• Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. (hindawi.com)
  • Cellular senescence is a multifaceted process that arrests the proliferation of cells that are at risk of neoplastic transformation. (nature.com)
  • With its absence, the human body will be functioning without its "brake" of cell proliferation. (pharmiweb.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)
  • Instead of devolving into unchecked proliferation, it undergoes a permanent arrest of the cell cycle which could prevent cancers from growing rapidly. (sens.org)
  • 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)
  • 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)
  • Genes involved in cell proliferation and extracellular matrix production are down-regulated while genes promoting apoptosis are upregulated. (jcadonline.com)
  • 13 Thus, the application of radiation therapy following surgery appears to prevent keloid scar recurrence by decreasing fibroblast proliferation, arresting the cell cycle and inducing premature cellular senescence. (jcadonline.com)
  • 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)
  • Indeed, this process is controlled by the same oncoproteins and tumor suppressors that normally control cell cycle progression, cell differentiation, and cell proliferation. (oncotarget.com)
  • Senescent cells continue to survive and resist apoptosis, yet the cell cycle is arrested to prevent further proliferation [ 11 ]. (biomedcentral.com)
  • catenin signaling and influences CRC cell proliferation and experiments in CRC cell lines and an tumor xenograft model. (immune-source.com)
  • The oncoprotein murine double minute 2 (MDM2) promotes cell survival, proliferation, invasion, and therapeutic resistance in many types of cancer. (villajoyosacf.info)
  • We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. (bvsalud.org)
  • Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. (frontiersin.org)
  • In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. (frontiersin.org)
  • Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
  • In this review, we summarize the evidence linking cellular senescence to the pathogenesis of CKD and discuss current understanding of the mechanism and regulators controlling senescence. (frontiersin.org)
  • The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA) leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. (hindawi.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)
  • Deciphering the purpose, causes, and consequences of cellular senescence will provide us with a better understanding of the role they may play in a wide variety of diseases and how we can use therapies to remove them to improve human health. (sens.org)
  • This term might be the most unfamiliar to you, so let's take a deeper dive into the causes and consequences of cellular senescence. (sens.org)
  • In reality, senescent cells are highly metabolically active which means that there are still many cellular processes happening within the cytoplasm. (sens.org)
  • These signals can help recruit immune cells to clear up cellular damage and these molecules can also support tissue repair and remodeling. (sens.org)
  • So far, it seems like cellular senescence is a great mechanism to have in our bodies, but as is the case with many cellular processes, too much of a good thing can become a bad thing. (sens.org)
  • 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)
  • 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)
  • They are involved in a range of cellular processes, depending upon the transcriptional repressor that recruits them to DNA, and they suppress the transcription of genes that cause apoptosis (reviewed in Bergman et al, 2006a). (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)
  • Changes in cortical neurones included alterations in insulin and other signalling pathways, cell cycle, cellular senescence, inflammatory mediators, and components of the mitochondrial respiratory electron transport chain. (biomedcentral.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)
  • Taken together, these data indicate that the reduction of JHDM1B leads to a more aggressive cellular phenotype in mammary gland cells, by virtue of its negative regulatory activity on ribosome biogenesis. (oncotarget.com)
  • Although cellular senescence plays an important role in tissue homeostasis, the dramatic accumulation of senescent cells in old age has deleterious effects on damage repair and systemic inflammation [ 11 ]. (biomedcentral.com)
  • Finally, we discuss how certain hallmarks of ageing (epigenetic alterations, mitochondrial dysfunction, telomere attrition, cellular senescence, and altered intercellular communication) predispose the ageing population to severe COVID-19. (ersjournals.com)
  • Research over the past decades have provided extensive knowledge on cellular processes of growth factor signaling, apoptosis, autophagy, senescence, cell cycle control, DNA repair which have been instrumental for understanding physiology as well as cancer biology. (ki.se)
