• This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
  • Here we show that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)-directed FOXM1 phosphorylation switch. (elsevierpure.com)
  • During normal DNA replication, the checkpoint kinase ATR (ataxia-telangiectasia and Rad3-related) is activated by ETAA1 to block this switch until the S phase ends. (elsevierpure.com)
  • Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. (bioone.org)
  • The cell cycle delay was totally dependent on the Gcn2 kinase, a sensor of the nutritional status, and was accompanied by phosphorylation of the translation initiation factor eIF2alpha and by a general depression of translation. (ox.ac.uk)
  • SFN induces cell cycle arrest and apoptosis in cancer cells, inhibits tubulin polymerization, activates checkpoint 2 kinase, and inhibits histone deacetylase activity. (sproutnet.com)
  • When damaged DNA cannot be repaired, a functional DDR machinery triggers a signaling cascade, leading to cell senescence or apoptosis. (encyclopedia.pub)
  • JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. (bioone.org)
  • Similar to these drugs, eribulin is a microtubule inhibitor that induces apoptosis of cancer cells by stopping mitosis in the G2/M phase of the cell cycle . (shu.edu)
  • These cells do not undergo apoptosis, and the primary outcome of caspase-2 activation is continued, cell division. (nature.com)
  • This indicates a role distinct from caspase-2's reported role in inducing apoptosis to remove damaged or aneuploid cells [7][8]. (nature.com)
  • therefore, we overexpressed Bcl-X L to distinguish caspase-2's role in cell division and DNA protection from its role in apoptosis. (nature.com)
  • While other groups have demonstrated non-apoptotic roles for caspase-2 in DNA repair, cell cycle arrest [2], this is the first demonstration that these roles are regulated by a distinct pathway to apoptosis. (nature.com)
  • If apoptosis is not an essential mechanism for its tumor suppression function, then a role in regulating the cell cycle may be. (nature.com)
  • The overexpression of XPO1 is one mechanism by which neoplastic cells inactivate TSPs and thereby circumvent cell-cycle regulation, genome survey and apoptosis. (karyopharm.com)
  • Selinexor inhibits XPO1, resulting in the accumulation of TSPs and other key mediators in the nucleus, restoring cell-cycle checkpoints and inducing growth arrest and apoptosis in malignant cells. (karyopharm.com)
  • RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
  • A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)
  • In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
  • however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
  • PARP is a family of enzymes that comprises 17 members with different functions, such as maintenance of genomic stability, transcriptional regulation, and cell death [ 16 ] [ 17 ] . (encyclopedia.pub)
  • A collection of basic cutting-edge techniques for studying the mechanisms underlying cell cycle regulation and checkpoint control. (buynsellbooksonline.com)
  • Results: RB reconstitution in RB-deficient lines restored regulation of topoIIα, thymidylate synthase, and cyclin A. Similarly, RB overexpression in RB-proficient cells caused further regulation of some RB/E2F target genes including thymidylate synthase and topoIIα. (elsevierpure.com)
  • Conclusions: These results demonstrate that RB reconstitution into RB-deficient NSCLC lines establishes regulation of certain RB/E2F target genes and restores G1 arrest mechanisms. (elsevierpure.com)
  • and the M (mitosis) phase, during which the duplicated chromosomes (known as the sister chromatids) separate into two daughter nuclei, and the cell divides into two daughter cells, each with a full copy of DNA. (wikipedia.org)
  • DSBs are first detected and signaled by the DNA damage checkpoint that triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. (cea.fr)
  • Thus, ATR couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G 2 checkpoint. (elsevierpure.com)
  • Many chemotherapeutic agents explore defects in the cell cycle machinery of cancer cells to halt the cycle through mitosis inhibition. (medicalxpress.com)
  • However, existing mitosis-targeting chemotherapeutic agents do not discriminate between healthy and malignant cell lines, resulting in severe side-effects . (medicalxpress.com)
  • The challenge therefore is to identify molecular targets associated with mitosis of cancer cells. (medicalxpress.com)
  • 3.A.2 In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization. (texasgateway.org)
  • In the mitosis, the chromosomes are aligned and the two sister chromatids are separated, each becoming the genetic material of the daughter cells. (androbose.in)
  • Mitosis brings about the division of the nuclear material or Karyokinesis in 4 phases called prophase , metaphase , anaphase , and telophase . (androbose.in)
