2002 Fiscal Year Final Research Report Summary
Development of a gene set and monoclonal antibodies for the diagnosis of hepatocellular carcinoma.
| Project/Area Number |
12557051
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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 | 展開研究 |
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| Research Field |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ABURATANI Hiroyuki The University of Tokyo, Center for Collaborative Research, Professor, 国際・産学共同研究センター, 教授 (10202657)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Naohiko Institute of Immunology Co., Ltd, Antibody Development Division, Researcher, 研究員
KODAMA Tatsuhiko The University of Tokyo, Center for Collaborative Research, Professor, 先端科学技術研究センター, 教授 (90170266)
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| Project Period (FY) |
2000 – 2002
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| Keywords | microarray / tumor marker / GPC3 / hepatocellular carcinoma |
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| Research Abstract |
We aimed at developing a novel algorithm for diagnosis of hepatocellular carcinoma (HCC) by analyzing a correlation between gene expression profiles and clinical and/or pathological parameters. Particularly we analyzed the function of HCC-specific genes and its role in hepatocarcinogenesis. We performed gene expression profiling analysis to identify a novel marker for diagnosis and therapeutics.
1)Novel algorithms, using cluster analysis, PCA and SVM, were developed to analyze gene expression data for discrimination between cancer and normal tissues and gene selection for prognosis estimation.
2)With gene expression profiling of nodule-in-nodule type of HCC, we identified 16 genes differentially expressed between well differentiated and moderately differentiated tumors.
3)We demonstrated GPC3 protein level is elevated in HCCs as well as its RNA level and that GPC3 inhibits BMP-7 signaling through the Smad pathway by reporterr gene assay. It is a heparan sulfate proteoglycan anchored to the plasma membrane we demonstrated that its NH(2)-terminal portion [soluble GPC3 (sGPC3)] is cleaved between Arg(358) and Ser(359) of GPC3 and that sGPC3 can be specifically detected in the sera of patients with HCC.
4) In immunohistochemistry GPC3 is positive in 84% of HCC cases.
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[Publications] Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, Tokita S, Iwanari H, Ito Y, Nakano K, Nezu J, Tsunoda H, Yoshino T, Ohizumi I, Tsuchiya M, Ohnishi S, Makuuchi M, Hamakubo T, Kodama T, Aburatani H.: "Identification of Soluble Amino Terminal Fragment of Glypican-3 as a Serological Marker for Early Stage Hepatocellular Carcinoma."Cancer Research. 64. 2418-2423 (2004)
Description
「研究成果報告書概要(和文)」より
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[Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling."Int J Cancer.. 103(4). 455-465 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, Tokita S, Iwanari H, Ito Y, Nakano K, Nezu J, Tsunoda H, Yoshino T, Ohizumi I, Tsuchiya M, Ohnishi S, Makuuchi M, Hamakubo T, Kodama T, Aburatani H.: "Identification of Soluble Amino Terminal Fragment of Glypican-3 as a Serological Marker for Early Stage Hepatocellular Carcinoma."Cancer Research. 64. 2418-2423 (2004)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling."Int J Cancer. 103(4). 455-465 (2003)
Description
「研究成果報告書概要(欧文)」より
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