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
2018
OATP1B2 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