AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Cell CycleProtein Inhibitors of Activated STATCell Cycle ProteinsGenes, cdcCheckpoint Kinase 2DNA DamageG2 PhaseCell Cycle CheckpointsMitosisProtein-Serine-Threonine KinasesAtaxia Telangiectasia Mutated ProteinsS PhaseProtein KinasesDNA RepairHydroxyureaG2 Phase Cell Cycle CheckpointsSpindle ApparatusM Phase Cell Cycle CheckpointsDNA-Binding ProteinsG1 PhaseNuclear ProteinsDNA ReplicationGamma RaysTumor Suppressor Protein p53Mad2 ProteinsSchizosaccharomycesSaccharomyces cerevisiae ProteinsTumor Suppressor ProteinsMutationSchizosaccharomyces pombe ProteinsFungal ProteinsSaccharomyces cerevisiaeAtaxia TelangiectasiaPhosphorylationcdc25 PhosphatasesChromosomal InstabilityRadiation, IonizingCyclinsCyclin-Dependent Kinase Inhibitor p21Ultraviolet RaysIntracellular Signaling Peptides and ProteinsCDC2 Protein Kinase5-Lipoxygenase-Activating Protein InhibitorsMolecular Sequence DataGenes, FungalCyclin BApoptosisRadiation ToleranceCell DivisionGenomic InstabilitySignal TransductionCell LineG1 Phase Cell Cycle CheckpointsCell Line, TumorCyclin B1DNA, FungalHeLa CellsS Phase Cell Cycle CheckpointsNocodazoleBase SequenceProtein BindingDNA Breaks, Double-StrandedModels, BiologicalRetinoblastoma ProteinAmino Acid SequenceFibroblastsGene DeletionAneuploidyCell NucleusBRCA1 ProteinCarrier ProteinsRepressor ProteinsCDC28 Protein Kinase, S cerevisiaeFlow CytometryCyclin-Dependent Kinase 2Cells, CulturedTumor Cells, CulturedCell ProliferationHistonesChromosomes, FungalEnzyme InhibitorsGenes, p53SUMO-1 ProteinKinetochoresRNA, Small InterferingPhenotypeDNASmall Ubiquitin-Related Modifier ProteinsNeoplasm ProteinsCyclin EMimosineMethyl MethanesulfonateDNA Repair EnzymesCell SurvivalCDC2-CDC28 KinasesProteinsSumoylationCyclin-Dependent KinasesCalcium-Binding ProteinsGene Expression Regulation, Neoplastic
ApoptosisKinaseGrowth inhibitionProgressionProliferationTarget genesRegulationPARPInducesPathwaysReplicationSquamous cell carcPathwayTopoisomerase inhibitorsPhosphorylationResistanceKinasesOncogenicRegulatesInactivationCyclinTumorsArrestImmuneColorectal cancerEffectorMutationsSpindleSurvivalSusceptibilityHistoneMitosisDepletionPrognosisCellularAtaxia telangiMismatch repairPotentCytotoxicGenomicCytotoxicityCDKsSynthetic lethalityChromatinTumorigenesisHepatocellularHDACMammalianDefectiveTumoursCdk4KnockdownMutantMechanismMRNA and proteinSynthesisInhibitsFLT3-ITDMutationMalignancyOvarian carcinoma
Apoptosis18
  • Weighed against its homologs Plk1 (and its own connected signaling pathway) offers attracted much interest because overexpression of Plk1 can be firmly correlated with carcinogenesis (10 11 Furthermore inhibition of Plk1 using RNA disturbance (RNAi) or particular little molecule inhibitors causes development arrest or apoptosis in tumor cells (12-14). (biospraysehatalami.com)
  • Sirtuins are NAD + -dependent histone deacetylases regulating important metabolic pathways in prokaryotes and eukaryotes and are involved in many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, cell metabolism, and caloric restriction. (biomedcentral.com)
  • Cell phone routine analyses suggest M-VCR-R is considered the most powerful mix in triggering reduction in G0/G1, G2/M arrest, overriding the spindle checkpoint resulting in elevated apoptosis currently-reliant manner (Figure 3B). (immune-source.com)
  • Pacritinib is an equipotent inhibitor of FLT3 and JAK2, which can be good at lessening JAK2/STAT5 and FLT-3 JAK2 signaling in FLT3 and JAK2 mutant tissues, respectively.33 A combination of pracinostat and pacritinib resulted in synergistic effects using a complete inhibition of downstream STAT5 signaling, an elevated effectiveness on cellular proliferation and the induction of apoptosis. (immune-source.com)
  • Treating SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective cytokinesis, polyploidy and apoptosis, which was effective irrespective of the EGFR status. (oncotarget.com)
  • Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN. (oncotarget.com)
  • It also exhibited greater suppression on cell proliferation as well as cell migration or invasion capabilities and induction of apoptosis in Hep3B cells than single siRNA simultaneously. (biomedcentral.com)
  • Silencing of VEGF and KSP plays a key role in inhibiting cell proliferation, migration, invasion and inducing apoptosis of Hep3B cells. (biomedcentral.com)
  • Both inhibition of WDR5 by siRNA and OICR-9429 could reduce proliferation, and increase apoptosis and chemosensitivity to cisplatin in vitro and in vivo . (thno.org)
  • In pediatric solid tumors and brain tumors, PLK1 inhibition leads to apoptosis in vitro and in tumor xenografts. (childrenscolorado.org)
  • 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)
  • 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)
  • In addition, some of the MMR components participate in recombination and double-strand break repair as well as cell cycle regulation and apoptosis. (aacrjournals.org)
  • In addition, cell cycle distribution analysis revealed that G0/G1 phase arrest was induced following pristimerin treatment in CAL‑27 and SCC‑25 cells, which was strongly associated with upregulation of p21 and p27, coupled with downregulation of cyclin D1 and cyclin E. Meanwhile, pristimerin induced significant apoptosis of CAL‑27 and SCC‑25 cells, alongside decreased levels of caspase‑3 and specific cleavage of poly (ADP‑ribose) polymerase. (spandidos-publications.com)
