| Project/Area Number |
05404046
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
BABA Shozo HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE,SECOND DEPARTMENT OF SURGERY,PROFESSOR, 医学部, 教授 (40107818)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Yusuke INSTITUTE OF MEDICAL SCIENCE UNIVERSITY OF TOKYO,LABORATORY OF MOLECULAR MEDICIN, 医科学研究所, 教授 (70217909)
SUGIMURA Haruhiko HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE,PATHOLOGY,PROFESSOR, 医学部, 教授 (00196742)
FUJITA Michiya HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE,BIOCHEMISTRY,PROFESSOR, 医学部, 教授 (60014031)
小里 俊幸 浜松医科大学, 医学部, 助手 (00252180)
中井 勝彦 浜松医科大学, 医学部, 講師 (50217642)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1995: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | MISSMATCH REPAIR GENE / APC GENE / p53 / VEGF / VGEF / 遺伝性大腸癌 / 発症前診断法 / DNA複製エラー / DCC遺伝子 / p53 / K-ras / 癌遺伝子 / 癌抑制遺伝子 / 家族性大腸腺腫症 / HNPCC / K-ras遺伝子 / p53遺伝子 |
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| Research Abstract |
Multi step carcinogenesis of colorectal cancer have been clarified. Various gene as an oncogene. In 1993, mismatch repair genes have been indentified as the causing genes of HNPCC.
Firstly, germ line mutation of APC gene were analyzed in 26 family trees of familial adenomatous polyposis identifying point mutations and deletions in various site. All the point mutations end up with stop colon. Presymptomatic diagnosis is now possible either PCR and RNase protection assay and in-vitro synthesized protein assay. Germ line mutation was also identified in bMLH-L in the largest family of HNPCC in Japan by using blood samples and mouth-wash samples which contain exfoliated mucosal cells. Similar result was obtained, however, penetration rate of HNPCC is not known yet. HNPCC family including 394 cases which met Amsterdam Criteria were collectedfrom major institutions in Japan. Analizing those cases, it was revealed that gastric cancer in male and indometrial cancer in female are the most prominment second primary cancer. Tumors in there cases shows replication error demonstrating micro satelite instability.
Gene analusisi was also made villous adenoma cancer and dysplasia assosiated with ulcerative colitis. It was revealed that in colorectal cancer tissue, uPA,IL-1, VEGF,and PDECGF are predominately high in comparison to the normal mucosa.
Efficacy of neoangiogenesis inhibitor was studied by the use of xenogratted nude mouse. Original tumor was obtained from liver metastatic lesion and low metastatic strains. High metastic strain show g reater accumulation of mutated genes.
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