• As local cell density increases, tensile forces on E-cadherin adhesions are reduced, which prompts the accumulation of the G2 checkpoint kinase Wee1 and downstream inhibitory phosphorylation of Cdk1. (ibecbarcelona.eu)
  • The WEE-1 kinase is a key regulator of several cell cycle checkpoints including G2/M. WEE-1 inhibition can force cells in a state of arrest to continue the cell cycle, ultimately leading to cell death. (almacgroup.com)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • Inhibiting WEE1 abrogates G2 cell cycle arrest, resulting The tyrosine kinase WEE1 regulates cyclin-dependent kinase in premature entry into mitosis and leading to aberrantly 1 (CDK1), which drives cells from the G2 phase into mitosis, high CDK2 activity in S-phase cells, with the deregulated and CDK2, which drives cells into and through the S phase DNA replication resulting in replication stress [1, 5]. (sagepub.com)
  • Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
  • EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. (jcpjournal.org)
  • 8 , 9 Cell cycle program is regulated by cyclin/cyclin-dependent kinase (CDK) complexes. (jcpjournal.org)
  • Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
  • Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. (oncotarget.com)
  • We discovered that WEE1 kinase phosphorylates histone H2B at Tyr37 in a short window of 30-40 minutes in late S phase. (wustl.edu)
  • We obsevered that WEE1 kinase deposit pY37-H2B epigenetic marks upstream of Hist1 cluster, suppressing global histone transcription in both yeast and mammalian cells. (wustl.edu)
  • WEE1 kinase has been reported to be aberrantly expressed in melanomas, glioblastoma multiforme (GBMs), triple negative breast cancers (TNBCs) and prostate cancer. (wustl.edu)
  • The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5. (wikidata.org)
  • Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2. (wikidata.org)
  • The Wee1 class of protein-tyrosine kinase has an important role in cell cycle control. (berkeley.edu)
  • We investigated control mechanisms that regulate the activity, localization, and stability of Wee1, especially the bud neck-localized protein kinase Hsl1 and its more distant paralogs (Gin4 and Kcc4), in particular their recruitment to septin filaments, which assemble at the presumptive site of cell division. (berkeley.edu)
  • In oocytes, caffeine induces the dephosphorylation of MPF by inhibiting the transcription factor Myt1 and activity of the G2 checkpoint kinase Wee1, converting inactive MPF into its active form. (molcells.org)
  • Inhibitory phosphorylation of MPF correlated with phosphorylation changes of cdc25C, the MPF phosphatase, and physical interaction of cdk1 with wee1, the MPF kinase, during M-phase exit. (ox.ac.uk)
  • 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 chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. (arigobio.cn)
  • Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. (arigobio.cn)
  • In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. (arigobio.cn)
  • 12 The activation of cyclin/CDK complex accelerates cell cycle progression, which are regulated by phosphorylation. (jcpjournal.org)
  • mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. (wikidata.org)
  • Regulation of the cell cycle is performed by a phosphorylation cascade involving cyclin/CDK complexes and three restriction checkpoints G1/S G2/M and metaphase which sense flaws in critical stages and subsequently stall cycle progression [5] [6]. (techblessing.com)
  • the cyclin B-cdk 1 complex) is activated at M-phase onset by removal of inhibitory phosphorylation of cdk1 at thr-14 and tyr-15. (ox.ac.uk)
  • Thus, control of MPF activity via inhibitory phosphorylation is believed to be particularly crucial in regulating transition into, rather than out of, M-phase. (ox.ac.uk)
  • Using the in vitro cell cycle system derived form Xenopus eggs, here we show, however, that inhibitory phosphorylation of cdk1 contributes to control MPF activity during M-phase exit. (ox.ac.uk)
  • Treatment of M-phase extracts with a mutant cyclin B1-cdk1AF complex, refractory to inhibition by phosphorylation, impaired binding of the Anaphase Promoting Complex/Cyclosome (APC/C) to its co-activator Cdc20 and altered M-phase exit. (ox.ac.uk)
  • PROCEDURE: The Children's Oncology Group AINV18P1 phase 1 trial evaluated the CDK4/6 inhibitor, palbociclib, in combination with standard four-drug re-induction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. (bvsalud.org)
