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 inhibitionFramework to leverage physical therapists for the assessment and treatment of chemotherapy-induced peripheral neurotoxicity (CIPN)
Stoller S, Capozza S, Alberti P, Lustberg M, Kleckner I. Framework to leverage physical therapists for the assessment and treatment of chemotherapy-induced peripheral neurotoxicity (CIPN). Supportive Care In Cancer 2023, 31: 293. PMID: 37086308, PMCID: PMC11552664, DOI: 10.1007/s00520-023-07734-2.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neurotoxicityPhysical therapy guidelinesPhysical therapistsPhysical therapyCIPN assessmentPeripheral neurotoxicityOncology teamTherapy guidelinesHome-based exercise prescriptionBurden of chemotherapyManual therapy interventionsClinical practice guidelinesPhysical therapy assessmentLimited effective treatmentsQuality of lifePhysical performance measuresSymptom management researchCIPN treatmentNeurologic symptomsMotor dysfunctionPatient functionExercise prescriptionAerobic trainingChemotherapy agentsPractice guidelines
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
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 carriersDifferential Contribution of Neuronal Uptake Transporters to Oxaliplatin Peripheral Neurotoxicity
Huang K, Leblanc A, Alberti P, Sprowl J, Wang J, Lustberg M, Cavaletti G, Hu S, Sparreboom A. Differential Contribution of Neuronal Uptake Transporters to Oxaliplatin Peripheral Neurotoxicity. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.03083.Peer-Reviewed Original ResearchDorsal root gangliaPeripheral neurotoxicityColorectal cancerOxaliplatin-induced peripheral neurotoxicityVon Frey hair testChronic peripheral neurotoxicityOxaliplatin-induced neurotoxicityVivo cultureColorectal cancer cellsWild-type ratsEx vivo cultureOxaliplatin therapyAfford neuroprotectionObserved neuroprotectionNeurological injuryRoot gangliaOxaliplatin accumulationSystemic clearanceConventional chemotherapyGlial cellsPreclinical modelsSprague-DawleySensory neuronsMouse modelSide effects
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