanical ventilation, and obesity is an economically complicating factor. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Primary headache disorders in the adult general population of Pakistan - a cross sectional nationwide prevalence survey.

PubMed

Herekar, A A; Ahmad, A; Uqaili, U L; Ahmed, B; Effendi, J; Alvi, S Z; Shahab, M A; Javed, U; Herekar, A D; Khanani, Rafiq; Steiner, T J

2017-12-01

The large geographical gaps in our knowledge of the prevalence and burden of headache disorders include almost all of Eastern Mediterranean Region (EMR). We report a nationwide population-based study in Pakistan, an EMR country with the sixth largest population in the world, conducted as a project within the Global Campaign against Headache. We surveyed six locations from the four provinces of Pakistan: Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan. We randomly selected and visited rural and urban households in each. One adult member (18-65 years) of each household, also randomly selected, was interviewed by a trained non-medical interviewer from the same location using a previously-validated structured questionnaire translated into Urdu, the national language. We estimated 1-year prevalences of the headache disorders of public-health importance and examined their associations with demographic variables using multivariate analysis. There were 4223 participants (mean age 34.4 ± 11.0 years; male 1957 [46.3%], female 2266 [53.7%]; urban 1443 [34.2%], rural 2780 [65.8%]). Participation proportion was 89.5%. Headache in the previous year was reported by 3233 (76.6% [95% CI: 75.3-77.8%]). The age- and gender-adjusted 1-year prevalence of migraine was 22.5% [21.2-23.8%] (male 18.0% [16.8-19.2%], female 26.9% [25.6-28.2%]), of tension-type headache (TTH) 44.6% [43.1-46.1%] (male 51.2% [49.7-52.7%], female 37.9% [36.4-39.4%]), of probable medication-overuse headache 0.7% [0.5-1.0%] (male 0.7% [0.5-1.0%], female 0.8% [0.5-1.1%]) and of other headache on ≥15 days/month 7.4% [6.6-8.2%] (male 4.4% [3.8-5.0%], female 10.4% [9.5-11.3%]). Migraine was more prevalent in females by a factor of 3:2 although this association barely survived (P = 0.039) after correcting for other factors. TTH was more prevalent in males by about 4:3 (P = 0.026). All headache and migraine were age-related, peaking in the age group 40-49 years; TTH peaked a decade earlier. Higher

ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1

PubMed Central

Renes, Johan; de Vries, Elisabeth G E; Nienhuis, Edith F; Jansen, Peter L M; Müller, Michael

1999-01-01

The present study was performed to investigate the ability of the multidrug resistance protein (MRP1) to transport different cationic substrates in comparison with MDR1-P-glycoprotein (MDR1). Transport studies were performed with isolated membrane vesicles from in vitro selected multidrug resistant cell lines overexpressing MDR1 (A2780AD) or MRP1 (GLC4/Adr) and a MRP1-transfected cell line (S1(MRP)). As substrates we used 3H-labelled derivatives of the hydrophilic monoquaternary cation N-(4′,4′-azo-n-pentyl)-21-deoxy-ajmalinium (APDA), the basic drug vincristine and the more hydrophobic basic drug daunorubicin. All three are known MDR1-substrates. MRP1 did not mediate transport of these substrates per se. In the presence of reduced glutathione (GSH), there was an ATP-dependent uptake of vincristine and daunorubicin, but not of APDA, into GLC4/Adr and S1(MRP) membrane vesicles which could be inhibited by the MRP1-inhibitor MK571. ATP- and GSH-dependent transport of daunorubicin and vincristine into GLC4/Adr membrane vesicles was inhibited by the MRP1-specific monoclonal antibody QCRL-3. MRP1-mediated daunorubicin transport rates were dependent on the concentration of GSH and were maximal at concentrations ⩾10 mM. The apparent KM value for GSH was 2.7 mM. Transport of daunorubicin in the presence of 10 mM GSH was inhibited by MK571 with an IC50 of 0.4 μM. In conclusion, these results demonstrate that MRP1 transports vincristine and daunorubicin in an ATP- and GSH-dependent manner. APDA is not a substrate for MRP1. PMID:10188979

The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo

NASA Astrophysics Data System (ADS)

Shi, Dayong; Li, Jing; Guo, Shuju; Su, Hua; Fan, Xiao

2009-05-01

To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3), 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTT assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%, respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.

Why do workers behave unsafely at work? Determinants of safe work practices in industrial workers.

PubMed

Garcia, A M; Boix, P; Canosa, C

2004-03-01

To explore the relation between safety climate (workers' perceptions regarding management's attitudes towards occupational safety and health) and workers' behaviour at work. Cross sectional survey of workers at the pottery industry in Castellon, Spain. Sampling was stratified by plant size and workers' gender, according to data on the working population at this setting. A total of 734 production workers were interviewed. Information was collected on safety climate and workers' behaviour towards occupational risks with a specific questionnaire. A safety climate index (SCI, scale 0-100) was constructed adding scores for each item measuring safety climate in the questionnaire. Workers' unsafe behaviour was analysed for the different safety climate index levels. Mean score for SCI was 71.90 (SD 19.19). There were no differences in SCI scores according to age, gender, education, children at charge, seniority at work, or type of employment. Small workplaces (<50 workers) showed significantly worse SCI (mean 67.23, SD 19.73) than the largest factories (>200 workers). Lower levels of SCI (SCI <50) were related to workers' unsafe behaviours (full/high accord with the statement "I excessively expose myself to hazards in my work", adjusted odds ratio ORa 2.79, 95% CI 1.60 to 4.88), and to lack of compliance with safety rules (ORa 12.83, 95% CI 5.92 to 27.80). Safety climate measures workers' perception of organisational factors related to occupational health and safety (for example, management commitment to risk prevention or priorities of safety versus production). In this study these factors are strongly associated with workers' attitudes towards safety at work. Longitudinal studies can further clarify the relation between safety climate and workers' behaviour regarding occupational safety and health.

Influence of Military Training and Standardized Nutrition in Military Unit on Soldiers' Nutritional Status and Physical Fitness.

PubMed

Tomczak, Andrzej; Bertrandt, Jerzy; Kłos, Anna; Kłos, Krzysztof

2016-10-01

Tomczak, A, Bertrandt, J, Kłos, A, and Kłos, K. Influence of military training and standardized nutrition in military unit on soldiers' nutritional status and physical fitness. J Strength Cond Res 30(10): 2774-2780, 2016-Despite suspension of conscription in Polish Army, trainings of soldiers are still carried out. It is expected that they will be effective and will contribute to obtaining optimum level of psychophysical efficiency that enables fulfillment of military tasks. Total of 60 soldiers took part in the study. During the 9-month military service, soldiers had 200 hours of physical training and basic military training (shooting, drill, anti-chemical training, topography, general tactics, and military equipment operation). The training lasted 8 hours everyday. To assess fitness level, 4 trials were done: long jump, pull-ups, sit-ups, and 1,000 m run. Evaluation of food was based on the analysis of full board menus using the "Tables of composition and nutritional value of food products." Energy value was assessed, and content of basic nutrients was calculated. Assessment of nutritional status was based on anthropometric measurements, such as body height, body mass, and thickness of 4 selected skinfolds. Body height and body mass were the basis for the body mass index calculation. Soldiers serving in the mechanized infantry unit, after completing the training, got better results only in 1,000 m run (from 250.3 to 233.61 seconds). During the research, an average energy value of a daily food ration planned for consumption was 4,504 kcal. This value consisted of 13.2% of energy from protein, 31.9% of energy from fat, and 54.9% from carbohydrates. In the course of military service, percentage of subjects indicating overweight increased from 10.2 to 25.4%.

Tectorigenin sensitizes paclitaxel-resistant human ovarian cancer cells through downregulation of the Akt and NFκB pathway.

PubMed

Yang, Yeong-In; Lee, Kyung-Tae; Park, Hee-Juhn; Kim, Tae Jin; Choi, Youn Seok; Shih, Ie-Ming; Choi, Jung-Hye

2012-12-01

Paclitaxel (Taxol) is currently used as the front-line chemotherapeutic agent for several cancers including ovarian carcinoma; however, the drug frequently induces drug resistance through multiple mechanisms. The new strategy of using natural compounds in combination therapies is highly attractive because those compounds may enhance the efficacy of chemotherapy. In this study, we found that tectorigenin, an isoflavonoid isolated from flower of Pueraria thunbergiana, enhanced the growth-inhibitory effect of paclitaxel in paclitaxel-resistant ovarian cancer cells (MPSC1(TR), A2780(TR) and SKOV3(TR)) as well as their naive counterparts. The combination of tectorigenin with paclitaxel resulted in a synergistic apoptosis compared with either agent alone through activation of caspases-3, -8 and -9. Treatment with tectorigenin inhibited the nuclear translocation of NFκB and the expression of NFκB-dependent genes such as FLIP, XIAP, Bcl-2, Bcl-xL and COX-2, which are known to be associated with chemoresistance. In addition, the tectorigenin-paclitaxel combination inhibited the phosphorylation of IκB and IKK and the activation of Akt in paclitaxel-resistant cancer cells. Moreover, tectorigenin-paclitaxel-induced cell growth inhibition was enhanced by pretreatment with the Akt inhibitor LY294002 or overexpression of the dominant negative Akt (Akt-DN), but reduced by overexpression of constitutively activated Akt (Akt-Myr). Furthermore, we found that Akt-Myr, at least in part, reversed tectorigenin-paclitaxel-induced nuclear translocation of NFκB and the phosphorylation of IκB and IKK. These data suggest that tectorigenin could sensitize paclitaxel-resistant human ovarian cancer cells through inactivation of the Akt/IKK/IκB/NFκB signaling pathway, and promise a new intervention to chemosensitize paclitaxel-induced cytotoxicity in ovarian cancer.

Hierarchical clustering of HPV genotype patterns in the ASCUS-LSIL triage study

PubMed Central

Wentzensen, Nicolas; Wilson, Lauren E.; Wheeler, Cosette M.; Carreon, Joseph D.; Gravitt, Patti E.; Schiffman, Mark; Castle, Philip E.

2010-01-01

Anogenital cancers are associated with about 13 carcinogenic HPV types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common which complicate the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the ASCUS-LSIL triage study using unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered using complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: Cluster 1 included all CIN3 histology with abnormal cytology; Cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion (HSIL) cytology; Cluster 3 included older women with normal or low grade histology/cytology and low viral load; Cluster 4 included younger women with low grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: Group 1 included only HPV16; Group 2 included nine carcinogenic types plus non-carcinogenic HPV53 and HPV66; and Group 3 included non-carcinogenic types plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and HSIL. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease using unsupervised hierarchical clustering can address complex genotype distributions on a population level. PMID:20959485

Rapid transcriptome characterization and parsing of sequences in a non-model host-pathogen interaction; pea-Sclerotinia sclerotiorum

PubMed Central

2012-01-01

Background White mold, caused by Sclerotinia sclerotiorum, is one of the most important diseases of pea (Pisum sativum L.), however, little is known about the genetics and biochemistry of this interaction. Identification of genes underlying resistance in the host or pathogenicity and virulence factors in the pathogen will increase our knowledge of the pea-S. sclerotiorum interaction and facilitate the introgression of new resistance genes into commercial pea varieties. Although the S. sclerotiorum genome sequence is available, no pea genome is available, due in part to its large genome size (~3500 Mb) and extensive repeated motifs. Here we present an EST data set specific to the interaction between S. sclerotiorum and pea, and a method to distinguish pathogen and host sequences without a species-specific reference genome. Results 10,158 contigs were obtained by de novo assembly of 128,720 high-quality reads generated by 454 pyrosequencing of the pea-S. sclerotiorum interactome. A method based on the tBLASTx program was modified to distinguish pea and S. sclerotiorum ESTs. To test this strategy, a mixture of known ESTs (18,490 pea and 17,198 S. sclerotiorum ESTs) from public databases were pooled and parsed; the tBLASTx method successfully separated 90.1% of the artificial EST mix with 99.9% accuracy. The tBLASTx method successfully parsed 89.4% of the 454-derived EST contigs, as validated by PCR, into pea (6,299 contigs) and S. sclerotiorum (2,780 contigs) categories. Two thousand eight hundred and forty pea ESTs and 996 S. sclerotiorum ESTs were predicted to be expressed specifically during the pea-S. sclerotiorum interaction as determined by homology search against 81,449 pea ESTs (from flowers, leaves, cotyledons, epi- and hypocotyl, and etiolated and light treated etiolated seedlings) and 57,751 S. sclerotiorum ESTs (from mycelia at neutral pH, developing apothecia and developing sclerotia). Among those ESTs specifically expressed, 277 (9.8%) pea ESTs

Long-Term Coarse Particulate Matter Exposure and Heart Rate Variability in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Adhikari, Richa; D’Souza, Jennifer; Solimon, Elsayed Z.; Burke, Gregory L.; Daviglus, Martha; Jacobs, David R.; Park, Sung Kyun; Sheppard, Lianne; Thorne, Peter S.; Kaufman, Joel D.; Larson, Timothy V.; Adar, Sara D.

2017-01-01

Background Reduced heart rate variability, a marker of impaired cardiac autonomic function, has been linked to short-term exposure to airborne particles. This research adds to the literature by examining associations with long-term exposures to coarse particles (PM10-2.5). Methods Using electrocardiogram recordings from 2,780 participants (45-84 years) from three Multi-Ethnic Study of Atherosclerosis sites, we assessed the standard deviation of normal-to-normal intervals (SDNN) and root-mean square differences of successive normal-to-normal intervals (rMSSD) at a baseline (2000-2002) and follow-up (2010-2012) examination (mean visits/person=1.5). Annual average concentrations of PM10-2.5 mass, copper, zinc, phosphorus, silicon, and endotoxin were estimated using site-specific spatial prediction models. We assessed associations for baseline heart rate variability and rate of change in heart rate variability over time using multivariable mixed models adjusted for time, sociodemographic, lifestyle, health, and neighborhood confounders, including co-pollutants. Results In our primary models adjusted for demographic and lifestyle factors and site, PM10-2.5 mass was associated with 1.0% (95% CI: -4.1, 2.1%) lower SDNN levels per interquartile range of 2 μg/m3. Stronger associations, however, were observed prior to site adjustment and with increasing residential stablity. Similar patterns were found for rMSSD. We found little evidence for associations with other chemical species and with with the rate of change in heart rate variability, though endotoxin was associated with increasing heart rate variability over time. Conclusion We found only weak evidence that long-term PM10-2.5 exposures are associated with lowered heart rate variability. Stronger associations among residentially stable individuals suggest that confirmatory studies are needed. PMID:27035690

Effects of different lasers on organic/inorganic ratio of radicular dentin.

PubMed

Lopes, F C; Roperto, R; Akkus, A; Akkus, O; Souza-Gabriel, A E; Sousa-Neto, M D

2016-04-01

The aim of this study was to evaluate the chemical stability of endodontic-treated root dentin after different laser irradiations through Raman spectroscopy. Fifty maxillary canines were selected and prepared with K3 system. Roots were randomly distributed into five groups (n = 10) according to the surface treatment: GI (water), GII (NaOCl + EDTA), GIII (NaOCl + EDTA + 980 nm Diode laser), GIV (NaOCl + EDTA+ 1064 nm Nd: YAG laser) and GV (NaOCl + EDTA+ 2780 nm Er,Cr: YSGG laser). Lasers were applied for 20 s. Samples were bisected, and the organic and inorganic content of dentin was analyzed by Raman spectroscopy. Data were submitted to ANOVA and Tukey tests (p < 0.05). None of the surface treatments alter the inorganic content (cts) (p = 0.183). Roots irradiated with Er,Cr: YSGG laser had a reduced collagen content (GV-290.7 ± 41.7) compared with the water-treated roots (GI-328.3 ± 63.5) and those treated with NaOCl + EDTA (GII-333.9 ± 55.8). Roots irradiated with Er,Cr: YSGG laser also showed a higher inorganic/organic ratio (GV-9.5 ± 1.1) than roots treated with water (GI-7.7 ± 1.5), NaOCl + EDTA (GII-8.0 ± 1.4) and diode laser (GIII-8.2 ± 1.6). Both organic and inorganic contents increased from cervical to apical thirds in all groups. None of the surface treatments were able to promote changes in the inorganic content of the root dentin; treatment with NaOCl + EDTA combined with Er,Cr: YSGG altered collagen.

Pleistocene climate and biome evolution modulated at orbital, millennial, and centennial time scales

NASA Astrophysics Data System (ADS)

Hooghiemstra, H.

2013-05-01

For the northern Andes we present a multi-proxy record of environmental and climatic change at millennial- to century-scale resolution of the full Pleistocene. The composite record includes the 540-m Funza core (2250-27 ka; 1050-yr resolution) from the Bogotá basin (~4°N, 2550 m asl, 2100 samples), the 58-mcd core (284-27 ka; 60-yr resolution) from the Fúquene basin (~5°N, 2540 m asl 4700 samples), and the 12-m core (last 14 ka; 25-yr resolution) from the La Cocha basin (1°N, 2780 m asl, 550 samples). At high elevations climatic variability is mainly driven by the 41-kyr component of orbital forcing changing into a dominant 100-kyr frequency during the last 0.9 Ma. High elevation intraAndean environments are mainly driven by temperature and atmospheric pCO2 while changes in moisture is an important driver of the Andean environments on the Amazonian flank. The Pleistocene is reflected by MIS 87 to 1, the last interglacial-glacial cycle by D/O-cycles 28 to 1 (and during MIS 7-6 another 15 D/O-style cycles), and the Holocene shows many events with an acceleration of climate change. Repeatedly the subpáramo shrub biome is temporarily lost suggesting vertical migration of forest exceeded the maximum migration capacity of the subpáramo biome. Continuous changes in altitidinal vegetation distribution caused mountains above ~1500 m were alternatingly covered by different biomes. Forests reached only ~125 ka modern species compositions indicating most of the Pleistocene record shows nonanalog vegetation associations, however not preventing modern ecological ranges can be applied to reconstruct past environments. Comparison with Greenland, Antarctic and marine climate records is demonstrated.