  • Pristimerin has also been reported to induce apoptosis of various human cancer cells, including in multiple myeloma ( 10 ), breast ( 11 ), liver ( 12 ), pancreatic ( 13 ) and prostate cancer ( 14 ). (spandidos-publications.com)
  • In addition to apoptosis induction ( 11 ), the mechanisms involved in the anticancer effects of pristimerin include stimulation of reactive oxygen species generation ( 15 ), blocking of nuclear factor-κB ( 16 ) and proteasome inhibition ( 10 ). (spandidos-publications.com)
  • Pristimerin exhibited potent anti-proliferative and apoptosis-inducing effects on the OSCC cell lines CAL-27 and SCC-25. (spandidos-publications.com)
Kinase32
  • For example, Cdk, or cyclin dependent kinase, is a major control switch for the cell cycle and it allows the cell to move from G1 to S or G2 to M by adding phosphate to protein substrates. (wikipedia.org)
  • In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.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)
  • All of these members contain a conserved C-terminal amino acid sequence termed the polo box domain which provides a docking site for certain proteins (1) and a kinase domain which is predicted to activate many protein kinases including Aurora A/B PKA ERK1/2 RSK1/2 Akt/PKB and MEK1 (2). (biospraysehatalami.com)
  • You can find six phosphorylation sites in RSK1 that are crucial for its activation and its own subsequent part in substrate phosphorylation (21 22 Of the phosphorylation of Ser-380 can be very important to RSK1 activation traveling functions such as for example rules of gene manifestation and protein synthesis and cell cycle regulation as a downstream Nisoxetine hydrochloride kinase in the Mos-MAPK pathway (23). (biospraysehatalami.com)
  • Combined Aurora kinase and EGFR targeting using a monoclonal anti-EGFR antibody was more effective compared to single EGFR and Aurora kinase inhibition. (oncotarget.com)
  • Comparing pan-Aurora kinase and Aurora-A targeting hints towards a strong and clinically relevant biological effect mediated via Aurora kinase B. Taken together, our findings characterize a new poor risk group in SCCHN patients defined by elevated EGFR and Aurora-A protein expression. (oncotarget.com)
  • The G1 checkpoint is regulated by a multitude of molecules such as the retinoblastoma family of proteins, cyclins, cyclin dependent kinases (CDKs) and cyclin dependent kinase inhibitors (CDKis). (temple.edu)
  • CAOV3 cells, which are atRA sensitive, have been shown to express p16INK4a (p16), a cyclin dependent kinase inhibitor regulating the G1 checkpoint. (temple.edu)
  • Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors. (icr.ac.uk)
  • 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)
  • Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining. (xenbase.org)
  • Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
  • Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.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)
  • Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
  • An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.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)
  • It is inhibited by Cyclin-dependent kinase inhibitors (CKI). (biomedcentral.com)
  • p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
  • P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)
  • 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)
  • These effects were associated with inhibition of the mitogen‑activated protein kinase/extracellular signal‑regulated kinase 1/2 and protein kinase B signaling pathways. (spandidos-publications.com)
  • The underlying mechanisms of these effects were primarily mediated by G 1 phase cell cycle arrest and inhibition of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulate kinase 1/2 (Erk 1/2) and protein kinase B (Akt) signaling pathways. (spandidos-publications.com)
  • When the inhibitor Rho kinase (Y27632, small GTPase), a regulator of actin polymerization, was tested, encystment of was blocked [39]. (globaltechbiz.com)
  • Cyclic AMP exhibits its mechanism via protein kinase mediated system. (globaltechbiz.com)
  • Cell-free DNA in the supernatant of pleural effusion can be used to detect driver and resistance mutations, and can guide tyrosine kinase inhibitor treatment decisions. (cdc.gov)
Growth inhibition7
  • Studies with pitavastatin in primary patient derived tumor cells and established PDA lines, revealed dose dependent growth inhibition. (oncotarget.com)
  • All-trans retinoic acid (atRA) mediated growth inhibition results in the arrest of the cell cycle during the G1 phase in CAOV3 cells but not SKOV3 ovarian carcinoma cells. (temple.edu)
  • Our results show that overexpression of p16 in SKOV3 cells leads to growth inhibition following atRA treatment. (temple.edu)
  • Nevertheless, these results show that p16 plays a role in atRA mediated growth inhibition in ovarian carcinoma cells and that modulation of p16 expression can determine the growth response to atRA. (temple.edu)
  • and 3) the truncated form of HOXA1 is induced by atRA treatment and may play a role in mediating growth inhibition by atRA, perhaps by acting in a dominant negative fashion. (temple.edu)
  • 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)
