Establishment of New Therapeutics for Pancreatic Cancer through the Induction of p21, p27

1. 与普通胰腺导管腺癌相比，胰腺导管内黏液高分泌肿瘤中p53和细胞周期蛋白A的表达降低。本研究的目的是阐明IMHN和胰腺导管腺癌生物学差异背后的分子差异。在导管内黏液高分泌肿瘤（IMHN）中，核染色阳性确定p53和细胞周期蛋白A的发生率明显低于导管腺癌。此外，在导管腺癌中，p53和细胞周期蛋白A在地形上共同表达。综上所述，这些结果提示p53和cyclin A的过表达在胰腺导管腺癌的发生中发挥了作用，这两种抗原在IMHN中的稀疏表达可能是其低级别恶性特征的部分原因。PPARγ配体Troglitazone通过上调WAF1/CIP /p21表达对胰腺癌细胞生长和分化的抑制作用，本研究的目的是评估PPARγ配体Troglitazone是否抑制胰腺癌细胞的生长，并阐明其潜在的机制，特别关注细胞周期G1后期的限制性点控制。曲格列酮通过上调p21蛋白和mRNA的表达，具有明显的生长抑制作用，与G1期细胞周期阻滞有关。曲格列酮可引起管腔内细胞凋亡的导管结构形态学改变。综上所述，曲格列酮通过上调p21的表达对胰腺癌细胞株具有生长抑制和诱导分化的作用，为有效治疗胰腺癌提供了新的分子靶点。有效诱导p21和p27的新药筛选体系的建立，由于曲格列酮对p21 mRNA的转录活性较低，p21 mRNA的上调表达主要是由于mRNA的稳定化，提示利用p21启动子稳定转染的胰腺癌细胞系筛选体系有待进一步研究。少

1. Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinomaThe 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 … More 1/p21The 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 p27Troglitazon 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