2024
Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow
Poulos M, Ramalingam P, Winiarski A, Gutkin M, Katsnelson L, Carter C, Pibouin-Fragner L, Eichmann A, Thomas J, Miquerol L, Butler J. Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow. Stem Cell Reviews And Reports 2024, 20: 1135-1149. PMID: 38438768, PMCID: PMC11087254, DOI: 10.1007/s12015-024-10703-9.Peer-Reviewed Original ResearchBone marrowEndothelial cellsMouse modelAdult bone marrowArteriole endothelial cellsAdult BMOff-target activityHematopoietic dysfunctionAdult marrowHematopoietic homeostasisEndothelial cell subtypesVascular subtypeCre-expressing lineEndothelial subtypesEndothelial-specificMouse linesHSC activationCell subtypesEC subtypesParacrine signalingPerivascular cellsModulate HSC activationMarrowSubtypesAdult endothelium
2023
Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections
Jeffries L, Mis E, McWalter K, Donkervoort S, Brodsky N, Carpier J, Ji W, Ionita C, Roy B, Morrow J, Darbinyan A, Iyer K, Aul R, Banka S, Chao K, Cobbold L, Cohen S, Custodio H, Drummond-Borg M, Elmslie F, Finanger E, Hainline B, Helbig I, Hewson S, Hu Y, Jackson A, Josifova D, Konstantino M, Leach M, Mak B, McCormick D, McGee E, Nelson S, Nguyen J, Nugent K, Ortega L, Goodkin H, Roeder E, Roy S, Sapp K, Saade D, Sisodiya S, Stals K, Towner S, Wilson W, Disorders D, Borras S, Clark C, Dean J, Miedzybrodzka Z, Ross A, Tennant S, Dabir T, Donnelly D, Humphreys M, Magee A, McConnell V, McKee S, McNerlan S, Morrison P, Rea G, Stewart F, Cole T, Cooper N, Cooper-Charles L, Cox H, Islam L, Jarvis J, Keelagher R, Lim D, McMullan D, Morton J, Naik S, O’Driscoll M, Ong K, Osio D, Ragge N, Turton S, Vogt J, Williams D, Bodek S, Donaldson A, Hills A, Low K, Newbury-Ecob R, Norman A, Roberts E, Scurr I, Smithson S, Tooley M, Abbs S, Armstrong R, Dunn C, Holden S, Park S, Paterson J, Raymond L, Reid E, Sandford R, Simonic I, Tischkowitz M, Woods G, Bradley L, Comerford J, Green A, Lynch S, McQuaid S, Mullaney B, Berg J, Goudie D, Mavrak E, McLean J, McWilliam C, Reavey E, Azam T, Cleary E, Jackson A, Lam W, Lampe A, Moore D, Porteous M, Baple E, Baptista J, Brewer C, Castle B, Kivuva E, Owens M, Rankin J, Shaw-Smith C, Turner C, Turnpenny P, Tysoe C, Bradley T, Davidson R, Gardiner C, Joss S, Kinning E, Longman C, McGowan R, Murday V, Pilz D, Tobias E, Whiteford M, Williams N, Barnicoat A, Clement E, Faravelli F, Hurst J, Jenkins L, Jones W, Kumar V, Lees M, Loughlin S, Male A, Morrogh D, Rosser E, Scott R, Wilson L, Beleza A, Deshpande C, Flinter F, Holder M, Irving M, Izatt L, Josifova D, Mohammed S, Molenda A, Robert L, Roworth W, Ruddy D, Ryten M, Yau S, Bennett C, Blyth M, Campbell J, Coates A, Dobbie A, Hewitt S, Hobson E, Jackson E, Jewell R, Kraus A, Prescott K, Sheridan E, Thomson J, Bradshaw K, Dixit A, Eason J, Haines R, Harrison R, Mutch S, Sarkar A, Searle C, Shannon N, Sharif A, Suri M, Vasudevan P, Canham N, Ellis I, Greenhalgh L, Howard E, Stinton V, Swale A, Weber A, Banka S, Breen C, Briggs T, Burkitt-Wright E, Chandler K, Clayton-Smith J, Donnai D, Douzgou S, Gaunt L, Jones E, Kerr B, Langley C, Metcalfe K, Smith A, Wright R, Bourn D, Burn J, Fisher R, Hellens S, Henderson