Anti-allergic action of aged black garlic extract in RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.

PubMed

Yoo, Jae-Myung; Sok, Dai-Eun; Kim, Mee Ree

2014-01-01

Garlic (Allium sativum) has been used as a food as well as a component of traditional medicine. Aged black garlic (ABG) is known to have various bioactivities. However, the effect of ABG on allergic response is almost unknown. In the present study, we investigated whether ABG can inhibit immunoglobulin E-mediated allergic response in RBL-2H3 cells as well as in vivo passive cutaneous anaphylaxis (PCA). In in vitro tests, ethyl acetate extract (EBG) of ABG significantly inhibited the release of β-hexosaminidase (IC₅₀, 1.53 mg/mL) and TNF-α (IC₅₀, 0.98 mg/mL). Moreover, BG10, an active fraction of EBG, dramatically suppressed the release of β-hexosaminidase (IC₅₀, 53.60 μg/mL) and TNF-α (IC₅₀, 27.80 μg/mL). In addition, BG10 completely blocked the formation of prostaglandin E₂ and leukotriene B₄ at ≥25 μg/mL. When the effect of BG10 on FcɛRI receptor cascade was investigated, BG10 significantly inhibited the phosphorylation of Syk, but not Lyn. Furthermore, BG10 dose dependently decreased the phosphorylation of cytosolic phospholipase A₂ (cPLA₂) and 5-lipoxygenase (5-LO) as well as the expression of cyclooxygenase-2 (COX-2). Consistent with what has been mentioned earlier, BG10 also significantly inhibited the PCA reaction in mice. In conclusion, these results indicate that ABG suppresses the allergic response, and the mechanism for its anti-allergic action may involve suppressions of Syk, cPLA₂, 5-LO, and COX-2. The anti-allergic actions of ABG, EBG, or BG10 suggest that they may be useful as functional foods for allergic diseases.

Sports injuries and illnesses in the Sochi 2014 Olympic Winter Games.

PubMed

Soligard, Torbjørn; Steffen, Kathrin; Palmer-Green, Debbie; Aubry, Mark; Grant, Marie-Elaine; Meeuwisse, Willem; Mountjoy, Margo; Budgett, Richard; Engebretsen, Lars

2015-04-01

Systematic surveillance of injuries and illnesses is the foundation for developing preventive measures in sport. To analyse the injuries and illnesses that occurred during the XXII Olympic Winter Games, held in Sochi in 2014. We recorded the daily occurrence (or non-occurrence) of injuries and illnesses (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Sochi 2014 medical staff. NOC and Sochi 2014 medical staff reported 391 injuries and 249 illnesses among 2780 athletes from 88 NOCs, equalling incidences of 14 injuries and 8.9 illnesses per 100 athletes over an 18-day period of time. Altogether, 12% and 8% of the athletes incurred at least one injury or illness, respectively. The percentage of athletes injured was highest in aerial skiing, snowboard slopestyle, snowboard cross, slopestyle skiing, halfpipe skiing, moguls skiing, alpine skiing, and snowboard halfpipe. Thirty-nine per cent of the injuries were expected to prevent the athlete from participating in competition or training. Women suffered 50% more illnesses than men. The rate of illness was highest in skeleton, short track, curling, cross-country skiing, figure skating, bobsleigh and aerial skiing. A total of 159 illnesses (64%) affected the respiratory system, and the most common cause of illness was infection (n=145, 58%). Overall, 12% of the athletes incurred at least one injury during the games, and 8% an illness, which is similar to prior Olympic Games. The incidence of injuries and illnesses varied substantially between sports. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparative study between laser and conventional techniques for class V cavity preparation in gamma-irradiated teeth (in vitro study).

PubMed

Rasmy, Amr H M; Harhash, Tarek A; Ghali, Rami M S; El Maghraby, Eman M F; El Rouby, Dalia H

2017-01-01

The purpose of this study was to compare laser with conventional techniques in class V cavity preparation in gamma-irradiated teeth. Forty extracted human teeth with no carious lesions were used for this study and were divided into two main groups: Group I (n = 20) was not subjected to gamma radiation (control) and Group II (n=20) was subjected to gamma radiation of 60 Gray. Standard class V preparation was performed in buccal and lingual sides of each tooth in both groups. Buccal surfaces were prepared by the Er,Cr:YSGG laser (Waterlase iPlus) 2780 nm, using the gold handpiece with MZ10 Tip in non-contact and the "H" mode, following parameters of cavity preparation - power 6 W, frequency 50 Hz, 90% water and 70% air, then shifting to surface treatment laser parameters - power 4.5 W, frequency 50 Hz, 80% water and 50% air. Lingual surfaces were prepared by the conventional high-speed turbine using round diamond bur. Teeth were then sectioned mesio-distally, resulting in 80 specimens: 40 of which were buccal laser-treated (20 control and 20 gamma-irradiated specimens) and 40 were lingual conventional high-speed bur specimens (20 control and 20 gamma-irradiated specimens). Microleakage analysis revealed higher scores in both gamma groups compared with control groups. Chi-square test revealed no significant difference between both control groups and gamma groups (p=1, 0.819, respectively). A significant difference was revealed between all 4 groups (p=0.00018). Both laser and conventional high-speed turbine bur show good bond strength in control (non-gamma) group, while microleakage is evident in gamma group, indicating that gamma radiation had a dramatic negative effect on the bond strength in both laser and bur-treated teeth.

Comparison of Various Anthropometric and Body Fat Indices in Identifying Cardiometabolic Disturbances in Chinese Men and Women

PubMed Central

Zhang, Zhe-qing; Deng, Juan; He, Li-ping; Ling, Wen-hua; Su, Yi-xiang; Chen, Yu-ming

2013-01-01

Background Although many adiposity indices may be used to predict obesity-related health risks, uncertainty remains over which of them performs best. Objective This study compared the predictive capability of direct and indirect adiposity measures in identifying people at higher risk of metabolic abnormalities. Methods This population-based cross-sectional study recruited 2780 women and 1160 men. Body weight and height, waist circumference (WC), and hip circumference (HC) were measured and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were calculated. Body fat (and percentage of fat) over the whole body and the trunk were determined by bioelectrical impedance analysis (BIA). Blood pressure, fasting lipid profiles, and glucose and urine acid levels were assessed. Results In women, the ROC and the multivariate logistic regression analyses both showed that WHtR consistently had the best performance in identifying hypertension, dyslipidemia, hyperuricemia, diabetes/IFG, and metabolic syndrome (MetS). In men, the ROC analysis showed that WHtR was the best predictor of hypertension, WHtR and WC were equally good predictors of dyslipidemia and MetS, and WHtR was the second-best predictor of hyperuricemia and diabetes/IFG. The multivariate logistic regression also found WHtR to be superior in discriminating between MetS, diabetes/IFG, and dyslipidemia while BMI performed better in predicting hypertension and hyperuricemia in men. The BIA-derived indices were the second-worst predictors for all of the endpoints, and HC was the worst. Conclusion WHtR was the best predictor of various metabolic abnormalities. BMI may be used as an alternative measure of obesity for identifying hypertension in both sexes. PMID:23951031

[Spatial variability and evaluation of soil heavy metal contamination in the urban-transect of Shanghai].

PubMed

Liu, Yun-Long; Zhang, Li-Jia; Han, Xiao-Fei; Zhuang, Teng-Fei; Shi, Zhen-Xiang; Lu, Xiao-Zhe

2012-02-01

Soil heavy metal concentrations along the typical urban-transect in Shanghai were analyzed to indicate the effect of urbanization and industrialization on soil environment quality. Spatial variation structure and distribution of 5 heavy metals (Cu, Cr, Mn, Pb and Zn) in the top soil of urban-transect were analyzed. The single pollution index and the composite pollution index were used to evaluate the soil heavy metal pollution. The results showed that the average concentrations of the Cu, Pb, Zn, Cr, Mn were 27.80, 28.86, 99.36, 87.72, 556.97 mg x kg(-1), respectively. Cu, Cr, Mn, Pb and Zn were medium in variability, Mn was distributed lognormally, while Cu, Cr, Pb and Zn were distributed normally. The results of semivariance analysis showed that Mn was fit for the exponential model, Cr, Pb, Cu and Zn were fit for the linear model. The spatial distribution maps of heavy metal content of the topsoil in this city-transect were produced by means of the universal kriging interpolation. Cu was spatially distributed in ribbon, Cr and Mn were distributed in island, while the spatial distribution of Pb and Zn showed the mixed characteristic of ribbon and island. With the result of soil pollution evaluation, it showed that the pollution of Cr, Zn and Pb was relatively severe. Cr, Zn, Pb, Mn and Cu were significantly correlated, and heavy metal co-contamination existed in soil. Difference of soil heavy metals pollution along "Urban-suburban-rural" was obvious, the special variation of heavy metal concentrations in the soil closely related to the degree of industrialization and urbanization of the city.

Negative Ion Photoelectron Spectroscopy Reveals Remarkable Noninnocence of Ligands in Nickel Bis(dithiolene) Complexes [Ni(dddt) 2 ] - and [Ni(edo) 2 ] -

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

Liu, Xing; Hou, Gao-Lei; Wang, Xuefeng

2016-04-21

[Ni(dddt) 2] – (dddt = 5,6-dihydro-1,4-dithiine-2,3-dithiolate) and [Ni(edo) 2] – (edo = 5,6-dihydro-1,4-dioxine-2,3-dithiolate) are two donor-type nickel bis(dithiolene) complexes, with the tendency of donating low binding energy electrons. These two structurally similar complexes differ only with respect to the outer atoms in the ligand framework where the former has four S atoms while the latter has four O atoms. Herein, we report a negative ion photoelectron spectroscopy (NIPES) study on these two complexes to probe electronic structures of the anions and their corresponding neutrals. The NIPE spectra exhibit the adiabatic electron detachment energy (ADE) or, equivalently, the electron affinity (EA)more » of the neutral [Ni(L) 2] 0 to be relatively low for this type complexes, 2.780 and 2.375 eV for L = dddt and edo, respectively. The 0.4 eV difference in ADEs shows significant substitution effect for sulfur in dddt by oxygen in edo, i.e., noninnocence of the ligands, which has decreased the electronic stability of [Ni(edo) 2] – by lowering its electron binding energy by ~0.4 eV. The observed substitution effect on gas-phase EA values correlates well with the measured redox potentials for [Ni(dddt) 2] –/0 and [Ni(edo) 2] –/0 in solutions. The singlet-triplet splitting (ΔE ST) of [Ni(dddt) 2] 0 and [Ni(edo) 2] 0 is also determined from the spectra to be 0.57 and 0.53 eV, respectively. Accompanying DFT calculations and molecular orbital (MO) composition analyses show significant ligand contributions to the redox MOs and allow the components of the orbitals involved in each electronic transition and spectral assignments to be identified.« less

Acceptance of and attitudes towards human papillomavirus vaccination in Japanese mothers of adolescent girls.

PubMed

Hanley, Sharon J B; Yoshioka, Eiji; Ito, Yoshiya; Konno, Ryo; Hayashi, Yuri; Kishi, Reiko; Sakuragi, Noriaki

2012-08-24

To better understand how to achieve high uptake rates of human papillomavirus (HPV) vaccination in Japan, we investigated acceptance of and attitudes towards HPV vaccination in 2192 mothers of girls aged 11-14 yrs. A school-based survey was conducted in five elementary and fourteen junior high schools in Sapporo, Japan. Responses from 862 participants were analyzed. Ninety-three percent of mothers would accept the vaccine for their daughter if free, but only 1.5% was willing to pay the minimum recommended price of ¥ 40,000. Vaccine acceptance was higher in mothers who had heard of HPV vaccine (adjusted odds ratio, aOR=2.58, confidence interval, CI=1.47-4.53), and who believed susceptibility to (aOR=2.30, CI=1.34-3.92) and severity of (aOR=3.73, CI=1.41-9.88) HPV to be high. Recommendations from a doctor (aOR=12.60, CI=7.06-21.48) and local health board (aOR=27.80, CI=13.88-55.86) were also positively associated with increased HPV vaccine acceptance. Concerns about side effects of both the HPV vaccine (aOR=0.03, CI=0.01-0.08) and routine childhood vaccines in general (aOR=0.11, CI=0.02-0.78) emerged as barriers to vaccination. Not participating in routine cervical screening also emerged as a deterrent (aOR=0.49, CI=0.27-0.91). While most mothers (66.8%) agreed that 10-14 yr was an appropriate age for vaccination, a further 30.6% believed >15 yr to be more appropriate. In conclusion, attitudes of Japanese mothers toward HPV vaccination are encouraging. While lower vaccine acceptance in mothers who do not undergo regular cervical screening needs further investigation, this study indicates that high uptake may be possible in a publically funded HPV vaccination program if physicians actively address safety concerns and justify why the vaccine is needed at a particular age. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of enamel mineral loss around cavities prepared by the Er,Cr:YSGG laser and restored with different materials

NASA Astrophysics Data System (ADS)

Navarro, Ricardo Scarparo; Lago, Andréa. Dias Neves; Bonifácio, Clarissa Calil; Mendes, Fausto Medeiros; de Freitas, Patrícia Moreira; Baptista, Alessandra; Nunez, Silvia Cristina; Matos, Adriana Bona; Imparato, José Carlos P.

2018-02-01

The aim of this study was to evaluate the enamel demineralization around cavities prepared by Er,Cr:YSGG laser (2780 nm) and restored with different materials after an acid challenge. The human dental enamel samples were randomly divided in 12 groups (n=10): G1- high-speed drill (HD); G2- Er,Cr:YSGG laser L (3 W, 20 Hz, 53.05 J/cm2)(air 65% - water 55%); G3- L (4 W, 20 Hz, 70.74 J/cm2); G4- L (5 W, 20 Hz, 88.43 J/cm2). Each group was divided in subgroups: 1- glass ionomer cement (GIC), 2- resin modified GIC (RMGIC), 3- composite resin (C). Samples were submitted to an acid challenge (4.8 pH) for7 days. The calcium ion contend (ppm/mm2) from demineralizing solutions were analyzed by atomic emission spectrometry. ANOVA and LSD tests were performed (α=5%). The significant lower average values of calcium loss were observed on G2 + GIC, G2 + RMGIC, G1 + RMGIC (p<0.05) the significant higher values were observed on G1 + C, G4 +GIC, G4 + C (p<0.05). The composite resin showed higher calcium loss than RMGIC and GIC (p<0.05). The lased cavities using lower fluence (53.05J/cm2) showed significant reduced demineralization than higher fluences (70.74 and 88.43J/cm2) (p<0.05). Neither the techniques nor the restorative materials used were able to avoid the enamel demineralization. The findings of this in vitro study suggest that the Er,Cr:YSGG lased cavities restored with GIC or RMGIC or conventional drill cavities with RMGIC were effective on reducing the demineralization around restorations, showing an important potential in preventing secondary caries.

Synthesis, antiproliferative and apoptotic activities of N-(6(4)-indazolyl)-benzenesulfonamide derivatives as potential anticancer agents.

PubMed

Abbassi, Najat; Chicha, Hakima; Rakib, El Mostapha; Hannioui, Abdellah; Alaoui, Mdaghri; Hajjaji, Abdelouahed; Geffken, Detlef; Aiello, Cinzia; Gangemi, Rosaria; Rosano, Camillo; Viale, Maurizio

2012-11-01

Recently, it has been reported that compounds bearing a sulfonamide moiety possess many types of biological activities, including anticancer activity. The present work reports the synthesis and antiproliferative evaluation of some N-(6(4)-indazolyl)benzenesulfonamides and 7-ethoxy-N-(6(4)-indazolyl)benzenesulfonamides. All compounds were evaluated for their in vitro antiproliferative activity against three tumor cell lines: A2780 (human ovarian carcinoma) A549 (human lung adenocarcinoma) and P388 (murine leukemia). The results indicated that sulfonamides 2c, 3c, 6d, 8, 13, 3b and 16 were endowed with a pharmacologically interesting antiproliferative activity with compounds 2c and 3c showing the lower IC(50) (from 0.50 ± 0.09 to 1.83 ± 0.52 μM and from 0.58 ± 0.17 to 5.83 ± 1.83 μM, respectively). Moreover, these indazoles were able to trigger apoptosis through the upregulation of the typical apoptosis markers p53 and bax. As regard to the hypothetic targets of these compounds, a preliminary docking analysis showed that all compounds seemed to interact with β-tubulin, in particular compound 3b that showed the lower Ki. The cytofluorimetric analysis of the cell cycle phases indicates that all compounds, when administered at their IC(75), caused a block in the G2/M phase of the cell cycle with the generation of subpopulations of cells with a number of chromosome >4n. When the IC(50)s were applied we observed a prevalent block in the G0/G1 phase except for compounds 16 and 8 where a partial G2/M block was present with a concomitant decrease of cells in the G0/G1 and S phases of the cell cycle. Altogether these results suggest a possible, but not exclusive, interaction with microtubules. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat.