  • We watch, with much interest, as the Wee1 inhibitor continues through clinical trials with the hope of becoming an effective treatment for cancer patients across the globe. (almacgroup.com)
  • Bang, Yung-Jue 2020-02-07 00:00:00 Background The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. (sagepub.com)
  • Adavosertib (AZD1775) is a first-in-class, potent, selec- Electronic supplementary material The online version of this tive WEE1 inhibitor. (sagepub.com)
  • The aim of this study was to assess niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase (PARP) inhibitor, for its ability to radiosensitize human tumor cells. (oncotarget.com)
  • These results indicate that human tumor cells are significantly radiosensitized by the potent and selective PARP-1 inhibitor, niraparib, in the in vitro setting. (oncotarget.com)
  • Western blotting Subconfluent cells were lysed at 41C for 30 min using lysis buffer containing 10mM Tris HCl, 1 Triton X 100, and 150mM NaCl having a finish protease inhibitor cocktail and a phosphate inhibitor cocktail. (wee1signaling.com)
  • Abrogating G2/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma. (musc.edu)
  • The tumor suppressor protein p53 is inhibition also exploits the G1 checkpoint deficiency seen involved in regulation of the G1 checkpoint. (sagepub.com)
  • Thus, WEE1 inhibition sensitizes cancers have loss-of-function TP53 mutations, meaning that tumor cells to DNA-damaging chemotherapy and can lead to they become more dependent on the G2/M- and S-phase unstable DNA replication, DNA damage and mitotic catas- checkpoints to halt progression of the cell cycle [3, 4]. (sagepub.com)
  • 6 , 7 Therefore, the inhibition of cancer cell proliferation by inducing cell cycle arrest and apoptosis is being an important preventive strategy against cancer. (jcpjournal.org)
  • Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
  • Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)
  • Similar phenotypes were induced by IGF:WEE1 co-inhibition, also via exacerbation of RRM2 downregulation. (nature.com)
  • Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. (elifesciences.org)
  • Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma. (unifi.it)
  • BACKGROUND: Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. (bvsalud.org)
  • As a structure-specific endonuclease, MUS81 is involved in cell cycle regulation and regulates the DNA damage repair approach. (rockinhibitor.com)
  • All eukaryotic cells precisely regulates histone levels by shutting off histone transcription at the end of DNA synthesis. (wustl.edu)
  • 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)
  • The main mechanism of action of the cell cycle checkpoints is through the regulation of the activities of a family of protein kinases known as the cyclin-dependent kinases (CDKs), which bind to different classes of regulator proteins known as cyclins, with specific cyclin-CDK complexes being formed and activated at different phases of the cell cycle. (wikipedia.org)
  • BACKGROUND: This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) - an inhibitory regulator of cancer stem cells (CSCs) - in recurrent glioblastoma. (bvsalud.org)
  • 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)
  • In addition HIV-1 Vpr protein alters the cell-cycle regulation by hijacking centrosome functions. (biomedcentral.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • A comparison of their known functions has identified, besides a common role within protein folding, multiple roles for the cyclophilins within pre-mRNA splicing and cellular signalling, and within transcription and cell cycle regulation for the parvulins. (biomedcentral.com)
  • The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. (wikidata.org)
  • We also studied the roles of other classes of protein kinases (Cla4) and additional post-translational modifications (SUMOylation) in septin complex assembly, formation of different septin-based supramolecular ensembles, disassembly of septin-containing structures, and the function of septin organization in the events required for cell division and membrane septation during cytokinesis. (berkeley.edu)
  • 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)
  • Currently one of three WEE1 inhibitors in clinical development, the Debio 0123 program was initiated based on the deepened understanding of the DNA damage response (DDR) of cancer cells. (almacgroup.com)
