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肝门部胆管癌神经侵犯裸鼠动物模型的建立
俞文隆1,房文铮2,徐冬云2,金光植3,陈颖4,洪俊峰5,张永杰1,于观贞2*
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(1. 第二军医大学东方肝胆外科医院胆道二科, 上海 200438;
2. 第二军医大学长征医院肿瘤科, 上海 200070;
3. 第二军医大学东方肝胆外科医院病理科, 上海 200438;
4. 第二军医大学长海医院病理科, 上海 200433;
5. 第二军医大学东方肝胆外科医院超声科, 上海 200438
*通信作者)
摘要:
目的建立裸鼠肝门部胆管癌原位种植瘤神经侵犯模型。方法裸鼠全身麻醉后,逐层开腹,将胆管癌细胞系QBC939种植于裸鼠胆总管与门静脉组织间隙处,B超观察肿瘤生长情况,2周后处死裸鼠,肿瘤组织行病理学和S100免疫组化染色,观察神经侵犯情况。结果 B超显示肿瘤成功种植于肝门部,原位种植成瘤率为100%(10/10);肿瘤细胞呈侵袭性生长,腹膜后淋巴结肿大,肿瘤组织内神经侵犯率达80%。结论裸鼠肝门部胆管癌原位移植瘤及神经侵犯模型的建立,为研究胆管癌的神经侵犯机理以及探讨胆管癌防治策略提供了理想的工具。
关键词:  胆管肿瘤  动物模型  神经侵犯  S100蛋白质类
DOI:10.3724/SP.J.1008.2015.01379
投稿时间:2015-03-19修订日期:2015-06-08
基金项目:上海市科委科技引导类项目(134119a0202),上海市浦江人才计划(13PJD002).
Establishment of a nude mouse model of human hilar cholangiocarcinoma nerve infiltration
YU Wen-long1,FANG Wen-zheng2,XU Dong-yun2,JIN Guang-zhi3,CHEN Ying4,HONG Jun-feng5,ZHANG Yong-jie1,YU Guan-zhen2*
(1. Department of Hepatobiliary Surgery Ⅱ, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;
2. Department of Medical Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200070, China;
3. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;
4. Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
5. Department of Ultrasonography, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
*Corresponding author.)
Abstract:
Objective To construct the implantation model of human hilar cholangiocarcinoma in situ in nude mice and to analyze the nerve infiltration of cholangiocarcinoma cells in these tumors. Methods After anesthesia, nude mice were given laparotomy. Then, cultured human hilar cholangiocarcinoma cell line QBC939 was injected in the interaction between the hilar bile duct and portal vein of nude mice. Ultrasonic assay was used to determine the location and the status of the tumor. Two weeks after implantation, nude mice were sacrificed for the anatomical and pathological observation. In addition, S100 protein was detected using immunohistochemistry to determine the status of nerve infiltration in the tumor specimens. Results All nude mice implanted with QBC939 cells developed tumors in situ as revealed by Ultrasonic assay and anatomy. Tumor cells were highly aggressive and invaded into the surrounding organs and lymph node. 8 of 10 (80%) tumor specimens had nerve infiltration. Conclusion The implantation model of human hilar cholangiocarcinoma in situ with high ratio of nerve infiltration in nude mice serves as ideal platinum for exploring the mechanism of the development and progression of hilar cholangiocarcinoma and determining the effective treatment strategies.
Key words:  bile duct neoplasm  animal models  nerve infiltration  S100 proteins