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  • mitotic
  • Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby aberrations in the chromatin structure, may also override the DNA damage defense response and facilitate the radiation-induced mitotic cell death. (aacrjournals.org)
  • 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)
  • 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)
  • Evidence such as tumour specific aneuploidy, presence of aneuploidy in various preneoplastic conditions, increased frequency of genetic instability in aneuploid cell lines compared with diploid cells, and mutation of mitotic checkpoint genes suggests that aneuploidy possibly plays an active role in carcinogenesis. (bmj.com)
  • Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1 , were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. (aacrjournals.org)
  • To elucidate the frequency and physiological consequences of nonmutational silencing of mitotic checkpoint genes in human colorectal cancers, we have established hBUB1/hBUBR1 LightCycler RT-PCR 3 for accurate quantification of their transcripts and determined the expression levels in surgically resected cancer tissues and their neighboring normal colonic mucosa. (aacrjournals.org)
  • molecular
  • "Molecular heterogeneity of the Jk(null) phenotype: expression analysis of the Jk(S291P) mutation found in Finns. (tcdb.org)
  • Among molecular cell cycle-targeted drugs currently in the pipeline for testing in early-phase clinical trials, HDAC inhibitors may have therapeutic potential as radiosensitizers. (aacrjournals.org)
  • At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. (hindawi.com)
  • A mutation that results in an increase in a gene's activity or in acquiring a new molecular function or a new pattern of gene expression. (bioportfolio.com)
  • Subsequent cytological and/or molecular analysis of these cells may inform individual breast cancer risk assessment or even permit early diagnosis of cancer while avoiding the use of ionizing radiation. (biomedcentral.com)
  • candidate genes
  • In melanoma, microsatellite mapping has been carried out on selected chromosomes, also analysed for mutations in candidate genes (CDKN2A). (dkfz.de)
  • To test the hypothesis that an association between common genetic variations, reported by single nucleotide polymorphisms (SNP) in relevant candidate genes, is associated with individual patient variability in normal tissue radiation response and toxicity. (clinicaltrials.gov)
  • irradiation
  • Primary fibroblasts from BRCA1 mutation-carrying members of breast cancer families display a G1/S cell cycle checkpoint defect following UVA irradiation but show normal levels of micronuclei following oxidative stress or mitomycin C treatment. (lancs.ac.uk)
  • For example, UV induced unique time-dependent patterns of change in a set of 44 genes at 6 h post irradiation that was not induced by IR. (renci.org)
  • DNA double-strand breaks (dsbs) persist in A-T cells after irradiation, but the underlying defect is unclear. (mysciencework.com)
  • Ku70-deficient (NHEJ(-)) ATM(-/-) chicken DT40 cells show radiosensitivity and high radiation-induced chromosomal aberration frequencies, while Rad54-defective (HR(-)) ATM(-/-) cells show only slightly elevated aberration levels after irradiation, placing ATM and HR on the same pathway. (mysciencework.com)
  • malignant
  • However, the role of cholera toxin in the tumorigenesis of transitional cell carcinoma (TCC), the most common malignant tumor of the bladder, remains to be elucidated. (spandidos-publications.com)
  • Similar to what is observed in sporadic hematological malignancies, acquired additional genetic events cooperate with inherited RUNX1 mutations to progress the overt malignant phase. (springer.com)
  • The intraduct approach is an umbrella term for several different techniques, including nipple aspiration (NA), ductal lavage (DL) and duct endoscopy (DE), that allow sampling of breast fluid and exfoliated epithelial cells - the cells at risk for malignant transformation. (biomedcentral.com)
  • The intraduct approach, with its ability to examine directly those cells that are most at risk for malignant transformation and their surrounding milieu, intuitively offers the potential for refining personal risk estimates, thus aiding clinical management decisions, and it may facilitate detection of early breast cancer. (biomedcentral.com)
  • frequency
  • Overall, the frequency of ATM mutations found in breast cancer patients in the general population has been low, and many of the ATM variants found are too rare to be evaluated easily in case-control studies. (biomedcentral.com)
  • radiosensitivity
  • Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease that presents with clinical features such as microcephaly, mental and growth retardation, immunodeficiency, radiosensitivity, and increased risk for cancer, particularly B-cell non-Hodgkin's lymphoma ( 6 - 8 ). (aacrjournals.org)
  • Fibroblasts
