Search results for " 4′"

showing 5 items of 5 documents

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

PBD Polo box domainMTD maximal tolerance doseCDC25 cell division cycle 25HIF-1α hypoxia-inducible factor 1 αMST microscale thermophoresisIC50 50% inhibition concentrationMFP M phase promoting factorPARP-1 poly(ADP-ribose) polymerase-10302 clinical medicineFOXO forkhead box ONec-1 necrostatin 1CDC2 cell division cycle protein 2 homologGeneral Pharmacology Toxicology and PharmaceuticsMitotic catastropheCDK cyclin-dependent kinase0303 health sciencesChemistryPolo-like kinaseMono-targeted therapyCell cycleBUBR1 budding uninhibited by benzimidazole-related 1Polo box domain030220 oncology & carcinogenesisPLK1 Polo-like kinaseNecroptosisSpindle damagePLK1IHC immunohistochemistryOriginal articleNecroptosisCell cyclePLK1APC/C anaphase-promoting complex/cyclosomePLK3ABC avidin-biotin complexPI propidium iodide03 medical and health sciencesFBS fetal bovine serumPDB Protein Data BankKd the dissociation constantKinase activity030304 developmental biologyAkt/PKB signaling pathwayCell growthlcsh:RM1-950LC3 light chain 3lcsh:Therapeutics. PharmacologyCancer researchDAPKs death-associated protein kinase3-MA 3-methyladenineDAPI 4′6-diamidino-2-phenylindoleSAC spindle assembly checkpointActa Pharmaceutica Sinica B
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Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

2019

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…

0301 basic medicineMaleCancer ResearchBiopsyL-amp GB EGFR-low amplified glioblastomamedicine.disease_causewt wildtypeMYBPC3 myosin-binding protein C0302 clinical medicineHIC1 hypermethylated in cancer 1Gene duplicationIn Situ Hybridization FluorescenceIDH2 isocitrate dehydrogenase 2MutationRB-pat RB signaling pathwayEGFRvIII epidermal growth factor receptor variant number IIIPAH phenylalanine hydroxylaseGBM glioblastoma IDH-wildtype (glioblastoma multiforme primary glioblastoma).ANOVA ANalysis Of VArianceN-amp GB EGFR-no amplified glioblastomaMiddle AgedCDKN2A cyclin-dependent kinase inhibitor 2Alcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensPrognosisPrimary tumorImmunohistochemistryH-amp GB EGFR-high amplified glioblastomaErbB ReceptorsTKR-pat tyrosine-kinase receptors signaling pathway030220 oncology & carcinogenesisDisease ProgressionCDK6 cyclin-dependent kinase 6CDH1 Cadherin 1FemaleCREM cAMP response element modulatorIHC immunohistochemistryAdultOriginal articleDNA Copy Number VariationsCDKN1B cyclin-dependent kinase inhibitor 1BBiologyRARB retinoic acid receptor betaCNS central nervous systemlcsh:RC254-282IDH1 isocitrate dehydrogenase 1BCL2 B-cell cll/ lymphoma 2CNAs copy number algerationsWHO World Health Organization03 medical and health sciencesYoung Adultp53-pat p53 signaling pathwaymedicineBiomarkers TumorTMA tissue microarrayPTENHumansProtein kinase BPI3K/AKT/mTOR pathwaySurvival analysisAgedGenetic heterogeneityGene AmplificationGFAP glial fibrillary acidic proteinMLPA multiplex ligation-dependent probe amplificationmedicine.diseaseFISH fluorescence in situ hibridizationSurvival AnalysisCDKN2B cyclin-dependent kinase inhibitor 2BPTEN phosphatase and tensin homologEGFR epidermal growth factor receptorCNV-load load of copy number variations030104 developmental biologyMutationPARK2 parkinCancer researchbiology.proteinTCGA The Cancer Genome AtlasLARGE1 acetylglucosaminyltransferase-like protein 1GlioblastomaCHD7 Chromodomain Helicase DNA Binding Protein 7DAPI 4′6-diamidino-2-phenylindoleNeoplasia (New York, N.Y.)
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Consensus guidelines for the detection of immunogenic cell death

2014

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defect…

HSV-1 herpes simplex virus type IΔψm mitochondrial transmembrane potentialmedicine.medical_treatmentDAMP damage-associated molecular patterndetectionFLT3LG fms-related tyrosine kinase 3 ligandReviewmember 3calreticulinEukaryotic translation initiation factor 2ARFP red fluorescent protein0302 clinical medicineMOMP mitochondrial outer membrane permeabilizationImmunology and AllergyGFP green fluorescent proteinHMGB10303 health scienceseducation.field_of_studyToll-like receptorBAK1 BCL2-antagonist/killer 1H2B histone 2Bendoplasmic reticulum stre3. Good healthBAX BCL2-associated X proteinXBP1 X-box binding protein 1cell deathOncologyPDIA3 protein disulfide isomerase family A030220 oncology & carcinogenesisendoplasmic reticulum stressImmunogenic cell deathHSP heat shock proteinimmunotherapyTLR Toll-like receptorautophagyATF6 activating transcription factor 6ImmunologyICD immunogenic cell deathEIF2A eukaryotic translation initiation factor 2AGuidelinesBiologyBCL2 B-cell CLL/lymphoma 2 proteinER endoplasmic reticulumPI propidium iodideATP release03 medical and health sciencesImmune systemimmunogenicmedicineIFN interferonAntigen-presenting celleducation030304 developmental biologyCALR calreticulinDamage-associated molecular patternImmunotherapyCTL cytotoxic T lymphocyteHMGB1 high mobility group box 1IL interleukinG3BP1 GTPase activating protein (SH3 domain) binding protein 1APC antigen-presenting cellCancer cellImmunologyDiOC6(3) 33′-dihexyloxacarbocyanine iodideDAPI 4′6-diamidino-2-phenylindoleOncoImmunology
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The LepR-mediated leptin transport across brain barriers controls food reward