  • So instead of "correcting errors" causing the cancer, as in most targeted therapies, Patrik Ernfors and his research group will take an entirely new strategy by hypothesizing that the marked cellular changes in cancer cells may lead to acquired vulnerabilities. (ki.se)
  • Moreover, momordicine I decreased the oxidative phosphorylation capacity of glioma cells and inhibited tumor sphere formation in temozolomide (TMZ)-resistant GBM cells. (excli.de)
  • The underlying mechanisms involved in genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by Western blotting, flow cytometry and immunofluorescence assays. (biomedcentral.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)
  • 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)
  • 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)
  • According to recent data, Ras-transformed cells require autophagy to survive and maintain malignant phenotype [ 5 - 10 ]. (aging-us.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)
  • Given that autophagy is initiated upon suppressed mTORC1 activity, a protective autophagy in Ras-transformed cells with a high level of mTORC1 activity appears to be mTORC1-independent [ 20 , 21 ]. (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)
  • Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). (frontiersin.org)
  • These secreted factors are collectively referred to as the senescence-associated secretory phenotype or the SASP. (sens.org)
  • Senescent cells take on a senescence associated secretory phenotype (SASP), in which production of proinflammatory cytokines, chemokines, growth factors, and proteases are increased by selective chromatin alterations [ 12 ]. (biomedcentral.com)
  • 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)
  • 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)
  • While most molecular biologists thought signaling pathways worked by sensing signals extrinsic to the cell and relaying the information to the nucleus, Elledge was proposing an internal signaling pathway that senses cell-intrinsic events. (the-scientist.com)
  • In this study, published in the journal Proceedings of the National Academy of Sciences (PNAS), the scientists postulate that the initiation of a tumor and the type and aggressivity of the same depend on a specific combination of defects in several processes that safeguard cell integrity, such as DNA repair pathways and cell cycle check-points. (rdworldonline.com)
  • Whether or not a tumor develops depends on the moment of the cell cycle in which the damage occurs, which repair pathways components are affected, and which others are impaired in terms of apoptosis and cell cycle arrest", explains the North-American Travis H. Stracker, head of the "Genomic Instability and Cancer" group and an expert in DNA repair pathways and its implications on human health. (rdworldonline.com)
  • Stable monoubiquitinated form of wild type p53, accumulates in the cytoplasm and interacts with BAK or BAX proteins in mitochondria to induce apoptosis Thus Kevetrin activates both transcription dependent and transcription independent pathways to promote apoptosis. (shu.edu)
  • These pathways link RASSF proteins into the control of motility, genetic stability, apoptosis, the cell cycle, regulation of protein stability, senescence and DNA repair. (louisville.edu)
  • 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)
  • The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • Cell-based functional bioassays of bio-relevant activities of enzymes, receptors, and signaling molecules and pathways. (wuxibiology.com)
  • Activated p53 transcriptionally regulates hundreds of genes that are involved in multiple biological processes, including in DNA damage repair, cell cycle arrest, apoptosis and senescence. (nih.gov)
  • While there are ongoing research projects to define new markers or causes of senescence, we do know that senescence can be induced by damage to DNA, shortening of telomeres (which are the protective caps at the end of DNA molecules), mitochondrial damage, and something called epigenetic factors, which refers to changes to our chromosomes that affect the way DNA is packaged and genes are expressed. (sens.org)
  • Somatic mutations in other genes involved in cell growth are also needed for a melanoma to develop. (medlineplus.gov)
  • In addition, Kevetrin increased expression of p53 target genes such as p21 (Waf1), an inhibitor of cell cycle progression. (shu.edu)
  • The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas. (louisville.edu)
  • 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)
  • 912, 2202, and 1227 genes were significantly differentially expressed between cases with self-reported T2D and controls in neurones, astrocytes, and endothelial cells respectively. (biomedcentral.com)
