Grant-in-Aid for Scientific Research (B)
|Research Institution||KYOTO UNIVERSITY|
IMAMURA Masayuki Graduate School of Medicine, Kyoto University Professor, 医学研究科, 教授 (00108995)
ONODERA Hisashi Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (50240825)
OHSHIO Gakuji Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (80131100)
HOSOTANI Ryo Graduate School of Medicine, Kyoto University Assistant Porfessor, 医学研究科, 講師 (00139908)
SHIMADA Yutaka Graduate School of Medicine, Kyoto University Assistant Porfessor, 医学研究科, 講師 (30216072)
ARII Shigeki Graduate School of Medicine, Kyoto University Assistant Porfessor, 医学研究科, 講師 (50151171)
|Project Fiscal Year
1995 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥7,600,000 (Direct Cost : ¥7,600,000)
Fiscal Year 1996 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1995 : ¥5,900,000 (Direct Cost : ¥5,900,000)
|Keywords||cancer of digestive organs / invasion and metastasis / gene / matrix metalloproteinase / vascular endothelial growth factor / 消化器癌 / 浸潤転移 / 遺伝子 / 細胞外マトリックス分解酵素 / 血管新生因子 / FGF / VEGF / マトリックスメタロプロテアーゼ / Rho / Signal sequence|
There was strong correlation between the expression of VEGF and depth of tumor, lymph node metastasis, and the microvessel count in esophageal cancer. There was also a significant correlation between the VEGF expression and the p53 mutaion. MRP1/CD9 which is a cell motility inhibiting protein was related to the depth of invasion and lymph node metastasis. However, KAI1 which is a family protein of MRP1/CD9 is reduced in most cancer cells and suggests that this protein is related to esophageal carcinogenesis. On the other hand, E-Cadherin, alpha-Catenin, and beta-Catenin have no correlation to clinico-pathological charcteristics of esophageal cancer.
Northern blot hybridization with surgically-extirpated specimen clarified that degree of mRNA expression in VEGF,MMP-9, and MT-MMP was positively correlated with hepatic metastasis, respectively. The Patient with more than 2 highly-expressed genes in their primary lesions was found to be regarded as a high ri
sk patient for hepatic metastasis.
We reveled that MMP-9, MT-MMP and b-FGF were strongly participated in the invasion into tumor capsule which was an important phenotype representing the invasion potential of hepatocellular carcinoma.
Activation of MMP and expression of VEGF were determined in surgically obtained pancreatic cancer tisuue, with the use of gelatin zymography, Western blotting or immunohistochemistry. Activited form of MMP-2 was found in all of the pancreatic cancer tissues and MMP-2 activation ratio in cancer tissue was significantly higher than those in chronic pancreatitis tissues ; meanwhile, expression of activated form of MMP-9 in pancreatic cancer tissue was low and not different from chronic pancreatitis tissue. MMP-2 activation ratio of the primary cancer tissue was significantly correlated with peripancreatic invasion of the tumor, and lymph node metastasis and liver metastasis. Expression of VEGF in pancreatic cancer tissue was seen in 70% of the tissues studied and was well correlated with the vascular density of the tumor.
5.A novel gene responsible for prognosis of patients with HCC
We discovered a gene which specifically expressed in the liver and designated as kan-1. Later on, it was identified that the gene encodes acid CoA-amino acid N-acyltransferase. We showed that kan-1 mRNA expression was adversely correlated with survival time of HCC patients, being regarded as a novel and useful predictive factor for a prognosis of HCC. Less