PubMed

Garjani, Alireza; Andalib, Sina; Biabani, Sajjad; Soraya, Hamid; Doustar, Yousef; Garjani, Afagh; Maleki-Dizaji, Nasrin

2011-09-01

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration. Copyright © 2011 Elsevier B.V. All rights

microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP

PubMed Central

Li, Xiaodi; Chen, Wei; Zeng, Wenshu; Wan, Chunling; Duan, Shiwei; Jiang, Songshan

2017-01-01

Background: microRNAs (miRNAs) have regulatory roles in various cellular processes, including apoptosis. Recently, X-linked inhibitor of apoptosis protein (XIAP) has been reported to be dysregulated in epithelial ovarian cancer (EOC). However, the mechanism underlying this dysregulation is largely unknown. Methods: Using bioinformatics and a literature analysis, a panel of miRNAs dysregulated in EOC was chosen for further experimental confirmation from hundreds of miRNAs that were predicted to interact with the XIAP 3′UTR. A dual-luciferase reporter assay was employed to detect the interaction by cellular co-transfection of an miRNA expression vector and a reporter vector with the XIAP 3′UTR fused to a Renilla luciferase reporter. DAPI and TUNEL approaches were used to further determine the effects of an miR-137 mimic and inhibitor on cisplatin-induced apoptosis in ovarian cancer cells. Results: We identified eight miRNAs by screening a panel of dysregulated miRNAs that may target the XIAP 3′UTR. The strongest inhibitory miRNA, miR-137, suppressed the activity of a luciferase reporter gene fused with the XIAP 3′UTR and decreased the levels of XIAP protein in SKOV3 ovarian cancer cells. Furthermore, forced expression of miR-137 increased cisplatin-induced apoptosis, and the depressed expression of miR-137 decreased cisplatin-induced apoptosis in SKOV3 and primary EOC cells. Consistently, the disruption of miR-137 via CRISPR/Cas9 inhibited apoptosis and upregulated XIAP in A2780 cells. Furthermore, the effect of miR-137 on apoptosis could be rescued by XIAP in SKOV3 cells. In addition, miR-137 expression is inversely correlated with the level of XIAP protein in both ovarian cancer tissues and cell lines. Conclusions: Our data suggest that multiple miRNAs can regulate XIAP via its 3′UTR. miR-137 can sensitise ovarian cancer cells to cisplatin-induced apoptosis, providing new insight into overcoming drug resistance in ovarian cancer. PMID:27875524

IL6 induces TAM resistance via kinase-specific phosphorylation of ERα in OVCA cells.

PubMed

Wang, Yue; Niu, Xiu Long; Guo, Xiao Qin; Yang, Jing; Li, Ling; Qu, Ye; Xiu Hu, Cun; Mao, Li Qun; Wang, Dan

2015-06-01

About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology.

Identifying injuries and motor vehicle collision characteristics that together are suggestive of diaphragmatic rupture.

PubMed

Reiff, Donald A; McGwin, Gerald; Metzger, Jesse; Windham, Samuel T; Doss, Marilyn; Rue, Loring W

2002-12-01

Diaphragmatic rupture (DR) remains a diagnostic challenge because of the lack of an accurate test demonstrating the injury. Our purpose was to identify motor vehicle collision (MVC) characteristics and patient injuries that collectively could identify the presence of a DR. The National Automotive Sampling System was used to identify occupants involved in MVCs from 1995 to 1999 who sustained abdominal (Abbreviated Injury Scale score >or= 2) and/or thoracic injuries (Abbreviated Injury Scale score >or= 2). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to quantify the association between patient injuries, vehicle collision characteristics, and DR. Sensitivity and specificity were also calculated to determine the ability of organ injury and MVC characteristics to correctly classify patients with and without DR. Overall, occupants sustaining a DR had a significantly higher delta-V (DeltaV) (49.8 kilometers per hour [kph] vs. 33.8 kph, p< 0.0001) and a greater degree of occupant compartment intrusion (70.6 cm vs. 48.3 cm, p< 0.0001). Specific abdominal and thoracic organ injuries were associated with DR, including thoracic aortic tears (OR, 5.2; 95% CI, 2.2-12.5), splenic injury (OR, 8.4; 95% CI, 3.9-17.8), pelvic fractures (OR, 4.7; 95% CI, 2.7-8.0), and hepatic injuries (OR, 4.2; 95% CI, 1.7-10.6). Combining frontal or near-side lateral occupant compartment intrusion >or= 30 cm or DeltaV >or= 40 kph with specific organ injuries generated a sensitivity for indicating the likelihood of diaphragm injury ranging from 68% to 89%. Patients with any of the following characteristics had a sensitivity for detecting DR of 91%: splenic injury, pelvic fracture, DeltaV >or= 40 kph, or occupant compartment intrusion from any direction >or= 30 cm. Specific MVC characteristics combined with patient injuries have been identified that are highly suggestive of DR. For this subpopulation, additional invasive procedures including exploratory laparotomy, laparoscopy

Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia

PubMed Central

Mkulama, Mtawa AP; Chishimba, Sandra; Sikalima, Jay; Rouse, Petrica; Thuma, Philip E; Mharakurwa, Sungano

2008-01-01

Background In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less than 5 kg and also in expectant mothers. SP is also the choice drug for intermittent preventive therapy in pregnancy and serves as stand-by treatment during ACT stock outs. The current study assessed the status of Plasmodium falciparum point mutations associated with antifolate drug resistance in the area around Macha. Methods A representative sample of 2,780 residents from the vicinity of Macha was screened for malaria by microscopy. At the same time, blood was collected onto filter paper and dried for subsequent P. falciparum DNA analysis. From 188 (6.8%) individuals that were thick film-positive, a simple random sub-set of 95 P. falciparum infections were genotyped for DHFR and DHPS antifolate resistance mutations, using nested PCR and allele-specific restriction enzyme digestion. Results Plasmodium falciparum field samples exhibited a high prevalence of antifolate resistance mutations, including the DHFR triple (Asn-108 + Arg-59 + Ile-51) mutant (41.3%) and DHPS double (Gly-437 + Glu-540) mutant (16%). The quintuple (DHFR triple + DHPS double) mutant was found in 4 (6.5%) of the samples. Levels of mutated parasites showed a dramatic escalation, relative to previous surveys since 1988. However, neither of the Val-16 and Thr-108 mutations, which jointly confer resistance to cycloguanil, was detectable among the human infections. The Leu-164 mutation, associated with high grade resistance to both pyrimethamine and cycloguanil, as a multiple mutant with Asn-108, Arg-59 and (or) Ile-51, was also absent. Conclusion This study points to escalating levels of P. falciparum antifolate resistance in the vicinity of Macha. Continued monitoring is recommended to ensure timely policy

Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer.

PubMed

Hu, Jianguo; Zhang, Luo; Mei, Zhiqiang; Jiang, Yuan; Yi, Yuan; Liu, Li; Meng, Ying; Zhou, Lili; Zeng, Jianhua; Wu, Huan; Jiang, Xingwei

2018-05-22

Ubiquitin E3 ligase MARCH7 plays an important role in T cell proliferation and neuronal development. But its role in ovarian cancer remains unclear. This study aimed to investigate the role of Ubiquitin E3 ligase MARCH7 in ovarian cancer. Real-time PCR, immunohistochemistry and western blotting analysis were performed to determine the expression of MARCH7, MALAT1 and ATG7 in ovarian cancer cell lines and clinical specimens. The role of MARCH7 in maintaining ovarian cancer malignant phenotype was examined by Wound healing assay, Matrigel invasion assays and Mouse orthotopic xenograft model. Luciferase reporter assay, western blot analysis and ChIP assay were used to determine whether MARCH7 activates TGF-β-smad2/3 pathway by interacting with TGFβR2. MARCH7 interacted with MALAT1 by miR-200a (microRNA-200a). MARCH7 may function as a competing endogenous RNA (ceRNA) to regulate the expression of ATG7 by competing with miR-200a. MARCH7 regulated TGF-β-smad2/3 pathway by interacting with TGFβR2. Inhibition of TGF-β-smad2/3 pathway downregulated MARCH7, MALAT1 and ATG7. MiR-200a regulated TGF-β induced autophagy, invasion and metastasis of SKOV3 cells by targeting MARCH7. MARCH7 silencing inhibited autophagy invasion and metastasis of SKOV3 cells both in vitro and in vivo. In contrast, MARCH7 overexpression promoted TGF-β induced autophagy, invasion and metastasis of A2780 cells in vitro by depending on MALAT1 and ATG7. We also found that TGF-β-smad2/3 pathway regulated MARCH7 and ATG7 through MALAT1. These findings suggested that TGFβR2-Smad2/3-MALAT1/MARCH7/ATG7 feedback loop mediated autophagy, migration and invasion in ovarian cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer.

PubMed

Shigeta, S; Toyoshima, M; Kitatani, K; Ishibashi, M; Usui, T; Yaegashi, N

2016-07-07

Fallopian tubal epithelium is a candidate for the origin of high-grade serous ovarian cancer. Transferrin-containing follicular fluid and/or retrograde menstrual blood are possible risk factors for carcinogenesis. Accumulation of DNA double-strand breaks (DNA-DSBs) in the fallopian tubal epithelium is considered to play an important role in the development of cancer. However, the mechanisms by which DNA-DSBs accumulate have not yet been fully elucidated. The hydroxyl radical, which is produced in a Fenton reaction catalyzed by an iron ion, serves as a potent DNA-DSB-inducing molecule, raising the potential of an iron ion transporter of transferrin in the formation of DNA-DSBs. We studied the potential involvement of transferrin in DNA damage and the development of ovarian cancer. Treatment with transferrin facilitated the formation of histone 2AX phosphorylated at Serine 139 (γH2AX), which is known as a DNA-DSB marker, in human fallopian tube secretory epithelial cells and A2780 ovarian cancer cells. Knockdown of transferrin receptor 1 (TfR1), but not transferrin receptor 2, suppressed the transferrin uptake and consequent formation of γH2AX. As hydroxyl radicals in reactive oxygen species (ROS) are involved in DNA-DSBs, the formation of ROS was determined. Treatment with TfR1-specific small interference RNAs significantly diminished transferrin-induced formation of ROS. Moreover, TfR1-dependent uptake of transferrin was revealed to augment the formation of DNA-DSBs in the presence of hydrogen peroxide, which served as a substrate for the Fenton reaction. An ex vivo study with murine fallopian tubes further demonstrated that transferrin treatment introduced DNA-DSBs in the fallopian tubal epithelium. Collectively, these data suggested that the transferrin-TfR1 axis accounts for the induction of DNA-DSBs that potentially lead to DNA damage/genome instability. These findings also suggested that exposure to transferrin initiates and promotes the development of

Therapeutic effect of Chinese herbal medicines for post stroke recovery

PubMed Central

Han, Shi-You; Hong, Zhi-You; Xie, Yu-Hua; Zhao, Yong; Xu, Xiao

2017-01-01

Abstract Background: Stroke is a condition with high morbidity and mortality, and 75% of stroke survivors lose their ability to work. Stroke is a burden to the family and society. The purpose of this study was to evaluate the effectiveness of Chinese herbal patent medicines in the treatment of patients after the acute phase of a stroke. Methods: We searched the following databases through August 2016: PubMed, Embase, Cochrane library, China Knowledge Resource Integrated Database (CNKI), China Science Periodical Database (CSPD), and China Biology Medicine disc (CBMdisc) for studies that evaluated Chinese herbal patent medicines for post stroke recovery. A random-effect model was used to pool therapeutic effects of Chinese herbal patent medicines on stroke recovery. Network meta-analysis was used to rank the treatment for each Chinese herbal patent medicine. Results: In our meta-analysis, we evaluated 28 trials that included 2780 patients. Chinese herbal patent medicines were effective in promoting recovery after stroke (OR, 3.03; 95% CI: 2.53–3.64; P < .001). Chinese herbal patent medicines significantly improved neurological function defect scores when compared with the controls (standard mean difference [SMD], −0.89; 95% CI, −1.44 to −0.35; P = .001). Chinese herbal patent medicines significantly improved the Barthel index (SMD, 0.73; 95% CI, 0.53–0.94; P < .001) and the Fugl–Meyer assessment scores (SMD, 0.60; 95% CI, 0.34–0.86; P < .001). In the network analysis, MLC601, Shuxuetong, and BuchangNaoxintong were most likely to improve stroke recovery in patients without acupuncture. Additionally, Mailuoning, Xuesaitong, BuchangNaoxintong were the patented Chinese herbal medicines most likely to improve stroke recovery when combined with acupuncture. Conclusions: Our research suggests that the Chinese herbal patent medicines were effective for stroke recovery. The most effective treatments for stroke recovery were MLC601, Shuxuetong

Precise Gravity Measurements for Lunar Laser Ranging at Apache Point Observatory

NASA Astrophysics Data System (ADS)

Crossley, D. J.; Murphy, T.; Boy, J.; De Linage, C.; Wheeler, R. D.; Krauterbluth, K.

2012-12-01

Lunar Laser Ranging (LLR) at Apache Point Observatory began in 2006 under the APOLLO project using a 3.5 m telescope on a 2780 m summit in New Mexico. Recent improvements in the technical operations are producing uncertainties at the few-mm level in the 1.5 x 10^13 cm separation of the solar orbits of the Earth and Moon. This level of sensitivity permits a number of important aspects of gravitational theory to be tested. Among these is the Equivalence Principle that determines the universality of free fall, tests of the time variation of the Gravitational Constant G, deviations from the inverse square law, and preferred frame effects. In 2009 APOLLO installed a superconducting gravimeter (SG) on the concrete pier under the main telescope to further constrain the deformation of the site as part of an initiative to improve all aspects of the modeling process. We have analyzed more than 3 years of high quality SG data that provides unmatched accuracy in determining the local tidal gravimetric factors for the solid Earth and ocean tide loading. With on-site gravity we have direct measurements of signals such as polar motion, and can compute global atmospheric and hydrological loading for the site using GLDAS and local hydrology models that are compared with the SG observations. We also compare the SG residuals with satellite estimates of seasonal ground gravity variations from the GRACE mission. Apache Point is visited regularly by a team from the National Geospatial-Intelligence Agency to provide absolute gravity values for the calibration of the SG and to determine secular gravity changes. Nearby GPS location P027 provides continuous position information from the Plate Boundary Observatory of Earthscope that is used to correlate gravity/height variations at the site. Unusual aspects of the data processing include corrections for the telescope azimuth that appear as small offsets at the 1 μGal level and can be removed by correlating the azimuth data with the SG

Thoracic cavity segmentation algorithm using multiorgan extraction and surface fitting in volumetric CT

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

Bae, JangPyo; Kim, Namkug, E-mail: namkugkim@gmail.com; Lee, Sang Min

2014-04-15

Purpose: To develop and validate a semiautomatic segmentation method for thoracic cavity volumetry and mediastinum fat quantification of patients with chronic obstructive pulmonary disease. Methods: The thoracic cavity region was separated by segmenting multiorgans, namely, the rib, lung, heart, and diaphragm. To encompass various lung disease-induced variations, the inner thoracic wall and diaphragm were modeled by using a three-dimensional surface-fitting method. To improve the accuracy of the diaphragm surface model, the heart and its surrounding tissue were segmented by a two-stage level set method using a shape prior. To assess the accuracy of the proposed algorithm, the algorithm results ofmore » 50 patients were compared to the manual segmentation results of two experts with more than 5 years of experience (these manual results were confirmed by an expert thoracic radiologist). The proposed method was also compared to three state-of-the-art segmentation methods. The metrics used to evaluate segmentation accuracy were volumetric overlap ratio (VOR), false positive ratio on VOR (FPRV), false negative ratio on VOR (FNRV), average symmetric absolute surface distance (ASASD), average symmetric squared surface distance (ASSSD), and maximum symmetric surface distance (MSSD). Results: In terms of thoracic cavity volumetry, the mean ± SD VOR, FPRV, and FNRV of the proposed method were (98.17 ± 0.84)%, (0.49 ± 0.23)%, and (1.34 ± 0.83)%, respectively. The ASASD, ASSSD, and MSSD for the thoracic wall were 0.28 ± 0.12, 1.28 ± 0.53, and 23.91 ± 7.64 mm, respectively. The ASASD, ASSSD, and MSSD for the diaphragm surface were 1.73 ± 0.91, 3.92 ± 1.68, and 27.80 ± 10.63 mm, respectively. The proposed method performed significantly better than the other three methods in terms of VOR, ASASD, and ASSSD. Conclusions: The proposed semiautomatic thoracic cavity segmentation method, which extracts multiple organs (namely, the rib, thoracic wall, diaphragm, and heart

Reduction of costs for anemia-management drugs associated with the use of ferric citrate

PubMed Central

Thomas, Anila; Peterson, Leif E

2014-01-01

Background Ferric citrate is a novel phosphate binder which has the potential to reduce usage of erythropoietin-stimulating agents (ESAs) and intravenous (IV) iron used for anemia management during hemodialysis (HD) among patients with end-stage renal disease (ESRD). Currently, the potential health care cost savings on a national scale due to the use of ferric citrate in ESRD are undetermined. Methods Per-patient-per-year costs of ESAs (Epogen® and Aranesp® [Amgen Inc., CA, USA]) and IV iron (Venofer® [American Regent, Inc., NY, USA] and Ferrlecit® [Sanofi US, Bridgewater, NJ, USA]) were based on RED BOOK™ (Truven Health Analytics New York, NY, USA) costs combined with the Centers for Medicare and Medicaid Services (CMS) base rate and actual usage in 2011 for the four drugs. The annual number of outpatients undergoing HD in the US was based on frequencies reported by the USRDS (United States Renal Data System). Monte Carlo uncertainty analysis was performed to determine total annual costs and cost reduction based on ferric citrate usage. Results Total annual cost of ESAs and IV iron for anemia management in ESRD determined by Monte Carlo analysis assuming CMS base rate value was 5.127 (3.664–6.260) billion USD. For actual utilization in 2011, total annual cost of ESAs and IV iron was 3.981 (2.780–4.930) billion USD. If ferric citrate usage reduced ESA utilization by 20% and IV iron by 40%, then total cost would be reduced by 21.2% to 4.038 (2.868–4.914) billion USD for the CMS base rate, and by 21.8% to 3.111 (2.148–3.845) billion USD, based on 2011 actual utilization. Conclusion It is likely that US health care costs for anemia-management drugs associated with ESRD among HD patients can be reduced by using ferric citrate as a phosphate binder. PMID:24899820

Human management and landscape changes at Palaikastro (Eastern Crete) from the Late Neolithic to the Early Minoan period

NASA Astrophysics Data System (ADS)

Cañellas-Boltà, N.; Riera-Mora, S.; Orengo, H. A.; Livarda, A.; Knappett, C.

