2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2018
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nature Communications 2018, 9: 3196. PMID: 30097571, PMCID: PMC6086912, DOI: 10.1038/s41467-018-05032-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BlockingCarcinogenesisCarcinoma, Non-Small-Cell LungCell ProliferationCytotoxicity, ImmunologicHistocompatibility Antigens Class IHumansLung NeoplasmsLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred NODMice, SCIDMutant ProteinsMutationPeptidesPhenotypeProgrammed Cell Death 1 ReceptorReproducibility of ResultsSurvival AnalysisTobaccoConceptsImmune checkpoint blockersCheckpoint blockersQuantitative immunofluorescenceNon-small cell lung carcinoma patientsCell lung carcinoma patientsNon-small cell lung carcinomaPatient-derived xenograft modelsIntratumoral T cellsMultiplexed quantitative immunofluorescencePD-1 blockadeLevels of CD3Lung carcinoma patientsCell lung carcinomaT cell proliferationPre-treatment samplesTIL phenotypeSurvival benefitCarcinoma patientsEffector capacityLung carcinomaT cellsWhole-exome DNA sequencingXenograft modelFavorable responseBlockers
2011
Glucose and Inflammation Control Islet Vascular Density and β-Cell Function in NOD Mice Control of Islet Vasculature and Vascular Endothelial Growth Factor by Glucose
Akirav EM, Baquero MT, Opare-Addo LW, Akirav M, Galvan E, Kushner JA, Rimm DL, Herold KC. Glucose and Inflammation Control Islet Vascular Density and β-Cell Function in NOD Mice Control of Islet Vasculature and Vascular Endothelial Growth Factor by Glucose. Diabetes 2011, 60: 876-883. PMID: 21307078, PMCID: PMC3046848, DOI: 10.2337/db10-0793.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorIslet vascular densityNOD miceEndothelial cell densityGlucose toleranceEndothelial growth factorΒ-cellsVascular densityInsulin contentIslet vasculatureAnti-CD3 monoclonal antibodyEndothelial cellsGrowth factorDiabetic NOD micePrediabetic NOD miceAltered glucose toleranceImproved glucose toleranceEndothelial cell destructionType 1 diabetesAnti-CD3 mAbΒ-cell functionΒ-cell massHigh glucose levelsΒ-cell proliferationTransfer of supernatants