Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model
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DOI：
10.4061/2011/490463
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发表时间：
2011-01-01
影响因子：
1.8
通讯作者：
Wagman, Lawrence D.
中科院分区：
文献类型：
--
作者：
Soriano, Perry A.;Liu, Nian;Wagman, Lawrence D.
介绍。我们检查了新辅助化疗背景下的小鼠肝切除模型的肝再生（LR）。方法。 C57BL/6 小鼠随机接受对照、奥沙利铂 (15 mg/kg) 或伊立替康 (100 mg/Kg 或 250 mg/Kg) 溶液的新辅助腹腔 (IP) 注射。最终 IP 治疗后 14 天进行肝切除术 (70%)。在术后第 0、1、2、3 和 7 天 (D) 处死动物。收集肝脏残余物和血清用于分析。独立样本的 T 检验用于统计比较。结果。对于奥沙利铂，LR 百分比在 D1 或 D2 时没有差异，但在 D3 时显着较低（89.0% 与 70.0%，P = 0.048），D7 时没有差异（P = 0.21）。两种剂量水平（100 mg/Kg 和 250 mg/Kg）的伊立替康治疗小鼠的 LR 没有显着差异。在奥沙利铂治疗的动物中，BrdU 掺入显着减少（D1、2、3）。结论。在肝切除术后小鼠模型中，新辅助奥沙利铂而非伊立替康会损害早期 LR，这与 DNA 合成减少相关。
Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. T-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, P = 0.048) with no difference on D7 (P = 0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis.