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https://www.readbyqxmd.com/read/29724012/frondoside-a-enhances-the-anti-cancer-effects-of-oxaliplatin-and-5-fluorouracil-on-colon-cancer-cells
#1
Samir Attoub, Kholoud Arafat, Tamam Khalaf, Shahrazad Sulaiman, Rabah Iratni
Over recent years, we have demonstrated that Frondoside A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, has potent in vitro and in vivo anti-cancer effects against human pancreatic, breast, and lung cancer. We have also demonstrated that Frondoside A is able to potentiate and/or synergize the anti-cancer effects of major classical cytotoxic agents, namely, gemcitabine, paclitaxel, and cisplatin, in the treatment of pancreatic, breast, and lung cancer, respectively. This study evaluates the impact of Frondoside A alone and in combination with the standard cytotoxic drugs oxaliplatin and 5-fluorouracil (5-FU) in the treatment of colon cancer using three human colon cancer cell lines, namely, HT-29, HCT-116, and HCT8/S11...
May 1, 2018: Nutrients
https://www.readbyqxmd.com/read/29685191/flow-cytometric-detection-of-gamma-h2ax-to-evaluate-dna-damage-by-low-dose-diagnostic-irradiation
#2
Kainat Khan, Shikha Tewari, Namrata Punit Awasthi, Surendra Prasad Mishra, Gaurav Raj Agarwal, Madhup Rastogi, Nuzhat Husain
INTRODUCTION: γH2AX assay has been used for DNA damage assessment at higher doses of radiation exposure. Its expression has not been studied in cases with diagnostic low dose radiation exposure. Concerns have been raised about the after-effects of radiation in diagnostic procedures like Computed Tomography (CT) scan, Angiography etc especially when such scans are repeated within short span of time. The purpose of the present study was to assess immediate DNA damage after exposure to low level of ionizing radiation by the flow cytometric method of gamma-H2AX...
June 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29554819/in-vitro-evaluation-of-the-genotoxicity-of-ceo-2-nanoparticles-in-human-peripheral-blood-lymphocytes-using-cytokinesis-block-micronucleus-test-comet-assay-and-gamma-h2ax
#3
Serpil Könen-Adıgüzel, Serap Ergene
Engineered nanoparticles (ENPs) are used in a wide range of applications because of their unique properties. Cerium dioxide nanoparticles (CeO2 NPs) are one of the important ENPs, and they can cause negative health effects, such as genotoxicity, in humans and other living organisms. The aim of this work was to analyze the genotoxic effects of short-term (3-24 h) CeO2 NPs exposure to cultured human blood lymphocytes. Three genotoxicity systems "cytokinesis-block micronucleus test, comet assay, and gamma H2AX test" were used to show the genotoxic potential of CeO2 NPs (particle size <25 nm, concentrations: 6, 12, and 18 µg/mL)...
May 2018: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/29485113/atr-kinase-regulates-its-attenuation-via-ppm1d-phosphatase-recruitment-to-chromatin-during-recovery-from-dna-replication-stress-signalling
#4
Debadrita Bhattacharya, Disha Hiregange, Basuthkar J Rao
In eukaryotes, in response to replication stress, DNA damage response kinase, ATR is activated, whose signalling abrogation leads to cell lethality due to aberrant fork remodelling and excessive origin firing. Here we report that inhibition of ATR kinase activity specifically during replication stress recovery results in persistent ATR signalling, evidenced by the presence of ATR-dependent phosphorylation marks (gamma H2AX, pChk1 and pRad17) and delayed cell cycle re-entry. Further, such disruption of ATR signalling attenuation leads to double-strand breaks, fork collapse and thereby 'replication catastrophe'...
March 2018: Journal of Biosciences
https://www.readbyqxmd.com/read/29463775/the-transcriptional-coactivator-ada2b-recruits-a-structural-maintenance-protein-to-double-strand-breaks-during-dna-repair-in-plants
#5
Jianbin Lai, Jieming Jiang, Qian Wu, Ning Mao, Danlu Han, Huan Hu, Chengwei Yang
DNA damage occurs in all cells and can hinder chromosome stability and cell viability. Structural Maintenance of Chromosomes5/6 (SMC5/6) is a protein complex that functions as an evolutionarily conserved chromosomal ATPase critical for repairing DNA double-strand breaks (DSBs). However, the mechanisms regulating this complex in plants are poorly understood. Here, we identified the transcriptional coactivator ALTERATION/DEFICIENCY IN ACTIVATION2B (ADA2b) as an interactor of SMC5 in Arabidopsis ( Arabidopsis thaliana )...