  • Oxaliplatin causes cell-cycle arrest promotes accelerated senescence and induces apoptosis in Bexarotene (LGD1069) cancer cells7 8 9 The p53 protein is involved in many biological processes the best known of which are cell-cycle arrest and DNA repair10 11 p53 also regulates apoptosis after exposure to hypoxia and cytotoxic drugs and is one of the most commonly mutated genes in many types of cancer12. (immune-source.com)
  • In contrast silencing p53 significantly decreases the inhibitory effects of oxaliplatin suggesting an important role for p53 in this process13 14 The p53 protein regulates a group Bexarotene (LGD1069) of cytochrome P450 (CYP) genes in human and mouse liver cells and influences the efficacy of chemotherapeutic treatment regimens15 16 However a role for p53 in regulating CYP450 genes in the intestinal tract has not yet been reported. (immune-source.com)
  • 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)
  • The genes of cells program a process that, when triggered, results in death of the cell. (msdmanuals.com)
  • Methods Cell viability was measured by CellTiter-Glo and Trypan blue exclusion assay. (uaeu.ac.ae)
  • The most promising candidate, CYT997, was tested for its invitro effects on cell viability and cell death, colony formation, cell cycle changes, and cell migration/invasion in HCC cells. (stanford.edu)
  • We tested four major extracts of M. charantia and found that momordicine I reduced glioma cell viability without serious cytotoxic effects on astrocytes. (excli.de)
  • Embryo morphology al ows options, the discovery of cell-free DNA in the evaluation of its growth, viability, and biological fluids has led to major advances in implantation capacity. (who.int)
  • Therefore, based on clinical experience as well as cytotoxic activity against multiple human cancer cells, we hypothesized that induction of apoptosis is the underlying mechanism for the treatment of psoriasis. (hindawi.com)
  • In this Review, we discuss the multiple molecular mechanisms of p53 regulation and how they modulate the induction of apoptosis or cell cycle arrest following DNA damage. (nih.gov)
  • Apoptosis was partially blocked by the caspase-3 inhibitor Ac-DEVD-CHO. (hindawi.com)
  • Mitochondrial regulation of apoptosis further downstream was investigated, showing changes in the mitochondrial membrane potential, cytochrome c release into the cytoplasm, and enhanced activation of cleaved caspase-3 and Poly ADP-ribose polymerase (PARP). (hindawi.com)
  • There was also no translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. (hindawi.com)
  • Apoptosis was determined by caspase 3/7 activation, PARP cleavage and Annexin V staining. (uaeu.ac.ae)
  • Mechanism of action studies showed that Kevetrin strongly induced apoptosis by activation of Caspase 3 and cleavage of PARP. (shu.edu)
  • 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)
  • He mentioned this to David Stillman , who was at Stanford to interview for a faculty position, and who studied cell cycle regulation of proteins as a postdoc in Kim Nasmyth 's lab at the MRC Laboratory of Molecular Biology in the U.K. Stillman pointed out that ribonucleotide reductase was cell cycle regulated-rather than remaining stable, the RNA and protein levels fluctuate throughout the cell cycle. (the-scientist.com)
  • Senescent cells secrete various proteins and molecules that cause inflammation. (sens.org)
  • Well, it turns out that some of those inflammatory proteins and molecules that make up the SASP can have negative effects on other cells and tissues. (sens.org)
  • If the repair is defective and the cell accumulates many genomic errors, "watch-out" proteins step in, such as tumor suppressor p53. (rdworldonline.com)
  • Such proteins activate programmed cell death (apoptosis) or cell cycle arrest (senescence). (rdworldonline.com)
  • 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)
  • mRNA and protein expression comparison We calculated the fold transform in level of mRNAs and proteins transcripts in CD30hi cells in comparison to CD30lo cells in semi quantitative method. (smadsignaling.com)
  • Per Svenningsson , Professor in Neurology at the the Department of Clinical Neuroscience , studies proteins that are central to the development of Parkinson's disease and investigates pharmaceuticals that may potentially protect brain cells from damage. (ki.se)
  • Such biological functions depend on their lectinic properties (recognition of N-acetyllactosamine sequences displayed on the cell surface, in the extracellular matrix, or intracellular glycoconjugates) ( Table 1 ). (encyclopedia.pub)
  • Momordicine I also induced apoptosis, intracellular reactive oxygen species (ROS) production, and senescence in glioma cells. (excli.de)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • We also highlight potential options of targeting senescent cells for the treatment of CKD. (frontiersin.org)
  • We also highlight potential options for targeting senescent cells in developing therapeutics for CKD patients. (frontiersin.org)
  • Figure 5: Potential deleterious effects of senescent cells. (nature.com)
  • Researchers have found that senescent cells accumulate in our body as we age. (sens.org)
  • As the interest in defining senescent cells has grown, so has the interest in deciphering why they exist in the first place. (sens.org)
  • The leading hypothesis for why senescent cells exist is that they serve as a preventative measure against cancer. (sens.org)
  • Because they are no longer dividing, it might sound like senescent cells are inactive and prevent cancer by completely shutting down. (sens.org)
  • Senescent cells are great for the initial prevention of cancer, but remember the SASP I just mentioned? (sens.org)
  • Although senescent cells start out as helpers that prevent cancer, too many of them can become a detriment to human health. (sens.org)
  • Researchers have found that senescent cells accumulate around the body as we age, so conditions such as Alzheimer's disease, heart disease, and liver fibrosis may be significantly worsened by the increased inflammation that comes with the accumulation of senescent cells. (sens.org)
  • There is still a lot to be discovered about how senescent cells work and scientists are very interested in understanding what other roles they might be playing in a wide variety of diseases. (sens.org)
  • This has also prompted many research groups to investigate how we might be able to remove senescent cells around the body with drugs or cell therapies which could help improve the health of many individuals. (sens.org)
  • Senescent cells are unable to form the autophagolysosomes and to remove the damaged mitochondria resulting in apoptotic death. (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)
  • Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
  • Nephron progenitors, the self-renewing cells that give rise to nephrons, are particularly metabolically active, relying primarily on glycolysis for energy generation early in development. (lww.com)
  • Nephron progenitors, the cell population that give rise to the functional unit of the kidney, are metabolically active and self-renew under glycolytic conditions. (lww.com)
  • Cells begin to produce p16(INK4A) when they are no longer able to undergo cell division. (medlineplus.gov)
  • The p53 gene determines whether a cell should survive a damage or should undergo apoptosis. (samplefellow.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)
  • In response to severe DNA damage, cells undergo apoptosis to prevent transformation into over here tumour cells. (smadsignaling.com)
  • 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)
  • 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)
  • A switch from glycolysis to mitochondrial respiration drives these cells toward differentiation, but the mechanisms that control this switch are poorly defined. (lww.com)
  • In recent years, molecular mechanisms of cell aging, their connection with oncological diseases and inflammation have been discovered. (vechnayamolodost.ru)
  • Cancer cells exploit a variety of protective mechanisms that allow them to acquire selective advantage and proliferate under unfavorable conditions. (aging-us.com)
  • However, it has widely been demonstrated that tumor cells negatively manage immune attack by activating several immune-suppressive mechanisms. (encyclopedia.pub)
  • Patrik Ernfors , Professor of Molecular Neurodevelopment at the Department of Medical Biochemistry and Biophysics , was appointed a Wallenberg Scholar in 2010 for his research about the mechanisms behind cell division of stem cells, and the possible ability of the brain to heal itself. (ki.se)
  • Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. (bvsalud.org)
  • Significance This study provides a new insight to better understand the mechanism of action of Salinomycin, at least in breast cancer cells. (uaeu.ac.ae)
  • Studies have shown that the elusive molecular mechanism of Ser46 phosphorylation of p53 induce apoptosis in the tumor cells, which makes the molecular mechanism a potential target for cancer therapy. (samplefellow.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)
  • The mechanism that limits cell division involves a structure called a telomere. (msdmanuals.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)
  • Studies of the genetics of p53 pathway components - in particular p53 itself and its negative regulator MDM2 - in cancer cells has proven useful in the development of targeted therapies. (ox.ac.uk)
  • CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. (bvsalud.org)
  • Then I thought, there must be a sensory pathway that recognizes the DNA damage that's going on in the cell," says Elledge. (the-scientist.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)
  • In some circumstances, the activation of a stress-response pathway will actually help the tumour cell to survive and proliferate. (southampton.ac.uk)
  • 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)