  • Required for vitamin D-mediated growth inhibition by being itself inactivated. (proteopedia.org)
Progression20
  • The switches maintain the orderly progression of the cell cycle and act as checkpoints to ensure that each phase has been properly completed before progression to the next phase. (wikipedia.org)
  • A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. (mdpi.com)
  • During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. (oncotarget.com)
  • Therefore it would be interesting to examine the control mechanism of cell cycle progression in which RSK1 affects Myt1 in meiosis and Plk1 affects Myt1 in mitosis. (biospraysehatalami.com)
  • 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)
  • Interestingly, the most primordial defense responses employed by myeloid cells against pathogens, such as complement activation, antibody-dependent cell cytotoxicity and phagocytosis, actually seem to favor cancer progression. (frontiersin.org)
  • In this review, we discuss how rudimentary defense mechanisms deployed by myeloid cells can promote tumor progression. (frontiersin.org)
  • 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)
  • Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (proteopedia.org)
  • The most relevant articles summarising existing knowledge on RCC genomics, including tumour cell evolution and progression, were selected for this review. (springer.com)
  • 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)
  • PD-1 blocks cell cycle progression in the G 1 phase. (shu.edu)
  • Thus, PD-1 targets Ras and PI3K/Akt signaling to inhibit transcription of Skp2 and to activate Smad3 as an integral component of a pathway that regulates blockade of cell cycle progression in T lymphocytes. (shu.edu)
  • Accumulation of p27 in the nucleus, therefore, blocks cell cycle progression of T-lymphocytes that are being induced to act against cancer antigens. (shu.edu)
  • Orderly progression through the cell cycle involves passage through sequential checkpoints. (shu.edu)
  • 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)
  • In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect of the interferon receptor genes cluster as an adaptive mechanism to deleterious chromosomal instability in metastatic progression. (bvsalud.org)
  • PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. (biomedcentral.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)
Proliferation18
Target genes3
  • 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)
  • XLS 97 kb) 12861_2017_153_MOESM8_ESM.xls (98K) GUID:?B2FE5241-0444-4D48-99D4-D5E55E4120EF Extra file 9: Desk S7: Target genes of the very best portrayed 18 miRNAs. (clinical-research-informatics.com)
  • Subsequently, T cells receiving PD-1 signals displayed impaired Cdk2 activation and failed to phosphorylate two critical Cdk2 substrates, the retinoblastoma gene product (Rb) and the TGFβ-specific transcription factor Smad3 , leading to suppression of E2F target genes but enhanced Smad3 transactivation (Figure 3). (shu.edu)
Regulation12
  • This example clearly shows the combined effects that positive and negative feedback loops have on cell-cycle regulation. (wikipedia.org)
  • Ultrasensitivity plays a large role in cell-cycle regulation. (wikipedia.org)
  • Taken together these findings provide insights into the regulation of Plk1 during cell division and diapause cyst formation and the correlation between the activity of Plk1 and RSK1. (biospraysehatalami.com)
  • 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. (thno.org)
  • 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)
  • 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)
  • Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (By similarity). (proteopedia.org)
  • In the nucleus, R-SMAD-SMAD4 complexes cooperate with transcriptional coregulators that further define target gene recognition and transcriptional regulation. (shu.edu)
  • 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)
  • It is interesting to study the initiation and regulation of differentiation in cells having no G1 phase, Mouse monoclonal to Ractopamine as typically, cell differentiation occurs from your G1 phase of the cell cycle. (globaltechbiz.com)
PARP9
  • The concept of synthetic lethality (SL) holds great promise for the treatment of human cancers, best exemplified by the now widespread use of PARP inhibitors in BRCA mutant cancers. (nature.com)
  • The concept has now been extended to embrace synthetic lethal drug sensitivity, such as that observed with PARP inhibitors in combination with DNA-damaging chemotherapy in a variety of BRCA defective tumors 10 . (nature.com)
  • Regardless, the overall insufficient drug-able targets portrayed in HGSOC tumours and the truth that the entire prognosis for HGSOC hasn't improved drastically within the last several decades, regardless of the latest addition of PARP inhibitors [11], shows that there's a critical have to understand the systems that result in tumour development and advancement. (2011globalhealth.org)
  • Poly (ADP-ribose) polymerase (PARP) inhibitors target tumor cells with a homologous recombination repair (HRR) deficiency based on the concept of synthetic lethality. (biomedcentral.com)
  • Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. (biomedcentral.com)