  • The DNA in cancer cells can be damaged by a variety of treatments such as radiation, antimetabolites, alkylating agents, DNA topoisomerase inhibitors and platinum-based chemotherapy. (almacgroup.com)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. (tocris.com)
  • As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)
  • The regulation of DNA repair by the cell cycle is largely the result of chromatin alterations that happen through DNA replication, compression, and dissociation that permit cells to divide effectively [8]. (rockinhibitor.com)
  • This finding provides a novel concept that paraspeckles formed by liquid-liquid phase separation potentially affect drug metabolism via negative regulation of PXR function. (aspetjournals.org)
  • Contradictionary findings about miR-17 functions within cell cycle regulation have been described. (techblessing.com)
  • It also helped to open a very exciting avenue of research involving investigators with expertise in different aspects of growth control and cancer.Giordano's lab also discovered the tumor suppressor gene RB2/p130 and the cell cycle kinases CDK9 and CDK10, two other key players in cell cycle regulation and cell differentiation. (newswise.com)
  • Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. (arigobio.cn)
  • The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
  • We employed TNF as being a proinflammatory cytokine to en hance TGFB induced EMT in our model system, and we discover that genes that propagate TNF signaling are upregulated and strongly enriched in GC16 and GC19. (pka-signal.com)
  • Additional examination of GC16 and GC19 exposed en richment for more pathways broadly linked with cancer and EMT, the majority of which overlap or crosstalk with TNF, MAPK, or EGFR signaling. (pka-signal.com)
  • GC16 is enriched for your cytokines and inflammatory response and interleukin one processing pathways, when GC19 is enriched for T cell receptor signaling. (pka-signal.com)
  • EMPs also mediate long range signaling and alter downstream cell function. (nartsignaling.com)
  • Dependence of various cancer cells on WEE1 signaling suggests that targeting epigenetic activity of WEE1 is a viable strategy. (wustl.edu)
  • 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)
  • Required in higher cells for entry into S-phase and mitosis. (arigobio.cn)
  • additionally, at the finish of mitosis, CyclinB1 is prompted to degrade the complex, enabling cells to complete the replication cycle [10]. (rockinhibitor.com)
  • The collective outcome of these events is initiation of intra-S phase and G2 checkpoints in response to DNA damage or replication stress and maintenance of chromatin integrity during repair of damaged DNA, prior to entry into mitosis. (wustl.edu)
  • As the eukaryotic cell cycle is a complex process, eukaryotes have evolved a network of regulatory proteins, known as the cell cycle control system, which monitors and dictates the progression of the cell through the cell cycle. (wikipedia.org)
  • The E2F gene family is a group of transcription factors that target many genes that are important for control of the cell cycle, including cyclins, CDKs, checkpoint regulators, and DNA repair proteins. (wikipedia.org)
  • The three pocket proteins are Retinoblastoma (Rb), p107, and p130, which bind to the E2F transcription factors to prevent progression past the G1 checkpoint. (wikipedia.org)
  • I'm using cell and molecular biology techniques, biochemistry as well as microscopy to characterise the plant SUN proteins. (brookes.ac.uk)
  • This includes finding out what other proteins the SUNs bind to and what functions they have during cell division. (brookes.ac.uk)
  • Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
  • Transcripts found in unfertilized oocytes also encoded a large number of proteins implicated in cell adherence, tight junction and focal adhesion, suggesting high complexity in terms of structure and cellular interactions in embryos prior to midblastula transition (MBT). (biomedcentral.com)
  • The oocyte is loaded with maternal mRNAs and proteins that control the cell maintenance and fate and the formation of the body plan prior to the onset of zygotic genome expression [ 3 , 4 ]. (biomedcentral.com)
  • Cell lysates had been resolved by SDS-PAGE, and proteins had been electro transferred to polyvinylidene fluoride membranes (Millipore, USA). (rockinhibitor.com)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • In eukaryotic cells, various proteins and nucleic acids are orderly arranged in the nucleus and cytoplasm ( Handwerger and Gall, 2006 ). (aspetjournals.org)
