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2000 Fiscal Year Final Research Report Summary

Evaluation of Indication for Liver Transplantation in Primary Liver Cancers : Focused on Analysis of Multicentric Liver Cancers and Relapse of Prediction.

Research Project

Project/Area Number 10470048
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionTOHOKU University

Principal Investigator

FUKUMOTO Manabu  Tohoku University, Institute of Development, Aging and Cancer (IDAC), Department of Pathology, Professor, 加齢医学研究所, 教授 (60156809)

Co-Investigator(Kenkyū-buntansha) SATOMI Susumu  Tohoku University, Graduate School of Medicine, Department of Surgery, Professor, 医学研究科, 教授 (00154120)
MANABE Noboru  Kyoto University, Graduate School of Agriculture, Department of Animal Sciences, Associate Professor, 農学研究科, 助教授 (80243070)
SHIMAHARA Yasuyuki  Kyoto University, Graduate School of Medicine, Department of Gastroenterological Surgery, Associate Professor, 医学研究科, 助教授 (30196498)
YAEGASHI Hiroshi  Tohoku University, Institute of Development, Aging and Cancer (IDAC), Department of Pathology, Assistant Professor, 医学研究科, 助手 (40182290)
Project Period (FY) 1998 – 2000
Keywordshepatoma / intrahepatic cholangiocarcinoma / Thorotrast / p53 / mdm2 / genomic instability / microsatellite / 遺伝子不安定性
Research Abstract

Since prognosis of intrahepatic cholangiocarcinoma (ICCI) is poorer and has lower priority of liver transplantation compared with hepatocellular carcinoma, we performed genetic analysis in ICC to characterize ICC.A radiological contrast medium used for angiography during World War II, Thorotrast plays a crucial role for induction of ICC.In previous years, we observed A-T transitional change most often among p53 mutations while p53 mutations are not frequent in non-Thorotarst ICC.We further investigated mem-2 gene amplification and protein overexpression which causes inhibition of p53 protein in non-Thorotrast ICC.In combination with p53 mutations, we found that p53 inactivation in more than a half of non-Thorotarast ICC cases, indicating that p53 inactivation is an important step toward ICC.We presumed that transitional changes of the p53 gene happen via genomic instability. We found microsatellite instability (MSI) in more than 70% of Thorotrast ICC cases. Although MSI phenotype was closely associated with MSI, MSI tended to be observed in the cases with lower amount of Thorotrast deposit and with longer incubation period for ICC.In non-Thorotrast ICC cases, the frequency of MSI is observed in less than 1/3 cases and those without p53 mutations. These suggest that carcinogenesis of ICC is composed of two processes with MSI and without MSI.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Suwa H, et al: "Overexpression of the rhoc gene correlates with progression of ductal adenocarciroma of the pancreas."Brit J Cancer. 77(1). 147-52 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Harada T. et al: "Membrane-type matrixmetalloproteinase-1(MT1-MTP) gene is over-expressed in highly invasive hepatocellular carcinomas"J Hepatol. 28(2). 231-239 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suwa H, et al: "Detection of maltiple hepatiu mlcrometastasis in pancreatic adenocarcinoma with a solitary liver metastasis by direct sequencing of the k-ras gene : a case report."Surgery. 125. 113-116 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toda Y, et al: "Appliacation of tyramide gignal amplification (TSA) system to immunonis to chemistry : a potent method to localize antigens which are not detectable by ordinary method"Pathol Int. 49. 479-83 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kamikawa T, et al: "Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast."Radiat Res. S118-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada I. et al: "High rate of small TP53 mutation and infre guent loss of heterozygosity in malignard livertumors associated with thorotrast : implications for alpha-particle carcine genes"Radiat Res. 152. S125-127 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okabe H. et al: "Comprehensive allelotype study of hepatocellular carcinoma : potential differences in pathways tohepatocellular carcinoma between hepatitis B virus-positive and negative tumors."Hepatol. 31. 1073-9 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakayama K. et al: "Allelotype analysis of gallbladder carcinoma associated with anomalous junction of pancreatico blliary duct"Cancer Lett. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suwa H, Ohshio G, Imamura T, Watanabe G, Arii S, Imamura M, Hiai H, Fukumoto M: "Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas."Brit J Cancer. 77 (1). 147-52 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harada T, Arii S, Mise M, Imamura T, Higashitsuji H, Furutani M, Niwano M, Ishigami S, Fukumoto M, Seiki M, Sato H, Imamura M: "Membrane-type matrixmetalloproteinase-1 (MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas."J Hepatol. 28 (2). 231-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suwa H, Hosotani R, Okino T, Monden K, Arii S, Inoue K, Kogire M, Ohshio G, Fukumoto M, Imamura M: "Detection of multiple hepatic micrometastasis in pancreatic adenocarcinoma with a solitary liver metastasis by direct sequencing of the K-ras gene : a case report."Surgery. 125. 113-6 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toda Y, Kono K, Abiru H, Kokuryo K, Endoh M, Yaegashi H, Fukumoto M: "Application of tyramide signal amplification (TSA) system to immunohistochemistry : a potent method to localize antigens which are not detectable by ordinary method."Pathol Int. 49. 479-83 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kamikawa T,Amenomori M,Itoh T, Momoi H, Hiai H, Machinami R, Ishikawa Y, Mori T, Shimahara Y, Yamaoka Y, Fukumoto M: "Analysis of genetic changes in intrahepatic cholangiocarcinoma induced by thorotrast."Radiat Res. S118-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada I, Horiuchi H, Mori M, Ishikawa Y, Fukumoto M, Mori T, Kato Y, Kitagawa T, Machinami R: "High rate of small TP53 mutations and infrequent loss of heterozygosity in malignant liver tumors associated with thorotrast : implications for alpha-particle carcinogenesis."Radiat Res. 152. S125-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okabe H, Ikai I, Matsuo K, Satoh S, Momoi H, Kamikawa T, Katsura N, Nishitai R, Takeyama O, Fukumoto M, Yamaoka Y: "Comprehensive allelotype study of hepatocellular carcinoma : potential differences in pathways to hepatocellular carcinoma between hepatitis B virus-positive and negative tumors."Hepatol. 31. 1073-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakayama K, Konno M, Kanzaki A, Morikawa T, Miyashita H, Fujioka T, Takafumi Uchida T, Kohji Miyazaki K, Takao S, Aikou T, Fukumoto M, Takebayashi Y: "Allelotype analysis of gallbladder carcinoma associated with anomalous junction of pancreaticobiliary duct."Cancer Lett.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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