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https://www.readbyqxmd.com/read/28103177/hbxip-a-binding-protein-of-hbx-regulates-maintenance-of-the-g2-m-phase-checkpoint-induced-by-dna-damage-and-enhances-sensitivity-to-doxorubicin-induced-cytotoxicity
#1
Hong-Rong Fei, Yun-Sheng Zhou, Ruo-Tong Li, Ming-Feng Yang, Jian Ma, Feng-Ze Wang
To maintain the integrity of the genome, cells need to detect and repair DNA damage before they complete cell division. Hepatitis B x-interacting protein (HBXIP), a binding protein of HBx (Hepatitis B virus x protein), is aberrantly overexpressed in human cancer cells and show to promote cell proliferation and inhibit apoptosis. The present study is designed to investigate the role of HBXIP on the DNA damage response. Our results show that HBXIP acts as an important regulator of G2/M checkpoint in response to DNA damage...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28099140/telomerase-antagonist-imetelstat-increases-radiation-sensitivity-in-esophageal-squamous-cell-carcinoma
#2
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/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
#3
T Squillaro, I Antonucci, N Alessio, A Esposito, M Cipollaro, Mab Melone, G Peluso, L Stuppia, U 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...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28096236/inhibitory-effects-of-%C3%AE-and-%C3%AE-tocopherols-on-estrogen-stimulated-breast-cancer-in-vitro-and-in-vivo
#4
Min Ji Bak, Soumyasri Das Gupta, Joseph Wahler, Hong Jin Lee, Xiaowei Li, Mao-Jung Lee, Chung S Yang, Nanjoo Suh
Estrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress and DNA damage. Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert anti-tumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in estrogen-mediated breast cancer. To address this, we examined the effects of α-, γ- and δ-tocopherols as well as a natural γ-tocopherol rich mixture of tocopherols, γ-TmT, on estrogen-stimulated MCF-7 cells in vitro and in vivo...
January 17, 2017: Cancer Prevention Research
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
#5
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/28059653/sulforaphane-suppresses-the-growth-of-glioblastoma-cells-glioblastoma-stem-cell-like-spheroids-and-tumor-xenografts-through-multiple-cell-signaling-pathways
#6
Khadijeh Bijangi-Vishehsaraei, M Reza Saadatzadeh, Haiyan Wang, Angie Nguyen, Malgorzata M Kamocka, Wenjing Cai, Aaron A Cohen-Gadol, Stacey L Halum, Jann N Sarkaria, Karen E Pollok, Ahmad R Safa
OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28057860/contribution-of-canonical-nonhomologous-end-joining-to-chromosomal-rearrangements-is-enhanced-by-atm-kinase-deficiency
#7
Ragini Bhargava, Caree R Carson, Gabriella Lee, Jeremy M Stark
A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative role of these EJ pathways during rearrangement formation has remained controversial. Along these lines, we have tested whether the DNA damage response mediated by the Ataxia Telangiectasia Mutated (ATM) kinase may affect the relative influence of C-NHEJ vs...
January 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28054019/validation-data-supporting-the-characterization-of-novel-copper-complexes-as-anticancer-agents
#8
Ceyda Acilan, Buse Cevatemre, Zelal Adiguzel, Didem Karakas, Engin Ulukaya, Nádia Ribeiro, Isabel Correia, João Costa Pessoa
Three copper(II) complexes, Cu(Sal-Gly)(phen), Cu(Sal-Gly)pheamine, Cu(Sal-Gly)phepoxy were synthesized and characterized for their anticancer properties and mechanism of action (Acilan et al., in press) [1]. Here, we provide supporting data on colon cancer cell lines complementing our previous findings in cervix cells. This paper also contains a data table for the fold changes and p-values of all genes analyzed in this study via a custom RT-qPCR array. All compounds induced DNA damage (based on 8-oxo-guanidine, ɣH2AX staining in cells) and apoptosis (based on elevated DNA condensation/fragmentation, Annexin V staining, caspase 3/7 activity and mitochondrial membrane depolarization) in HCT-116 colon cancer cells...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/28052399/molecular-trail-for-the-anticancer-behavior-of-a-novel-copper-carbohydrazone-complex-in-brca1-mutated-breast-cancer
#9
Rakesh Sathish Nair, Manoj Easwaran Potti, Ratheeshkumar Thankappan, Sivakumar Krishnankutty Chandrika, M R Prathapachandra Kurup, Priya Srinivas
Novel chelated metal complexes were synthesized from carbohydrazones to thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild-type and mutated breast cancer cells: MCF-7 (BRCA1(+) /ER(+) ), MDA-MB-231 (BRCA1(+) /ERα(-) ), HCC-1937 (BRCA1(-) /ERα(-) ), HCC1937/wt BRCA1, MX1 (BRCA1(-) /ERα(-) ), and MDA-MB-436 (BRCA1(-) /ERα(-) ) were screened for anti-cancer activity...
