• 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)
  • Members of the 'O' class of FOX proteins provide the instructions for genes responsible for regulating cellular replication and senescence, resistance to oxidative stress, metabolism, and DNA repair. (foundmyfitness.com)
  • [3] FOXO proteins translate these cues into changes in gene expression that modulate and coordinate an organism's longevity and overall health. (foundmyfitness.com)
  • FOXO proteins' ability to shuttle between sites within the cell places them at the nexus of essential cellular processes. (foundmyfitness.com)
  • Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
  • This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. (rupress.org)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin. (xenbase.org)
  • Targeting Dvl proteins increases imatinib susceptibility of the K562 and MEG-01 cell lines. (bvsalud.org)
  • 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)
  • 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)
  • Cell lysates had been resolved by SDS-PAGE, and proteins had been electro transferred to polyvinylidene fluoride membranes (Millipore, USA). (rockinhibitor.com)
  • 05. Between the 69 ejaculated proteins, 68 may very well be linked to Gene Ontology data. (smadpathway.com)
  • 2nd, we qualitatively examined genes to search for commonality of function amid proteins with high NSAF. (smadpathway.com)
  • In addition, a PPI network can be modeled as an undirected graph, where vertices represent proteins and edges represent interactions between proteins, to prioritize disease associated genes or pathways and to understand the modus operandi of disease mechanisms [ 9 , 10 ]. (hindawi.com)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
  • In response to genotoxic stress, it contributes to turn off CDK1 activity by mediating the degradation of CDC25A in collaboration with Chk1, thereby preventing cell cycle progression before the completion of DNA repair. (wikipedia.org)
  • Correspondingly, most cancer signaling pathways seem to converge on one or more TFs, termed "master regulators" (MRs) [ 4 ], which direct tumor development, progression, and metastasis through hierarchical control of gene expression patterns. (aging-us.com)
  • During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. (oncotarget.com)
  • At the molecular level, pitavastatin induced expression of the cyclin dependent kinase (CDK) inhibitor p21 in a cholesterol independent manner, blocked repressive phosphorylation of the Retinoblastoma tumor suppressor protein at CDK targeted sites, and reduced expression of E2F target genes required for progression through the G1/S boundary. (oncotarget.com)
  • In addition, the absence of Htz1 affects DNA replication and cell cycle progression and causes lethality or sickness in combination with S-phase checkpoint mutants [21]. (irjs.info)
  • Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. (rupress.org)
  • Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. (biomedcentral.com)
  • In the present study, we investigated the relationship of gene expression profiles with malignant progression of human glioma. (biomedcentral.com)
  • Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (proteopedia.org)
  • This prevents the normal progression from G1 to S phase, thus providing a check on replication of damaged DNA (Banin et al. (reactome.org)
  • 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)
  • Genomic stability relies around the precise execution of DNA replication, chromosome segregation, DNA repair and genomic monitoring mechanisms, and their integration with cell cycle progression and also other processes. (rockinhibitor.com)
  • The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. (nih.gov)
  • RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
  • When damaged DNA cannot be repaired, a functional DDR machinery triggers a signaling cascade, leading to cell senescence or apoptosis. (encyclopedia.pub)
  • Alan Eastman mostly deals with Apoptosis, Molecular biology, Cell cycle, Programmed cell death and Biochemistry. (research.com)
  • His Apoptosis study integrates concerns from other disciplines, such as Intracellular pH, Intracellular and Chinese hamster ovary cell. (research.com)
  • Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. (research.com)
  • Alan Eastman focuses on Apoptosis, Cancer research, Molecular biology, Cell biology and DNA damage. (research.com)
  • Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. (biomedcentral.com)
  • Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. (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)
  • Regulation of gene expression plays a central role in embryonic development. (biomedcentral.com)
  • Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). (proteopedia.org)
  • Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (PubMed:11086025, PubMed:17881511). (proteopedia.org)
  • 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)
  • Taken together, our results indicate that Tzfp recognizes a sequence-specific motif (tbs) and may play a role in the regulation of the genes carrying the tbs. (lookformedical.com)
  • Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
  • Down regulation of BRG1 in WM 266 4 cells inhibits melanoma invasiveness Most established melanoma cell lines express high levels of BRG1, such as two metastatic melanoma cell lines, A375SM and WM 266 4. (histaminereceptor-signal.com)
  • As a structure-specific endonuclease, MUS81 is involved in cell cycle regulation and regulates the DNA damage repair approach. (rockinhibitor.com)
  • 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)
  • Identification of master regulator (MR) genes offers a relatively rapid and efficient way to characterize disease-specific molecular programs. (aging-us.com)
  • Background: The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. (idhinhibitor.com)
  • The concepts of his DNA damage study are interwoven with issues in CHEK1, Cell cycle checkpoint, DNA repair, Regulator and Topoisomerase-I Inhibitor. (research.com)
  • Wnt/ß-catenin and Wnt/PCP signaling pathway components are effectively repressed after Dvl silencing in K562 cells, while regulator of Wnt/Ca2+ signaling showed increase in both CML cell lines. (bvsalud.org)
  • F-box/WD repeat-containing protein 1A (FBXW1A) also known as βTrCP1 or Fbxw1 or hsSlimb or pIkappaBalpha-E3 receptor subunit is a protein that in humans is encoded by the BTRC (beta-transducin repeat containing) gene. (wikipedia.org)
  • This gene encodes a member of the F-box protein family which is characterized by an approximately 40 residue structural motif, the F-box. (wikipedia.org)
  • The protein encoded by this gene belongs to the Fbxw class as, in addition to an F-box, this protein contains multiple WD40 repeats. (wikipedia.org)
  • βTrCP has also emerged as an important player in protein translation, cell growth and survival. (wikipedia.org)
  • In response to mitogens, PDCD4, an inhibitor of the translation initiation factor eIF4A, is rapidly degraded in a βTrCP- and S6K1-dependent manner, allowing efficient protein translation and cell growth. (wikipedia.org)
  • At the same time, βTrCP mediates the degradation of the pro-apoptotic protein BimEL to promote cell survival. (wikipedia.org)
  • What does this gene/protein do? (cancerindex.org)
  • Following this, the differentially expressed genes (DEGs) were included in Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein‑protein interaction network and survival analyses. (cancerindex.org)
  • The protein is also required for efficient DNA replication during a normal S phase. (idhinhibitor.com)
  • The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
  • RPA, replication protein A. (rupress.org)
  • In this report, we describe a testis zinc finger protein (Tzfp) that binds to the upstream flanking sequence of the Aie1 gene. (lookformedical.com)
  • The DNA damage study combines topics in areas such as CHEK1, Cell cycle checkpoint, MRE11 Homologue Protein and Molecular biology. (research.com)
  • 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)
  • We showed SMAD1, AHR, mTOR, BRD7 protein expressions are significantly affected by Dvl silencing and overexpression in CML cell lines. (bvsalud.org)
  • A rise in the levels of the p53 protein induces the expression of p21 cyclin-dependent kinase inhibitor. (reactome.org)
  • This gene encodes a protein phosphatase 1 binding protein. (nih.gov)
  • A) Loss of DUSP6 protein manifestation in shRNA-modified A431 cells as determined by western blot. (synanet2020.com)
  • A) Averaged outcomes of reverse-phase antibody array evaluation of 46 signalling protein in A431 cells stably expressing shDUSP6, shDUSP7, or non-silencing shRNA control. (synanet2020.com)
  • The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. (frontiersin.org)
  • The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. (hindawi.com)
  • It may also function in M PHASE CELL CYCLE CHECKPOINTS and as an enhancer of TUMOR SUPPRESSOR PROTEIN P53-mediated transcriptional activation. (bvsalud.org)
  • RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
  • Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)
  • Given the previously reported role of DUSP4 as a p53 target, a potential cell cycle checkpoint, and in mediating senescence downstream of replication stress, we hypothesized that DUSP4 may be a critical oncogenic driver in breast cancer. (biomedcentral.com)
