• These include the assumption that aging is caused by molecular damage, the disposable soma theory, the hallmarks of aging, which he branded a "pseudo-paradigm", and the concept of cellular senescence, which he argued has been outgrown by recent research progress. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
  • Etoposide-induced senescence model may help investigate the initiation of cellular senescence in chondrocytes, and provide a useful model to develop therapeutic approaches to target senescence in OA. (aging-us.com)
  • Cellular senescence has been described as one of the major drivers of aging [ 6 ] and has been implicated in the pathogenesis of many age-related diseases [ 7 ]. (aging-us.com)
  • Recently, cellular senescence has emerged as a new target to treat OA [ 8 ]. (aging-us.com)
  • Because a specific marker for cellular senescence has yet to be identified, a combination of markers should be used to identify SnCs [ 14 ]. (aging-us.com)
  • Considering the role of cellular senescence in age-related diseases including OA, the therapeutic potential of senolytic (drugs that induced SnCs death) and senomorphic (drugs that modulate the SASP) compounds have been contemplated with growing interest [ 15 ]. (aging-us.com)
  • Those groups are not specifically targeting cellular senescence, but can hardly avoid having senescent cells taking up their therapeutic mitochondria. (fightaging.org)
  • Exogenous mitochondrial transplantation improved mitochondrial dysfunction and alleviated cellular senescence hallmarks, such as increased cell size, increased senescence-associated β-galactosidase activity, augmented NF-κB activity, increased inflammatory cytokines , and upregulated the cyclin-dependent kinase inhibitors p21 and p16 . (fightaging.org)
  • Further, cellular senescence properties were improved by exogenous mitochondrial transplantation in oxidative stress -induced senescent ARPE-19 cells. (fightaging.org)
  • These results indicate that exogenous mitochondrial transplantation modulates cellular senescence and may be considered a novel therapeutic strategy for AMD. (fightaging.org)
  • 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)
  • Research into apoptosis, necrosis, autophagy, and cellular senescence is very important for understanding the intracellular functions that control cell survival and death. (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, which is morphologically characterized by an enlarged and flattened cell shape, was first described by Hayflick [ 9 ]. (hindawi.com)
  • Cellular senescence refers to active cells that eventually enter a state of irreversible growth arrest. (hindawi.com)
  • Moreover, replicative senescence of MSCs exhibits reduced functionality, and cellular senescence might impair the regenerative potential of MSCs [ 10 ]. (hindawi.com)
  • The mechanisms underlying the cellular senescence of MSCs are still poorly understood. (hindawi.com)
  • Studies show that replicative senescence or cellular senescence is induced by intrinsic or extrinsic environmental factors [ 11 ]. (hindawi.com)
  • Cellular senescence is a complex process, and its molecular mechanisms are unknown. (hindawi.com)
  • Additionally, Abedin and King showed that FGF-2 suppresses the cellular senescence of human MSCs [ 17 ]. (hindawi.com)
  • Accelerated senescence is a primary response to cellular stresses including DNA damaging agents (e.g., ionizing radiation) and is widely believed to be caused by continuous proliferative signaling in the presence of cell cycle arrest. (lonza.com)
  • Ly294002 (a phosphatidylinositol-3-kinase [PI3K] inhibitor) or rapamycin (an mTOR inhibitor) blocked the induction of cellular senescence markers suggesting roles for PI3K and mTOR. (lonza.com)
  • Tumor suppressor genes can promote cellular senescence, a state in which cells stop dividing, preventing the replication of damaged DNA. (pharmiweb.com)
  • Abstract Cellular senescence is a stress response that imposes stable cell-cycle arrest in damaged cells, preventing their propagation in tissues. (biotech2012.org)
  • Cellular dormancy and heterogeneity in cell cycle length provide important explanations for treatment failure after adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC), yet the molecular control of the dormant versus cycling state remains unknown. (ox.ac.uk)
  • Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
  • Cellular senescence is a cell fate program that entails essentially irreversible proliferative arrest in response to damage signals. (aging-us.com)
