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https://www.readbyqxmd.com/read/29166623/anticancer-potential-of-zno-nanoparticle-ferulic-acid-conjugate-on-huh-7-and-hepg2-cells-and-diethyl-nitrosamine-induced-hepatocellular-cancer-on-wistar-albino-rat
#1
E Preedia Babu, A Subastri, A Suyavaran, S Nithyananthan, M Suresh Kumar, K Premkumar, R Bharathidasan, C Thirunavukkarasu
Drawbacks and limitations of recently available therapies to hepatocellular cancer (HCC) devoted the scientist to focus on emerging new strategies. ZnO nanoparticles (ZnONPs) based chemotherapeutics has been emanating as a promising approach to maximize therapeutic synergy facilitating the discovery of novel multitargeted combinations. In the present study we conjugated ZnONPs with ferulic acid (ZnONPs-FAC) characterized by computational, spectroscopic and microscopic techniques. In vitro anticancer potential has been evaluated by assessing cell viability, morphology, ROS generation, mitochondrial membrane permeability, comet assay, immunofluorescent staining of 8-OHdG, Ki67 and γ-H2AX, cell cycle analysis and western blot analysis and in vivo anticancer potential against DEN induced HCC was analyzed by histopathological and immunohistochemical methods...
November 19, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29165554/the-effect-of-1-5%C3%A2-t-cardiac-magnetic-resonance-on-human-circulating-leucocytes
#2
William R Critchley, Anna Reid, Julie Morris, Josephine H Naish, John P Stone, Alexandra L Ball, Triin Major, David Clark, Nick Waldron, Christien Fortune, Jakub Lagan, Gavin A Lewis, Mark Ainslie, Erik B Schelbert, Daniel M Davis, Matthias Schmitt, James E Fildes, Christopher A Miller
Aims: Investigators have proposed that cardiovascular magnetic resonance (CMR) should have restrictions similar to those of ionizing imaging techniques. We aimed to investigate the acute effect of 1.5 T CMR on leucocyte DNA integrity, cell counts, and function in vitro, and in a large cohort of patients in vivo. Methods and results: In vitro study: peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers, and histone H2AX phosphorylation (γ-H2AX) expression, leucocyte counts, and functional parameters were quantified using flow cytometry under the following conditions: (i) immediately following PBMC isolation, (ii) after standing on the benchside as a temperature and time control, (iii) after a standard CMR scan...
November 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29163782/bmi1-reduces-atr-activation-and-signalling-caused-by-hydroxyurea
#3
Xiaozeng Lin, Fengxiang Wei, Peter Whyte, Damu Tang
BMI1 facilitates DNA damage response (DDR) induced by double strand DNA breaks; however, it remains unknown whether BMI1 functions in single strand DNA (ssDNA) lesions-initiated DDR. We report here that BMI1 reduces hydroxyurea-elicited ATR activation, thereby reducing the S-phase checkpoints. Hydroxyurea induces ssDNA lesions, which activate ATR through binding TOPBP1 as evidenced by phosphorylation of ATR at threonine 1989 (ATRpT1989). ATR subsequently phosphorylates H2AX at serine 139 (γH2AX) and CHK1 at serine 345 (CHK1pS345), leading to phosphorylation of CDK1 at tyrosine 15 (CDK1pY15) and S-phase arrest...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163714/downregulation-of-eukaryotic-initiation-factor-4a1-improves-radiosensitivity-by-delaying-dna-double-strand-break-repair-in-cervical-cancer
#4
Shanhui Liang, Xingzhu Ju, Yuqi Zhou, Yiran Chen, Guihao Ke, Hao Wen, Xiaohua Wu
Expression of eukaryotic initiation factor 4A1 (eIF4A1) following brachytherapy has been reported to predict improved radiosensitivity and tumor-specific survival in cervical cancer. Therefore, the present study investigated the function of eIF4A1 in cervical cancer and the mechanism by which eIF4A1 regulates cervical cancer radiosensitivity. It was determined that the downregulation of eIF4A1 in HeLa and SiHa cells notably attenuated cell proliferation, in addition to repressing cervical cancer migration and invasion, and promoting cell apoptosis...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29158830/sustained-release-talazoparib-implants-for-localized-treatment-of-brca1-deficient-breast-cancer
#5
Jodi E Belz, Rajiv Kumar, Paige Baldwin, Noelle Castilla Ojo, Ana S Leal, Darlene B Royce, Di Zhang, Anne L van de Ven, Karen T Liby, Srinivas Sridhar
Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0...
