2021
Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry
Martinez-Morilla S, Villarroel-Espindola F, Wong PF, Toki MI, Aung TN, Pelekanou V, Bourke-Martin B, Schalper KA, Kluger HM, Rimm DL. Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass CytometryMultiplex Discovery with Imaging Mass Cytometry. Clinical Cancer Research 2021, 27: 1987-1996. PMID: 33504554, PMCID: PMC8026677, DOI: 10.1158/1078-0432.ccr-20-3340.Peer-Reviewed Original Research
2019
Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma
Gupta S, McCann L, Chan YGY, Lai EW, Wei W, Wong PF, Smithy JW, Weidler J, Rhees B, Bates M, Kluger HM, Rimm DL. Closed system RT-qPCR as a potential companion diagnostic test for immunotherapy outcome in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2019, 7: 254. PMID: 31533832, PMCID: PMC6751819, DOI: 10.1186/s40425-019-0731-9.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD8 AntigensFemaleFollow-Up StudiesGene Expression ProfilingHumansInterferon Regulatory Factor-1MaleMelanomaMiddle AgedMonitoring, ImmunologicPrognosisProgrammed Cell Death 1 Ligand 2 ProteinProgression-Free SurvivalReal-Time Polymerase Chain ReactionRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSkin NeoplasmsConceptsCompanion diagnostic testsImmunotherapy outcomesMelanoma patientsClinical benefitAnti-PD-1 therapyImmune checkpoint inhibitor therapyMRNA expressionQuantitative immunofluorescenceDiagnostic testsCheckpoint inhibitor therapyReal-time quantitative reverse transcription polymerase chain reactionMetastatic melanoma patientsQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionYale Pathology archivesParaffin-embedded tissue sectionsAdjuvant settingICI therapyOS associationInhibitor therapyBaseline variablesMetastatic melanomaPredictive biomarkersPolymerase chain reactionSiglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.Peer-Reviewed Original ResearchConceptsNormalization cancer immunotherapyTumor microenvironmentSiglec-15Antibody blockadeCancer immunotherapyImmune suppressorMyeloid cellsAntigen-specific T cell responsesB7-H1/PDTumor-infiltrating myeloid cellsB7-H1 moleculesAnti-tumor immunityT cell responsesPotential targetImmune evasion mechanismsInhibits tumor growthMacrophage colony-stimulating factorColony-stimulating factorB7-H1Evasion mechanismsMouse modelHuman cancer cellsTumor growthCell responsesGenetic ablation
2017
High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence
Wasserman BE, Carvajal-Hausdorf DE, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumeister V, Rimm DL. High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Laboratory Investigation 2017, 97: 1521-1526. PMID: 28892092, PMCID: PMC5711560, DOI: 10.1038/labinvest.2017.93.Peer-Reviewed Original ResearchConceptsInvasive breast cancerBreast cancerQuantitative immunofluorescenceRT-qPCRFormalin-fixed paraffin-embedded tissue blocksRT-qPCR assaysEquivocal categoryReal-time quantitative reverse transcription polymerase chain reactionHER2 receptor statusQuantitative reverse transcription polymerase chain reactionParaffin-embedded tissue blocksReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionIHC/FISHMRNA measurementsAssessment of HER2Low-resource settingsReceptor statusPolymerase chain reactionPathology reportsCT cutsSingle-use cartridgeResource settingsHER2 mRNATissue blocksDifferential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer
Schalper KA, Carvajal-Hausdorf D, McLaughlin J, Altan M, Velcheti V, Gaule P, Sanmamed MF, Chen L, Herbst RS, Rimm DL. Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer. Clinical Cancer Research 2017, 23: 370-378. PMID: 27440266, PMCID: PMC6350535, DOI: 10.1158/1078-0432.ccr-16-0150.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterleukin-10Lymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingRNA, MessengerV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerB7-H4PD-L1IDO-1Lung cancerLung carcinomaQuantitative immunofluorescenceIFNγ stimulationElevated PD-L1Major clinicopathologic variablesMultiplexed quantitative immunofluorescenceOptimal clinical trialsT-cell infiltratesCell lung cancerImmune evasion pathwaysHuman lung carcinomaLung adenocarcinoma A549Cancer Genome AtlasClinicopathologic variablesMarker levelsClinical trialsStage ITherapeutic resistanceTCGA datasetA549 cells
2016
Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo
Cocco E, Lopez S, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, Menderes G, Zammataro L, Buza N, Hui P, Wong S, Zhao S, Bai Y, Rimm DL, Ratner E, Litkouhi B, Silasi DA, Azodi M, Schwartz PE, Santin AD. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. British Journal Of Cancer 2016, 115: 303-311. PMID: 27351214, PMCID: PMC4973158, DOI: 10.1038/bjc.2016.198.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesCyclin EDNA Copy Number VariationsFemaleGene Knockdown TechniquesHeterograftsHumansIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMutationOncogene ProteinsPhosphatidylinositol 3-KinasesRNA, MessengerTissue Array AnalysisUterine NeoplasmsConceptsUterine serous carcinomaSerous carcinomaTumor growthCyclin E1 (CCNE1) gene amplificationRecurrent uterine serous carcinomaPrimary USC cell linesNovel therapeutic optionsSingle-agent treatmentIdeal therapeutic targetUSC cell linesCyclin E1 expressionUSC patientsUSC xenograftsInhibited cell growthCell cycle analysisAggressive variantTherapeutic optionsCCNE1 amplificationEndometrial tumorsCYC065Therapeutic targetClinical optionPIK3CA driver mutationsDriver mutationsXenograftsEvaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma
Vassilakopoulou M, Avgeris M, Velcheti V, Kotoula V, Rampias T, Chatzopoulos K, Perisanidis C, Kontos CK, Giotakis AI, Scorilas A, Rimm D, Sasaki C, Fountzilas G, Psyrri A. Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma. Clinical Cancer Research 2016, 22: 704-713. PMID: 26408403, DOI: 10.1158/1078-0432.ccr-15-1543.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellFemaleFollow-Up StudiesGene ExpressionHumansImmunohistochemistryKaplan-Meier EstimateLaryngeal NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPrognosisProportional Hazards ModelsRetrospective StudiesRisk FactorsRNA, MessengerConceptsLaryngeal squamous cell carcinomaSquamous cell carcinomaPrimary laryngeal squamous cell carcinomaPD-L1 expressionTumor-infiltrating lymphocytesPD-L1 mRNA expressionTIL densityCell carcinomaAssessment of TILsLaryngeal squamous cell cancerStromal tumor-infiltrating lymphocytesSuperior disease-free survivalTumor PD-L1 expressionMRNA expressionPD-L1 protein expressionPD-L1 mRNA levelsHigher TIL densityImmune checkpoint inhibitorsPD-L1 levelsDisease-free survivalT cell infiltrationSquamous cell cancerSecond independent cohortAdjacent tissue specimensFresh-frozen tumors
2014
In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients
Vassilakopoulou M, Togun T, Dafni U, Cheng H, Bordeaux J, Neumeister VM, Bobos M, Pentheroudakis G, Skarlos DV, Pectasides D, Kotoula V, Fountzilas G, Rimm DL, Psyrri A. In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients. PLOS ONE 2014, 9: e99131. PMID: 24968015, PMCID: PMC4072595, DOI: 10.1371/journal.pone.0099131.Peer-Reviewed Original ResearchConceptsBreast cancer patientsMetastatic breast cancer patientsFISH HER2Cancer patientsHER2 mRNAPrognostic factorsTrastuzumab-treated metastatic breast cancer patientsMultivariate Cox regression modelECD HER2Log rank pMetastatic breast cancerStrong prognostic factorCox regression modelKaplan-Meier estimatesHER2 mRNA levelsHER2-ICDChemotherapy regimensMetastatic cohortTrastuzumab treatmentBreast cancerTissue microarrayMRNA statusPerformance of markersHER2 receptorPredictive valueIn Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas
Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL. In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clinical Cancer Research 2014, 20: 2773-2782. PMID: 24647569, DOI: 10.1158/1078-0432.ccr-13-2702.Peer-Reviewed Original ResearchB7-H1 AntigenBreast NeoplasmsCell Line, TumorFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIn Situ HybridizationKaplan-Meier EstimateLymphatic MetastasisLymphocytes, Tumor-InfiltratingMiddle AgedMultivariate AnalysisNeoplasm Recurrence, LocalPrognosisReceptor, ErbB-2Receptors, EstrogenRNA, MessengerTissue Array Analysis
2013
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation 2013, 94: 107-116. PMID: 24217091, PMCID: PMC6125250, DOI: 10.1038/labinvest.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorChi-Square DistributionCohort StudiesConnecticutFemaleGreeceHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMalePrognosisReproducibility of ResultsRNA, MessengerSurvival AnalysisTissue Array AnalysisConceptsNon-small cell lung cancerPD-L1 expressionCell lung cancerPD-L1Tissue microarrayBetter outcomesNSCLC casesLung cancerDeath ligand 1 (PD-L1) expressionCell death ligand 1PD-L1 protein expressionEarly phase clinical trialsLigand 1 expressionTumor-infiltrating lymphocytesDeath ligand 1Significant better outcomePD-L1 mRNAPD-L1 proteinPhase clinical trialsNormal human placentaPrediction of responseQuantitative fluorescence approachesFrequency of expressionPD-1Prognostic value
2012
Lin28 regulates HER2 and promotes malignancy through multiple mechanisms
