2021
Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes
Apostolidi M, Vathiotis IA, Muthusamy V, Gaule P, Gassaway BM, Rimm DL, Rinehart J. Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes. Cancer Research 2021, 81: 4346-4359. PMID: 34185676, PMCID: PMC8373815, DOI: 10.1158/0008-5472.can-20-4190.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsBiomarkers, TumorCarrier ProteinsCell Line, TumorCollagenCyclic N-OxidesDrug CombinationsGenome, HumanHumansIndolizinesLamininMCF-7 CellsMembrane ProteinsMiceNeoplasm InvasivenessNeoplasm TransplantationNeoplasmsOxidation-ReductionPhenotypePhosphorylationProtein IsoformsProteoglycansProteomicsPyridazinesPyridinium CompoundsPyrrolesPyruvate KinaseThyroid HormonesTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPyruvate kinase M2TEPP-46Breast cancerAggressive breast cancer cell phenotypesCharacteristic nuclear staining patternAggressive breast cancer subtypeAggressive breast cancer phenotypeBreast cancer cell phenotypeCDK inhibitor dinaciclibCombination of dinaciclibLack of biomarkersEffective therapeutic approachBreast cancer phenotypeBreast cancer subtypesCancer phenotypePhosphorylation of PKM2Cyclin-dependent kinase (CDK) pathwayMouse xenograft modelAggressive cancer phenotypeNuclear staining patternLower survival rateImpaired redox balancePrognostic valueCancer cell phenotype
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
2017
Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors
Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors. Advances In Anatomic Pathology 2017, 24: 311-335. PMID: 28777143, PMCID: PMC5638696, DOI: 10.1097/pap.0000000000000161.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBiopsyBrain NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellEndometrial NeoplasmsFemaleGastrointestinal NeoplasmsHead and Neck NeoplasmsHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMelanomaMesotheliomaOvarian NeoplasmsPathologyPhenotypePredictive Value of TestsSkin NeoplasmsSquamous Cell Carcinoma of Head and NeckUrogenital NeoplasmsConceptsTumor-infiltrating lymphocytesDifferent tumor typesSolid tumorsTumor typesTIL assessmentImmune responsePrimary brain tumorsCommon solid tumorsInvasive breast carcinomaRoutine clinical biomarkersWorking Group guidelinesPrognostic implicationsBreast carcinomaGroup guidelinesGynecologic systemGastrointestinal tractSimple biomarkerBrain tumorsGenitourinary systemPredictive valueClinical biomarkersStandardized methodologyTumorsAvailable evidenceImmunotherapy
2016
Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer
Mani NL, Schalper KA, Hatzis C, Saglam O, Tavassoli F, Butler M, Chagpar AB, Pusztai L, Rimm DL. Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer. Breast Cancer Research 2016, 18: 78. PMID: 27473061, PMCID: PMC4966732, DOI: 10.1186/s13058-016-0737-x.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientQuantitative immunofluorescenceBreast cancerSame cancerSingle biopsyMultiplexed quantitative immunofluorescenceTumor-infiltrating lymphocytesPotential predictive markerPrimary breast carcinomaCytokeratin-positive epithelial cellsCD20-positive lymphocytesCD8 levelsLymphocyte scoreQIF scoresLymphocyte countLymphocyte subpopulationsMultiple biopsiesSubpopulation countsPredictive markerPrognostic informationBreast carcinomaBiopsyB lymphocytesCD3Breast tumorsRAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response
2014
Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)
