Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice
| العنوان: | Neuronal uptake transporters contribute to oxaliplatin neurotoxicity in mice |
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| المؤلفون: | Navjot Pabla, Maryam B. Lustberg, Alix F. Leblanc, Kevin M. Huang, Eric D. Eisenmann, Mingqing Chen, Jing Wang, Yang Li, Jiyoung Kim, Sherry H. Xia, Timothy C. Cope, Muhammad Erfan Uddin, Charles L. Loprinzi, Kristen W. Hong, Alice A. Gibson, Alex Sparreboom, Paola Alberti, Alessia Chiorazzi, Stephen N. Housley, Anne M. Noonan, Shuiying Hu, Duncan DiGiacomo, Guido Cavaletti, Jason A. Sprowl |
| المساهمون: | Huang, K, Leblanc, A, Uddin, M, Kim, J, Chen, M, Eisenmann, E, Gibson, A, Li, Y, Hong, K, Digiacomo, D, Xia, S, Alberti, P, Chiorazzi, A, Housley, S, Cope, T, Sprowl, J, Wang, J, Loprinzi, C, Noonan, A, Lustberg, M, Cavaletti, G, Pabla, N, Hu, S, Sparreboom, A |
| المصدر: | J Clin Invest |
| بيانات النشر: | American Society for Clinical Investigation, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Colorectal cancer, ved/biology.organism_classification_rank.species, Pharmacology, Oxaliplatin, neuropathy, neurotoxicity, OCT2, animal model, rodent model, neurophysiology, Neuroprotection, Mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Medicine, Model organism, Mice, Knockout, Neurons, business.industry, ved/biology, Concise Communication, Neurotoxicity, Organic Cation Transporter 2, Cancer, Transporter, General Medicine, medicine.disease, Rats, Oxaliplatin, 030104 developmental biology, 030220 oncology & carcinogenesis, Genetically Engineered Mouse, Female, Neurotoxicity Syndromes, business, Neuroglia, medicine.drug |
| الوصف: | Peripheral neurotoxicity is a debilitating toxicity that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurotoxicity remains controversial. Among candidate transporters investigated in genetically-engineered mouse models, we provide evidence for a critical role of the organic cation transporter 2 (OCT2) in satellite glial cells to oxaliplatin-induced neurotoxicity, and demonstrate that targeting OCT2 using genetic and pharmacological approaches ameliorates acute and chronic forms of neurotoxicity. The relevance of this transport system was verified in transporter-deficient rats as a secondary model organism, and translational significance of preventative strategies was demonstrated in preclinical models of colorectal cancer. These studies suggest that pharmacological targeting of OCT2 could be exploited to afford neuroprotection in cancer patients requiring treatment with oxaliplatin. |
| تدمد: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci136796 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84b13294d8f521a5fe344054501b6777 https://doi.org/10.1172/jci136796 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....84b13294d8f521a5fe344054501b6777 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15588238 00219738 |
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| DOI: | 10.1172/jci136796 |