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ataxia telangiectasia mutated

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https://www.readbyqxmd.com/read/29463243/anacardic-acid-inhibits-pancreatic-cancer-cell-growth-and-potentiates-chemotherapeutic-effect-by-chmp1a-atm-p53-signaling-pathway
#1
Maiyon Park, Danielle Upton, Melodie Blackmon, Valerie Dixon, Scott Craver, Dawn Neal, Derek Perkins
BACKGROUND: Pancreatic cancer is one of the leading causes of cancer related death and its incidence has risen steadily. Although anticancer drugs have been developed based on the new molecular findings, the drugs have produced unsatisfactory results due to toxicity and resistance. Thus, a complementary therapeutic intervention is urgently needed for pancreatic cancer patients. METHODS: The aim of this study was to assess the potential therapeutic effect of Anacardic acid on pancreatic cancer in vitro and elucidate its underlying mechanisms...
February 20, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29458134/antiviral-activity-of-pyrrole-imidazole-polyamides-against-sv40-and-bk-polyomaviruses
#2
Terri G Edwards, Chris Fisher
The ability of antiviral polyamides (AVP) to act upon polyomaviruses (PyV) was evaluated. Initial studies found that a single treatment of AVP protected SV40-infected BSC-1 cells from cytopathic effect (CPE) for as long as 11 days p.i.. AVP substantially suppressed SV40 genome copy numbers over the duration of the experiment. Immunofluorescence analysis of ataxia-telangiectasia mutated (ATM) activation and large T antigen (LTag) expression clearly demonstrated that AVP treatment at day 1 p.i. delayed the onset of productive SV40 replication by approximately 3 days, and substantially limited the infection relative to vehicle-treated controls...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29434894/down-expression-of-poly-adp-ribose-polymerase-in-p53-regulated-pancreatic-cancer-cells
#3
Zhenyu Hou, Yunfeng Cui, Huizhi Xing, Xiaoyan Mu
The present study investigated whether poly(ADP-ribose) polymerase (PARP) has an effect on p53-regulated pancreatic cancer. The results of the present study demonstrated that the expression of PARP affects proliferation and apoptosis of pancreatic cancer cells. Olaparib was used to suppress the expression level of PARP-1 in PanC-1 cells. Decreased expression of PARP-1 suppressed cell proliferation and induced apoptosis of PanC-1 cells when compared with controls. Furthermore, decreased expression of PARP-1 resulted in decreased levels of pro-caspase-3 expression, increased caspase-3 activity, suppressed B-cell lymphoma 2 (Bcl-2) protein expression and increased p53 protein expression in PanC-1 cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434868/cytotoxic-effect-of-efavirenz-in-bxpc-3-pancreatic-cancer-cells-is-based-on-oxidative-stress-and-is-synergistic-with-ionizing-radiation
#4
Markus Hecht, Thomas Harrer, Verena Körber, Eric O Sarpong, Fabian Moser, Nora Fiebig, Manuela Schwegler, Michael Stürzl, Rainer Fietkau, Luitpold V Distel
The non-nucleoside reverse transcriptase inhibitor (NNRTI) Efavirenz is frequently used in human immunodeficiency virus treatment, but also efficient against cancer in mouse models. Its radiosensitizing effect makes it a promising drug for combination with radiotherapy. The efficacy of Efavirenz combined with irradiation was assessed with immunostaining of DNA-damage markers and colony formation assays in BxPC-3 pancreatic cancer cells. Gene expression and protein phosphorylation of the Efavirenz-sensitive BxPC-3 cells was compared to the resistant primary fibroblasts SBL-5...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434792/pine-needle-oil-induces-g2-m-arrest-of-hepg2-cells-by-activating-the-atm-pathway
#5
Bing Qiu, Wei Jiang, Wenliang Qiu, Wenling Mu, Yujing Qin, Yongcui Zhu, Jianying Zhang, Qingyi Wang, Dongjie Liu, Zhangyi Qu
