2024
Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer
Nassar A, Nie X, Zhang T, Yeung J, Norris P, He J, Ogura H, Babar M, Muldoon A, Libreros S, Chen L. Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer. Metabolites 2024, 14: 312. PMID: 38921447, PMCID: PMC11205345, DOI: 10.3390/metabo14060312.Peer-Reviewed Original ResearchMass spectrometryLipid metabolismTherapeutic efficacy of treatmentLipidomic studiesEfficacy of treatmentStudy of lipidsEmergence of lipidomicsLipid categoriesSpectrometryEnergy storageTumor microenvironmentPharmaceutical candidatesTherapeutic efficacyLipidomicsCancer patientsLipid profileCancer samplesCancerLarge-scale studiesCancer researchTargeted approachAlterationsDisease developmentCell growthMetabolismIs Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer
Babar M, Nassar A, Nie X, Zhang T, He J, Yeung J, Norris P, Ogura H, Muldoon A, Chen L, Libreros S. Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer. Metabolites 2024, 14: 314. PMID: 38921449, PMCID: PMC11205484, DOI: 10.3390/metabo14060314.Peer-Reviewed Original ResearchResolution of inflammationPro-resolving mediatorsTherapeutic effectOral squamous cell carcinomaT cell responsesSquamous cell carcinomaEicosapentaenoic acid derivativeExcessive neutrophil infiltrationDendritic cell migrationEndogenous lipid mediatorsMetastasis of cancer cellsPro-inflammatory cytokinesSpecialized pro-resolving mediatorsCell carcinomaTumor microenvironmentIschemia-related injuryLung inflammationTumor progressionNeutrophil infiltrationCell debris clearanceCystic fibrosisLung cancerAcute inflammationHerpes virusTherapeutic approachesUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity.
Tianxiang Zhang, Weiwei Yu, Xiaoxiao Cheng, Jacky Yeung, Viviana Ahumada, Paul C Norris, Mackenzie J Pearson, Xuan Yang, Willemijn van Deursen, Christina Halcovich, Ala Nassar, Mathew D Vesely, Yu Zhang, Jianping Zhang, Lan Ji, Dallas B Flies, Linda Liu, Solomon Langermann, William J LaRochelle, Rachel Humphrey, Dejian Zhao, Qiuyu Zhang, Jindong Zhang, Runxia Gu, Kurt A Schalper, Miguel F Sanmamed, Lieping ChenPeer-Reviewed Original Research In Press
2022
Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs
NASSAR A. Drug Design Strategies: Role of Structural Modifications of Drug Candidates to Improve PK Parameters of New Drugs. 2022, 323-343. DOI: 10.1002/9781119851042.ch10.Peer-Reviewed Original ResearchDrug candidatesSuccessful drug designDrug metabolism scientistsDrug designDrug discoveryStructural modificationsMetabolic stabilityDiverse propertiesActive metabolitePass metabolismToxicity relationshipsSoft drugsReactive metabolitesInhibition/inductionMetabolism studiesPharmacokinetic issuesRenal clearanceSafe drugPK parametersMetabolic clearanceMetabolic inactivationNew drugsDrugsMetabolitesClearanceAccelerating Metabolite Identification Mass Spectrometry Technology Drives Metabolite Identification Studies Forward
NASSAR A. Accelerating Metabolite Identification Mass Spectrometry Technology Drives Metabolite Identification Studies Forward. 2022, 267-302. DOI: 10.1002/9781119851042.ch8.Peer-Reviewed Original ResearchDrug candidatesDrug discoveryLC-MSLiquid chromatography-mass spectrometryChromatography-mass spectrometryMetabolite identification studiesSuccessful drug candidatesFlight mass spectrometryDrug discovery effortsMass spectrometry technologyTriple quadrupoleADMET studiesStructural assignmentMass spectrometryMetabolite characterizationLead compoundsSpectrometry technologyIon trapDiscovery effortsOverall safety profileHuman-specific metabolitesSpectrometryDrug development processMetabolism issuesMetabolite profilingCase Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy
NASSAR A, WISNEWSKI A, KING I. Case Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy. 2022, 893-922. DOI: 10.1002/9781119851042.ch26.Peer-Reviewed Original ResearchNuclear magnetic resonance spectroscopyCollision-induced dissociationFourier transform ion cyclotron resonance mass spectrometerIon cyclotron resonance mass spectrometerAccurate mass measurementsMass spectrometry studiesHydrogen-deuterium exchangeMagnetic resonance spectroscopyMass spectral rearrangementsExact massSpectrometry studiesEnzyme catalysisReactive intermediatesMass spectrometerDecomposition productsResonance spectroscopyConjugation reactionsElemental compositionPossibility of rearrangementMass measurementsSpectral rearrangementsReactionDissociationRadioactive componentsLoss of nitrogenRole of Structural Modifications of Drug Candidates to Enhance Metabolic Stability
Nassar A. Role of Structural Modifications of Drug Candidates to Enhance Metabolic Stability. 2022, 303-322. DOI: 10.1002/9781119851042.ch9.Peer-Reviewed Original ResearchDrug candidatesStructural modificationsMetabolic stabilityDrug discovery processADME propertiesMetabolite characterizationDrug designDrug discoveryBalance of propertiesToxicity relationshipsExcretion studiesMetabolic instabilityDiscovery processHuman patientsStabilityPropertiesSuccess rateModificationDrugsCandidatesCharacterizationAbsorptionPatientsChemical Structural Alert and Reactive Metabolite Concept as Applied in Medicinal Chemistry to Minimize the Toxicity of Drug Candidates
NASSAR A. Chemical Structural Alert and Reactive Metabolite Concept as Applied in Medicinal Chemistry to Minimize the Toxicity of Drug Candidates. 2022, 345-372. DOI: 10.1002/9781119851042.ch11.Peer-Reviewed Original ResearchAryl hydroxamic acidsDrug candidatesMedicinal chemistryChemical groupsQuinone methideChemical structural alertsReactive metabolitesArylpropionic acidsStructural alertsLarge clinical trialsHydroxamic acidPreclinical safety studiesToxicity problemsToxicity warningExamples of drugsPotential toxicityAdverse reactionsClinical trialsMedium-chain fatty acidsSide effectsStable metaboliteAcidHuman drugsSafety studiesNitroaromaticsDrug Metabolism Handbook: Concepts and Applications in Cancer Research
John Wiley & Sons.Books
2021
Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas
Yeung J, Yaghoobi V, Miyagishima D, Vesely MD, Zhang T, Badri T, Nassar A, Han X, Sanmamed MF, Youngblood M, Peyre M, Kalamarides M, Rimm DL, Gunel M, Chen L. Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas. Neuro-Oncology 2021, 23: 1922-1935. PMID: 33914067, PMCID: PMC8563319, DOI: 10.1093/neuonc/noab075.Peer-Reviewed Original ResearchConceptsColony-stimulating factor-1Myeloid cellsMalignant meningiomasTumor microenvironmentCSF1/CSF1RRNA-seqRNA sequencingHuman meningiomasImmune subsetsGene expressionT cellsTreatment strategiesNormalization cancer immunotherapyImportant regulatorCell typesNovel immunocompetent murine modelDeath ligand 1 (PD-L1) expressionCell death receptor-1Immunosuppressive myeloid cellsDeath receptor-1Ligand 1 expressionFactor 1Immune cell typesImmunocompetent murine modelEffective treatment strategiesA 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
2019
PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus
Han X, Vesely MD, Yang W, Sanmamed MF, Badri T, Alawa J, López-Giráldez F, Gaule P, Lee SW, Zhang JP, Nie X, Nassar A, Boto A, Flies DB, Zheng L, Kim TK, Moeckel GW, McNiff JM, Chen L. PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus. Science Translational Medicine 2019, 11 PMID: 31826980, DOI: 10.1126/scitranslmed.aax1159.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritisAutoantibodiesAutoimmunityDendritic CellsHumansInflammationInterferon Type ILupus Erythematosus, CutaneousLupus Erythematosus, SystemicMembrane ProteinsMice, Inbred BALB CMice, Inbred MRL lprMyeloid CellsNeutrophilsReceptors, Antigen, T-CellSignal TransductionTerpenesUp-RegulationConceptsPlasmacytoid dendritic cellsDiscoid lupus erythematosusSystemic lupus erythematosusCutaneous lupus lesionsPD-1HLupus erythematosusLupus lesionsAutoimmune diseasesKO miceT cellsMyeloid cellsHuman systemic lupus erythematosusBALB/c backgroundCutaneous lupus erythematosusInappropriate immune responseProgression of lupusSystemic autoimmune diseaseImmune cell expansionSuppression of autoimmunityAgonistic monoclonal antibodyDeath-1 homologCutaneous lupusProinflammatory neutrophilsDendritic cellsDLE lesionsLC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.
