2023
Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma model
2015
Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma
Wengrod J, Wang D, Weiss S, Zhong H, Osman I, Gardner LB. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma. Science Signaling 2015, 8: ra27. PMID: 25759478, PMCID: PMC4580977, DOI: 10.1126/scisignal.aaa0899.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAutophagyCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsEnzyme ActivationEukaryotic Initiation Factor-2Gene Knock-In TechniquesHumansImmunoblottingImmunohistochemistryImmunoprecipitationMass SpectrometryMechanistic Target of Rapamycin Complex 1MelanomaMicroscopy, FluorescenceMultiprotein ComplexesMutationPhosphoprotein PhosphatasesPhosphorylationProtein Serine-Threonine KinasesSirolimusTOR Serine-Threonine KinasesTunicamycinConceptsKinase complex mTORC1Amino acid-sensing systemsProtein phosphatase 6Activation of GCN2Amino acid deprivationEukaryotic initiation factorPharmacological inhibitionWild-type alleleKinase GCN2Human melanoma samplesGCN2 activationRegulatory subunitCatalytic subunitInitiation factorsPathways downstreamPP6cGCN2MTORC1PhosphorylationAutophagyMutantsMelanoma samplesSubunitsMutationsActivation