Over the last two decades, inducing DNA damage of cancer cells by natural medicines has become a research hotspot in the field of cancer treatment. Although various natural medicines have anticancer effects, very few studies have been conducted to explore the anti-cancer effect of pine needle oil. In the present study, the role of pine needle oil in inducing G2/M arrest in HepG2 cells was investigated. The data revealed that pine needle oil could induce DNA damage in a dose-dependent manner. In the pine needle oil-treated HepG2 cells, the protein levels of phosphorylated (p)-ataxia-telangiectasia mutated (ATM), γ-H2A histone family, member X, p-p53, p-checkpoint kinase 2 and p-cell division cycle 25C were evidently increased, indicating that pine needle oil facilitated G2/M arrest in HepG2 cells through the ATM pathway...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29427417/-tp53-haploinsufficiency-rescues-emergency-granulopoiesis-in-fancc-mice
#6
Liping Hu, Weiqi Huang, Ling Bei, Larisa Broglie, Elizabeth A Eklund
Emergency (stress) granulopoiesis is an episodic process for the production of granulocytes in response to infectious challenge. We previously determined that Fanconi C, a component of the Fanconi DNA-repair pathway, is necessary for successful emergency granulopoiesis. Fanconi anemia results from mutation of any gene in this pathway and is characterized by bone marrow failure (BMF) in childhood and clonal progression in adolescence. Although murine Fanconi anemia models exhibit relatively normal steady-state hematopoiesis, FANCC -/-mice are unable to mount an emergency granulopoiesis response...
February 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29416613/efficient-inhibition-of-cervical-cancer-by-dual-drugs-loaded-in-biodegradable-thermosensitive-hydrogel-composites
#7
Shan Xu, Xiaobo Du, Gang Feng, Yu Zhang, Jie Li, Binwei Lin, Linglin Yang, Shaozhi Fu, Jingbo Wu
Background and Purpose: We aimed to explore the anti-tumor effect and mechanism of the combination of cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG, or PECE) and paclitaxel (PTX)-loaded MPEG-PCL polymeric micelles called PDMP on human cervical carcinoma (HeLa) cell. In our previous studies, we found that PDMP in situ treatment of lung cancer will be liable to have potential in Lung cancer patients. Results: Compared with other treatments, PDMP was most effective in prolonging survival time (P < 0...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29399146/loperamide-an-antidiarrheal-agent-induces-apoptosis-and-dna-damage-in-leukemia-cells
#8
Xin He, Lei Zhu, Shu Li, Zhigang Chen, Xiaoying Zhao
Loperamide, an antidiarrheal agent, is frequently used to treat patients with leukemia with symptoms of diarrhea during treatment. However, the effect of loperamide on leukemia cells is unknown. The MTT assay was used to explore the cytotoxic effect of loperamide on leukemia cells. Morphological analysis and flow cytometry were performed to determine the level of apoptosis in leukemia cells following loperamide treatment. Western blotting was conducted to test the activation of the apoptotic pathway. The comet assay was used to determine the DNA damage induced by loperamide...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29397781/ionizing-radiation-deregulates-the-microrna-expression-profile-in-differentiated-thyroid-cells
#9
Ricardo Cortez Cardoso Penha, Simona Pellecchia, Roberto Pacelli, Luis Felipe Ribeiro Pinto, Alfredo Fusco
BACKGROUND: Ionizing Radiation (IR) is a well-known risk factor for papillary thyroid cancer, and it has been reported to deregulate microRNA expression, which is important to thyroid carcinogenesis. Therefore, we have investigated the impact of IR on microRNA expression profile of the normal thyroid cell line (FRTL-5 CL2) and as well as its effect on radiosensitivity of thyroid cancer cell lines, especially the human anaplastic thyroid carcinoma cell line (8505c). METHODS: The global microRNA expression profile of irradiated FRTL-5 CL2 cells (5 Gy X-ray) was characterized and data were confirmed by qRT-PCR evaluating the expression of rno-miR-10b-5p, rno-miR-33-5p, rno-miR-128-1-5p, rno-miR-199a-3p, rno-miR-296-5p, rno-miR-328a-3p and rno-miR-541-5p in irradiated cells...
