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h2ax and irradiation

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https://www.readbyqxmd.com/read/27922110/%C3%AE-h2ax-53bp1-pkap-1-foci-and-their-linear-tracks-induced-by-in-vitro-exposure-to-radon-and-its-progeny-in-human-peripheral-blood-lymphocytes
#1
Defang Ding, Yaping Zhang, Jing Wang, Xufei Wang, Dunhuang Fan, Linfeng He, Xuxia Zhang, Yun Gao, Qiang Li, Honghong Chen
The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876069/mgdg-extracted-from-spinach-enhances-the-cytotoxicity-of-radiation-in-pancreatic-cancer-cells
#2
Hiroaki Akasaka, Yoshiyuki Mizushina, Kenji Yoshida, Yasuo Ejima, Naritoshi Mukumoto, Tianyuan Wang, Sachiko Inubushi, Masao Nakayama, Yuki Wakahara, Ryohei Sasaki
BACKGROUND: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. METHODS: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs)...
November 22, 2016: Radiation Oncology
https://www.readbyqxmd.com/read/27826196/the-medicinal-fungus-antrodia-cinnamomea-regulates-dna-repair-and-enhances-the-radiosensitivity-of-human-esophageal-cancer-cells
#3
Yu-Ming Liu, Yu-Kuo Liu, Ling-Wei Wang, Yu-Chuen Huang, Pin-I Huang, Tung-Hu Tsai, Yu-Jen Chen
This study investigated the adjunctive effects of Antrodia cinnamomea mycelial fermentation broth (AC-MFB), a Taiwanese medicinal fungus, in enhancing the radiosensitivity of esophageal cancer cells. Human CE81T/VGH squamous and BE3 adenocarcinoma esophageal cancer cells were used in this study. A colony formation assay showed that pretreatment with AC-MFB decreased the survival of irradiated esophageal cancer cells, with a maximum sensitizer enhancement ratio of 1.91% and 37% survival. A DNA histogram study showed that AC-MFB pretreatment enhanced cell cycle arrest at the G2/M phase, the most radiosensitive phase...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27821478/mcl-1-depletion-impairs-dna-dsb-repair-and-re-initiation-of-stalled-dna-replication-forks
#4
Abid R Mattoo, Raj K Pandita, Sharmistha Chakraborty, Vijaya Charaka, Kalpana Mujoo, Clayton R Hunt, Tej K Pandita
Myeloid cell leukemia-1 : MCL-1) is a pro-survival BCL-2 protein family member highly expressed in hematopoietic stem cells (HSCs) and regulated by growth factor signals that manifest anti-apoptotic activity. Here we report that depletion of MCL-1, but not its isoform MCL1S, increases genomic instability and cell sensitivity to ionizing radiation (IR) induced death. MCL-1 association with genomic DNA increased post-irradiation and it co-localized with 53BP1 in foci. Post-irradiation, MCL-1 depleted cells exhibited decreased γ-H2AX foci, decreased phosphorylation of ATR and higher levels of residual 53BP1 and RIF1 foci, suggesting DNA DSB repair by homologous recombination (HR) was compromised...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27806616/development-of-a-transmission-alpha-particle-dosimetry-technique-using-a549-cells-and-a-ra-223-source-for-targeted-alpha-therapy
#5
R Al Darwish, A H Staudacher, Y Li, M P Brown, E Bezak
PURPOSE: In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells...
November 2016: Medical Physics
https://www.readbyqxmd.com/read/27788031/quantification-of-radiation-biomarkers-in-leukocytes-of-breast-cancer-patients-treated-with-different-modalities-of-3d-crt-or-imrt
#6
Sebastian Zahnreich, Anne Ebersberger, Heiko Karle, Bernd Kaina, Heinz Schmidberger
The goal of this study was to determine whether the quantification of radiation biomarkers in peripheral leukocytes of 111 breast cancer patients after adjuvant treatment with different modalities of three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) revealed any difference in the patients' radiation burden by out-of-field doses and an associated risk of second malignancies. Whole-breast radiation therapy was performed by 3D-CRT using either a hard wedge (n = 32) or a virtual wedge (n = 49) at dose rates of 3 and 6 Gy per min each...
October 27, 2016: Radiation Research
https://www.readbyqxmd.com/read/27779695/enhancement-of-radiosensitivity-by-inhibition-of-c-jun-n-terminal-kinase-activity-in-a-lewis-lung-carcinoma%C3%A2-bearing-subcutaneous-tumor-mouse-model
#7
Chun-Hao Li, Sa-Hoe Lim, Hyang-Hwa Ryu, Kyung-Sub Moon, Tae-Young Jung, Shin Jung
Stereotactic radiosurgery has been recognized as an effective treatment approach for metastatic brain tumors. By increasing the sensitivity of the tumor to radiation and decreasing the marginal dose, it is possible to improve therapeutic efficacy and decrease side-effects. In radiation-induced cells, c-Jun N-terminal kinase (JNK) signaling mediates the phosphorylation of H2AX, which indicates DNA damage sensitivity and modulates the effect of radiation. Lewis lung cancer (LLC) and breast cancer (4T1) cells were irradiated with a Gamma Knife in cell culture tubes...