  • The G 2 gap phase further separates S-phase from mitosis, allowing for continued cell growth and maturation before cell division. (rupress.org)
  • Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)
  • Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
  • Cell proliferation includes a series of events that is tightly regulated by several checkpoints and layers of control mechanisms. (frontiersin.org)
  • In conclusion, we provide useful experimental approaches and bioinformatics to identify informative and predictive genes at the single-cell level, which opens up new means to describe and understand cell proliferation and subpopulation dynamics. (frontiersin.org)
  • However, most of our knowledge about cell proliferation comes from studies that average data from large and mixed cell populations. (frontiersin.org)
  • K405R mutant expressing cancer cells have reduced G1/S transition and slower proliferation compared to wildtype. (oncotarget.com)
  • Collectively, these findings suggest that SAMHD1 acetylation enhances its dNTPase activity and promotes cancer cell proliferation. (oncotarget.com)
  • Binding of one molecule of eribulin to two microtubules can inhibit cell proliferation by 50%, and such binding is reversible. (shu.edu)
  • This reduced ability to arrest proliferation was found to be due to an impaired ability to downregulate cyclin D1, a key gatekeeper of the G1/S checkpoint. (tmc.edu)
  • These findings indicate that pancreatic cancer cells have increased tolerance for elevated ER stress compared to normal cells, and this tolerance results in continued tumor cell proliferation under proteotoxic conditions. (tmc.edu)
  • In recent years, interest in the possible molecular regulators of cell proliferation and differentiation in a wide range of regeneration models has grown significantly, but the cell kinetics of this process remain largely a mystery. (mdpi.com)
  • Amputation-induced proliferation occurred predominantly within the epidermal and intestinal epithelium, as well as wound-adjacent muscle fibers, where clusters of cells at the same stage of the cell cycle were found. (mdpi.com)
  • Cell proliferation involves the replication of all cellular contents with the required energy for this to happen. (hindawi.com)
  • To prevent aberrant cell proliferation, these pathways are tightly regulated. (hindawi.com)
  • This activation is necessary for both cell proliferation as well as glucose uptake and use. (hindawi.com)
  • MTT colorimetric assays, colony formation assays and 5‑ethynyl‑20‑deoxyuridine incorporation assays were also conducted to evaluate ACC cell proliferation. (cancerindex.org)
  • Many factors are involved in causing and permitting the unregulated proliferation of cells that occurs in cancer. (msdmanuals.com)
  • Overview of Cancer Cancer is an unregulated proliferation of cells. (msdmanuals.com)
  • Therefore, we are trying to understand the independent mechanism by which mammalian cells effectively inhibit the replication machinery during stress preventing it from drifting towards a catastrophic path of genomic instability. (nii.res.in)
  • While genomic instability contributes to the poor prognosis for GBM patients [ 5 ] , the damaged DNA offers a target for pharmacological approaches that induce cancer cell death by a mechanism called synthetic lethality. (encyclopedia.pub)
  • and the metaphase-to-anaphase transition, also known as the spindle checkpoint. (wikipedia.org)
  • The researchers screened 20 solid cancer cell lines relative to gene silencing to identify a highly responsive chemo-resistant ovarian cancer cell line that underwent significant depletion in mitotic spindle-dynamics for effective experimental cancer treatment. (medicalxpress.com)
  • The centrosomes which help in the arrangement of microtubules to form spindle fibers, move to the opposite poles of the cell. (androbose.in)
  • Attachment of each kinetochore to a spindle fiber is assessed at the M checkpoint. (openstax.org)
  • The identified DEGs included 20 downregulated genes and 51 upregulated genes, which were highly associated with the cell cycle, organelle fission, chromosome segregation, cell division and spindle stability. (cancerindex.org)
  • The molecular processes behind cell cycle progression have been dissected by numerous morphological studies on live or fixed single cells using a plethora of techniques to visualize components and processes during cell division. (frontiersin.org)
  • Molecular Cell 15: 245-258. (nii.res.in)
  • Molecular Cell 11: 997-1008. (nii.res.in)
  • Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. (springer.com)
  • Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.com)