  • Fibroblasts isolated from an Amyotrophic Lateral Sclerosis (ALS)-patient carrying a mutation in Matrin-3 (p.Q66K -MATR3) gene were reprogrammed to the pluripotency stage by using non-integrating episo. (bioportfolio.com)
  • Methods and materials Fibroblasts from individuals carrying mutations in the BRCA1 gene were compared with those from those wild-type for BRCA1 in their response to long wavelength uv (UVA), hydrogen peroxide, and mitomycin C (MMC). (lancs.ac.uk)
  • Ontology
  • Gene ontology analysis of this UV-specific pattern identified RNA transcription as the biological process controlled by the set of co-regulated genes. (renci.org)
  • locus
  • A tissue bank of 600 consecutive bladder cancers has been used in the analysis of homozygous deletions and mutations at the p16 gene locus and correlated with clinical markers. (dkfz.de)
  • alleles
  • "Two novel Jk(null) alleles derived from 222C>A in Exon 5 and 896G>A in Exon 9 of the JK gene. (tcdb.org)
  • predisposition
  • Currently, women who carry mutations in high-risk breast cancer predisposition genes must make a difficult choice between regular surveillance, risk-reducing surgery, or taking part in trials of chemopreventive agents. (biomedcentral.com)
  • cancer
  • 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)
  • This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias. (biomedcentral.com)
  • Transitional cell carcinoma (TCC), also termed urothelial cell carcinoma, is the most common type of bladder cancer in the United States. (spandidos-publications.com)
  • One defining feature of cancer is the rapid creation of abnormal cells which grow beyond their usual boundaries, and which can invade adjoining parts of the body and spread to other organs, a process referred to as metastasis. (ndri.com)
  • When this happens, a tumor, abnormal body cells grouped together in the form of a mass or lump, can start to form and grow.Breast cancer often starts as a small lump in the breast and is one of the most common cancers in women. (ndri.com)
  • TAILORx study designed to examine whether women with early-stage lymph node-negative breast cancer can be assigned to individualized treatment plans based on certain genes that may predict whether their cancer will return. (ndri.com)
  • A major effort has been directed to analysis of polymorphisms (SNPs) in cancer-related genes. (dkfz.de)
  • Two polymorphisms in the 3 -untranslated region of the p16 gene were found to be prognostic factors and this study has also been extended to bladder cancer. (dkfz.de)
  • There are four major histological types of lung cancer: SCLC, 3 adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. (aacrjournals.org)
  • We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10 −6 ). (springer.com)
  • Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes, including the nevoid basal cell carcinoma (Gorlin) syndrome associated with germ-line PTCH mutations ( 4 ) and Turcot syndrome type 2 caused by germ-line APC mutations ( 5 ). (aacrjournals.org)
  • We investigated the antitumor effect of Cordyceps militaris extract (CME) on A549 cisplatin-resistant (CR) lung cancer cells. (usda.gov)
  • In breast cancer, some cells begin growing abnormally. (themainstreetmarket.com)
  • Breast cancer is considered a heterogeneous disease, meaning that it is a different disease in different women, a different disease in different age groups and has different cell populations within the tumor itself. (themainstreetmarket.com)
  • Some cancer cells are fast growing while others are slow. (themainstreetmarket.com)
  • Some cancer cells are stimulated by the estrogen in the body while others result from an out-of-control oncogene (cancer gene). (themainstreetmarket.com)
  • Lobular carcinoma in situ (LCIS) refers to abnormal cells in the lining of a lobule that seldom become invasive cancer. (themainstreetmarket.com)
  • The abnormal cells have not spread beyond the duct invading the surrounding breast tissue, but women with DCIS remain at an increased risk for invasive breast cancer. (themainstreetmarket.com)
  • Even when a tumor in the breast seems to have been completely removed or destroyed, the disease may return due to undetected cancer cells that remained in the body following treatment. (themainstreetmarket.com)
  • Purpose There is evidence to suggest that the breast cancer predisposing gene, BRCA1, is involved in cell cycle control and the response to damage but mouse brca1+/− heterozygotes have no distinctive phenotype. (lancs.ac.uk)
  • The ductal approach to breast cancer, encompassing nipple aspiration, ductal lavage and duct endoscopy, allows assessment of breast ductal epithelial cells and their local microenvironment in a graded process of increasing invasiveness. (biomedcentral.com)
  • Mutations in DNA damage responsive genes may reduce the effectiveness of checkpoint functions designed keep cells functioning normally and this can lead to the development of cancer. (renci.org)
  • Observations by Rudolf Virchow in the nineteenth century indicated a link between inflammation and cancer, and suggested that immune and inflammatory cells are frequently present within tumors. (frontiersin.org)