  • However, PARP inhibitor resistance has partially precluded their use in clinical applications, and the major mechanism underlying this resistance is the restoration of HRR. (biomedcentral.com)
  • Therefore, determining how to use PARP inhibitors in more clinical applications and how to avoid adverse effects, as well as prognosis and treatment response biomarkers, require additional research. (biomedcentral.com)
  • This review elaborates on future prospects for the application of PARP inhibitors in pancreatic cancer. (biomedcentral.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)
Induces5
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
  • We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
  • The phosphorylation of pRB, and relief of transcriptional repression by pRB induces genes involved in the induction of S-phase entry. (shu.edu)
  • Mechanistically, inhibition of KRASG12D in advanced PDAC and human patient derived organoids induces FAS expression in cancer cells and facilitates CD8+ T cell-mediated death. (bvsalud.org)
  • It can be not clear why stimulation GSK-3 inhibition of 5 HT4 receptors in some but not in other circumstances, induces an enhancement of each cholinergic and non cholinergic transmission. (others-signal.com)
Pathways11
  • 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)
  • nevertheless scientific trials have got generally confirmed too little response in these tumours to inhibition of the pathways [5,6]. (2011globalhealth.org)
  • To recognize genes in charge of regulating particular signalling pathways and/or tumorigenic properties that donate to poor scientific outcome, we used a previously released Poor Prognosis Personal (PPS) [3] being a conceptual construction to execute integrative proteogenomic analyses of individual HGSOC tumours. (2011globalhealth.org)
  • 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)
  • We shall consider each subtype in turn describing genes and pathways of oncogenesis and how these relate to prognosis and treatment response. (springer.com)
  • We hence investigated whether depletion of DUSP6 might even more connect to substitute cell signalling pathways uniquely. (synanet2020.com)
  • Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). (proteopedia.org)
  • The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway evaluation suggested that furthermore to Wnt and changing growth aspect (TGF) signaling pathways, that have been reported in response to follicle formation broadly, another mixed band of signaling pathways that regulate lipid synthesis and fat burning capacity, like the phosphatidylinositol signaling program and glycerolipid signaling and fat burning capacity, are Gemzar biological activity in charge of follicle formation also. (clinical-research-informatics.com)
  • The suppressive effect of PD-1 on Skp2 expression was mediated by inhibition of both PI3K/Akt and Ras/MEK/Erk pathways and was only partially reversed by IL-2, which restored activation of MEK/Erk but not Akt. (shu.edu)
  • 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)
  • P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. (elifesciences.org)
Replication13
Squamous cell carc8
  • The 13 homeobox genes were analyzed because previous studies done by our laboratory observed differences in expression of these homeobox genes when comparing atRA sensitive oral squamous carcinoma cells (SCC) to atRA resistant oral squamous cell carcinoma cells. (temple.edu)
  • Tobacco and alcohol, which are highly associated with head and neck squamous cell carcinoma, have not been shown to play a role in the development of malignancies of the salivary glands. (medscape.com)
  • The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8 + T cells (Tex) in HNSCC. (elifesciences.org)
  • In the present study, the anticancer potential of pristimerin was investigated in two oral squamous cell carcinoma (OSCC) cell lines, CAL‑27 and SCC‑25. (spandidos-publications.com)
  • Because it is very invasive, the prognosis of oral squamous cell carcinoma (OSCC) is poor ( 5 ). (spandidos-publications.com)
  • risk of esophageal squamous cell carcinoma. (who.int)
  • PMID:18786442 mutations and the risk of esophageal squamous cell carcinoma. (who.int)
  • Arbyn M, Bergeron C, Klinkhamer P, Martin-Hirsch squamous cell carcinoma in a high-risk region in Iran. (who.int)
Pathway3
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
  • RNAi is a specific gene regulatory mechanism in which activation of an intracellular pathway triggered by small-interfering RNA (siRNA) of 21-23 nucleotides (nt), leading to gene silencing through degradation of a homologous target mRNA[ 3 ]. (biomedcentral.com)
  • Although these systems aren't known completely, research survey that appearance of cyst encoding protein and genes is normally upregulated, like the Wnt/-catenin pathway functionally. (globaltechbiz.com)
Topoisomerase inhibitors3
  • Because MMR is assumed to modulate cytotoxicity to various chemotherapeutic agents that act upon DNA, our objectives have been to define its possible involvement in the cytotoxicity of topoisomerase inhibitors. (aacrjournals.org)
  • Our results also indicate that neither p53 status, nor cell cycle alterations correlate with the sensitivity of colorectal cancer cells to topoisomerase inhibitors. (aacrjournals.org)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
Phosphorylation11