  • Accordingly, pre-treatment with 350 nM LSD1 inhibitor for 3 days followed by exposure to serial dilutions of ruxolitinib led to synergistic growth inhibition in non-DS-AMKL and ML-DS cell lines (Supplementary Fig. 4 ), as well as in all ML-DS patient samples (Fig. 1A ). (nature.com)
  • Studies with pitavastatin in primary patient derived tumor cells and established PDA lines, revealed dose dependent growth inhibition. (oncotarget.com)
  • We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. (rupress.org)
  • The novel PLK1 inhibitor, onvansertib, is the first available for oral administration and has shown tumor growth inhibition in hematologic tumors, osteosarcoma, ovarian carcinoma, breast cancer and colon adenocarcinoma cells. (childrenscolorado.org)
  • We identified that inhibition of MMP2 and MMP9 action par tially inhibitor supplier abrogated the BRG1 mediated raise in invasive ability. (histaminereceptor-signal.com)
  • It was previously found that the inhibition of MUS81 elevated susceptibility to PARP inhibitors by means of HR deficiency at the cellular level [14]. (rockinhibitor.com)
  • He revealed the interfacial inhibition paradigm based on molecular mechanisms of topoisomerase inhibitors, and has championed its broad relevance for molecular pharmacology and drug discovery. (cancer.gov)
  • BRCAness as PARP Inhibitors" Encyclopedia , https://encyclopedia.pub/entry/13660 (accessed December 11, 2023). (encyclopedia.pub)
  • Among the novel means to sensitize GBM to DNA-damaging therapies, a promising strategy is to combine them with inhibitors of the DNA damage repair (DDR) machinery, such as inhibitors for poly(ADP-ribose) polymerase (PARP). (encyclopedia.pub)
  • 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)
  • 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)
  • To understand the determinants of response to topoisomerase inhibitors, he is studying the repair pathway centered on tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2) and poly(ADP-ribose)polymerases (PARP). (cancer.gov)
  • Multiple mutations affecting embryonic development have been induced by chemical and insertional mutagenesis resulting in the identification of genes with important roles in development in Drosophila [ 23 - 25 ]. (biomedcentral.com)
  • DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
  • This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape. (biomedcentral.com)
  • We find that together with loss-of-function mutations in p53 and, to some degree, potentiated by cMyc overexpression, Dusp4 deletion aids in cell cycle checkpoint escape while simultaneously potentiating hallmarks of replicative stress, including multinucleation and Chk1 phosphorylation. (biomedcentral.com)
  • By definition, mutations that cause CIN in cancer cells produce "sub-lethal" deficiencies in an essential cellular process (chromosome maintenance) and therefore may represent genetic vulnerabilities in tumor cells that could be exploited for therapeutic benefit in the treatment of cancer. (ubc.ca)
  • These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)
  • For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
  • These modifications comprise point mutations, changes in the gene copy number, complete rearrangements, and epigenetic alterations [ 3 ] . (encyclopedia.pub)
  • Unraveling of GBM biology found mutations [ 1 ] in other genes that also result in BRCAness and confer sensitivity to PARPi treatment. (encyclopedia.pub)
  • Exceptions to this limitation occur when analyzing histone variants that have few gene copies, or when assessing putative gain-of function histone mutations, such as those identified in pediatric glioblastoma and glioma (e.g. (aging-us.com)
  • The difficulty of testing histone point mutations in mammals has therefore contributed to the uncertainty of whether canonical histone PTMs are correlative with gene expression or causal. (aging-us.com)
  • Phenotype and gene expression changes are often surprisingly moderate or specific in yeast that harbor point mutations in the N-terminal tails of histones H2A, H2B, H3 and H4 [ 9 , 16 - 19 ]. (aging-us.com)
  • For example, studies suggest that ccRCC is closely associated with tumor suppressor von-Hippel Lindau ( VHL ) gene mutations that lead to stabilization of hypoxia inducible factors (HIF-1 α and HIF-2 α , also known as HIF1A and EPAS1) in both sporadic and familial forms [ 5 , 6 ]. (hindawi.com)
  • Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). (proteopedia.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)
  • 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)
  • This killing process occurs only if two molecular pathways are simultaneously deficient in one cell, whereas the isolated defect is innocuous [ 6 ] . (encyclopedia.pub)
  • 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)
  • Here we discuss the ATAD5-luciferase assay and expand upon the value of HTS in identifying other potential cancer drugs, focusing on cell-based assays that involve DNA damage or repair pathways. (oncotarget.com)