  • In experimental models of multiple myeloma, a Myc-dependent hematologic malignancy, JQ1 produces a potent antiproliferative effect associated with cell cycle arrest and cellular senescence. (healthblogs.org)
  • Changes in chromatin structure have been implicated in ATM activation and cellular senescence, DZ2002 but the exact mechanism remains uncharacterized.18 For example, treatment with HDAC inhibitors can result in cellular senescence by inducing ATM phosphorylation.18?20 Here we show that treatment DZ2002 with an HMT inhibitor causes related phenotypes. (innovation-ecosystems-agora.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)
  • 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)
  • Regulation and function of Myb-binding protein 1A (MYBBP1A) in cellular senescence and pathogenesis of head and neck cancer. (nih.gov)
  • Cellular senescence-the permanent arrest of cycling in normally proliferating cells such as fibroblasts-contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. (ncl.ac.uk)
  • Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of 'deep' cellular senescence. (ncl.ac.uk)
  • 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)
  • In fact, many studies have demonstrated the oleuropein and its derivative have proved pharmacological activity against proliferation of cancer cells and several tumor cell lines by different mechanisms such arrest cell cycle and cause apoptosis in cancerous cells, by modulation of miRNA expression and upregulation and downregulation of several genes. (springer.com)
  • Our study demonstrates that survivin and APE1/Ref-1 are significantly higher in human prostate cancer specimens compared to noncancerous controls and that APE1/Ref-1 redox-specific inhibition with small molecule inhibitor, APX3330 and a second-generation inhibitor, APX2009, decreases prostate cancer cell proliferation and induces cell cycle arrest. (oncotarget.com)
  • AKAP12 knockdown in benign meningioma cells SF4433 increases proliferation, cell cycle, migration, invasion, and confers an anaplastic profile. (nature.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)
  • In addition, their osteogenic differentiation potential was increased, and genes involved in cell adhesion, FGF-2 signalling, cell cycle, stemness, cell differentiation, and cell proliferation were upregulated, compared to that of the MSCs cultured on uncoated plates. (hindawi.com)
  • AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. (scite.ai)
  • Pathway-directed microarrays revealed increased transcription of insulin-like growth factor I (IGF-1), a modulator of cell growth and proliferation upstream of mTOR. (lonza.com)
  • CCK-8 and colony formation assay showed that HRE significantly inhibited RCC cells proliferation. (bvsalud.org)
  • 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)
  • catenin signaling and influences CRC cell proliferation and experiments in CRC cell lines and an tumor xenograft model. (immune-source.com)
  • Furthermore, the TNFRSF13B was knocked down in 22Rv1 and PC-3 human prostate cancer cell lines via transfecting short hairpin RNAs and cell proliferation and colony formation assays were performed. (biomedcentral.com)
  • Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. (proteopedia.org)
  • The oncoprotein murine double minute 2 (MDM2) promotes cell survival, proliferation, invasion, and therapeutic resistance in many types of cancer. (villajoyosacf.info)
  • Bowen, 2004} detected keratinocyte proliferation by PCNA (proliferating cell nuclear antigen) marking, 13,9% of keratinocytes were stained, compared with 6,4% in normal skin. (globale-dermatologie.com)
  • and here we're going to get a bit technical, sorry: c-Myc is a protein that regulates cell proliferation. (healthblogs.org)
  • In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. (biomedcentral.com)
  • proliferation in the pancreatic malignancy cell collection PANC-1. (innovation-ecosystems-agora.com)
  • We monitored these cells during their expansion ex vivo with respect to proliferation kinetics, surface marker profile and differentiation potential. (biomedcentral.com)
  • 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)
  • Our group found that the proliferation and differentiation ability of aged human bone marrow mesenchymal stem cells (hBM-MSCs) was decreased whereas cell senescence was increased [ 7 ]. (biomedcentral.com)
  • They also found that downregulation of miR10a/10b in clonal cells interfered with cell proliferation and enhanced cell apoptosis by activating the NF-κB-dependent p53 pathway [ 13 ]. (biomedcentral.com)
  • Although senescent cells repress proliferation-promoting genes, they also induce the gene program necessary for the implementation of senescence. (rupress.org)