  • Impaired insulin signalling was shared by neurovascular unit cells with, additionally, apoptotic pathway changes in astrocytes and dysregulation of advanced glycation end-product signalling in endothelial cells. (biomedcentral.com)
  • The genetics of the p53 pathway, apoptosis and cancer therapy. (ox.ac.uk)
  • These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. (bvsalud.org)
  • Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (nature.com)
  • Sager, R. Senescence as a mode of tumor suppression. (nature.com)
  • The biosynthesis performed by the BCCP protein allows for the transfer of CO2 within active sites of the cell. (wikipedia.org)
  • To study the potential role in this metabolic shift of von Hippel-Lindau (VHL), a protein component of a ubiquitin ligase complex, the authors generated nephron progenitor cell-specific VHL knockout mice. (lww.com)
  • Elledge had found that Rnr2 protein levels increased when yeast cells were grown in the presence of agents that damaged DNA. (the-scientist.com)
  • He found that RNR2 RNA levels increased dramatically, even more than the protein levels, upon exposure of cells to DNA damage and that mutations in RNR2 resulted in hypersensitivity to DNA damage. (the-scientist.com)
  • Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. (uaeu.ac.ae)
  • The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
  • Our data reveal consistent ENKUR downregulation at both RNA and protein levels across MPN patient specimens and experimental models, with a concomitant upregulation of a cell cycle marker, CDC20. (stanford.edu)
  • Ribosome biogenesis, the process of ribosome production, is frequently up-regulated in cancer in order to respond to the increased demand of protein synthesis in highly proliferating cells. (oncotarget.com)
  • for proteomics data, fold change was calculated by taking the ratio of imply sum of XCorr of that protein in CD30hi to CD30lo cells. (smadsignaling.com)
  • Alzheimer Disease Alzheimer disease is a progressive loss of mental function, characterized by degeneration of brain tissue, including loss of nerve cells, the accumulation of an abnormal protein called beta-amyloid. (msdmanuals.com)
  • Since then, many research teams have become interested in determining the hallmarks of cell senescence, the factors that induce it, and the effect of senescence on other cells and the body as a whole. (sens.org)
  • The study also demonstrates that mice with a high degree of chromosomal instability and defective programmed cell death (apoptosis), two hallmarks of cancer, rarely develop tumors. (rdworldonline.com)
  • This is due to irregularities in the regulation of cell division and an increased frequency of mutagenesis in actively dividing cells. (vechnayamolodost.ru)
  • It arrested cell cycle at the G2/M phase with associated up-regulations of p21, p-MEK1/2, p-ERK, and down-regulation of cyclin B1. (stanford.edu)
  • As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)
  • Their de-regulation in tumors could be responsible for both a surge in ribosome biogenesis, and the loss of cell cycle control [ 1 ]. (oncotarget.com)
  • Stabilized wild type p53 induced apoptosis by inducing the expression of PUMA. (shu.edu)
  • CYP2S1 knockdown conferred a cell survival advantage after oxaliplatin treatment to cells harboring wild-type p53 and cytotoxicity and antitumor activity. (immune-source.com)
  • Results Inhibition of CRC cell growth by oxaliplatin is usually associated with Bexarotene (LGD1069) the presence of wild-type p53 To investigate the cytotoxicity of the anticancer agent oxaliplatin in CRC cells CCK8 assays were performed using HCT116 SW480 and HT29 cells treated with various concentrations of oxaliplatin for 24?h. (immune-source.com)
  • 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)
  • Cells continually experience stress and damage from exogenous and endogenous sources, and their responses range from complete recovery to cell death. (nature.com)
  • His first experimental results contained a serendipitous artifact that laid the foundation for a scientific career studying how eukaryotic cells deal with damage to their DNA. (the-scientist.com)
  • Elledge's idea that eukaryotic cells sense the progress of DNA replication and transform that information into a DNA-damage response was new. (the-scientist.com)
  • Those results led him to study how cells monitor roadblocks to replication and DNA damage, such as nicks and double-stranded breaks, and how the cell handles that information. (the-scientist.com)
  • The master tumor suppressor p53 controls transcription of a wide-ranging gene network involved in apoptosis, cell cycle arrest, DNA damage repair, and senescence. (whiterose.ac.uk)
  • Throughout our lives, the cells in our bodies can experience external damage from the sun or chemicals in our environment. (sens.org)
  • Normally, our cells are pretty good at repairing and coping with damage that occurs. (sens.org)
  • There are a few different things that can happen once cell damage occurs. (sens.org)