  • In addition studies on HeLa cells using Plk1 siRNA interference and overexpression showed that phosphorylation of RSK1 increased upon interference and decreased after overexpression suggesting that Plk1 inhibits RSK1. (biospraysehatalami.com)
  • Recent surveys along with the HDACi trichostatin A display that JAK2/STAT3 signaling was lowered by upregulation of your phrase of suppressors of cytokine signaling (SOCS) 3 and 1 genes.40 A potential strong impact in the HDAC inhibition for the phosphorylation of FLT3, STAT5 and JAK2 was not examined with this study. (immune-source.com)
  • Dawson et al.43 prove that JAK2 inhibition results in cheaper amounts of histone H3 Y41 phosphorylation about the marketer of LMO2, while increasing the binding of heterochromatin healthy proteinwith the very same site, producing decrease concept of LMO2. (immune-source.com)
  • It really has been demonstrated formerly that phosphorylation of H3 (on S10) contributes to improved productivity of your following H3 acetylation, contributing to synergistic modifications of gene expression.44 Pacritinib, and also aiming for JAK2, can be a potent FLT3 inhibitor. (immune-source.com)
  • Dr. Otto Warburg first described, more than 80 years ago, that a fundamental biochemical difference between tumor cells and their normal counterparts was that tumor cells rely on aerobic glycolysis for ATP generation, unlike most normal differentiated cells of the body, which use mitochondrial oxidative phosphorylation. (aacrjournals.org)
  • EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. (proteopedia.org)
  • regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (proteopedia.org)
  • 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)
  • Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. (proteopedia.org)
  • A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. (lookformedical.com)
  • The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
Resistance7
  • ABT-869 , VX-680 or sunitinib), leads to an upregulation of JAK2 exercise, triggering second resistance.33 For that reason, although combinations of FLT3 inhibitors and HDACi happen to be described to exhibit synergy in vitro,23, 24 this mixture without having the more JAK2 inhibition can result in opposition after chronic dosing and not show improved effectiveness from the in vivo placing. (immune-source.com)
  • MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma. (icr.ac.uk)
  • 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)
  • 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)
  • 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)
  • On the other hand,our data showing that resistance to these drugs can be achieved by the functional complementation of hMLH1 in an hMLH1-defective cell line have allowed us to establish that MMR is a critical determinant for chemosensitivity. (aacrjournals.org)
  • For chemotherapy drugs, one of the best characterized resistance mechanisms is overexpression of MDR1 , a cell membrane transporter that causes efflux of certain drugs (eg, vinca alkaloids, taxanes, anthracyclines). (msdmanuals.com)
Kinases4
  • An example that reveals the interaction of the multiple negative and positive feedback loops is the activation of cyclin-dependent protein kinases, or Cdks14. (wikipedia.org)
  • Cell department is controlled through cooperation of different kinases. (biospraysehatalami.com)
  • Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases. (proteopedia.org)
  • 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)
Oncogenic2
  • In human tumors, an association between the deregulation of the expression of homeobox genes and oncogenic transformation has been reported. (temple.edu)
  • Validation studies confirmed the prognostic capacity of and suggested an oncogenic part for this protein given the association between manifestation and pro-proliferative signalling. (2011globalhealth.org)
Regulates2
Inactivation4
  • Hypermethylation of CpG islands within gene promoter regions is a major cause of tumor suppressor gene inactivation, and a subset of cancers exhibits concurrent hypermethylation of multiple CpG islands, which is referred to as the CpG island methylator phenotype (CIMP) [ 3 ]. (biomedcentral.com)
  • These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)
  • The higher incidence of ccRCC in male patients may partially be accounted by mono-allelic inactivation of the chromatin remodelling gene, KDM5C on the X chromosome [ 6 ]. (springer.com)
  • The inactivation of MMR genes, usually hMSH2 or hMLH1, is associated with human colorectal cancers and is responsible for the characteristic microsatellite instability (MSI)+ phenotype of these tumors. (aacrjournals.org)
Cyclin2
  • Several genetic alterations have been described in SCCHN, including mutations in the p53 tumor suppressor gene and mutations in genes that encode cell cycle proteins such as p16 and cyclin D1. (oncotarget.com)
  • To reveal the roles of CDC2/Cyclin B1 in human malignant gliomas, CDC2 in glioma cell line, it was down-regulated by retrovirus vectors expressing short hairpin RNAs (shRNAs) ex vivo and in vivo. (biomedcentral.com)
Tumors9
  • Because most tumors are deficient in one or more aspects of the function of the p53 tumor suppressor, either as a consequence of mutations within p53, or impairment of upstream and downstream modulators of p53 activity 19 , targeting MK2 has the potential to selectively enhance tumor cell killing without increasing the genotoxic effects of chemotherapy on normal p53-wild type tissues. (nature.com)
