2021
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer
2017
Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy
Wisnewski AV, Kanyo J, Asher J, Goodrich JA, Barnett G, Patrylak L, Liu J, Redlich CA, Nassar AF. Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy. Xenobiotica 2017, 48: 488-497. PMID: 28489470, PMCID: PMC5863241, DOI: 10.1080/00498254.2017.1329569.Peer-Reviewed Original ResearchConceptsCollision-induced dissociation (CID) fragmentation patternsReaction productsLower airwaysChemical reactivityLow molecular weight fractionWeight fractionHigh molecular weight fractionAliphatic diisocyanateMolecular weight fractionFragmentation patternsHexamethylenediisocyanateLC-MSHDI vaporAirways of rabbitsBronchoalveolar lavage fluidRabbit bronchoalveolar lavage fluidMoleculesDiisocyanate vaporsMs. 4Albumin. 5Occupational asthmaReactivityBAL fluidAsthma pathogenesisLavage fluid
2016
Identification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction
Wisnewski AV, Liu J, Nassar AF. Identification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction. Toxicology In Vitro 2016, 36: 97-104. PMID: 27453132, PMCID: PMC5010927, DOI: 10.1016/j.tiv.2016.07.011.Peer-Reviewed Original ResearchPopulation pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients
Nassar AF, Wisnewski AV, King I. Population pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients. Xenobiotica 2016, 47: 394-407. PMID: 27440490, DOI: 10.1080/00498254.2016.1201703.Peer-Reviewed Original ResearchConceptsPopulation pharmacokinetic analysisInter-patient variabilityPharmacokinetic analysisSignificant single-agent activitySingle-agent activityPopulation PK analysisVolume of distributionHigh inter-patient variabilityInter-occasion variabilityAlkylating agentCancer patientsTotal clearanceTotal body waterClinical trialsHematologic malignanciesPK analysisDosing cyclesOrgan functionSolid tumorsAntineoplastic alkylating agentCentral compartmentNONMEM analysisRapid clearancePatientsClearance
2015
Metabolic disposition of the anti-cancer agent [14C]laromustine in male rats
Nassar AF, Wisnewski A, King I. Metabolic disposition of the anti-cancer agent [14C]laromustine in male rats. Xenobiotica 2015, 45: 711-721. PMID: 25798740, PMCID: PMC4681490, DOI: 10.3109/00498254.2015.1016475.Peer-Reviewed Original ResearchConceptsQuantitative whole-body autoradiographyBolus doseDrug-derived radioactivityPeak plasma concentrationWhole-body autoradiographyGroup 1 animalsUrinary bladder contentsLong-Evans ratsExcretion of drugsSmall intestine contentsRecovery of radioactivityNovel sulfonylhydrazineAnti-cancer agentsSpinal cordMale ratsPlasma concentrationsIntravenous administrationRenal cortexBladder contentsTotal bodyMetabolic dispositionOrgan exposureSmall intestineRatsMedical guidelines