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https://www.readbyqxmd.com/read/28640454/direct-quantification-of-gamma-h2ax-by-cell-based-high-throughput-screening-for-evaluation-of-genotoxicity-of-pesticides-in-a-human-thyroid-cell-lines
#1
Jerome M Hershman, Bryan France, Kevin Hon, Robert Damoiseaux
Genotoxicity is thought to be the cause of many cancers. Genotoxicity due to environmental toxins may be partly responsible for the dramatic increase in the incidence of papillary thyroid cancer over the past two decades. Here, we present a fully automatable assay platform that directly quantifies the phosphorylation of nuclear histone gamma H2AX (γH2AX), a specific cellular marker for DNA double strand breaks (DSBs) via immunohistochemistry and laser scanning cytometry. It multiplexes γH2AX with total cell number measured as propidium iodide and calculates the percentage of cells with DSBs...
June 22, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28635637/a-short-term-biological-indicator-for-long-term-kidney-damage-after-radionuclide-therapy-in-mice
#2
Giovanni Pellegrini, Klaudia Siwowska, Stephanie Haller, Daniel J Antoine, Roger Schibli, Anja Kipar, Cristina Müller
Folate receptor (FR)-targeted radionuclide therapy using folate radioconjugates is of interest due to the expression of the FR in a variety of tumor types. The high renal accumulation of radiofolates presents, however, a risk of radionephropathy. A potential option to address this challenge would be to use radioprotectants, such as amifostine. Methods for early detection of kidney damage that-in this case-cannot be predicted based on dose estimations, would facilitate the development of novel therapies. The aim of this study was, therefore, to assess potentially changing levels of plasma and urine biomarkers and to determine DNA damage at an early stage after radiofolate application...
June 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28631426/hsp90%C3%AE-regulates-atm-and-nbn-functions-in-sensing-and-repair-of-dna-double-strand-breaks
#3
Rosa Pennisi, Antonio Antoccia, Stefano Leone, Paolo Ascenzi, Alessandra di Masi
The molecular chaperone heat shock protein 90 (Hsp90α) regulates cells proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ATM and NBN, but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cells lines...
June 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28627647/differences-in-telomerase-activity-and-the-effects-of-azt-in-aneuploid-and-euploid-cells-in-colon-cancer
#4
Xiao Fang, Tenghui Hu, Hua Yin, Junjun Yang, Weian Tang, Siqi Hu, Xingxiang Xu
Telomerase-targeted treatments for cancer have received a great deal of attention because telomerase is detected in nearly all cancer cells but is not expressed in most normal tissues. Aneuploidy refers to a chromosome number that is not a multiple of the base chromosome number and can indicate either hypo- or hyperploid chromosome numbers. Most solid tumors are aneuploid. In the present study, we sought to determine whether there are differences in telomerase activity and hTERT gene expression between aneuploid and euploid cells...
June 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28624023/enhanced-radiation-damage-caused-by-iodinated-contrast-agents-during-ct-examination
#5
Ling Wang, Qiang Li, Xi-Ming Wang, Guang-Yu Hao, Jie-Bao, Su Hu, Chun-Hong Hu
OBJECTIVE: To access the effect of iodinate contrast agent (ICA) on DNA double-stand breaks (DSBs) in human peripheral blood lymphocytes during computed tomography (CT) examinations. MATERIALS AND METHODS: This present study was approved by the institutional ethics committee; written informed patient consent was obtained from 70 patients. A total of 48 patients underwent computed tomography urography (CTU), in which only one time CT scanning was examined after injecting ICA, and 22 patients received unenhanced whole abdominal CT, among them 10 patients were selected to get ICA injection immediately after irradiation...
July 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28621664/post-meiotic-dna-double-strand-breaks-occur-in-tetrahymena-and-require-topoisomerase-ii-and-spo11
#6
Takahiko Akematsu, Yasuhiro Fukuda, Jyoti Garg, Jeffrey S Fillingham, Ronald E Pearlman, Josef Loidl
Based on observations of markers for DNA lesions, such as phosphorylated histone H2AX (γH2AX) and open DNA ends, it has been suggested that post-meiotic DNA double-strand breaks (PM-DSBs) enable chromatin remodeling during animal spermiogenesis. However, the existence of PM-DSBs is unconfirmed, and the mechanism responsible for their formation is unclear. Here, we report the first direct observation of programmed PM-DSBs via the electrophoretic separation of DSB-generated DNA fragments in the ciliate Tetrahymena thermophila...
June 16, 2017: ELife
https://www.readbyqxmd.com/read/28612525/-the-role-of-dna-double-strain-damage-repairing-mechanisms-in-diabetic-atheroscolersis
#7
Li Zeng, Qun-Fang Ding, Ting-Yuan Xu, Fang Luo, Ning Ge, Shi-Tong Li
OBJECTIVES: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. METHODS: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28609451/anti-cancer-agents-in-saudi-arabian-herbals-revealed-by-automated-high-content-imaging
#8
Dina Hajjar, Stephan Kremb, Salim Sioud, Abdul-Hamid Emwas, Christian R Voolstra, Timothy Ravasi
Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia's traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action...
