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https://www.readbyqxmd.com/read/28454371/synergistic-effects-of-a-novel-lipid-soluble-extract-from-pinellia-pedatisecta-schott-and-cisplatin-on-human-cervical-carcinoma-cell-lines-through-the-regulation-of-dna-damage-response-signaling-pathway
#1
Mingxing Zhang, Hongwei Zhang, Yi Yu, Haixia Huang, Guiling Li, Congjian Xu
Herbal medicines have been recognized as an attractive approach for cancer therapy with minimal side effects. The present study investigated the type of interaction between a novel lipid-soluble extract from Pinellia pedatisecta Schott (PE) and cisplatin (CDDP) on human cervical cancer SiHa and CaSki cell lines in vitro. The mechanism of this combination was studied using cell proliferation, invasion and apoptosis assays, and by analyzing cell cycle distribution and protein expression, with a focus on DNA damage response (DDR) activation...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28448462/targeting-the-atr-chk1-axis-in-cancer-therapy
#2
REVIEW
Stuart Rundle, Alice Bradbury, Yvette Drew, Nicola J Curtin
Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation...
April 27, 2017: Cancers
https://www.readbyqxmd.com/read/28448050/single-molecule-analysis-of-laser-localized-psoralen-adducts
#3
Jing Huang, Himabindu Gali, Julia Gichimu, Marina A Bellani, Durga Pokharel, Manikandan Paramasivam, Michael M Seidman
The DNA Damage Response (DDR) has been extensively characterized in studies of double strand breaks (DSBs) induced by laser micro beam irradiation in live cells. The DDR to helix distorting covalent DNA modifications, including interstrand DNA crosslinks (ICLs), is not as well defined. We have studied the DDR stimulated by ICLs, localized by laser photoactivation of immunotagged psoralens, in the nuclei of live cells. In order to address fundamental questions about adduct distribution and replication fork encounters, we combined laser localization with two other technologies...
April 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447739/neural-precursor-cell-expressed-developmentally-downregulated-8%C3%A2-activating-enzyme-inhibitor-mln4924-sensitizes-colorectal-cancer-cells-to-oxaliplatin-by-inducing-dna-damage-g2-cell-cycle-arrest-and-apoptosis
#4
Wanwei Zheng, Zhongguang Luo, Jun Zhang, Pei Min, Wenshuai Li, Diannan Xu, Ziqiang Zhang, Panpan Xiong, Hong Liang, Jie Liu
Oxaliplatin-based chemotherapy is a primary treatment for patients with metastatic colorectal cancer (CRC); however, its efficacy is limited. Therefore, novel therapeutic agents are urgently required. MLN4924 is a first‑in‑class inhibitor of neural precursor cell expressed, developmentally downregulated 8 (NEDD8)‑activating enzyme E1, and has entered various phase‑I/II clinical trials for cancer therapy due to its significant anticancer efficacy. The aim of the present study was to examine the synergistic effect and underlying mechanisms of MLN4924 and oxaliplatin combined treatment for CRC...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446681/minute-virus-of-mice-mvm-inhibits-transcription-of-the-cyclin-b1-gene-during-infection
#5
Matthew S Fuller, Kinjal Majumder, David J Pintel
Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus then exploits to prepare the nuclear environment for effective parvovirus takeover. An essential aspect of the MVM-induced DDR is the establishment of a potent pre-mitotic block, which we previously found to be independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others previously reported, depends upon the significant, specific depletion of cyclin B1 and its encoding RNA, which precludes cyclin B1/CDK1 complex function thus preventing mitotic entry...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446595/dna-damage-signaling-mediates-the-functional-antagonism-between-replicative-senescence-and-terminal-muscle-differentiation
#6
Lucia Latella, Alessandra Dall'Agnese, Francesca Boscolo Sesillo, Chiara Nardoni, Marianna Cosentino, Armin Lahm, Alessandra Sacco, Pier Lorenzo Puri
The molecular determinants of muscle progenitor impairment to regenerate aged muscles are currently unclear. We show that, in a mouse model of replicative senescence, decline in muscle satellite cell-mediated regeneration coincides with activation of DNA damage response (DDR) and impaired ability to differentiate into myotubes. Inhibition of DDR restored satellite cell differentiation ability. Moreover, in replicative human senescent fibroblasts, DDR precluded MYOD-mediated activation of the myogenic program...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28444183/calcium-dysregulation-and-cdk5-atm-pathway-involved-in-a-mouse-model-of-fragile-x-associated-tremor-ataxia-syndrome
#7
Gaëlle Robin, José R López, Glenda M Espinal, Susan Hulsizer, Paul J Hagerman, Isaac N Pessah
