2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer
Elfiky AA, Aziz SA, Conrad PJ, Siddiqui S, Hackl W, Maira M, Robert CL, Kluger HM. Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer. Journal Of Translational Medicine 2011, 9: 133. PMID: 21834980, PMCID: PMC3173341, DOI: 10.1186/1479-5876-9-133.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisAutomationBiomarkers, TumorCarcinoma, Renal CellCell Line, TumorChromonesDrug SynergismHumansImidazolesInhibitory Concentration 50Kidney NeoplasmsMolecular Targeted TherapyMorpholinesMultivariate AnalysisPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsQuinolinesSirolimusTOR Serine-Threonine KinasesConceptsRenal cell carcinomaRCC cell linesNVP-BEZ235PI3KMTOR expressionMetastatic renal cell carcinomaPI3K subunitsHigh mTOR expressionAutomated Quantitative AnalysisRCC cell growthRenal cell cancerExpression of p85PI3K inhibitor LY294002Cell linesWarrants further investigationK inhibitor LY294002PI3K inhibitorsMulti-variable analysisCell cancerCell carcinomaClinical trialsSitu protein expressionNephrectomy casesTissue microarrayMTOR inhibitors
2008
An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT. An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer. Cancer Research 2008, 68: 6084-6091. PMID: 18676830, PMCID: PMC2680495, DOI: 10.1158/0008-5472.can-07-6854.Peer-Reviewed Original ResearchConceptsPIK3CA mutationsBreast cancerAKT1 mutationsPTEN lossPathway aberrationsHormone receptor-positive breast cancer patientsHormone receptor-positive breast cancerPTEN mutationsReceptor-positive breast cancer patientsHormone receptor-positive cancersPI3K pathway aberrationsCell linesReceptor-positive breast cancerAdjuvant tamoxifen therapyReceptor-positive cancersBreast cancer patientsDifferent breast cancer subtypesDownstream PI3K/AktBasal-like tumorsBreast cancer subtypesHuman breast cancerPI3K inhibitor LY294002PI3K/AktK inhibitor LY294002PI3K inhibitionIschemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons
Miyawaki T, Mashiko T, Ofengeim D, Flannery RJ, Noh KM, Fujisawa S, Bonanni L, Bennett MV, Zukin RS, Jonas EA. Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 4892-4897. PMID: 18347331, PMCID: PMC2290755, DOI: 10.1073/pnas.0800628105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisbcl-Associated Death Proteinbcl-X ProteinBrain IschemiaCaspase InhibitorsChromonesHippocampusIon Channel GatingIschemic PreconditioningLarge-Conductance Calcium-Activated Potassium ChannelsMaleMitochondriaMorpholinesNeuronsPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein TransportProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionConceptsMitochondrial outer membraneSmac/DIABLOPI3K/AktOuter membraneCytochrome cFeatures of apoptosisSpecific PI3K inhibitor LY294002PI3K inhibitor LY294002K inhibitor LY294002Mitochondrial translocationMitochondrial releaseMitochondrial membraneVulnerable CA1 pyramidal cellsLarge conductance channelBad translocationInhibitor LY294002PI3KNeuronal deathChannel activityVivo 1 hDIABLOMitochondriaAktTranslocationBcl
2006
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, Shanabrough M, Burdakov D, Rother E, Janoschek R, Alber J, Belgardt BF, Koch L, Seibler J, Schwenk F, Fekete C, Suzuki A, Mak TW, Krone W, Horvath TL, Ashcroft FM, Brüning JC. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. Journal Of Clinical Investigation 2006, 116: 1886-1901. PMID: 16794735, PMCID: PMC1481658, DOI: 10.1172/jci27123.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromonesDietEatingFemaleHypoglycemic AgentsHypothalamusInsulinLeptinMaleMembrane PotentialsMiceMice, KnockoutMorpholinesNeuronsObesityPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoinositide-3 Kinase InhibitorsPotassium ChannelsPro-OpiomelanocortinPTEN PhosphohydrolaseSecond Messenger SystemsTolbutamideConceptsPOMC neuronsATP-sensitive potassium channel activityBasal firing rateHypothalamic proopiomelanocortin (POMC) neuronsElectrical activityKATP channel activationPI3K inhibitor LY294002PTEN knockout micePotassium channel activityK inhibitor LY294002PI3K pathwayProopiomelanocortin neuronsHypothalamic receptorsICV administrationFood intakeKATP channelsKnockout miceMelanocortin systemLeptinFiring rateNeuronsMiceSTAT3 phosphorylationK pathwayInhibitor LY294002
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