• Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the importance of other tumor suppression mechanisms. (nature.com)
  • Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (nature.com)
  • To date, various mechanisms have been suggested to explain the powerful tumor-suppressive effect of p53, including the induction of cell cycle arrest, senescence, and apoptosis. (nature.com)
  • Depending on the severity of the DNA damage, the cells may no longer be able to undergo repair and either go through apoptosis or cell senescence. (wikipedia.org)
  • The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
  • In other situations the response is cell cycle arrest or programmed cell death (apoptosis), providing a barrier to further tumour development that the tumour may ultimately circumvent through the acquisition of a mutation in one of the genes within the stress-response pathway. (southampton.ac.uk)
  • They can trigger apoptosis, a process of programmed cell death, when a cell becomes irreparably damaged or poses a risk of becoming cancerous. (pharmiweb.com)
  • Research into apoptosis, necrosis, autophagy, and cellular senescence is very important for understanding the intracellular functions that control cell survival and death. (dojindo.com)
  • p53 is a tumor suppressor that has a central role in regulating cell cycle arrest, DNA repair, and apoptosis. (novusbio.com)
  • Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. (sagepub.com)
  • For example, panitumumab has been discovered to have an enhanced effect on radiation in the preclinical setting of upper aerodigestive tract cancer.8 Moreover, it has been found that the p53reactivating small-molecule RITA (reactivation of p53 and induction of tumor cell apoptosis), alone or in combination with cisplatin, can induce the reactivation of p53 in many HNSCC cell lines.9,10 However, this effect is not universal. (sagepub.com)
  • The HNSCC cell line JHU-028 can express wild type (wt) p53, but the cells do not undergo apoptosis in response to RITA treatment.10 Previously, we used RITA combined with X-ray to investigate the effect of RITA on X-ray susceptibility for the treatment of HSCC cell line FaDu (which is HPV-negative cell line) and found that RITA could enhance the radiation response of HSCC (data not shown). (sagepub.com)
  • p53 can activate a variety of signaling pathways to inhibit tumors, such as cell cycle arrest, cell senescence, apoptosis or iron death. (medicaltrend.org)
  • Consistently, KLF4 depletion from breast cancer cells restores p53 levels and causes p53-dependent apoptosis. (uu.nl)
  • The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS. (lookformedical.com)
  • With aging, the cell stops dividing: it does not respond to growth factors and becomes resistant to apoptosis. (vechnayamolodost.ru)
  • tumor suppressor p53 may induce cell cycle arrest or apoptosis in response to a variety of stress signals such as DNA damage oncogenic stimuli or hypoxia (reviewed in reference 49). (bio2009.org)
  • Here, we review the role of ferroptosis in p53-mediated tumor suppression, with a focus on what cellular factors are critical for p53-dependent ferroptosis during tumor suppression and how p53 modulates both the canonical (GPX4-dependent) and the non-canonical (GPX4-independent) ferroptosis pathways. (nature.com)
  • Cellular senescence is a phenomenon characterized by the cessation of cell division. (wikipedia.org)
  • Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. (wikipedia.org)
  • Cellular senescence can be initiated by a wide variety of stress inducing factors. (wikipedia.org)
  • Depletion of NAD+ can lead to DNA damage and cellular senescence in vascular smooth muscle cells. (wikipedia.org)
  • Two proteins, senescence-associated beta-galactosidase and p16Ink4A, are regarded as biomarkers of cellular senescence. (wikipedia.org)
  • Recently, the role of telomeres in cellular senescence has aroused general interest, especially with a view to the possible genetically adverse effects of cloning. (wikipedia.org)
  • BRAFV600E and Ras are two oncogenes implicated in cellular senescence. (wikipedia.org)
  • In this manuscript, we report the in vitro mutagenicity of waterpipe smoke condensate (WSC), the alteration in cellular parameters of lung alveolar cells in response to WSC exposure and discuss the implication of cellular responses in the pathophysiology of chronic obstructive pulmonary disease (COPD). (nih.gov)
  • However, WSC induced cell cycle arrest and cellular senescence mediated by the p53-p21 pathway. (nih.gov)
  • This is the multihit theory of tumorigenesis, in which a series of multiple triggering events in the genetic and cellular makeup of a cell ultimately cause cancer. (medscape.com)
  • Examples include exposure to toxic compounds or radiation, loss of contact with other cells or the extra-cellular matrix, lack of oxygen (hypoxia), acidic pH, the activation of oncogenes, induction of cellular senescence, oxidative damage or depletion of essential metabolites. (southampton.ac.uk)
  • CtBP activity is modified by UV radiation and glycolytic metabolism, suggesting that CtBPs regulate cell survival in response to cellular stress. (southampton.ac.uk)
  • Cellular senescence is a multifaceted process that arrests the proliferation of cells that are at risk of neoplastic transformation. (nature.com)
  • There is now substantial evidence that cellular senescence is a barrier to malignant tumorigenesis in vivo . (nature.com)
  • There is also mounting evidence that cellular senescence contributes to ageing. (nature.com)
  • Proliferating cells can initiate an additional response by adopting a state of permanent cell-cycle arrest that is termed cellular senescence. (nature.com)
  • Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing. (nature.com)
  • Campisi, J. Cellular senescence as a tumor-suppressor mechanism. (nature.com)
  • Tumor suppressor genes can promote cellular senescence, a state in which cells stop dividing, preventing the replication of damaged DNA. (pharmiweb.com)
  • Initiation and propagation of tumors reflect underlying genomic alterations such as mutations, polymorphisms, and copy number variations found in genes of multiple cellular pathways. (hindawi.com)
  • Irreversible cell cycle arrest is one of the phenomena that characterize cellular senescence. (dojindo.com)
  • The activation/upregulation of these proteins are used as indicators of cellular senescence. (dojindo.com)
  • Doxorubicin (DOX) is known as an anticancer drug that acts in the G2/M phase of the cell cycle to arrest cell proliferation and induce cellular senescence (see the upper left figure). (dojindo.com)
  • Cellular senescence is controlled by various factors such as cell type and physiological conditions, such as oxidative stress. (dojindo.com)
  • Therefore, it is desirable to determine and confirm cellular senescence using multiple indicators. (dojindo.com)