  • Ideally, the damage gets repaired, and the cell goes right back to its normal function. (sens.org)
  • The best option would be for a cell to successfully repair any damage that occurs, but when this isn't possible (and the damage hasn't reached a critical level of inducing apoptosis) a cell will become senescent to try and avoid becoming cancerous. (sens.org)
  • During cell division, tissue rejuvenation occurs: new cells take the place of damaged ones, while repair (elimination of DNA damage) occurs more intensively and regeneration is possible in case of tissue damage. (vechnayamolodost.ru)
  • This can provide Ras-expressing tumor cells additional selective advantages under stress or damage. (aging-us.com)
  • One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
  • The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)
  • The p53 gene is a tumor suppressor gene that is activated whenever a cell is subjected to cell damage. (samplefellow.com)
  • In addition to its contribution to small and large vessel disease, T2D may directly damage cells of the brain neurovascular unit. (biomedcentral.com)
  • Conversely, intact damage can lead to transcription and replication arrest, leading to cell death and senescence (Hoeijmakers, 2009). (villajoyosacf.info)
  • P53 deficiency results in reduced repair activity and decreased cell survival after UV-induced DNA damage, suggesting the involvement of p53 in nucleotide excision repair (NER) (Smith et al. (villajoyosacf.info)
  • In presence of DNA damage, the tumour suppressor p53 plays a crucial purpose inside the selection among survival and death of your cell. (smadsignaling.com)
  • Other triggers include an excess number of cells and possibly damage to a cell. (msdmanuals.com)
  • Sometimes damage to a cell directly causes its death. (msdmanuals.com)
  • Results Salinomycinwas able to inhibit the growth of the three cell lines in time- and concentration-dependent manners. (uaeu.ac.ae)
  • AREG binds to the EGF receptor present on the plasma membrane to promote growth but also promotes apoptosis by regulating miRNA. (samplefellow.com)
  • L1CAM plays a role in neural development, axon guidance, and cell migration. (pharmiweb.com)
  • CYT997 inhibited HCC cell migration and invasion, and down-regulated the expressions of acetylated tubulins, beta-tubulin, glypican-3 (GPC3), beta-catenin, and c-Myc. (stanford.edu)
  • Figure 2: Telomere-dependent senescence. (nature.com)
  • Stephen Elledge has built a career studying how eukaryotic cells maintain genomic integrity. (the-scientist.com)
  • Analysis of a comprehensive display identifying genomic markers for drug sensitivities in malignancy cell lines (22) suggested that mutational status of may correlate with level of sensitivity to inhibitors that selectively target the insulin-like growth element I receptor (IGF1R) and the related insulin receptor (IR). (giknet.org)
  • however, AREG has dual functions as a cell growth inhibitor as well as a cell growth proliferator. (samplefellow.com)
  • The DDR brings about temporal cell cycle arrest, when the degree of DNA harm is low, Docetaxel Microtubule Formation inhibitor so the cell can restore it. (smadsignaling.com)
  • patients with type E (AD) tumor had higher incidence of nodal metastasis at MGCD0103 cell line TGF-beta inhibitor mediastinal lymph node than did patients in tumor groups, and all mediastinal positive nodes existed in lower mediastinal area. (hsdpathway.com)
  • Stem cells derived from human dental tissues with properties of self-renewal, multilineage differentiation and immunomodulation have been intensively investigated for stem cell-based regenerative medicine [ 1 , 2 ]. (biomedcentral.com)
  • Background In the present study, we investigated the effect of Salinomycin on the survival of three human breast cancer cell lines MCF-7, T47D and MDA-MB-231 grown in adherent culture conditions. (uaeu.ac.ae)
  • However, lymphoid homeostasis is highly dynamic, depending on the continuous production of naïve cells in central hematopoietic organs, their activation, survival, and generation of immune memory in peripheral organs. (encyclopedia.pub)
  • However, it is unclear why a Ser46 phosphorylated p53 favors apoptosis over survival (Feng et al. (samplefellow.com)
  • 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)
  • 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)
  • They facilitate adhesion between leukocytes and endothelial cells, enabling leukocyte extravasation into tissues during inflammation. (pharmiweb.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 this study, we investigated the transcriptomic changes in cortical neurones, and associated astrocytes and endothelial cells of the neurovascular unit, in the ageing brain. (biomedcentral.com)