A, Montgomery T, Splitt M, Straub V, Wright M, Zwolinski S, Allen Z, Bernhard B, Brady A, Brooks C, Busby L, Clowes V, Ghali N, Holder S, Ibitoye R, Wakeling E, Blair E, Carmichael J, Cilliers D, Clasper S, Gibbons R, Kini U, Lester T, Nemeth A, Poulton J, Price S, Shears D, Stewart H, Wilkie A, Albaba S, Baker D, Balasubramanian M, Johnson D, Parker M, Quarrell O, Stewart A, Willoughby J, Crosby C, Elmslie F, Homfray T, Jin H, Lahiri N, Mansour S, Marks K, McEntagart M, Saggar A, Tatton-Brown K, Butler R, Clarke A, Corrin S, Fry A, Kamath A, McCann E, Mugalaasi H, Pottinger C, Procter A, Sampson J, Sansbury F, Varghese V, Baralle D, Callaway A, Cassidy E, Daniels S, Douglas A, Foulds N, Hunt D, Kharbanda M, Lachlan K, Mercer C, Side L, Temple I, Wellesley D, Consortium G, Ambrose J, Arumugam P, Baple E, Bleda M, Boardman-Pretty F, Boissiere J, Boustred C, Caulfield M, Chan G, Craig C, Daugherty L, de Burca A, Devereau A, Elgar G, Foulger R, Fowler T, FurióTarí P, Hackett J, Halai D, Hamblin A, Henderson S, Holman J, Hubbard T, Ibáñez K, Jackson R, Jones L, Kasperaviciute D, Kayikci M, Lahnstein L, Lawson K, Leigh S, Leong I, Lopez F, MaleadyCrowe F, Mason J, McDonagh E, Moutsianas L, Mueller M, Murugaesu N, Need A, Odhams C, Patch C, Perez-Gil D, Polychronopoulos D, Pullinger J, Rahim T, Rendon A, Riesgo-Ferreiro P, Rogers T, Ryten M, Savage K, Sawant K, Scott R, Siddiq A, Sieghart A, Smedley D, Smith K, Sosinsky A, Spooner W, Stevens H, Stuckey A, Sultana R, Thomas E, Thompson S, Tucci A, Walsh E, Watters S, Welland M, Williams E, Witkowska K, Network U, Acosta M, Adam M, Adams D, Agrawal P, Alejandro M, Alvey J, Amendola L, Andrews A, Ashley E, Azamian M, Bacino C, Bademci G, Baker E, Balasubramanyam A, Baldridge D, Bale J, Bamshad M, Barbouth D, Bayrak-Toydemir P, Beck A, Beggs A, Behrens E, Bejerano G, Bennet J, Berg-Rood B, Bernstein J, Berry G, Bican A, Bivona S, Blue E, Bohnsack J, Bonnenmann C, Bonner D, Botto L, Boyd B, Briere L, Brokamp E, Brown G, Burke E, Burrage L, Butte M, Byers P, Byrd W, Carey J, Carrasquillo O, Chang T, Chanprasert S, Chao H, Clark G, Coakley T, Cobban L, Cogan J, Coggins M, Cole F, Colley H, Cooper C, Craigen W, Crouse A, Cunningham M, D'Souza P, Dai H, Dasari S, Davids M, Dayal J, Deardorff M, Dell'Angelica E, Dhar S, Dipple K, Doherty D, Dorrani N, Douine E, Draper D, Duncan L, Earl D, Eckstein D, Emrick L, Eng C, Esteves C, Estwick T, Falk M, Fernandez L, Ferreira C, Fieg E, Findley L, Fisher P, Fogel B, Forghani I, Fresard L, Gahl W, Glass I, Godfrey R, Golden-Grant K, Goldman A, Goldstein D, Grajewski A, Groden C, Gropman A, Gutierrez I, Hahn S, Hamid R, Hanchard N, Hassey K, Hayes N, 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Renteria G, Reuter C, Rives L, Robertson A, Rodan L, Rosenfeld J, Rosenwasser N, Ruzhnikov M, Sacco R, Sampson J, Samson S, Saporta M, Scott C, Schaechter J, Schedl T, Scott D, Sharma P, Shin J, Signer R, Sillari C, Silverman E, Sinsheimer J, Sisco K, Smith E, Smith K, Solem E, Solnica-Krezel L, Stoler J, Stong N, Sullivan J, Sun A, Sutton S, Sweetser D, Sybert V, Tabor H, Tamburro C, Tekin M, Telischi F, Thorson W, Tifft C, Toro C, Tran A, Tucker B, Urv T, Vanderver A, Velinder M, Viskochil D, Vogel T, Wahl C, Wallace S, Walley N, Walsh C, Walker M, Wambach J, Wan J, Wang L, Wangler M, Ward P, Wegner D, Wener M, Wenger T, Perry K, Westerfield M, Wheeler M, Whitlock J, Wolfe L, Woods J, Yamamoto S, Yang J, Yu G, Zastrow D, Zhao C, Zuchner S, Khokha M, Bönnemann C, Lucas C, Lakhani S. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections. Genetics In Medicine 2023, 26: 101023. PMID: 37947183, PMCID: PMC10932913, DOI: 10.1016/j.gim.2023.101023.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsPatient's immune cellsBlood mononuclear cellsImmune cell subtypesEarly-onset epilepsyAffected individualsInduced seizuresCardiac dysrhythmiasRecurrent infectionsClinical syndromeFrequent infectionsMononuclear cellsPatient cohortImmune cellsMultisystem syndromeHealthy donorsMultisystem disorderCardiac arrhythmiasBiallelic variantsCell subtypesDevelopmental delayGene variantsProtein overexpressionRecessive variantsMissense variantsA discrete ‘early-responder’ stromal-cell subtype orchestrates immunocyte recruitment to injured tissue
Yaghi O, Hanna B, Langston P, Michelson D, Jayewickreme T, Marin-Rodero M, Benoist C, Mathis D. A discrete ‘early-responder’ stromal-cell subtype orchestrates immunocyte recruitment to injured tissue. Nature Immunology 2023, 24: 2053-2067. PMID: 37932455, PMCID: PMC10792729, DOI: 10.1038/s41590-023-01669-w.Peer-Reviewed Original ResearchConceptsMesenchymal stromal cellsStromal cellsMouse modelMouse model of muscular dystrophyModels of muscular dystrophyAcute injuryUnique surface markersRecruitment of neutrophilsResponse to injuryStromal cell subtypesImmunomodulatory programsImmunocyte recruitmentCell collaborationTissue regenerationStroma-specificTNF-aSurface markersDay 1IL-1BCell subtypesInflammatory programMuscular dystrophyInduce inflammationSubtypesOncostatin MMapping the gene space at single-cell resolution with gene signal pattern analysis
Venkat A, Damo M, Joshi N, Krishnaswamy S. Mapping the gene space at single-cell resolution with gene signal pattern analysis. The Journal Of Immunology 2023, 210: 251.03-251.03. DOI: 10.4049/jimmunol.210.supp.251.03.Peer-Reviewed Original ResearchGene-gene relationshipsGene spaceSingle-cell RNA sequencing analysisGene signalsSingle-cell resolutionRNA sequencing analysisMelanoma patient samplesScRNA-seq analysisTranscriptional programsCellular heterogeneityGene representationSequencing analysisCell typesSingle cellsPattern analysisCell subtypesCell subpopulationsMultiscale viewEffector functionsCellsMouse modelComputational methodsGenesCell spacePatient samplesInvestigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions
Apsley A, Etzel L, Hastings W, Heim C, Noll J, O’Donnell K, Schreier H, Shenk C, Ye Q, Shalev I. Investigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions. Clinical Epigenetics 2023, 15: 33. PMID: 36855187, PMCID: PMC9976543, DOI: 10.1186/s13148-023-01437-5.Peer-Reviewed Original ResearchConceptsComplete blood countImmune cell proportionsAcute psychosocial stressCell proportionPsychosocial stressPsychosocial stress altersImmune cell subtypesAcute laboratory stressorEarly life adversityStress-exposed individualsChild maltreatmentPediatric cohortBlood countCell subtypesAcute stressStress-induced changesPathophysiological statesLife adversityCritical covariatesLaboratory stressorYoung adultsEffects of maltreatmentDNAm alterationsClinical populationsDNA methylation