2018-03-01

On the east Mediterranean island of Crete, a hierarchical society centred on large palatial complexes emerges during the Bronze Age. The economic basis for this significant social change has long been debated, particularly concerning the role of olive cultivation in the island's agricultural system. With the aim of studying vegetation changes and human management to understand the landscape history from Late Neolithic to Bronze Age, two palaeoenvironmental records have been studied at Kouremenos marsh, near the site of Palaikastro (Eastern Crete). Pollen, NPP and charcoal particles analyses evidenced seven phases of landscape change, resulting from different agricultural and pastoral practices and the use of fire probably to manage vegetation. Moreover, the Kouremenos records show the importance of the olive tree in the area. They reflect a clear trend for its increasing use and exploitation from 3600 cal yr BC (Final Neolithic) to the Early Minoan period, that is coeval with an opening of the landscape. The increase of Olea pollen was due to the expansion of the tree and its management using pruning and mechanical cleaning. The onset of olive expansion at c. 3600 cal yr BC places Crete among the first locales in the eastern Mediterranean in the management of this tree. Between c. 2780 and 2525 cal yr BC the landscape was largely occupied by olive and grasslands, coinciding with an increase in grazing practices. The high Olea pollen percentages (40-45%) suggest an intensive and large-scale exploitation of the olive tree. The results suggest that a complex and organized landscape with complementary land uses and activities was already in place since the Final Neolithic. The notable expansion of olive trees suggests the relevance of olive exploitation in the socio-economic development of Minoan towns of eastern Crete. Other crops, such as cereals and vine, and activities such as grazing have also played an important role in the configuration of the past landscape.

Fungicide dissipation and impact on metolachlor aerobic soil degradation and soil microbial dynamics.

PubMed

White, Paul M; Potter, Thomas L; Culbreath, Albert K

2010-02-15

Pesticides are typically applied as mixtures and or sequentially to soil and plants during crop production. A common scenario is herbicide application at planting followed by sequential fungicide applications post-emergence. Fungicides depending on their spectrum of activity may alter and impact soil microbial communities. Thus there is a potential to impact soil processes responsible for herbicide degradation. This may change herbicide efficacy and environmental fate characteristics. Our study objective was to determine the effects of 4 peanut fungicides, chlorothalonil (2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile), tebuconazole (alpha-[2-(4-chlorophenyl)ethyl]-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol), flutriafol (alpha-(2-fluorophenyl)-alpha-(4-fluorophenyl)-1H-1,2,4-triazole-1-ethanol), and cyproconazole (alpha-(4-chlorophenyl)-alpha-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol) on the dissipation kinetics of the herbicide, metolachlor (2-chloro-N-(6-ethyl-o-tolyl)-N-[(1RS)-2-methoxy-1-methylethyl]acetamide), and on the soil microbial community. This was done through laboratory incubation of field treated soil. Chlorothalonil significantly reduced metolachlor soil dissipation as compared to the non-treated control or soil treated with the other fungicides. Metolachlor DT(50) was 99 days for chlorothalonil-treated soil and 56, 45, 53, and 46 days for control, tebuconazole, flutriafol, and cyproconazole-treated soils, respectively. Significant reductions in predominant metolachlor metabolites, metolachlor ethane sulfonic acid (MESA) and metolachlor oxanilic acid (MOA), produced by oxidation of glutathione-metolachlor conjugates were also observed in chlorothalonil-treated soil. This suggested that the fungicide impacted soil glutathione-S-transferase (GST) activity. Fungicide DT(50) was 27-80 days but impacts on the soil microbial community as indicated by lipid biomarker analysis were minimal. Overall study results indicated that

QTL mapping of downy and powdery mildew resistances in PI 197088 cucumber with genotyping-by-sequencing in RIL population.

PubMed

Wang, Yuhui; VandenLangenberg, Kyle; Wen, Changlong; Wehner, Todd C; Weng, Yiqun

2018-03-01

Host resistances in PI 197088 cucumber to downy and powdery mildew pathogens are conferred by 11 (3 with major effect) and 4 (1 major effect) QTL, respectively, and three of which are co-localized. The downy mildew (DM) and powdery mildew (PM) are the two most important foliar diseases of cucurbit crops worldwide. The cucumber accession PI 197088 exhibits high-level resistances to both pathogens. Here, we reported QTL mapping results for DM and PM resistances with 148 recombinant inbred lines from a cross between PI 197088 and the susceptible line 'Coolgreen'. Phenotypic data on responses to natural DM and PM infection were collected in multi-year and multi-location replicated field trials. A high-density genetic map with 2780 single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing and 55 microsatellite markers was developed, which revealed genomic regions with segregation distortion and mis-assemblies in the '9930' cucumber draft genome. QTL analysis identified 11 and 4 QTL for DM and PM resistances accounting for more than 73.5 and 63.0% total phenotypic variance, respectively. Among the 11 DM resistance QTL, dm5.1, dm5.2, and dm5.3 were major-effect contributing QTL, whereas dm1.1, dm2.1, and dm6.2 conferred susceptibility. Of the 4 QTL for PM resistance, pm5.1 was the major-effect QTL explaining 32.4% phenotypic variance and the minor-effect QTL pm6.1 contributed to disease susceptibility. Three PM QTL, pm2.1, pm5.1, and pm6.1, were co-localized with DM QTL dm2.1, dm5.2, and dm6.1, respectively, which was consistent with the observed linkage of PM and DM resistances in PI 197088. The genetic architecture of DM resistance in PI 197088 and another resistant line WI7120 (PI 330628) was compared, and the potential of using PI 197088 in cucumber breeding for downy and powdery mildew resistances is discussed.

Lost productive life years caused by chronic conditions in Australians aged 45-64 years, 2010-2030.

PubMed

Schofield, Deborah J; Shrestha, Rupendra N; Cunich, Michelle; Tanton, Robert; Kelly, Simon; Passey, Megan E; Veerman, Lennert J

2015-09-21

To estimate (1) productive life years (PLYs) lost because of chronic conditions in Australians aged 45-64 years from 2010 to 2030, and (2) the impact of this loss on gross domestic product (GDP) over the same period. A microsimulation model, Health&WealthMOD2030, was used to project lost PLYs caused by chronic conditions from 2010 to 2030. The base population consisted of respondents aged 45-64 years to the Australian Bureau of Statistics Survey of Disability, Ageing and Carers 2003 and 2009. The national impact of lost PLYs was assessed with Treasury's GDP equation. Lost PLYs due to chronic disease at 2010, 2015, 2020, 2025 and 2030 (ie, whole life years lost because of chronic disease); the national impact of lost PLYs at the same time points (GDP loss caused by PLYs); the effects of population growth, labour force trends and chronic disease trends on lost PLYs and GDP at each time point. Using Health&WealthMOD2030, we estimated a loss of 347,000 PLYs in 2010; this was projected to increase to 459,000 in 2030 (32.28% increase over 20 years). The leading chronic conditions associated with premature exits from the labour force were back problems, arthritis and mental and behavioural problems. The percentage increase in the number of PLYs lost by those aged 45-64 years was greater than that of population growth for this age group (32.28% v 27.80%). The strongest driver of the increase in lost PLYs was population growth (accounting for 89.18% of the increase), followed by chronic condition trends (8.28%). Our study estimates an increase of 112 000 lost PLYs caused by chronic illness in older workers in Australia between 2010 and 2030, with the most rapid growth projected to occur in men aged 55-59 years and in women aged 60-64 years. The national impact of this lost labour force participation on GDP was estimated to be $37.79 billion in 2010, increasing to $63.73 billion in 2030.

Urban-rural and geographic differences in overweight and obesity in four sub-Saharan African adult populations: a multi-country cross-sectional study.

PubMed

Ajayi, IkeOluwapo O; Adebamowo, Clement; Adami, Hans-Olov; Dalal, Shona; Diamond, Megan B; Bajunirwe, Francis; Guwatudde, David; Njelekela, Marina; Nankya-Mutyoba, Joan; Chiwanga, Faraja S; Volmink, Jimmy; Kalyesubula, Robert; Laurence, Carien; Reid, Todd G; Dockery, Douglas; Hemenway, David; Spiegelman, Donna; Holmes, Michelle D

2016-10-28

Overweight and obesity are on the rise in developing countries including sub-Saharan Africa. We undertook a four-country survey to show the collective burden of these health conditions as they occur currently in sub-Saharan Africa and to determine the differences between urban and rural populations and other socio-economic factors. Participants were nurses in two hospitals in Nigeria (200), school teachers in South Africa (489) and Tanzania (229), and village residents in one peri-urban (297) and one rural location in Uganda (200) who completed a standardised questionnaire. Their height and weight were measured and body mass index calculated. Factor analysis procedure (Principal component) was used to generate a wealth index. Univariate and multivariate analyses with binary logistic regression models were conducted to examine the associations between potential correlates and the prevalence of overweight and obesity with 95 % confidence intervals. The prevalence of overweight and obese (combined) was 46 %, 48 %, 68 %, 75 % and 85 % in rural Uganda, peri-urban Uganda, Nigeria, Tanzania and South Africa (SA), respectively. Rural Uganda, Peri- urban Uganda, Nigeria, Tanzania and SA had obesity prevalence of 10 %, 14 %, 31 %, 40 % and 54 %, respectively (p < 0.001). Overall, prevalence of overweight was 374 (31 %) and obesity, 414 (34 %). Female sex was a predictor of overweight and obesity (combined) in peri-urban Uganda [AOR = 8.01; 95 % CI: 4.02, 15.96) and obesity in rural Uganda [AOR = 11.22; 95%CI: 2.27, 55.40), peri-urban Uganda [AOR = 27.80; 95 % CI: 7.13, 108.41) and SA [AOR = 2.17; 95 % CI: 1.19, 4.00). Increasing age was a predictor of BMI > =25 kg/m 2 in Nigeria [Age > =45 - AOR = 9.11; 95 % CI: 1.72, 48.16] and SA [AOR = 6.22; 95 % CI: 2.75, 14.07], while marital status was predictor of BMI > =25 kg/m 2 only in peri-urban Uganda. [Married - AOR = 4.49; 95 % CI: 1.74, 11.57]. Those in Nigeria [AOR�

Physicochemical Properties, Antioxidant and Anti-proliferative Capacities of Dried Leaf and Its Extract from Xao tam phan (Paramignya trimera).

PubMed

Nguyen, Van Tang; Sakoff, Jennette A; Scarlett, Christopher J

2017-06-01

Xao tam phan (Paramignya trimera) has been used for the treatment of cancer and cancer-like aliments. Among different parts of the P. trimera plant, leaf is considered as a residual part after harvesting of the root. This study aimed to determine the physiochemical properties and the antioxidant and anti-proliferative capacities of P. trimera leaf (PTL) using microwave drying for the preparation of dry sample; MeOH and microwave-assisted extraction for the preparation of crude extract; and freeze-drying for the preparation of powdered extract. The results showed that total phenolic, total flavonoid, proanthocyanidin, and saponin contents of PTL prepared by microwave drying at 450 W were 25.4 mg gallic acid equiv. (GAE), 86.3 mg rutin equiv. (RE), 5.6 mg catechin equiv. (CE), and 702.1 mg escin equiv. (EE) per gram dried sample, respectively. Gallic acid, protocatechuic acid, ellagic acid, rutin, and quercetin were identified in the PTL MeOH extract. Dried PTL displayed potent antioxidant activity, while the powdered PTL extract exhibited great anti-proliferative capacity on various cancer cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, and SMA (glioblastoma). Anti-proliferative capacity on pancreatic cancer cells (MiaCaPa2, BxPc3, and CFPAC1) of PTL extract (200 μg/ml) was significantly higher (P < 0.05) than those of ostruthin (20 μg/ml) and gemcitabine (50 nm), and to be comparable to the powdered P. trimera root extract and a saponin-enriched extract from quillajia bark (a commercial product). The findings from this study allow us to conclude that the PTL is a rich source of phytochemicals that possess promising antioxidant and anti-proliferative activities, therefore it shows potential as lead compounds for application in the nutraceutical, medicinal and pharmaceutical industries. © 2017 Wiley

Association of Loss of Independence With Readmission and Death After Discharge in Older Patients After Surgical Procedures.

PubMed

Berian, Julia R; Mohanty, Sanjay; Ko, Clifford Y; Rosenthal, Ronnie A; Robinson, Thomas N

2016-09-21

Older adults are at increased risk for adverse events after surgical procedures. Loss of independence (LOI), defined as a decline in function or mobility, increased care needs at home, or discharge to a nonhome destination, is an important patient-centered outcome measure. To evaluate LOI among older adult patients after surgical procedures and examine the association of LOI with readmission and death after discharge in this population. This retrospective cohort study examined 9972 patients 65 years and older with known baseline function, mobility, and living situation undergoing inpatient operations from January 2014 to December 2014 at 26 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program Geriatric Surgery Pilot Project. A total of 4895 patients were excluded because they were totally dependent, classified as class 5 by the American Society of Anesthesiologists, undergoing orthopedic or spinal procedures, or died prior to discharge. Loss of independence at time of discharge. Readmission and death after discharge. Of the 5077 patients included in this study, 2736 (53.9%) were female and 3876 (76.3%) were white, with a mean (SD) age of 75 (7) years. For this cohort, LOI increased with age; LOI occurred in 1386 of 2780 patients (49.9%) aged 65 to 74 years, 1162 of 1726 (67.3%) aged 75 to 84 years, and 479 of 571 (83.9%) 85 years and older (P < .001). Readmission occurred in 517 patients (10.2%). In a risk-adjusted model, LOI was strongly associated with readmission (odds ratio, 1.7; 95% CI, 1.4-2.2) and postoperative complication (odds ratio, 6.7; 95% CI, 4.9-9.0). Death after discharge occurred in 69 patients (1.4%). After risk adjustment, LOI was the strongest factor associated with death after discharge (odds ratio, 6.7; 95% CI, 2.4-19.3). Postoperative complication was not significantly associated with death after discharge. Loss of independence, a patient-centered outcome, was associated with

VizieR Online Data Catalog: TU UMa light curves and maxima, CL Aur minima (Liska+, 2016)

NASA Astrophysics Data System (ADS)

Liska, J.; Skarka, M.; Mikulasek, Z.; Zejda, M.; Chrastina, M.

2016-02-01

Differential photometry for RR Lyrae star TU UMa in the 1st and 2nd file. The measurements were obtained using 24-inch and 1-inch telescopes, respectively. The observations were performed at the Masaryk University Observatory in Brno (3 nights, 24-inch), and at the private observatory in Brno (16 nights, 1-inch) in the Czech Republic from December 2013 to June 2014. Observing equipments consisted of 24-inch Newtonian telescope (600/2780mm, diameter/focal length) and a Moravian Instruments CCD camera G2-4000 with Stromgren photometric filters vby, and of 1-inch refractor (a photographic lens Sonnar 4/135mm, lens focal ratio/focal length) and ATIK 16IC CCD camera with green photometric filter with similar throughput as the Johnson V filter. Exposures were v - 60s, b - 30s, y - 30s, green - 30s. For the small aperture telescope, five frames were combined to a single image to achieve a better signal-to-noise ratio. The time resolution of a such combined frame is about 170s. CCD images were calibrated in a standard way (dark frame and flat field corrections). The C-Munipack software (Motl 2009) was used for this processing as well as for differential photometry. The comparison star BD+30 2165 was the same for both instruments, but the control stars were BD+30 2164 (for the 24-inch telescope) and HD 99593 (for the 1-inch telescope). The 3rd file contains maxima timings of TU UMa adopted from the GEOS RR Lyr database, from the latest publications, together with maxima timings determined in our study. Times of maxima were calculated from our observations, sky-surveys data (Hipparcos, NSVS, Pi of the Sky, SuperWASP), photographic measurements (project DASCH), and from several published datasets, in which the maxima were omitted or badly determined - Boenigk (1958AcA.....8...13B), Liakos, Niarchos (2011IBVS.6099....1L, 2011IBVS.5990....1L), Liu, Janes (1989ApJS...69..593L), Preston et al. (1961ApJ...133..484P). The 4th file contains minima timings of eclipsing binary CL Aur

Cr-enriched yeast: beyond fibers for the management of postprandial glycemic response to bread.

