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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
#1
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/29129974/screening-of-pesticides-with-the-potential-of-inducing-dsb-and-successive-recombinational-repair
#2
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
#3
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/29054934/radiation-induced-dna-damage-in-operators-performing-endovascular-aortic-repair
#4
Tamer El-Sayed, Ashish S Patel, Jun S Cho, James A Kelly, Francesca E Ludwinski, Prakash Saha, Oliver T Lyons, Alberto Smith, Bijan Modarai
Background -Radiation exposure during fluoroscopically-guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR. Methods -Expression of the DNA damage/repair marker, gamma-H2AX (γ-H2AX) and DNA damage response (DDR) marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infra-renal [IEVAR], branched [BEVAR] and fenestrated [FEVAR]) and open aortic repair using flow cytometry...
October 20, 2017: Circulation
https://www.readbyqxmd.com/read/29034758/feasibility-study-on-the-use-of-gold-nanoparticles-in-fractionated-kilovoltage-x-ray-treatment-of-melanoma
#5
So-Ra Kim, Eun-Hee Kim
PURPOSE: Despite the high radioresistance of melanoma, unresectable lesions can be subjected to radiation treatment with the use of gold nanoparticles (AuNPs) as a dose-enhancing agent preferentially loaded on these lesions. The modality of single high-dose treatment has been investigated to confirm its therapeutic efficiency for AuNP-treated melanoma cells. This study explores the feasibility of utilizing AuNPs in fractionated radiation therapy of melanoma for further therapeutic gain...
October 16, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28963924/efficient-repair-of-dna-double-strand-breaks-in-individuals-from-high-level-natural-radiation-areas-of-kerala-coast-south-west-india
#6
Vinay Jain, Divyalakshmi Saini, P R Vivek Kumar, G Jaikrishan, Birajalaxmi Das
High level natural radiation areas (HLNRA) of Kerala coastal strip (55km long and 0.5km wide) in southwest India exhibit wide variations in the level of background dose (< 1.0-45.0mGy/year) due to thorium deposits in the beach sand. The areas with ≤1.5mGy/year are considered as normal level natural radiation area (NLNRA), whereas areas with >1.5mGy/year are HLNRA. Individuals belonging to HLNRA were stratified into two groups, Low dose group (LDG: 1.51-5.0mGy/year) and high dose group (HDG: >5.0mGy/year)...
September 20, 2017: Mutation Research
https://www.readbyqxmd.com/read/28889235/genotoxic-potential-of-diesel-exhaust-particles-from-the-combustion-of-first-and-second-generation-biodiesel-fuels-the-fuelhealth-project
#7
Magdalena Kowalska, Aneta Wegierek-Ciuk, Kamil Brzoska, Maria Wojewodzka, Sylwia Meczynska-Wielgosz, Joanna Gromadzka-Ostrowska, Remigiusz Mruk, Johan Øvrevik, Marcin Kruszewski, Anna Lankoff
Epidemiological data indicate that exposure to diesel exhaust particles (DEPs) from traffic emissions is associated with higher risk of morbidity and mortality related to cardiovascular and pulmonary diseases, accelerated progression of atherosclerotic plaques, and possible lung cancer. While the impact of DEPs from combustion of fossil diesel fuel on human health has been extensively studied, current knowledge of DEPs from combustion of biofuels provides limited and inconsistent information about its mutagenicity and genotoxicity, as well as possible adverse health risks...
November 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28829673/oxygen-enhancement-ratio-in-radiation-induced-initial-dsbs-by-an-optimized-flow-cytometry-based-gamma-h2ax-analysis-in-a549-human-cancer-cells
#8
Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Mitsuru Uesaka, Ryuichi Okayasu
High-linear energy transfer (LET) heavy ions cause higher therapeutic effects than low-LET radiation due to lower dependency on oxygen concentration in tumor cell killing. The lethality after irradiation largely depends on DNA double-strand breaks (DSBs), however the detailed LET dependency for DSB induction under oxic and hypoxic conditions has not been reported. Therefore, we evaluated the oxygen enhancement ratio (OER) of heavy ion-induced DSB induction using a highly-optimized flow cytometry-based method of γ-H2AX detection...
November 2017: Radiation Research
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
#9
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...
August 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28612525/-the-role-of-dna-double-strain-damage-repairing-mechanisms-in-diabetic-atheroscolersis
#10
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/28565765/pravastatin-reduces-radiation-induced-damage-in-normal-tissues
#11
Hiroshi Doi, Seiji Matsumoto, Soichi Odawara, Toshiyuki Shikata, Kazuhiro Kitajima, Masao Tanooka, Yasuhiro Takada, Tohru Tsujimura, Norihiko Kamikonya, Shozo Hirota
Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28494285/effects-of-in-situ-exposure-to-tritiated-natural-environments-a-multi-biomarker-approach-using-the-fathead-minnow-pimephales-promelas
#12
B Gagnaire, C Adam-Guillermin, A Festarini, I Cavalié, C Della-Vedova, C Shultz, S B Kim, H Ikert, C Dubois, S Walsh, F Farrow, D Beaton, E Tan, K Wen, M Stuart
Aquatic ecosystems are chronically exposed to radionuclides as well as other pollutants. Increased concentrations of pollutants in aquatic environments can present a risk to exposed organisms, including fish. The goal of this study was to characterize the effects of tritium, in the context of natural environments, on the health of fathead minnow, Pimephales promelas. Fish were exposed to tritium (activity concentrations ranging from 2 to 23,000Bq/L) and also to various concentrations of several metals to replicate multiple-stressor environments...