  • Recently, it was revealed that the ordered localization of proteins and nucleic acids in the membraneless intracellular microenvironment is modulated by liquid-liquid phase separation (LLPS) ( Shin and Brangwynne, 2017 ). (aspetjournals.org)
  • Many strikingly miR-17 -20 and -106b had been found to market cell proliferation by raising the intracellular activity of E2F transcription elements even though miR-17 -20 and -106b straight focus on the transcripts that encode because of this proteins family members. (techblessing.com)
  • Additionally utilizing a cocktail of development and differentiation elements (XXL-medium) differentiation of USSC into cells of neuronal lineage (XXL-USSC) expressing neurofilament and Vandetanib trifluoroacetate sodium route proteins was acquired [3]. (techblessing.com)
  • His early research includes seminal work done in 1989, demonstrating the importance of cell cycle proteins in the functioning of DNA tumor viruses. (newswise.com)
  • Those complexes, in turn, activate different downstream targets to promote or prevent cell cycle progression. (wikipedia.org)
  • Unfortunately, the molecular and cellular basis of microparticle production and downstream cell function is poorly understood. (nartsignaling.com)
  • and the metaphase-to-anaphase transition, also known as the spindle checkpoint. (wikipedia.org)
  • Molecular Biology of the Cell, 19 (7). (cshl.edu)
  • 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)
  • Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
  • In addition, tumor-associated antigens (TAAs) produced by irradiated tumor cells can be captured by antigen-presenting cells (APCs) in the TME and presented to T cells. (nature.com)
  • The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)
  • T cell-based immunotherapy, such as immune checkpoint blockade or adoptive T cell transfer, is limited by the ability of T cells to detect major histocompatibility complex (MHC)-presented antigen by tumor cells. (elifesciences.org)
  • Human tumor cells derived from lung, breast and prostate cancers were tested for radiosensitization by niraparib using clonogenic survival assays. (oncotarget.com)
  • Niraparib also sensitized tumor cells to H 2 O 2 and converted H 2 O 2 -induced single strand breaks (SSBs) into DSBs during DNA replication. (oncotarget.com)
  • Finally, we showed that ssDNA lesions are converted to toxic DSBs in cells lacking functional ataxia telangiectasia mutated (ATM), likely due to failure to form 53BP1 bodies and/or a role for ATM in SSB repair or fork protection [ 14 ]. (nature.com)
  • Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. (nature.com)
  • Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
  • Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
  • Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)
  • 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)
  • ATR phosphorylates the CHK1 which in turn phosphorylates and activates WEE1. (wustl.edu)
  • Objective This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose. (sagepub.com)
  • Patients and methods Nineteen patients received adavosertib 175 mg twice daily (bid) for 2.5 days (five doses) in combina- tion with carboplatin (AUC 5) alone or paclitaxel (175 mg/m ) plus carboplatin, or adavosertib 225 mg bid for 2.5 days in combination with paclitaxel plus carboplatin in 21-day cycles. (sagepub.com)
  • Conclusions Adavosertib 175 mg bid for 2.5 days was chosen as the recommended Phase II dose in combination with pacli- taxel and carboplatin in Asian patients. (sagepub.com)
  • Furthermore these microRNAs downregulate WEE1 which is involved with G2/M changeover also. (techblessing.com)
  • Conclusions/Significance Mir-17 -20 and -106b downregulate a common group of pro- and anti-proliferative focus on genes to effect cell routine development of USSC and boost intracellular activity of E2F transcription elements to govern G1/S changeover. (techblessing.com)
  • 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)
  • For a century, the nucleus has been the focus of extensive investigations in cell biology. (brookes.ac.uk)
  • Journal of Cell Biology, 83 (2 PART). (cshl.edu)
  • Journal of Cell Biology, 95 (2). (cshl.edu)
  • Nature Cell Biology, 9 (5). (cshl.edu)
