| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
1. Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinoma
The aim of the present study is to clarify the molecular differences underlying the biological differences between IMHN and ductal adenocarcinoma of the pancreas. In Intraductal mucin-hypersecreting neoplasm (IMHN), the incidence of p53 and cyclin A ascertained by positive nuclear staining was significantly lower than that in ductal adenocarcinoma. Furthermore, in ductal adenocarcinoma, p53 and cyclin A are topographically co-expressed. In conclusion, these results suggest that the overexpression of p53 and cyclin A plays a role in tumorigenesis of the pancreatic ductal adenocarcinoma, and sparse expression of both antigens in IMHN may partly contribute to its low-grade malignant characteristics.
2. Growth Inhibition and Differentiation of Pancreatic Cancer Cell Lines by PPAR γ Ligand Troglitazone through the Up-expression of WAF1/CIP
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1/p21
The aim of this study is to assess whether the PPARγ ligand, troglitazone, inhibits the growth of pancreatic cancer cells, and to clarify the underling mechanisms with a special focus on restriction point control of the late G1 phase of the cell cycle. Troglitazone had marked growth inhibitory effects linked to the G1 phase cell cycle arrest through the up-expression of p21 protein and mRNA. Troglitazone induced significant morphological changes of duct structure with apoptotic cells in the lumen. In conclusion, Troglitazone had growth inhibitory and differentiation induction effects on the pancreatic cancer cell lines through the up-expression of p21, suggesting a new molecular target for effective therapy against pancreatic cancer.
3. Establishment of screening system of new drugs which effectively induce p21 and p27
Troglitazon has little trnscriptional activity of p21 mRNA and the up-expression of p21 mRNA was mainly due to stabilization of mRNA, suggesting that screening system using p21 promorter stable transfectant of pancreatic cancer cell line needs further studies. Less
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