2017: PloS One
https://www.readbyqxmd.com/read/28607084/systems-guided-forward-genetic-screen-reveals-a-critical-role-of-the-replication-stress-response-protein-etaa1-in-t-cell-clonal-expansion
#9
Lisa A Miosge, Yovina Sontani, Aaron Chuah, Keisuke Horikawa, Tiffany A Russell, Yan Mei, Mayura V Wagle, Debbie R Howard, Anselm Enders, David C Tscharke, Christopher C Goodnow, Ian A Parish
T-cell immunity requires extremely rapid clonal proliferation of rare, antigen-specific T lymphocytes to form effector cells. Here we identify a critical role for ETAA1 in this process by surveying random germ line mutations in mice using exome sequencing and bioinformatic annotation to prioritize mutations in genes of unknown function with potential effects on the immune system, followed by breeding to homozygosity and testing for immune system phenotypes. Effector CD8(+) and CD4(+) T-cell formation following immunization, lymphocytic choriomeningitis virus (LCMV) infection, or herpes simplex virus 1 (HSV1) infection was profoundly decreased despite normal immune cell development in adult mice homozygous for two different Etaa1 mutations: an exon 2 skipping allele that deletes Gly78-Leu119, and a Cys166Stop truncating allele that eliminates most of the 877-aa protein...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28606252/-research-on-the-effect-of-iodinate-contrast-agent-on-the-dna-radiation-damage-at-ct
#10
L Wang, Q Li, W Zhong, S Hu, C H Hu
Objective: To evaluate the effect of iodinate contrast agent (ICA) on the formation of DNA double-stand breaks (DSBs) in human peripheral blood lymphocytes during computed tomography (CT) examinations. Methods: Peripheral venous blood (16 ml/person) of 36 volunteers were collected during the period of February to May 2016. Each blood sample was divided into 8 tubes and 4 groups on average, which were marked as groups of A, B, C, D randomly. 25 μl ICA was respectively added into one tube of each group and the groups of B, C, D accepted the same CT scan for once, twice and three times...
June 6, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28605880/js-k-a-nitric-oxide-prodrug-induces-dna-damage-and-apoptosis-in-hbv-positive-hepatocellular-carcinoma-hepg2-2-15-cell
#11
Zhengyun Liu, Guangmin Li, Ying Gou, Dongyan Xiao, Guo Luo, Joseph E Saavedra, Jie Liu, Huan Wang
Hepatocellular carcinoma (HCC) is the most important cause of cancer-related death, and 85% of HCC is caused by chronic HBV infection, the prognosis of patients and the reduction of HBV DNA levels remain unsatisfactory. JS-K, a nitric oxide-releasing diazeniumdiolates, is effective against various tumors, but little is known on its effects on HBV positive HCC. We found that JS-K reduced the expression of HBsAg and HBeAg in HBV-positive HepG2.2.15 cells. This study aimed to further examine anti-tumor effects of JS-K on HepG2...
June 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28604675/identification-of-the-elementary-structural-units-of-the-dna-damage-response
#12
Francesco Natale, Alexander Rapp, Wei Yu, Andreas Maiser, Hartmann Harz, Annina Scholl, Stephan Grulich, Tobias Anton, David Hörl, Wei Chen, Marco Durante, Gisela Taucher-Scholz, Heinrich Leonhardt, M Cristina Cardoso
Histone H2AX phosphorylation is an early signalling event triggered by DNA double-strand breaks (DSBs). To elucidate the elementary units of phospho-H2AX-labelled chromatin, we integrate super-resolution microscopy of phospho-H2AX during DNA repair in human cells with genome-wide sequencing analyses. Here we identify phospho-H2AX chromatin domains in the nanometre range with median length of ∼75 kb. Correlation analysis with over 60 genomic features shows a time-dependent euchromatin-to-heterochromatin repair trend...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28602099/zerumbone-regulates-dna-repair-responding-to-ionizing-radiation-and-enhances-radiosensitivity-of-human-prostatic-cancer-cells
#13
Pai-Kai Chiang, Wei-Kung Tsai, Marcelo Chen, Wun-Rong Lin, Yung-Chiong Chow, Chih-Chiao Lee, Jong-Ming Hsu, Yu-Jen Chen
INTRODUCTION: Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation-induced DSB in human prostate cancer cells. MATERIALS AND METHODS: The human prostate cancer PC3 and DU145 cell lines were used...
June 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28601509/olaparib-hydroxamic-acid-derivatives-as-dual-parp-and-hdac-inhibitors-for-cancer-therapy
#14
Zigao Yuan, Shaopeng Chen, Qinsheng Sun, Ning Wang, Dan Li, Shuangshuang Miao, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines...