  • This killing process occurs only if two molecular pathways are simultaneously deficient in one cell, whereas the isolated defect is innocuous [ 6 ] . (encyclopedia.pub)
  • The molecular mechanisms underlying the role of JAM3 in placental dysfunction remain unclear. (bioone.org)
  • The protein is associated with microtubules , and Chatterjee and colleagues silenced the gene via short interfering RNA (siRNA) a molecular biological mechanism to study genes, targeting the CKAP5 encapsulated in lipid nanoparticles for in vivo delivery. (medicalxpress.com)
  • Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. (oncotarget.com)
  • In the further studies, we will investigate the molecular mechanisms by which Znf179 regulates p35 expression. (tmu.edu.tw)
  • Furthermore, the underlying molecular mechanism of carcinogenesis is poorly understood, and prognostic prediction of ACC has low accuracy. (cancerindex.org)
  • In the present study, a bioinformatics approach was used to investigate the molecular mechanisms and prognosis of ACC. (cancerindex.org)
  • The available information suggests that surveillance mechanisms or 'checkpoints' which are known to regulate the eukaryotic cell cycle may be absent or altered in E. histolytica . (ias.ac.in)
  • Emerging evidences suggest that microRNA target genes that regulate DNA replication and cell cycle progression and we aim to determine how microRNA regulate the DNA replication machinery as cell progresses from one phase to the next. (nii.res.in)
  • Summing up, we are trying to understand the mechanisms by which microRNAs regulate mammalian cell cycle and DNA replication in normal and pathological conditions. (nii.res.in)
  • One such protein is the cytoskeleton-associated protein 5 (CKAP5), widely expressed in a variety of cells to regulate the dynamics of microtubules in human cells. (medicalxpress.com)
  • Cancer results from unchecked cell division caused by a breakdown of the mechanisms that regulate the cell cycle. (texasgateway.org)
  • In conclusion, pancreatic cancer cells demonstrate a globally compromised ability to regulate the unfolded protein response. (tmc.edu)
  • In the present study, we investigated whether the TKIs ibrutinib, PD180970, and cabozantinib, which have different on-targets, selectively regulate AD pathology in 3.5- to 4-month-old 5xFAD mice (a model of the early phase of AD). (biomedcentral.com)
  • Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
  • Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
  • Here, we used quantitative real-time PCR, profiling the expression of 93 genes in single-cells from three different cell lines. (frontiersin.org)
  • We found that the total transcript level per cell and the expression of most individual genes correlated with progression through the cell cycle, but not with cell size. (frontiersin.org)
  • Detailed analysis of cell cycle predictive genes allowed us to define subpopulations with distinct gene expression profiles and to calculate a cell cycle index that illustrates the transition of cells between cell cycle phases. (frontiersin.org)
  • Here, we employed single-cell gene expression profiling to describe the dynamic transition between cell proliferative states in three different cell lines using a panel consisting of 93 marker genes. (frontiersin.org)
  • It has also been shown that although this organism contains sequence homologs of genes which are known to control the cell cycle of most eukaryotes, these genes may be structurally altered and their equivalent function yet to be demonstrated in amoeba. (ias.ac.in)
  • c Reactome functional enrichment of cell cycle genes based on shared differentially expressed (DE) genes from previous studies. (biomedcentral.com)
  • From M/G1 to S phase, the shared DE genes from both cell lines were significantly enriched. (biomedcentral.com)
  • PARP inhibitors (PARPis) can induce synthetic lethality in cancer cells with preexistent defects in the homologous recombination (HR) repair pathway, such as deleterious mutations of the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) suppressor genes [ 7 ] [ 8 ] . (encyclopedia.pub)
  • Proto-oncogenes are normal genes that, when mutated in certain ways, become oncogenes , genes that cause a cell to become cancerous. (texasgateway.org)
  • Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. (biomedcentral.com)
  • Using a microarray approach and subsequent functional annotation analysis, we identified the differentially expressed genes in Znf179 knockdown cells and found that several genes are involved in development, cellular growth, and cell cycle control. (tmu.edu.tw)
  • Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
  • This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. (cdc.gov)
  • Therefore, we conclude that DDK regulates a largely checkpoint-independent role of Claspin function. (caltech.edu)
