Establishment of Animal Models of Hilar Cholangiocarcinoma with Perineural Invasion_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Zhenkai ¹ , ZHANG Bingyuan ² , DAI Dongdong ² , GAO Yuan ² , ZHANG Xianxiang ² , HU Jilin ² ,  LU Yun ²

1.Department of General Surgery， Haiyang Branch of Affiliated Hospital of Medical College， Qingdao University， Haiyang 265100， Shandong Province， China;;
2. Department of General Surgery， Huangdao Branch of Affiliated Hospital of Medical College， Qingdao University， Qingdao 266555， Shandong Province， China;

Corresponding author：

LU Yun, Email: cloudylucn@126.com

Keywords：

Hilar cholangiocarcinoma; Perineural invasion; Animal model

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To establish perineural invasion xenograft model of hilar cholangiocarcinoma.
Methods　 The cultured cells of cholangiocarcinoma cell line QBC939 were inoculated subcutaneously in the nude mice so as to
establish primary subcutaneous model of cholangiocarcinoma. The primary tumor tissues were inoculated intraperitoneally
around the liver in the nude mice so as to establish the second generation intraperitoneal xenograft model. The successful xenografted tumor tissues were obtained for anatomical and pathological examinations.
Results 　The tumor formation rate of primary subcutaneous xenograft of hilar cholangiocarcinoma was 100% （5/5）， and no nerve infiltration was observed. The tumor formation rate of the second generation intraperitoneal xenograft was 45% （9/20）， and two mice （2/9， 22%） manifested nerve infiltration. The rate of nerve infiltration was 10% （2/20）， and the tumor cells had different size and diversity， irregular shape， low differentiation， decreased cytoplasm and nucleus karyomegaly， visible atypical and fission phase， and no obvious gland tube structure by pathological examination.
Conclusions 　Hilar cholangiocarcinoma cell has the particular features of perineural invasion， it is a good experiment platform for researching the mode and biological characteristics of perineural invasion of hilar cholangiocarcinoma by applicated QBC939 cell lines to establish the perineural invasion xenograft model of cholangiocarcinoma.

Citation： LI Zhenkai,ZHANG Bingyuan,DAI Dongdong,GAO Yuan,ZHANG Xianxiang,HU Jilin,LU Yun. Establishment of Animal Models of Hilar Cholangiocarcinoma with Perineural Invasion. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(5): 487-491. doi: Copy

