Search results for " Member 1"

showing 10 items of 102 documents

Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2.

2006

International audience; Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to induce apoptosis since they lack and have a truncated cytoplasmic death domain, respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL-induced apoptosis and we demonstrate here that this occurs through distinct mechanisms. While DcR1 prevents the assembly of the…

MESH : Hela CellsMESH: Membrane GlycoproteinsMESH: Membrane MicrodomainsDecoy Receptor 1ApoptosisMESH : Membrane GlycoproteinsReceptors Tumor Necrosis FactorTNF-Related Apoptosis-Inducing LigandMESH : TNF-Related Apoptosis-Inducing LigandJurkat Cells0302 clinical medicineMESH : Tumor Necrosis Factor Decoy ReceptorsMESH: Jurkat CellsDecoy receptorsReceptorCells CulturedMESH : Jurkat CellsMESH : Tumor Necrosis Factor-alpha0303 health sciencesMembrane GlycoproteinsMESH : Protein BindingArticlesMESH : Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsTumor Necrosis Factor Receptor-Associated Peptides and ProteinsCell biology030220 oncology & carcinogenesisCaspasesDeath-inducing signaling complexApoptosis/drug effects; Apoptosis Regulatory Proteins/antagonists & inhibitors; Apoptosis Regulatory Proteins/pharmacology; Caspases/metabolism; Cells Cultured; Death Domain Receptor Signaling Adaptor Proteins; Enzyme Activation/drug effects; GPI-Linked Proteins; HeLa Cells; Humans; Jurkat Cells; Membrane Glycoproteins/antagonists & inhibitors; Membrane Glycoproteins/pharmacology; Membrane Microdomains/drug effects; Protein Binding/drug effects; Receptors TNF-Related Apoptosis-Inducing Ligand; Receptors Tumor Necrosis Factor/metabolism; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor Decoy Receptors; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Tumor Necrosis Factor-alpha/pharmacologyMESH : Apoptosis Regulatory ProteinsMESH: TNF-Related Apoptosis-Inducing LigandProtein BindingMESH: Cells CulturedDeath Domain Receptor Signaling Adaptor ProteinsMESH: Enzyme ActivationBiologyMESH: Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsGPI-Linked Proteins03 medical and health sciencesMembrane MicrodomainsCell surface receptorMESH : Cells Cultured[SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular BiologyReceptors Tumor Necrosis Factor Member 10cHumansMESH: Protein Binding[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyMESH: Receptors TNF-Related Apoptosis-Inducing LigandMESH : Receptors TNF-Related Apoptosis-Inducing LigandMolecular Biology[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology030304 developmental biologyDeath domainMESH: CaspasesMESH: HumansTumor Necrosis Factor-alphaMESH: Apoptosis Regulatory ProteinsMESH: ApoptosisMESH : HumansCell BiologyMESH: Receptors Tumor Necrosis FactorMESH: Tumor Necrosis Factor Decoy ReceptorsMESH : Receptors Tumor Necrosis FactorEnzyme ActivationMESH: Hela CellsReceptors TNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor Decoy ReceptorsApoptosisMESH: Tumor Necrosis Factor-alphaMESH : Membrane MicrodomainsMESH : CaspasesApoptosis Regulatory ProteinsMESH : Enzyme ActivationMESH : ApoptosisMESH : Death Domain Receptor Signaling Adaptor ProteinsTumor Necrosis Factor Decoy ReceptorsHeLa CellsMESH: Death Domain Receptor Signaling Adaptor Proteins
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Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level

2011

International audience; TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which ma…