October 25, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27778526/the-reneb-operational-basis-complement-of-established-biodosimetric-assays
#8
Andrzej Wojcik, Ursula Oestreicher, Lleonard Barrios, Anne Vral, Georgia Terzoudi, Elizabeth Ainsbury, Kai Rothkamm, Francois Trompier, Ulrike Kulka
PURPOSE: To set up an operational basis of the Realizing the European Network of Biodosimetry (RENEB) network within which the application of seven established biodosimetric tools (the dicentric assay, the FISH assay, the micronucleus assay, the PCC assay, the gamma-H2AX assay, electron paramagnetic resonance and optically stimulated luminescence) will be compared and standardized among the participating laboratories. METHODOLOGY: Two intercomparisons were organized where blood samples and smartphone components were irradiated, coded and sent out to participating laboratories for dosimetric analysis...
October 25, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27765919/zoledronic-acid-is-an-effective-radiosensitizer-in-the-treatment-of-osteosarcoma
#9
Eun Ho Kim, Mi-Sook Kim, Kyung-Hee Lee, Jae-Soo Koh, Won-Gyun Jung, Chang-Bae Kong
To overcome radioresistance in the treatment of osteosarcoma, a primary malignant tumor of the bone, radiotherapy is generally combined with radiosensitizers. The purpose of this study was to investigate a third-generation bisphosphonate, zoledronic acid (ZOL), as a radiosensitizer for osteosarcoma. We found that exposure of KHOS/NP osteosarcoma cells to 20 μM ZOL decreased the γ-radiation dose needed to kill 90% of cells. This radiosensitizing effect of ZOL was mediated through decreased mitochondrial membrane potential, increased levels of reactive oxygen species, increased DNA damage (as assessed by counting γ-H2AX foci), decreased abundance of proteins involved in DNA repair pathways (ATR, Rad52, and DNA-PKcs), and decreased phosphorylation of PI3K-Akt and MAPK pathway proteins (Raf1, MEK1/2, ERK1/2, and Akt), as compared to γ-irradiation alone...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27744293/regulation-of-dna-replication-and-chromosomal-polyploidy-by-the-mll-wdr5-rbbp5-methyltransferases
#10
Fei Lu, Xiaojun Wu, Feng Yin, Christina Chia-Fang Lee, Min Yu, Ivailo S Mihaylov, Jiekai Yu, Hong Sun, Hui Zhang
DNA replication licensing occurs on chromatin, but how the chromatin template is regulated for replication remains mostly unclear. Here, we have analyzed the requirement of histone methyltransferases for a specific type of replication: the DNA re-replication induced by the downregulation of either Geminin, an inhibitor of replication licensing protein CDT1, or the CRL4CDT2 ubiquitin E3 ligase. We found that siRNA-mediated reduction of essential components of the MLL-WDR5-RBBP5 methyltransferase complexes including WDR5 or RBBP5, which transfer methyl groups to histone H3 at K4 (H3K4), suppressed DNA re-replication and chromosomal polyploidy...
October 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27740890/late-dna-damage-mediated-by-homologous-recombination-repair-results-in-radiosensitization-with-gemcitabine
#11
Michael M Im, Sheryl A Flanagan, Jeffrey J Ackroyd, Brendan Knapp, Aaron Kramer, Donna S Shewach
Gemcitabine (dFdCyd) shows broad antitumor activity in solid tumors in chemotherapeutic regimens or when combined with ionizing radiation (radiosensitization). While it is known that mismatches in DNA are necessary for dFdCyd radiosensitization, the critical event resulting in radiosensitization has not been identified. Here we hypothesized that late DNA damage (≥24 h after drug washout/irradiation) is a causal event in radiosensitization by dFdCyd, and that homologous recombination repair (HRR) is required for this late DNA damage...
October 14, 2016: Radiation Research
https://www.readbyqxmd.com/read/27720638/genetic-modification-of-h2ax-renders-mesenchymal-stromal-cell-derived-dopamine-neurons-more-resistant-to-dna-damage-and-subsequent-apoptosis
#12
Peizhou Jiang, Peng Huang, Shu-Hui Yen, Abba C Zubair, Dennis W Dickson
BACKGROUND AIMS: Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients...
