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  • damage
  • In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. (frontiersin.org)
  • expression
  • The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. (frontiersin.org)
  • CHK1
  • In addition, this study implicates ATR as a direct upstream activator of Chk1 in human cells. (asm.org)
  • This renders cancer cells particularly dependent on a proficient replication stress response for their survival, making the ATR-CHK1 pathway an attractive target for cancer treatment. (springer.com)
  • Mutations
  • 2016 ). Hypomorphic mutations in the ATR gene are associated with a rare autosomal recessive disorder, Seckel syndrome (OMIM #210600), characterized by intrauterine growth retardation, dwarfism, microcephaly, and mental retardation (Ogi et al. (springer.com)
  • Approximately 50% of T-cell lymphoblastic leukemias (T-ALL) carry activating Notch-1 mutations ( 4 ). (aacrjournals.org)
  • Ten years of intense studies on the stability of different human and monkey embryonic stem cells demonstrated that, irrespective of their origin, long-term in vitro cultures lead to the accumulation of chromosomal and gene mutations as well as epigenetic changes that can cause oncogenic transformation of cells. (deepdyve.com)
  • It is known that patients with bladder cancer have mutations in cell cycle checkpoint genes that are associated with malignant growth and genetic instability. (spandidos-publications.com)
  • mutation
  • Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAF V600E mutation and PTEN loss, and H3, harboring WT (wild-type) BRAF and PTEN loss, with the MAPK (BRAF) inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. (mdpi.com)
  • We aimed to assess whether CHEK2 was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation in BRCA1 or BRCA2 had been identified. (biomedcentral.com)
  • This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms. (biomedcentral.com)
  • As part of an international breast cancer genetics study aiming to investigate candidate genes conferring an intermediate-risk of breast cancer, we mutation screened the coding exons and the adjacent proximal introns of CHEK2 in 1415 cases and 1204 controls. (biomedcentral.com)
  • MA-11 cells did not show radiation-induced expression of the G 1 cell cycle inhibitor p21, indicative of a defective G 1 checkpoint and consistent with a point mutation detected in the tumor suppressor TP53 gene. (aacrjournals.org)
  • Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.com)
  • We attempted to gain insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1 . (biomedcentral.com)
  • mitotic
  • Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. (hindawi.com)
  • Mitotic cells might undergo senescence by failing to replicate. (hindawi.com)
  • Following pretreatment with the HDAC inhibitor, the efficiency of clonogenic regrowth after irradiation was reduced, which is in accordance with the concept of increased probability of mitotic cell death when the chromatin structure is disrupted. (aacrjournals.org)
  • The tumor cell response to DNA damage involves a temporary cell cycle delay at the G 1 -S or G 2 -M boundaries, to activate a cascade of responses to the damage, ultimately leading to cell survival if the DNA is properly repaired, or, if not, to apoptotic or mitotic cell death ( 7 ). (aacrjournals.org)
  • cytotoxic activity
  • The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb of Allium atroviolaceum in MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. (frontiersin.org)
  • Originally known as host defence peptides for their substantial bacteriotoxic effects, many cationic antimicrobial peptides also exhibit a potent cytotoxic activity against cancer cells. (jove.com)
  • Stability
  • In individual cells, the circadian clock mechanism consists of oscillating feedback loops of transcription of "core" oscillator genes and posttranslational modifications of their protein products that regulate protein stability, activity, and/or localization. (pnas.org)
  • It affects a plethora of cellular processes including protein trafficking, stability and signalling and is therefore important for all cell types, and organisms from yeast to humans. (sheffield.ac.uk)
  • This review summarizes the research data on the genetic and epigenetic stability of different lines of pluripotent stem cells after long-term in vitro culture. (deepdyve.com)
  • chromatin
  • For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. (mdpi.com)
  • For example, MARVELD2 exhibited myogenic hypermethylation in transcription-type chromatin that overlapped a silenced promoter in Mb and Mt while TEAD4 had myogenic hypomethylation in intronic subregions displaying enhancer-type or transcription-type chromatin in these cells. (mdpi.com)
  • These studies have demonstrated that relationships between DNA methylation and gene expression are much more complex than previously assumed and often highly dependent on the context of the gene region, the surrounding chromatin epigenetics, and the cell type [ 8 , 9 , 10 ]. (mdpi.com)
  • cancers
  • The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. (biomedcentral.com)
  • inhibitors
  • Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. (biomedcentral.com)
  • This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias. (biomedcentral.com)
  • mRNA
  • This DNA damage response promptly reduces histone gene expression as well as mRNA levels for HiNF-P and p220(NPAT) and causes accumulation of unprocessed histone H4 precursor RNAs. (umassmed.edu)
  • See reference mRNA sequence for the RAD9A gene (NM_004584.2). (nih.gov)