2018

Objective Leptin is a key hormone in the control of appetite and body weight. Predominantly produced by white adipose tissue, it acts on the brain to inhibit homeostatic feeding and food reward. Leptin has free access to circumventricular organs, such as the median eminence, but entry into other brain centers is restricted by the blood–brain and blood–CSF barriers. So far, it is unknown for which of its central effects leptin has to penetrate brain barriers. In addition, the mechanisms mediating the transport across barriers are unclear although high expression in brain barriers suggests an important role of the leptin receptor (LepR). Methods We selectively deleted LepR in brain endothelia…

Male0301 basic medicineLeptinHFD high-fat dietEndothelial cellsWhite adipose tissueCSF cerebrospinal fluidMice0302 clinical medicineCPP conditioned place preferenceBBB blood–brain barrierCells Culturedmedia_commonLeptindigestive oral and skin physiologyi.p. intraperitonealmedicine.anatomical_structureLepRBlood-Brain BarrierBlood–brain barrier; Endothelial cells; LepR; Leptin; Obesity; RewardMedian eminenceqPCR quantitative polymerase chain reactionReceptors LeptinOriginal ArticleChoroid plexusmedicine.medical_specialtylcsh:Internal medicinemedia_common.quotation_subjectHyperphagiaBiologyBlood–brain barrierVTA ventral tegmental areaBC bottle choice testCapillary PermeabilityBlood–brain barrierARC arcuate nucleus03 medical and health sciencesPBS phosphate buffered salineRewardInternal medicinemedicineAnimalsObesitylcsh:RC31-1245Molecular BiologyCircumventricular organsBlood-Nerve BarrierLeptin receptorNCD normal chow dietAppetiteCell Biology030104 developmental biologyEndocrinologyLepR leptin receptorChoroid PlexusBSA bovine serum albuminPFA paraformaldehyde030217 neurology & neurosurgeryDAPI 4′6-diamidino-2-phenylindoleMolecular Metabolism
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Anti-inflammatory Function of High-Density Lipoproteins via Autophagy of IκB Kinase

2015

Background & Aims: Plasma levels of high-density lipoprotein (HDL) cholesterol are frequently found decreased in patients with inflammatory bowel disease (IBD). Therefore, and because HDL exerts anti-inflammatory activities, we investigated whether HDL and its major protein component apolipoprotein A-I (apoA-I) modulate mucosal inflammatory responses in vitro and in vivo. Methods: The human intestinal epithelial cell line T84 was used as the in vitro model for measuring the effects of HDL on the expression and secretion of tumor necrosis factor (TNF), interleukin-8 (IL-8), and intracellular adhesion molecule (ICAM). Nuclear factor-κB (NF-κB)-responsive promoter activity was studied by …

WT wild typeApolipoprotein BEMSA electrophoretic mobility shift assayMPO myeloperoxidaseIκB kinaseDSS dextran sodium sulphatemTOR the mammalian target of rapamycinRT-PCR real-time polymerase chain reactionNF-κBchemistry.chemical_compound540 ChemistryApoA-I apolipoprotein A-I10038 Institute of Clinical ChemistryOriginal ResearchTNF tumor necrosis factorbiologyIBD inflammatory bowel diseaseChemistryGastroenterologyMyeloperoxidase10076 Center for Integrative Human PhysiologyMEICS murine endoscopic index of colitis severityTumor necrosis factor alphalipids (amino acids peptides and proteins)3-MA 3-methyl adenineNF-κB nuclear factor κBHDL high-density lipoproteinLC3II light chain 3 IIPBS phosphate-buffered salinep-IKK phosphorylated IκB kinase610 Medicine & healthICAM intracellular adhesion molecule246-Trinitrobenzenesulfonic acidTg transgenicmedicineAutophagyCD Crohn’s disease2715 GastroenterologyColitislcsh:RC799-869KO knockoutHepatologyApolipoprotein A-IAutophagyInflammatory Bowel DiseaseTNBS 246-trinitrobenzenesulfonic acidmedicine.diseaseMolecular biologyIL interleukinsiRNA small interfering RNAPI-3 phosphatidylinositol-3Immunologybiology.protein2721 Hepatologylcsh:Diseases of the digestive system. GastroenterologyPFA paraformaldehydeLipoproteinDAPI 4′6-diamidino-2-phenylindoleCMGH Cellular and Molecular Gastroenterology and Hepatology
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