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins, are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28440428/inhibition-of-atr-potentiates-the-cytotoxic-effect-of-gemcitabine-on-pancreatic-cancer-cells-through-enhancement-of-dna-damage-and-abrogation-of-ribonucleotide-reductase-induction-by-gemcitabine
#8
Shuang Liu, Yubin Ge, Tingting Wang, Holly Edwards, Qihang Ren, Yiqun Jiang, Chengshi Quan, Guan Wang
Pancreatic cancer is a highly malignant disease with a dismal prognosis. Gemcitabine (GEM)-based chemotherapy is the first-line treatment for patients with advanced disease, although its efficacy is very limited, mainly due to drug resistance. Ataxia telangiectasia and Rad3-related (ATR) plays a critical role in the DNA damage response (DDR) which has been implicated in GEM resistance. Thus, targeting ATR represents a promising approach to enhance GEM antitumor activity. In the present study, we tested the antitumor activity of AZ20, a novel ATR-selective inhibitor, alone or combined with GEM in 5 pancreatic cancer cell lines...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439991/melatonin-a-pleiotropic-molecule-that-modulates-dna-damage-response-and-repair-pathways
#9
REVIEW
Maryam Majidinia, Alireza Sadeghpour, Saeed Mehrzadi, Russel J Reiter, Nasrin Khatami, Bahman Yousefi
DNA repair is responsible for maintaining the integrity of the genome. Perturbations in the DNA repair pathways have been identified in several human cancers. Thus, compounds targeting DNA damage response (DDR) hold great promise in cancer therapy. A great deal of effort, in pursuit of new anticancer drugs, has been devoted to understanding the basic mechanisms and functions of the cellular DNA repair machinery. Melatonin, a widely-produced indoleamine in all organisms is associated with a reduced risk of cancer and has multiple regulatory roles on the different aspects of the DDR and DNA repair...
April 25, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28439615/wip1-phosphatase-as-pharmacological-target-in-cancer-therapy
#10
REVIEW
Soňa Pecháčková, Kamila Burdová, Libor Macurek
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target...
April 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28436431/dna-single-strand-break-induced-dna-damage-response-causes-heart-failure
#11
Tomoaki Higo, Atsuhiko T Naito, Tomokazu Sumida, Masato Shibamoto, Katsuki Okada, Seitaro Nomura, Akito Nakagawa, Toshihiro Yamaguchi, Taku Sakai, Akihito Hashimoto, Yuki Kuramoto, Masamichi Ito, Shungo Hikoso, Hiroshi Akazawa, Jong-Kook Lee, Ichiro Shiojima, Peter J McKinnon, Yasushi Sakata, Issei Komuro
The DNA damage response (DDR) plays a pivotal role in maintaining genome integrity. DNA damage and DDR activation are observed in the failing heart, however, the type of DNA damage and its role in the pathogenesis of heart failure remain elusive. Here we show the critical role of DNA single-strand break (SSB) in the pathogenesis of pressure overload-induced heart failure. Accumulation of unrepaired SSB is observed in cardiomyocytes of the failing heart. Unrepaired SSB activates DDR and increases the expression of inflammatory cytokines through NF-κB signalling...
April 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28436392/the-dna-damage-response-in-neurons-die-by-apoptosis-or-survive-in-a-senescence-like-state
#12
Edward Fielder, Thomas von Zglinicki, Diana Jurk
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28432356/a-role-of-human-rnase-p-subunits-rpp29-and-rpp21-in-homology-directed-repair-of-double-strand-breaks
#13
Enas R Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28426349/rna-binging-protein-rbm14-regulates-dissociation-and-association-of-non-homologous-end-joining-proteins
#14
Nicholas Simon, Ming Yuan, Mihoko Kai
Defects in DNA damage response (DDR) are associated with multiple diseases, including cancers and neurodegenerative disorders. Emerging evidence indicates involvement of RNA-binding proteins (RBPs) in DDR. However, functions of the RBPs in DDR pathways remain elusive. We have shown previously that the RNA-binding protein RBM14 is required for non-homologous end joining (NHEJ). Here we show that RBM14 is required for efficient recruitment of XRCC4 and XLF to chromatin and release of KU proteins from chromatin upon DNA damage...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28426283/identification-of-the-proteome-complement-of-humantlk1-reveals-it-binds-and-phosphorylates-nek1-regulating-its-activity
#15
Vibha Singh, Zachary M Connelly, Xinggui Shen, Arrigo De Benedetti
