Project/Area Number |
12576002
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 海外学術 |
Research Field |
Pathological medical chemistry
|
Research Institution | University of Tsukuba |
Principal Investigator |
MIWA Masanao Institute of Basic Medical Science, Department of Biochemistry and Molecular Oncology, Professor, 基礎医学系, 教授 (20012750)
|
Co-Investigator(Kenkyū-buntansha) |
TODOROKI Takeshi Institute of Basic Medical Science, Department of Surgery, Associate Professor, 臨床医学系, 助教授 (70114105)
UCHIDA Kazuhiko Institute of Basic Medical Science, Department of Biochemistry and Molecular Oncology, Associate Professor, 基礎医学系, 助教授 (90211078)
HONJO Satoshi Tochigi Cancer Center Research Institute, Epidemiology Unit, Chief Investigator, 室長
YAMAZAKI Hiroshi Hokkaido Univ., Graduate School of, Associate Professor, 大学院・薬学研究科・代謝分析学, 助教授 (30191274)
藤田 健一 北海道大学, 大学院・薬学研究科, 助手 (60281820)
有吉 範高 北海道大学, 大学院・薬学研究科, 助教授 (00243957)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
|
Keywords | biliary tract cancer / gall bladder cancer / xanthogranulomatous cholecystitis / intrahepatic cholangiocarcinoma / COX-2 / CGH / genomic instability / microsatellite instability / ミクロサテライト不安定性 / 薬剤代謝酵素 / 症例・対照研究 / がん遺伝子 / 黄色肉芽腫瘍胆襄炎 |
Research Abstract |
The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis. The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. To elucidate cytogenetic, we analyzed DNA copy number abnormalities of these cancers in genome-wide scale by comparative genomic hybridization. Poorly-differentiated carcinomas have more frequent chromosomal gain at 18p11 than well-differentiated carcinomas. Frequent decrease in copy number were observed at 1pter-p36 (34%) and 21q13-qter (28%). Alterations found in this study might be candidate for novel genes and prognostic factors in the intrahepatic bile duct cancer with chronic inflammation. We also found that the microsatellite instability (MSI) of intrahepatic cholangiocarcinoma in Thailand, was classified as low frequency MSI and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis.
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