December 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28487501/oocyte-exposure-to-zno-nanoparticles-inhibits-early-embryonic-development-through-the-%C3%AE-h2ax-and-nf-%C3%AE%C2%BAb-signaling-pathways
#13
Jing Liu, Yong Zhao, Wei Ge, Pengfei Zhang, Xinqi Liu, Weidong Zhang, Yanan Hao, Shuai Yu, Lan Li, Meiqiang Chu, Lingjiang Min, Hongfu Zhang, Wei Shen
The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389334/loss-of-dusp3-activity-radiosensitizes-human-tumor-cell-lines-via-attenuation-of-dna-repair-pathways
#14
Thompson E P Torres, Lilian C Russo, Alexsandro Santos, Gabriela R Marques, Yuli T Magalhaes, Sartaj Tabassum, Fabio L Forti
BACKGROUND: Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28388353/deficiency-in-dna-damage-response-a-new-characteristic-of-cells-infected-with-latent-hiv-1
#15
Dorota Piekna-Przybylska, Gaurav Sharma, Sanjay B Maggirwar, Robert A Bambara
Viruses can interact with host cell molecules responsible for the recognition and repair of DNA lesions, resulting in dysfunctional DNA damage response (DDR). Cells with inefficient DDR are more vulnerable to therapeutic approaches that target DDR, thereby raising DNA damage to a threshold that triggers apoptosis. Here, we demonstrate that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs). We found that phosphorylation of histone H2AX on Ser139 (gamma-H2AX), a biomarker of DSBs, and phosphorylation of ATM at Ser1981, Chk2 at Thr68, and p53 at Ser15, part of signaling pathways associated with DSBs, are elevated in these cells...
May 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28351323/gamma-h2ax-can-it-be-established-as-a-classical-cancer-prognostic-factor
#16
REVIEW
Viktoria-Varvara Palla, Georgios Karaolanis, Ioannis Katafigiotis, Ioannis Anastasiou, Paul Patapis, Dimitrios Dimitroulis, Despoina Perrea
Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to double-strand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28098348/impact-of-lysosomal-storage-disorders-on-biology-of-mesenchymal-stem-cells-evidences-from-in-vitro-silencing-of-glucocerebrosidase-gba-and-alpha-galactosidase-a-gla-enzymes
#17
Tiziana Squillaro, Ivana Antonucci, Nicola Alessio, Anna Esposito, Marilena Cipollaro, Mariarosa Anna Beatrice Melone, Gianfranco Peluso, Liborio Stuppia, Umberto Galderisi
Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues...
December 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28052107/ubiquitin-accumulation-on-disease-associated-protein-aggregates-is-correlated-with-nuclear-ubiquitin-depletion-histone-de-ubiquitination-and-impaired-dna-damage-response
#18
Adi Ben Yehuda, Marwa Risheq, Ofra Novoplansky, Kirill Bersuker, Ron R Kopito, Michal Goldberg, Michael Brandeis
Deposition of ubiquitin conjugates on inclusion bodies composed of protein aggregates is a definitive cytopathological hallmark of neurodegenerative diseases. We show that accumulation of ubiquitin on polyQ IB, associated with Huntington's disease, is correlated with extensive depletion of nuclear ubiquitin and histone de-ubiquitination. Histone ubiquitination plays major roles in chromatin regulation and DNA repair. Accordingly, we observe that cells expressing IB fail to respond to radiomimetic DNA damage, to induce gamma-H2AX phosphorylation and to recruit 53BP1 to damaged foci...
2017: PloS One
https://www.readbyqxmd.com/read/28034704/antioxidants-taken-orally-prior-to-diagnostic-radiation-exposure-can-prevent-dna-injury
#19
Nivethan Velauthapillai, Joe Barfett, Hussein Jaffer, David Mikulis, Kieran Murphy
PURPOSE: To evaluate efficacy of oral antioxidant treatment given to patients before radiologic procedures in reducing x-ray-induced DNA damage. MATERIALS AND METHODS: In a single-center prospective controlled trial, antioxidant treatment with 2 g ascorbate, 1.2 g N-acetylcysteine, 600 mg lipoic acid, and 30 mg beta carotene was given to 5 consecutive participants before undergoing clinically indicated technetium-99m methylene diphosphonate ((99m)Tc MDP) bone scans for cancer staging...
March 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/27814570/chromosomal-aberrations-clastogens-vs-aneugens
#20
REVIEW
Masayuki Mishima
Current anticancer therapy may be one of the most important exogenous sources of exposure to genotoxic agents in US, Japan, and Europe, where approximately 40-55 percent of the population is diagnosed with cancer at a certain point in their life. This review focuses on recent efforts to integrate a novel biomarker, gamma-H2AX, into anticancer drug screening to classify the mode of action (MoA) for genotoxic outcome into clastogenicity and aneugenicity, a distinction that has considerable impact on risk assessment and control strategy...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
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