  • LLPS, which was originally studied in the field of physical chemistry, has been extended to the field of cell biology since the 2010s. (aspetjournals.org)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • Transmembrane and intracellular signal transduction mechanisms are the focus of our group, especially understanding how extracellular stimuli control cell growth and division, cell morphology, and gene expression at the biochemical level. (berkeley.edu)
  • He has published over 600 papers on gene therapy, cell cycle, genetics of cancer, and epidemiology. (newswise.com)
  • The transforming gene products of these viruses, such as the E1A oncoproteins of adenovirus 5, led to the identification of cellular factor p60, known as cyclin A. This research was the first demonstration of a physical link between cellular transformation and the cell cycle, thereby paving the way for the melding of these two areas of research. (newswise.com)
  • At M-phase exit, MPF is destroyed by ubiquitin-dependent cyclin proteolysis. (ox.ac.uk)
  • Arrestins present elevated expression in differentiated cells and inhibit cellular responses to growth stimuli. (pka-signal.com)
  • Notably, we found that the expression of the CHK1 phosphatase PP1α is increased in Spi1/PU.1-overexpressing cells. (oncotarget.com)
  • MKN45 was a gastric cancer cell line that was made use of as a good manage, as a result of its high expression of c Met and phospho Met. (wee1signaling.com)
  • DNA damage is the main indication for a cell to "restrict" and not enter the cell cycle. (wikipedia.org)
  • RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
  • Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. (tocris.com)
  • These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)
  • When this damage occurs, the cells respond by pausing the cell cycle temporarily to allow for DNA repair, hence reducing the effectiveness of cytotoxic therapies against the cancer cells. (almacgroup.com)
  • Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • Numerous genes transcribed in oocytes are involved in multiple aspects of cell maintenance and protection, including metabolism, signal perception and transduction, RNA processing, cell cycle, defense against pathogens and DNA damage. (biomedcentral.com)
  • One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
  • Endogenous biomolecules (such as lactate dehydrogenase) or previously added exogenous labels (such as the radioisotope 51Cr) that leak into the media are then measured as an indirect readout of the damage caused by effector cells. (technologynetworks.com)
  • Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab. (nature.com)
  • Microarray analyses detected a suite of master developmental regulators that control differentiation and maintenance of diverse cell lineages. (biomedcentral.com)
  • MicroRNAs also appear as important regulators of cell cycle events [27] [28]. (techblessing.com)
  • 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)
  • Pathway for polyarginine entry into mammalian cells. (xcessbio.com)
  • Clonogenic survival analyses indicated that micromolar concentrations of niraparib radiosensitized tumor cell lines derived from lung, breast, and prostate cancers independently of their p53 status but not cell lines derived from normal tissues. (oncotarget.com)
  • WEE1 phosphorylates H2B at Tyr37 upstream of histone cluster 1, Hist1. (wustl.edu)
  • Immunoprecipitation assays using PXR-overexpressing HepG2 (ShP51) cells revealed that PXR interacts with not only DAZAP1 but also NEAT1_2, a long noncoding RNA included in the paraspeckle, and that the interaction between PXR and NEAT1_2 was disassociated by rifampicin. (aspetjournals.org)
  • For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.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)
  • This clinical phase of Debio 0123 is highly anticipated in light of the therapeutic potential of the molecule. (almacgroup.com)
  • Here, we describe the pre-clinical in vitro and in vivo study of irradiated haNK cells engineered to express a second-generation chimeric antigen receptor (CAR) targeting programmed death-ligand 1 (PD-L1). (elifesciences.org)
  • While many methods have been developed to screen and evaluate the efficacy of immune cell‑mediated killing, there is a need for a more robust in vitro assay to accurately predict the in vivo behavior of therapies. (technologynetworks.com)
  • While the data provided by these assays help piece together an understanding of different facets of immune cell‑mediated killing, it is important to note that the parameters being reported often do not correlate with target cell killing efficacy in vivo. (technologynetworks.com)