PubMed

Yanni, Amalia E; Stamataki, Nikoleta; Stoupaki, Maria; Konstantopoulos, Panagiotis; Pateras, Irene; Tentolouris, Nikolaos; Perrea, Despoina; T Karathanos, Vaios

2017-06-01

Efforts regarding the amelioration of postprandial glycemic response to bread are mainly focused in the addition of soluble dietary fibers. The current study presents another approach which is based on the supplementation of flour with Cr-enriched yeast. Cr is known for its beneficial effects on improvement of glucose tolerance and enhancement of insulin sensitivity. Twelve normoglycemic subjects were provided with white bread (WB, reference food) or whole wheat bread with Cr-enriched yeast (WWCrB, rich in insoluble fibers) or white wheat bread with Cr-enriched yeast (WCrB, poor in fibers) or whole wheat-rye-barley bread enriched with oat beta glucans (BGB, rich in soluble fibers) with 1-week intervals in amounts that yielded 50 g of available carbohydrates. Postprandial glucose, insulin and ghrelin responses as well as glycemic index (GI) were evaluated. Ingestion of WWCrB, WCrB and BGB elicited lower incremental area under the curve (iAUC) for 120-min glycemic response compared to WB (1033.02 ± 282.32, 701.69 ± 330.86 and 748.95 ± 185.42 vs 2070.87 ± 518.44 mg/dL min, respectively, P < 0.05 for WCrB and BGB). The GI was calculated as 62.35 ± 11.78 for WWCrB, 34.22 ± 11.93 for WCrB and 37.90 ± 5.00 for BGB (P < 0.05 vs WB, GI = 100). iAUC for 120-min insulin response to BGB was significantly lower than WB (2780.04 ± 303.26 vs 3915.53 ± 490.57 μU/mL min, P < 0.05), while ghrelin remained suppressed for almost 120 min after the consumption of WWCrB and BGB. Supplementation of flour with Cr-enriched yeast induces milder postprandial glycemic response to bread without the necessity of high fiber amounts, providing with another strategy for the management of glycemic control.

Internet-based treatment of stress urinary incontinence: 1- and 2-year results of a randomized controlled trial with a focus on pelvic floor muscle training.

PubMed

Sjöström, Malin; Umefjord, Göran; Stenlund, Hans; Carlbring, Per; Andersson, Gerhard; Samuelsson, Eva

2015-12-01

To evaluate the long-term effects of two non-face-to-face treatment programmes for stress urinary incontinence (SUI) based on pelvic floor muscle training (PFMT). The present study was a randomized controlled trial with online recruitment of 250 community-dwelling women aged 18-70 years with SUI ≥ one time/week. Diagnosis was based on validated self-assessed questionnaires, 2-day bladder diary and telephone interview with a urotherapist. Consecutive computer-generated block randomization was carried out with allocation by an independent administrator to 3 months of treatment with either an internet-based treatment programme (n = 124) or a programme sent by post (n = 126). Both interventions focused mainly on PFMT. The internet group received continuous e-mail support from a urotherapist, whereas the postal group trained on their own. Follow-up was performed after 1 and 2 years via self-assessed postal questionnaires. The primary outcomes were symptom severity (International Consultation on Incontinence Questionnaire Short Form [ICIQ-UI SF]) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]). Secondary outcomes were the Patient Global Impression of Improvement, health-specific quality of life (EQ-visual analogue scale [EQ-VAS]), use of incontinence aids, and satisfaction with treatment. There was no face-to-face contact with the participants at any time. Analysis was based on intention-to-treat. We lost 32.4% (81/250) of participants to follow-up after 1 year and 38.0% (95/250) after 2 years. With both interventions, we observed highly significant (P < 0.001) improvements with large effect sizes (>0.8) for symptoms and condition-specific quality of life (QoL) after 1 and 2 years, respectively. No significant differences were found between the groups. The mean (sd) changes in symptom score were 3.7 (3.3) for the internet group and 3.2 (3.4) for the postal group (P = 0.47) after 1 year, and 3.6 (3.5) for the

Anaesthetic, analgesic and cardiorespiratory effects of intramuscular medetomidine-ketamine combination alone or with morphine or tramadol for orchiectomy in cats.

PubMed

Zeiler, Gareth E; Dzikiti, Brighton T; Fosgate, Geoffrey T; Stegmann, Frik G; Venter, Frans J; Rioja, Eva

2014-07-01

To compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats. Randomised, blinded, prospective clinical study. Thirty client-owned cats. Cats (n = 10 in each group) received a combination of medetomidine (60 μgkg(-1) ) and ketamine (10 mg kg(-1) ) alone (MedK); combined with morphine (0.2 mg kg(-1) ) (MedKM), or combined with tramadol (2 mg kg(-1) ) (MedKT) IM. Time of induction, surgical and recovery events were recorded, and physiological parameters measured and recorded. Analgesia was evaluated with a visual analogue scale, a composite scoring system and the von Frey mechanical threshold device, every hour from three to eight hours post-drug administration injection. Data were analyzed with a linear mixed model, Kruskal-Wallis or Chi-square tests (p < 0.05). Median (IQR) induction and recovery times (minutes) were not significantly (p = 0.125) different between groups: 5.6 (2.7-8.0), 7.4 (5.1-9.6) and 8.0 (5.8-14.9) for induction and 128.5 (95.1-142.8), 166.4 (123.1-210.0) and 142.9 (123.4-180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two cats (MedKM) required alfaxalone for endotracheal intubation. In all groups, three or four cats required additional isoflurane for surgery. Arterial oxygen tension overall (mean ± SD: 66 ± 2 mmHg) was low. Surgery resulted in increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did not differ significantly between groups. Von Frey responses decreased over time; changes over time varied by treatment (p < 0.001), MedK returning to baseline values more rapidly than MedKM and MedKT. No cat required rescue analgesics. All three protocols can provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia may be

The effect of orientation difference in fused deposition modeling of ABS polymer on the processing time, dimension accuracy, and strength

NASA Astrophysics Data System (ADS)

Tanoto, Yopi Y.; Anggono, Juliana; Siahaan, Ian H.; Budiman, Wesley

2017-01-01

There are several parameters that must be set before manufacturing a product using 3D printing. These parameters include the orientation deposition of that product, type of material, form fill, fill density, and other parameters. The finished product of 3D printing has some responses that can be observed, measured, and tested. Some of those responses are the processing time, the dimensions of the end product, its surface roughness and the mechanical properties, i.e. its yield strength, ultimate tensile strength, and impact resistance. This research was conducted to study the relationship between process parameters of 3D printing machine using a technology of fused deposition modeling (FDM) and the generated responses. The material used was ABS plastic that was commonly used in the industry. Understanding the relationship between the parameters and the responses thus the resulting product can be manufactured to meet the user needs. Three different orientations in depositing the ABS polymer named XY(first orientation), YX (second orientation), and ZX (third orientation) were studied. Processing time, dimensional accuracy, and the product strength were the responses that were measured and tested. The study reports that the printing process with third orientation was the fastest printing process with the processing time 2432 seconds followed by orientation 1 and 2 with a processing time of 2688 and 2780 seconds respectively. Dimension accuracy was also measured from the width and the length of gauge area of tensile test specimens printed in comparison with the dimensions required by ASTM 638-02. It was found that the smallest difference was in thickness dimension, i.e. 0.1 mm thicker in printed sample using second orientation than as required by the standard. The smallest thickness deviation from the standard was measured in width dimension of a sample printed using first orientation (0.13 mm). As with the length dimension, the closest dimension to the standard was

Intimate partner violence and HIV infection among married Indian women.

PubMed

Silverman, Jay G; Decker, Michele R; Saggurti, Niranjan; Balaiah, Donta; Raj, Anita

2008-08-13

Despite reductions in prevalence of human immunodeficiency virus (HIV) infection among the general population of India, women account for a rising percentage of all HIV cases with husbands' risk behavior described as the major source of women's infection. Intimate partner violence (IPV) has been described as being associated with heterosexual transmission of HIV to women in India and elsewhere. To assess the relationship between experiencing IPV and the occurrence of HIV infection in a nationally representative sample of married Indian women tested for HIV. The Indian National Family Health Survey 3 was conducted across all Indian states in 2005 through 2006. The nationally representative sample included 124,385 married women; analyses conducted in 2007 and 2008 were limited to 28,139 married women who provided IPV data and HIV test results via systematic selection into respective subsamples. Prevalence estimates of lifetime IPV and HIV infection were calculated and demographic differences assessed. Intimate partner violence was conceptualized as physical violence with or without sexual violence and then was further categorized as physical violence only vs physical and sexual violence. Regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for HIV infection among Indian women based on experiences of IPV after adjusting for demographics and women's HIV risk behaviors. One-third of married Indian women (35.49%) reported experiencing physical IPV with or without sexual violence from their husbands; 7.68% reported both physical and sexual IPV, and 27.80% reported experiencing physical IPV in the absence of sexual violence. Approximately 1 in 450 women (0.22%) tested positive for HIV. In adjusted models, married Indian women experiencing both physical and sexual violence from husbands demonstrated elevated HIV infection prevalence vs those not experiencing IPV (0.73% vs 0.19%; adjusted OR, 3.92; 95% CI, 1.41-10.94; P = .01

Reworking of Archean mantle in the NE Siberian craton by carbonatite and silicate melt metasomatism: Evidence from a carbonate-bearing, dunite-to-websterite xenolith suite from the Obnazhennaya kimberlite

NASA Astrophysics Data System (ADS)

Ionov, Dmitri A.; Doucet, Luc S.; Xu, Yigang; Golovin, Alexander V.; Oleinikov, Oleg B.

2018-03-01

The Obnazhennaya kimberlite in the NE Siberian craton hosts a most unusual cratonic xenolith suite, with common rocks rich in pyroxenes and garnet, and no sheared peridotites. We report petrographic and chemical data for whole rocks (WR) and minerals of 20 spinel and garnet peridotites from Obnazhennaya with Re-depletion Os isotope ages of 1.8-2.9 Ga (Ionov et al., 2015a) as well as 2 pyroxenites. The garnet-bearing rocks equilibrated at 1.6-2.8 GPa and 710-1050 °C. Some xenoliths contain vermicular spinel-pyroxene aggregates with REE patterns in clinopyroxene mimicking those of garnet. The peridotites show significant scatter of Mg# (0.888-0.924), Cr2O3 (0.2-1.4 wt.%) and high NiO (0.3-0.4 wt.%). None are pristine melting residues. Low-CaO-Al2O3 (≤0.9 wt.%) dunites and harzburgites are melt-channel materials. Peridotites with low to moderate Al2O3 (0.4-1.8 wt.%) usually have CaO > Al2O3, and some have pockets of calcite texturally equilibrated with olivine and garnet. Such carbonates, exceptional in mantle xenoliths and reported here for the first time for the Siberian mantle, provide direct evidence for modal makeover and Ca and LREE enrichments by ephemeral carbonate-rich melts. Peridotites rich in CaO and Al2O3 (2.7-8.0 wt.%) formed by reaction with silicate melts. We infer that the mantle lithosphere beneath Obnazhennaya, initially formed in the Mesoarchean, has been profoundly modified. Pervasive inter-granular percolation of highly mobile and reactive carbonate-rich liquids may have reduced the strength of the mantle lithosphere leading the way for reworking by silicate melts. The latest events before the kimberlite eruption were the formation of the carbonate-phlogopite pockets, fine-grained pyroxenite veins and spinel-pyroxene symplectites. The reworked lithospheric sections are preserved at Obnazhennaya, but similar processes could erode lithospheric roots in the SE Siberian craton (Tok) and the North China craton, where ancient melting residues and

Soil, water, and streambed quality at a demolished asphalt plant, Fort Bragg, North Carolina, 1992-94

USGS Publications Warehouse

Campbell, T.R.

1996-01-01

contaminant level of 5.0 micrograms per liter. One well contained a fluoride concentration of 5.2 milligrams per liter that exceeded the U.S. Environmental Protection Agency maximum contaminant level of 4.0 milligrams per liter. Total and dissolved metals concentrations were generally typical of background levels. Some of the wells contained elevated levels of chloride (maximum of 749 milligrams per liter), specific conductance (maximum of 2,780 microsiemens per centimeter at 25 degrees Celsius), and dissolved solids (maximum of 1,520 milligrams per liter). Twelve of twenty-two soil samples that were collected at various depths at monitoring-well locations did not contain volatile organic compounds or polynuclear aromatic hydrocarbons. The remaining ten soil samples contained very low concentrations of polynuclear aromatic hydrocarbons and (or) analytical laboratory-related volatile organic compounds. The maximum concentrations were for fluoranthene and pyrene, at 780 and 750 micrograms per kilogram, respectively. In general, the polynuclear aromatic hydrocarbon concentrations were in sediment near the land surface. Streambed sediment from an unnamed, eastern tributary to Tank Creek in the eastern part of the site contained a small number of organochlorine pesticide compounds (a maximum of 1,400 milligrams per kilogram of 4,4'-DDD) and total petroleum hydrocarbons (113 milligrams per kilogram). Concentrations of metals and other inorganic constituents were generally typical of background concentrations. Surface water in this tributary did not contain elevated concentrations of anthropogenic chemicals.

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

PubMed

Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

2017-02-01

Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and

Associations Between Exposure to and Expression of Negative Opinions About Human Papillomavirus Vaccines on Social Media: An Observational Study.

PubMed

Dunn, Adam G; Leask, Julie; Zhou, Xujuan; Mandl, Kenneth D; Coiera, Enrico

2015-06-10

Groups and individuals that seek to negatively influence public opinion about the safety and value of vaccination are active in online and social media and may influence decision making within some communities. We sought to measure whether exposure to negative opinions about human papillomavirus (HPV) vaccines in Twitter communities is associated with the subsequent expression of negative opinions by explicitly measuring potential information exposure over the social structure of Twitter communities. We hypothesized that prior exposure to opinions rejecting the safety or value of HPV vaccines would be associated with an increased risk of posting similar opinions and tested this hypothesis by analyzing temporal sequences of messages posted on Twitter (tweets). The study design was a retrospective analysis of tweets related to HPV vaccines and the social connections between users. Between October 2013 and April 2014, we collected 83,551 English-language tweets that included terms related to HPV vaccines and the 957,865 social connections among 30,621 users posting or reposting the tweets. Tweets were classified as expressing negative or neutral/positive opinions using a machine learning classifier previously trained on a manually labeled sample. During the 6-month period, 25.13% (20,994/83,551) of tweets were classified as negative; among the 30,621 users that tweeted about HPV vaccines, 9046 (29.54%) were exposed to a majority of negative tweets. The likelihood of a user posting a negative tweet after exposure to a majority of negative opinions was 37.78% (2780/7361) compared to 10.92% (1234/11,296) for users who were exposed to a majority of positive and neutral tweets corresponding to a relative risk of 3.46 (95% CI 3.25-3.67, P<.001). The heterogeneous community structure on Twitter appears to skew the information to which users are exposed in relation to HPV vaccines. We found that among users that tweeted about HPV vaccines, those who were more often exposed to

Associations Between Exposure to and Expression of Negative Opinions About Human Papillomavirus Vaccines on Social Media: An Observational Study

PubMed Central

Leask, Julie; Zhou, Xujuan; Mandl, Kenneth D; Coiera, Enrico

2015-01-01

Background Groups and individuals that seek to negatively influence public opinion about the safety and value of vaccination are active in online and social media and may influence decision making within some communities. Objective We sought to measure whether exposure to negative opinions about human papillomavirus (HPV) vaccines in Twitter communities is associated with the subsequent expression of negative opinions by explicitly measuring potential information exposure over the social structure of Twitter communities. Methods We hypothesized that prior exposure to opinions rejecting the safety or value of HPV vaccines would be associated with an increased risk of posting similar opinions and tested this hypothesis by analyzing temporal sequences of messages posted on Twitter (tweets). The study design was a retrospective analysis of tweets related to HPV vaccines and the social connections between users. Between October 2013 and April 2014, we collected 83,551 English-language tweets that included terms related to HPV vaccines and the 957,865 social connections among 30,621 users posting or reposting the tweets. Tweets were classified as expressing negative or neutral/positive opinions using a machine learning classifier previously trained on a manually labeled sample. Results During the 6-month period, 25.13% (20,994/83,551) of tweets were classified as negative; among the 30,621 users that tweeted about HPV vaccines, 9046 (29.54%) were exposed to a majority of negative tweets. The likelihood of a user posting a negative tweet after exposure to a majority of negative opinions was 37.78% (2780/7361) compared to 10.92% (1234/11,296) for users who were exposed to a majority of positive and neutral tweets corresponding to a relative risk of 3.46 (95% CI 3.25-3.67, P<.001). Conclusions The heterogeneous community structure on Twitter appears to skew the information to which users are exposed in relation to HPV vaccines. We found that among users that tweeted about

Comparison of flat cleaved and cylindrical diffusing fibers as treatment sources for interstitial photodynamic therapy.

PubMed

Baran, Timothy M; Foster, Thomas H

2014-02-01

fibers delivering 2780-3600 J. For the same number of fibers, cylindrical diffusers allow for a shorter treatment duration compared to flat cleaved fibers. For the same energy delivered per fiber, diffusers allow for the insertion of fewer fibers in order to deliver the same light dose to a target volume.

Vegetation, climate and fire-dynamics in East Africa inferred from the Maundi crater pollen record from Mt Kilimanjaro during the last glacial-interglacial cycle

NASA Astrophysics Data System (ADS)

Schüler, Lisa; Hemp, Andreas; Zech, Wolfgang; Behling, Hermann

2012-04-01

The pollen, charcoal and sedimentological record from the Maundi crater, located at 2780 m elevation on the south-eastern slope of Mt Kilimanjaro, is one of the longest terrestrial records in equatorial East Africa, giving an interesting insight into the vegetation and climate dynamics back to the early last Glacial period. Our sediment record has a reliable chronology until 42 ka BP. An extrapolation of the age-depth model, as well as matching with other palaeo-records from tropical East Africa, suggest a total age of about 90 ka BP at the bottom of the record. During the last Glacial the distribution as well as the composition of the vegetation belts classified as colline savanna, submontane woodland, montane forest, ericaceous belt, and alpine vegetation changed. The early last Glacial is characterized by high amounts of Poaceae and Asteraceae pollen suggesting a climatically dry but stable phase. Based on the absence of pollen grains in samples deposited around 70 ka BP, we assume the occurrence of distinct drought periods. During the pre-LGM (Last Glacial Maximum) a higher taxa diversity of the ericaceous and montane zone is recorded and suggests a spread of forest and shrub vegetation, thus indicating a more humid period. The taxa diversity increases steadily during the recorded time span. The decent of vegetation zones indicate dry and cold conditions during the LGM and seem to have been detrimental for many taxa, especially those of the forest vegetation; however, the early last Glacial seems to have been markedly drier than the LGM. The reappearance of most of the taxa (most importantly Alchemilla, Araliaceae, Dodonea, Hagenia, Ilex, Myrsine, Moraceae, Piperaceae) during the deglacial and Holocene period suggest a shift into humid conditions. An increase in ferns and the decrease in grasses during the Holocene also indicate increasing humidity. Fire played an important role in controlling the development and elevation of the ericaceous zone and the tree

Exercise effects on bone mineral density, falls, coronary risk factors, and health care costs in older women: the randomized controlled senior fitness and prevention (SEFIP) study.