MESH: CASP8 and FADD-Like Apoptosis Regulating ProteinMESH : Antineoplastic Combined Chemotherapy ProtocolsCASP8 and FADD-Like Apoptosis Regulating ProteinTRAILApoptosisMESH : Models BiologicalMitochondrionMESH : RNA Small InterferingMESH: Caspase 8TNF-Related Apoptosis-Inducing LigandMESH : TNF-Related Apoptosis-Inducing LigandMESH : Tumor Necrosis Factor Decoy Receptors0302 clinical medicineRNA interferenceNeoplasmsAntineoplastic Combined Chemotherapy ProtocolsMESH: RNA Small InterferingMESH: NeoplasmsRNA Small InterferingReceptorSensitizationCaspase 80303 health sciencesMESH : Caspase 8MESH: Drug Resistance Neoplasm3. Good healthCell biologyMESH: Antineoplastic Combined Chemotherapy ProtocolsMESH : Drug Resistance Neoplasmmedicine.anatomical_structure030220 oncology & carcinogenesisRNA InterferenceMESH : GPI-Linked ProteinsMESH: TNF-Related Apoptosis-Inducing LigandDeath Domain Receptor Signaling Adaptor ProteinsProgrammed cell deathMESH: Cell Line Tumorc-FLIPMESH: RNA InterferenceBiologyGPI-Linked ProteinsCaspase 8Models Biological03 medical and health sciencesCell Line TumorReceptors Tumor Necrosis Factor Member 10cmedicineTRAIL-R4HumanscancerChemotherapy[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyMESH: Receptors TNF-Related Apoptosis-Inducing LigandMESH : Receptors TNF-Related Apoptosis-Inducing Ligand[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular BiologyMolecular Biology030304 developmental biologyOriginal PaperMESH: HumansMESH : Cell Line TumorMESH: ApoptosisMESH : HumansMESH: Models BiologicalMESH : CASP8 and FADD-Like Apoptosis Regulating ProteinCell BiologyMESH: Tumor Necrosis Factor Decoy ReceptorsMESH : NeoplasmsReceptors TNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor Decoy ReceptorsDrug Resistance NeoplasmApoptosisMESH : RNA InterferenceMESH: GPI-Linked ProteinsMESH : ApoptosisMESH : Death Domain Receptor Signaling Adaptor ProteinsMESH: Death Domain Receptor Signaling Adaptor ProteinsTumor Necrosis Factor Decoy Receptors
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The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients

2008

Background: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCBl. We have investigated the effects of possible relevant CYP3A5 and ABCBl single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. Material/Methods: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for gen-otyping CYP3A5*3 [6986A>G] as well as ABCBl at exons 21 [2677G>T] and 26 [3435C>T]. Results:87.5…

MaleCYP3A5ATP Binding Cassette Transporter Subfamily BGenotypeHomozygoteABCB1Polymorphism Single NucleotideTacrolimusWhite PeopleLiver Transplantationliver transplantPharmacogeneticssingle nucleotide polymorphismTacrolimuSettore BIO/14 - FarmacologiaCytochrome P-450 CYP3AHumansFemaleATP Binding Cassette Transporter Subfamily B Member 1Tacrolimus; single nucleotide polymorphisms; CYP3A5; ABCB1; liver transplantImmunosuppressive Agents
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Promoter methylation of MGMT, MLH1 and RASSF1A tumor suppressor genes in head and neck squamous cell carcinoma: Pharmacological genome demethylation …

2012

Promoter hypermethylation of tumor suppressor genes (TSGs) is a common feature of primary cancer cells. However, to date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis have not been well-defined. In the present study, we analyzed the promoter methylation status of the genes mutL homolog 1 (MLH1), Ras-association domain family member 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in 23 HNSCC samples, three control tissues and one HNSCC cell line (UM-SCC 33) using methylation-specific PCR (MSP). The expression of the three proteins was quantified by semi-quantitative immunohistochemical analysis. The cell line was treate…

MaleCancer Researchmedicine.disease_causePolymerase Chain Reactionchemistry.chemical_compoundRas association domain family member 1Genes Tumor Suppressortumor suppressor geneEnzyme InhibitorsPromoter Regions GeneticDNA Modification MethylasesAged 80 and overNuclear ProteinsArticlesGeneral MedicineMethylationMiddle AgedImmunohistochemistryPrimary tumorOncologyDealkylationHead and Neck NeoplasmsDNA methylationAzacitidineCarcinoma Squamous CellFemaleMutL Protein Homolog 1Molecular Sequence DataDown-RegulationBiologyhead and neck squamous cell carcinomamutL homolog 15-azacytidineCell Line TumormedicineHumansEpigeneticsneoplasmsO-6-methylguanine-DNA methyltransferaseAdaptor Proteins Signal TransducingAgedCell ProliferationBase SequenceDose-Response Relationship DrugTumor Suppressor ProteinsSequence Analysis DNADNA Methylationmedicine.diseaseHead and neck squamous-cell carcinomaMolecular biologyDemethylating agentSquamous carcinomastomatognathic diseasesDNA Repair EnzymeschemistryCase-Control StudiesCpG IslandsCarcinogenesisOncology Reports
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Unique pharmacology of KAR-2, a potential anti-cancer agent: absorption modelling and selective mitotic spindle targeting.

2008

Abstract Bis-indols are a large group of the anti-cancer agents, which effectively arrest the uncontrolled division of the cancerous cells. Their use in clinical chemotherapy is still limited because of: (i) the non-specific targeting of the mitotic cells; (ii) low bioavailability of the drugs. KAR-2 has been identified as a tubulin binding agent which displays significantly lower cytotoxicity but favourable anti-cancer potency than its mother molecule, vinblastine. The objective of this paper, on one hand, was to show that the human intestinal epithelial Caco-2 cells, used for pharmacokinetic studies display distinct sensitivity against KAR-2 and vinblastine due to their distinct targeting…

MaleCell divisionStereochemistryPharmaceutical ScienceBiological Transport ActiveSpindle ApparatusBiologyVinblastinePermeabilityInjectionsmedicineAnimalsHumansATP Binding Cassette Transporter Subfamily B Member 1Rats WistarCytotoxicityMitosisChromatography High Pressure LiquidModels StatisticalAntineoplastic Agents PhytogenicIn vitroSpindle apparatusVinblastineRatsSpectrometry FluorescenceIntestinal AbsorptionTubulin Binding AgentBiophysicsInterphaseCaco-2 CellsAlgorithmsmedicine.drugEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
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Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.

2001

The expression of P-glycoprotein is induced in cell cultures upon exposure to various inducers. Therefore, the aim of the present study was to evaluate the in-vivo relevance of this observation, i.e. the influence of chronic pretreatments with selected drugs -- all of which are ligands to P-glycoprotein (P-gp) as demonstrated in radioligand binding studies and all of which have some or a considerable effect on P-gp expression in Caco-2 cells -- on the effective intestinal permeabilities of the model compound talinolol in rats employing in-situ single-pass intestinal perfusion of three different gut segments. Talinolol was selected, because it shows high selectivity for one of the exsorptive…

MaleColonDuodenumAdrenergic beta-AntagonistsPharmaceutical ScienceBiologyPharmacologyLigandsVinblastineJejunumPropanolamineschemistry.chemical_compoundmedicineAnimalsATP Binding Cassette Transporter Subfamily B Member 1Rats WistarP-glycoproteinIntestinal permeabilityStereoisomerismmedicine.diseaseCalcium Channel BlockersAntineoplastic Agents PhytogenicVinblastineRatsmedicine.anatomical_structureJejunumchemistryBiochemistryVerapamilDuodenumbiology.proteinVerapamilPerfusionTalinololmedicine.drugEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
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Acitretin, an Enhancer of Alpha-Secretase Expression, Crosses the Blood-Brain Barrier and Is Not Eliminated by P-Glycoprotein

2011

<i>Background:</i> ADAM10 (a disintegrin and metalloproteinase 10) has been demonstrated to act as the main physiological α-secretase. Enzymatic activity of the α-secretase on the one hand prevents the formation of toxic Aβ peptides and on the other hand promotes the secretion of a neurotrophic and neuroprotective amyloid precursor protein fragment (APPs-α) by cleaving the amyloid precursor protein within its Aβ sequence. Enhancement of ADAM10’s gene expression may therefore present a valuable therapeutic approach for the treatment of Alzheimer’s disease (AD), where Aβ peptides are severely involved in the pathogenesis. <i>Objective:</i> In cell culture and in a tran…

MaleGenetically modified mouseATP Binding Cassette Transporter Subfamily BTime FactorsADAM10PharmacologyTransfectionAcitretinADAM10 ProteinMiceNeuroblastomachemistry.chemical_compoundCell Line TumormedicineAmyloid precursor proteinAnimalsHumansATP Binding Cassette Transporter Subfamily B Member 1Chromatography High Pressure LiquidP-glycoproteinMice KnockoutAnalysis of VarianceReporter genebiologyMembrane ProteinsMolecular biologyAcitretinADAM ProteinsGene Expression RegulationNeurologychemistryAlpha secretaseBlood-Brain Barrierbiology.proteinTamibaroteneNeurology (clinical)Amyloid Precursor Protein Secretasesmedicine.drugNeurodegenerative Diseases
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Pharmacodynamic effects of aripiprazole and ziprasidone with respect to p-glycoprotein substrate properties.