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2.	Seyama Y， Makuuchi M. Current surgical treatment for bile duct cancer[J]. World J Gastroenterol， 2007， 13(10)：1505-1515.
3.	Aishima S， Kuroda Y， Nishihara Y. Proposal of progression model for intrahepatic cholangiocarcinoma：clinicopathologicdifferences between hilar type and peripheral type[J]. Am J Surg Pathol， 2007， 31(7)：1059-1067.
4.	Bhuiya MR， Nimura YJ， Kamiya J， et al. Clinicopathologic studies on perineural invasion of bile duct carcinoma[J]. Ann Surg， 1992， 215(4)：344-349.
5.	郑秀海，王曙光，倪嘉，等. 人胆管癌鸡胚移植瘤模型的建立及其生物学特性的研究[J]. 第三军医大学学报， 2003， 25(9)：757-759.
6.	Tang WH， Yuan ST， Wang BS， et al. Establishment of a subcu-taneous model of the human extrahepatic bile duct carcinoma in nude mice via transplantation of histologically intact tumor tissue[J]. J Exp Clin Cancer Res， 2004， 23(4)：661-667.
7.	Tonge DA， Golding JP， Edbladh M， et al. Effects of extracellular matrix components on axonal outgrowth from peripheral nerves of adult animals in vitro[J]. Exp Neurol， 1997， 146(1)：81-90.
8.	唐文皓，袁胜涛，王炳生，等. 人胆管癌裸鼠移植瘤2号模型的建立[J]. 中华肝胆外科杂志， 2003， 9(12)：751-753.
9.	王曙光，韩本立，段恒春，等. 肝外胆管癌细胞系的建立[J]. 中华实验外科杂志， 1997， 14(2)：67-68.
10.	Ku JL， Yoon KA， Kim IJ， et al. Establishment and characterisation of six human biliary tract cancer cell lines[J]. Br J Cancer， 2002， 87(2)：187-193.
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12.	Arisato H. Experimental induction of biliary tract carcinoma associated with proliferative cholangitis in Syrian hamster[J]. Hokkaido Igaku Zasshi， 1996， 71(5)：623-636.
13.	Kinami Y， Miyakoshi M， Fujikawa K. Bile acid load on the DNA distribution pattern of bile ductules and cholangiocarcinoma induced by diisopropanolnitrosamine in hamsters[J]. Oncology，.
14.	Liu X， Zou S， Qiu F. Expression of nuclear factor kappa B in hepatitis C virus core gene transfected cholangiocarcinoma cells[J]. Chin Med J (Engl)， 2002， 115(7)：998-1001.
15.	Liu XF， Zhou XT， Zou SQ. Inhibition of hepatitis C virus-transfected cholangiocarcinoma by antisense oligodeoxynucleotide innude mice[J]. Hepatobiliary Pancreat Dis Int， 2004， 3(1)：115-119.
16.	傅赞，赵翰林，王若宁，等. 抑癌基因p15对人胆管癌细胞增殖影响与基因治疗适合靶点选择的相关性[J]. 中国临床康复， 2003， 7(32)：4322-4324.
17.	李大江，陈健，陈长宏，等. 胆管癌细胞系QBC939裸鼠肝门部胆管原位种植瘤模型的建立[J]. 中华实验外科杂志， 2007， 24(1)：102-103.
18.	李成刚，黄志强，韦立新. 肝门部胆管癌神经浸润的临床病理学研究[D]. 中国人民解放军军医进修学院， 2008：1-86.
19.	Yamaguchi R， Nagino M， Oda K， et al. Perineural invasion has a negative impact on survival of patients with gallbladder carcinoma[J]. Br J Surg， 2002， 89(9)：1130-1136.
20.	王大东，黄志强，周宁新. 胆管癌神经浸润转移模式的三维重建[J]. 中华外科杂志， 2000， 38(3)：207.
21.	Feng YJ， Zhang BY， Yao RY， et al. Muscarinic acetylcholine receptor M3 in proliferation and perineural invasion of cholangiocarcinoma cells[J]. Hepatobiliary Pancreat Dis Int， 2012， 11(4)：418-423.
22.	李成刚，黄志强，韦立新，等. 肝门部胆管癌神经浸润及围肝门神经丛的分布[J]. 中华医学杂志， 2012， 92(38)：2699-2702.
23.	李振凯，卢云，张炳远. 肝门胆管癌神经浸润的临床病理学研究现状[J]. 中华临床医师杂志：电子版， 2011， 5(11)：3287-3289.
24.	李成刚，黄志强，韦立新，等. 肝门部胆管癌神经浸润特征的临床病理学分析[J]. 世界华人消化杂志， 2008， 16(4)：379-384.
25.	刘磊，黄强，刘臣海，等. 肝外胆管癌神经及脉管浸润转移的危险因素[J]. 肿瘤， 2012， 32(5)：376-379.
26.	， 55(1)：77-86.