Feng C, Neumeister V, Ma W, Xu J, Lu L, Bordeaux J, Maihle NJ, Rimm DL, Huang Y. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle 2012, 11: 2486-2494. PMID: 22713243, DOI: 10.4161/cc.20893.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2HER2 expressionLin28 expressionEpidermal growth factor receptor 2Growth factor receptor 2Primary breast tumorsFactor receptor 2Cancer cell growthMajor therapeutic targetMultiple mechanismsAdvanced human malignanciesClinical outcomesPoor prognosisBreast cancerReceptor 2Therapeutic targetBreast tumorsNovel mechanistic insightsHuman malignanciesLin28 overexpressionReceptor tyrosine kinasesCancerCell proliferationHuman cancersPowerful predictorQuantitative In Situ Measurement of Estrogen Receptor mRNA Predicts Response to Tamoxifen
Bordeaux JM, Cheng H, Welsh AW, Haffty BG, Lannin DR, Wu X, Su N, Ma XJ, Luo Y, Rimm DL. Quantitative In Situ Measurement of Estrogen Receptor mRNA Predicts Response to Tamoxifen. PLOS ONE 2012, 7: e36559. PMID: 22606272, PMCID: PMC3350519, DOI: 10.1371/journal.pone.0036559.Peer-Reviewed Original Research
2010
PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer
VanHouten J, Sullivan C, Bazinet C, Ryoo T, Camp R, Rimm DL, Chung G, Wysolmerski J. PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 11405-11410. PMID: 20534448, PMCID: PMC2895115, DOI: 10.1073/pnas.0911186107.Peer-Reviewed Original ResearchConceptsPMCA2 expressionBreast cancerT47D breast cancer cellsIntracellular calcium levelsBreast cancer progressionBreast cancer cellsEpithelial cell apoptosisPoor outcomeIntracellular calciumCalcium levelsMammary gland involutionCancer progressionCell apoptosisCancer cellsMammary involutionApoptosisGland involutionCancerMammary epithelial cell apoptosisOutcomesPMCA2Triggers apoptosisApical surfaceExpressionOverexpression
1998
A Mutation in α-Catenin Disrupts Adhesion in Clone A Cells Without Perturbing its Actin and β-Catenin Binding Activity
Roe S, Koslov E, Rimm D. A Mutation in α-Catenin Disrupts Adhesion in Clone A Cells Without Perturbing its Actin and β-Catenin Binding Activity. Cell Communication & Adhesion 1998, 5: 283-296. PMID: 9762469, DOI: 10.3109/15419069809040298.Peer-Reviewed Original ResearchMeSH KeywordsActinsAlpha CateninBeta CateninCadherinsCell AdhesionCloning, MolecularColonic NeoplasmsCytoskeletal ProteinsCytoskeletonDesmoplakinsExonsGamma CateninHeLa CellsHumansIntercellular JunctionsMutationOctoxynolPrecipitin TestsProtein BindingRecombinant Fusion ProteinsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSequence Analysis, DNASolubilityTrans-ActivatorsTransfectionTumor Cells, CulturedConceptsN-terminusE-cadherin-catenin complexBundles F-actinCo-sedimentation assaysCell-cell adhesionFull-length proteinClone A cellsCo-precipitation experimentsInternal deletion mutationsWhole cell lysatesAdhesive complexesMutant proteinsA mutantsMutant bindsHuman colon carcinoma cell lineColon carcinoma cell lineMutant formsLength proteinWild typeCytoplasmic connectionsF-actinAdhesive phenotypeDeletion mutationsCell lysatesCarcinoma cell lines
1994
Molecular Cloning Reveals Alternative Splice Forms of Human α(E)-Catenin
Rimm DL, Kebriaei P, Morrow JS. Molecular Cloning Reveals Alternative Splice Forms of Human α(E)-Catenin. Biochemical And Biophysical Research Communications 1994, 203: 1691-1699. PMID: 7945318, DOI: 10.1006/bbrc.1994.2381.Peer-Reviewed Original ResearchMeSH KeywordsAlpha CateninAlternative SplicingAmino Acid SequenceAnimalsBase SequenceCadherinsCell LineChickensCloning, MolecularConserved SequenceCytoskeletal ProteinsDNA, ComplementaryDrosophilaHominidaeHumansMiceMolecular Sequence DataPhylogenyPolymerase Chain ReactionRNA, MessengerSequence Homology, Amino AcidTranscription, GeneticConceptsCadherin cell-cell adhesion complexCell-cell adhesion complexAmino acid proteinAlternative splice formsSuperfamily of proteinsAmino acid insertionTranscription sitesAdhesion complexesCytoplasmic domainDistinct transcriptsMolecular cloningSingle geneAcid proteinSplice formsAcid insertionSecond transcriptCatenin geneSplice siteNon-epithelial tissuesVinculinTranscriptsCateninHuman alphaSouthern blottingProtein
1984
Structural analysis of the murine IgG3 constant region gene.
Wels J, Word C, Rimm D, Der-Balan G, Martinez H, Tucker P, Blattner F. Structural analysis of the murine IgG3 constant region gene. The EMBO Journal 1984, 3: 2041-2046. PMID: 6092053, PMCID: PMC557641, DOI: 10.1002/j.1460-2075.1984.tb02089.x.Peer-Reviewed Original ResearchConceptsConstant region genesMembrane exonsMRNA precursorsHeavy chain constant region genesAmino acid sequenceRegion genesSwitch recombination regionC gamma 3 geneGamma 3 chainCarbohydrate addition sitesProtein domainsC deltaCarboxyl terminusComplete sequenceAcid sequenceRemarkable homologyGamma 3 geneAddition siteSwitch sitesSecondary structureMembrane formClass switch mechanismExonsGenesC mu