  • Today, mRNA-based reprogramming has proven to be the only non-viral, non-integrating method for reliable, safe and efficient generation of clinically relevant human iPS cell lines. (tebu-bio.com)
  • Already a recognised European service provider in genomics, proteomics and cell-based assays, tebu-bio now brings researchers across Europe access to Toray's 3D-Gene microRNA and mRNA technology profiling services. (tebu-bio.com)
  • cellular
  • Specifically, although fibroblasts from NONO-deficient mice showed approximately normal circadian cycles, they displayed elevated cell doubling and lower cellular senescence. (pnas.org)
  • In ERα + cells, estradiol inhibited Notch activity and Notch-1 IC nuclear levels and affected Notch-1 cellular distribution. (aacrjournals.org)
  • These findings suggested that HHUS1 and HHUS1B have related but not identical functions in cell cycle checkpoint control and perhaps other as of yet undefined cellular processes. (aacrjournals.org)
  • dependent
  • This response may alter the E2F/pocket protein combinations that control E2F dependent genes and block H4 gene expression by inhibiting histone-specific transcription factors and processing of histone gene transcripts, as well as by destabilizing histone mRNAs. (umassmed.edu)
  • Ball HL, Cortez D (2005) ATRIP oligomerization is required for ATR-dependent checkpoint signaling. (springer.com)
  • Inhibitor
  • Moreover, ERK1/2 in CUL4A -overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A -induced expression of MDR1 / P-gp was decreased significantly. (mdpi.com)
  • Essentially, in tumor cells with intact p53 function, DNA damage leads to rapid p53 stabilization by posttranslational protein modifications as well as induction of the G 1 phase inhibitor p21 ( 7 ). (aacrjournals.org)
  • vivo
  • However, overexpression of ATR complements the radioresistant DNA synthesis defect of cells lacking ATM, demonstrating that these two kinases have overlapping functions in vivo. (asm.org)
  • Despite different origin, all pluripotent lines demonstrate considerable similarity of the major biological properties: active self-renewal and differentiation into various somatic and germ cells in vitro and in vivo, similar gene expression profiles, and similar cell cycle structure. (deepdyve.com)
  • In this work, we have designed a novel cationic peptide of 27 amino acids (Cypep-1), which shows efficacy against a number of cancer cell types, both in vitro and in vivo, while normal human fibroblasts were significantly less affected. (jove.com)
  • We have previously characterized the MA-11 human breast carcinoma cell line for its ability to form experimental organ-specific metastases in vivo . (aacrjournals.org)
  • regulatory
  • However, a retrograde signal mediating light-responsive gene expression may have been established alongside gene transfer, because essential light sensing and regulatory systems were originally incorporated into plant cells by the photosynthetic endosymbiont. (frontiersin.org)
  • inhibition
  • In T47D:A18 (ERα + ) cells, the same targets were affected, and Notch inhibition potentiated the effects of tamoxifen. (aacrjournals.org)
  • Therefore, the objective of this study was to evaluate the therapeutic efficacy of a combination of non-toxic, low dose of 5-aza 2′ dC with EGCG, on growth inhibition of breast cancer cells. (springer.com)
  • The results revealed significantly greater inhibition of growth of breast cancer cells by co-treatment with 5-aza 2′ dC and EGCG compared to individual treatments, whereas it has no significant toxicity to MCF-10A cells. (springer.com)
  • Findings of this study suggest that potentiation of growth inhibition of breast cancer cells by 5-aza 2′ dC and EGCG combination treatment, at least in part, is mediated by epigenetic mechanism. (springer.com)
  • transcription
  • This releases a cytoplasmic subunit (N IC ), which activates CSL transcription factors, modulating cell fate decisions ( 1 ). (aacrjournals.org)
  • The abundance of HRAD9B RNA, as judged by quantitative reverse transcription-PCR, is very low in most testicular tumors, particularly those of germ cell origin, i.e. , seminomas, relative to normal testis control, nonseminomas, or Leydig tumor cells. (aacrjournals.org)
  • Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1 / P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. (mdpi.com)
  • Early reprogramming methods utilized retroviral (including lentiviral) vectors to introduce reprogramming-associated transcription factors to the target cells. (tebu-bio.com)
  • radiation
  • Sequence analysis of the ATM gene in 20 patients with RTOG grade 3 or 4 acute and/or late tissue radiation side effects. (semanticscholar.org)
  • We have previously found that the mechanism of the G 2 phase response to ionizing radiation comprises repression of the genes for Plk1 and cyclin B1, PLK and CCNB1 ( 10 ). (aacrjournals.org)
  • mammals
  • In mammals, individual clocks in most cells are synchronized by a brain "master clock" in the suprachiasmatic nucleus of the hypothalamus to orchestrate all rhythmic physiology ( 2 ). (pnas.org)
  • In most mammals, cycles of the addition and removal of DNA methylation constitute phases of reprogramming when the developing embryo must negotiate lineage defining and developmental commitment events. (springer.com)
  • clamp
  • In terms of cell cycle checkpoint control, several groups have suggested that HRAD9-HHUS1-HRAD1 form a proliferating cell nuclear antigen-like heterotrimer clamp, sometimes referred to as the 9-1-1 complex (4) , that is recruited onto damaged DNA via a clamp loader function of HRAD17. (aacrjournals.org)