  • We propose a model where caspase-2 regulates the cell cycle and protects DNA replication forks to prevent DNA damage accrual in a pathway distinct from its apoptotic role. (nature.com)
  • If caspase-2 regulates cell division through the same pathway, it would be expected to phenocopy the cell cycle results of caspase-2 null cells. (nature.com)
  • Consistent with our evidence that caspase-2 regulates a replication checkpoint, the chromosomal aberrations detected in caspase-2-deficient cells are not repaired before metaphase. (nature.com)
  • Positive feedback plays an essential role in regulating the progression from G1 to S phase, particularly involving the phosphorylation of Rb by a Cyclin/CDK protein complex. (wikipedia.org)
  • Once recruited to DSB, these complexes get activated and induce the phosphorylation of numerous targets including transducing kinases, which subsequently phosphorylate downstream effectors to delay cell cycle and promote DNA repair. (cea.fr)
  • Additionally, the checkpoint kinases modify the chromatin surrounding DNA damages through phosphorylation of the H2A histone (H2AX in mammals). (cea.fr)
  • Pancreatic cancer cells exhibited altered UPR activation characterized by a delay in both phosphorylation of eIF2α and induction of spliced XBP1. (tmc.edu)
  • In normal cells, glucose participates in cellular energy production through glycolysis as well as through its complete catabolism via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (hindawi.com)
  • ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
  • Chk1 facilitates the arrest of cell cycle progression and the inhibition of replication origin firing. (caltech.edu)
  • Inhibition of Znf179 expression by RNA interference significantly attenuated neuronal differentiation of P19 cells and a primary culture of cerebellar granule cells. (tmu.edu.tw)
  • Both the initiation and inhibition of cell division are triggered by events external to the cell when it is about to begin the replication process. (openstax.org)
  • Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein. (wikipedia.org)
  • It is known that replication factors are downregulated during stress and we have observed that cullin 4-based ubiquitin ligase mediate the proteolysis of Mcm10, a protein essential for the initiation and elongation phases of DNA replication. (nii.res.in)
  • Resection is accompanied by the binding of replication protein A (RPA) to the 3' single-stranded overhangs, which helps recruiting the checkpoint complexes. (cea.fr)
  • Ensure healthy lives and promote well-being for all at all ages: We are presently engaged in a pilot study investigating the potential of the ZFP36L1 protein as a therapeutic target in osteosarcoma cells. (westminster.ac.uk)
  • SAM domain and HD domain containing protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in non-cycling myeloid cells. (oncotarget.com)
  • One culprit that has been identified is the p53 protein (coded for by the p53 gene), a major regulator at the G 1 checkpoint. (texasgateway.org)
  • All cancers start when a gene mutation gives rise to a faulty protein that plays a key role in cell reproduction. (texasgateway.org)
  • The change in the cell that results from the malformed protein may be minor-perhaps a slight delay in the binding of Cdk to cyclin or an Rb protein that detaches from its target DNA while still phosphorylated. (texasgateway.org)
  • Under conditions of moderate ER stress, the UPR promotes cell cycle arrest which allows time for successful protein load reduction and enables cell survival. (tmc.edu)
  • Activation of the unfolded protein response after ER stress induction was determined by comparing expression of key UPR mediators in non-tumorigenic pancreatic ductal cells to pancreatic cancer cells. (tmc.edu)
  • Collectively, our results suggest that induction of the Znf179 gene may be associated with p35 expression and p27 protein accumulation, which leads to cell cycle arrest in the G0/G1 phase, and is critical for neuronal differentiation of P19 cells. (tmu.edu.tw)
  • As at the G 1 checkpoint, cell size and protein reserves are assessed. (openstax.org)
  • These signaling pathways are disrupted in GBM, and despite the accumulation of DNA damage, cancerous cells will thrive, maintaining survival and pathological cell division [ 2 ] [ 4 ] . (encyclopedia.pub)
  • Most of the identified module pairs cover cooperative pathways and components essential to the cell cycle. (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)
  • Lipids, amino acids, and nucleotides necessary for the biosynthesis of the daughter cells are mostly provided by intermediate metabolites of these pathways. (hindawi.com)
  • The first is a stochastic model of the progression of cell cycle states, which is applied to experimental data for two synchronized isogenic MMR + and MMR − colon cancer cell lines treated with and without IUdR. (aacrjournals.org)
