TY - JOUR
T1 - Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity
T2 - Phenotypic and genotypic insights
AU - Marmiroli, Paola
AU - Riva, Beatrice
AU - Pozzi, Eleonora
AU - Ballarini, Elisa
AU - Lim, Dmitry
AU - Chiorazzi, Alessia
AU - Meregalli, Cristina
AU - Distasi, Carla
AU - Renn, Cynthia L.
AU - Semperboni, Sara
AU - Morosi, Lavinia
AU - Ruffinatti, Federico A.
AU - Zucchetti, Massimo
AU - Dorsey, Susan G.
AU - Cavaletti, Guido
AU - Genazzani, Armando
AU - Carozzi, Valentina A.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0186250
DO - 10.1371/journal.pone.0186250
M3 - Article
C2 - 29020118
AN - SCOPUS:85031024728
VL - 12
SP - e0186250
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
ER -