  • Common detection indicators for assessing cellular senescence include features related to cell cycle progression (DNA synthesis, p16/p21 expression, etc.), features related to morphology (of the cell, nucleus, nucleolus, etc. (dojindo.com)
  • Cellular senescence was reported by Hayflick in 1981. (dojindo.com)
  • Subsequent studies have revealed that cellular senescence is caused not only by telomere length reduction, but also by external factors such as oncogene activation, oxidative stress, and DNA damage. (dojindo.com)
  • The induction and control mechanisms of cellular senescence - in which genetic and external factors are intricately involved - have yet to be fully elucidated. (dojindo.com)
  • Recently, various fields have given particular attention to cellular senescence due to the recent discoveries of SASP (a known cancer-causing factor) and senescence-related phenomena in stem cell research. (dojindo.com)
  • Cellular senescence is a fundamental cellular program that is activated after a finite number of cell divisions and operates to avoid further cell proliferation. (plos.org)
  • In addition cellular senescence constitutes a tumor suppressor mechanism [1] , [2] . (plos.org)
  • The tumor suppressor pathways, ARF/MDM2/p53 and p16 INK4a /Rb, have been shown to play critical roles in the induction of cellular senescence [3] . (plos.org)
  • Normally, p53 allows cells to sense and respond to cellular stress such as DNA damage or hypoxia (2). (novusbio.com)
  • p53 can control diverse transcriptional programs to regulate senescence and cell death programs as well as cellular metabolism (2). (novusbio.com)
  • p53 integrates a variety of signals and allows cells to respond in a manner that is highly dependent on cellular context (2). (novusbio.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Because age-related cellular senescence and type 2 diabetes (T2D) have been recognised as risk factors for CRC development, the recent finding that type 2 diabetic patients present an elevated circulating volume of senescent cells raises the question whether type 2 diabetes facilitates the process of CRC tumorigenesis by inducing premature cell senescence. (frontiersin.org)
  • In this review, we will discuss the mechanisms according to which T2D induces cellular senescence and the role of type 2 diabetes-induced cellular senescence in the pathogenesis and progression of colorectal cancer. (frontiersin.org)
  • More recently, cellular senescence has been considered as an additional cause of age-related tumorigenesis. (frontiersin.org)
  • Senescence is a stress-response cellular state characterised by proliferative arrest but active metabolism ( 7 ). (frontiersin.org)
  • However, cellular senescence is not exclusive to ageing. (frontiersin.org)
  • Age-related and metabolic diseases such as type 2 diabetes (T2D) represent a source of cellular stress due to their disruptive effect on normal physiological processes and, therefore, can induce premature senescence ( 10 ). (frontiersin.org)
  • In this study, we investigated how higher-order chromatin structure modulates differential expression of the human INK4b-ARF-INK4a locus during progenitor cell differentiation, cellular ageing and senescence of cancer cells. (biomedcentral.com)
  • We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras -transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition. (aging-us.com)
  • Treatment of control ERas cells with PD0325901 for 24 h results in mitochondria damage and apoptotic death of a part of cellular population. (aging-us.com)
  • The INK and CIP/KIP families of cyclin dependent kinase inhibitors (CDKis) protect cells from oncogenic signals-initiated cellular transformation. (sigmaaldrich.com)
  • INK4a and INK4b are induced by oncogenic Ras and are involved in cell cycle G1 arrest and cellular senescence. (sigmaaldrich.com)
  • The hsa-miR-371-373 cluster (counteracting cellular senescence and linked with differentiation potency), as well as hsa-miR-520c/-520h (inhibiting the tumor suppressor p21) were 3.9-16.3 fold up-regulated in two of the three cisplatin resistant cell lines. (biomedcentral.com)
  • WM 1119 induces cell-cycle exit and cellular senescence, and inhibits growth of B-cell lymphoma cells in vitro (IC 50 = 0.25 μM). (rndsystems.com)
  • In order to protect against itself, special cellular mechanisms of tumor suppression have formed in the body. (vechnayamolodost.ru)
  • Even among cells which are genetically identically, single-cell sequencing of RNA or epigenetic modifications can reveal important cellular diversity. (technologynetworks.com)
  • Cellular senescence was first identified as a type of irreversible cell cycle arrest that occurs when cells reach the end of their replicative potential ( Hayflick and Moorhead, 1961 ). (rupress.org)
  • Senescent cells also undergo dramatic changes in their morphology and in the organization and architecture of their cellular compartments. (rupress.org)
  • A cellular process that selectively eliminates cells with mutations from further development through short-range cell-cell interaction. (bvsalud.org)
  • The tumor suppressor TP53 (also called p53) has been among the most extensively studied genes since its discovery in 1979 [ 1 , 2 ]. (nature.com)
  • Mutations in genes relating to genome maintenance has been linked with premature aging diseases, supporting the role of cell senescence in aging (see DNA damage theory of aging). (wikipedia.org)
  • Somatic mutations in other genes involved in cell growth are also needed for a melanoma to develop. (medlineplus.gov)
  • We also assessed the effect of WSC on the expression of genes involved in cell cycle arrest and inflammation. (nih.gov)
  • Although Brg1-containing complexes are not essential for general cell survival, they participate in transcriptional regulation of several hundred genes including those involved in interferon and stress response, immune cells differentiation, neurogenesis, cell cycle etc. and is absolutely necessary for mouse embryogenesis. (thermofisher.com)
  • p21 and other tumor suppressor genes' inactivation are therefore most likely involved in the first steps of the cancer model, with later stages possibly involving protooncogene activation and inflammation. (medscape.com)
  • Tumor suppressor genes code for proteins that inhibit cell division and growth, acting as a control mechanism to prevent excessive cell proliferation. (pharmiweb.com)
  • Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
  • Of the 31 genes, the 21 upregulated genes were primarily associated with cell paracrine and intracellular signaling, transcription regulation and cell adhesion and migration, and their transcriptional products included transforming growth factor-β2 (TGF-β2), insulin-like growth factor-binding protein 2 and transcriptional factor AP-2α/γ ( 11 ). (spandidos-publications.com)
  • The INK4/ARF locus encodes three tumor suppressor genes (p15 Ink4b , Arf and p16 Ink4a ) and is frequently inactivated in a large number of human cancers. (plos.org)
