2022
Programmed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC
Fernandez AI, Gavrielatou N, McCann L, Shafi S, Moutafi MK, Martinez-Morilla S, Vathiotis IA, Aung TN, Yaghoobi V, Bai Y, Chan YG, Weidler J, Herbst R, Bates M, Rimm DL. Programmed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC. Journal Of Thoracic Oncology 2022, 17: 1078-1085. PMID: 35764237, DOI: 10.1016/j.jtho.2022.06.007.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHigh negative predictive valueLow stage patientsICI therapyPD-L1Negative predictive valueAdjuvant settingLong-term benefitsPredictive valueProgrammed Death Ligand 1PD-L1 mRNA levelsCurrent predictive biomarkersHigh PD-L1Death ligand 1Lung cancer managementPD-L1 mRNAUseful objective methodReal-time reverse transcription-polymerase chain reactionMRNA levelsStandard of careReverse transcription-polymerase chain reactionQuantitative real-time reverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMRNA expression levelsAdvanced NSCLC
2019
Siglec-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
Differential 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
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
2011
Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma
Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, Lee JS, Lin HY, Ciardiello F, Herbst RS, Langley RR, Heymach JV. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma. Journal Of Clinical Investigation 2011, 121: 1313-1328. PMID: 21436589, PMCID: PMC3070607, DOI: 10.1172/jci42405.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApoptosisBevacizumabCell Line, TumorDrug Resistance, NeoplasmErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMaleMiceMice, NudeNeovascularization, PathologicRNA, MessengerRNA, NeoplasmStromal CellsUp-RegulationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsMouse xenograft modelHuman lung adenocarcinomaTumor cellsPrimary resistanceLung adenocarcinomaXenograft modelFGFR pathwayProgression-free survivalVEGF inhibitor bevacizumabEndothelium of tumorsInhibitors of angiogenesisCombination regimensTreatment of cancerVEGF inhibitorsPericyte coverageAntiangiogenic therapyVascular remodelingAngiogenesis inhibitorsTherapeutic efficacyTumor growthStromal pathwaysClinical useEGFRAcquired ResistanceEGFR pathway
2004
Oblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)A Rational Therapeutic to Enhance Apoptosis in Therapy of Lung Cancer
Herbst RS, Frankel SR. Oblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)A Rational Therapeutic to Enhance Apoptosis in Therapy of Lung Cancer. Clinical Cancer Research 2004, 10: 4245s-4248s. PMID: 15217967, DOI: 10.1158/1078-0432.ccr-040018.Peer-Reviewed Original ResearchConceptsOblimersen sodiumLung cancerBcl-2 mRNASmall cell lung cancer patientsNon-small cell lung cancerBcl-2 protein translationFirst-line salvage therapyCell lung cancer patientsPhase IPrior chemotherapy regimenCombination of docetaxelBcl-2 antisense therapyCell lung cancerTraditional cytotoxic chemotherapyLung cancer patientsChemotherapy regimenSalvage therapyCytotoxic chemotherapyAntitumor responseCancer patientsHuman bcl-2 mRNAPreclinical studiesResponse durationResponse rateAnticancer treatment
2003
Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy.
Swisher SG, Roth JA, Komaki R, Gu J, Lee JJ, Hicks M, Ro JY, Hong WK, Merritt JA, Ahrar K, Atkinson NE, Correa AM, Dolormente M, Dreiling L, El-Naggar AK, Fossella F, Francisco R, Glisson B, Grammer S, Herbst R, Huaringa A, Kemp B, Khuri FR, Kurie JM, Liao Z, McDonnell TJ, Morice R, Morello F, Munden R, Papadimitrakopoulou V, Pisters KM, Putnam JB, Sarabia AJ, Shelton T, Stevens C, Shin DM, Smythe WR, Vaporciyan AA, Walsh GL, Yin M. Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clinical Cancer Research 2003, 9: 93-101. PMID: 12538456.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAgedAged, 80 and overApoptosisCarcinoma, Non-Small-Cell LungCombined Modality TherapyFemaleGene Transfer TechniquesGenes, p53Genetic TherapyGenetic VectorsHumansLung NeoplasmsMaleMiddle AgedRadiotherapyReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTime FactorsTumor Suppressor Protein p53ConceptsNon-small cell lung cancerAd-p53 gene transferCell lung cancerRadiation therapyViable tumorLung cancerTumor regressionNonmetastatic non-small cell lung cancerProspective single-arm phase II studyIntratumoral injectionSingle-arm phase II studyAd-p53 gene therapyArm phase II studyCommon adverse eventsPhase II studyCompletion of therapyLung cancer patientsCourse of treatmentStable diseaseAdverse eventsBronchoscopic findingsII studyPartial responseProgressive diseaseComplete response
2000
Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.
Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, Ellis LM, Davis DW, McConkey DJ, Fidler IJ. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Research 2000, 60: 4959-67. PMID: 10987313.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCell DivisionCytokinesDNA, AntisenseEndothelial Growth FactorsHumansLymphokinesMaleMiceMice, NudeNeoplasm TransplantationNeovascularization, PathologicRNA, MessengerTransfectionTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsBrain metastasesCell carcinomaHuman lung squamous carcinoma cellsLung squamous carcinoma cellsLung squamous cell carcinomaExperimental brain metastasesParenchymal brain metastasesSquamous cell carcinomaInternal carotid arteryVascular endothelial growth factorRenal cell carcinomaEndothelial growth factorImportant therapeutic targetInhibition of VEGFSquamous carcinoma cellsLung adenocarcinoma cellsCancer cell linesDifferent human cancer cell linesCarotid arteryNude miceTherapeutic targetKM12SM cellsMetastasisHuman cancer cell linesVEGF expression
1991
Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells.
Herbst RS, Nielsch U, Sladek F, Lai E, Babiss LE, Darnell JE. Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells. The New Biologist 1991, 3: 289-96. PMID: 1878351.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAnimalsBase SequenceCCAAT-Enhancer-Binding ProteinsDNADNA-Binding ProteinsGene Expression RegulationHepatocyte Nuclear Factor 1Hepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 3-alphaHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 3-gammaHepatocyte Nuclear Factor 4LiverMolecular Sequence DataNuclear ProteinsOligonucleotidesPhosphoproteinsPrealbuminRatsRNA, MessengerTranscription FactorsTumor Cells, CulturedConceptsTranscription factorsHepatocyte-enriched transcription factorsDNA-binding proteinsTransthyretin gene expressionRegulation of genesDNA-binding activityRat hepatoma cell lineLevel of expressionTranscriptional activityGene expressionHepatoma cell lineDifferential regulationCellular concentrationGenesHepatoma cellsCell linesExpressionRegulationTransthyretin geneLFB1HNF4HNF3ProteinEBPDifferent rates
1990
The state of cellular differentiation determines the activity of the adenovirus E1A enhancer element: evidence for negative regulation of enhancer function
Herbst RS, Pelletier M, Boczko EM, Babiss LE. The state of cellular differentiation determines the activity of the adenovirus E1A enhancer element: evidence for negative regulation of enhancer function. Journal Of Virology 1990, 64: 161-172. PMID: 2136708, PMCID: PMC249075, DOI: 10.1128/jvi.64.1.161-172.1990.Peer-Reviewed Original ResearchMeSH KeywordsAdenovirus Early ProteinsAdenoviruses, HumanAnimalsBase SequenceCell DifferentiationCell LineCell NucleusDNA-Binding ProteinsEnhancer Elements, GeneticGene ExpressionGene Expression Regulation, ViralGenes, ViralHeLa CellsHumansMolecular Sequence DataMutationOncogene Proteins, ViralPromoter Regions, GeneticRNA, MessengerSuppression, GeneticTranscription, GeneticViral Structural ProteinsConceptsE1A gene transcriptionFetal fibroblast cellsGene transcriptionHepatoma cell lineFibroblast cellsCell phenotypeCell linesLiver hepatocytesRodent hepatocytesRat liver hepatocytesSimilar binding activityFurther suppressionHeLa cellsEnhancer elementsCellsBinding activityHepatocytesViral genomeDifferentiated cellsE1A enhancerNegative regulationCellular differentiationImportant mechanismPhenotypeHigh levelsCis effect of the type 5 adenovirus E1A gene enhancer element on cellular transformation
Herbst R, Pelletier M, Babiss L. Cis effect of the type 5 adenovirus E1A gene enhancer element on cellular transformation. Journal Of Cellular Biochemistry 1990, 42: 33-44. PMID: 2137130, DOI: 10.1002/jcb.240420104.Peer-Reviewed Original ResearchConceptsCREF cellsViral DNA replicationDNA replicationWild-type virusEnhancer elementsGene enhancer elementsRodent embryo fibroblastsCis effectViral DNA integrationE1A gene expressionE1A mRNAsCytoplasmic mRNA levelsE1B mRNAsDNA template concentrationCellular transformationGene expressionDNA integrationViral E1AEmbryo fibroblastsType 5 adenovirusMutant virusMRNA levelsMRNACellsMRNA concentrations
1988
Regulation of adenovirus and cellular gene expression and of cellular transformation by the E1B-encoded 175-amino-acid protein
Herbst RS, Hermo H, Fisher PB, Babiss LE. Regulation of adenovirus and cellular gene expression and of cellular transformation by the E1B-encoded 175-amino-acid protein. Journal Of Virology 1988, 62: 4634-4643. PMID: 2972843, PMCID: PMC253576, DOI: 10.1128/jvi.62.12.4634-4643.1988.Peer-Reviewed Original ResearchConceptsE1A 289R proteinViral early gene expressionCellular gene expressionGene expressionE1A proteinsEarly gene expressionRat embryo fibroblast cellsEnhancer-dependent transcriptionViral E1A proteinsE1A gene productsAltered cell growthEmbryo fibroblast cellsTranscription initiationProtein functionCommon pathwayCellular transformationCREF cellsE1A 13SGene productsGene promoterFoci formationViral genomeHeLa cellsCell growthType 5 adenovirus