  • We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. (oncotarget.com)
  • Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. (elifesciences.org)
  • 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)
  • The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. (genominfo.org)
  • It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
  • These effects resulted in significant accumulation of unreplicated single-stranded DNA and increased cell death, indicative of replication catastrophe. (nature.com)
  • Compared to the eukaryotic cell cycle, the prokaryotic cell cycle (known as binary fission) is relatively simple and quick: the chromosome replicates from the origin of replication, a new membrane is assembled, and the cell wall forms a septum which divides the cell into two. (wikipedia.org)
  • Intensities of c Met immunoreactivity had been defined as: 0, total absence of membrane staining or membrane staining in under 30 of cancer cells, 1t, faint and partial membrane staining in not less than 30 of cancer cells, 2t, robust and finish staining in at least 30 of cancer cells. (wee1signaling.com)
  • The most commonly used method for measuring immune cell‑mediated killing is the release assay, where effector cell‑mediated disruption of the target cell membrane results in leakage of its cytoplasmic contents into the culture medium. (technologynetworks.com)
  • Inhibitory effect of EESR on cancer cell growth and proliferation was determined by water-soluble tetrazolium salt assay. (jcpjournal.org)
  • However cultured USSC quickly end proliferation upon addition of XXL-medium and such cell routine exit events are inherently connected to neurogenesis [4]. (techblessing.com)
  • Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. (wikipedia.org)
  • First, given evidence that IGFs regulate the response to IR, we also found evidence that IGF-1R depletion induced endogenous DNA lesions marked by γH2AX foci in prostate cancer cells [ 10 ]. (nature.com)
  • However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. (nature.com)
  • Here, we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. (elifesciences.org)
  • The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. (jcpjournal.org)
  • EESR showed significant antioxidant activity and inhibitory effect on HT29 cell growth in a dose-dependent manner. (jcpjournal.org)
  • By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells. (oncotarget.com)
  • Role for non-proteolytic control of M-phase-promoting factor activity at M-phase exit. (ox.ac.uk)
  • Here, we show that epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell-cycle progression. (ibecbarcelona.eu)
  • 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)
  • As the cell progresses through G1, depending on internal and external conditions, it can either delay G1, enter a quiescent state known as G0, or proceed past the restriction point. (wikipedia.org)
  • 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)
  • Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. (tocris.com)
  • Belfast, Northern Ireland- March 5, 2020 - Debiopharm - a Swiss biopharmaceutical company, has announced the advancement of its first-in-human, phase 1 study as patients with advanced solid tumours will be administered with cancer treatment Debio 0123 in combination with carboplatin. (almacgroup.com)
  • The abnormal cell growth is one of the critical characteristics of cancer for invasion or spreading out to other parts of the body. (jcpjournal.org)
  • PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. (elifesciences.org)
  • 4 xCELLigence real-time cell analysis 6 Diverse cancer immunotherapy applications 6 How does the xCELLigence real-time cell analysis assay work? (technologynetworks.com)
  • Cancer immunotherapies can be divided into four major categories: - Cytokines/immunomodulation agents - Monoclonal antibodies - Cell‑based therapies - Oncolytic viruses Though monoclonal antibodies currently represent the largest class of commercialized cancer immunotherapies, cell‑based therapies are rapidly making headway. (technologynetworks.com)
  • This class of personalized therapies involves collecting immune cells from an individual, engineering them to recognize and kill cancer cells, before culturing, and reintroducing them into the same individual. (technologynetworks.com)