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https://www.readbyqxmd.com/read/28108515/prostate-cancer-patients-with-late-radiation-toxicity-exhibit-reduced-expression-of-genes-involved-in-dna-double-strand-break-repair-and-homologous-recombination
#1
Bregje van Oorschot, Lon Uitterhoeve, Ilja Oomen, Rosemarie Ten Cate, Jan Paul Medema, Harry Vrieling, Lukas J A Stalpers, Perry D Moerland, Nicolaas A P Franken
Severe late damage to normal tissue is a major limitation of cancer radiotherapy in prostate cancer patients. In a recent retrospective study, late radiation toxicity was found to relate to a decreased decay of γ-H2AX foci and reduced induction of DNA double strand break repair genes. Here we report evidence of prognostic utility in prostate cancer for γ-H2AX foci decay ratios and gene expression profiles derived from ex vivo-irradiated patient lymphocytes. Patients were followed ≥2 years after radiotherapy...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107384/an-approach-to-elucidate-nbs1-function-in-dna-repair-using-frequent-nonsynonymous-polymorphism-in-wild-medaka-oryzias-latipes-populations
#2
Kento Igarashi, Junya Kobayashi, Takafumi Katsumura, Yusuke Urushihara, Kyohei Hida, Tomomi Watanabe-Asaka, Hiroki Oota, Shoji Oda, Hiroshi Mitani
Nbs1 is one of the genes responsible for Nijmegen breakage syndrome, which is marked with high radiosensitivity. In human NBS1 (hNBS1), Q185E polymorphism is known as the factor to cancer risks, although its DSB repair defect has not been addressed. Here we investigated the genetic variations in medaka (Oryzias latipes) wild populations, and found 40 nonsynonymous single nucleotide polymorphisms (SNPs) in medaka nbs1 (olnbs1) gene within 5 inbred strains. A mutation to histidine in Q170 residue in olNbs1, which corresponds to Q185 residue of hNBS1, was widely distributed in the closed colonies derived from the eastern Korean population of medaka...
2017: PloS One
https://www.readbyqxmd.com/read/28099140/telomerase-antagonist-imetelstat-increases-radiation-sensitivity-in-esophageal-squamous-cell-carcinoma
#3
Xuping Wu, Jing Zhang, Sijun Yang, Zhihui Kuang, Guolei Tan, Gang Yang, Qichun Wei, Zhigang Guo
The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28062703/tas-116-a-novel-hsp90-inhibitor-selectively-enhances-radiosensitivity-of-human-cancer-cells-to-x-rays-and-carbon-ion-radiation
#4
Younghyun Lee, Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Jac A Nickoloff, Ryuichi Okayasu
Hsp90 inhibitors have been investigated as cancer therapeutics in monotherapy and to augment radiotherapy; however, serious adverse effects of early-generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here, we investigated the radiosensitizing effects of TAS-116 in low linear energy transfer (LET) X-ray and high LET carbon ion-irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of noncancerous human fibroblasts...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#5
Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28025714/bone-marrow-mesenchymal-stem-cell-transplantation-improves-radiation-induced-heart-injury-through-dna-damage-repair-in-rat-model
#6
Song Gao, Zhiying Zhao, Rong Wu, Yuecan Zeng, Zhenyong Zhang, Jianing Miao, Zhengwei Yuan
Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR + BMSCs transplantation groups obtained at different time points...
December 26, 2016: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28012437/autophagy-deficient-keratinocytes-display-increased-dna-damage-senescence-and-aberrant-lipid-composition-after-oxidative-stress-in-vitro-and-in-vivo
#7
Xiuzu Song, Marie Sophie Narzt, Ionela Mariana Nagelreiter, Philipp Hohensinner, Lucia Terlecki-Zaniewicz, Erwin Tschachler, Johannes Grillari, Florian Gruber
Autophagy allows cells fundamental adaptations to metabolic needs and to stress. Using autophagic bulk degradation cells can clear crosslinked macromolecules and damaged organelles that arise under redox stress. Accumulation of such debris results in cellular dysfunction and is observed in aged tissue and senescent cells. Conversely, promising anti-aging strategies aim at inhibiting the mTOR pathway and thereby activating autophagy, to counteract aging associated damage. We have inactivated autophagy related 7 (Atg7), an essential autophagy gene, in murine keratinocytes (KC) and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28005992/do-exogenous-dna-double-strand-breaks-change-incomplete-synapsis-and-chiasma-localization-in-the-grasshopper-stethophyma-grossum
#8
Adela Calvente, Juan Luis Santos, Julio S Rufas
Meiotic recombination occurs as a programmed event that initiates by the formation of DNA double-strand breaks (DSBs) that give rise to the formation of crossovers that are observed as chiasmata. Chiasmata are essential for the accurate chromosome segregation and the generation of new combinations of parental alleles. Some treatments that provoke exogenous DSBs also lead to alterations in the recombination pattern of some species in which full homologous synapsis is achieved at pachytene. We have carried out a similar approach in males of the grasshopper Stethophyma grossum, whose homologues show incomplete synapsis and proximal chiasma localization...
2016: PloS One
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
December 2016: Oncology Reports
https://www.readbyqxmd.com/read/27778526/the-reneb-operational-basis-complement-of-established-biodosimetric-assays
#16
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
#17
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
#18
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
#19
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
#20
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
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