  • In addition, CKI may also inhibit NHEJ, the major repair mechanism for DSBs. (biomedcentral.com)
  • Further evaluation of the UPR-mediated effects on cell cycle progression revealed that pancreatic cancer cells showed a compromised ability to inhibit G1 to S phase progression after ER stress. (tmc.edu)
  • Over a decade ago, this phytochemical was identified as a likely chemopreventive agent based on its ability to induce Phase 2 detoxification enzymes, as well as to inhibit Phase 1 enzymes involved in carcinogen activation. (sproutnet.com)
  • A lack of HGH can inhibit cell division, resulting in dwarfism, whereas too much HGH can result in gigantism. (openstax.org)
  • Crowding of cells can also inhibit cell division. (openstax.org)
  • The decision to commit to a new round of cell division occurs when the cell activates cyclin-CDK-dependent transcription which promotes entry into S phase. (wikipedia.org)
  • This deficiency results in reduced cyclin D1 repression through an eIF2α-mediated mechanism. (tmc.edu)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • One of the critical processes monitored by the cell cycle checkpoint surveillance mechanism is the proper replication of DNA during the S phase. (texasgateway.org)
  • [ 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)
  • The M phase is the actual division phase wherein the mother cell divides into two daughter cells. (androbose.in)
  • The G1 checkpoint, also known as the restriction point in mammalian cells and the start point in yeast, is the point at which the cell becomes committed to entering the cell cycle. (wikipedia.org)
  • When fast-dividing mammalian cells are grown in culture (outside the body under optimal growing conditions), the length of the cycle is about 24 hours. (openstax.org)
  • Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. (babraham.ac.uk)
  • Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
  • By applying the random forests algorithm, a supervised machine learning approach, we show how a multi-gene signature that classifies individual cells into their correct cell cycle phase and cell size can be generated. (frontiersin.org)
  • The outcomes highlighted the importance of the gene of interest as a therapeutic target to investigate genetically unstable ovarian cancers to further elucidate its mechanisms of action. (medicalxpress.com)
  • The gene, which is called MYBL2 , encodes a transcription factor that helps to control the cell division cycle. (elifesciences.org)
  • This suggests that additional mechanisms must be acting to reduce expression of their remaining copy of the gene. (elifesciences.org)
  • Polyploidy is often witnessed in cells prior to differentiation, in embryonic cells or in diseases such as cancer. (ias.ac.in)
  • b Effects on DNA repair in cancer cells by CKI. (biomedcentral.com)
  • Previous studies in our laboratory have described increased and preferential radiosensitization of mismatch repair-deficient (MMR − ) HCT116 colon cancer cells with 5-iododeoxyuridine (IUdR). (aacrjournals.org)
  • Dose-dependent response of CKAP5 knockdown across various cancer cell lines. (medicalxpress.com)
  • In this work, Chatterjee and the team screened the effect of CKAP5 silencing in solid cancer cell lines and in normal non-cancer epithelial cell lines as a negative control. (medicalxpress.com)
  • Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells. (oncotarget.com)
  • What causes uncontrolled cell growth, and why does it often cause cancer? (texasgateway.org)
  • Cancer comprises many different diseases caused by a common mechanism-uncontrolled cell growth. (texasgateway.org)
  • In turn, as a result of research into the abnormal cancer cell, the basic understanding of the cell has greatly improved. (medscape.com)
  • Work across many laboratories is geared toward elucidating the genetics behind cancer, discovering cellular mechanisms that lead to cancer, and elucidating intracellular and intercellular interactions that allow this progression. (medscape.com)
  • Cancer is characterized by uncontrolled growth and division of a cell, with extension beyond the normally limiting basement membrane and through the boundaries of normal cells. (medscape.com)
  • 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 this dissertation, I investigated the role of endoplasmic reticulum (ER) stress and its effects on the cell cycle in pancreatic cancer cells. (tmc.edu)
  • The study of the underpinning mechanisms of chemoradiation response was carried out through in vitro models of cervical cancer. (biomedcentral.com)
  • Notably, surgical treatment has also the potential advantage of removing chemoradioresistant residual tumor foci, with a higher local control and possibly better survival, since resistance of cancer cells to CRT remains a major therapeutic drawback. (biomedcentral.com)