February 3, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29396668/targeting-ataxia-telangiectasia-mutated-and-rad3-related-kinase-atr-in-pten-deficient-breast-cancers-for-personalized-therapy
#10
Nouf Al-Subhi, Reem Ali, Tarek Abdel-Fatah, Paul M Moseley, Stephen Y T Chan, Andrew R Green, Ian O Ellis, Emad A Rakha, Srinivasan Madhusudan
PURPOSE: Phosphate and tensin homolog (PTEN), a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in PTEN-deficient triple-negative breast cancer (TNBC). METHODS: PTEN, ATR and pCHK1Ser345 protein level was evaluated in 1650 human breast cancers. ATR blockade by VE-821 was investigated in PTEN-proficient- (MDA-MB-231) and PTEN-deficient (BT-549, MDA-MB-468) TNBC cell lines...
February 2, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29395063/the-augmented-r-loop-is-a-unifying-mechanism-for-myelodysplastic-syndromes-induced-by-high-risk-splicing-factor-mutations
#11
Liang Chen, Jia-Yu Chen, Yi-Jou Huang, Ying Gu, Jinsong Qiu, Hao Qian, Changwei Shao, Xuan Zhang, Jing Hu, Hairi Li, Shunmin He, Yu Zhou, Omar Abdel-Wahab, Dong-Er Zhang, Xiang-Dong Fu
Mutations in several general pre-mRNA splicing factors have been linked to myelodysplastic syndromes (MDSs) and solid tumors. These mutations have generally been assumed to cause disease by the resultant splicing defects, but different mutations appear to induce distinct splicing defects, raising the possibility that an alternative common mechanism is involved. Here we report a chain of events triggered by multiple splicing factor mutations, especially high-risk alleles in SRSF2 and U2AF1, including elevated R-loops, replication stress, and activation of the ataxia telangiectasia and Rad3-related protein (ATR)-Chk1 pathway...
February 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29388453/53bp1-loss-suppresses-the-radiosensitizing-effect-of-icotinib-hydrochloride-in-colorectal-cancer-cells
#12
Ai Huang, Jing Yao, Tao Liu, Zhenyu Lin, Sheng Zhang, Tao Zhang, Hong Ma
BACKGROUND: This study aimed to investigate the influence of the expression of P53-binding protein 1 (53BP1), a key component in DNA damage repair pathways, on the radiosensitizing effect of icotinib hydrochloride in colorectal cancer and to elucidate the mechanisms underlying this influence. MATERIALS AND METHODS: Real-time RT-PCR and western blotting were performed to verify the gene-knockout effect of 53BP1 small hairpin RNA (siRNA), and colony formation assay was employed to investigate the influence of 53BP1 downregulation on the radiosensitizing effect of icotinib hydrochloride in HCT116 cells...
February 1, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29386061/dihydroisotanshinone-i-combined-with-radiation-inhibits-the-migration-ability-of-prostate-cancer-cells-through-dna-damage-and-ccl2-pathway
#13
I-Yun Lee, Yin-Yin Lin, Yao-Hsu Yang, Yu-Shin Lin, Chun-Liang Lin, Wei-Yu Lin, Yu-Ching Cheng, Li-Hsin Shu, Ching-Yuan Wu
BACKGROUND: Radiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 μM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells. METHODS: DT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay...
January 31, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29385673/post-translational-regulation-of-the-rsf1-chromatin-remodeler-under-dna-damage
#14
Sunwoo Min, Yong Won Choi, Hansol Yun, Sujin Jo, Jae-Hoon Ji, Hyeseong Cho
Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown...
