2023
Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy
Li Y, Drabison T, Nepal M, Ho R, Leblanc A, Gibson A, Jin Y, Yang W, Huang K, Uddin M, Chen M, DiGiacomo D, Chen X, Razzaq S, Tonniges J, McTigue D, Mims A, Lustberg M, Wang Y, Hummon A, Evans W, Baker S, Cavaletti G, Sparreboom A, Hu S. Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy. JCI Insight 2023, 8: e164646. PMID: 37347545, PMCID: PMC10443802, DOI: 10.1172/jci.insight.164646.Peer-Reviewed Original ResearchConceptsPeripheral neurotoxicitySide effectsDose-limiting peripheral neurotoxicityDorsal root ganglion neuronsMultiple malignant diseasesUptake of vincristineAction potential amplitudeEffective preventative treatmentMechanical allodyniaThermal hyperalgesiaSensory neuropathyGanglion neuronsMalignant diseasePlasma levelsDose selectionVincristine accumulationUntargeted metabolomics analysisAntitumor effectsClinical developmentPotential amplitudePreventative treatmentNeuronal transporterNeuronal morphologyVincristinePharmacological inhibition
2022
Targeting OCT2 with Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neurotoxicity
Nepal M, Taheri H, Li Y, Talebi Z, Uddin M, Jin Y, DiGiacomo D, Gibson A, Lustberg M, Hu S, Sparreboom A. Targeting OCT2 with Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neurotoxicity. Cancer Research Communications 2022, 2: 1334-1343. PMID: 36506732, PMCID: PMC9730833, DOI: 10.1158/2767-9764.crc-22-0172.Peer-Reviewed Original ResearchConceptsDRG neuronsPeripheral neurotoxicitySide effectsOxaliplatin-Induced Peripheral NeurotoxicityOxaliplatin-based regimensOxaliplatin-based treatmentPharmacokinetics of oxaliplatinEffect of duloxetineMouse DRG neuronsWild-type miceCytotoxicity of oxaliplatinConcentration-dependent mannerColorectal cancerCancer patientsPlasma levelsOIPNPlasma pharmacokineticsDuloxetinePrevention strategiesTherapeutic candidateOxaliplatinTumor cell linesTranslational feasibilityMiceComplete protection
2021
Effects of plant-based versus marine-based omega-3 fatty acids and sucrose on brain and liver fatty acids in a mouse model of chemotherapy
Ormiston K, Gaudier-Diaz MM, TinKai T, Fitzgerald J, Cole RM, Andridge R, Lustberg M, DeVries AC, Orchard T. Effects of plant-based versus marine-based omega-3 fatty acids and sucrose on brain and liver fatty acids in a mouse model of chemotherapy. Nutritional Neuroscience 2021, 25: 2650-2658. PMID: 34772330, PMCID: PMC9095756, DOI: 10.1080/1028415x.2021.1998296.Peer-Reviewed Original ResearchConceptsAlpha-linolenic acidDietary alpha-linolenic acidBrain PUFAsMouse modelDocosahexaenoic acidEicosapentaenoic acidLiver PUFABrain nOmega-3 fatty acidsChemotherapy-treated miceHigh ALA dietLow ALA intakeBrain fatty acidsUseful surrogate markerFatty acidsLiver docosahexaenoic acidToxic side effectsLiver fatty acidALA intakeNeurotrophic markersALA dietDHA dietSurrogate markerLower brainSide effectsTargeting OCT3 attenuates doxorubicin-induced cardiac injury