  • Many cancer risk factors are associated with a source of inflammation or act through inflammatory mechanisms such as those evoked by bacterial and viral infections ( 14 ), tobacco smoke ( 15 ), obesity ( 16 , 17 ), and aging or cell senescence ( 18 , 19 ). (frontiersin.org)
  • We also aimed to investigate whether there are other ATM mutations or variants contributing to breast cancer risk in our population. (biomedcentral.com)
  • We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. (biomedcentral.com)
  • protein
  • Combined with D-type (D1, D2, D3) cyclin, Cdk4/6 is activated and phosphorylates the retinoblastoma protein (Rb), promoting the escape of E2F from phosphorylated Rb, and therefore inducing cell transit from the G1 phase into the S phase. (spandidos-publications.com)
  • The tumor suppressor protein p53 is the primary regulator of the G 1 checkpoint ( 7 ). (aacrjournals.org)
  • 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)
  • notably
  • The 11q22.3 region notably encompasses genes such as ACAT1 , NPAT , and ATM . (springer.com)
  • Notably, the failure of uvsB mutants to restrain septum formation in the presence of DNA damage is suppressed by the musN227 mutation. (genetics.org)
  • growth
  • In most cases, it isn't clear what triggers abnormal cell growth in breast tissue, but doctors do know that between 5 percent and 10 percent of breast cancers are inherited. (ndri.com)
  • The musN227 mutation partially suppresses the poor growth and DNA damage sensitivity of uvsB mutants. (genetics.org)
  • senescence
  • Pathologies, as atherosclerosis, cardiac fibrosis, and cardiomyopathy, are often linked to the failure of cardiovascular tissue cells to reenter the cell cycle, namely, senescence, due to endogenous or exogenous causes. (hindawi.com)
  • This review will focus on the cardiovascular pathologies correlated to senescence, the effect of aging on the cardiac endogenous resources of stem cells, and the potential strategies of regenerative medicine to be applied to maintain the heart younger and healthier. (hindawi.com)
  • While it is commonly accepted as an aging-related phenomenon, senescence might happen also during the embryonic development with the biological meaning of replacing transient structures or specific cell types with other ones [ 3 - 5 ]. (hindawi.com)
  • eukaryotic
  • In eukaryotic cells, appropriate intracellular levels of ROS play a crucial role in regulating several biologic processes. (biomedcentral.com)
  • In eukaryotic cells, the Mre11-Rad50-Nbs1 (MRN) complex is fundamental for the response to DSBs, for the localization of the sites of damages and for the activation of ATM itself. (biomedcentral.com)
  • In addition to their checkpoint function, several observations suggest that the ATM kinases regulate additional facets of the eukaryotic DDR. (genetics.org)
  • expression
  • "Cloning and functional expression of a urea transporter from human bone marrow cells. (tcdb.org)
  • The use of techniques that produce a functional MUTATION or an effect on GENE EXPRESSION of a specific gene of interest in order to identify the role or activity of the gene product of that gene. (bioportfolio.com)
  • Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1 , ATM , and other genes. (springer.com)
  • BIND, REACTOME, HPRD, CPATH) with gene expression data generated for this project and visualization tools. (renci.org)
  • The genotoxins also produced unique time-dependent gene expression. (renci.org)
  • As expected, treatment with IR caused significantly less change in gene expression in ATM- and p53-deficient cell lines. (renci.org)
  • normal tissues
  • Differential cDNA library screening was performed on 7 human lung adenocarcinomas and 7 human lung squamous cell carcinomas and their corresponding adjacent normal tissues using a human lung cDNA library constructed from the normal bronchoalveolar cells of a 72-year-old male smoker. (aacrjournals.org)
  • Ninety-two genes/sequences were differentially expressed in adenocarcinomas and/or squamous cell carcinomas compared with their corresponding normal tissues. (aacrjournals.org)
  • human
  • "RACH2, a novel human gene that complements a fission yeast cell cycle checkpoint mutation. (tcdb.org)
  • In experimental metastasis models, the human breast carcinoma cell line MA-11 invariably disseminates to the central nervous system. (aacrjournals.org)
  • 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)
  • The Silencer Select Human Epigenetics siRNA Library is an excellent solution for investigating the impact of loss of gene function on developmental, disease, or evolutionary biology. (thermofisher.com)
  • The Silencer Select Human Epigenetics siRNA Library contains three siRNAs per target for 451 epigenetic enzymes, ensuring comprehensive coverage of epigenetics-based gene function studies. (thermofisher.com)
  • The Silencer Select Human Drug Targets siRNA Library contains three unique, non-overlapping siRNAs per target for 7,926 genes. (thermofisher.com)
  • clinical
  • 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)