Project/Area Number |
08670594
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | OKAYAMA UNIVERSITY |
Principal Investigator |
YUMOTO Yasuhiro OKAYAMA UNIVERSITY RADIOISOTOPE CENTER,Associate Professor, アイソトープ総合センター, 助教授 (30033369)
|
Co-Investigator(Kenkyū-buntansha) |
HIGASHI Toshihiro OKAYAMA UNIVERSITY MEDICAL SCHOOL,Associate Professor, 医学部, 助教授 (80173136)
HANAFUSA Tadashi OKAYAMA UNIVERSITY RADIOISOTOPE CENTER,Assistant, アイソトープ総合センター, 助手 (00228511)
|
Project Period (FY) |
1996 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | HCC / Multi-step carcinogenesis / RLGS / AP-PCR-SSCP / Teromerase / Methylation / Hepatoma / APPCR-SSCP法 / 遺伝子異常 |
Research Abstract |
The examination of genetic changes in tumor suppresser genes, oncogenes and abnormality of gene should be a valuable to elucidate the mechanisms of hepatocarcinogenesis in early stage of hepatocellular carcinoma. Restriction landmark genome scanning (RLGS) analysis was applied to detect chromosomal aberrations in 14 cases of HCC with LC showing multiple changes of DNA fragment of multi-centric HCC.Various different patterns were detected in each nodule of multi-centric HCC, and each part of encapsulated mosaic pattern of HCC by both RLGS analysis and AP-PCR-SSCP method. Gene instability produced by DNA hypermethylation or hypomethylation was able to be detected as new spot in early stage of hepatocarcinogenesis, whereas these gene instability was observed infrequently in nontumor-bearing liver samples. We postulated that the changed methylation pattern is important in early stage of hepatocarcinogenesis. Methylation of promoter regions of p15 and p16 were detected in early stage of hepatocarcinogenesis. In 2 cases of 5 small HCC and 3 cases of 18 advanced HCC, the DNA fragment which was obtained by AP- PCR-SSCP method with 20 base pare of synthesized primer, was sequenced and registered to the database as AMFW1417 of candidate for new gene in long arm(q) of the chromosome 9th. The positivity of surgical samples for well differentiated, moderately differentiated, and poorly differentiated HCC was 88%, 87%, and 0%, respectively. The telomerase activity was observed infrequently in liver samples of LC without HCC.
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