Huang KM, Thomas M, Magdy T, Eisenmann ED, Uddin ME, DiGiacomo DF, Pan A, Keiser M, Otter M, Xia SH, Li Y, Jin Y, Fu Q, Gibson AA, Bonilla IM, Carnes CA, Corps KN, Coppola V, Smith SA, Addison D, Nies AT, Bundschuh R, Chen T, Lustberg MB, Wang J, Oswald S, Campbell MJ, Yan PS, Baker SD, Hu S, Burridge PW, Sparreboom A. Targeting OCT3 attenuates doxorubicin-induced cardiac injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2020168118. PMID: 33495337, PMCID: PMC7865186, DOI: 10.1073/pnas.2020168118.Peer-Reviewed Original ResearchConceptsOrganic cation transporter 3Cardiac injuryCardiovascular functionSide effectsTranslational relevanceCalcium-binding proteins S100A8Irreversible cardiac injuryCurrent preventative strategiesPotential translational relevanceCardiac damagePlasma levelsCardiac accumulationBreast cancerAntitumor effectsPharmacological targetingPreventative strategiesModest protectionProteins S100A8Critical transporterTransporter 3Pharmacological inhibitorsOverexpression modelIntervention strategiesDoxorubicinCardiotoxicity
2020
Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
Huang KM, Leblanc AF, Uddin ME, Kim JY, Chen M, Eisenmann ED, Gibson A, Li Y, Hong KW, DiGiacomo D, Xia S, Alberti P, Chiorazzi A, Housley SN, Cope TC, Sprowl JA, Wang J, Loprinzi CL, Noonan A, Lustberg M, Cavaletti G, Pabla N, Hu S, Sparreboom A. Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice. Journal Of Clinical Investigation 2020, 130: 4601-4606. PMID: 32484793, PMCID: PMC7456253, DOI: 10.1172/jci136796.Peer-Reviewed Original ResearchConceptsOrganic cation transporter 2Peripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityOxaliplatin-containing therapyOxaliplatin-induced neurotoxicitySatellite glial cellsOxaliplatin neurotoxicityChronic formCancer patientsGlial cellsPreclinical modelsPreventive strategiesMouse modelPharmacological approachesPharmacological targetingTranslational significanceNeurotoxicityTransporter 2PatientsUptake transportersCancerAnticancer drugsCandidate transportersSolute carriers
2018
Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy
Orchard T, Gaudier-Diaz M, Phuwamongkolwiwat-Chu P, Andridge R, Lustberg M, Bomser J, Cole R, Belury M, DeVries A. Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy. Nutrients 2018, 10: 2004. PMID: 30567351, PMCID: PMC6316589, DOI: 10.3390/nu10122004.Peer-Reviewed Original ResearchConceptsDHA dietSynaptic damageSecond injectionPro-inflammatory cytokines IL-1βChemotherapy-treated miceKC/GROCytokines IL-1βLong-term brainLow-sucrose dietTwo-injection regimenQuality of lifeSpecific brain regionsBrain DHARegion-specific effectsC57BL/6 miceCancer survivorsFunction markersIL-1βIL-6Synaptic markersIL-5Mouse modelNeuroinflammationSucrose dietChemotherapyA Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer
Borniger J, Walker W, Surbhi, Emmer K, Zhang N, Zalenski A, Muscarella S, Fitzgerald J, Smith A, Braam C, TinKai T, Magalang U, Lustberg M, Nelson R, DeVries A. A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. Cell Metabolism 2018, 28: 118-129.e5. PMID: 29805100, PMCID: PMC6031468, DOI: 10.1016/j.cmet.2018.04.021.Peer-Reviewed Original ResearchConceptsTumor-bearing miceSleep abnormalitiesMetabolic abnormalitiesIL-6Non-metastatic breast cancerHypocretin/orexin neuronsHypothalamic hypocretin/orexin neuronsPeripheral sympathetic denervationSerum leptin concentrationsTumor-induced increaseTumor-induced changesEnhanced sleep qualityHypocretin/orexinPeripheral inflammationSympathetic denervationExogenous ghrelinOrexin neuronsLeptin concentrationsInterleukin-6Serum glucoseMammary cancerBreast cancerSleep qualityMouse modelCentral neuromodulatorsOATP1B2 deficiency protects against paclitaxel-induced neurotoxicity
