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Extrahepatic bile duct cancer is a high mortal malignancy. Angiopoietin (Ang) and its receptor Tie, which are known to contribute to angiogenesis, have recently been reported to participate in the proliferation and differentiation of malignant tumor cells. The aim of this study is to investigate the expression and the significance of Ang-1, 2 and Tie-2 in extrahepatic bile duct carcinoma cells. We used immunohistochemistry to study 119 cases of surgically resected human extrahepatic bile duct carcinoma, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) to confirm the expression of Ang-1, 2 and Tie-2 mRNA. Among these 119 cases, 52 (43.7%), 50 (42.0%) and 89 (74.8%) cases showed positive staining for Ang-1, 2 and Tie-2, respectively, in bile duct carcinoma cells. In 38 cases of normal mucosa, 6 (15.8%), 10 (26.3%) and 9 (23.7%) cases were positive for Ang-1, 2 and Tie-2, respectively. The positivity for Ang-1 and Tie-2 in normal mucosa was significantly different from all carcinomas (p<0.01 and p<0.001, respectively). We found no significant correlation between Ang-1 and Ang-2 expression and other clinicopathological factors such as histological differentiation, grade of tumor invasion or survival rate after surgery. In contrast, Tie-2 expression correlated significantly with degree of desmoplasia, cancer stage and survival of patients. RT-PCR analyses of five surgically resected tumor samples and three human bile duct cancer cell lines all showed positive expression of Ang-1, 2 and Tie-2 mRNAs. High expressions of Ang-1, 2 and Tie-2 in human extrahepatic bile duct carcinoma cells suggested that Ang-Tie system may be involved in the progression of human bile duct cancer., Acta medica Nagasakiensia, 53(4), pp.89-95 ; 2009

BACKGROUND: Bilioenterostomy is a common surgical technique that is widely used. Recently, clinical studies have revealed that biliary carcinomas can occur after bilioenterostomy. The present study was designed to evaluate whether hochu-ekki-to (TJ-41), a Japanese herbal drug, could prevent chemically induced biliary carcinomas in bilioenterostomized hamsters. MATERIALS AND METHODS: Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl) amine every 2 weeks at a dose of 10 mg/kg. N-nitrosobis(2-oxopropyl) amine administration was started 4 weeks after surgery. The animals were simultaneously p.o. administered TJ-41 in water every day at a dose of 1000 mg/kg (TJ-41 group). The control hamsters were administered water alone. The hamsters were sacrificed 22 weeks after surgery, and the development of biliary carcinomas, the presence and degree of cholangitis, and the cell kinetic status of the biliary epithelium were evaluated histologically. RESULTS: Intrahepatic bile duct carcinomas developed in 15/17 (88%) hamsters in the control group and in only 8/17 (47%) hamsters in the TJ-41 group (P < 0.05). The degree of cholangitis was not different between the two groups. However, the proliferating cell nuclear antigen labeling index of the biliary epithelium in the TJ-41 group (6.46%) was significantly lower than the controls (9.67%) (P < 0.05). These findings indicated that TJ-41 reduced accelerated biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of carcinogenesis. CONCLUSION: TJ-41 has a preventive effect on chemically induced carcinoma of the biliary tract after bilioenterostomy., Journal of Surgical Research Volume, 151(1), pp.22-27; 2009