2017: Theranostics
https://www.readbyqxmd.com/read/29155797/immunofluorescence-microscopy-of-%C3%AE-h2ax-and-53bp1-for-analyzing-the-formation-and-repair-of-dna-double-strand-breaks
#6
Henning D Popp, Susanne Brendel, Wolf-Karsten Hofmann, Alice Fabarius
DNA double-strand breaks (DSB) are serious DNA lesions. Analysis of the formation and repair of DSB is relevant in a broad spectrum of research areas including genome integrity, genotoxicity, radiation biology, aging, cancer, and drug development. In response to DSB, the histone H2AX is phosphorylated at Serine 139 in a region of several megabase pairs forming discrete nuclear foci detectable by immunofluorescence microscopy. In addition, 53BP1 (p53 binding protein 1) is another important DSB-responsive protein promoting repair of DSB by nonhomologous end-joining while preventing homologous recombination...
November 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29150048/dna-dependent-protein-kinase-modulates-the-anti-cancer-properties-of-silver-nanoparticles-in-human-cancer-cells
#7
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29143974/%C3%AE-h2ax-formation-in-the-urinary-bladder-of-rats-treated-with-two-norharman-derivatives-obtained-from-o-toluidine-and-aniline
#8
T Toyoda, Y Totsuka, K Matsushita, T Morikawa, N Miyoshi, K Wakabayashi, K Ogawa
Aminomethylphenylnorharman (AMPNH) and aminophenylnorharman (APNH) are mutagenic norharman derivatives obtained from o-toluidine and aniline, respectively. APNH is carcinogenic to the urinary bladder of rats and present in urine samples of healthy volunteers, indicating that norharman derivatives may be associated with cancer development in the urinary bladder of humans. To evaluate the possible role of AMPNH and APNH in bladder carcinogenesis, we examined the formation of γ-H2AX, a DNA damage response marker, in the urinary bladder of rats...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#9
Pasupathi Sundaramoorthy, Qinhong Wang, Zhihong Zheng, Yiqun Jiao, Benny J Chen, Phuong L Doan, Nelson J Chao, Yubin Kang
BACKGROUND: Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs) from radiation injury is an important goal in the development of medical countermeasure agents (MCM). We recently identified thioredoxin (TXN) as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI) and in enhancing hematopoietic reconstitution following a lethal dose of irradiation...
November 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29133620/evaluation-of-cdk12-protein-expression-as-a-potential-novel-biomarker-for-dna-damage-response-targeted-therapies-in-breast-cancer
#10
Kalnisha Naidoo, Patty T Wai, Sarah L Maguire, Frances Daley, Syed Haider, Divya Kriplani, James Campbell, Hasan Mirza, Anita Grigoriadis, Andrew Tutt, Paul M Moseley, Tarek M A Abdel-Fatah, Stephen Yt Chan, Srinivasan Madhusudan, Emad A Rakha, Ian O Ellis, Christopher J Lord, Yinyin Yuan, Andrew R Green, Rachael Natrajan
Disruption of Cyclin Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and poly(ADP-ribose) polymerase 1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. We therefore aimed to assess the frequency and distribution of CDK12 protein expression by immunohistochemistry (IHC) in independent cohorts of breast cancer and correlate this with outcome and genomic status. We found that 21% of primary unselected breast cancers were CDK12 high, and 10...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29132682/-biomarkers-of-radiation-induced-dna-repair-processes
#11
REVIEW
Alexis Vallard, Chloé Rancoule, Jean-Baptiste Guy, Sophie Espenel, Sylvie Sauvaigo, Claire Rodriguez-Lafrasse, Nicolas Magné
The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29130659/-dna-repair-function-and-mutation-of-an-h2b-monoubiquitination-factor-wdr70-in-ovarian-cancer
#12
Zi-Zhi Tang, Hai-Bin Wang, Ming Zeng, Cong Liu, De-Hua Li
OBJECTIVE: To investigate the roles of enzyme DCAF proteinDNA damagebinding protein 1 (DDB1)/cullin4 (CRL4) complex family members CRL4WD40 repeat domain protein 70 (WDR70) in DNA repair process and its mutation in ovarian cancer. METHODS: Immunofluorescent assay was employed to measure H2AX (γH2AX) and phosphorylated replication protein A2 (RPA32) formed in siDDB1 or siWDR70 ovarian cancer cells after the treatments of chemical medicine and radioactive threapy...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29129974/screening-of-pesticides-with-the-potential-of-inducing-dsb-and-successive-recombinational-repair
#13
Karen Suárez-Larios, Ana-María Salazar-Martínez, Regina Montero-Montoya
A study was realized to ascertain whether eight selected pesticides would induce double strand breaks (DSB) in lymphocyte cultures and whether this damage would induce greater levels of proteins Rad51 participating in homologous recombination or of p-Ku80 participating in nonhomologous end joining. Only five pesticides were found to induce DSB of which only glyphosate and paraoxon induced a significant increase of p-Ku80 protein, indicating that nonhomologous end joining recombinational DNA repair system would be activated...