January 31, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29382425/-knockdown-of-dna-pkcs-inhibits-cell-cycle-and-its-mechanism-of-drug-resistant-bel7402-5-fu-hepatocellular-carcinoma-cells
#15
Dayu Li, Yun Liu, Chunbo Yu, Xiping Liu, Fang Fan
Objective To study the effect of the knock-down of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on the cell cycle of the multidrug-resistant (MDR) Bel7402/5-Fu hepatocellular carcinoma cells and its MDR mechanism. Methods After cationic liposome-mediated siDNA-PKcs oligonucleotide transfection, the drug sensitivity of Bel7402/5-Fu cells to 5-fluorouracil (5-Fu) and adriamycin (ADM) was determined by MTT assay; the cell cycle were detected by flow cytometry; meanwhile, the protein expressions of cell cycle-related proteins P21, cell cycle protein B1 (cyclin B1), cell cycle division protein 2 (CDC2) were tested by Western blotting; the expressions of ataxia telangiectasia mutated (ATM) and p53 at both mRNA and protein levels were detected by real-time PCR and Western blot analysis...
December 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29378956/atr-chk1-activation-mitigates-replication-stress-caused-by-mismatch-repair-dependent-processing-of-dna-damage
#16
Dipika Gupta, Bo Lin, Ann Cowan, Christopher D Heinen
The mismatch repair pathway (MMR) is essential for removing DNA polymerase errors, thereby maintaining genomic stability. Loss of MMR function increases mutation frequency and is associated with tumorigenesis. However, how MMR is executed at active DNA replication forks is unclear. This has important implications for understanding how MMR repairs O6-methylguanine/thymidine (MeG/T) mismatches created upon exposure to DNA alkylating agents. If MeG/T lesion recognition by MMR initiates mismatch excision, the reinsertion of a mismatched thymidine during resynthesis could initiate futile repair cycles...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29369707/ataxia-telangiectasia-mutated-and-rad3-related-inhibition-and-topoisomerase-i-trapping-create-a-synthetic-lethality-in-cancer-cells
#17
Lee Zou
No abstract text is available yet for this article.
January 25, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29369221/the-association-of-single-nucleotide-polymorphism-rs189037c-t-in-atm-gene-with-coronary-artery-disease-in-chinese-han-populations-a-case-control-study
#18
Xiang Ding, Yong He, Qiukui Hao, Shanping Chen, Ming Yang, Sean X Leng, Jirong Yue, Birong Dong
Accumulated evidence has indicated that ataxia telangiectasia mutated (ATM) is closely related to atherosclerosis and cardiovascular diseases. So we aimed to examine potential association between a gene variant [single nucleotide polymorphisms (SNPs), i.e., rs189037C>T] in the promoter of ATM gene and coronary artery disease (CAD) in Chinese Han populations.In this hospital-based case-control study, a total of 1308 participants were divided into CAD group (652 patients) and control group (656 subjects) after performing coronary angiography...
January 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#19
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29349619/1h-15n-and-13c-chemical-shift-assignments-of-the-micelle-immersed-fat-c-terminal-fatc-domains-of-the-human-protein-kinases-ataxia-telangiectasia-mutated-atm-and-dna-dependent-protein-kinase-catalytic-subunit-dna-pkcs-fused-to-the-b1-domain-of-streptococcal
#20
Munirah S Abd Rahim, Lisa A M Sommer, Anja Wacker, Martin Schaad, Sonja A Dames
FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent NMR- and CD-monitored interaction studies indicated that the FATC domains of all PIKKs can interact with membrane mimetics albeit with different preferences for membrane properties such as surface charge and curvature. Thus they may generally act as membrane anchoring unit. Here, we present the 1H, 15N, and 13C chemical shift assignments of the DPC micelle immersed FATC domains of the human PIKKs ataxia-telangiectasia mutated (ATM, residues 3024-3056) and DNA protein kinase catalytic subunit (DNA-PKcs, residues 4096-4128), both fused to the 56 residue long B1 domain of Streptococcal protein G (GB1)...
January 18, 2018: Biomolecular NMR Assignments
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