  • Ectopic expression of gene BCL2 enhances the survival and proliferation of chimpanzee and pig-tailed macaque iPSCs within the pre-implantation embryo, although the identity and long-term contribution of the transplanted cells warrants further investigation. (stanford.edu)
  • Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells. (nih.gov)
  • Introduction The commitment to cell proliferation is set up when extracellular signals converge on the cell cycle and induce the expression of D-type cyclins, their association with CDK4 and/or CDK6, as well as the activation from the holoenzyme complex [1C3]. (healthandwellnesssource.org)
  • Launch The dedication to cell proliferation is set up when extracellular indicators converge on the cell routine and stimulate the appearance of D-type cyclins, their association with CDK4 and/or CDK6, as well as the activation from the holoenzyme complicated [1C3]. (healthandwellnesssource.org)
  • The cyclin D-associated kinases are essential for the proliferation of Rb-positive cells because they initiate the phosphorylation-dependent cascade that inactivates this tumor suppressor [2, 4]. (healthandwellnesssource.org)
  • Unchecked proliferation of Rb-positive tumor cells is often connected with mutations that dysregulate this pathway: like the overexpression of D-type cyclins, the overexpression or mutation of CDK4, or mutations in the Printer ink4 category of CDK inhibitors [3, 5, 6]. (healthandwellnesssource.org)
  • 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)
  • Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE), and flow cytometry methods. (hindawi.com)
  • 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)
  • Inhibition of mammalian target of rapamycin signaling by everolimus induces senescence in adult T-cell leukemia-lymphoma and apoptosis in peripheral T-cell lymphomas. (edu.lb)
  • Everolimus specifically induced oncoprotein Tax degradation and senescence in ATL cells and cell cycle arrest and apoptosis in HTLV-I-negative malignant T-cells. (edu.lb)
  • Everolimus-mediated apoptosis was also associated with an upregulation of p53 upregulated modulator of apoptosis (PUMA-α) proteins, an increase in Bax proteins and downregulation of Bcl-x(L) proteins in all tested HTLV-I-positive and -negative malignant cell lines. (edu.lb)
  • Annexin-V-FITC, AO/EB and TEM experiments revealed that HRE significantly promoted apoptosis of RCC cells. (bvsalud.org)
  • In RCC4 cells, pretreatment with IGF-1, attenuated HRE-induced apoptosis and G2/M arrest. (bvsalud.org)
  • 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)
  • 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)
  • Indeed apoptosis is inhibited in senescent cells. (globale-dermatologie.com)
  • Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. (biomedcentral.com)
  • The hypoxia-induced apoptosis, cell survival, and cell paracrine function of aged hBM-MSCs were investigated in vitro. (biomedcentral.com)
  • Through lentivirus-mediated upregulation of miR-10a and downregulation of KLF4 in aged hBM-MSCs in vitro, we revealed that miR-10a decreased hypoxia-induced cell apoptosis and increased cell survival of aged hBM-MSCs by repressing the KLF4-BAX/BCL2 pathway. (biomedcentral.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 cells (SnCs) have been described to accumulate in osteoarthritis (OA) joint tissues in response to injury, thereby participating in OA development and progression. (aging-us.com)
  • Indeed, senescent cells (SnCs) are described to accumulate in joint tissues in response to injury and during aging, thereby participating in its development and progression [ 8 - 10 ]. (aging-us.com)
  • Researchers here report on in vitro experiments to show that introducing functional mitochondria into a cell culture containing senescent cells reduces markers of senescence. (fightaging.org)
  • It is an interesting question as to how this would work in living tissue, where the numbers of senescent cells are low, and mitochondria will be introduced into all cells. (fightaging.org)
  • For all strategies that might leave senescent cells intact but modulate their harmful signaling , the question is whether or not this is a good idea. (fightaging.org)
  • This particularly the case for strategies that might allow senescent cells to re-enter the cell cycle and replicate again. (fightaging.org)
  • Some fraction of senescent cells become senescent for good reasons, such as potentially cancerous mutations or other forms of damage that produce dysfunction. (fightaging.org)