  • In addition, Kevetrin increased expression of p53 target genes such as p21 (Waf1), an inhibitor of cell cycle progression. (shu.edu)
  • BCLC9-miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes and up-regulate FOXO1 and FOXO3A gene expression. (oncotarget.com)
  • To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. (molcells.org)
  • Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. (sagepub.com)
  • In this study, using RNA sequencing data from the HSCC cell line FaDu, we aimed to screen differentially expressed genes (DEGs) between 8 Gy X-ray-treated FaDu cells and 0 Gy X-ray-treated FaDu cells, as well as those between 8 Gy X-ray + RITA treated FaDu cells and 8 Gy X-ray treated FaDu cells. (sagepub.com)
  • Additionally, a protein-protein interaction (PPI) network was constructed to identify key genes involved in enhanced X-ray susceptibility of FaDu cells treated with RITA. (sagepub.com)
  • Bioinformatic analyzing approaches were used to identified the over-expressed genes in prostate cancer tumor tissues from three GEO datasets. (biomedcentral.com)
  • p53 is one of the most important tumor suppressor genes, and more than half of cancer patients carry mutations in the p53 gene. (medicaltrend.org)
  • B lymphoma Moloney murine leukemia virus insertion region 1 homolog (BMI-1) is an oncogene which functions by regulating P16 and P19 cell cycle inhibitor genes and is also associated with erythroplakia and tongue cancer. (cancertools.org)
  • Prior to senescence, mutant RasV12 activation in primary human fibroblasts compromised mitosis, associated with abnormal expression of mitotic genes that enter M-phase. (nih.gov)
  • We describe the identification of KLF4 in a functional genomic screen for genes that bypass RASV12-induced senescence. (uu.nl)
  • Genes necessary for cell cycle progression, such as E2F-dependent genes, are incorporated into the SAHF and are thereby silenced, contributing to the stability of the growth arrest. (rupress.org)
  • Although senescent cells repress proliferation-promoting genes, they also induce the gene program necessary for the implementation of senescence. (rupress.org)
  • The transcriptional activation from CACNA1F the p21 gene by these inhibitors is normally marketed by chromatin redecorating pursuing acetylation of histones H3 and H4 in the p21 promoter area (32 54 This activation of p21 takes place within a p53-unbiased fashion and for that reason HDAC inhibitors are appealing realtors for cancers therapy being that they are operative in cells with mutated p53 genes a hallmark of several tumors. (bio2009.org)
  • Without p16(INK4A) to regulate cell growth and division (proliferation), cells can continue to grow and divide without control, which can lead to tumor formation. (medlineplus.gov)
  • In addition, we studied the effect of WSC on the proliferation and cell cycle of alveolar type II cells and vascular endothelial cells. (nih.gov)
  • We have also developed interests in other pathways which regulate gene transcription and cancer cell proliferation in response to stress and changes in cell metabolism. (southampton.ac.uk)
  • Role of CtBP transcriptional repressors in cancer cell proliferation and survival In common with p53, CtBP1 and CtBP2 proteins were discovered through their physical association with a viral oncoprotein. (southampton.ac.uk)
  • With its absence, the human body will be functioning without its "brake" of cell proliferation. (pharmiweb.com)
  • Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
  • CAFs provide cancer cells with nutrition and promote the proliferation, invasion and metastasis of cells ( 6 - 9 ). (spandidos-publications.com)
  • It was discovered when pulmonary fibroblasts slowed down their proliferation and eventually ended in cell death after cell passaging had been performed for more than 8 months. (dojindo.com)
  • Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo . (oncotarget.com)
  • Treatment of miR122 positive cells with an inhibitor of TGFBR1 activation, abolished tumor dormancy program and recovered cell proliferation rate through a Smad-independent TGF-β response. (oncotarget.com)
  • Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. (molcells.org)
  • Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target. (molcells.org)
  • CCK-8, plate colony formation and EdU assays were performed to assess the cell proliferation. (biomedcentral.com)
  • In addition, SNHG4 or RRM2 knockdown significantly induced cell cycle arrest and cell senescence, and inhibited DNA damage repair and cell proliferation, and the effects can be partially reversed by let-7a knockdown or RRM2 reoverexpression. (biomedcentral.com)
  • Developmentally regulated EZH2 levels are one of the factors that can determine the higher order chromatin structure and expression pattern of the INK4b-ARF-INK4a locus, coupling human progenitor cell differentiation to proliferation control. (biomedcentral.com)
  • Development and homeostasis require the coordinate regulation of cell proliferation and differentiation. (biomedcentral.com)
  • Bruggeman SWM, Valk-Lingbeek ME, van der Stoop PPM, Jacobs JJL, Kieboom K, et al: Ink4A and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. (karger.com)
  • Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signalling. (nih.gov)
  • However, in untransformed cells, KLF4 acts as a potent inhibitor of proliferation. (uu.nl)
  • Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. (lookformedical.com)
  • Tissue regeneration occurs due to the proliferation of stem cells, which can not only divide, but also differentiate into cells of the tissue whose regeneration is taking place. (vechnayamolodost.ru)
  • Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)
  • miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. (oncotarget.com)
  • HCC stem-like cells can be directed towards cell differentiation and tumor dormancy by restoring miR122 expression. (oncotarget.com)
  • We found that INK4b and INK4a , but not ARF , are upregulated following the differentiation of haematopoietic progenitor cells, in ageing fibroblasts and in senescing malignant rhabdoid tumour cells. (biomedcentral.com)
  • During progenitor cell differentiation and ageing, PcG silencer EZH2 attenuates, causing loss of PRC binding and transcriptional activation of INK4b and INK4a . (biomedcentral.com)
  • Primary Human bronchial epithelial cells when grown in vitro have a limited lifespan and begin to deviate both in phenotype and morphology, losing the plasticity required around passage 4 or 5, for air-liquid interface (ALI) differentiation. (cancertools.org)
  • These Human bronchial epithelial cells expressing BMI-1 retain both viability and differentiation potential of wild-type human bronchial epithelium while importantly not demonstrating changes in cell karyotype. (cancertools.org)
  • Normal human bronchial epithelial cells were grown in a growth factor-supplemented medium and differentiated at ALI in bronchial epithelial differentiation medium. (cancertools.org)
  • 2 The authors applied their DC3 method in the joint analysis of scRNA-seq, single-cell ATAC sequencing (scATAC-seq) and bulk chromatin immunoprecipitation (Hi-ChIP) on mouse embryonic stem cells after four days of retinoic acid-induced differentiation. (technologynetworks.com)
  • Induction of p21 expression by genotoxic stress and its role during terminal differentiation of various cell types have been investigated intensively. (bio2009.org)
  • While p21 is usually activated by p53-dependent mechanisms in response to DNA damage to make sure cell cycle arrest and repair a number of realtors that promote differentiation like phorbol ester 67346-49-0 or okadaic acidity can up-regulate p21 separately of p53 (for an assessment see reference point 16). (bio2009.org)
  • Senescent cells contribute to the aging phenotype, including frailty syndrome, sarcopenia, and aging-associated diseases. (wikipedia.org)
  • Although senescent cells can no longer replicate, they remain metabolically active and commonly adopt an immunogenic phenotype consisting of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE), and stain positive for senescence-associated β-galactosidase activity. (wikipedia.org)
  • Senescent cells can undergo conversion to an immunogenic phenotype that enables them to be eliminated by the immune system. (wikipedia.org)
  • This phenotype consists of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE) and stain positive for senescence-associated β-galactosidase activity. (wikipedia.org)
  • CAFs maintain their phenotype for numerous passages during culture in vitro without exposure to cancer cells, while NFs cannot be infinitely proliferous like cancer cells ( 10 ). (spandidos-publications.com)
  • According to recent data, Ras-transformed cells require autophagy to survive and maintain malignant phenotype [ 5 - 10 ]. (aging-us.com)
  • Moreover, we describe for the first time an association of the up-regulation of micro-RNA species such as hsa-miR-512-3p/-515/-517/-518/-525 and down-regulation of hsa-miR-99a/-100/-145 with a cisplatin resistant phenotype in human germ cell tumors. (biomedcentral.com)
  • The Warburg phenotype provides tumors an enhanced resistance against cytotoxic insults. (springer.com)
  • The senescence-associated secretory phenotype (SASP) is a hallmark of senescence with an important physiological impact, but how it is established is unclear. (rupress.org)
  • Once activated, p53 coordinates multiple downstream pathways, thereby maintaining the homeostasis of the host cell or organism (if the stress is mild, transient, and repairable) or eliminating damaged cells (if the stress is acute, prolonged, and difficult to resist). (nature.com)
  • In single celled organisms these pathways are generally involved in ensuring the survival and replication of the individual cell. (southampton.ac.uk)
  • Stress-response pathways play a key role in the patho-physiology and treatment of many diseases, including cancer.At almost every stage of the development of a tumour, cells are exposed to some form of stress. (southampton.ac.uk)
  • Many current and prospective treatments for cancer work by either inhibiting, or re-activating stress response pathways.Our work focuses on the role of regulators of gene transcription in the response of cancer cells to stress. (southampton.ac.uk)
  • A particular interest of our work has been how HDM2 and HDMX protein synthesis is controlled in response to cell-signalling pathways in different cell types, and how this affects p53 function in these cells. (southampton.ac.uk)
  • Two powerful tumour suppressor pathways, controlled by the p53 and retinoblastoma (pRB) proteins, are important for establishing and maintaining the senescence growth arrest. (nature.com)
  • These pathways respond to somewhat different stimuli but interact and cooperate to control the senescence response. (nature.com)
  • Figure 4: Senescence controlled by the p53 and p16-pRB pathways. (nature.com)
  • These marker proteins are known to be tumor suppressors and regulate the cell cycle mainly through two pathways (p16Ink4a-RB and p53-p21CIP1). (dojindo.com)
  • The scientists identified two key pathways involved in cell dormancy and used miniature bowel tumours grown from the cells of mice with cancer, to test different drugs targeting these pathways. (manufacturingchemist.com)
  • p53-mediated ferroptosis is required for its tumor suppression in mouse models. (nature.com)
  • What is the physiological ferroptosis inducer(s) for p53 during tumor suppression? (nature.com)
  • Senescent cells affect tumour suppression, wound healing and possibly embryonic/placental development and a pathological role in age-related diseases. (wikipedia.org)
  • Sager, R. Senescence as a mode of tumor suppression. (nature.com)
  • The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. (aging-us.com)
  • Our data show that suppression of MEK/ERK pathway in senescent cells provides a new strategy for elimination of Ras-expressing cells. (aging-us.com)
  • KLF4 (GKLF/EZF) encodes a transcription factor that is associated with both tumour suppression and oncogenesis. (uu.nl)
  • Senescent cells display persistent DDR that appears to be resistant to endogenous DNA repair activities. (wikipedia.org)
  • Such senescent cells in mammalian culture and tissues retain DSBs and DDR markers. (wikipedia.org)
  • The nucleus of senescent cells is characterized by senescence-associated heterochromatin foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS). (wikipedia.org)
  • Figure 5: Potential deleterious effects of senescent cells. (nature.com)
  • Scientists have discovered that, in the absence of resident stem cells, senescent cells can instruct neighboring somatic cells to reprogram. (dojindo.com)
  • None of the individual biomarkers that have been identified so far have been deemed to be specific to senescent cells. (dojindo.com)
  • The development of drugs that eliminate senescent cells in the body (senolytic drugs) is also attracting the attention of researchers as a possible strategy to extend healthy life expectancy. (dojindo.com)
  • Over lifetime, due to the action of several stressors such as DNA damage and telomere shortening, senescent cells accumulate in the organism and release a variety of pro-inflammatory cytokines responsible for low-grade inflammation. (frontiersin.org)
  • Senescent ERas cells do not develop cytoprotective autophagy upon inhibition of MEK/ERK pathway due to spatial dissociation of lysosomes and autophagosomes in the senescent cells. (aging-us.com)
  • Senescent cells are unable to form the autophagolysosomes and to remove the damaged mitochondria resulting in apoptotic death. (aging-us.com)
  • However, the accumulation of senescent cells can have detrimental consequences, such as in age-related pathologies. (rupress.org)
  • It is widely recognized that the accumulation of various harmful genetic alterations in normal cells may induce malignant cancer cells ( 1 ). (spandidos-publications.com)
  • Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
  • It turned out that old cells, on the one hand, act as tumor suppressors (since they irreversibly stop dividing themselves and reduce the risk of transformation of surrounding cells), and on the other hand, the specific metabolism of old cells can cause inflammation and degeneration of neighboring precancerous cells into malignant ones. (vechnayamolodost.ru)
  • But at the same time, renewing tissues are subject to hyperproliferation, which leads to the formation of tumors, including malignant ones. (vechnayamolodost.ru)
  • The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53 em2Hwl /Korl KO mice. (biomedcentral.com)
  • This protein prevents tumor cell growth at several points during the malignant process when it is under many types of stress, including DNA damage, oncogene activation, hypoxia, telomere attrition and deficiency of normal growth signal [ 3 ]. (biomedcentral.com)
  • At 15 to 25 weeks of age, the homozygote variants of these mice were found to be dramatically susceptible to the development of multiple tumor types, and malignant lymphoma and sarcomas were frequently observed in the thymus and major visceral organs of these animals [ 9 ]. (biomedcentral.com)
  • von Hippel-Lindau (VHL) disease, or von Hippel-Lindau syndrome, is a rare genetic disorder characterized by visceral cysts and benign tumors in multiple organ systems that have subsequent potential for malignant change. (medscape.com)
  • Clinical hallmarks of VHL disease include the development of retinal and central nervous system (CNS) hemangioblastomas (blood vessel tumors), pheochromocytomas , multiple cysts in the pancreas and kidneys, and an increased risk for malignant transformation of renal cysts into renal cell carcinoma. (medscape.com)
  • This locus encodes both p16 INK4a , which prevents inactivation of the tumor suppressor RB, and p19 ARF , which stabilizes the tumor suppressor p53 [7] , [8] . (plos.org)
  • In addition, miR122 transfected cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein inactivation. (oncotarget.com)
  • Inactivation of CDKN2A and CDKN2B are found in a wide variety of human malignancies and murine tumor models. (sigmaaldrich.com)
  • Remarkably, inactivation of the cyclin-D1 target and the cell-cycle inhibitor p21CIP1 not only neutralizes the cytostatic action of KLF4, but also collaborates with KLF4 in oncogenic transformation. (uu.nl)
  • The DNA damage response (DDR) arrests cell cycle progression until DNA damage, such as double-strand breaks (DSBs), are repaired. (wikipedia.org)
  • However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. (medlineplus.gov)
  • Studies have focused on the genetic and epigenetic status of CAFs, since they are critical in tumor progression and differ phenotypically and functionally from normal fibroblasts. (spandidos-publications.com)
  • Finally, CAFs promote cancer progression and act in cancer cell drug resistance. (spandidos-publications.com)
  • As a result, changes in SA-ß-Gal expression, cell cycle progression, and mitochondrial membrane potential were observed. (dojindo.com)
  • We have reported that the expression of BMI1 , a member of PcG, in hematopoietic stem cells or progenitor cells predicts the prognosis of patients with MDS and progression to acute leukemia. (karger.com)
  • Telomere shortening is involved in the progression of CELL AGING. (lookformedical.com)
  • Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. (springer.com)
  • In this way, p16(INK4A) controls cell division. (medlineplus.gov)
  • Cells begin to produce p16(INK4A) when they are no longer able to undergo cell division. (medlineplus.gov)
  • CDKN2A gene mutations involved in cancer impair production of functional p16(INK4A) or, less commonly, p14(ARF), which can result in uncontrolled cell growth and tumor formation. (medlineplus.gov)
  • Finally, we demonstrate that Polycomb proteins and associated epigenetic marks are crucial for the control of the replication timing of the INK4a/ARF locus during senescence. (plos.org)
  • Agherbi H, Gaussmann-Wenger A, Verthuy C, Chasson L, Serrano M, Djabali M (2009) Polycomb Mediated Epigenetic Silencing and Replication Timing at the INK4a/ARF Locus during Senescence. (plos.org)
  • In the absence of Bmi1, M33, or Phc2, primary embryonic fibroblasts (MEFs) are unable to progress into S phase, undergo premature senescence after only a few passages in culture and show an increased accumulation of the tumor suppressors p16 INK4a , p19 ARF and p15 INK4b [4] , [10] . (plos.org)
  • The INK4b-ARF-INK4a tumour suppressor locus controls the balance between progenitor cell renewal and cancer. (biomedcentral.com)
  • The INK4b-ARF-INK4a tumor suppressor locus (Figure 1A ) plays a central role in controlling the equilibrium between progenitor cell renewal and cancer risk [ 1 - 8 ]. (biomedcentral.com)
  • also known as CDK4I, Cyclin-dependent kinase 4 inhibitor A, Multiple tumor suppressor 1, MTS-1, p16-INK4, p16-INK4a, p16INK4A) is encoded by the CDKN2A (also known as CDKN2, MTS1) gene (Gene ID 1029) in human. (sigmaaldrich.com)
  • BMI-1 is thought to repress, p16(Ink4a), a cyclin-dependent kinase inhibitor and tumor suppressor that induces cell cycle arrest at the Gap 1 phase. (cancertools.org)
  • The defining characteristic of senescence is a highly stable cell cycle arrest, triggered by the up-regulation of cyclin-dependent kinase inhibitors such as p16 INK4a and p21 CIP1a . (rupress.org)
  • However, this results in a false positive for cells that naturally have these two proteins such as maturing tissue macrophages with senescence-associated beta-galactosidase and T-cells with p16Ink4A. (wikipedia.org)
  • Both proteins are also involved in stopping cell division in older cells (senescence). (medlineplus.gov)
  • These proteins help regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. (medlineplus.gov)
  • The p14(ARF) and p53 proteins are often made in cells that are unable to undergo cell division. (medlineplus.gov)
  • Together, the germline and somatic mutations impair the function of proteins that regulate division and senescence, leading to uncontrolled cell growth and the formation of a melanoma. (medlineplus.gov)
  • Some Example Projects: Regulation of HDM2 and HDMX proteins The HDM2 oncoprotein is the major negative regulator of p53 function in the cell. (southampton.ac.uk)
  • Many tumor suppressor proteins play a role in DNA repair, helping to correct genetic mutations and maintain the stability of the genome. (pharmiweb.com)
  • Some tumor suppressor proteins are involved in maintaining cell adhesion, preventing cells from breaking away and spreading to other parts of the body (metastasis). (pharmiweb.com)
  • Cell adhesion molecules are a diverse group of proteins that play a crucial role in mediating cell-to-cell interactions and cell-to-extracellular matrix interactions. (pharmiweb.com)