  • We hence investigated whether depletion of DUSP6 might even more connect to substitute cell signalling pathways uniquely. (synanet2020.com)
  • Alternatively, dasatinib may possibly not be capable of mitigating non apoptotic pathways of motor neuron degeneration caused by mutant SOD1, because non apoptotic programmed cell death has also been implicated in motor neuron harm in G93A mice. (smadpathway.com)
  • Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test. (hindawi.com)
  • We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC. (hindawi.com)
  • Delineating the pathogenesis of ccRCC by investigating the gene and epigenetic changes and their effects on key molecules and their respective biologic pathways is of crucial importance for the improvement of current diagnostics, prognostics, and drug development [ 4 ]. (hindawi.com)
  • In early mitosis, βTrCP mediates the degradation of EMI1, an inhibitor of the APC/C ubiquitin ligase complex, which is responsible for the anaphase-metaphase transition (by inducing the proteolysis of Securin) and mitotic exit (by driving the degradation of mitotic CDK1 activating cyclin subunits). (wikipedia.org)
  • 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)
  • The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.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)
  • The oncogenic kinase PLK1 controls cell cycle and growth and is a cancer therapeutic target. (childrenscolorado.org)
  • Polo-like kinase-1 (PLK1) is highly expressed in rapidly dividing normal cells and is overexpressed in many types of cancer, including Group 3 medulloblastoma, and is associated with poor prognosis. (childrenscolorado.org)
  • It is inhibited by Cyclin-dependent kinase inhibitors (CKI). (biomedcentral.com)
  • MTT colorimetric assays, colony formation assays and 5‑ethynyl‑20‑deoxyuridine incorporation assays were also conducted to evaluate ACC cell proliferation. (cancerindex.org)
  • The cell cycle is the process of accurate self-reproduction and proliferation of a cell. (intechopen.com)
  • Misregulation of the cell cycle may result in malignant cell proliferation, tumorigenesis or cell death. (intechopen.com)
  • However, a function for SET8 in mammalian cell proliferation has not been determined. (rupress.org)
  • Furthermore, the expression of the CYCA gene (involved in cell cycle and proliferation) was significantly downregulated in NAV and TDL isolates. (unav.edu)
  • Then, q-PCR-based gene profiling, revealed that this activity was related to the downregulation of several genes involved in drug resistance (yip1), virulence (gp63) and parasite proliferation (Cyclin 1 and Cyclin 6). (unav.edu)
  • CDC2 gene plays an important role in the proliferation of human gliomas. (biomedcentral.com)
  • Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
  • Examples of cell-based assays include RNAi [ 3 ], second messenger, cell proliferation, and reporter assays [ 4 ]. (oncotarget.com)
  • 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)
  • Our research involves a direct path from identification and mechanistic studies of CIN genes in yeast, to mining sequence data for orthologs mutated in cancer, to interrogation of the function of somatic variants and finally, the identification of (1) therapeutic target genes defined by synthetic lethality and (2) small-molecule inhibitors of those targets. (ubc.ca)
  • The worst prognosis is in Group 3 patients, who often have high MYC expression, a transcription factor that triggers or blocks any array of target genes. (childrenscolorado.org)
  • βTrCP also cooperates with mTOR and CK1α to induce the degradation of DEPTOR (an mTOR inhibitor), thereby generating an auto-amplification loop to promote the full activation of mTOR. (wikipedia.org)
  • We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
  • Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (PubMed:18033802). (proteopedia.org)
  • 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)
  • However, overexpression of aurora-A in particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar. (lookformedical.com)
  • However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. (nature.com)
  • Transcription factors (TFs) drive gene expression programs that shape specific phenotypes [ 3 ], and are frequently dysregulated in cancer [ 4 ]. (aging-us.com)
  • Thus, MRs comprise typically a small number of TF-encoding genes (and their products) that control a disproportionate level of gene expression, giving rise to distinct molecular phenotypes associated with a particular disease. (aging-us.com)