October 6, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27693457/compromized-dna-repair-as-a-basis-for-identification-of-cancer-radiotherapy-patients-with-extreme-radiosensitivity
#13
Pavel Lobachevsky, Trevor Leong, Patricia Daly, Jai Smith, Nickala Best, Jonathan Tomaszewski, Ella R Thompson, Na Li, Ian G Campbell, Roger F Martin, Olga A Martin
A small percentage of cancer radiotherapy patients develop abnormally severe side effects as a consequence of intrinsic radiosensitivity. We analysed the γ-H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and plucked eyebrow hair follicles from 16 patients who developed severe late radiation toxicity following radiotherapy, and 12 matched control patients. Longer retention of the γ-H2AX signal and lower colocalization efficiency of repair factors in over-responding patients confirmed that DNA repair in these individuals was compromised...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27690219/mk-8776-a-novel-chk1-kinase-inhibitor-radiosensitizes-p53-defective-human-tumor-cells
#14
Kathleen A Bridges, Xingxing Chen, Huifeng Liu, Crosby Rock, Thomas A Buchholz, Stuart D Shumway, Heath D Skinner, Raymond E Meyn
Radiotherapy is commonly used to treat a variety of solid tumors but improvements in the therapeutic ratio are sorely needed. The aim of this study was to assess the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor cells. Cells derived from NSCLC and HNSCC cancers were tested for radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation-induced G2 block was determined using flow cytometry. Effects on repair of radiation-induced DNA double strand breaks (DSBs) were determined on the basis of rad51, γ-H2AX and 53BP1 foci...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27686523/the-second-gamma-h2ax-assay-inter-comparison-exercise-carried-out-in-the-framework-of-the-european-biodosimetry-network-reneb
#15
Jayne Moquet, Stephen Barnard, Albena Staynova, Carita Lindholm, Octávia Monteiro Gil, Vanda Martins, Ute Rößler, Anne Vral, Charlot Vandevoorde, Maria Wojewódzka, Kai Rothkamm
PURPOSE: Within the EU RENEB project, seven laboratories have taken part in training and harmonisation activities to strengthen triage gamma-H2AX-based radiation exposure assessment. This has culminated in a second triage biodosimetry exercise. MATERIALS AND METHODS: Whole blood and separated lymphocyte samples were homogenously irradiated with (60)Co gamma rays at 0.5, 2.5 (blind samples), 0 and 2 Gy (reference samples). Following post-exposure incubations of 4 and 24 h, 16 samples were shipped on ice packs to each partner...
August 15, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27666928/the-purine-scaffold-hsp90-inhibitor-pu-h71-sensitizes-cancer-cells-to-heavy-ion-radiation-by-inhibiting-dna-repair-by-homologous-recombination-and-non-homologous-end-joining
#16
Younghyun Lee, Huizi Keiko Li, Aya Masaoka, Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Jac A Nickoloff, Ryuichi Okayasu
BACKGROUND AND PURPOSE: PU-H71 is a purine-scaffold Hsp90 inhibitor developed to overcome limitations of conventional Hsp90 inhibitors. This study was designed to investigate the combined effect of PU-H71 and heavy ion irradiation on human tumor and normal cells. MATERIALS AND METHODS: The effects of PU-H71 were determined by monitoring cell survival by colony formation, and DNA double-strand break (DSB) repair by γ-H2AX foci and immuno-blotting DSB repair proteins...
October 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27636029/downregulation-of-a-novel-human-gene-rogdi-increases-radiosensitivity-in-cervical-cancer-cells
#17
Yi-Fan Chen, Jonathan J Cho, Tsai-Hua Huang, Chao-Neng Tseng, Eng-Yen Huang, Chung-Lung Cho
ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation...
August 12, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27633574/comparison-of-human-lung-cancer-cell-radiosensitivity-after-irradiations-with-therapeutic-protons-and-carbon-ions
#18
Otilija D Keta, Danijela V Todorović, Tanja M Bulat, Pablo Ga Cirrone, Francesco Romano, Giacomo Cuttone, Ivan M Petrović, Aleksandra M Ristić Fira
The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons...
September 15, 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27609226/3-3-diindolylmethane-mitigates-total-body-irradiation-induced-hematopoietic-injury-in-mice
#19
Lu Lu, Jiali Dong, Deguan Li, Junling Zhang, Saijun Fan
We have reported that hematopoietic system injury induced by total body irradiation (TBI) leads to generation of intracellular reactive oxygen species (ROS) and DNA damage, which are ameliorated by antioxidant agents. In the present study, we reported that administration of DIM, a potent antioxidant agent, not only protected mice against TBI-induced lethality, also ameliorated TBI-induced hematopoietic injury. The latter effect was probably attributable to DIM's inhibition of TBI-induced increases in ROS production in hematopoietic stem cells (HSCs) and the phosphorylation of histone H2AX (γ-H2AX)...
September 5, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27600610/effect-of-combined-treatment-of-radiation-and-tissue-specific-recombinant-oncolytic-adenovirus-on-bladder-cancer-cells
#20
Hongjuan Zhang, Fang Wang, Chunjie Mao, Zuncheng Zhang, Shengjun Fu, Jianzhong Lu, Zhenxing Zhai, Renju Li, Shuwen Li, Ron Rodriguez, Zhiping Wang
PURPOSE: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. MATERIALS AND METHODS: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed...
October 14, 2016: International Journal of Radiation Biology
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