  • Dr. Atkins' major research interests are cancer immunotherapy, treatment of melanoma and renal cell carcinoma, predictive markers for response to biologic therapy, and antiangiogenic and targeted therapies. (melanoma.org)
  • RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
  • In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. (nature.com)
  • One study reported an increased survival benefit with simultaneous RT compared with sequential administration, 8 while another study found no significant difference between the two strategies, 9 possibly because simultaneous RT plus immunotherapy and the administration of an ICI before RT may kill cancer cells as well a substantial number of immune cells, leading to poor systemic response and toxic side effects. (nature.com)
  • Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
  • However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
  • In contrast to normal cells, most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactate fermentation, even in the presence of oxygen, a less efficient metabolism compared to a low rate of glycolysis followed by mitochondrial oxidation of pyruvate [ 2 ]. (hindawi.com)
  • In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)
  • Metabolic adaptations of cancer cells. (hindawi.com)
  • Glucose and glutamine are the 2 major substrates used by cancer cells. (hindawi.com)
  • Cancer cells, particularly those arising from the bone marrow or lymphatic system, may have a short generation time, and there usually are a smaller percentage of cells in G0 (resting phase). (msdmanuals.com)
  • A subpopulation of cells within a cancer has the properties of stem cells. (msdmanuals.com)
  • A cancer may release cells into the circulation at a very early stage of development. (msdmanuals.com)
  • Circulating cancer cells are present in many patients with advanced cancer and even in some with localized disease. (msdmanuals.com)
  • Although most circulating cancer cells die, an occasional cell may penetrate into tissues, generating a metastasis at a distant site. (msdmanuals.com)
  • Experiments suggest that the abilities to invade, migrate, and successfully implant and stimulate new blood vessel growth are all important properties of the cells that cause metastases, which are likely a subpopulation of the primary cancer. (msdmanuals.com)
  • Cancer cells often present neoantigens on their cell surface that can be detected as "non-self" by the immune system, resulting in an attack by the immune system. (msdmanuals.com)
  • DNA damage is the main indication for a cell to "restrict" and not enter the cell cycle. (wikipedia.org)
  • If a cell cannot reproduce, the mutation is not propagated and the damage is minimal. (texasgateway.org)
  • Cells become senescent when there are DNA damage or any other problem. (androbose.in)
  • This illustration shows the proposed relative location of the 2 known cell cycle arrest points in cells with MTD (microtubule damage). (shu.edu)
  • In contrast, while caspase-2-deficiency led to an increased proportion of S-phase cells and a progressive decrease in the proportion of G1-phase cells following treatment with arresting concentrations of the DNA damaging agent camptothecin and increased DNA damage following S-phase arrest, overexpression of Bcl-X L did not change the cell cycle profiles or the amount of DNA damage. (nature.com)
  • For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)
  • In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G 1 checkpoint. (openstax.org)
  • The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. (medscape.com)
  • 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)
  • A phase II study showed that patients with resected local-regionally advanced head and neck squamous cell carcinoma (HNSCC) had improved survival when pembrolizumab was added to adjuvant RT (NCT02641093). (nature.com)
  • In our previous study, we show that the expression of Znf179 is upregulated during P19 cell neuronal differentiation. (tmu.edu.tw)
  • Its prominent properties are A lack of cell differentiation Local invasion of adjoining tissue Metastasis, which is spread to distant sites through. (msdmanuals.com)
  • A p53 dependent checkpoint pathway prevents re-replication. (nii.res.in)
  • In general, NHEJ is the preferred pathway in the G1 phase of the cell cycle, while HR is favored in S and G2 phases. (cea.fr)
  • Considerable attention has focused on SFN as a 'blocking' agent, with the ability to modulate the Nrf2/Keap1 pathway, but recent evidence suggests that SFN acts by numerous other mechanisms. (sproutnet.com)