  • We also consider important differences between COVID-19 and influenza, mainly the protean clinical presentation and associated lymphopenia of COVID-19, the contrasting role of interferon-γ in mediating the host immune response to these viruses, and the tropism for vascular endothelial cells of SARS-CoV-2, commenting on the potential limitations of influenza as a model for COVID-19. (ersjournals.com)
  • Specifically, we argue that the hypercoagulable and hyperinflammatory state of severe COVID-19 is a consequence of the expanded tropism of SARS-CoV-2, which allows it to infect vascular endothelial cells, and that cytokine storm physiology contributes to a lesser degree. (ersjournals.com)
  • E. Wells containing endothelial cells with microspheres were analyzed for fluorescence. (hsdpathway.com)
  • Conclusion Our data are the first to link senescence and histone modifications to Salinomycin. (uaeu.ac.ae)
  • Cells are potent to go under abnormal growth processes and finally lead to tumor/cancer. (pharmiweb.com)
  • Specifically, we discuss how the interaction of p53 with DNA and chromatin affects gene expression, and how p53 post-translational modifications, its temporal expression dynamics and its interactions with chromatin regulators and transcription factors influence cell fate. (nih.gov)
  • Mutations in the CDKN2A gene are found in up to one-quarter of head and neck squamous cell carcinomas (HNSCC). (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)
  • 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)
  • This miRNA functions as a tumor suppressor and dysregulation or loss of the host gene from which this miRNA is processed is associated with cancer progression in numerous cell types. (cancerindex.org)
  • The proposal combines highly innovative and systematic approaches to identify the hierarchical cell organization in glioblastoma tumors, gene-regulatory networks governing the different cell states and finally the identification of selective vulnerability of tumor initiating cells. (ki.se)
  • DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. (bvsalud.org)
  • Neuroblastoma is one of the most common solid tumors of childhood, arising from immature sympathetic nervous system cells. (biomedcentral.com)
  • NBs belong to the subgroup of small round blue cell tumors and can often pose a challenge to the pathologist because of their similarities with lymphomas, rhabdomyosarcomas, the Ewing family of tumors and desmoplastic round cell tumors. (biomedcentral.com)
  • While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. (frontiersin.org)
  • If the cell detects errors in any of these phases, cell growth is halted and highly complex DNA repair processes are triggered. (rdworldonline.com)
  • Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages, bone maintenance and repair. (biomedcentral.com)
  • 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)
  • Dental follicle stem cells (DFSCs) show mesenchymal stem cell properties with the potential for alveolar bone regeneration. (biomedcentral.com)
  • Compared to other dental stem cells, dental follicle stem cells (DFSCs) are mainly isolated from human dental follicles within the developing wisdom teeth germ, so their plasticity is much better with the advantages of easier clinical access and less ethical controversy [ 3 , 4 ]. (biomedcentral.com)
  • With aging, the cell stops dividing: it does not respond to growth factors and becomes resistant to apoptosis. (vechnayamolodost.ru)
  • Oxaliplatin treatment upregulates p53 and activated p53 enhances growth inhibition in CRC cells treated with oxaliplatin. (immune-source.com)
  • This study is the first to report that inhibition of oxaliplatin-induced cell growth may be dependent on p53 and may involve increased expression of cytochrome enzymes (CYP2S1) in CRC cells. (immune-source.com)
  • As shown in Fig. 1A oxaliplatin inhibited cell growth in these three CRC cell lines in a Bexarotene (LGD1069) dose-dependent manner with HCT116 cells being more sensitive to oxaliplatin than SW480/HT29 cells (Fig. 1A). (immune-source.com)
  • Our results demonstrate that tumor growth, peritoneal dissemination and peritoneum or organ metastasis implanted MKN45 cells were significantly decreased in shAhR and Biseugenol-treated mice and that endoplasmic reticulum (ER) stress was caused. (oncotarget.com)
  • Cancer Lett, 300:215-224.doi:10.1016/j. squamous cell carcinoma in north-eastern Iran. (who.int)
  • The molecules are found on the cell surface, where they facilitate adhesion to neighboring cells or the extracellular matrix, creating stable cell structures and supporting tissue organization. (pharmiweb.com)
  • In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. (ersjournals.com)
  • References 2 and 3 describe the characteristics of cancer cells and the importance of mutations in cancer development. (nature.com)
  • These mutations, classified as germline mutations, are typically inherited and are present in essentially all of the body's cells. (medlineplus.gov)
  • TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. (bvsalud.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)