2013

Introduction Aripiprazole, an atypical antipsychotic drug with mixed antagonism and agonism on dopamine D2 and serotonin receptors, is a substrate of the efflux transporter P-glycoprotein (P-gp). Here we tested the pharmacodynamic consequences of these properties in a P-gp deficient mouse model by studying the effects of aripiprazole and of ziprasidone on motor coordination. Methods The motor behaviour of wild-type (WT) and P-gp deficient [abcb1ab(-/-)] mice was investigated on a RotaRod. Mice received acute injections of either aripirazole or ziprasidone. For comparison, the dopamine receptor antagonist haloperidol and serotonin receptor ligands buspirone and ketanserin were also applied. …

MaleKetanserinmedicine.drug_classAripiprazoleAtypical antipsychoticPharmacologyMotor ActivityQuinolonesRotarod performance testPiperazinesBuspironeMiceDopamine receptor D2medicineAnimalsPharmacology (medical)ZiprasidoneATP Binding Cassette Transporter Subfamily B Member 1Mice KnockoutChemistryGeneral MedicineBuspironeSerotonin Receptor AgonistsPsychiatry and Mental healthThiazolesDopamine receptorRotarod Performance TestHaloperidolAripiprazoleKetanserinSerotonin Antagonistsmedicine.drugAntipsychotic AgentsPharmacopsychiatry
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Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

2012

Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS). Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing. Results: Seventeen SNPs representing 1…

MaleLinkage disequilibriumendocrine system diseasesGenome-wide association studyPrimary biliary cirrhosisGenotypeBLOOD-GROUPBileChildPOPULATIONAged 80 and overGeneticseducation.field_of_studyPrimary sclerosing cholangitisdigestive oral and skin physiologyMiddle AgedFucosyltransferasesChild PreschoolDISEASESFemaleNeprilysinReceptors Tumor Necrosis Factor Member 14B-LYMPHOCYTEAdultRiskGenome-wide association studyAdolescentGenotypeSUSCEPTIBILITY LOCIFUT2Cholangitis SclerosingPopulationT-LYMPHOCYTE ATTENUATORSingle-nucleotide polymorphismBiologyPolymorphism Single Nucleotidedigestive systemArticlePrimary sclerosing cholangitisGenetic predispositionmedicineImmunogeneticsHumansGenetic Predisposition to DiseaseeducationMETAANALYSISAgedNON-SECRETOR STATUSHepatologymedicine.diseaseGENEdigestive system diseasesSingle nucleotide polymorphismGenetic LociImmunology
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Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein

2010

According to in vitro studies the enantiomers of venlafaxine display different degrees of serotonin and noradrenaline reuptake inhibition. Therefore, clarification of the enantiomeric drug distribution between serum and brain is highly warranted. To elucidate if P-glycoprotein (P-gp) in a stereoselective manner transports venlafaxine and its metabolites out of the brain we used abcb1ab double-knockout mice that do not express P-gp. A single dose of racemic venlafaxine (10 mg/kg bw) was intraperitoneally injected to knockout (-/-) and wildtype (+/+) mice. Serum and brain samples were collected 1, 3, 6 and 9 h following drug administration for analysis by LC/MS/MS. One to six hours post-dose,…

MaleMedicin och hälsovetenskapVenlafaxinePharmacologyBlood–brain barrierMedical and Health SciencesMicemedicineAnimalsPharmacology (medical)ATP Binding Cassette Transporter Subfamily B Member 1Biological PsychiatryP-glycoproteinPharmacologyMice KnockoutbiologyChemistryVenlafaxine HydrochlorideBiological TransportStereoisomerismCyclohexanolsIn vitroPsychiatry and Mental healthmedicine.anatomical_structureNeurologyBlood-Brain BarrierKnockout mousebiology.proteinStereoselectivityNeurology (clinical)SerotoninEnantiomerSelective Serotonin Reuptake Inhibitorsmedicine.drug
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