  • The mechanisms by which isocyanates cause asthma remain unclear, hampering disease prevention, diagnosis, and treatment.7 It is assumed the reactive nature of N=C=O groups underlies isocyanate asthma, with a hapten-based mechanism as the most obvious pathway to pathogenesis.8 However, the critical "self" reaction targets for isocyanate in vivo remain uncertain. (cdc.gov)
  • It has long been noted that caspase-2-deficient cells proliferate faster [2], and elegant studies have shown that caspase-2 induces cell cycle arrest following cytokinesis failure [5]. (nature.com)
  • For a century, the nucleus has been the focus of extensive investigations in cell biology. (brookes.ac.uk)
  • During the last decade, the non-random spatial arrangement of the genome into the nucleus of eukaryotic cells, as emerged as a key regulator of genome functions and notably of the propagation of a stable genome. (cea.fr)
  • A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. (lookformedical.com)
  • The G 2 checkpoint bars entry into the mitotic phase if certain conditions are not met. (openstax.org)
  • Much is known about the control of the G 1 /S, G 2 /M, and metaphase/anaphase transitions, but thus far, no control mechanism has been identified for the S/G 2 transition. (elsevierpure.com)
  • Much is known about the control of the G1/S, G2/M, and metaphase/anaphase transitions, but thus far, no control mechanism has been identified for the S/G2 transition. (elsevierpure.com)
  • These checkpoints occur near the end of G 1 , at the G 2 /M transition, and during metaphase ( Figure 10.10 ). (openstax.org)
  • Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. (babraham.ac.uk)
  • These resistance mechanisms frequently involve reinstatement of ERK1/2 signalling and BRAFi are now deployed in combination with one of three approved MEK1/2 inhibitors (MEKi) to provide more durable, but still transient, clinical responses. (babraham.ac.uk)
  • One class of drugs that explores this killing mechanism are the inhibitors of poly(ADP-ribose) polymerase (PARP) enzyme, an important DDR component. (encyclopedia.pub)
  • All living organisms are the products of repeated rounds of cell growth and division. (wikipedia.org)
  • Such data are only indirectly related to quantitative changes in cells at different states of division and growth. (frontiersin.org)
  • Cy5 is labeled as magenta, and the cell membrane is stained with rabbit anti-human epidermal growth factor receptor and goat anti rabbit488 antibody. (medicalxpress.com)
  • We solve this problem by identifying the cell-surface molecule CD163 as the critical missing component in cell-culture systems, enabling the growth of LDV in immortalized cell lines for the first time. (bvsalud.org)
  • Uncontrolled growth of the mutated cells outpaces the growth of normal cells in the area, and a tumor (- oma ) can result. (texasgateway.org)
  • Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. (shu.edu)
  • Because of its mutated aggressive genetics, this cell has a selective growth advantage over its neighbors. (medscape.com)
  • Herein, we identified that vascular endothelial growth factor (VEGF)-C, a potent lymphangiogenic factor, is up-regulated in endometriotic cells and contributes to increased lymphangiogenesis. (endometriosistreatmentreport.com)
  • An event may be as simple as the death of a nearby cell or as sweeping as the release of growth-promoting hormones, such as human growth hormone (HGH). (openstax.org)
  • External influences, such as growth factors, play a large role in carrying the cell past the G 1 checkpoint. (openstax.org)
  • Initial exponential tumor growth is followed by a plateau phase when cell death nearly equals the rate of formation of daughter cells. (msdmanuals.com)
  • External insults (eg, infections, radiation, drugs) may disrupt stem cell homeostasis in marrow environment, leading to altered growth. (medscape.com)
  • Using the yeast cell cycle as an example, we identified 101 cooperative module associations among 82 modules, and importantly, we established a cell cycle-specific cooperative module network. (biomedcentral.com)
  • Ultraviolet irradiation of fission yeast cells in G1 phase induced a delay in chromatin binding of replication initiation factors and, consistently, a transient delay in S-phase entry. (ox.ac.uk)
  • The G 1 checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. (openstax.org)
  • We show that caspase-2 protects cells from a range of S-phase-related defects, including delayed exit from S-phase, increased stalled replication forks, increased new replication origins, and decreased repair of S-phase-associated chromosomal aberrations [6]. (nature.com)
  • Caspase-2-deficient cells show a significantly higher percentage of S-phase-associated chromosomal aberrations. (nature.com)
  • The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. (lookformedical.com)
  • Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)
