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

被引：59

作者：

Marmiroli, Paola ^{[1
]}

Riva, Beatrice ^{[2
]}

Pozzi, Eleonora ^{[1
]}

Ballarini, Elisa ^{[1
]}

Lim, Dmitry ^{[2
]}

Chiorazzi, Alessia ^{[1
]}

Meregalli, Cristina ^{[1
]}

Distasi, Carla ^{[2
]}

Renn, Cynthia L. ^{[3
]}

Semperboni, Sara ^{[1
]}

Morosi, Lavinia ^{[4
]}

Ruffinatti, Federico A. ^{[2
]}

Zucchetti, Massimo ^{[4
]}

Dorsey, Susan G. ^{[3
]}

Cavaletti, Guido ^{[1
]}

Genazzani, Armando ^{[2
]}

Carozzi, Valentina A. ^{[1
]}

机构：

[1] Univ Milano Bicocca, Sch Med & Surg, Expt Neurol Unit, Monza, Italy

[2] Univ Piemonte Orientale, Dept Pharmaceut Sci, Novara, Italy

[3] Univ Maryland, Sch Nursing, Dept Pain & Translat Symptom Sci, Baltimore, MD 21201 USA

[4] IRCCS, Dept Oncol, Ist Ric Farmacol Mario Negri, Milan, Italy

来源：

PLOS ONE | 2017年 / 12卷 / 10期

关键词：

COLON-CANCER PATIENTS; COLORECTAL-CANCER; 1ST-LINE TREATMENT; INDUCED NEUROPATHY; CHEMOTHERAPY; MICE; FLUOROURACIL; POLYMORPHISM; LEUCOVORIN; CISPLATIN;

D O I：

10.1371/journal.pone.0186250

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：25

共 42 条

[41] Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients [J].