  • Since the expression of genes defining discrete phenotypes is highly coordinated, application of reverse engineering algorithms to transcriptome datasets allows interpreting transcriptional networks by defining MRs and their associated regulons and gene circuits. (aging-us.com)
  • This shows that H3K56 hyperacetylation and/or Valrubicin the constitutive existence of H3K56Ac through the entire cell cycle may be the root cause from the serious phenotypes seen in 2008), illustrating the remarkable substrate selectivity of Hst4 and Hst3. (wwec2012.net)
  • The cancer therapeutic potential of Chk1 inhibitors: how mechanistic studies impact on clinical trial design. (research.com)
  • B) Histone enrichment in Selumetinib tyrosianse inhibitor the promoters of BUD3, ARG3 and FIG1 by ChIP analysis. (irjs.info)
  • Initial, we tested for statistical enrichment of genes with individual Gene Ontology functional annotations, using ONTOLOGIZER version two.0, with the Phrase for Term calculation method and Bonferroni corrected P 0. (smadpathway.com)
  • Immune checkpoint inhibitors are effective in the treatment of some hepatocellular carcinomas (HCCs), but these tumors do not always respond to inhibitors of programmed cell death 1 (PDCD1, also called PD1). (stanford.edu)
  • We investigated mechanisms of resistance of liver tumors in mice to infiltrating T cells.Mice were given hydrodynamic tail vein injections of clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) and transposon vectors to disrupt Trp53 and overexpress C-Myc (Trp53KO/C-MycOE mice). (stanford.edu)
  • tumors were analyzed by mass cytometry using markers to detect T cells and other lymphocytes. (stanford.edu)
  • Tumors from mice given anti-PD1 had larger numbers of memory CD8+ T cells (CD44+CD62L-KLRG1int) and T cells that expressed PD1, lymphocyte activating 3 (LAG3), and TIGIT compared with mice not given the antibody. (stanford.edu)
  • In Trp53KO/C-MycOE mice and mice with tumors grown from Hepa1-6 cells, injection of the combination of anti-PD1 and anti-TIGIT significantly reduced tumor growth, increased the ratio of cytotoxic to regulatory T cells in tumors, and prolonged survival.PVRL1, which is up-regulated by HCC cells, stabilizes cell surface PVR, which interacts with TIGIT, an inhibitory molecule on CD8+ effector memory T cells. (stanford.edu)
  • Effective immunotherapy of stromal-rich tumors requires simultaneous targeting of cancer cells and immunosuppressive elements of the microenvironment. (aacrjournals.org)
  • Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and accounts for approximately 60% to 70% of all renal tumors [ 1 ]. (hindawi.com)
  • Small tumors have a greater percentage of actively dividing cells than do large tumors. (msdmanuals.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)
  • 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)
  • Furthermore, these three genes predicted overall survival and recurrence‑free survival in patients with ACC from the TCGA cohort. (cancerindex.org)
  • Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated. (biomedcentral.com)
  • Although MM remains incurable, the survival of MM patients has improved considerably due to the application of autologous stem cell transplantation, novel agents, and advanced treatment strategies. (bvsalud.org)
  • Maintenance of genomic stability is crucial for standard development, cell homeostasis and tumor suppression [7]. (rockinhibitor.com)
  • During recovery from DNA replication and DNA damage, βTrCP instead targets Claspin in a Plk1-dependent manner. (wikipedia.org)
  • We have also developed a strategy to identify genes in yeast synthetic lethal (SL) interaction networks as a means for identifying novel cancer drug targets. (ubc.ca)
  • To identify candidate drug targets, we have been testing synthetic lethal interactions, predicted in yeast, using RNAi, gene knockouts, and mutants in both C. elegans and mammalian cell culture, to identify evolutionarily conserved SL gene pairs involving CIN genes somatically mutated in cancer. (ubc.ca)
  • Multiple genes negatively impact overall cellular fitness and are targets for effective treatment. (childrenscolorado.org)
  • Although CD4 T cells are the main targets of HIV infection, macrophages also become infected and resist the cytopathic effects of infection, contributing potentially to HIV reservoir persistence. (nih.gov)
  • for example, Chu and Chen [ 13 ] combined PPI and gene expression data to construct a cancer perturbed PPI network in cervical carcinoma to study gain- and loss-of-function genes as potential drug targets. (hindawi.com)
  • Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
  • CBP/p300 can also be important for transcription, but the recruitment of CBP/p300 and their associated histone acetylation marks do not absolutely correlate with a requirement for gene activation. (aging-us.com)