Wisnewski AV, Liu J, Nassar AF. LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate. EC Pharmacology And Toxicology 2019, 7: 205-219. PMID: 31143884, PMCID: PMC6536005.Peer-Reviewed Original ResearchDilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?
Wisnewski AV, Nassar AF, Liu J, Bello D. Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure? Chemical Research In Toxicology 2019, 32: 557-565. PMID: 30724074, PMCID: PMC6465083, DOI: 10.1021/acs.chemrestox.8b00262.Peer-Reviewed Original ResearchConceptsRespiratory tract exposureMDI exposureUrine biomarkersSkin exposureUrine of miceFuture translational investigationsWestern blot studiesUrinary biomarkersRespiratory tractExposure surveillanceTranslational investigationsDisease preventionMDI conjugatesMiceUrineBiomarkersCollision-induced dissociation (CID) fragmentation patternsExposureUnderstanding pathwaysMDIIndustrial hygieneAlbuminMS/MSTractPrevention
2018
Development and Validation of LC–MS-MS Assay for the Determination of the Emerging Alkylating Agent Laromustine and Its Active Metabolite in Human Plasma
Nassar AF, Wisnewski AV, Wu T, Lam TT, King I. Development and Validation of LC–MS-MS Assay for the Determination of the Emerging Alkylating Agent Laromustine and Its Active Metabolite in Human Plasma. Journal Of Chromatographic Science 2018, 57: 195-203. PMID: 30395213, DOI: 10.1093/chromsci/bmy100.Peer-Reviewed Original Research
2017
Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+ ion in exposed human cells
Wisnewski AV, Liu J, Redlich CA, Nassar AF. Polymerization of hexamethylene diisocyanate in solution and a 260.23 m/z [M+H]+ ion in exposed human cells. Analytical Biochemistry 2017, 543: 21-29. PMID: 29175138, PMCID: PMC5826792, DOI: 10.1016/j.ab.2017.11.017.Peer-Reviewed Original ResearchConceptsHexamethylene diisocyanateCollision-induced dissociation (CID) fragmentation patternsNucleophilic additionImportant industrial chemicalPrimary aminesFragmentation patternsO groupLC-MS/MSLC-MS/MS analysisLC-MSReaction productsIonsMS analysisFormula CIndustrial chemicalsDiisocyanatePolymerizationPolymersReaction targetWaterSolutionAminesDefinitive characterizationMoleculesDimersReaction 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 fluidAutomation of sample preparation for mass cytometry barcoding in support of clinical research: protocol optimization
Nassar AF, Wisnewski AV, Raddassi K. Automation of sample preparation for mass cytometry barcoding in support of clinical research: protocol optimization. Analytical And Bioanalytical Chemistry 2017, 409: 2363-2372. PMID: 28124752, PMCID: PMC5863240, DOI: 10.1007/s00216-017-0182-4.Peer-Reviewed Original Research
2016
UPLC–MS for metabolomics: a giant step forward in support of pharmaceutical research
Nassar AF, Wu T, Nassar SF, Wisnewski AV. UPLC–MS for metabolomics: a giant step forward in support of pharmaceutical research. Drug Discovery Today 2016, 22: 463-470. PMID: 27919805, PMCID: PMC5721520, DOI: 10.1016/j.drudis.2016.11.020.Peer-Reviewed Original ResearchCorrigendum to “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” [Toxicol. In vitro (2016) 97–104]
Wisnewski AV, Liu J, Nassar AF. Corrigendum to “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” [Toxicol. In vitro (2016) 97–104]. Toxicology In Vitro 2016, 38: 193. PMID: 27784537, DOI: 10.1016/j.tiv.2016.10.008.Peer-Reviewed Original Research