1. Harder J， Blum HE. Cholangiocarcinoma[J]. Praxis （Bern 1994)， 2002， 91(34)：1352-1356.
2. Seyama Y， Makuuchi M. Current surgical treatment for bile duct cancer[J]. World J Gastroenterol， 2007， 13(10)：1505-1515.
3. Aishima S， Kuroda Y， Nishihara Y. Proposal of progression model for intrahepatic cholangiocarcinoma：clinicopathologicdifferences between hilar type and peripheral type[J]. Am J Surg Pathol， 2007， 31(7)：1059-1067.
4. Bhuiya MR， Nimura YJ， Kamiya J， et al. Clinicopathologic studies on perineural invasion of bile duct carcinoma[J]. Ann Surg， 1992， 215(4)：344-349.
5. 郑秀海，王曙光，倪嘉，等. 人胆管癌鸡胚移植瘤模型的建立及其生物学特性的研究[J]. 第三军医大学学报， 2003， 25(9)：757-759.
6. Tang WH， Yuan ST， Wang BS， et al. Establishment of a subcu-taneous model of the human extrahepatic bile duct carcinoma in nude mice via transplantation of histologically intact tumor tissue[J]. J Exp Clin Cancer Res， 2004， 23(4)：661-667.
7. Tonge DA， Golding JP， Edbladh M， et al. Effects of extracellular matrix components on axonal outgrowth from peripheral nerves of adult animals in vitro[J]. Exp Neurol， 1997， 146(1)：81-90.
8. 唐文皓，袁胜涛，王炳生，等. 人胆管癌裸鼠移植瘤2号模型的建立[J]. 中华肝胆外科杂志， 2003， 9(12)：751-753.
9. 王曙光，韩本立，段恒春，等. 肝外胆管癌细胞系的建立[J]. 中华实验外科杂志， 1997， 14(2)：67-68.
10. Ku JL， Yoon KA， Kim IJ， et al. Establishment and characterisation of six human biliary tract cancer cell lines[J]. Br J Cancer， 2002， 87(2)：187-193.
11. Ogura Y， Mizumoto R， Tabata M， et al. Surgical treatment of carcinoma of the hepatic duct confluence：analysis of 55 resected carcinomas[J]. World J Surg， 1993， 17(1)：85-92.
12. Arisato H. Experimental induction of biliary tract carcinoma associated with proliferative cholangitis in Syrian hamster[J]. Hokkaido Igaku Zasshi， 1996， 71(5)：623-636.
13. Kinami Y， Miyakoshi M， Fujikawa K. Bile acid load on the DNA distribution pattern of bile ductules and cholangiocarcinoma induced by diisopropanolnitrosamine in hamsters[J]. Oncology，.
14. Liu X， Zou S， Qiu F. Expression of nuclear factor kappa B in hepatitis C virus core gene transfected cholangiocarcinoma cells[J]. Chin Med J (Engl)， 2002， 115(7)：998-1001.
15. Liu XF， Zhou XT， Zou SQ. Inhibition of hepatitis C virus-transfected cholangiocarcinoma by antisense oligodeoxynucleotide innude mice[J]. Hepatobiliary Pancreat Dis Int， 2004， 3(1)：115-119.
16. 傅赞，赵翰林，王若宁，等. 抑癌基因p15对人胆管癌细胞增殖影响与基因治疗适合靶点选择的相关性[J]. 中国临床康复， 2003， 7(32)：4322-4324.
17. 李大江，陈健，陈长宏，等. 胆管癌细胞系QBC939裸鼠肝门部胆管原位种植瘤模型的建立[J]. 中华实验外科杂志， 2007， 24(1)：102-103.
18. 李成刚，黄志强，韦立新. 肝门部胆管癌神经浸润的临床病理学研究[D]. 中国人民解放军军医进修学院， 2008：1-86.
19. Yamaguchi R， Nagino M， Oda K， et al. Perineural invasion has a negative impact on survival of patients with gallbladder carcinoma[J]. Br J Surg， 2002， 89(9)：1130-1136.
20. 王大东，黄志强，周宁新. 胆管癌神经浸润转移模式的三维重建[J]. 中华外科杂志， 2000， 38(3)：207.
21. Feng YJ， Zhang BY， Yao RY， et al. Muscarinic acetylcholine receptor M3 in proliferation and perineural invasion of cholangiocarcinoma cells[J]. Hepatobiliary Pancreat Dis Int， 2012， 11(4)：418-423.
22. 李成刚，黄志强，韦立新，等. 肝门部胆管癌神经浸润及围肝门神经丛的分布[J]. 中华医学杂志， 2012， 92(38)：2699-2702.
23. 李振凯，卢云，张炳远. 肝门胆管癌神经浸润的临床病理学研究现状[J]. 中华临床医师杂志：电子版， 2011， 5(11)：3287-3289.
24. 李成刚，黄志强，韦立新，等. 肝门部胆管癌神经浸润特征的临床病理学分析[J]. 世界华人消化杂志， 2008， 16(4)：379-384.
25. 刘磊，黄强，刘臣海，等. 肝外胆管癌神经及脉管浸润转移的危险因素[J]. 肿瘤， 2012， 32(5)：376-379.
26. ， 55(1)：77-86.

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Establishment of Animal Models of Hilar Cholangiocarcinoma with Perineural Invasion

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