  • Histone PTMs often correlate with the activity of the gene (or of a regulatory element such as an enhancer) that is in their proximity, suggesting a causal relationship. (aging-us.com)
  • The function of histone PTMs in mammals remains uncertain because the multiple genes encoding each canonical histone, renders in vivo mutational analysis unfeasible in most instances. (aging-us.com)
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
  • 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)
  • This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. (cancerindex.org)
  • The top 14 hub genes were subsequently confirmed by reverse transcription‑quantitative polymerase chain reaction in ACC and adrenocortical adenoma samples. (cancerindex.org)
  • allows binding of transcription factors on outer DNA helix gene silencing (NO TRANSCRIPTION)! (freezingblue.com)
  • It is found predominantly in the cell's nucleus, where it binds to DNA and influences transcription, but also in the cytoplasm - the watery part of the cell. (foundmyfitness.com)
  • The mouse Tzfp gene, mapped to chromosome 7 B2-B3, encodes a 465-amino acid transcription factor containing a conserved N-terminal BTB/POZ domain and three C-terminal PLZF-like C(2)H(2) zinc fingers. (lookformedical.com)
  • Dr. Pommier also discovered that the natural compound, ecteinascidin 743 (commercialized as Yondelis) and its analog trabectedin acts by alkylating DNA and killing cancer cells by trapping transcription-coupled nucleotide excision repair (TC-NER) (Takebayashi et al, Nature Med 2001). (cancer.gov)
  • This pathway sets a complex cascade of biological events in motion with a wide range of effects on the body's cells. (foundmyfitness.com)
  • 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)
  • The study incorporates disciplines such as Cancer research and Topoisomerase-I Inhibitor in addition to Cell cycle checkpoint. (research.com)
  • His work carried out in the field of DNA damage brings together such families of science as CHEK1, Cell cycle checkpoint, Cell killing, Cell biology and Topoisomerase-I Inhibitor. (research.com)
  • He discovered the indenoisoquinolines as novel Top1 inhibitors, which are in clinical development, and the mitochondrial topoisomerase gene, TOP1mt. (cancer.gov)
  • Dr. Pommier conceptualized the "interfacial inhibitors" mechanism based on his finding that DNA topoisomerase inhibitors act by trapping topoisomerase-DNA complexes (Capranico et al. (cancer.gov)
  • Dr. Pommier discovered the 6th vertebrate topoisomerase gene, TOP1MT (Zhang et al. (cancer.gov)
  • 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)
  • Using a genetically engineered mouse model, we generated mammary-specific Dusp4 -deleted primary epithelial cells to investigate the necessary conditions in which DUSP4 loss may drive breast cancer oncogenesis. (biomedcentral.com)
  • The analyzed gene datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database. (cancerindex.org)
  • Genes that maintain genome structure are evolutionarily conserved and are often somatically mutated in cancer. (ubc.ca)
  • We have established an extensive genome instability gene catalog in yeast that provides a resource to identify cross-species, candidate human genes that are somatically mutated and could cause chromosome instability (CIN) in cancer. (ubc.ca)
  • Prominent among the hits were members of the statin class of HMG-CoA reductase inhibitors, cholesterol lowering drugs that are also being evaluated in cancer. (oncotarget.com)
  • Scientists working in basic, translational, and clinical cancer metabolism research are invited to join the Academy in New York on April 17th to discuss the intersection between cell signaling and metabolism. (nyas.org)
  • Cancer Cell Metabolism: Unique Features Inform New Therapeutic Opportunities. (nyas.org)
  • In turn, as a result of research into the abnormal cancer cell, the basic understanding of the cell has greatly improved. (medscape.com)
  • [ 1 ] Identifying candidate precursors or enabling genes may pave the way for cancer screening, as with the ret proto-oncogene and medullary thyroid carcinoma . (medscape.com)
  • A few gene therapy trials now target head and neck cancer, which makes up only 4% of all cancers but has a dismal prognosis in advanced stages. (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)
  • [ 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)
  • p21 and other tumor suppressor genes' inactivation are therefore most likely involved in the first steps of the cancer model, with later stages possibly involving protooncogene activation and inflammation. (medscape.com)
  • His Cancer research study combines topics in areas such as Cancer, Cell cycle, Cisplatin, Immunology and Chronic lymphocytic leukemia. (research.com)
  • Alan Eastman interconnects Cancer, Cell cycle, Gemcitabine, Immunology and DNA repair in the investigation of issues within Cancer research. (research.com)