  • Senolytics that destroy senescent cells seem a safer proposal, and efficient senolytics may turn out to be required in advance of some of the other rejuvenation therapies on the horizon, such as partial reprogramming and mitochondrial transfer. (fightaging.org)
  • 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)
  • However, senescent cells accumulate in tissues in advanced age, where they might promote tissue degeneration and Kaempferol inhibition malignant transformation. (biotech2012.org)
  • Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some types of senescent cells, can induce senescence in mouse and human cells. (aging-us.com)
  • Two schools of thought exist, one states that SK develops from an accumulation of senescent cells, whereas the other states that cells hyperproliferate. (globale-dermatologie.com)
  • However, the accumulation of senescent cells can have detrimental consequences, such as in age-related pathologies. (rupress.org)
  • Abaza L, Talorete TP, Yamada P, Kurita Y, Zarrouk M, Isoda H (2007) Induction of growth inhibition and differentiation of human leukemia HL-60 cells by a Tunisian gerboui olive leaf extract. (springer.com)
  • The differentiation of mesenchymal stem cells (MSCs) into multiple cell lineages can be exploited as an attractive strategy for cell-based therapy and regenerative medicine [ 1 ]. (hindawi.com)
  • The ECM provides structural and biochemical support to the cells and has various other functions including cell adhesion, cell to cell communication, and differentiation [ 17 , 18 ]. (hindawi.com)
  • Despite growing experience and knowledge concerning human MSC and their use in cell-based strategies, the molecular mechanisms that govern MSC self-renewal, expansion and multilineage differentiation are not well understood and remain an active area of investigation. (biomedcentral.com)
  • We demonstrated previously that miR-10a is significantly decreased in aged hBM-MSCs and restoration of the miR-10a level attenuated cell senescence and increased the differentiation capacity of aged hBM-MSCs by repressing Krüpple-like factor 4 (KLF4). (biomedcentral.com)
  • We also found that miR-10a increased differentiation and decrease senescence in old hBM-MSCs through the target gene Krüpple-like factor 4 (KLF4) [ 7 ]. (biomedcentral.com)
  • However, other studies have suggested that miR-10a may have additional effects other than regulating cell senescence and differentiation. (biomedcentral.com)
  • SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
  • Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. (oaepublish.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)
  • 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)
  • Studies of signal transduction pathways leading to accelerated senescence have revealed that inhibition of mammalian target of rapamycin (mTOR) by rapamycin rescues cells from senescence. (lonza.com)
  • Furthermore, silencing TNFRSF13B expression resulted in decreased colony formation of 22Rv1 and PC-3 cells through modulating the cell cycle and p53 signalling pathways. (biomedcentral.com)
  • However, downstream signaling pathways linking TNFα-related inflammation to senescence are not fully characterized. (aging-us.com)
  • By gene expression profiling, we identified the crucial involvement of inflammatory and JAK/STAT pathways in TNFα-mediated senescence. (aging-us.com)
  • Rabbit Polyclonal to Pim-1 (phospho-Tyr309) Open in a separate windows Number 4 Effects of G9a inhibition within the ATM and ATR pathways. (innovation-ecosystems-agora.com)
  • The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. (ncl.ac.uk)
  • Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. (mdpi.com)
  • Supplemental Fig. 2 Inhibition of mTOR signaling pathway is critical for palbociclib-induced senescence in 983BR vemurafenib resistant cells, related to Figure. (figshare.com)
  • We demonstrated mitochondrial dysfunction in replicative senescence -induced ARPE-19 cells after repeated passage . (fightaging.org)
  • We demonstrate that PLL provides favourable microenvironment for MSC culture by reversing the replicative senescence. (hindawi.com)
  • Unlike embryonic stem cells, adult stem cells (MSCs) have a limited lifespan and stop proliferating during in vitro culture due to replicative senescence [ 8 ]. (hindawi.com)
  • Furthermore, the induction of senescence was associated with enhancing reactive oxygen species (ROS) level. (scite.ai)
  • Although localized disease can be treated by surgery alone, the standard therapy for patients with metastatic disease usually comprises intensive induction chemotherapy, local surgery and myeloablative chemotherapy followed by autologous stem cell transplant, external radiotherapy and retinoic acid treatment. (biomedcentral.com)
