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

通过诱导 p21、p27 建立胰腺癌新疗法

• 批准号: 10670461
• 负责人: KAWA Shigeyuki
• 金额: $ 2.3万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670461/
• 关键词: pancreatic cancer; p21; p27; vitamine A; vitamine D; PPARγ; toglitazon; cyclin A

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

1.与普通胰腺导管腺癌相比，胰腺导管内粘蛋白高分泌肿瘤中p53和cyclin A的表达降低本研究的目的是阐明IMHN和胰腺导管腺癌之间生物学差异背后的分子差异。在导管内粘蛋白高分泌肿瘤（IMHN）中，核染色阳性确定的 p53 和细胞周期蛋白 A 的发生率显着低于导管腺癌。此外，在导管腺癌中，p53 和细胞周期蛋白 A 在局部共表达。总之，这些结果表明p53和cyclin A的过度表达在胰腺导管腺癌的肿瘤发生中发挥作用，并且IMHN中这两种抗原的稀疏表达可能部分导致其低度恶性特征。 2． PPAR γ 配体曲格列酮通过上调 WAF1/CIP 抑制胰腺癌细胞系的生长和分化…更多 1/p21 本研究的目的是评估 PPARγ 配体曲格列酮是否抑制胰腺癌细胞的生长，并阐明其潜在机制，特别关注细胞周期晚期 G1 期的限制点控制。 Troglitazone 通过上调 p21 蛋白和 mRNA 的表达，具有与 G1 期细胞周期停滞相关的显着生长抑制作用。曲格列酮诱导导管结构发生显着形态学变化，管腔内出现凋亡细胞。综上所述，曲格列酮通过上调p21表达对胰腺癌细胞系具有生长抑制和诱导分化作用，为胰腺癌的有效治疗提供了新的分子靶点。 3．有效诱导p21和p27的新药筛选体系的建立曲格列酮的p21 mRNA转录活性很小，p21 mRNA的上表达主要是由于mRNA的稳定化，提示利用p21启动子稳定转染胰腺癌细胞株的筛选体系有待进一步研究。较少的

项目成果

Masakazu Kobayashi: "Malignant insulinoma presenting a non-functioning metastatic liver tumor 14 years after resection of the primary tumor"J of Gastroenterol. Vol.33. 891-894 (1998)

Masakazu Kobayashi：“恶性胰岛素瘤在原发性肿瘤切除 14 年后呈现无功能的转移性肝肿瘤”J of Gastroenterol。

Masakazu Kobayashi et. al.: "Malignant insulinoma presenting a non-functioning metastatic liver tumor 14 years after resection of the primary tumor"J of Gastroenterol. Vo. 33. 891-894 (1998)

小林正和等。