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
Targeting 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