January 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28052383/liver-damage-and-senescence-increases-in-patients-developing-hepatocellular-carcinoma
#10
Silvia Rey, Cristina Quintavalle, Katharina Burmeister, Diego Calabrese, Manuel Schlageter, Luca Quagliata, Gieri Cathomas, Joachim Diebold, Alfredo Molinolo, Markus H Heim, Luigi M Terracciano, Matthias S Matter
BACKGROUND & AIMS: Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes a continuous damage leading to liver cirrhosis and eventually HCC. However, only a minority of cirrhotic patients develop HCC. To asses a possible differential impact of liver inflammation in patients developing HCC versus patients remaining tumor-free we designed a longitudinal study and analyzed liver tissue of the same patient (n = 33) at two points in time: once when no HCC was present and once, several years later, when a HCC was present...
January 3, 2017: Journal of Gastroenterology and Hepatology
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
#11
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/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#12
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/28046013/homologous-recombination-defective-arabidopsis-mutants-exhibit-enhanced-sensitivity-to-abscisic-acid
#13
Sujit Roy, Kali Pada Das
Abscisic acid (ABA) acts as an important plant hormone in regulating various aspects of plant growth and developmental processes particularly under abiotic stress conditions. An increased ABA level in plant cells inhibits DNA replication and cell division, causing plant growth retardation. In this study, we have investigated the effects of ABA on the growth responses of some major loss-of-function mutants of DNA double-stand break (DSB) repair genes in Arabidopsis during seed germination and early stages of seedling growth for understanding the role of ABA in the induction of genome instability in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28035411/ellagic-acid-inhibits-human-glioblastoma-growth-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
Dongliang Wang, Qianxue Chen, Yinqiu Tan, Baohui Liu, Chao Liu
Ellagic acid (EA) is present in various fruits and plants and has recently been found to possess anticarcinogenic effects. The objective of this study was to investigate the anti‑glioblastoma effect of EA and its mechanisms in vitro and in vivo. We first studied the anticancer activity of EA in U87 and U118 human glioblastoma cell lines. The cell viability and cell proliferation were examined by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine staining respectively. The cell cycle was detected with propidium iodide staining method by flow cytometry and the DNA damage of the cells caused by EA exposure was evaluated by detection of γ-H2AX foci...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28035404/arrb1-enhances-the-chemosensitivity-of-lung-cancer-through-the-mediation-of-dna-damage-response
#15
Hongchang Shen, Liguang Wang, Jiangang Zhang, Wei Dong, Tiehong Zhang, Yang Ni, Hongxin Cao, Kai Wang, Yun Li, Yibing Wang, Jiajun Du
ARRB1 (also known as β-arrestin-1) serves as a multifunctional adaptor contributing to the regulation of signaling pathways. ARRB1 may be involved in DNA damage accumulation; however the underlying mechanism involved is unclear. In the present study, non-small cell lung cancer (NSCLC) cell lines (H520 and SK-MES-1) were transfected with ARRB1 plasmids or small interfering ribonucleic acid (siRNA) and received treatment with DNA-damaging agents (cisplatin and etoposide). A mouse xenograft model was used to assess the impact of ARRB1 on the efficacy of cisplatin in vivo...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28034704/antioxidants-taken-orally-prior-to-diagnostic-radiation-exposure-can-prevent-dna-injury
#16
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...
December 26, 2016: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28028228/large-scale-heterochromatin-remodeling-linked-to-overreplication-associated-dna-damage
#17
Wei Feng, Christopher J Hale, Ryan S Over, Shawn J Cokus, Steven E Jacobsen, Scott D Michaels
Previously, we have shown that loss of the histone 3 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAX-RELATED 5 (ATXR5) and ATXR6 (ATXR6) results in the overreplication of heterochromatin. Here we show that the overreplication results in DNA damage and extensive chromocenter remodeling into unique structures we have named "overreplication-associated centers" (RACs). RACs have a highly ordered structure with an outer layer of condensed heterochromatin, an inner layer enriched in the histone variant H2AX, and a low-density core containing foci of phosphorylated H2AX (a marker of double-strand breaks) and the DNA-repair enzyme RAD51...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28025714/bone-marrow-mesenchymal-stem-cell-transplantation-improves-radiation-induced-heart-injury-through-dna-damage-repair-in-rat-model
#18
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
#19
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/28009280/three-dimensional-architecture-of-the-human-brca1-a-histone-deubiquitinase-core-complex
#20
Otto J P Kyrieleis, Pauline B McIntosh, Sarah R Webb, Lesley J Calder, Janette Lloyd, Nisha A Patel, Stephen R Martin, Carol V Robinson, Peter B Rosenthal, Stephen J Smerdon
BRCA1 is a tumor suppressor found to be mutated in hereditary breast and ovarian cancer and plays key roles in the maintenance of genomic stability by homologous recombination repair. It is recruited to damaged chromatin as a component of the BRCA1-A deubiquitinase, which cleaves K63-linked ubiquitin chains attached to histone H2A and H2AX. BRCA1-A contributes to checkpoint regulation, repair pathway choice, and HR repair efficiency through molecular mechanisms that remain largely obscure. The structure of an active core complex comprising two Abraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape architecture in which a dimer of Abraxas/BRCC36 heterodimers sits at the base, with BRCC45/Merit40 pairs occupying each arm...
December 20, 2016: Cell Reports
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