2022
Molecular and cellular evolution of the primate dorsolateral prefrontal cortex
Ma S, Skarica M, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Ž, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin MR, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM, Sousa AMM, Sestan N. Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science 2022, 377: eabo7257. PMID: 36007006, PMCID: PMC9614553, DOI: 10.1126/science.abo7257.Peer-Reviewed Original ResearchConceptsMolecular differencesSingle-nucleus transcriptomesSubset of speciesNeuropsychiatric risk genesCellular evolutionCellular repertoireEvolutionary specializationDorsolateral prefrontal cortexRate-limiting enzymeDivergent featuresRisk genesAnthropoid primatesPrefrontal cortexPrimate dorsolateral prefrontal cortexCertain interneuronsNeuropeptide somatostatinDopamine productionGranular neuronsTyrosine hydroxylaseCell subtypesExpressionTranscriptomeAdult humansGenesPrimatesSingle-Cell Transcriptomics Revealed Subtype-Specific Tumor Immune Microenvironments in Human Glioblastomas
Xiao Y, Wang Z, Zhao M, Deng Y, Yang M, Su G, Yang K, Qian C, Hu X, Liu Y, Geng L, Xiao Y, Zou Y, Tang X, Liu H, Xiao H, Fan R. Single-Cell Transcriptomics Revealed Subtype-Specific Tumor Immune Microenvironments in Human Glioblastomas. Frontiers In Immunology 2022, 13: 914236. PMID: 35669791, PMCID: PMC9163377, DOI: 10.3389/fimmu.2022.914236.Peer-Reviewed Original ResearchConceptsTumor immune microenvironmentTumor-associated macrophages/microgliaImmune microenvironmentTumor cellsHuman glioblastomaMacrophages/microgliaAggressive brain tumorDifferent tumor subtypesM2-type polarizationNon-malignant cellsPoor prognosisImmune infiltrationPrimary tumorGBM patientsBrain tumorsPatient stratificationTumor subtypesMajor subtypesMalignant cellsTumor angiogenesisCell subtypesTumor microenvironmentPersonalized treatmentGBM cellsIntra-tumor heterogeneity
2021
G2S3: A gene graph-based imputation method for single-cell RNA sequencing data
Wu W, Liu Y, Dai Q, Yan X, Wang Z. G2S3: A gene graph-based imputation method for single-cell RNA sequencing data. PLOS Computational Biology 2021, 17: e1009029. PMID: 34003861, PMCID: PMC8189489, DOI: 10.1371/journal.pcbi.1009029.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomic datasetsTranscriptomic datasetsGene expressionSingle-cell RNA sequencing technologySingle-cell transcriptomic studiesSingle-cell RNA sequencing dataRNA sequencing technologyRNA sequencing dataSingle-cell resolutionGene expression profilesAdjacent genesTranscriptomic studiesSequencing technologiesSequencing dataExpression profilesGene graphDownstream analysisGenesCell trajectoriesDropout eventsCell subtypesExpressionHigh data sparsityCells
2020
Imaging and optogenetic modulation of vascular mural cells in the live brain
