CAJ | 학술논문

目的模拟临床肝癌切除病例构建姑息性肝切除裸鼠模型,用于研究手术对残癌的影响并探索干预策略. 方法采用肝左叶单瘤源接种技术,构建高转移潜能MHCC97H细胞裸鼠原位移植瘤模型,成功建模后14 d行姑息性肝切除.姑息术后14d,分析肿瘤相关基因差异表达；观察35 d,检测肝内、肺脏及腹腔转移；剩余裸鼠用于观察生存期.计量资料比较用t检验,生存分析用Kaplan-Meier法(Log Rank检验),P＜0.05为差异有统计学意义. 结果原位移植瘤模型成功率100％,成功构建裸鼠姑息性肝切除模型,无手术相关死亡裸鼠.姑息组裸鼠肝内转移结节多于假手术组[(11.7±4.7)个对比(6.3±2.8)个,t=-2.412,P＜0.05],腹腔转移结节多于假手术组[(9.8±3.4)个对比(5.2±2.6)个,t=-2.641,P＜0.05],肺转移结节也多于假手术组[(14.3±4.7)个对比(8.7±4.7)个,t=-2.348,P＜0.05].应用生物信息学技术进一步分析发现,肿瘤转移抑制蛋白1、肿瘤坏死因子β1、Smad2、白细胞介素1β及基质金属蛋白酶7基因在姑息组残癌基因功能网络中处于核心位置.姑息组裸鼠生存期为(60.8±2.7)d,假手术组裸鼠生存期为(51.3±1.4)d,差异有统计学意义(x2=12.850,P＜0.01).结论单瘤源姑息性肝切除模型能有效模拟临床肝切除病例,为术后残癌生物学特性的研究及干预提供一个新的平台.
목적 모의림상간암절제병례구건고식성간절제라서모형,용우연구수술대잔암적영향병탐색간예책략. 방법 채용간좌협단류원접충기술,구건고전이잠능MHCC97H세포라서원위이식류모형,성공건모후14 d행고식성간절제.고식술후14d,분석종류상관기인차이표체；관찰35 d,검측간내、폐장급복강전이；잉여라서용우관찰생존기.계량자료비교용t검험,생존분석용Kaplan-Meier법(Log Rank검험),P＜0.05위차이유통계학의의. 결과 원위이식류모형성공솔100％,성공구건라서고식성간절제모형,무수술상관사망라서.고식조라서간내전이결절다우가수술조[(11.7±4.7)개대비(6.3±2.8)개,t=-2.412,P＜0.05],복강전이결절다우가수술조[(9.8±3.4)개대비(5.2±2.6)개,t=-2.641,P＜0.05],폐전이결절야다우가수술조[(14.3±4.7)개대비(8.7±4.7)개,t=-2.348,P＜0.05].응용생물신식학기술진일보분석발현,종류전이억제단백1、종류배사인자β1、Smad2、백세포개소1β급기질금속단백매7기인재고식조잔암기인공능망락중처우핵심위치.고식조라서생존기위(60.8±2.7)d,가수술조라서생존기위(51.3±1.4)d,차이유통계학의의(x2=12.850,P＜0.01).결론 단류원고식성간절제모형능유효모의림상간절제병례,위술후잔암생물학특성적연구급간예제공일개신적평태.
Objective To construct a high metastatic potential human hepatocellular carcinoma (HCC)orthotopic transplantation model with palliative liver resection in nude mice.Methods A human HCC orthotopic nude mice model was established by administering a single inoculation of the highly metastatic MHCC97H tumor tissue (size 2 mm × 2 mm × 2 mm) into the left liver lobe.At day 14 post-inoculation,a random group of the mice received palliative liver resection; the unresected mice served as controls.Changes in expression levels of 113 genes with metastasis-related functions were evaluated in the residual HCC tissues.At day 35 post-resection,a random group of the mice were sacrificed by cervical dislocation and a comprehensive metastases examination was performed.The remaining mice were used to observe life span.All statistical analyses were performed by the SPSS v17.0 software,and significance was defined as P ＜ 0.05.Results The nude mouse model of highly metastatic HCC with palliative liver resection was successfully established.Incidences of intrahepatic and abdominal metastases were higher in the palliative resected group (vs.unresected group:11.7 ± 4.7 vs.6.3 ± 2.8,t =-2.412,P ＜ 0.05 and 9.8 ± 3.4 vs.5.2 ± 2.6,t =-2.641,P ＜ 0.05respectively).In addition,the palliative resected group showed significantly enhanced pulmonary metastasis (vs.unresected group:14.3 ± 4.7 vs.8.7 ± 4.7,t =-2.348,P ＜ 0.05).Differential gene expression levels were found for MTSS1,TGFβ1,SMAD2,IL-1β,and MMP7,and were situated in the central position of gene function net of residual HCC.The life-span of the palliative resected group was significantly longer than that of the unresected group (60.8 ± 2.7 vs.51.3 ± 1.4days,x2=12.850,P＜0.01).Conclusion The highly metastatic human HCC nude mouse model with palliative liver resection that was successfully constructed in this study represents a useful investigational tool to assess the biological characteristics of residual cancer and to screen therapeutic strategies.