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Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights.

Abstract

Peripheral neurotoxicity is one of the most distressing side effects of oxaliplatin therapy for cancer. Indeed, most patients that received oxaliplatin experience acute and/or chronic severe sensory peripheral neuropathy. However, despite similar co-morbidities, cancer stage, demographics and treatment schedule, patients develop oxaliplatin-induced peripheral neurotoxicity with remarkably different severity. This suggests individual genetic variability, which might be used to glean the mechanistic insights into oxaliplatin neurotoxicity. We characterized the susceptibility of different mice strains to oxaliplatin neurotoxicity investigating the phenotypic features of neuropathy and gene expression profiles in dorsal root ganglia of six genetically different mice strains (Balb-c, C57BL6, DBA/2J, AJ, FVB and CD1) exposed to the same oxaliplatin schedule. Differential gene expression in dorsal root ganglia from each mice strain were assayed using a genome-wide expression analysis and selected genes were validated by RT-PCR analysis. The demonstration of consistent differences in the phenotypic response to oxaliplatin across different strains is interesting to allow the selection of the appropriate strain based on the pre-defined read-out parameters. Further investigation of the correlation between gene expression changes and oxaliplatin-induced neurotoxicity phenotype in each strain will be useful to deeper investigate the molecular mechanisms of oxaliplatin neurotoxicity.

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  • Authors+Show Affiliations

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.

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    School of Nursing, Department of Pain and Translational Symptom Science, University of Maryland, Baltimore, Maryland, United States of America.

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

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    Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.

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    Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

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    School of Nursing, Department of Pain and Translational Symptom Science, University of Maryland, Baltimore, Maryland, United States of America.

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    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

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    Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.

    Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

    Source

    PloS one 12:10 2017 pg e0186250

    MeSH

    Acute Disease
    Animals
    Biopsy
    Chronic Disease
    Ganglia, Spinal
    Gene Expression Regulation
    Genetic Predisposition to Disease
    Mice
    Mice, Inbred Strains
    Myelin Sheath
    Neural Conduction
    Neuralgia
    Neurons
    Neurotoxicity Syndromes
    Organoplatinum Compounds
    Pain Measurement
    Peripheral Nervous System
    Real-Time Polymerase Chain Reaction
    Sciatic Nerve
    Skin
    Spinal Cord Dorsal Horn

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29020118