Pectasides E, Rampias T, Sasaki C, Perisanidis C, Kouloulias V, Burtness B, Zaramboukas T, Rimm D, Fountzilas G, Psyrri A. Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC). PLOS ONE 2014, 9: e94273. PMID: 24722213, PMCID: PMC3983114, DOI: 10.1371/journal.pone.0094273.Peer-Reviewed Original ResearchMeSH KeywordsAutomationBiomarkers, TumorCarcinoma, Squamous CellCohort StudiesEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimateMaleMultivariate AnalysisNeoplasm MetastasisPhenotypePrognosisProportional Hazards ModelsSquamous Cell Carcinoma of Head and NeckTreatment OutcomeConceptsProgression-free survivalSquamous cell carcinomaOverall survivalCell carcinomaE-cadherinPrimary squamous cell carcinomaNeck squamous cell carcinomaHigh-risk HNSCCKaplan-Meier analysisNovel therapeutic approachesMesenchymal transition phenotypeHigh metastatic potentialLow E-cadherinImproved OSInferior OSIndependent predictorsPoor prognosisCarcinoma prognosisClinicopathological parametersInclusion criteriaTherapeutic approachesTransition phenotypeMetastatic potentialMesenchymal transitionProtein expression analysis
2009
Defining Molecular Phenotypes of Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma
Weinberger PM, Yu Z, Kountourakis P, Sasaki C, Haffty BG, Kowalski D, Merkley MA, Rimm DL, Camp RL, Psyrri A. Defining Molecular Phenotypes of Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma. Otolaryngology 2009, 141: 382-389. PMID: 19716018, DOI: 10.1016/j.otohns.2009.04.014.Peer-Reviewed Original ResearchConceptsOropharyngeal squamous cell carcinomaSquamous cell carcinomaCell carcinomaHuman Papillomavirus–Associated Oropharyngeal Squamous Cell CarcinomaP16 expressionTertiary care academic medical centerDNA presenceHPV DNA presenceVascular endothelial growth factorCross-sectional studyAcademic medical centerEndothelial growth factorEpidermal growth factor receptorMolecular phenotypesGrowth factor receptorOSCC specimensCervical cancerUnsupervised hierarchical clusteringMedical CenterDifferent molecular phenotypesTumorsGrowth factorExpression patternsFactor receptorProtein expression
2001
β-Catenin Dysregulation in Thyroid Neoplasms Down-Regulation, Aberrant Nuclear Expression, and CTNNB1 Exon 3 Mutations Are Markers for Aggressive Tumor Phenotypes and Poor Prognosis
Garcia-Rostan G, Camp R, Herrero A, Carcangiu M, Rimm D, Tallini G. β-Catenin Dysregulation in Thyroid Neoplasms Down-Regulation, Aberrant Nuclear Expression, and CTNNB1 Exon 3 Mutations Are Markers for Aggressive Tumor Phenotypes and Poor Prognosis. American Journal Of Pathology 2001, 158: 987-996. PMID: 11238046, PMCID: PMC1850336, DOI: 10.1016/s0002-9440(10)64045-x.Peer-Reviewed Original ResearchMeSH KeywordsAdenomaAdultAgedBeta CateninBiomarkers, TumorCarcinomaCell DivisionCell NucleusCytoskeletal ProteinsDown-RegulationExonsFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedOncogene Protein p21(ras)PhenotypePoint MutationPolymorphism, Single-Stranded ConformationalPrognosisSurvival RateThyroid NeoplasmsTrans-ActivatorsConceptsPoor prognosisTumor differentiationBeta-catenin expressionConventional prognostic indicatorsAggressive tumor phenotypeNuclear beta-catenin localizationThyroid tumor samplesBeta-catenin dysregulationAberrant nuclear expressionΒ-catenin dysregulationDifferentiated tumorsPrognostic indicatorThyroid cancerThyroid neoplasmsNuclear immunoreactivityBeta-catenin alterationsNuclear expressionTumor samplesProgressive lossCarcinomaTumor phenotypeSingle-strand conformational polymorphismBeta-catenin mutationsHuman cancersDown regulation
1980
Construction of coliphage lambda Charon vectors with BamHI cloning sites
Rimm D, Horness D, Kucera J, Blattner F. Construction of coliphage lambda Charon vectors with BamHI cloning sites. Gene 1980, 12: 301-309. PMID: 6265323, DOI: 10.1016/0378-1119(80)90113-4.Peer-Reviewed Original Research