The Tousled Like kinases (TLKs) are involved in numerous cellular functions, including the DNA Damage Response (DDR), but only a handful of substrates have been identified thus far. Through a novel proteomic screen, we have now identified 165 human proteins interacting with TLK1, and we have focused this work on NEK1 because of its known role in the DDR, upstream of ATR and Chk1. TLK1 and NEK1 were found to interact by coIP, and their binding is strengthened following exposure of cells to H2O2. Following incubation with doxorubicin, TLK1 and NEK1 relocalize with nuclear repair foci along with γH2AX...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28415827/camptothecin-resistance-is-determined-by-the-regulation-of-topoisomerase-i-degradation-mediated-by-ubiquitin-proteasome-pathway
#16
Koji Ando, Ankur K Shah, Vibhu Sachdev, Benjamin P Kleinstiver, Julian Taylor-Parker, Moira M Welch, Yiheng Hu, Ravi Salgia, Forest M White, Jeffrey D Parvin, Al Ozonoff, Lucia E Rameh, J Keith Joung, Ajit K Bharti
Proteasomal degradation of topoisomerase I (topoI) is one of the most remarkable cellular phenomena observed in response to camptothecin (CPT). Importantly, the rate of topoI degradation is linked to CPT resistance. Formation of the topoI-DNA-CPT cleavable complex inhibits DNA re-ligation resulting in DNA-double strand break (DSB). The degradation of topoI marks the first step in the ubiquitin proteasome pathway (UPP) dependent DNA damage response (DDR). Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401005/chk1-inhibition-potentiates-the-therapeutic-efficacy-of-parp-inhibitor-bmn673-in-gastric-cancer
#17
Yuping Yin, Qian Shen, Peng Zhang, Ruikang Tao, Weilong Chang, Ruidong Li, Gengchen Xie, Weizhen Liu, Lihong Zhang, Prabodh Kapoor, Shumei Song, Jaffer Ajani, Gordon B Mills, Jianying Chen, Kaixiong Tao, Guang Peng
Globally, gastric cancer is the second leading cause of cancer deaths because of the lack of effective treatments for patients with advanced tumors when curative surgery is not possible. Thus, there is an urgent need to identify molecular targets in gastric cancer that can be used for developing novel therapies and prolonging patient survival. Checkpoint kinase 1 (Chk1) is a crucial regulator of cell cycle transition in DNA damage response (DDR). In our study, we report that Chk1 plays an important role in promoting gastric cancer cell survival and growth, which serves as an effective therapeutic target in gastric cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28399610/dedicated-barrett-s-surveillance-sessions-managed-by-trained-endoscopists-improve-dysplasia-detection-rate
#18
Joanne Ooi, Patrick Wilson, Giles Walker, Paul Blaker, Sabina DeMartino, John O'Donohue, David Reffitt, Effie Lansepre, Fuju Chang, John Meenan, Jason M Dunn
Background and study aim Barrett's esophagus (BE)-associated dysplasia is an important marker for risk of progression to esophageal adenocarcinoma (EAC) and an indication for endoscopic therapy. However, BE surveillance technique is variable. The aim of this study was to assess the effect of dedicated BE surveillance lists on dysplasia detection rate (DDR). Patients and methods This was a prospective study of patients undergoing BE surveillance at two hospitals - community (UHL) and upper gastrointestinal center (GSTT)...
April 11, 2017: Endoscopy
https://www.readbyqxmd.com/read/28394347/new-factors-in-mammalian-dna-repair-the-chromatin-connection
#19
REVIEW
G Raschellà, G Melino, M Malewicz
In response to DNA damage mammalian cells activate a complex network of stress response pathways collectively termed DNA damage response (DDR). DDR involves a temporary arrest of the cell cycle to allow for the repair of the damage. DDR also attenuates gene expression by silencing global transcription and translation. Main function of DDR is, however, to prevent the fixation of debilitating changes to DNA by activation of various DNA repair pathways. Proper execution of DDR requires careful coordination between these interdependent cellular responses...
April 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28393815/assessment-of-treatment-response-to-splint-therapy-and-evaluation-of-tmj-function-using-joint-vibration-analysis-in-patients-exhibiting-tmj-disc-displacement-with-reduction-a-clinical-study
#20
Jyoti Devi, Mahesh Verma, Rekha Gupta
Context, Aim, and Objectives: Diagnosis of temporomandibular joint (TMJ) disc displacement with reduction (DDR) is difficult. Literature combining different subjective parameters of TMJ function with an objective evaluation of TMJ function using joint vibration analysis (JVA) is limited. Hence, the study was planned to diagnose temporomandibular disorder accurately, to do a subjective and objective evaluation of TMJ function, and to assess the effectiveness of different types of splint therapy over the conventional anterior repositioning appliance (ARA) group...
January 2017: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
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