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Genetic oncological and molecular epidemiological research on development and progression of the biliary tract cancer in Asia

Research Project

Project/Area Number 12576002
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Pathological medical chemistry
Research InstitutionUniversity 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)
Keywordsbiliary 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.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Ghosh, M., et al.: "Cyclooxygenase expression in the gallbladder"Int. J. Mol. Med.. 6. 527-532 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo S., et al.: "Coffee consumption and serum aminotransferases in middle-aged Japanese men"J Clin Epidemiol.. 54. 823-829 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamoto, T., et al.: "Expression of MUC1 mucins in the subserosal layre correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Clin. Cancer Res.. 7. 1333-1342 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamoto, T., et al.: "Expression of cyclooxygenase-2 in the subserosol layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Int. J. Cancer. 98. 427-434 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asano T., et al.: "Expressions of cyclooxygenase-2 and prostaglandin 3-receptors in carcinoma of the gallbladder : crucial role of arachidonate metabolism in tumor growth and progression"Clin. Cancer Res.. 8. 1157-1157 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 本荘 哲: "寄生虫感染症とがん 生態学的,生物学的,疫学的ブリーフレヴュー"癌の臨床. 49. 9-14 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ghosh M., et al.: "Cyclooxygenase expression in the gallbladder"Int. J. Mol. Med.. 6. 527-532 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo S., et al.: "Coffee consumption and serum aminotransferases in middle-aged Japanese men"Int. J. Clin Epidemiol.. 54. 823-829 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamoto T., et al.: "Expression of MUC1 mucins in the subserosal layre correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Clin. Cancer Res.. 7. 1333-1342 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamoto T., et aL.: "Expression of cycrooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Int. J. Cancer. 98. 427-434 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asano T., et al.: "Expressions of cyclooxygenase-2 and prostaglandin 3-receptors in carcinoma of the gallbladder crucial role of arachidonate metabolism in tumor growth and progression"Clin. Cancer Res.. 8. 1157-1167 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honjo S.: "Parasitic infection and cancer : an ecological, biological and epidemiological brief review (In Japanese)"Gan no Rinsho. 49. 9-14 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamoto, I., et al.: "Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Int.J.Cancer. 98. 427-434 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asano T., et al.: "Expressions of cyclooxygenase-2 and prostaglandin 3-receptors in carcinoma of the gallbladder : crucial role of arachidonate metabolism in tumor growth and progression"Clin. Cancer Res.. 8. 1157-1157 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanai M., et al.: "Involvement of poly(ADP-ribose) polymerase-1 and poly(ADP-ribosyl)ation in regulation of centrosome function"Mol Cell.Biol.. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本荘哲: "寄生虫感染症とがん生態学的,生物学的,疫学的ブリーフレヴュー"癌の臨床. 49. 9-14 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ujjin, P., et al.: "Variation in coumarin 7-hydroxylase activity associated with genetic polymorphism of cytochrome_P450 2A6 and the body status of iron stores in adult Thai males and females"Pharmacogenetics. 12. 241-249 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Topcu, Z., et al.: "CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka"Carcinogenesis. 23. 595-598 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamoto, T., et al.: "Expression of cyclooxygenase-2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carconoma of the gallbladder"Int. J. Cancer. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Honjo S., et al.: "Coffee consumption and serum aminotransferases in middle-aged Japanese men"J Clin Epidemiol.. 54. 823-829 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uchida, M., et al.: "Genetic and functional analysis of PARP, a DNA strand break-binding enzyme"Mut. Res.. 477. 89-96 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawamoto, T., et al.: "Expression of MUC1 mucins in the subserosal layre correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder"Clin. Cancer Res.. 7. 1333-1342 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Todoroki, T., et al.: "Treatment strategy for patients with middle and lower third bile duct cancer"Brit. J. Surg.. 88. 364-370 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita, K., et al.: "Role of human cytochromoe P450(CYP) in the metabolic activation of N-alkylnitrosamines : application of genetically engineered Salmonella typhimurium YG7108 expressingeach form of CYP together with human NADPH-cytochrome P450 reductase"Mut. Res.. 483. 35-41 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tanaka,M.,et al.: "HTLV-1 infection to mice : proliferation of cell clones with integrated HTLV-1 provirus in lymphoid organs"J.Virol.. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ghosh,M.,et al.: "Cyclooxygenase expression in the gallbladder"Int.J.Mol.Med.. 6. 527-532 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanai,M.,et al.: "Poly (ADP-ribose) polymerase localizes to the centrosomes and chromosomes"Biochem.Biophys.Res.Commun.. 278. 385-389 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Loriot,MA.,et al.: "Genetic polymorphism of cytochrome P450 2A6 in a case control study on lung cancer in a French population"Pharmacogenetics. 11. 39-44 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeshita,T.,et al.: "Relationships between cigarette smoking, alcohol drinking, the ALDH2 genotype and adenomatous types of colorectal polyps in male self-defense force officials"J.Epidemiol.. 10. 366-371 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Todoroki,T.,et al.: "Radical resection of hilar bile duct carcinoma and predictors of survival"Br.J.Surgery. 87. 306-313 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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