PubMed

Kemmler, Wolfgang; von Stengel, Simon; Engelke, Klaus; Häberle, Lothar; Kalender, Willi A

2010-01-25

: 2255 euros[95% CI, 1791 euros-2718 euros] vs controls: 2780 euros [2187 euros-3372 euros]; P = .20). Compared with a general wellness program, our 18-month exercise program significantly improved BMD and fall risk, but not predicted CHD risk, in elderly women. This benefit occurred at no increase in direct costs. clinicaltrials.gov Identifier: NCT00267839.

[Role of totally implantable systems for long-term vascular access in the treatment of the neoplastic patient].

PubMed

Aldrighetti, L; Caterini, R; Ronzoni, M; Jannello, A; Ferla, G

1995-05-01

To assess retrospectively the effectiveness, the safety and the impact on the quality of life of the Subcutaneous Infusion Ports (SIPs) for prolonged venous access in the treatment of neoplastic patients. Retrospective analysis of a case series collected-during 30 months (April 1991-September 1993). General Surgery Division and Radiochemotherapy Service. 35 patients (23 male, 12 female), aged between 27-80 years, received 37 SIPs. 2 patients received 2 SIPs. 34 patients were affected by neoplasm; 1 patient had short gut syndrome secondary to massive small bowel resection. The SIP was implanted in all patients in the operating room with the Seldinger technique ("catheter over wire"). The suclavian vein, through an infraclavicular approach, was the only site of venous access. One SIP was implanted in the hepatic artery. All neoplastic patients received chemotherapy. The patient with short gut syndrome had parenteral nutrition. An external infusion device (CADD-1, CADD-plus, Pharmacia) was used in 13 patients for the continuous infusion of either 5-Fluoro-Uracil (1000 mg/m2/die for 5 days, every 28 days) or 5-Fluoro-Deoxy-Uridine (0.15-0.30 mg/kg/die for 14 days, every 28 days). SIP management required the port "flush" with normal saline solution with heparin (100 U/ml) at least every 40 days, using Huber needle. All patients were treated as outpatients. All intraoperative and long-term complications, recorded in the charts of the patients, were reviewed. The rate of intraoperative complications was assessed over 37 procedures. Long-term complications were assessed over 28 patients (7 patients were excluded for lack of follow up data). Incidence of complications was analyzed over patient days, considering the cumulative permanence time of the SIP in a single patient. We recorded 4 intraoperative complications (10.8%). None of them required to stop the procedure and to delay the implant of the SIP. During the follow-up period (range 1-18 months) we had 1 major

Temperature and precipitation records from stalagmites grown under disequilibrium conditions: A model approach.

NASA Astrophysics Data System (ADS)

Mühlinghaus, C.; Scholz, D.; Mangini, A.

2009-04-01

records of the stalagmites, which were obtained by three independent model runs, follow a general trend over the whole growth period and reveal good correlations within certain time-frames. This is a promising first result of the model. In addition the calculated temperatures are robust to small variations of the input variables, giving confidence in the algorithm of the model and for further temperature reconstructions from kinetically grown stalagmites. Literature Dreybrodt, W., 1999. Chemical kinetics, speleothem growth and climate. Boreas 28, 347 -356. Kaufmann, G., Dreybrodt, W. , 2004. Stalagmite growth and palaeo-climate: an inverse approach. Earth and Planetary Science Letters 224, 529 - 545. Kilian, R., Biester, H., Behrmann, J., Baeza, O., Fesq-Martin, M., Hohner, M., Schimpf, D., Friedmann, A., Mangini, A., 2006: Millennium-scale volcanic impact on a superhumid and pristine ecosystem, Geology, 34: 609 - 612. Mühlinghaus, C., Scholz, D., Mangini, A., 2007. Modelling stalagmite growth and ^13C as a function of drip interval and temperature. Geochimica et Cosmochimica Acta 71, 2780 - 2790. Mühlinghaus, C.; Scholz, D., Mangini, A., 2008a. Temperature and precipitation records from stalagmites grown under disequilibrium conditions: A first approach. Advances in speleothem research, PAGES News, 16 Mühlinghaus, C., Scholz, D., Mangini, A., 2008b. Fractionation of stable isotopes in stalagmites under disequilibrium conditions. Geochimica et Cosmochimica Acta, Submitted. Schimpf, D., 2005. Datierung und Interpretation der Kohlenstoff- und Sauerstoffsotopie zweier holozäner Stalagmiten aus dem Süden Chiles (Patagonien). Master's thesis, Ruprecht-Karls- University, Heidelberg. Schimpf, D., Kilian, R., Mangini, A., Spötl, C., Kronz, A., in prep. Evaluation of chemical, isotopic and detrital proxies of a high-resolution stalagmite record from the southernmost Chilean Andes (53˚ S) Scholz, D., Mühlinghaus, C., Mangini, A., 2008. Modelling the evolution of ^13C and

The Tonalite-Trondhjemite-Granodiorite (TTG) to Calc-alkaline Granodiorite-Granite Transition: Evolution of the Archaean Basement of the Quadrilátero Ferrífero Province (Southeast Brazil)

NASA Astrophysics Data System (ADS)

Farina, F.; Albert, C.; Lana, C.; Stevens, G.

2014-12-01

The Bação, Bonfim and Belo Horizonte domes are the largest domes in the Archaean Southern São Francisco craton (Quadrilátero Ferrífero, Brazil). These domes are mainly formed by fine-grained banded gneisses typically intruded by leucogranitic veins and by weakly foliated granites, cropping out as large batholiths and small scale-domains closely associated to the gneisses. Granites and gneisses have high silica content (70-76 wt%), K2O ranging from 2wt% to 6wt%, Sr from 600 to 40 ppm and La/Yb from 150 to 5. Based on their K2O/Na2O ratios, these rocks are subdivided in three groups: sodic (K2O/Na2O≤0.7), transitional (0.7a ca. 3200 Ma age represent a significant subset in the detrital zircon population of the greenstone belt. Subsequent magmatic events took place at 2930-2870 Ma and 2780-2700 Ma. The geochronological data reveal that, although the sodic rocks represent a greater proportion of the older gneisses, sodic, transitional and potassic granitoids intruded contemporaneously. The geochemistry of sodic and transitional granites and gneisses suggests that they formed by partial melting of TTG source rocks that are not preserved in the rock record. MC-ICP-MS Hf isotope data on magmatic zircon, suggesting crustal reworking with minor or no involvement of juvenile magmas, support this interpretation. Further recycling of sodic

Occurrence and fate of the norsesquiterpene glucoside ptaquiloside (PTA) in soils

NASA Astrophysics Data System (ADS)

Zaccone, Claudio; Cavoski, Ivana; Costi, Roberta; Sarais, Giorgia; Caboni, Pierluigi; Miano, Teodoro M.; Lattanzio, Vincenzo

2014-05-01

The bracken fern Pteridium aquilinum (L.) Kuhn, one of the most common plant species on Earth, produces a wide range of secondary metabolites including the norsesquiterpene glucoside ptaquiloside (PTA). This bracken constituent causes acute poisoning, blindness and cancer in animals, and can be transferred to man when bracken is utilized as food. Also milk from cows eating bracken is thought to be the vector for the transfer of PTA to humans, as well as PTA-contaminated drinking waters. Although some studies on the effect of growth conditions and soil properties on the production and mobility of PTA have been carried out (mainly in the North of Europe), results are sometimes conflicting and further investigations are needed. The aim of the present work is to study the occurrence and the fate of PTA in soils showing different physico-chemical features, collected in different pedoclimatic areas (from the South of Italy), but having the extensive ("wild") livestock farming as common denominator. The PTA content was determined in both soil and fern samples by GC-MS; both the extraction protocol and recovery were previously tested through incubation studies. Soils samples were also characterizes from the physical and chemical point of view (pH, EC, texture, total carbonates, cation exchange capacity, organic C, total N, available nutrients and heavy metal concentration) in order to correlate the possible influence of soil parameters on PTA production, occurrence and mobility. PTA concentration in soil samples was always 2-780 µg/g), ii) the soil organic matter content (ranging from 3.4 to 22.8%), iii) the soil pH (ranging from 5.9 to 6.6), iv) the soil texture, v) the depth (0-10 cm; 10-20 cm), and vi) precipitations (ranging from 780 to 960 mm/a). This seems to suggest the degradation of the PTA by indigenous microbial community

The frequency of replacement of dental restorations may vary based on a number of variables, including type of material, size of the restoration, and caries risk of the patient.

PubMed

Roumanas, Eleni D

2010-03-01

The authors analyzed the dental records of 2780 Navy (cohort 1 = 1078 entered the Navy in 1997) and US Marine Corps recruits (cohort 2 =1053 entered the USMC in 1999-2000; cohort 3 = 649 entered the USMC in 2002-2005). The records were reviewed at 16 US Navy dental treatment facilities at the following time periods: cohort 1, 2001; cohort 2, 2002-2003; and cohort 3, 2005-2006. The mean age of the subjects was 20 years, and 85% were men. Only posterior teeth (not third molars) with amalgam or resin-based composite (including glass ionomer restorations) were evaluated. Teeth that had been restored with more than one material and restorations that did not involve the occlusal surface were excluded. The minimum follow-up time was 2 years with at least 2 periodic exams following the initial exam. The primary factor of interest was the type of restorative material (amalgam versus resin-based composite). Secondary factors included tooth number, number of restored surfaces (single or multiple), and caries risk of the patient. Caries risk status was defined using the Navy Dental Corps Oral Disease Risk Management protocol. The primary outcome measure of interest was the determination of the relative risk of replacement of an initially intact restoration during the subject's first years of military service. Restorations were classified as clinically acceptable or requiring replacement either as a result of new primary caries, secondary caries, defective restorations, or endodontic therapy. At the initial exam, 964 (15.2%) of the amalgam restorations and 199 (17.4%) of the resin-based composites required replacement and were excluded from further analysis. Of the remaining restorations, an additional 14.2% of the amalgam and 16.7% of the composite restorations required replacement during the observation period. The mean follow-up time was 3.0 years (cohort 1, 3.4 years; cohort 2, 3.1 years; cohort 3, 2.3 years). Replacement rates for resin-based composite restorations

Comparison of flat cleaved and cylindrical diffusing fibers as treatment sources for interstitial photodynamic therapy

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

Baran, Timothy M., E-mail: timothy.baran@rochester.edu; Foster, Thomas H.

��3600 J were required, compared to ten flat cleaved fibers delivering 2780–3600 J. Conclusions: For the same number of fibers, cylindrical diffusers allow for a shorter treatment duration compared to flat cleaved fibers. For the same energy delivered per fiber, diffusers allow for the insertion of fewer fibers in order to deliver the same light dose to a target volume.« less

Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity.

PubMed

Betanzos-Lara, Soledad; Novakova, Olga; Deeth, Robert J; Pizarro, Ana M; Clarkson, Guy J; Liskova, Barbora; Brabec, Viktor; Sadler, Peter J; Habtemariam, Abraha

2012-10-01

The synthesis and characterization of complexes [(η(6)-arene)Ru(N,N')X][PF(6)], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)I][PF(6)] and [(η(6)-etb)Ru(bpm)Cl][PF(6)]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru(II) arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-p-cym)Ru(bpm)Br][PF(6)], [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)Br][PF(6)] and [(η(6)-bip)Ru(bpm)I][PF(6)] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-hmb)Ru(bpm)Cl](+), [(η(6)-ind)Ru(bpm)Cl](+), [(η(6)-thn)Ru(bpm)Cl](+), [(η(6)-p-cym)Ru(phen)Cl](+) and [(η(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF(6)](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)] and [(η(6)-p

Artemisinin-based combination therapy in pregnant women in Zambia: efficacy, safety and risk of recurrent malaria.

PubMed

Nambozi, Michael; Kabuya, Jean-Bertin Bukasa; Hachizovu, Sebastian; Mwakazanga, David; Mulenga, Joyce; Kasongo, Webster; Buyze, Jozefien; Mulenga, Modest; Van Geertruyden, Jean-Pierre; D'Alessandro, Umberto

2017-05-16

In Zambia, malaria is one of the leading causes of morbidity and mortality, especially among under five children and pregnant women. For the latter, the World Health Organization recommends the use of artemisinin-based combination therapy (ACT) in the second and third trimester of pregnancy. In a context of limited information on ACT, the safety and efficacy of three combinations, namely artemether-lumefantrine (AL), mefloquine-artesunate (MQAS) and dihydroartemisinin-piperaquine (DHAPQ) were assessed in pregnant women with malaria. The trial was carried out between July 2010 and August 2013 in Nchelenge district, Luapula Province, an area of high transmission, as part of a multi-centre trial. Women in the second or third trimester of pregnancy and with malaria were recruited and randomized to one of the three study arms. Women were actively followed up for 63 days, and then at delivery and 1 year post-delivery. Nine hundred pregnant women were included, 300 per arm. PCR-adjusted treatment failure was 4.7% (12/258) (95% CI 2.7-8.0) for AL, 1.3% (3/235) (95% CI 0.4-3.7) for MQAS and 0.8% (2/236) (95% CI 0.2-3.0) for DHAPQ, with significant risk difference between AL and DHAPQ (p = 0.01) and between AL and MQAS (p = 0.03) treatments. Re-infections during follow up were more frequent in the AL (HR: 4.71; 95% CI 3.10-7.2; p < 0.01) and MQAS (HR: 1.59; 95% CI 1.02-2.46; p = 0.04) arms compared to the DHAPQ arm. PCR-adjusted treatment failure was significantly associated with women under 20 years [Hazard Ratio (HR) 5.35 (95% CI 1.07-26.73; p = 0.04)] and higher malaria parasite density [3.23 (95% CI 1.03-10.10; p = 0.04)], and still women under 20 years [1.78, (95% CI 1.26-2.52; p < 0.01)] had a significantly higher risk of re-infection. The three treatments were generally well tolerated. Dizziness, nausea, vomiting, headache and asthenia as adverse events (AEs) were more common in MQAS than in AL or DHAPQ (p < 0.001). Birth outcomes were not

Concentrations and loadings of polybrominated diphenyl ethers in dust from low-income households in California.

PubMed

Quirós-Alcalá, Lesliam; Bradman, Asa; Nishioka, Marcia; Harnly, Martha E; Hubbard, Alan; McKone, Thomas E; Eskenazi, Brenda

2011-04-01

California residents may experience the highest polybrominated diphenyl ether (PBDE) flame retardant exposures in the United States, the nation with the highest body burdens worldwide. It is hypothesized that Californians' high exposures are due to the state's strict furniture flammability standards. Ingestion of PBDE-contaminated dust, to which children may be particularly susceptible, is a dominant exposure pathway. Low-income populations may also face disparately high exposures due to the presence of older, deteriorated or poorly manufactured furniture treated with PBDEs. We collected up to two dust samples per home (54 samples total), several days apart, from low-income California households in the urban community of Oakland (n=13 homes) and the agricultural community of Salinas (n=15 homes). We measured BDE-47, BDE-99 and BDE-100, the major constituents of the penta-PBDE flame retardant formulation commonly used in furniture. All three PBDE congeners were detected in every sample with concentrations (loadings) ranging from 185 to 126,000ng/g (621-264,000ng/m(2)), 367-220,000ng/g (1550-457,000ng/m(2)), and 84-41,100ng/g (257-85,700ng/m(2)) for BDE-47, BDE-99 and BDE-100, respectively. Median concentrations (loadings) observed in Salinas homes for BDE-47, BDE-99 and BDE-100 were 3100ng/g (10,800ng/m(2)), 5480ng/g (19,500ng/m(2)), and 1060ng/g (3810ng/m(2)), respectively, and in Oakland homes 2780ng/g (10,700ng/m(2)), 4450ng/g (19,100ng/m(2)), and 1050ng/g (4000ng/m(2)), respectively. Maximum concentrations for BDE-47 and BDE-99 are the highest reported to date. Indoor concentrations and loadings did not significantly differ between communities; concentrations and loadings were strongly correlated between collections for all three congeners (Spearman rho=0.79-0.97, p<0.002). We estimated non-dietary ingestion of each congener for one child in each home (n=28 children) and found that estimated intake for BDE-47 and BDE-99 exceeded the U.S. Environmental Protection

Dendrimer-encapsulated naphthalocyanine as a single agent-based theranostic nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy

NASA Astrophysics Data System (ADS)

Taratula, Olena; Schumann, Canan; Duong, Tony; Taylor, Karmin L.; Taratula, Oleh

2015-02-01

dynamic light scattering (Fig. S1); absorption spectra of free SiNc 2 in THF before and after irradiation with the 785 nm laser diode for 30 min (Fig. S2); in vitro cytotoxicity of free DOX against A2780/AD human ovarian cancer cells (Fig. S3); the release profiles of SiNc from SiNc-NP under various conditions (Fig. S4); body weight curves of the mice with or without treatment (Fig. S5). See DOI: 10.1039/c4nr06050d

[Liposome-mediated glial growth factor 2 gene therapy in brain injury: an experimental study with rats].