  • Our study results indicate that DTL is a potential novel target gene for treating liver cancer through liver cancer cell senescence induction. (transhumanist.ru)
  • 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)
  • Our results demonstrated that targeting DTL reduced cell cycle regulators and chromosome segregation genes, resulting in increased cell micronucleation. (transhumanist.ru)
  • However, inhibition of STAT1/3 did not rescue cells from proliferative arrest, but rather suppressed cell cycle regulatory genes and altered TNFα-induced senescence. (aging-us.com)
  • 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)
  • 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)
  • Chronic exposure to IL-1β induces only partial expression of senescence markers and does not allow us to conclude on its ability to induce senescence in chondrocytes. (aging-us.com)
  • In this submission, we explored the effect of the mammalian target of rapamycin (mTOR) complex-1 (mTORC1) inhibitor everolimus (RAD001) on ATL and HTLV-negative malignant T-cell lines. (edu.lb)
  • 6. Supplemental Fig. 3 Overexpression of mTOR signaling overrides palbociclib-induced senescence in 983BR vemurafenib resistant cells, related to Figure. (figshare.com)
  • Rapamycin binds to a complex called mTOR (mechanistic target of rapamycin) found in our cells and inhibits its activity. (aging-matters.com)
  • Together these findings suggest that IGF-1R is a key regulator of IR-induced accelerated senescence in a pathway that requires intact mTOR activity upstream of both p53 and p21/waf1. (lonza.com)
  • In fact, several studies have shown that T2D induces senescence in multiple types of cells, including fibroblasts and endothelial cells ( 11 , 12 ). (frontiersin.org)
  • Evidence has been provided that activation of the vascular endothelial cells in the presence of the risk factors promotes oxidative stress and vascular inflammatory responses, leading to acceleration of atherosclerotic vascular disease. (frontiersin.org)
  • We investigated signal transduction leading to IR-induced accelerated senescence in human pulmonary artery endothelial cells (HPAEC). (lonza.com)
  • 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)
  • Using human umbilical vein endothelial cells (HUVECs) as a model, we show that TNFα induces permanent growth arrest and increases p21CIP1, p16INK4A, and SA-β-gal, accompanied by persistent DNA damage and ROS production. (aging-us.com)
  • catenin signaling and cytochromeP450 enzymes (CYP51A1) were correlated to oxaliplatin sensitivity in 21 colorectal cancer cell lines24. (immune-source.com)
  • Itraconazole targets cell cycle heterogeneity in colorectal cancer. (ox.ac.uk)
  • Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. (oaepublish.com)
  • Mechanisms of pathogenesis of atherosclerosis are complex interplay between bloodstream cells and arterial wall components that leads to a chronic state of vascular oxidative stress and inflammation ( Hansson and Hermansson, 2011 ). (frontiersin.org)
  • This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte senescence. (aging-us.com)
  • [ii] He went on to clarify the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells. (aging-matters.com)
  • Furthermore, our results provide insights into molecular mechanisms for targeting DTL in liver cancer cells. (transhumanist.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)
  • We investigated the effects of various concentrations of Tan IIA (5-10 μ g/mL) on mouse keratinocytes and human HaCat cells in vitro to confirm this hypothesis. (hindawi.com)
  • Because APE1/Ref-1 is expressed and elevated in prostate cancer, we sought to characterize APE1/Ref-1 expression and activity in human prostate cancer cell lines and determine the effect of selective reduction-oxidation (redox) function inhibition on prostate cancer cells in vitro and in vivo . (oncotarget.com)
  • However, MSCs need to be expanded in vitro in order to obtain sufficient cells for clinical trials since they are extremely rare in various tissues. (hindawi.com)
  • Here, we developed CellAgeClock, a new epigenetic clock that measures subtle ageing changes in primary human cells in vitro . (biorxiv.org)
  • Our method expands the scope of CpG methylation profiling from measuring human chronological and biological age from human samples in years, to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro , providing a novel accelerated discovery platform to test sought after geroprotectors. (biorxiv.org)