May 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28599419/a-conditionally-replicating-adenovirus-expressing-il-24-acts-synergistically-with-temozolomide-to-enhance-apoptosis-in-melanoma-cells-in-vitro
#15
Zhen Liang, Chun-Sheng Yang, Feng Gu, Lan-Sheng Zhang
Malignant melanoma is characterized by suppressed apoptosis in tumor cells and high levels of invasion. Temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and frequently. Therapeutic cytokines such as interleukin-24 (IL-24) and conditionally replicating adenoviruses have exhibited promising results as complementary therapies. Thus, the present study hypothesized that a conditionally replicating adenovirus expressing IL-24 combined with TMZ may exhibit increased antitumor activity compared with either treatment alone in melanoma A375 and M14 cell lines in vitro...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599315/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#16
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590415/the-dual-roles-of-myc-in-genomic-instability-and-cancer-chemoresistance
#17
REVIEW
Alpana Kumari, Watson P Folk, Daitoku Sakamuro
Cancer is associated with genomic instability and aging. Genomic instability stimulates tumorigenesis, whereas deregulation of oncogenes accelerates DNA replication and increases genomic instability. It is therefore reasonable to assume a positive feedback loop between genomic instability and oncogenic stress. Consistent with this premise, overexpression of the MYC transcription factor increases the phosphorylation of serine 139 in histone H2AX (member X of the core histone H2A family), which forms so-called γH2AX, the most widely recognized surrogate biomarker of double-stranded DNA breaks (DSBs)...
June 7, 2017: Genes
https://www.readbyqxmd.com/read/28587165/dynamic-in-vivo-profiling-of-dna-damage-and-repair-after-radiotherapy-using-canine-patients-as-a-model
#18
Nadine Schulz, Hassan Chaachouay, Katarzyna J Nytko, Mathias S Weyland, Malgorzata Roos, Rudolf M Füchslin, Franco Guscetti, Stephan Scheidegger, Carla Rohrer Bley
Time resolved data of DNA damage and repair after radiotherapy elucidates the relation between damage, repair, and cell survival. While well characterized in vitro, little is known about the time-course of DNA damage response in tumors sampled from individual patients. Kinetics of DNA damage after radiotherapy was assessed in eight dogs using repeated in vivo samples of tumor and co-irradiated normal tissue analyzed with comet assay and phosphorylated H2AX (γH2AX) immunohistochemistry. In vivo results were then compared (in silico) with a dynamic mathematical model for DNA damage formation and repair...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583009/inhibition-of-%C3%AE-synuclein-contributes-to-the-ameliorative-effects-of-dietary-flavonoids-luteolin-on-arsenite-induced-apoptotic-cell-death-in-the-dopaminergic-pc-12-cells
#19
Yi Wu, Xuejun Jiang, Kai Yang, Yinyin Xia, Shuqun Cheng, Qianghu Tang, LuLu Bai, Jingfu Qiu, Chengzhi Chen
Arsenite is a toxic metalloid that may increase the risk of Parkinson's disease by inducing dopaminergic neuronal apoptosis. Luteolin, a common dietary flavonoid, possesses variety of biological functions, but potential effects of luteolin on arsenite toxicity remain elusive. In this study, we demonstrated that luteolin prevented arsenite-induced apoptosis in the dopaminergic PC12 cells. Administering of luteolin to cells attenuated arsenite-induced ROS production, enhanced caspase-3 activity and γ-H2AX expression...
June 6, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28580170/cell-free-chromatin-from-dying-cancer-cells-integrate-into-genomes-of-bystander-healthy-cells-to-induce-dna-damage-and-inflammation
#20
Indraneel Mittra, Urmila Samant, Suvarna Sharma, Gorantla V Raghuram, Tannistha Saha, Pritishkumar Tidke, Namrata Pancholi, Deepika Gupta, Preeti Prasannan, Ashwini Gaikwad, Nilesh Gardi, Rohan Chaubal, Pawan Upadhyay, Kavita Pal, Bhagyeshri Rane, Alfina Shaikh, Sameer Salunkhe, Shilpee Dutt, Pradyumna K Mishra, Naveen K Khare, Naveen K Nair, Amit Dutt
Bystander cells of the tumor microenvironment show evidence of DNA damage and inflammation that can lead to their oncogenic transformation. Mediator(s) of cell-cell communication that brings about these pro-oncogenic pathologies has not been identified. We show here that cell-free chromatin (cfCh) released from dying cancer cells are the key mediators that trigger both DNA damage and inflammation in the surrounding healthy cells. When dying human cancer cells were cultured along with NIH3T3 mouse fibroblast cells, numerous cfCh emerged from them and rapidly entered into nuclei of bystander NIH3T3 cells to integrate into their genomes...
2017: Cell Death Discovery
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