Leblanc A, Sprowl J, Alberti P, Chiorazzi A, Arnold W, Gibson A, Hong K, Pioso M, Chen M, Huang K, Chodisetty V, Costa O, Florea T, de Bruijn P, Mathijssen R, Reinbolt R, Lustberg M, Sucheston-Campbell L, Cavaletti G, Sparreboom A, Hu S. OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity. Journal Of Clinical Investigation 2018, 128: 816-825. PMID: 29337310, PMCID: PMC5785270, DOI: 10.1172/jci96160.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiomarkersCell Line, TumorGenotypeHEK293 CellsHumansHyperalgesiaInhibitory Concentration 50Liver-Specific Organic Anion Transporter 1MCF-7 CellsMiceMice, Inbred DBAMice, KnockoutMice, TransgenicOrganic Anion TransportersPaclitaxelPeripheral Nervous System DiseasesPhenotypePyrimidinesConceptsPaclitaxel-induced neurotoxicityDose-limiting peripheral neurotoxicityTyrosine kinase inhibitor nilotinibAction potential amplitudeKinase inhibitor nilotinibPeripheral neurotoxicityThermal hyperalgesiaTherapeutic managementPotential amplitudeNeurotoxicityAnticancer propertiesNoncompetitive mechanismAnticancer drugsPaclitaxelAllodyniaHyperalgesiaPotential implicationsNilotinibOatp1b2Mice
2016
Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer
Himmel L, Lustberg M, DeVries A, Poi M, Chen C, Kulp S. Minocycline, a putative neuroprotectant, co-administered with doxorubicin-cyclophosphamide chemotherapy in a xenograft model of triple-negative breast cancer. Experimental And Toxicologic Pathology 2016, 68: 505-515. PMID: 27555377, PMCID: PMC5203928, DOI: 10.1016/j.etp.2016.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBlotting, WesternCell Line, TumorCell SurvivalCognition DisordersCyclophosphamideDNA DamageDoxorubicinFemaleHumansImmunohistochemistryMiceMice, NudeMinocyclineNeuroprotective AgentsTriple Negative Breast NeoplasmsXenograft Model Antitumor AssaysConceptsTriple-negative breast cancerChemotherapy-induced cognitive impairmentBreast cancer patientsNeural progenitor cellsPutative neuroprotectantCancer patientsBreast cancerXenograft modelDoublecortin-positive neural progenitor cellsFemale athymic nude miceDoxorubicin-cyclophosphamide chemotherapyProgenitor cellsEffects of minocyclineChemotherapeutic drug combinationsOrgan weight measurementsAbsence of minocyclineAthymic nude miceTNBC cell linesTumor-bearing miceAnti-oxidant pathwaysTumor-suppressive effectsBiomarkers of apoptosisTumor volume measurementsHuman neurologic diseasesMechanism of action
2014
CSF1-ETS2-induced microRNA in myeloid cells promote metastatic tumor growth
Mathsyaraja H, Thies K, Taffany D, Deighan C, Liu T, Yu L, Fernandez S, Shapiro C, Otero J, Timmers C, Lustberg M, Chalmers J, Leone G, Ostrowski M. CSF1-ETS2-induced microRNA in myeloid cells promote metastatic tumor growth. Oncogene 2014, 34: 3651-3661. PMID: 25241894, PMCID: PMC4369473, DOI: 10.1038/onc.2014.294.Peer-Reviewed Original ResearchConceptsTumor-infiltrating myeloid cellsMetastatic tumor growthMyeloid cellsMiR-21Breast cancerTumor growthHuman metastatic breast cancerMetastatic tumor burdenMetastatic breast cancerPro-tumor functionsAnti-angiogenic genesAttractive therapeutic targetTumor cell proliferationPro-angiogenic propertiesMature myeloid cellsTumor burdenMonocytes correlatesPoor prognosisMelanoma metastasesMouse modelTherapeutic targetSolid tumorsOncogenic roleSurvival rateTherapeutic efficacy