  • 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)
  • DTL depletion inhibited liver cancer cell growth, increased senescence, and reduced tumorigenesis. (transhumanist.ru)
  • On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. (aging-us.com)
  • It was also shown that inhibition of the p16 tumour suppressor gene delays growth arrest and therefore senescence of MSC [ 16 ]. (hindawi.com)
  • By using a direct in vivo shRNA screen, we show that liver cancer cells that have mutations in the gene encoding the tumor suppressor protein p53 (Trp53 in mice and TP53 in humans) and that are driven by the oncoprotein NRAS become addicted to MYC stabilization via a mechanism mediated by aurora kinase A (AURKA). (scite.ai)
  • DTL depletion resulted in the disruption of the mitotic proteins cyclin B, CDK1 , securin, seprase, Aurora A, and Aurora B as well as the upregulation of the cell cycle arrest gene [i]p21[/i]. (transhumanist.ru)
  • The tumor suppressor gene p53 regulates cell cycle arrest to allow time for DNA repair. (villajoyosacf.info)
  • Indeed, in a clone of cells, only one of the alleles is expressed, because the same X chromosome is inactivated by lyonisation{Allen, 1992}, in a clone, whereas in normal {Nakamura, 2001} skin (polyclonal), the inactivated HUMARA gene allele isn't always on the same X chromosome. (globale-dermatologie.com)
  • Our objective here is to propose a model that relates in a simple but quantitative manner cell metabolism, gene expression and growth, together with their temporal fluctuations. (bioss-cnrs.fr)
  • This concept emerged during the 1960s, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation. (aging-matters.com)
  • As a result, changes in SA-ß-Gal expression, cell cycle progression, and mitochondrial membrane potential were observed. (dojindo.com)
  • DTL (Cdc10-dependent transcript 2) is a critical regulator of cell cycle progression and genomic stability. (transhumanist.ru)
  • A clonogenic assay, immunostaining, double thymidine block, imaging flow cytometry analysis, and a tumor spheroid formation assay were used to analyze the role of DTL in tumor cell growth, cell cycle progression, micronucleation, ploidy, and tumorigenicity. (transhumanist.ru)
  • Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (proteopedia.org)
  • ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. (innovation-ecosystems-agora.com)
  • Transwell and wound healing assays showed that HRE can inhibit the migration and invasion of RCC cells. (bvsalud.org)
  • 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)
  • Preclinical validation shows itraconazole to be effective in multiple assays through Wnt inhibition, causing both cycling and dormant cells to switch to global senescence. (ox.ac.uk)
  • With a variety of assays we could show that MSC represent a cell population which can be expanded for therapeutic applications. (biomedcentral.com)
  • Growing evidence demonstrates that various cancer treatment modalities, including chemotherapy, radiation therapy, targeted therapy, immunotherapy, hormone therapy, stem cell or bone marrow transplant, and surgery [ 3 - 5 ] , cause premature senescence, as reviewed elsewhere [ 6 - 8 ] . (oaepublish.com)
  • Mesenchymal stem cells (MSCs) possess great therapeutic potential. (hindawi.com)
  • Human mesenchymal stem cells (MSC) with the capacity to differentiate into osteoblasts provide potential for the development of novel treatment strategies, such as improved healing of large bone defects. (biomedcentral.com)
  • In recent years mesenchymal stem cells (MSC) have generated a great deal of interest as a potential source for cell-based therapeutic strategies. (biomedcentral.com)
  • Aging is one of the key factors that regulate the function of human bone marrow mesenchymal stem cells (hBM-MSCs) and related changes in microRNA (miRNA) expression. (biomedcentral.com)
  • Targeting DTL induces cell cycle arrest and senescence and suppresses cell growth and colony formation through TPX2 inhibition in human hepatocellular carcinoma cells. (transhumanist.ru)
  • We demonstrate that, at clinically achievable concentrations, long-term treatment with everolimus resulted in a dramatic inhibitory effect on the growth of HTLV-I-positive and -negative malignant T-cells, while normal resting or activated T-lymphocytes were resistant. (edu.lb)
  • 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)
  • Immunodeficiencies are genetic diseases known to predispose an individual to cancer owing to defective immunity towards malignant cells. (biomedcentral.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)
  • D) Assessment of levels of same proteins in PANC-1 cells in which GLP and G9a were knocked down by siRNA, individually and in combination, for 72 h. (innovation-ecosystems-agora.com)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • This unrecognized transition previously, known as senescence after development arrest or SAGA today, is prompted in the CDK4/6 inhibitor-induced quiescent cell by the increased loss of MDM2 proteins and elevated focal localization from the chromatin-remodeling enzyme ATRX [17, 18]. (healthandwellnesssource.org)
  • Hence, we attempt to Angptl2 recognize what stabilizes MDM2 proteins in quiescent cells. (healthandwellnesssource.org)
  • A rescue assay indicated that DTL should be targeted through TPX2 downregulation for cancer cell growth inhibition. (transhumanist.ru)
  • The PD0332991-induced downregulation of MDM2 and entrance into senescence is normally observed in a variety of types of cancers cell lines, including those produced from well-differentiated and dedifferentiated liposarcoma (WD/DDLS), breasts cancer tumor, non-small cell lung cancers, and glioma [18]. (healthandwellnesssource.org)
  • The storage of iron or copper can prevent their harmful accumulation in cells. (biomedcentral.com)
  • This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entail inflammation-related senescence in human OA chondrocytes. (aging-us.com)
  • conditioned moderate, irritation, senescence, chondrocytes Launch Osteoarthritis (OA) may be the most common joint disorder impacting maturing people [1]. (biotech2012.org)
  • These molecules are essential for embryonic development, wound healing, immune cell recognition, and many other physiological functions. (pharmiweb.com)
  • Due to the role of oncogenic transcriptional activators NFĸB and STAT3 in survivin protein expression, and APE1/Ref-1 redox activity regulating their transcriptional activity, we assessed selective inhibition of APE1/Ref-1's redox function as a novel method to halt prostate cancer cell growth and survival. (oncotarget.com)
  • Cells are potent to go under abnormal growth processes and finally lead to tumor/cancer. (pharmiweb.com)
  • 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)
  • Moreover, DTL silencing inhibited the growth of patient-derived primary cultured HCC cells. (transhumanist.ru)
  • Human CRC cell dormancy and tumor growth can also be perturbed by itraconazole, which is found to inhibit Wnt signaling through noncanonical hedgehog signaling. (ox.ac.uk)
  • Required for vitamin D-mediated growth inhibition by being itself inactivated. (proteopedia.org)
  • D) Quantification of PANC-1 cell growth in smooth agarose by DNA measurement (see Methods). (innovation-ecosystems-agora.com)
  • ATM and ATR are important regulators of cell-cycle arrest caused by DNA damage, including senescence.13,14 To investigate the mechanism DZ2002 further underlying cell-growth inhibition induced by BRD4770, we examined the effect of BRD4770 treatment on ATM and ATR pathway activation. (innovation-ecosystems-agora.com)
  • Stochasticity of metabolism and growth at the single-cell level, Nature, 2014, 514:376-379. (bioss-cnrs.fr)
  • 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)
  • Because of its mutated aggressive genetics, this cell has a selective growth advantage over its neighbors. (medscape.com)
  • 7. Supplemental Fig. 4 Rb expression in palbociclib resistant cells. (figshare.com)
  • In addition p53 expression was high in HCT116 cells and lower in SW480/HT29 cells (Fig. 1C). (immune-source.com)
  • Let us underline nevertheless that such cytokeratin expression is found in embryonic cell lines and that the study only concerned 10 specimens. (globale-dermatologie.com)
  • Our experiments confirm and extend the involvement of CYP2S1 as a potential therapeutic target for enhancing oxaliplatin efficacy in colorectal epithelial cells. (immune-source.com)
  • Strong efficacy in inhibiting chronic inflammation and reversing aging-associated degeneration through amplification of the communication and crosstalk between ECM and cell. (haplnscience.com)
  • For example CYP2S1 which is usually most highly expressed in intestinal tract epithelial cells may be involved in metabolizing aromatic hydrocarbons and other xenobiotic substrates20 21 Madanayake also identified that human CYP2S1 is an important enzyme in the metabolism of COX-derived prostaglandins at nanomolar concentrations and the authors suggested that CYP2S1 may play an important role in modulating the inflammatory process23. (immune-source.com)