Tong L, Hill RA, Damisah EC, Murray KN, Yuan P, Bordey A, Grutzendler J. Imaging and optogenetic modulation of vascular mural cells in the live brain. Nature Protocols 2020, 16: 472-496. PMID: 33299155, DOI: 10.1038/s41596-020-00425-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRegional cerebral blood flowMural cellsBlood-brain barrier maintenanceCerebral ischemia mouse modelAge-related neurodegenerative diseasesCerebral blood flowSmooth muscle cell physiologyBrain blood vesselsIschemia mouse modelVascular mural cellsBrain microvesselsHigh-resolution intravital imagingVascular disordersMouse modelBlood flowMuscle cell physiologyTransgenic miceCalcium transientsAlzheimer's diseaseCalcium imagingCell subtypesBarrier maintenanceNeurodegenerative diseasesTwo-photon optogeneticsBlood vessels
2019
Immunohistochemical and molecular features of cholangiolocellular carcinoma are similar to well-differentiated intrahepatic cholangiocarcinoma
Balitzer D, Joseph NM, Ferrell L, Shafizadeh N, Jain D, Zhang X, Yeh M, di Tommaso L, Kakar S. Immunohistochemical and molecular features of cholangiolocellular carcinoma are similar to well-differentiated intrahepatic cholangiocarcinoma. Modern Pathology 2019, 32: 1486-1494. PMID: 31186529, DOI: 10.1038/s41379-019-0290-0.Peer-Reviewed Original ResearchConceptsCholangiolocellular carcinomaIntrahepatic cholangiocarcinomaLow-grade cytologic atypiaPrimary liver carcinomaCapture-based next-generation sequencingCanals of HeringNumber alterationsHistologic subtypeCarcinoma componentCytologic atypiaImmunohistochemistry resultsCholangiocarcinomaLiver carcinomaCarcinomaSelect intronsCell subtypesStem cell subtypesHepatocellular componentDistinct entityMutational profileSubtypesNext-generation sequencingCD56Genomic profilesCD117
2018
Defining Early-Onset Colon and Rectal Cancers
Jacobs D, Zhu R, Luo J, Grisotti G, Heller DR, Kurbatov V, Johnson CH, Zhang Y, Khan SA. Defining Early-Onset Colon and Rectal Cancers. Frontiers In Oncology 2018, 8: 504. PMID: 30460196, PMCID: PMC6232522, DOI: 10.3389/fonc.2018.00504.Peer-Reviewed Original ResearchEarly-onset colonRectal cancerCancer incidenceColon cancerEnd Results Program databaseSignet ring cell subtypeColorectal cancer incidenceRectal cancer incidenceColon cancer incidenceAdenocarcinoma histologyRectosigmoid locationBlack populationClinicopathological characteristicsClinicopathological featuresProgram databaseInclusion criteriaPercent changeColonCell subtypesCancerPatientsIncidence increasesIncidenceSimilar riseSuch cohorts
2014
Conditional density-based analysis of T cell signaling in single-cell data
Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GP. Conditional density-based analysis of T cell signaling in single-cell data. Science 2014, 346: 1250689. PMID: 25342659, PMCID: PMC4334155, DOI: 10.1126/science.1250689.Peer-Reviewed Original ResearchConceptsSingle-cell dataMitogen-activated protein kinase ERK2High-dimensional single-cell technologiesProtein kinase ERK2Single-cell technologiesNaïve cellsKinase ERK2Protein speciesCellular circuitsCell variationMolecular circuitsProteinMass cytometryAbundanceCellsCell subtypesComputational approachERK2Computational methodsSpeciesPERKCascadeFunctionT cellsPS6
2011
Learning to live together: harnessing regulatory T cells to induce organ transplant tolerance.