PubMed

Xue, Ya-jun; Dong, Yan; Han, Xi; Wei, Mei-yang; Ge, Jun-hui; Cai, Ru-jue; Hu, Guo-han; Luo, Chun; Zhu, Cheng; Lu, Yi-cheng

2006-09-05

To explore the protective effect of glial growth factor-2 (GGF2) on brain injury. Thirty-four SD rats underwent lateral fluid percussion to establish brain injury models and then were randomly divided into 4 groups: treatment group (n = 10, the plasmid pEGFP-N1-GGF2 mixed with liposome was injected into the brain tissue directly), vector control group (n = 10, the vector pEGFP-N1 mixed with liposome was injected into the brain tissue directly), liposome control group (n = 10, liposome was injected), and sham operation group (n = 4). Three assessment tasks were performed for neurobehavioral evaluation: Clivas Test, Beam Balance Test and Beam Walking Test. 10 days after brain injury, the rats were sacrificed and their brains were embedded in paraffin for HE staining, Nissle staining and immunohistochemical examination of MBP, NSE, and GFAP. The Clivas test score of the treatment group was 66.25 +/- 3.54, significantly higher than those of the vector control group and. liposome control group (58.31 +/- 3.72 and 57.21 +/- 3.93 respectively, both P < 0.05). The beam test score of the treatment group was 2.59 +/- 0.21, significantly lower than those the vector control group and liposome control group (3.41 +/- 0.25 and 3.24 +/- 0.22 respectively, both P < 0.05). The walking test score of the treatment group was 20.15 +/- 2.59, significantly lower than those of control group and liposome control group (27.00 +/- 3.47 and 27.80 +/- 3.00 respectively, both P < 0.05). The improvement in beam walking test was the greatest. The neuron number in the external granular layer and external pyramidal layer in cortex of the treatment group was 98 +/- 10, significantly more than those of the vector control group and liposome group (75 +/- 7 and 67 +/- 8, both P < 0.05). The neuron number in the internal pyramidal layer in cortex of the treatment group was 37 +/- 4, significantly more than those of the vector control group and liposome group (19 +/- 3 and 23 +/- 4 respectively, both P

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective, population-based cohort study.

PubMed

Ollila, M-M E; West, S; Keinänen-Kiukaanniemi, S; Jokelainen, J; Auvinen, J; Puukka, K; Ruokonen, A; Järvelin, M-R; Tapanainen, J S; Franks, S; Piltonen, T T; Morin-Papunen, L C

2017-02-01

What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m 2 ) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus—a prospective, population-based cohort study

PubMed Central

Ollila, M.-M.E.; West, S.; Keinänen-Kiukaanniemi, S.; Jokelainen, J.; Auvinen, J.; Puukka, K.; Ruokonen, A.; Järvelin, M.-R.; Tapanainen, J.S.; Franks, S.; Piltonen, T.T.; Morin-Papunen, L.C.

2017-01-01

STUDY QUESTION What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? SUMMARY ANSWER The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. WHAT IS KNOWN ALREADY PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. STUDY DESIGN, SIZE, DURATION In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. PARTICIPANTS/MATERIALS, SETTING, METHODS Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. MAIN RESULTS AND THE ROLE OF CHANCE PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m2) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28–4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years

[Effect of the night shift work on micturition patterns of nurses].

PubMed

Wang, Q; Hu, H; Liang, C; Wang, J; Xu, K X

2016-02-18

To compare the effects of rotational night shifts on the micturition patterns of female nurses. A total of 58 nurses without lower urinary tract symptoms were recruited, who worked in the Peking University People's Hospital during January and June in 2014. The nurses aged 20-43 years were divided into two groups, the night-shift group (n=28) and the non-shift group (n=30). The alcohol or coffee intaking were forbidden. In the night-shift group, nurses had worked on rotational shifts for at least 6 months. Their average age was (26.75±4.11) years. In the non-shift group, nurses took regular day-time work, whose average age was (27.80±5.60) years. A voiding diary was kept for 7 consecutive days at the end of 6 months, starting 2 days before their night duties until 4 days after completion of their night duties. For comparison, the non-shift group with regular shifts completed a 7-day voiding diary. In the 7-day recording voiding diary, the nurses were required to have the normal intake of liquid about 1 500-2 000 mL/d. The frequency volume charts of nocturia, the 8-hour interval urine production and frequency were compared between the two groups. Nocturia frequency was increased in the night-shift group [0.5 (0-2.4)] compared with the non-shift group [0 (0-2), P=0.02]. The volume of nocturia was increased in the night-shift group [125 mL (0-660 mL)] compared with the non-shift group [0 mL (0-340 mL), P<0.01]. The 8-hour interval indices showed that urine production changed with shift (P<0.01). In the consecutive 7 days, the nocturnal volume of the night-shift group increased on the day after night shift. When the night-shift nurses returned to daytime duty, the volume of urine decreased but nocturnal urine production remained high, and the frequency of nocturia also increased significantly (P<0.05). Compared with the 8-hour interval indices, the night-shift group's voiding volume [(542.35±204.66) mL] and voiding frequency (2.24±0.69) were more than those of the

[Effect of the night shift work on micturition patterns of nurses].

PubMed

Wang, Q; Hu, H; Liang, C; Wang, J; Xu, K X

2016-08-18

To compare the effects of rotational night shifts on the micturition patterns of female nurses. A total of 58 nurses without lower urinary tract symptoms were recruited, who worked in the Peking University People's Hospital during January and June in 2014. The nurses aged 20-43 years were divided into two groups, the night-shift group (n=28) and the non-shift group (n=30). The alcohol or coffee intaking were forbidden. In the night-shift group, nurses had worked on rotational shifts for at least 6 months. Their average age was (26.75±4.11) years. In the non-shift group, nurses took regular day-time work, whose average age was (27.80±5.60) years. A voiding diary was kept for 7 consecutive days at the end of 6 months, starting 2 days before their night duties until 4 days after completion of their night duties. For comparison, the non-shift group with regular shifts completed a 7-day voiding diary. In the 7-day recording voiding diary, the nurses were required to have the normal intake of liquid about 1 500-2 000 mL/d. The frequency volume charts of nocturia, the 8-hour interval urine production and frequency were compared between the two groups. Nocturia frequency was increased in the night-shift group [0.5 (0-2.4)] compared with the non-shift group [0 (0-2), P=0.02]. The volume of nocturia was increased in the night-shift group [125 mL (0-660 mL)] compared with the non-shift group [0 mL (0-340 mL), P<0.01]. The 8-hour interval indices showed that urine production changed with shift (P<0.01). In the consecutive 7 days, the nocturnal volume of the night-shift group increased on the day after night shift. When the night-shift nurses returned to daytime duty, the volume of urine decreased but nocturnal urine production remained high, and the frequency of nocturia also increased significantly (P<0.05). Compared with the 8-hour interval indices, the night-shift group's voiding volume [(542.35±204.66) mL] and voiding frequency (2.24±0.69) were more than those of the

Association of "Weekend Warrior" and Other Leisure Time Physical Activity Patterns With Risks for All-Cause, Cardiovascular Disease, and Cancer Mortality.

PubMed

O'Donovan, Gary; Lee, I-Min; Hamer, Mark; Stamatakis, Emmanuel

2017-03-01

More research is required to clarify the association between physical activity and health in "weekend warriors" who perform all their exercise in 1 or 2 sessions per week. To investigate associations between the weekend warrior and other physical activity patterns and the risks for all-cause, cardiovascular disease (CVD), and cancer mortality. This pooled analysis of household-based surveillance studies included 11 cohorts of respondents to the Health Survey for England and Scottish Health Survey with prospective linkage to mortality records. Respondents 40 years or older were included in the analysis. Data were collected from 1994 to 2012 and analyzed in 2016. Self-reported leisure time physical activity, with activity patterns defined as inactive (reporting no moderate- or vigorous-intensity activities), insufficiently active (reporting <150 min/wk in moderate-intensity and <75 min/wk in vigorous-intensity activities), weekend warrior (reporting ≥150 min/wk in moderate-intensity or ≥75 min/wk in vigorous-intensity activities from 1 or 2 sessions), and regularly active (reporting ≥150 min/wk in moderate-intensity or ≥75 min/wk in vigorous-intensity activities from ≥3 sessions). The insufficiently active participants were also characterized by physical activity frequency. All-cause, CVD, and cancer mortality ascertained from death certificates. Among the 63 591 adult respondents (45.9% male; 44.1% female; mean [SD] age, 58.6 [11.9] years), 8802 deaths from all causes, 2780 deaths from CVD, and 2526 from cancer occurred during 561 159 person-years of follow-up. Compared with the inactive participants, the hazard ratio (HR) for all-cause mortality was 0.66 (95% CI, 0.62-0.72) in insufficiently active participants who reported 1 to 2 sessions per week, 0.70 (95% CI, 0.60-0.82) in weekend warrior participants, and 0.65 (95% CI, 0.58-0.73) in regularly active participants. Compared with the inactive participants, the HR for CVD mortality was 0.60 (95% CI

[Growth assessment of children with neonatal short bowel syndrome (SBS)].

PubMed

Dalieri, M; Fabeiro, M; Prozzi, M; Barcellandi, P; Martínez, M; Galarraga, M; Fernández, A

2007-01-01

length of 41 cm (r: 20-75) and 2 out of 6 pts. did not have VIC. This group of patients required PN as the initial therapy with a mean duration of 629 days. Follow-up time while on EN was 627 days (r: 210-3010). Six patients (33%) achieved nutritional support independence (WOS) with a mean intestinal length of 60 cm (r: 27-80) after a mean duration of NS of 791 days, being assisted with dietary recommendations and vitamins and minerals supplementation. The group showing the greatest growth impairment was the EN-dependent group since we consider that early withdrawal of PN was decided based on inappropriate socio-environmental conditions. According to the present study, we conclude that is may be possible to achieve a normal growth in children with neonatal SBS under nutritional support and that complications related to this nutritional therapy or difficulties for adequately implementing it at home may affect the final height.

Multiproxy Holocene paleoclimate records from the southern Peruvian Andes - what new can we learn from the stable carbon isotope composition of high altitude organic matter deposits?

NASA Astrophysics Data System (ADS)

Skrzypek, Grzegorz; Engel, Zbyněk

2015-04-01

Interpretation of the Central Andean paleoclimate over the last millennia still represents a research challenge demanding deeper studies [1,2]. Several high-resolution paleoclimate proxies for the last 10,000 years have been developed for the northern hemisphere. However, similar proxies are very limited for South America, particularly for high altitudes where, for example, tree-ring chronologies are not available and instrumental records are very limited. Consequently, our knowledge of high altitude climate changes in arid regions of the Peruvian Andes mainly relies on ice-core and lake deposit studies. In our study, we used a new alternative proxy for interpretation of palaeoclimate conditions based on a peat core taken from the Carhuasanta Valley at the foot of Nevado Mismi in the southern Peruvian Andes (15° 30'S, 71° 43'W, 4809m a.s.l.). The stable carbon isotope composition (δ13C) of Distichia peat reflects mainly the relative variation of the mean air temperature during subsequent growing seasons [3], and allows reconstructions of palaeotemperature changes. In contrast, peat organic carbon concentration (C % wt) records mainly wetness in the valley, directly corresponding to the changes in runoff in the upper part of the catchment. The most prominent climate changes recorded in the peat over last 4ka occurred between 3040 and 2750 cal. yrs BP. The initial warming turned to a very rapid cooling to temperatures at least 2° C lower than the mean for the Late Holocene. Initially drier conditions within this event turned to a short wet phase after 2780 cal. yrs BP, when the temperature increased again. This event coincides with significant changes in peat and ice core records in the Central Andes that match the timing of the global climate event around 2.8 cal. ka BP. Climatic conditions in the study area became relatively dry and stable after the event for about 800 years. Highly variable temperatures and humidity prevailed during the last 2000 years, when

The 87Sr/86Sr aquatic isoscape of the Danube catchment from the source to the mouth as tool for studying fish migrations

NASA Astrophysics Data System (ADS)

Zitek, Andreas; Tchaikovsky, Anastassiya; Irrgeher, Johanna; Waidbacher, Herwig; Prohaska, Thomas

2014-05-01

Isoscapes - spatially distributed isotope patterns across landscapes - are increasingly used as important basis for ecological studies. The natural variation of the isotopic abundances in a studied area bears the potential to be used as natural tracer for studying e.g. migrations of animals or prey-predator relations. The 87Sr/86Sr ratio is one important tracer, since it is known to provide a direct relation of biological samples to geologically distinct regions, as Sr isotopes are incorporated into living tissues as a proxy for calcium and taken up from the environment without any significant fractionation. Although until now the focus has been mainly set on terrestrial systems, maps for aquatic systems are increasingly being established. Here we present the first 87Sr/86Sr aquatic isoscape of the Danube catchment, the second largest river catchment in Europe, from near its source starting at river km 2581 in Germany down to its mouth to river km 107 in Romania. The total length of the river Danube is 2780 km draining a catchment area 801 463 km2 (10 % of the European continent). The major purpose of this study was to assess the potential of the 87Sr/86Sr isotope ratio to be used as tool for studying fish migrations at different scales in the entire Danube catchment. Within the Joint Danube Research 3 (JDS 3), the biggest scientific multi-disciplinary river expedition of the World in 2013 aiming at the assessment of the ecological status and degree of human alterations along the river Danube, water samples were taken at 68 pre-defined sites along the course of the river Danube including the major tributaries as a basis to create the so called 'Isoscape of the Danube catchment'. The determination of 87Sr/86Sr isotope ratio in river water was performed by multicollector-sector field-inductively coupled plasma-mass spectrometry (MC-SF-ICP-MS). The JDS 3 data were combined with existing data from prior studies conducted within the Austrian part of the Danube catchment

Determination of Fluorine in Fourteen Microanalytical Geologic Reference Materials using SIMS, EPMA, and Proton Induced Gamma Ray Emission (PIGE) Analysis

NASA Astrophysics Data System (ADS)

Guggino, S. N.; Hervig, R. L.

2010-12-01

-DING) = 101 ± 1; ML3B-G (MPI-DING) = 49 ± 17. These values are lower than published values for BCR-2 and BHVO-2 (unmelted powders) and the “information values” for the MPI-DING glass standards. Proton Induced Gamma ray Emission (PIGE) was tested for the high silica samples. PIGE analyses (1.7 MeV Tandem Accelerator; reaction type: 19F(p, αγ)16O; primary current = 20-30 nA; incident beam voltage = 1.5 MeV) were calibrated with a crystal of fluor-topaz (F = 20.3 wt%) and gave F values of: NIST 610 = 266 ± 14 ppm; NIST 620 = 54 ± 5 ppm; and UTR-2 = 1432 ± 32 ppm. SIMS calibration defined by the PIGE analyses shows an excellent linear trend with low background similar to the basaltic calibration. The F concentrations of intermediate MPI-DING glasses were determined based on SIMS calibration generated from the PIGE analysis above. The F concentrations and 2σ errors (ppm) are: T1G = 219.9 ± 6.8; StHs/680-G = 278.0 ± 2.0 ppm. This study revealed a large matrix effect between the high-silica and basaltic glasses, thus requiring the use of appropriate standards and separate SIMS calibrations when analyzing samples of different compositions.

The Cooling and Lubrication Performance of Graphene Platelets in Micro-Machining Environments

NASA Astrophysics Data System (ADS)

Chu, Bryan

temperature and a 25% reduction in the surface roughness value over that of the baseline semi-synthetic cutting fluid. For the thermally-reduced platelets (with 4--8 graphene layers and in-solution characteristic lateral length of 562--2780 nm), a concentration of 0.2 wt% appears to be optimal. An investigation into the impingement dynamics of the graphene-laden colloidal solutions on a heated substrate reveals that the most important criterion dictating their machining performance is their ability to form uniform, submicron thick films of the platelets upon evaporation of the carrier fluid. As such, the characterization of the residual platelet film left behind on a heated substrate may be an effective technique for evaluating different graphene colloidal solutions for cutting fluids applications in micromachining. Graphene platelets have also recently been shown to reduce the aggressive chemical wear of diamond tools during the machining of transition metal alloys. However, the specific mechanisms responsible for this improvement are currently unknown. The modeling work presented in this thesis uses molecular dynamics techniques to shed light on the wear mitigation mechanisms that are active during the diamond cutting of steel when in the presence of graphene platelets. The dual mechanisms responsible for graphene-induced chemical wear mitigation are: 1) The formation of a physical barrier between the metal and tool atoms, preventing graphitization; and 2) The preferential transfer of carbon from the graphene platelet rather than from the diamond tool. The results of the simulations also provide new insight into the behavior of the 2D graphene platelets in the cutting zone, specifically illustrating the mechanisms of cleaving and interlayer sliding in graphene platelets under the high pressures in cutting zones.

Understanding the residence of Co in ore minerals - towards the development of novel Co extraction strategies for laterite deposits

NASA Astrophysics Data System (ADS)

Dybowska, Agnieszka; Norman, Rachel; Schofield, Paul; Herrington, Richard

2017-04-01

Cobalt has unique properties highly valued for many applications essential to the green economy. It has been classified as a critical raw material due to the particularly high risk of supply shortage and its importance for the value chain. Despite low crustal abundance (25ppm), Co is concentrated by various geological processes to concentrations suitable for mining, however the majority of Co is recovered as a by-product of Cu and Ni processing in three principal geological settings: hydrothermal, magmatic and lateritic. Cobalt-rich laterites, which provide 20% of the world's Co, are mainly processed using energy-inefficient pyrometallurgical techniques or high-pressure acid leaching technologies often optimised for extraction of other elements, which can leave between 50 and 80% of the Co unrecovered. In order to develop more efficient Co extraction strategies, understanding the residence of Co in ore minerals is essential. To this end, we are undertaking a detailed mineralogical, chemical and atomistic-scale characterization of Co in samples from a range of laterite deposits. Bulk samples representative of the average ore material were sourced from a variety of undeveloped laterite deposits: Shevchenko (Kazakhstan), Acoje (Philippines), Nkamouna (Cameroon) and Piauí (Brazil). Bulk chemical and mineralogical characterisation was undertaken with ICP-OES/MS and XRD, followed by spatially resolved chemical and mineralogical imaging at the micron scale using µXRD, EPMA, SEM and synchrotron-based µXRF. The chemical state and local environment of Co were determined using X ray spectroscopy (μXANES and μEXAFS). The total concentrations of Co ranged from 630 to 2780 mg/kg. The ore mineral assemblage in the various samples includes goethite, maghemite, hematite, quartz, talc, serpentines, chlorites, smectites, kaolinite and chromites. Manganese oxide minerals are present but, due to their poor crystallinity and low concentration, are not routinely detectable with bulk

[The disease burden of cardiovascular and circulatory diseases in China, 1990 and 2010].

PubMed

Liu, Jiangmei; Liu, Yunning; Wang, Lijun; Yin, Peng; Liu, Shiwei; You, Jinling; Zeng, Xinying; Zhou, Maigeng

2015-04-01

To analyze the death status of disease burden of cardiovascular and circulatory diseases in 1990 and 2010 in China, and to provide the basic information for cardiovascular and circulatory disease prevention and control. Using the results of the Global Burden of Diseases Study 2010 (GBD 2010) to describe the cardiovascular and circulatory diseases deaths status and disease burden in China. The measurement index included the mortality, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). At the same time, we used the population from 2010 national census as standard population to calculate the age-standardized mortality rate and DALY rate, YLL rate and YLD rates which will describe the mortality status and disease burden of total and different types of cardiovascular disease. We also calculated the change in 1990 and 2010 for all indexes, to describe the change of the burden of disease in the 20 years. In 2010, the total deaths of cardiovascular and circulatory diseases reached 3.136 2 million, the mortality rate reached 233.70 per 100 000 people and the age-standardized mortality rate was 256.90 per 100 000 people. The total DALYs, YLLs, and YLDs of cardiovascular and circulatory diseases reached 58.2055, 54.0488, and 4.1568 million person-years, respectively, and the age-standardized DALY rate, YLL rate and YLD rate were 4 639.04, 4 313.13, 325.91 per 100 000. In 1990, the deaths only 2.1675 million and the DALYs, YLLs and YLDs were 45.2679, 42.2922, and 2.9757 million person-years. The age-standardized mortality rate was 300.30 per 100 000 people. And the age-standardized DALY rate, YLL rate and YLD rate were 5 872.58, 5 523.42 and 349.16 per 100 000. Compared with the result in 1990, the total deaths, DALYs, YLLs, and YLDs were increased 44.72%, 28.58%, 27.80%, and 39.68%, respectively, while the age-standardized mortality rate, age-standardized DALY rate, age-standardized YLL rate, and

Providing physicians with feedback on medication adherence for people with chronic diseases taking long-term medication.

PubMed

Zaugg, Vincent; Korb-Savoldelli, Virginie; Durieux, Pierre; Sabatier, Brigitte

2018-01-10

adherence may improve processes of care (e.g. more medication changes, dialogue with patient, management of uncontrolled hypertension) compared to usual care (four studies, 2780 patients). None of the studies reported an adverse event due to the intervention. The certainty of evidence was low for all outcomes, mainly due to high risk of bias, high heterogeneity across studies, and indirectness of evidence. Across nine studies, we observed little or no evidence that provision of feedback to physicians regarding their patients adherence to prescribed medication improved medication adherence, patient outcomes, or health resource use. Feedback about medication adherence may improve processes of care, but due to the small number of studies assessing this outcome and high risk of bias, we cannot draw firm conclusions on the effect of feedback on this outcome. Future research should use a clear, standardised definition of medication adherence and cluster-randomisation to avoid the risk of contamination.

Smartphone and tablet self management apps for asthma.

PubMed

Marcano Belisario, José S; Huckvale, Kit; Greenfield, Geva; Car, Josip; Gunn, Laura H

2013-11-27

significant effect on asthma symptom scores (mean difference (MD) 0.01, 95% confidence interval (CI) -0.23 to 0.25), asthma-related quality of life (MD of mean scores 0.02, 95% CI -0.35 to 0.39), unscheduled visits to the emergency department (OR 7.20, 95% CI 0.37 to 140.76) or frequency of hospital admissions (odds ratio (OR) 3.07, 95% CI 0.32 to 29.83). The other included study found that the use of a smartphone app resulted in higher asthma-related quality of life scores at six-month follow-up (MD 5.50, 95% CI 1.48 to 9.52 for the physical component score of the SF-12 questionnaire; MD 6.00, 95% CI 2.51 to 9.49 for the mental component score of the SF-12 questionnaire), improved lung function (PEFR) at four (MD 27.80, 95% CI 4.51 to 51.09), five (MD 31.40, 95% CI 8.51 to 54.29) and six months (MD 39.20, 95% CI 16.58 to 61.82), and reduced visits to the emergency department due to asthma-related complications (OR 0.20, 95% CI 0.04 to 0.99). Both studies failed to find any statistical differences in terms of adherence to the intervention and occurrence of other asthma-related complications. The current evidence base is not sufficient to advise clinical practitioners, policy-makers and the general public with regards to the use of smartphone and tablet computer apps for the delivery of asthma self management programmes. In order to understand the efficacy of apps as standalone interventions, future research should attempt to minimise the differential clinical management of patients between control and intervention groups. Those studies evaluating apps as part of complex, multicomponent interventions, should attempt to tease out the relative contribution of each intervention component. Consideration of the theoretical constructs used to inform the development of the intervention would help to achieve this goal. Finally, researchers should also take into account: the role of ancillary components in moderating the observed effects, the seasonal nature of asthma and long

A Retirement and A Reservation: A Retrospective Autobiography

PubMed Central

Lee, Sok K

2012-01-01

A retirement is a rite of passage that requires careful planning, because it forces a retiree to make a shift in the paradigm in life. For 37 years, I was a healing professional, a breadwinner, and a working spouse. I am now a jobless loner, an inactive pensioner, and a homebound spouse. In this retrospective autobiography, I suggest a few points to help my younger colleagues to better their upcoming retirement: professional, financial, social, and familial. To overcome Erikson's identity crisis, I volunteered to be a wounded healer at Warm Springs Indian Reservation. My volunteer medical service at Warm Springs Indian Reservation was a good antidote to creatively overcome my postretirement blues. PMID:22745621

A retirement and a reservation: a retrospective autobiography.

PubMed

Lee, Sok K

2012-01-01

A retirement is a rite of passage that requires careful planning, because it forces a retiree to make a shift in the paradigm in life. For 37 years, I was a healing professional, a breadwinner, and a working spouse. I am now a jobless loner, an inactive pensioner, and a homebound spouse. In this retrospective autobiography, I suggest a few points to help my younger colleagues to better their upcoming retirement: professional, financial, social, and familial. To overcome Erikson's identity crisis, I volunteered to be a wounded healer at Warm Springs Indian Reservation. My volunteer medical service at Warm Springs Indian Reservation was a good antidote to creatively overcome my postretirement blues.

A movement, a spirit, a lifestyle change.

PubMed

Eberlee, J

1994-04-01

The Philippines' Department of Health (DOH) has found that young children face the most risk of pneumonia and other respiratory infections. Those from areas not served by physicians face the greatest risk. During the 1980s, DOH set up a 5-year pilot project in 8 rural areas in the southern Philippines to see whether midwives could diagnose and treat acute respiratory infections (ARIs). The midwives used a simple diagnostic method (WHO/ARI algorithm) based on two ARI signs: a respiratory rate of at least 50 breaths/minute and an indrawn chest. An indrawn chest indicated a need to refer a child to the hospital. The midwives did well at diagnosing and treating ARIs. DOH has since introduced the algorithm nationwide. This research addressed an important problem and was well planned and implemented. IDRC and the Council on Health Research for Development in Geneva sponsors the Essential National Health Research (ENHR) initiative in the Philippines. The ENHR strategy aims to better people's health by establishing priorities among different health problems. After priority setting, a participatory process involving communities, researchers, and policy and decision makers determines the relevant research questions. ENHR should result in better, more effective, and more equitable health care and reduce the burden of illness. The first ENHR agenda includes the following research priorities: impact of indigenous beliefs and practices on health; baseline epidemiologic studies on mental health problems; infectious diseases (especially tuberculosis); evaluation of implementation of national health programs; and development of strategies to encourage rational use of drugs in hospitals. It took more than 2 years to agree on these priorities--a complicated and democratic process. The next step is to obtain funding for these projects. The ENHR project wants to attempt advocacy work--creating demand for research and preparing policy makers for the data. Its goal is to be a catalyst in

76 FR 53324 - Airworthiness Directives; Agusta S.p.A. Model A109A, A109A II, A109C, and A109K2 Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... Airworthiness Directives; Agusta S.p.A. Model A109A, A109A II, A109C, and A109K2 Helicopters AGENCY: Federal... helicopters. That EAD currently requires inspecting the main rotor scissor fitting assembly to determine if... helicopter. DATES: Effective September 12, 2011. The incorporation by reference of certain publications...

A search for a new gauge boson A'

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

Jensen, Eric L.

2013-08-01

In the Standard Model, gauge bosons mediate the strong, weak, and electromagnetic forces. New forces could have escaped detection only if their mediators are either heavier than order(TeV) or weakly coupled to charged matter. New vector bosons with small coupling {alpha}' arise naturally from a small kinetic mixing with the photon and have received considerable attention as an explanation of various dark matter related anomalies. Such particles can be produced in electron-nucleus fixed-target scattering and then decay to e +e -+ pairs. New light vector bosons and their associated forces are a common feature of Standard Model extensions, but existingmore » constraints are remarkably sparse. The APEX experiment will search for a new vector boson A' with coupling α'/α fs > 6 × 10 -8 to electrons in the mass range 65MeV < mass A' < 550MeV. The experiment will study e +e - production off an electron beam incident on a high-Z target in Hall A at Jefferson Lab. The e - and e + will be detected in the High Resolution Spectrometers (HRSs). The invariant mass spectrum of the e +e - pairs will be scanned for a narrow resonance corresponding to the mass of the A'. A test run for the APEX experiment was held in the summer of 2010. Using the test run data, an A' search was performed in the mass range 175-250 MeV. The search found no evidence for an A' → e +e -reaction, and set an upper limit of {alpha}'/{alpha}{sub fs} ~ 10 -6.« less

Engineering a trifunctional proline utilization A chimaera by fusing a DNA-binding domain to a bifunctional PutA.

PubMed

Arentson, Benjamin W; Hayes, Erin L; Zhu, Weidong; Singh, Harkewal; Tanner, John J; Becker, Donald F

2016-12-01

Proline utilization A (PutA) is a bifunctional flavoenzyme with proline dehydrogenase (PRODH) and Δ 1 -pyrroline-5-carboxylate (P5C) dehydrogenase (P5CDH) domains that catalyses the two-step oxidation of proline to glutamate. Trifunctional PutAs also have an N-terminal ribbon-helix-helix (RHH) DNA-binding domain and moonlight as autogenous transcriptional repressors of the put regulon. A unique property of trifunctional PutA is the ability to switch functions from DNA-bound repressor to membrane-associated enzyme in response to cellular nutritional needs and proline availability. In the present study, we attempt to construct a trifunctional PutA by fusing the RHH domain of Escherichia coli PutA (EcRHH) to the bifunctional Rhodobacter capsulatus PutA (RcPutA) in order to explore the modular design of functional switching in trifunctional PutAs. The EcRHH-RcPutA chimaera retains the catalytic properties of RcPutA while acquiring the oligomeric state, quaternary structure and DNA-binding properties of EcPutA. Furthermore, the EcRHH-RcPutA chimaera exhibits proline-induced lipid association, which is a fundamental characteristic of functional switching. Unexpectedly, RcPutA lipid binding is also activated by proline, which shows for the first time that bifunctional PutAs exhibit a limited form of functional switching. Altogether, these results suggest that the C-terminal domain (CTD), which is conserved by trifunctional PutAs and certain bifunctional PutAs, is essential for functional switching in trifunctional PutAs. © 2016 The Author(s).

Engineering a trifunctional proline utilization A chimaera by fusing a DNA-binding domain to a bifunctional PutA

PubMed Central

Arentson, Benjamin W.; Hayes, Erin L.; Zhu, Weidong; Singh, Harkewal; Tanner, John J.; Becker, Donald F.

2016-01-01

Proline utilization A (PutA) is a bifunctional flavoenzyme with proline dehydrogenase (PRODH) and Δ1-pyrroline-5-carboxylate (P5C) dehydrogenase (P5CDH) domains that catalyses the two-step oxidation of proline to glutamate. Trifunctional PutAs also have an N-terminal ribbon–helix–helix (RHH) DNA-binding domain and moonlight as autogenous transcriptional repressors of the put regulon. A unique property of trifunctional PutA is the ability to switch functions from DNA-bound repressor to membrane-associated enzyme in response to cellular nutritional needs and proline availability. In the present study, we attempt to construct a trifunctional PutA by fusing the RHH domain of Escherichia coli PutA (EcRHH) to the bifunctional Rhodobacter capsulatus PutA (RcPutA) in order to explore the modular design of functional switching in trifunctional PutAs. The EcRHH–RcPutA chimaera retains the catalytic properties of RcPutA while acquiring the oligomeric state, quaternary structure and DNA-binding properties of EcPutA. Furthermore, the EcRHH–RcPutA chimaera exhibits proline-induced lipid association, which is a fundamental characteristic of functional switching. Unexpectedly, RcPutA lipid binding is also activated by proline, which shows for the first time that bifunctional PutAs exhibit a limited form of functional switching. Altogether, these results suggest that the C-terminal domain (CTD), which is conserved by trifunctional PutAs and certain bifunctional PutAs, is essential for functional switching in trifunctional PutAs. PMID:27742866

A Higher Education--A Polemic (For a Change)

ERIC Educational Resources Information Center

Peters, Lloyd

2015-01-01

The BBC Radio 4 comedy-drama "A Higher Education" was written in 1999 to present a satire of a dysfunctional and cash-strapped university (Northfield) led by the egotistical and amoral Head of Drama, Don Crookfield (played by Rik Mayall). For those of us passionately engaged in the provision of higher education today, the satire also…

Mapping a Space for a Rhetorical-Cultural Analysis: A Case of a Scientific Proposal

ERIC Educational Resources Information Center

Dorpenyo, Isidore Kafui

2015-01-01

This article analyzes a proposal submitted to a funding unit in Michigan Technological University by a PhD Forestry student. A rhetorical-cultural approach of the text provides evidence to argue that scientific writing is rooted in a cultural practice that valorizes certain kinds of thought, practices, rituals, and symbols; that a scientist's work…

Radionuclide-binding compound, a radionuclide delivery system, a method of making a radium complexing compound, a method of extracting a radionuclide, and a method of delivering a radionuclide

DOEpatents

Fisher, Darrell R.; Wai, Chien M.; Chen, Xiaoyuan

2000-01-01

The invention pertains to compounds which specifically bind radionuclides, and to methods of making radionuclide complexing compounds. In one aspect, the invention includes a radionuclide delivery system comprising: a) a calix[n]arene-crown-[m]-ether compound, wherein n is an integer greater than 3, and wherein m is an integer greater than 3, the calix[n]arene-crown-[m]-ether compound comprising at least two ionizable groups; and b) an antibody attached to the calix[n]arene-crown-[m]-ether compound. In another aspect, the invention includes a method of making a radium complexing compound, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising n phenolic hydroxyl groups; b) providing a crown ether precursor, the crown ether precursor comprising a pair of tosylated ends; c) reacting the pair of tosylated ends with a pair of the phenolic hydroxyl groups to convert said pair of phenolic hydroxyl groups to ether linkages, the ether linkages connecting the crown ether precursor to the calix[n]arene to form a calix[n]arene-crown-[m]-ether compound, wherein m is an integer greater than 3; d) converting remaining phenolic hydroxyl groups to esters; e) converting the esters to acids, the acids being proximate a crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound; and f) providing a Ra.sup.2+ ion within the crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound.

Burning a Candle in a Vessel, a Simple Experiment with a Long History

NASA Astrophysics Data System (ADS)

Vera, Francisco; Rivera, Rodrigo; Núñez, César

2011-09-01

The experiment in which a candle is burned inside an inverted vessel partially immersed in water has a history of more than 2,200 years, but even nowadays it is common that students and teachers relate the change in volume of the enclosed air to its oxygen content. Contrary to what many people think, Lavoisier concluded that any change in volume in this experiment is negligible; moreover, the explanation relating oxygen consumption in the air with its change in volume is known to be wrong. In this work we briefly review the history behind the candle experiment and its relationship with some typical erroneous explanations. One of the key factors behind Lavoisier's success was the use of experiments carefully designed to test different hypotheses. Following these steps, we performed several closed volume experiments where the candle wick was replaced by a capillary stainless steel cylinder supported and heated by a nichrome filament connected to an external power supply. Our recorded experiments are displayed as web pages, designed with the purpose that the reader can easily visualize and analyze modern versions of Lavoisier's experiments. These experiments clearly show an initial phase of complete combustion, followed by a phase of incomplete combustion with elemental carbon or soot rising to the top of the vessel, and a final phase where the hot artificial wick only evaporates a white steam of wax that cannot ignite because no oxygen is left in the closed atmosphere. After either a complete or incomplete combustion of the oxygen, our experiments show that the final gas volume is nearly equal to the initial air volume.