  • We studied the consequences of stable inducible JHDM1B silencing in cell lines derived from transformed and untransformed mammary epithelial cells. (oncotarget.com)
  • The immune system plays a key role in surveillance against cancer, but some tumour cells evolve to escape immune elimination [ 4 ]. (biomedcentral.com)
  • Inhibition of APE1/Ref-1 redox function significantly reduced NFĸB transcriptional activity, survivin mRNA and survivin protein levels. (oncotarget.com)
  • Since Myc is the common downstream protein of both BCR-ABL and AurA, we proposed the combinational effect of AKI603 and imatinib could be caused by inhibition of Myc. (scite.ai)
  • Basically, this protein gets all hyperactive and buzzy, going completely wacky and helping cancer/MM cells survive…with very bad consequences. (healthblogs.org)
  • C) Western blots for levels of phosphorylated Chk1 (Ser345), phosphorylated Chk2 (Thr68), and total cdc25C protein manifestation in PANC-1 cells treated with the indicated concentrations of BRD4770 for 72 h. (innovation-ecosystems-agora.com)
  • 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)
  • Exposure of HPAEC to X-rays (10 Gy, 2.4 Gy/min) upregulated senescence markers including p53, p21/waf1, and senescence-associated beta galactosidase (SA-ß-gal). (lonza.com)
  • The tested drug treatments reduced senescence and other ageing markers, further consolidating our approach as a screening platform. (biorxiv.org)
  • Lastly, we will explore the current therapeutic approaches and challenges in targeting senescence. (frontiersin.org)
  • In this study we asked if MSC are developing in an aberrant or unwanted way during ex vivo long-term cultivation and if artificial cultivation conditions exert any influence on their stem cell maintenance. (biomedcentral.com)
  • In vivo, transplantation of miR-10a-overexpressed aged hBM-MSCs promoted implanted stem cell survival and improved cardiac function after MI. (biomedcentral.com)
  • Ex vivo HSC expansion has been suggested as an approach to improve hematopoietic reconstitution from low-cell dose grafts. (stanford.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)
  • 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)
  • The mouse cardiac function of cardiac angiogenesis was measured and cell survival of aged hBM-MSCs was investigated. (biomedcentral.com)
  • Tumor suppressors are involved in regulating the cell cycle, ensuring that cells only divide when necessary and that the process is tightly controlled. (pharmiweb.com)
  • Previous studies proved that bone marrow (BM) stem cells play an important role in improving heart function and delaying cardiac remodeling [ 1 , 2 ] after ischemic damage through reducing fibrosis and increasing angiogenesis. (biomedcentral.com)
  • We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumor cells. (ox.ac.uk)
  • High molecular weight cytokeratin (1/68kD, 19/56,6 kD) was replaced by simple cytokeratin (8/52kD, 18/45kD) which is found in neoplasic cells. (globale-dermatologie.com)
  • HTLV-I-associated adult T-cell leukemia-lymphoma (ATL) and human T-cell lymphotropic virus type I (HTLV-I)-negative peripheral T-cell lymphomas carry poor prognosis mainly because of acquired resistance to chemotherapy. (edu.lb)
  • The CellAgeClock outperforms other epigenetic clocks in measuring subtle ageing changes in primary human cells in culture. (biorxiv.org)
  • Considerable effort has thus been devoted to generating induced pluripotent stem cells (iPSCs) from multiple non-human primate species. (stanford.edu)
  • In summary, we disclose transcriptomic and proteomic data, cell lines, and cell culture resources that may be broadly enabling for non-human primate iPSCs research. (stanford.edu)
  • This technologic and biologic revolution continued through the 1960s to today, and the explosion in technology has fueled the current expansion of knowledge into the working of the human cell. (medscape.com)
  • Mitochondrial transplantation into damaged cells or injured tissues is considered a novel cell-based therapeutic strategy. (fightaging.org)
  • Ig-superfamily CADMs are involved in mediating cell-to-cell adhesion, helping cells stick together and form tissues and organs. (pharmiweb.com)
  • However, the accurate quantitation of mixed cell types in chimeric and mosaic tissues is complicated by sample preparation bias, transgenic silencing, phenotypic similarity, and low-throughput analytical pipelines. (stanford.edu)
  • 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)
  • Here, we investigated the effects of extrinsic mitochondrial transplantation on senescence-induced ARPE-19 cells, an RPE cell line. (fightaging.org)