2001 Fiscal Year Final Research Report Summary
THE STUDY OF GENE ABNORMALITIES RELATED TO HEPATOCELLULAR CARCINOMA
| Project/Area Number |
12670487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
YUMOTO Yasuhiro OKAYAMA UNIVERSITY, RADIO-ISOTOPE CENTER, ASSOCIATE PROFESSOR, アイソトープ総合センター, 助教授 (30033369)
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| Co-Investigator(Kenkyū-buntansha) |
NOUSO Kazuhisa OKAYAMA UNIVERSITY, HOSPITAL, ASSISTANT, 医学部・附属病院, 助手 (10314668)
HIGASHI Toshihiro OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (80173136)
HANAFUSA Tadashi OKAYAMA UNIVERSITY, RADIO-ISOTOPE CENTER, ASSISTANT, アイソトープ総合センター, 助手 (00228511)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Hepatocellular carcinoma / Hepatocarcinogenesis / cDNA micro array / LOH / Reduced expression of the IGFBP-3 |
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| Research Abstract |
1) In order to disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) toward development of novel therapeuticf targets, we analyzed expression profiles of 22 primary (HCC) and their corresponding noncancerous tissues by means of cDNA micro arrays consisting of 1,176 genes (Atlas(TM) Human Cancer 1.2 cDNA expression array (Clontech Laboratoties, Inc., Palo Alto, CA)). Up-regulation of mitosis-promoting genes was observed in the majority of the tumors examined. The expression of 9 genes was enhanced 2 times or more in HCC cancerous tissue compared with noncancerous tissue in 5 or more of the 9 patients. In contrast, 8 genes were expressed at half the level or less in HCC cancerous tissue compared with noncancerous tissue. When standard clustering was performed to identify genes related to clinical phenotypes of the patients, 20 genes showed changes associated with the degree of differentiation of HCC. Thirteen of these genes were transcriptional factors or tissue-specific expression proteins related to cell deifferentiation or development. Our present analysis clarified a number of genes that characterize HCC. This information based on examination of clinical samples is considered to be useful for clarificfation of the mechanism of hepato-carcinogenesis and the diagnosis and treatment ot HCC.
2) Insulin-like growth factor binding proterin-3 (IGFBP-3) is postulated to be a mediator of growth suppression singnals. Reduced expression of the IGFBP-3 was observed in nine out of 12 human hepatocellular carcinomas (HCC) (75%). Promoter hypermethylation of the IGFBP-3 was detected in four out of 12 HCCs (33%) althoughn mutations were no identified. The expression of IGFBP-3 was restored by the demethylating agent 5-aza-2'-deoxycytidine in HCC cell line with promoter hypermethylation (HepG2). As IGFBP-3functions like a tumor suppressor gene, it may be used as a therapeutic target for HCC.
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Research Products
(12 results)
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[Publications] Hanafusa T, Yumoto Y, Nouso K, Nakatsukasa H, Onishi T, Fujikawa T, Taniyama M, Nakamura S, Uemura M, Takuma Y, Yumoto E, Higashi T and Tsuji T: "Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma."Cancer Letter. 176 (2). 149-158 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Eiichito Yumoto, Toshihiro Higashi, Kazuhiro Nouso, Harushige Nakatsukasa, Keishi Fujiwara, Yoshiyuki Kobayashi, Toru Onishi, Masayuki Uemura, Shinichiro Nakamura, Shuichiro Sato, Tadashi Hanafusa, Yasuhiro Yumoto, Tanimoto Kurimoto, Noriaki Tanaka: "Serum interferon-gammafulminant-inducing factor (IL-18) and IL-10 levels in patients with acute hepatitis and fulminant hepatic failure."J gastroenterol hepatol. (in press).
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「研究成果報告書概要(欧文)」より
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[Publications] Ishizaki M, Ashida K, Higashi T, Nakatsukasa H, Kaneyoshi T, Fujiwara K, Nouso, K, Kobayashi Y, Uemura M, Nakamura S, Tsuji T: "The formation of capsule and septum in human hepatocellular carcinoma."Virchow Arch. 438. 574-580 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Kaneyoshi T, Nakatsukasa H, Higashi T, Fujiwara K, Naito I, Nouso K, Kariyama K, Kobayashi Y, Onishi T, Yamano T, Uemura M, Nakamura S, Iwasaki Y, and Takao Tsuji: "Actual invasive potential of human hepatocellular carcinoma revealed by in situ gelatin zymography."Clin Cancer Res. 7 (12). 4027-4032
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「研究成果報告書概要(欧文)」より
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[Publications] Kobayashi Y, Higashi T, Nouso K, Nakatsukasa H, Ishizaki M, Kaneyoshi T, Toshikuni N, Kariyama K, Yamano T, Ohnishi T, Fujiwara K, Morii K, Nakayama E, and Tsuji T: "Expression MAGE, GAGE, and BAGE genes in human hepatocellular carcinoma."J Hepatology. 32. 612-617 (2000)
Description
「研究成果報告書概要(欧文)」より
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