April 2018: Plant Physiology
https://www.readbyqxmd.com/read/29462394/nondysplastic-ulcerative-colitis-has-high-levels-of-the-homologous-recombination-repair-protein-nucks1-and-low-levels-of-the-dna-damage-marker-gamma-h2ax
#6
Paula M De Angelis, Aasa R Schjølberg, Juliana B Hughes, Henrik S Huitfeldt, Solveig Norheim Andersen, Anne Carine Østvold
Background: The colon and rectum are continuously exposed to oxidative stress that generates reactive oxygen species, which are a major cause of DNA double-strand breaks (DSB). Furthermore, chronic inflammatory diseases such as ulcerative colitis (UC) are characterized by an excess of reactive nitrogen species that can also lead to DNA double-strand breakage and genomic instability. We investigated the expression of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) protein in UC and sporadic colorectal cancer (CRC) due to its involvement in both DNA double-strand break repair and inflammatory signaling...
February 15, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29353813/pharmacological-approach-to-increase-the-retention-of-radiation-induced-gamma-h2ax-foci-using-phosphatase-inhibitors-significance-in-radiation-biodosimetry
#7
Akshaykumar A Nayak, Kamalesh Dattaram Mumbrekar, Satish Rao
In a scenario of accidental mass radiation exposure, transportation and analyzing samples may take its time resulting in loss of biomarker information over this period. The present study aims to use phosphatases inhibitors for longer retention of foci signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals irradiated in vitro with X-rays, and γ-H2AX analysed using fluorescent microscopy and flow cytometric methods...
January 22, 2018: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
https://www.readbyqxmd.com/read/29352998/two-weeks-of-variable-stress-increases-gamma-h2ax-levels-in-the-mouse-bed-nucleus-of-the-stria-terminalis
#8
Brendan D Hare, Tina M Thornton, Mercedes Rincon, Borivoj Golijanin, S Bradley King, Diane M Jaworski, William A Falls
Recent reports demonstrate that DNA damage is induced, and rapidly repaired, in circuits activated by experience. Moreover, stress hormones are known to slow DNA repair, suggesting that prolonged stress may result in persistent DNA damage. Prolonged stress is known to negatively impact physical and mental health; however, DNA damage as a factor in stress pathology has only begun to be explored. Histone H2A-X phosphorylated at serine 139 (γH2AX) is a marker of DNA double-strand breaks (DSB), a type of damage that may lead to cell death if unrepaired...
March 1, 2018: Neuroscience
https://www.readbyqxmd.com/read/29215325/dosikit-a-new-portable-immunoassay-for-fast-external-irradiation-biodosimetry
#9
Julie Bensimon Etzol, Marco Valente, Sandrine Altmeyer, Caroline Bettencourt, Samuel Bouvet, Guillaume Cosler, François Desangles, Michel Drouet, Fabrice Entine, Francis Hérodin, Flora Jourquin, Yannick Lecompte, Patrick Martigne, Xavier Michel, Jérôme Pateux, Nicolas Ugolin, Sylvie Chevillard
DosiKit is a new field-radiation biodosimetry immunoassay for rapid triage of individuals exposed to external total-body radiation. Here, we report on the validation of this immunoassay in human blood cell extracts 0.5 h after in vitro exposure to137 Cs gamma rays, using γ-H2AX analysis. First, calibration curves were established for five donors at doses ranging from 0 to 10 Gy and dose rates ranging from ∼0.8 to ∼3 Gy/min. The calibration curves, together with a γ-H2AX peptide scale, enabled the definition of inter-experimental correction factors...
December 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/29187880/the-parp-1-inhibitor-olaparib-suppresses-brca1-protein-levels-increases-apoptosis-and-causes-radiation-hypersensitivity-in-brca1-lymphoblastoid-cells
#10
Emma C Bourton, Pia-Amata Ahorner, Piers N Plowman, Sheba Adam Zahir, Hussein Al-Ali, Christopher N Parris
The use of polyADPribose polymerase inhibitors in cancer treatment provides a unique opportunity to target DNA repair processes in cancer cells while leaving normal tissue intact. The PARP-1 enzyme repairs DNA single strand breaks (SSB). Therefore PARP-1 inhibition in BRCA1 negative cancers results in the formation of cytotoxic DNA double strand breaks (DSB) causing synthetic lethality. The use of PARP1 inhibitors is gaining momentum in the treatment of a variety of tumours with BRCA1 involvement including breast, ovarian, pancreatic and prostate cancer...
2017: Journal of Cancer
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
#11
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 Y T Chan, Srinivasan Madhusudan, Emad A Rhaka, 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 PARP1/2 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 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 10.5% were absent, by IHC. CDK12 positivity correlated with HER2 positivity but was not an independent predictor of breast cancer-specific survival taking HER2 status into account; however, absent CDK12 protein expression significantly correlated with a triple-negative phenotype...
January 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29129974/screening-of-pesticides-with-the-potential-of-inducing-dsb-and-successive-recombinational-repair
#12
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
#13
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...
January 2018: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/29054934/radiation-induced-dna-damage-in-operators-performing-endovascular-aortic-repair
#14
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, γ-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry...
December 19, 2017: Circulation
https://www.readbyqxmd.com/read/29034758/feasibility-study-on-the-use-of-gold-nanoparticles-in-fractionated-kilovoltage-x-ray-treatment-of-melanoma
#15
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...
January 2018: 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
#16
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)...
December 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
#17
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
#18
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
#19
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
#20
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
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