| Project/Area Number |
08407037
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KITAYAMA Joji (1999) Dept. Surgery, Faculty of Medicine, University of Tokyo, Associate Professor, 医学部・附属病院, 講師 (20251308)
武藤 徹一郎 (1996-1998) 東京大学, 医学部・附属病院, 教授 (20110695)
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| Co-Investigator(Kenkyū-buntansha) |
TSURUO Takashi Dept. Surgery, Faculty of Medicine, University of Tokyo, Professor, 分子生物学研究所, 教授 (00012667)
NAGAWA Hirokazu Dept. Surgery, Faculty of Medicine, University of Tokyo, Professor, 医学部・附属病院, 教授 (80228064)
MUTO Tetuichiro Dept. Surgery, Faculty of Medicine, University of Tokyo, Professor, 医学部・附属病院, 教授 (20110695)
富永 治 東京大学, 医学部・附属病院, 助手 (10261976)
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| Project Period (FY) |
1996 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥37,600,000 (Direct Cost: ¥37,600,000)
Fiscal Year 1999: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1998: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1997: ¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 1996: ¥16,600,000 (Direct Cost: ¥16,600,000)
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| Keywords | Colorectal cancer / Gene mutation / APC / RAS / BCL-2 / BCL-XL / Chemotherapy / P53 / p21 / BCC-XC / APC遺伝子 / replication error / 放射線治療 / アポトーシス / 細胞周期 / 癌抑制遺伝子 / P53 / Bcl-2 / Dihydropyrimidine dehydrogenase / Apoptosis / Cyclin / DCC |
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| Research Abstract |
Recent studies have shown that many genetic changes such as apc, ras, p53 and microsattelite instability, were involved in the development of colorectal cancers. We analyzed those genetic mutations in many clinical samples resected in our institute, and examined the mechanisms of colorectal cancer, and apotosis mechanisms and radiochemosensitivity.
1. In "so called" non-polypoid cancer ; DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 sm carcinomas (47 polypoid, 19non-polypoid) and 34 advance carcinomas were examined for K-ras codon 12 point mutations and APC mutations in the mutation cluster region. K-ras mutation : The frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs. 31% : p=0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs. 56% : p=0.0008), and was relatively low compared with that in polypoid adenomas (11% vs. 31%). The frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs. 43% : p=0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. In this non-polypoid pathway, APC mutation seems to be requisite, but K-ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas.
2. Transfection of antisense of Bcl-XL, but not of Bcl-2, significantly increased the sensitivity to 5-Fu in colorectal cancer cells. This indicates suppression of apotosis through Bcl-XL is critically involved in the effects of 5-Fu.
3. P53 and p21 were examined in surgical specimens of rectal cancers immunohistocchemically. The expression of p21, but not of p53, was sell correlated with the sensitivity of preoperative irradiation. This supports the effectiveness of the radiation therapy with p21 positive advanced rectal cancers.
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