Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights.
Paola MarmiroliBeatrice RivaEleonora PozziElisa BallariniDmitry LimAlessia ChiorazziCristina MeregalliCarla DistasiCynthia L RennSara SemperboniLavinia MorosiFederico A RuffinattiMassimo ZucchettiSusan G DorseyGuido CavalettiArmando GenazzaniValentina A CarozziPublished in: PloS one (2017)
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.
Keyphrases
- gene expression
- genome wide
- end stage renal disease
- escherichia coli
- dna methylation
- ejection fraction
- chronic kidney disease
- newly diagnosed
- drug induced
- papillary thyroid
- peritoneal dialysis
- prognostic factors
- intensive care unit
- copy number
- high glucose
- oxidative stress
- neuropathic pain
- early onset
- adipose tissue
- endothelial cells
- young adults
- transcription factor
- hepatitis b virus
- combination therapy
- acute respiratory distress syndrome
- replacement therapy
- patient reported
- single molecule