Chang A, Bhattacharya N. Learning to live together: harnessing regulatory T cells to induce organ transplant tolerance. The Yale Journal Of Biology And Medicine 2011, 84: 345-51. PMID: 22180672, PMCID: PMC3238321.Peer-Reviewed Original Research
2009
T-Cells in Multiple Sclerosis
Severson C, Hafler DA. T-Cells in Multiple Sclerosis. 2009, 51: 1-24. PMID: 19582415, DOI: 10.1007/400_2009_12.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsMultifocal demyelinating diseaseMultiple cell subtypesRegulatory T cellsT cell subsetsT cell functionCentral nervous systemRational therapeutic strategiesT cell activationDemyelinating diseaseMS pathogenesisMS pathophysiologyCell subsetsAdaptive immunityEffective treatmentTherapeutic strategiesNervous systemCell activationCell subtypesEvidence implicateSpecific toleranceFunctional defectsIntrinsic cellsCell functionT-Cells in Multiple Sclerosis
Severson C, Hafler D. T-Cells in Multiple Sclerosis. Results And Problems In Cell Differentiation 2009, 51: 75-98. DOI: 10.1007/400_2009_9012.Peer-Reviewed Original ResearchMultiple sclerosisT cellsMultifocal demyelinating diseaseMultiple cell subtypesRegulatory T cellsT cell subsetsT cell functionCentral nervous systemRational therapeutic strategiesT cell activationDemyelinating diseaseMS pathogenesisMS pathophysiologyCell subsetsAdaptive immunityEffective treatmentTherapeutic strategiesNervous systemCell activationCell subtypesEvidence implicateSpecific toleranceFunctional defectsIntrinsic cellsCell function
1997
Focal cortical dysplasia of Taylor, balloon cell subtype: MR differentiation from low-grade tumors.
Bronen RA, Vives KP, Kim JH, Fulbright RK, Spencer SS, Spencer DD. Focal cortical dysplasia of Taylor, balloon cell subtype: MR differentiation from low-grade tumors. American Journal Of Neuroradiology 1997, 18: 1141-51. PMID: 9194442, PMCID: PMC8337292.Peer-Reviewed Original ResearchConceptsFocal cortical dysplasiaLow-grade tumorsCortical dysplasiaMR findingsLobe locationLow-grade glial neoplasmTemporal lobe locationSubcortical white matterFrontal lobe locationSurgical resectionCortical thickeningClinical variablesIntractable epilepsyGlial neoplasmsHyperintense signalLateral ventricleMR featuresWhite matterNeoplastic tissueCell subtypesDysplasiaPatientsMR variablesNeoplasmsSurgical planning
1982
The clinical behavior of „mixed”︁ small cell/large cell bronchogenic carcinoma compared to „pure”︁ small cell subtypes
Radice P, Matthews M, Ihde D, Gazdar A, Carney D, Bunn P, Cohen M, Fossieck B, Makuch R, Minna J. The clinical behavior of „mixed”︁ small cell/large cell bronchogenic carcinoma compared to „pure”︁ small cell subtypes. Cancer 1982, 50: 2894-2902. PMID: 6291745, DOI: 10.1002/1097-0142(19821215)50:12<2894::aid-cncr2820501232>3.0.co;2-g.Peer-Reviewed Original ResearchConceptsSmall cell carcinomaSmall cell subtypeCell carcinomaResponse rateCombination chemotherapyClinical behaviorLong-term disease-free survivalCentral nervous system metastasesSmall cell carcinoma casesUntreated lung cancer patientsCell subtypesSmall cell lung cancerAggressive chemotherapy protocolsDistinct pathologic variantComplete response rateNervous system metastasesCell bronchogenic carcinomaDisease-free survivalIntensive combination chemotherapySmall cell cancerExtent of diseaseLarge cell carcinomaCell lung cancerLung cancer patientsLarge cell component
1980
Influence of Histologic Subtype of Small Cell Carcinoma of the Lung on Clinical Presentation, Response to Therapy, and Survival2
Carney D, Matthews M, Ihde D, Bunn P, Cohen M, Makuch R, Gazdar A, Minna J. Influence of Histologic Subtype of Small Cell Carcinoma of the Lung on Clinical Presentation, Response to Therapy, and Survival2. Journal Of The National Cancer Institute 1980, 65: 1225-1230. PMID: 6253711, DOI: 10.1093/jnci/65.6.1225.Peer-Reviewed Original ResearchConceptsSmall cell carcinomaHistologic subtypeCell carcinomaSame patientBiopsy tissueAggressive cytotoxic therapyChemotherapeutic response rateExtent of diseaseInitial performance statusIntermediate cell subtypeSignificant differencesPerformance statusCombination chemotherapyClinical presentationCytotoxic therapyTherapeutic decisionsPatientsLung cancer classificationResponse rateCell subtypesSubtypesTherapyCarcinomaLungWorking Party
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