  • Our results suggest that in young cells Polycomb proteins are recruited to the INK4/ARF locus through CDC6 and the resulting silent locus is replicated during late S-phase. (plos.org)
  • Evidence supporting the direct control of the cell cycle by Pc-G proteins in vertebrates came from studies on mouse Bmi1 mutants. (plos.org)
  • This is mainly because there are many proteins that regulate p53 levels in cells, the most important of which is MDM2. (medicaltrend.org)
  • According to this model, it is speculated that if p53 can not be inhibited by various negative transcriptional regulatory proteins, even if its level is not significantly increased, it may be able to exert its normal tumor suppressor function. (medicaltrend.org)
  • Next, in a classic pancreatic ductal adenocarcinoma (PDAC) model, the author once again observed the tumor suppressor effect of p53KQ/KQ. (medicaltrend.org)
  • For instance, single-cell RNA, assay for transposase-accessible chromatin (ATAC) and chromosome conformation (Hi-C) sequencing offers information on gene expression profiling, accessible chromatin regions and chromatin contacts, respectively. (technologynetworks.com)
  • Can ferroptosis be specifically induced in tumors but not in normal tissues? (nature.com)
  • They facilitate adhesion between leukocytes and endothelial cells, enabling leukocyte extravasation into tissues during inflammation. (pharmiweb.com)
  • Ig-superfamily CADMs are involved in mediating cell-to-cell adhesion, helping cells stick together and form tissues and organs. (pharmiweb.com)
  • Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. (molcells.org)
  • We examined 72 samples and compared the composition of immune cell infiltration, vascularization, the thickness of the peri-implant tissues, the severity of fibrotic processes and α-SMA expression in myofibroblasts. (bvsalud.org)
  • Currently, clinical trials are underway of drugs that selectively eliminate old cells in organs and tissues, thereby preventing degenerative changes in organs and cancer. (vechnayamolodost.ru)
  • In our body, there are renewing tissues in which there is a pool of constantly dividing cells that replace spent or dying cells. (vechnayamolodost.ru)
  • Stem cells that exist in almost all organs and tissues are able to divide indefinitely. (vechnayamolodost.ru)
  • Stem cells are present in the myocardium, in the brain (in the hypocampus and in the olfactory bulbs) and in other tissues. (vechnayamolodost.ru)
  • However, when cells in tissues are sequenced in bulk, rare cells are diluted and averaged out. (technologynetworks.com)
  • Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
  • Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
  • Theoretically, it is possible upon the discovery of the exact mechanism of biological immortality to genetically engineer cells with the same capability. (wikipedia.org)
  • Recently, evidence has been accumulating on the molecular mechanism underlying self-renewal of stem cells. (karger.com)
  • In a Cell review in 2009, he put forward a new view on the mechanism of p53. (medicaltrend.org)
  • The initiation and development of tumor cell is accompanied by elevated stresses, such as oncogene activation, DNA damage, genome instability, and reprogrammed tumor metabolism. (nature.com)
  • Upon senescence, Jmjd3 is overexpressed and the MLL1 protein is recruited to the locus provoking the dissociation of Polycomb from the INK4/ARF locus, its transcriptional activation and its replication during early S-phase. (plos.org)
  • 1. Artelt P, Grannemann R, Stocking C, Friel J, Bartsch J, Hauser H. The prokaryotic neomycin-resistance-encoding gene acts as a transcriptional silencer in eukaryotic cells. (koreamed.org)
  • ERK-dependent transcriptional up-regulation of Mcl1 was responsible for enhanced slippage of cells with mitotic defects and subsequent cell survival. (nih.gov)
  • We propose that activated Ras induces transcriptional changes that predispose cells undergoing OIS to mitotic stress and multinucleation. (nih.gov)
  • The tumor suppressor p53 directly interacts with Sp1 and may compete with the transcriptional repressor HDAC1 for binding to the C terminus of Sp1 leading to histone acetylation and concomitant manifestation of p21. (bio2009.org)
  • Researchers have recently discovered Mdm2 in human tumors and these scientists hypothesize that Mdm2 plays a role in tumorigenesis, with or without p53. (shu.edu)
  • Cisplatin (cis-diamminedichloroplatinum II, CDDP) is a chemotherapeutic agent widely used in the treatment of several solid tumors, among them testicular cancer, lung cancer, breast cancer, and bladder cancer. (biomedcentral.com)
  • Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53 em2Hwl /Korl KO mice, but were not detected in C57BL/6-Trp53 em1Hwl /Korl KO mice. (biomedcentral.com)
  • Activation of p53 efficiently counteracts deacetylase-mediated repression and induces cell cycle arrest by activating the p21 gene. (bio2009.org)
  • This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. (biomedcentral.com)
  • The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. (wikipedia.org)
  • These molecules are essential for embryonic development, wound healing, immune cell recognition, and many other physiological functions. (pharmiweb.com)
  • In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. (wikipedia.org)
  • In fact, several studies have shown that T2D induces senescence in multiple types of cells, including fibroblasts and endothelial cells ( 11 , 12 ). (frontiersin.org)
  • Mutations occur rarely, and in order for a cell to become cancerous - this is calculated for human fibroblasts - about 100 divisions must occur (this number of divisions usually occurs in a person at about the age of 40) [5]. (vechnayamolodost.ru)
  • This process is known as "replicative senescence", or the Hayflick limit. (wikipedia.org)
  • Mechanistically, replicative senescence can be triggered by a DNA damage response due to the shortening of telomeres. (wikipedia.org)
  • This induces replicative senescence. (wikipedia.org)
  • A classic paper that describes the limited replicative lifespan of normal human cells. (nature.com)
  • One of them is the replicative aging of cells (senescence), which consists in the irreversible stopping of cell division at the G1 stage of the cell cycle. (vechnayamolodost.ru)
  • [ 6 ] These events lead the cancer cell to escape normal cell growth and control mechanisms, to avoid system control mechanisms (ie, immunologic surveillance), and to establish a nutrient supply. (medscape.com)
  • Hence, it is of great importance to investigate the mechanisms that induce enzalutamide resistance in prostate cancer cells. (biomedcentral.com)
  • Cancer cells exploit a variety of protective mechanisms that allow them to acquire selective advantage and proliferate under unfavorable conditions. (aging-us.com)