  • Our findings indicate that tumor associated macrophages including Kupffer cells, have a profound impact on liver cancer and I am studying the molecular basis for these effects. (stanford.edu)
  • some mice were given intraperitoneal injections of antibodies against PD1, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), or CD8 before the cancer cells were injected. (stanford.edu)
  • Moreover, the identification of fork protection as a key mechanism of resistance to chemo- and poly (ADP-ribose) polymerase inhibitor therapy in ovarian cancer further increases the priority that should be accorded to the development of strategies targeting replicative stress. (bmj.com)
  • One example of such an assay is the ATAD5-luciferase HTS assay, which identified three antioxidants that could kill cancer cells without inducing mutagenesis. (oncotarget.com)
  • A few gene therapy trials now target head and neck cancer, which comprises only 4% of all cancers but has a dismal prognosis in advanced stages. (medscape.com)
  • Three of his indenoisoquinoline TOP1 inhibitors are in Phase 1/2 clinical development (Thomas & Pommier, Clin Cancer Res 2019): LMP400 (Indotecan), LMP776 (Indimitecan) and LMP744. (cancer.gov)
  • 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)
  • Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells (ie, small, round cells found in the lower layer of the epidermis). (medscape.com)
  • We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo . (oncotarget.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)
  • In vitro, both peptides were highly active against intracellular Leishmania major in mouse macrophages without exerting toxicity in host cells. (unav.edu)
  • To determine the general biological conse quence of BRG1 re expression in SK MEL5 cells, we investigated if BRG1 promotes alterations in the ability of melanoma cells for being invasive in vitro. (histaminereceptor-signal.com)
  • Over the last two decades, studies based on genome-wide gene expression and functional profiling have revealed the great diversity of transcriptional alterations occurring in liver carcinogenesis. (aging-us.com)
  • N. lugens genome data predicted the Toll 13 like gene includes two exons flanked from the 50 and 30 untrans lated areas, indicating a full coding sequence. (histaminereceptor-signal.com)
  • Replication of DNA is initiated at multiple sites along the genome, known as replication origins, which form bidirectional replication forks. (bmj.com)
  • These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)
  • Transcriptomic analyses provide an efficient approach to explore the temporal gene expression profiles in embryos and to search for the developmental regulators. (biomedcentral.com)
  • Early ontogeny is associated with dramatic gene expression changes that underlie and determine the developmental processes. (biomedcentral.com)
  • Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
  • Expression profiles analysis identifies the values of carcinogenesis and the prognostic prediction of three genes in adrenocortical carcinoma. (cancerindex.org)
  • We focused on the analysis of growth rate, treatment response, infection capacity, and gene expression, comparing these isolates with the widely studied strain L. infantum BCN 150. (unav.edu)
  • An investigation of PLK1 expression in DepMap found PLK1 is a critical mediator in 55 central nervous system cell lines, including eight medulloblastoma cell lines. (childrenscolorado.org)
  • Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. (biomedcentral.com)
  • Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. (biomedcentral.com)
  • So as to determine if re expression of BRG1 in SK MEL5 cells resulted in elevated secretion of lively MMP2 and MMP9, we carried out gelatin zymography on supernatants derived from control and BRG1 expres sing SK MEL5 cells. (histaminereceptor-signal.com)
  • To find out if loss of BRG1 compromises invasive skill in one of these extremely invasive cell lines, we down regulated BRG1 expression in WM 266 4 cells using a pool of siRNAs that target BRG1 but not the different ATPase, BRM. (histaminereceptor-signal.com)
  • Interestingly, BRM expression was slightly reduce in cells transfected with manage siRNA compared to untreated but then elevated in BRG1 down regulated cells. (histaminereceptor-signal.com)
  • We discovered that in WM 266 4 cells, BRM expression but not BRG1 or INI1 expression is sensitive to adjustments in WM 266 2 confluency. (histaminereceptor-signal.com)
  • However, regulated gene expression is still subject to growth-mediated feedbackIotic (257). (rockinhibitor.com)
