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

Marmiroli, P., Riva, B., Pozzi, E., Ballarini, E., Lim, D., Chiorazzi, A., et al. (2017). Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights. PLOS ONE, 12(10) [10.1371/journal.pone.0186250].

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

Marmiroli, Paola
Co-primo
;
Pozzi, Eleonora;Ballarini, Elisa;Chiorazzi, Alessia;Meregalli, Cristina;Semperboni, Sara;Morosi, Lavinia;Cavaletti, Guido;Carozzi, Valentina A.
Ultimo
2017

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
Articolo in rivista - Articolo scientifico
Acute Disease; Animals; Biopsy; Chronic Disease; Ganglia, Spinal; Gene Expression Regulation; 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; Genetic Predisposition to Disease; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
English
Marmiroli, P., Riva, B., Pozzi, E., Ballarini, E., Lim, D., Chiorazzi, A., et al. (2017). Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights. PLOS ONE, 12(10) [10.1371/journal.pone.0186250].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/176026
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