  • Immune cells abundantly infiltrate tumors, creating a complex environment mediated by repetitive cycles of antitumor responses and immune evasion ( 1 ). (frontiersin.org)
  • In addition to TAMs, solid tumors are also infiltrated by immunosuppressive, immature myeloid progenitor cells, commonly referred to as monocytic or polymorphonuclear myeloid-derived suppressor cells (M/PMN-MDSC) ( 11 - 13 ). (frontiersin.org)
  • This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. (medscape.com)
  • This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. (medscape.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)
  • 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)
Arrest5
  • 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)
  • cell cycle arrest. (biospraysehatalami.com)
  • Here we show that encysted embryos (cysts) of the primitive crustacean are ideal for such research because they undergo WNT7A complete cell cycle arrest when they enter diapause (a state of obligate dormancy). (biospraysehatalami.com)
  • however commonly used animal models are limited in that cell cycle arrest must be induced by treatment with drugs. (biospraysehatalami.com)
  • Remedy with alisertib up-controlled outrageous style p53 in Granta-519 MCL cells specifying G0/G1 arrest consequent to G2/M checkpoint activation. (immune-source.com)
Immune12
  • Over the past decade, cancer immunotherapy has been steering immune responses toward cancer cell eradication. (frontiersin.org)
  • Myeloid innate immune cells, such as granulocytes, monocytes, macrophages and dendritic cells (DCs), play an important role in cancer-cell recognition, initiation of inflammation and antitumor responses ( 2 ). (frontiersin.org)
  • Hence, myeloid cells play a dual role in cancer as they can initiate antitumor responses and communicate with cells of the adaptive immune system, but also promote local inflammation leading to chronic cancer-associated inflammation ( 5 , 6 ). (frontiersin.org)
  • The innate immune response by myeloid cells occurs as a succession of events starting at signaling through cytosolic or surface PRRs, followed by effector responses including the release of cytokines, reactive oxygen species (ROS), reactive nitrogen species (RNS), antibacterial peptides and degranulation ( Figure 1 ). (frontiersin.org)
  • Although immune checkpoint inhibitors (ICIs), in particular blockade of PD-1/PD-L1, show promising therapy response in some cancers, they are less effective in PCa which may be poor infiltration of cytotoxic T-cells [ 7 - 9 ]. (thno.org)
  • Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade (ICB) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. (bvsalud.org)
  • Cancer immunotherapy is a type of treatment that helps the immune system fight cancer cells. (healthline.com)
  • In this treatment , BCG is supplied directly to the bladder by a catheter that stimulates immune cells to attack bladder cancer cells. (healthline.com)
  • A vaccine containing these molecules may help the immune system better recognize and destroy cancer cells. (healthline.com)
  • Immune cells are removed from the body and sent to a laboratory, where they're modified to recognize prostate cancer cells. (healthline.com)
  • They're then injected back into the body, where they help the immune system find and destroy cancer cells. (healthline.com)
  • Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. (cdc.gov)
Colorectal cancer3
  • In this study, we examined the involvement of UHRF1 in aberrant DNA methylation and gene silencing in colorectal cancer (CRC). (biomedcentral.com)
  • We have shown that colorectal cancer cell lines defective in DNA MMR exhibit an increased sensitivity to both camptothecin, a topoisomerase I inhibitor, and etoposide, a topoisomerase II inhibitor. (aacrjournals.org)
  • Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage IV colorectal cancer. (cdc.gov)
Effector2
  • PRR on myeloid cells can be triggered by pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs), but also indirectly by secondary mechanisms such as complement activation and circulating antibodies (Abs), resulting in cytolytic and phagocytic effector mechanisms. (frontiersin.org)
  • Employing 16 different models of KRASG12D-driven PDAC, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer-associated fibroblasts. (bvsalud.org)
Mutations4
  • Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
  • These studies reveal that recurrent somatic mutations occur in only a handful of genes, with an overall mutational burden of roughly 1-2 per Mb. (springer.com)
  • The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. (biomedcentral.com)
  • For tumor cells with BRCA mutations, HRR loss would result in cell death. (biomedcentral.com)
Spindle1
  • As a new member of the kinesin superfamily of microtubule-based motors, kinesin Eg5, also called kinesin spindle protein (KSP) or KIF11 participates in mitosis, by separating the microtubules that are attached to the two centrosomes, and contributing to the bipolar arrangement of the spindles[ 6 ]. (biomedcentral.com)
Survival5
