2023
Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.
Horowitch B, Lee D, Ding M, Martinez-Morilla S, Aung T, Ouerghi F, Wang X, Wei W, Damsky W, Sznol M, Kluger H, Rimm D, Ishizuka J. Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma. Clinical Cancer Research 2023, 29: 2908-2918. PMID: 37233452, PMCID: PMC10524955, DOI: 10.1158/1078-0432.ccr-23-0215.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHuman melanoma cell linesMelanoma cell linesPD-L1Validation cohortYale-New Haven HospitalCombination of ipilimumabPD-L1 markersImmune checkpoint blockadePD-L1 biomarkerNew Haven HospitalSTAT1 levelsCell linesWestern blot analysisCheckpoint inhibitorsCheckpoint blockadeClinical responseOverall survivalImproved survivalResistance of cancersMetastatic melanomaMelanoma responsePredict responseTreatment responseDistinct patterns
2009
C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Jilaveanu LB, Zito CR, Aziz SA, Conrad PJ, Schmitz JC, Sznol M, Camp RL, Rimm DL, Kluger HM. C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas. Clinical Cancer Research 2009, 15: 5704-5713. PMID: 19737955, PMCID: PMC2763114, DOI: 10.1158/1078-0432.ccr-09-0198.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBenzenesulfonatesCell Line, TumorCell ProliferationCell SurvivalCohort StudiesDisease ProgressionFemaleGene SilencingHumansIndolesMaleMelanomaMiddle AgedNevusNiacinamidePhenolsPhenylurea CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafPyridinesRNA, Small InterferingSensitivity and SpecificitySkin NeoplasmsSorafenibYoung AdultConceptsExtracellular signal-regulated kinaseC-RafC-Raf expressionSubset of melanomasPhospho-c-RafSignal-regulated kinaseCell linesProtein kinase inhibitionMitogen-activated protein kinase inhibitionDecreased viabilityDecreased Bcl-2 expressionProtein kinaseCell signalingBcl-2 inhibitionRaf kinaseB-RafMelanoma cell linesPhospho-MEKSpecific siRNAsSitu protein expressionGW5074Major isoformsKinasePhospho-ERKBcl-2 expressionPhosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma
Aziz SA, Davies M, Pick E, Zito C, Jilaveanu L, Camp RL, Rimm DL, Kluger Y, Kluger HM. Phosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma. Clinical Cancer Research 2009, 15: 3029-3036. PMID: 19383818, PMCID: PMC4431617, DOI: 10.1158/1078-0432.ccr-08-2768.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCell ProliferationChromonesEnzyme InhibitorsHumansImmunoblottingImmunoenzyme TechniquesMelanomaMorpholinesNevus, PigmentedPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Array AnalysisSkin NeoplasmsTissue Array AnalysisTumor Cells, CulturedConceptsPhosphatidylinositol-3 kinasePI3K inhibitorsExpression of p85PI3KP110alpha subunitPathway membersK inhibitorsCell linesPI3K pathway membersReverse phase protein arrayGood drug targetPhase protein arrayPI3K pathwayTargets of drugsCellular processesPhospho-Akt levelsPI3K inhibitionMelanoma cell linesDrug targetsFull activationP85K pathwayLY294002Protein arraysResistant cell linesGab2-Mediated Signaling Promotes Melanoma Metastasis
Horst B, Gruvberger-Saal SK, Hopkins BD, Bordone L, Yang Y, Chernoff KA, Uzoma I, Schwipper V, Liebau J, Nowak NJ, Brunner G, Owens D, Rimm DL, Parsons R, Celebi JT. Gab2-Mediated Signaling Promotes Melanoma Metastasis. American Journal Of Pathology 2009, 174: 1524-1533. PMID: 19342374, PMCID: PMC2671382, DOI: 10.2353/ajpath.2009.080543.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBiomarkers, TumorBlotting, WesternCell MovementChromosomes, Artificial, BacterialComparative Genomic HybridizationFluorescent Antibody TechniqueGene DosageHumansIn Situ Hybridization, FluorescenceMelanomaNeoplasm InvasivenessNeoplasm MetastasisOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideReverse Transcriptase Polymerase Chain ReactionSignal TransductionTissue Array AnalysisConceptsPI3K-Akt pathwayBacterial artificial chromosome array comparative genomic hybridizationInvasive potentialGrowth factor independenceSingle nucleotide polymorphism arrayCritical biological featuresHyperactivation of AKTMelanoma tumor progressionNucleotide polymorphism arrayTumor cell migrationArray comparative genomic hybridizationAdaptor proteinComparative genomic hybridizationRas-ERKFactor independenceMetastatic melanoma samplesMelanoma cell linesGab2Polymorphism arrayCopy numberCell migrationHuman cancersUndefined roleWide searchGenomic hybridizationActivated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model
Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT. Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1193-1198. PMID: 19144919, PMCID: PMC2626610, DOI: 10.1073/pnas.0811902106.Peer-Reviewed Original ResearchConceptsBeta-catenin signalingNormal melanocyte developmentTranscriptional profiling revealsWnt/beta-catenin signalingMelanoma cellsUp-regulates genesWnt/ß-cateninMelanoma progressionSmall molecule activatorsRole of WntMelanocyte developmentCell fateTranscriptional changesB16 murine melanoma cellsCellular differentiationProfiling revealsMelanocyte differentiationMelanoma cell linesMurine melanoma cellsß-cateninHuman melanoma cell linesWnt3aMurine melanoma modelCell linesReduced expression
2007
Lack of Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Signaling Shows a New Type of Melanoma
Shields JM, Thomas NE, Cregger M, Berger AJ, Leslie M, Torrice C, Hao H, Penland S, Arbiser J, Scott G, Zhou T, Bar-Eli M, Bear JE, Der CJ, Kaufmann WK, Rimm DL, Sharpless NE. Lack of Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Signaling Shows a New Type of Melanoma. Cancer Research 2007, 67: 1502-1512. PMID: 17308088, DOI: 10.1158/0008-5472.can-06-3311.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseERK activationB-RafERK activityMitogen-Activated Protein Kinase SignalingSignal-regulated kinase kinaseN-RASERK MAPK cascadeProtein Kinase SignalingPrimary human melanocytesRNA expression profilesCell linesEpithelial-mesenchymal transformationDistinct melanoma subtypeMAPK cascadeKinase kinaseExtracellular signalsTranscriptional targetsKinase signalingProtein kinaseExpression profilesEpithelial markersMelanoma cell linesRAS/RAFPrimary human tumorsThe X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization
Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G. The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization. Journal Of Translational Medicine 2007, 5: 6. PMID: 17257402, PMCID: PMC1796544, DOI: 10.1186/1479-5876-5-6.Peer-Reviewed Original ResearchConceptsMetastatic melanomaXIAP expressionCell linesCy5-conjugated antibodiesMechanism of actionMelanoma cell linesPrimary lesionOvarian cancerTherapeutic approachesTissue microarrayDisease aggressionCarboplatin sensitivityChemotherapy resistanceMalignant progressionClinical specimensBenign counterpartsCarboplatinMelanomaChemotherapy sensitizationPrimary specimensPhenoxodiolResistant cellsMelanoma cellsHigh expressionMelanoma resistance
2005
"Lineage Addiction" in Human Cancer: Lessons from Integrated Genomics
GARRAWAY L, WEIR B, ZHAO X, WIDLUND H, BEROUKHIM R, BERGER A, RIMM D, RUBIN M, FISHER D, MEYERSON M, SELLERS W. "Lineage Addiction" in Human Cancer: Lessons from Integrated Genomics. Cold Spring Harbor Symposia On Quantitative Biology 2005, 70: 25-34. PMID: 16869735, DOI: 10.1101/sqb.2005.70.016.Peer-Reviewed Original ResearchMeSH KeywordsChromosomes, Human, Pair 3Cluster AnalysisDNA, NeoplasmGene AmplificationGene DosageGene Expression ProfilingGenomicsHumansIn Situ Hybridization, FluorescenceMelanomaMicrophthalmia-Associated Transcription FactorNeoplasmsOligonucleotide Array Sequence AnalysisOncogenesPolymorphism, Single NucleotideConceptsLineage addictionGenome-scale data setsHigh-density single nucleotide polymorphism arraysNovel cancer genesSingle nucleotide polymorphism arrayDNA microarray platformCell line collectionCell linesAdditional functional studiesTumor survival mechanismsSNP array dataDetailed genomic characterizationGene expression dataDistinct tissue typesIntegrated GenomicCopy number alterationsTissue of originGenome characterizationSurvival mechanismCancer genesGenomic characterizationMelanoma cell linesSurvival pathwaysExpression dataProgression of tumors
1999
Frequent Nuclear/Cytoplasmic Localization of β-Catenin without Exon 3 Mutations in Malignant Melanoma
Rimm D, Caca K, Hu G, Harrison F, Fearon E. Frequent Nuclear/Cytoplasmic Localization of β-Catenin without Exon 3 Mutations in Malignant Melanoma. American Journal Of Pathology 1999, 154: 325-329. PMID: 10027390, PMCID: PMC1850000, DOI: 10.1016/s0002-9440(10)65278-9.Peer-Reviewed Original ResearchConceptsCytoplasmic localizationPhosphorylation sitesE-cadherin-mediated cell-cell adhesionGlycogen synthase kinase 3beta phosphorylation sitesMelanoma cell linesN-terminal phosphorylation sitesWnt pathwayExon 3 mutationsCell linesGlycogen synthase kinase-3betaFactor transcription factorsBeta-catenin accumulatesCell-cell adhesionSynthase kinase-3betaBeta-catenin exon 3 mutationsDNA sequencing studiesAdenomatous polyposis coliAxin proteinTranscription factorsKinase-3betaAmino terminusBeta-CateninBeta-catenin mutationsWnt pathway activationSequencing studies