  • For instance, knockout of the H2A variant H2A.Z reveals that it is required for early mouse development [ 6 ], whereas loss of another variant, macroH2A1, has subtle effects on mouse physiology and gene expression [ 7 , 8 ]. (aging-us.com)
  • 14 ] combined PPI and gene expression data to construct tissue-specific PPI networks for 60 tissues and used them to prioritize disease genes. (hindawi.com)
  • is a CDK-substrate required for replication fork stability. (xenbase.org)
  • Through S phase of your cell cycle, WEE1 inhibits the association and function with the MUS81-SLX4 complex, and SLX4 cooperates to activate MUS81 in the course of M phase [5]. (rockinhibitor.com)
  • Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
  • 0.27 MB DOC) pone.0012143.s006.doc (268K) GUID:?28BD7F7C-6E7C-49DF-98FD-21EB74D5C547 Table S2: Differentially portrayed genes in htz1, swr1, swc2, swc5 and dual mutants in accordance with outrageous type. (irjs.info)
  • His Molecular biology study incorporates themes from Cell culture, Chinese hamster ovary cell and Deoxyribonuclease II, Biochemistry, DNA. (research.com)
  • The various areas that Alan Eastman examines in his CHEK1 study include G2-M DNA damage checkpoint, Molecular biology and DNA replication. (research.com)
  • Through hypoxia-inducible factor 1 (HIF-1) which elicits various molecular events, cells are able to overcome low O2. (stanford.edu)
  • The cell cycle is a complex process with myriad genes involved and elaborate and complex signaling mechanisms to allow for this critical cellular process. (biomedcentral.com)
  • To elucidate the mechanisms by which BRG1 professional motes invasion, we taken care of cells with an inhibitor of MMP2/MMP9 and performed invasion assays. (histaminereceptor-signal.com)
  • In contrast, the same chimera did not activate the reporter gene when an essential nucleotide fifth C was mutated to A at the tbs. (lookformedical.com)
  • depletion of DUSP6 reduced the viability of malignancy cell lines and improved the cytotoxicity of EGFR and additional targeted inhibitors, and cytotoxic providers, and drug level of sensitivity, tumour cells were plated in 96-well plates in 1% FBS/DMEM/L-glutamine with 3000 cells per well and incubated over night. (synanet2020.com)
  • The BRCA2 R3052W mutation fails to complement chemotherapeutic sensitivity and homology-directed repair functions in BRCA2 knockout cells. (frontiersin.org)
  • Overexpression of R3052W in DLD1 parental BRCA2 wild-type cells confers sensitivity to MMC DNA damage. (frontiersin.org)
  • Some drugs work only during a specific phase of the cell cycle, requiring prolonged administration to catch dividing cells during the phase of maximal sensitivity. (msdmanuals.com)
  • 2020). Based on their promising clinical activity and their superior medicinal properties over the camptothecins, the indenoisoquinolines represent the first non-camptothecin TOP1 inhibitors for the treatment of cancers. (cancer.gov)
  • Investigators used CRISPR-Cas9 screening to determine which genes were essential for medulloblastoma tumor growth. (childrenscolorado.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)
  • 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)
  • In this manuscript, we discuss the various cell-based HTS assays that have been developed to aid in the discovery of chemotherapeutic agents, focusing on those that exploit the DNA damage response. (oncotarget.com)
  • Regulates the activity of cellular genes, including c-myc and c-fos (By similarity). (proteopedia.org)
  • knockdown of Pvrl1 reduced cell-surface levels of PVR but not levels of Pvr messenger RNA. (stanford.edu)
  • Quantitative RTCPCR For evaluation of the mark genes' knockdown, cells were transfected in six-well plates and total RNA was extracted using RNeasy Minikit (Qiagen Inc.,) 48C72?h after transfection. (synanet2020.com)
  • His Programmed cell death research incorporates themes from Deoxyribonuclease II, Acetylation, Extracellular, Cell biology and Endonuclease. (research.com)
  • The zinc finger domain of Tzfp binds to the TGTACAGTGT motif (Tzfp binding site, termed tbs) located at the upstream flanking sequence of the Aie1 gene by gel mobility shift, DNase I footprinting, and competition analyses. (lookformedical.com)
  • Fusion with the host cell is most likely mediated by both E1 and E2, through conformational rearrangements of the heterodimer required for fusion rather than a classical class II fusion mechanism (PubMed:16533059, PubMed:29505618, PubMed:24698129). (proteopedia.org)
  • He demonstrated the interfacial inhibitor mechanism by co-crystal studies (Ionaviciu et al. (cancer.gov)
  • Both I and IP DNA from cell components incubated either with anti-Myc antibody or IgG were Rabbit Polyclonal to CRHR2 Selumetinib tyrosianse inhibitor amplified by real-time PCR (observe Table S4 for oligos). (irjs.info)
  • Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)