2017: Journal of Toxicology
https://www.readbyqxmd.com/read/29128690/transcriptome-based-biological-dosimetry-of-gamma-radiation-in-arabidopsis-using-dna-damage-response-genes
#14
Tae Ho Ryu, Jin Kyu Kim, Jeong-Il Kim, Jin-Hong Kim
Plants are used as representative reference biota for the biological assessment of environmental risks such as ionizing radiation due to their immobility. This study proposed a faster, more economical, and more effective method than conventional cytogenetic methods for the biological dosimetry of ionizing radiation in plants (phytodosimetry). We compared various dose-response curves for the radiation-induced DNA damage response (DDR) in Arabidopsis thaliana after relatively "low-dose" gamma irradiation (3, 6, 12, 24, and 48 Gy) below tens of Gy using comet (or single-cell gel electrophoresis), gamma-H2AX, and transcriptomic assays of seven DDR genes (AGO2, BRCA1, GRG, PARP1, RAD17, RAD51, and RPA1E) using quantitative real time PCR...
November 9, 2017: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/29128613/submicromolar-bisphenol-a-induces-proliferation-and-dna-damage-in-human-hepatocyte-cell-lines-in-vitro-and-in-juvenile-rats-in-vivo
#15
Seoyoung Kim, Gil-Im Mun, Eun Choi, Minjeong Kim, Ji Seong Jeong, Keon Wook Kang, Sunha Jee, Kyung-Min Lim, Yun-Sil Lee
An association between bisphenol A (BPA) exposure and hepatic tumors was suggested, but the employment of high-dose levels raises questions about its relevance to human health. Here, we demonstrate that submicromolar concentrations of BPA induce the proliferation and DNA damage in human hepatocyte cell lines. In HepG2 and NKNT-3, undifferentiated and differentiated hepatocyte cell lines, respectively, submicromolar BPA concentrations promoted the cell proliferation, as indicated by enhanced DNA synthesis and elevated expression of cell-cycle proteins...
November 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29126329/effect-of-benzo-a-pyrene-on-spindle-mis-orientation-and-fidelity-of-chromosome-segregation-in-lung-epithelial-beas-2b-cells
#16
Jose Thaiparambil, Oula Mansour, Randa El-Zein
Benzo[a]pyrene (B[a]P) is an environmental carcinogen found in tobacco smoke. It leads to high levels of DNA adducts in the lungs of cigarette smokers contributing to genomic instability. Alterations in the mitotic spindle apparatus play a major role in the generation of genomic instability through promoting chromosome mis-segregation and aneuploidy. To date, the effect of B[a]P exposure on altering the mitotic apparatus in normal lung epithelial cells remains unknown. In our study, BEAS-2B human bronchial epithelial cells were exposed to B[a]P and spindle dynamics were evaluated...
November 6, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29121093/fish-oil-omega-3-polyunsaturated-fatty-acids-attenuate-oxidative-stress-induced-dna-damage-in-vascular-endothelial-cells
#17
Chiemi Sakai, Mari Ishida, Hideo Ohba, Hiromitsu Yamashita, Hitomi Uchida, Masao Yoshizumi, Takafumi Ishida
OBJECTIVE: Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms. METHODS AND RESULTS: We determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/29118920/combination-therapy-with-extracorporeal-shock-wave-and-melatonin-markedly-attenuated-neuropathic-pain-in-rat
#18
Kuan-Hung Chen, Chien-Hui Yang, Christopher Glenn Wallace, Chung-Ren Lin, Chia-Kai Liu, Tsung-Cheng Yin, Tien-Hung Huang, Yi-Ling Chen, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29117787/reprogramming-of-adult-peripheral-blood-cells-into-human-induced-pluripotent-stem-cells-as-a-safe-and-accessible-source-of-endothelial-cells
#19
Pavel Simara, Lenka Tesarova, Daniela Rehakova, Simon Farkas, Barbara Salingova, Katerina Kutalkova, Eva Vavreckova, Pavel Matula, Petr Matula, Lenka Veverkova, Irena Koutna
New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors (EPCs) reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood...
November 8, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29117515/metformin-and-epothilone-a-treatment-up-regulate-pro-apoptotic-parp-1-casp-3-and-h2ax-genes-and-decrease-of-akt-kinase-level-to-control-cell-death-of-human-hepatocellular-carcinoma-and-ovary-adenocarcinoma-cells
#20
Aneta Rogalska, Barbara Bukowska, Agnieszka Marczak
High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy. Here, we investigated genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) in combination with respect to apoptosis in HepG2 and SKOV-3 cancer cells. Reactive oxygen species (ROS) was studied using 2',7'-dichlorodihydrofluoresein diacetate, and samples were analyzed for the presence and absence of the N-acetylcysteine (NAC). Expression of genes involved in programmed cell death, oxidative and alkylating DNA damage was measured...
November 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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