| Project/Area Number |
10470048
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | TOHOKU University |
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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)
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| 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)
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| Project Period (FY) |
1998 – 2000
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| Keywords | hepatoma / intrahepatic cholangiocarcinoma / Thorotrast / p53 / mdm2 / genomic instability / microsatellite / 遺伝子不安定性 |
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| 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.
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