  • Aberrations in microRNA activity has been linked to loss of cell cycle and replication control and this has led to oncogenic functions (thereby called oncomirs) being ascribed to them. (nii.res.in)
  • The integrity of DNA replication control and checkpoint mechanisms is essential for preventing tumorigenesis. (caltech.edu)
  • Moving forward from this initiation point, every parameter required during each cell cycle phase must be met or the cycle cannot progress. (openstax.org)
  • In eukaryotic cells the genetic material is surrounded by a membrane system called the nuclear envelope (NE). (brookes.ac.uk)
  • The Nuclear Envelope is a hallmark of eukaryotic cells. (brookes.ac.uk)
  • Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas. (medscape.com)
  • Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. (medscape.com)
  • Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. (medscape.com)
  • During the M phase, the replicated DNA condenses to form the X shaped chromosomes, wherein each sister chromatid is the entire replicated and condensed daughter DNA. (androbose.in)
  • A human cell at this point has 46 chromosomes (and 92 chromatids). (androbose.in)
  • Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. (openstax.org)
  • However, the most important role of the G 2 checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged. (openstax.org)
  • The centrosome cycle (1 or 2 MTOC indicates microtubule organizing centers) is shown to be coordinated with the DNA/chromosome cycle (2N or 4N DNA content). (shu.edu)
  • Exploring this border is now proving hugely rewarding, with implications for many aspects of cell function and plant responses to the environment. (brookes.ac.uk)
  • Exposure of RB-proficient cells to cisplatin, etoposide, or 5-fluorouracil elicited arrest in various phases of the cell cycle while lines deficient for RB exhibited different checkpoint responses. (elsevierpure.com)
  • Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. (cdc.gov)
  • The mechanism of virus restriction by these barriers is poorly understood. (bvsalud.org)
  • Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. (shu.edu)
  • Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
  • Homologous recombination is the main mechanism to repair DNA lesions that block replication forks and fill ssDNA gaps left behind the fork [11]. (nature.com)
  • Topline data from the Phase 2 portion of the SEAL study are expected in mid-2017. (karyopharm.com)
  • Abnormalities in this process lead to a group of diseases known as myeloid malignancies, which include acute myeloid leukaemia-in which the bone marrow produces abnormal white blood cells-and myelodysplastic syndromes, which are caused by too few mature blood cells being produced. (elifesciences.org)
  • This results in an increased number of mutations, leading to abnormal daughter cells. (texasgateway.org)
  • Eventually, all checkpoints in the cell become nonfunctional, and the abnormal cells can crowd out normal cells. (texasgateway.org)
  • This, in turn, creates a clonal population of a single abnormal cell. (medscape.com)
  • This system acts like a timer, or a clock, which sets a fixed amount of time for the cell to spend in each phase of the cell cycle, while at the same time it also responds to information received from the processes it controls. (wikipedia.org)
  • These results provide a global view of the cell cycle and the method can be used to discover the dynamic coordination properties of functional components in other cellular processes. (biomedcentral.com)
  • The main processes that take place during the G2 phase are the duplication of cell organelles and the rearrangement of the cytoskeleton. (androbose.in)
  • I am a senior lecturer in Cell Bilogy and a member of the plant biology group. (brookes.ac.uk)
  • Previous to this I completed my BSc in Cell and Human Biology here at Oxford Brookes University. (brookes.ac.uk)
  • Junctional adhesion molecule 3 (JAM3) is involved in epithelial cell junction, cell polarity, and motility. (bioone.org)
  • Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. (wikipedia.org)
  • A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable. (openstax.org)
  • Eventually, the pace of the cell cycle speeds up as the effectiveness of the control and repair mechanisms decreases. (texasgateway.org)
  • Furthermore, introduction of RB enhances the G1 checkpoint response to chemotherapeutics and decreases chemosensitivity. (elsevierpure.com)
  • mitotically active cells of intact segments do not significantly contribute to the blastemal cellular sources. (mdpi.com)
  • Studies on the protozoan parasite, Entamoeba histolytica suggest that in its proliferative phase, this organism may accumulate polyploid cells. (ias.ac.in)
  • The length of the cell cycle is highly variable, even within the cells of a single organism. (openstax.org)