  • One of the mechanisms of high basal autophagy activity in cancer Ras-expressing cells might be associated with high PP2A phosphatase activity targeting directly ULK1-Ser757 that could explain apparent contradiction: maintenance of high mTORC1 functions and high autophagic activity simultaneously [ 22 ]. (aging-us.com)
  • We compared microRNA expression patterns in three cisplatin resistant sublines derived from paternal cisplatin sensitive germ cell tumor cell lines in order to improve our understanding of the mechanisms of cisplatin resistance. (biomedcentral.com)
  • Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS. (lookformedical.com)
  • In recent years, molecular mechanisms of cell aging, their connection with oncological diseases and inflammation have been discovered. (vechnayamolodost.ru)
  • Up to 70% of hepatocellular carcinomas (HCC) show miR122 down-regulation [ 6 ] and the same applies for HCC-derived cell lines [ 7 ]. (oncotarget.com)
  • This is due to irregularities in the regulation of cell division and an increased frequency of mutagenesis in actively dividing cells. (vechnayamolodost.ru)
  • p21 has been recognized by virtue of its activation by p53 (13) its association with cyclin/cyclin-dependent kinase (CDK) complexes (23 66 and its up-regulation during senescence (47). (bio2009.org)
  • A tumor suppressor gene, also known as anti-onco gene, is an essential component of the body's defense against cancer. (pharmiweb.com)
  • Similarly, for p53 to function as a tumor suppressor gene, it also needs to get rid of MDM2-mediated degradation, so as to stabilize the p53 protein to function. (medicaltrend.org)
  • The p53 tumour suppressor protein is a key component of one such stress-response pathway, and virtually all cancers loose functionality of the p53-stress response pathway. (southampton.ac.uk)
  • Moreover, we show that the Polycomb protein BMI1 interacts with CDC6, an essential regulator of DNA replication in eukaryotic cells. (plos.org)
  • Reduction in tumor size in BCLC9-miR122 associated with an increase in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to phospho-p38 ratio. (oncotarget.com)
  • In cells, p53 is a very unstable protein with a short half-life. (medicaltrend.org)
  • The traditional theory is that when cells are stimulated, the binding of MDM2 and p53 will be destroyed, leading to the accumulation of p53 protein, which affects downstream gene expression and enables cells to respond to the stimulus. (medicaltrend.org)
  • In summary, the authors used p53 transgenic animal models to prove that the stability of p53 protein and the increase in protein levels are not necessary conditions for its tumor suppressor function. (medicaltrend.org)
  • Although DNA damage and other stimuli can significantly increase the level of p53 protein, this is not necessarily the case in the p53 tumor suppressor function. (medicaltrend.org)
  • Expression of polycomb protein BMI-1 maintains the plasticity of basal bronchial epithelial cells. (cancertools.org)
  • A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. (lookformedical.com)
  • Furthermore the p21 protein was shown previously to interact 67346-49-0 with the proliferating cell nuclear antigen (PCNA) thereby preventing DNA replication (10). (bio2009.org)
  • The foamy stromal cells between the capillaries stain positive for glial fibrillary acid protein and neuron-specific enolase. (medscape.com)
  • Macroautophagy (hereafter referred to as autophagy) plays an important role in cancer cells survival upon various conditions of intra- and extracellular stress. (aging-us.com)
  • Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53 em2Hwl /Korl and C57BL/6-Trp53 em1Hwl /Korl knockout (KO) mice over 16 weeks. (biomedcentral.com)
  • p53's ability to inhibit tumors can be considered as a specific outcome of its stress-responsive effects. (nature.com)
  • He has also examined the cooperativity of Withaferin A with other interventions that are known to inhibit gliomas such as combination therapies of Withaferin A with temozolomide, with other ginsenosides and with alternating electric fields (known as tumor treating fields or TTFields). (stanford.edu)
  • Cells are potent to go under abnormal growth processes and finally lead to tumor/cancer. (pharmiweb.com)
  • 3) p53 null mice develop tumors with 100% penetrance. (nature.com)
  • Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA. (koreamed.org)
  • We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. (molcells.org)
  • This led to the tumours collapsing in the mice - dormant cells disappeared and the tumour stopped growing. (manufacturingchemist.com)
  • Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice over 16 weeks. (biomedcentral.com)
  • Numerous Trp53 KO mice containing large deletions of the Trp53 gene have been produced to investigate the role of Trp53 during the developmental process or tumor formation in mammals. (biomedcentral.com)
  • The first Trp53 KO mice were generated by the recombination of intron 4 and exon 5 in C57BL/6 mice using embryonic stem cell (ESC) targeting techniques. (biomedcentral.com)
  • Similar tumors were also observed in KO mice having the exon 2 or exon 2-6 deletion in C57BL/6 mice. (biomedcentral.com)
  • Hayflick, L. The limited in vitro lifetime of human diploid cell strains. (nature.com)
  • Hayflick LimitThe phenomenon of cell aging was first discovered in 1961 by Leonard Hayflick and colleagues on fibroblast culture. (vechnayamolodost.ru)
  • It turned out that cells in human fibroblast culture live for a limited time under good conditions and are able to double approximately 50±10 times, and this number was called the Hayflick limit [6, 7]. (vechnayamolodost.ru)
  • Without one of these tumor suppressors, cells can grow and divide unchecked, leading to the development of cancer. (medlineplus.gov)
  • Mutations in the CDKN2A gene are also associated with melanoma, a type of skin cancer that begins in pigment-producing cells called melanocytes. (medlineplus.gov)
  • In turn, as a result of research into the abnormal cancer cell, the basic understanding of the cell has greatly improved. (medscape.com)
  • Cancer is characterized by uncontrolled growth and division of a cell, with extension beyond the normally limiting basement membrane and through the boundaries of normal cells. (medscape.com)
  • In the late 1990s work from a number of groups, including Blaydes et al , demonstrated that HDM2 could be targeted in cancer cells to re-activate the p53 stress-response pathway. (southampton.ac.uk)
  • We have undertaken a series of projects examining how HDM2, and its paralogue HDMX is regulated in cancer cells (see Phillips et al, 2010, 2008, 2007, 2006a, 2006b and Phelps et al 2005, 2003). (southampton.ac.uk)
  • References 2 and 3 describe the characteristics of cancer cells and the importance of mutations in cancer development. (nature.com)
  • Based on the heterogeneity within a specific tumor type, a combination of genomic alterations defines the cancer subtype, biologic behavior, and in some cases, response to therapeutics. (hindawi.com)
