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-  2015 

阿霉素前体药物PADM靶向治疗高转移性人肝癌裸鼠原位移植模型的动物实验研究 Targeting Therapy of High Metastatic Human Hepatocellular Carcinoma with New Adriamycin Prodrug PADM in Orthotopic Nude Mice Model:Animal Experimental Study

Keywords: PADM,阿霉素,,肝细胞,靶向治疗

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Abstract:

目的:比较阿霉素(ADM)与阿霉素前体药物(PADM)治疗高转移性人肝癌裸鼠原位移植模型的疗效和毒副作用,初步探索PADM的作用机制。方法:建立HCCLM9人肝癌裸鼠原位移植模型成功后,随机分为PADM组、ADM组和对照组,每8d给药一次,每4d记录一次一般状况。当肿瘤进展导致裸鼠死亡时,即终止实验,余裸鼠行安乐死,取血行常规、生化及肿瘤标志物检查;解剖裸鼠,详细记录解剖所见;进行组织病理学检查,观察肺及其他转移情况;行免疫组化检测Cat B、Ki-67和VEGF表达,行统计学分析。结果:在肿瘤局部控制指标中,PADM组和ADM组的肝肿瘤质量、体积均显著低于对照组(P<0.05)。在区域控制指标中,PADM组和ADM组ePCI值和腹膜后淋巴结转移率均显著低于对照组(P<0.05)。在控制远处转移指标中,PADM组肺转移率显著低于对照组和ADM组(P<0.05)。PADM组和ADM组的血清AFP水平显著低于对照组(P<0.05)。在血常规指标中,PADM组白细胞计数显著高于ADM组(P<0.05);PADM组血小板计数显著高于对照组(P<0.05)。在肝功能指标中,PADM组和ADM组GGT、AST水平均显著低于对照组(P<0.05)。在肾功能指标中,PADM组BUN和Cr显著低于ADM组和对照组(P<0.05)。免疫组化指标中,Cat B和VEGF的表达在3组中差异无统计学意义(P>0.05);但Ki-67阳性率在3组中具有显著差异(P<0.05),PADM组最低,其次为ADM组,对照组阳性率最高。结论:与ADM比较,PADM有更好的抗癌转移和抑制肿瘤细胞增殖的作用,同时可降低血液和肾脏毒性

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