  • Patients characterized by elevated EGFR and elevated Aurora-A protein expression in tumor tissue represent a risk group with poor disease-free and overall survival (EGFR low Aurora-A low versus EGFR high Aurora-A high , p=0.024). (oncotarget.com)
  • 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)
  • 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)
  • A proliferative exhausted CD8 + T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. (elifesciences.org)
  • Identification of an eight-gene signature for survival prediction for patients with hepatocellular carcinoma based on integrated bioinformatics analysis. (cdc.gov)
Susceptibility1
  • Pancreatic cancer is the third most common cancer related to early-onset gene mutation in breast cancer (BRCA, breast cancer susceptibility genes) as well as ovarian cancer. (biomedcentral.com)
Histone2
  • The mammalian sirtuin (SIRT) family, evolutionally conserved proteins belonging to class III histone deacetylases (HDACs), comprises seven members. (biomedcentral.com)
  • Histone modification is a vital mechanism of gene expression and a promising therapy target. (thno.org)
Mitosis2
  • Dramatic change in chromosomal DNA morphology between interphase and mitosis is a defining features of the eukaryotic cell cycle. (icr.ac.uk)
  • Mechanistically, we discovered that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, which in turn results in delayed mitosis and catastrophic cell division. (bvsalud.org)
Depletion8
  • Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. (nature.com)
  • Depletion of UHRF1 rapidly induced genome-wide DNA demethylation in CRC cells. (biomedcentral.com)
  • Despite the substantial demethylation, however, UHRF1 depletion only minimally reversed CpG island hypermethylation-associated gene silencing. (biomedcentral.com)
  • The combination of UHRF1 depletion and HDAC inhibition also induced marked changes in the gene expression profiles such that cell cycle-related genes were strikingly downregulated. (biomedcentral.com)
  • Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. (rupress.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)
  • 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)
  • these effects were not observed in mice with depletion of CD8+ T cells. (stanford.edu)
Prognosis1
  • Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects. (elifesciences.org)
Cellular4
  • Multiple genes negatively impact overall cellular fitness and are targets for effective treatment. (childrenscolorado.org)
  • 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)
  • Cell Cycle The cell cycle is an integral part of cellular processes. (globaltechbiz.com)
  • Although older chemotherapeutic drugs are often toxic to normal cells, advances in genetics and cellular and molecular biology have led to development of more selective drugs. (msdmanuals.com)
Ataxia telangi1
  • 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)
Mismatch repair2
  • Opportunistic testing of BRCA1, BRCA2 and mismatch repair genes improves the yield of phenotype driven hereditary cancer gene panels. (cdc.gov)
  • Screening for Lynch Syndrome by Immunohistochemistry of Mismatch Repair Proteins: Significance of Indeterminate Result and Correlation With Mutational Studies. (cdc.gov)
Potent4
  • SB939 proved potent inhibition primarily in JAK2V617F- or FLT3-ITD-harboring cell phone lines (Body 2a). (immune-source.com)
  • We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. (icr.ac.uk)
  • We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. (proteopedia.org)
  • In the present study, the potent antitumor effects of pristimerin on OSCC cells were investigated. (spandidos-publications.com)
Cytotoxic1
  • Cytotoxic drugs damage DNA and kill many normal cells as well as cancer cells. (msdmanuals.com)
Genomic6
  • Infinium BeadChip assays and bisulfite pyrosequencing revealed significant demethylation across entire genomic regions, including CpG islands, gene bodies, intergenic regions, and repetitive elements. (biomedcentral.com)
  • The most common non-clear cell renal cancers have also undergone genomic profiling and are characterised by distinct genomic landscapes. (springer.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)
  • Spatial genomic analysis combined with single cell transcriptomic and epigenomic profiling of epithelial and mesenchymal lineages reveals that EMT promotes with the emergence of chromosomal instability (CIN). (bvsalud.org)
  • According to some comprehensive genomic analyses, four major driver genes have been identified in pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. (biomedcentral.com)
  • Maintenance of genomic stability is crucial for standard development, cell homeostasis and tumor suppression [7]. (rockinhibitor.com)
Cytotoxicity1
  • E, F) Silencing of DUSP6 improved the cytotoxicity of EGFR inhibitors, erlotinib (E) and cetuximab (F) in A431 cells. (synanet2020.com)
CDKs1
  • The transition of one phase to the other in the Go/G1, S, and G2/M phases of the cell cycle in malignancy cells occurs only after passing through the checkpoints, regulated by cyclins and CDKs, which is usually impaired in malignancy. (globaltechbiz.com)
Synthetic lethality1
  • We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. (nature.com)
Chromatin2
  • The next most prevalent aberrations include a cohort of chromatin-modifying genes with diverse roles including PBRM1 , SETD2 , BAP1 , and KMD5C . (springer.com)
  • In embryonic stem cells, SMAD2/3-TIF1γ recognizes specific chromatin marks, promoting access of SMAD2/3-SMAD4 to otherwise repressed targets. (shu.edu)
Tumorigenesis1
  • 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)
Hepatocellular3
  • The purpose of this study is to examine the therapeutic potential of dual gene targeted siRNA cocktail on human hepatocellular carcinoma Hep3B cells. (biomedcentral.com)
  • Simultaneous silencing of VEGF and KSP using siRNA cocktail yields promising results for eradicating hepatocellular carcinoma cells, a new direction for liver cancer treatment. (biomedcentral.com)
  • Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (PubMed:14602201). (proteopedia.org)
HDAC1
  • LMO2 is really a transcription component linked to standard hematopoiesis, but also leukemogenesis that may be overexpressed in most AML cells.43 Interestingly, LMO2 ranges were downregulated synergistically in MOLM-13 cells with pacritinib and pracinostat, and could be a consequence of a different synergistic discussion involving JAK2 and HDAC. (immune-source.com)
Mammalian1
  • Four polo family members are present in mammalian cells: Plk1 Plk2/Snk Plk3/Fnk/Prk and Plk4/Sak. (biospraysehatalami.com)
Defective2
  • Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
  • gene was first identified during screening of for mutants defective in cell division. (biospraysehatalami.com)
Tumours1
  • Correlation with outcome needs to be more comprehensively furnished, particularly for small renal masses, rarer non-clear cell renal cancers, and for all tumours undergoing targeted therapy. (springer.com)
Cdk43
  • These events resulted in upregulation of the Cdk4/6 inhibitor p15 INK4B and repression of the Cdk-activating phosphatase Cdc25A. (shu.edu)
  • Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. (elifesciences.org)
  • This study provides fundamental insight into the functional impact of CDK4 inhibition on cells in the tumor microenvironment, which is of high importance and interest to the field. (elifesciences.org)
Knockdown2
  • 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)
  • knockdown of Pvrl1 reduced cell-surface levels of PVR but not levels of Pvr messenger RNA. (stanford.edu)
Mutant3
  • In vitro mixture reports in a variety of cell phone product lines with either wt or mutant JAK2 or FLT3 also shown synergy, largely in cells that moved the mutant proteins. (immune-source.com)
  • Consistent because of this, related in vitro synergy was discovered within the JAK2 wt Establish-2 tissue and F36-P microscopic cells but not in FLT3 mutant mobile product lines using the precise pan-JAK inhibitor ruxolitinib in conjunction with pracinostat (records not demonstrated). (immune-source.com)
  • We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRASG12D, on early and advanced PDAC and its influence on the tumor microenvironment. (bvsalud.org)
Mechanism7
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • Here, we review the role, mechanism of action, and biological function of the seven sirtuins, as well as their inhibitors and activators. (biomedcentral.com)
  • Increasing evidences supporting the potential use of SIRT inhibitors (SIRTi) for the treatment of cancer, HIV infection, and muscular diseases and of SIRT activators (SIRTa) for age-related disorders have led to the identification of many SIRT modulators over recent years, mainly through chemical library screening and catalytic mechanism-based design approaches, often combined with structure-activity relationship (SAR) investigations. (biomedcentral.com)
  • Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. (icr.ac.uk)
  • Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters. (icr.ac.uk)
  • 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)
  • Another signalling mechanism involves high expression of PKC-like genes (21 types) during the process of encystation [48]. (globaltechbiz.com)
MRNA and protein3
  • siRNA cocktail showed a further downregulation on KSP mRNA and protein levels compared to KSP-siRNA or VEGF-siRNA, but not on VEGF expression. (biomedcentral.com)
  • However, no sigificant difference in the mRNA and protein levels of ANG2, involving inhibition of angiogenesis was found in HUVECs cultured with supernatant of Hep3B cells treated with siRNA cocktail, compared to that of VEGF-siRNA. (biomedcentral.com)
  • B) Schema of DUSP6 mRNA and protein. (synanet2020.com)
Synthesis1
  • The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. (icr.ac.uk)
Inhibits1
  • 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)
FLT3-ITD1
  • Our party recently discovered that treatment of FLT3-ITD tissue with FLT3 inhibitors inadequate JAK2 process (e.g. (immune-source.com)
Mutation2
  • SL originally described a relationship between two genes, where alteration of either gene alone results in viable cells, but alteration (mutation, loss, or inhibition) of both genes simultaneously was lethal. (nature.com)
  • Mutation gene sequencing has shown several gene associations that may account for its carcinogenesis, revealing a promising research direction. (biomedcentral.com)
Malignancy1
Ovarian carcinoma1
  • Of the 13 homeobox genes analyzed in the ovarian carcinoma cell model system, we found HOXA1 and HOXB4 to be upregulated by atRA in CAOV3 cells but not in SKOV3 cells. (temple.edu)