  • Consideration of tumor heterogeneity is therefore important in the critical analysis of gene associations in cancer. (hindawi.com)
  • The relationship between p53 and Mdm2 has been shown to be vital to the normal functioning of the human cell, and also has other implications in cancer. (shu.edu)
  • Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. (koreamed.org)
  • In 2012, he became a member of the Canary Center at Stanford University where he has leveraged his experience in cell and preclinical studies to develop imaging modalities to track therapeutic responses against cancer as well as detecting early stage cancers. (stanford.edu)
  • He also has professional interests in stem cell research, the biology of aging, cancer as well as telomere and telomerase biology. (stanford.edu)
  • An antifungal medication, commonly prescribed for toenail infections, could help eliminate dormant cells within bowel tumours, according to new research funded by Cancer Research UK and published in the Journal of Experimental Medicine . (manufacturingchemist.com)
  • Dr Simon Buczacki, co-lead author and Cancer Research UK clinician scientist, said: "One of the biggest challenges in treating any cancer is the diversity of different cells within the same tumour. (manufacturingchemist.com)
  • We have targeted a type of cell that lies asleep within bowel tumours, remaining unresponsive to treatment and putting the patient at risk of their cancer coming back. (manufacturingchemist.com)
  • The Cambridge team characterised the molecular nature of dormant bowel cancer cells. (manufacturingchemist.com)
  • Tumours are made up of many different types of cancer cells, which can evolve separately and respond to treatments differently. (manufacturingchemist.com)
  • The presence of drug-resistant, dormant tumour cells is a problem in many types of cancer. (manufacturingchemist.com)
  • If we find ways to target these cells in bowel cancer, it might provide insights into tackling the problem of dormant tumour cells more broadly. (manufacturingchemist.com)
  • Prostate cancer threatens the health of men over sixty years old, and its incidence ranks first among all urinary tumors among men. (biomedcentral.com)
  • Enzalutamide remains the first-line drug for castration-resistant prostate cancer, however, tumors inevitably become resistant to enzalutamide. (biomedcentral.com)
  • Despite a large number of promising inhibitors for Ras/Raf/MEK/ERK pathway, recent works show that cancer cells often develop an autophagy-dependent resistance to inhibitors of Ras pathway [ 16 ]. (aging-us.com)
  • There is emerging evidence indicating that the PcG complexes are indispensable for sustaining stem cell activity and cancer stem cells. (karger.com)
  • Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold) in all three cell lines. (biomedcentral.com)
  • Cancer Lett, 300:215-224.doi:10.1016/j. squamous cell carcinoma in north-eastern Iran. (who.int)
  • 99:209 -215.doi:10.1007/s11060 - 010 - 0129 -5 cell carcinoma-a population-based study in with and without cervical cancer in Tbilisi, Georgia. (who.int)
  • An image depicting head and neck squamous cell carcinoma in vitro can be seen below. (medscape.com)
  • Head and neck squamous cell carcinoma in vitro (cell culture). (medscape.com)
  • However, the debate regarding which single function of p53 is absolutely critical for its tumor suppressor role is ongoing [ 7 ]. (nature.com)
  • Another important function of p53 is to respond to environmental stimuli and help cells overcome difficulties caused by various stresses, including DNA damage, excessive ROS, and insufficient nutrients. (medicaltrend.org)
  • Brg1 is also involved in cell growth arrest, senescence and tumour supression. (thermofisher.com)
  • Further, PARP-1 and PARP-1 fragment's involvement in various forms of cell death e.g. autophagy, necrosis and parthanatos are also indicated. (shu.edu)
  • Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels via the extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway. (biomedcentral.com)
  • Mutations in the CDKN2A gene are found in up to one-quarter of head and neck squamous cell carcinomas (HNSCC). (medlineplus.gov)
  • It forces cells back into a short cycle of growth before slamming on an irreversible 'stop' button, entering a permanent standstill that's known as senescence. (manufacturingchemist.com)
  • VCAMs are involved in mediating the adhesion of leukocytes to vascular endothelial cells, facilitating the recruitment of immune cells during inflammation. (pharmiweb.com)
  • PECAM-1 is expressed on the surface of platelets and endothelial cells and is involved in cell adhesion and signaling during immune responses. (pharmiweb.com)
  • In 2002, he joined Stanford University where he initially utilized his experience from Geron Corporation to research cardiovascular and endothelial progenitor cell function. (stanford.edu)
  • [ 2 ] Diagnosed in 50% of patients with VHL disease, these hemangiomas are composed of endothelial cells and pericytes. (medscape.com)
  • Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, et al: Polycomb complexes repress developmental regulators in murine embryonic stem cells. (karger.com)
  • These mutations, classified as germline mutations, are typically inherited and are present in essentially all of the body's cells. (medlineplus.gov)
  • Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
  • Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. (koreamed.org)
  • In some circumstances, the activation of a stress-response pathway will actually help the tumour cell to survive and proliferate. (southampton.ac.uk)
  • Telomeres are DNA tandem repeats at the end of chromosomes that shorten during each cycle of cell division. (wikipedia.org)
  • The successive shortening of the chromosomal telomeres with each cell cycle is also believed to limit the number of divisions of the cell, contributing to aging. (wikipedia.org)
  • Keeps telomeres long a) Found in what cell type? (freezingblue.com)
  • ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
  • RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (lookformedical.com)
  • Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. (lookformedical.com)
  • Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. (koreamed.org)
  • Western Blotting Analysis: A 1:500 dilution of this antibody detected p16INK4a in 10 µg of HEK293 cell lysate. (sigmaaldrich.com)
  • In vitro and in vivo experiments showed that SNHG4 overexpression markedly enhanced cell resistance to enzalutamide. (biomedcentral.com)
  • We created an in vitro model of acquired cisplatin resistance by long term exposure of three well established germ cell tumor cell lines to cisplatin, resulting in sublines with significantly increased resistance to cisplatin. (biomedcentral.com)
  • Cells grown in vitro from neoplastic tissue. (lookformedical.com)