| Project/Area Number |
14370187
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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 | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
NIITSU Yoshiro Sapporo Medical University, Professor, 医学部, 教授 (10045502)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Junnji Sapporo Medical University, Associate Professor, 医学部, 助教授 (20244345)
TAKAYAMA Tetsuji Sapporo Medical University, Assistant Professor, 医学部, 講師 (10284994)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | colorectal cancer / Chemoprevention / K-ras |
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| Research Abstract |
Aim : We previously demonstrated that aberrant crypt foci(ACF) are precursors of adenoma-carcinoma sequence in colorectal carcinogenesis, and ACF are frequently positive for K-ras mutation. In this study, we examined the inhibitory effect of FTI and GGTI targeting mutated K-ras in ACF. Methods : P344 rats were administered with colorectal carcinogen(dimethylhydralazine ; DMH). FTI-287 or GGTI-297 were intraperioneously injected to the rats, and they were sacrificed at 8 weeks for examination of ACF and 24 weeks for polyps. ACF identification was performed by methyleneblue staining under stereoscopic microscope. Results : The rats treated with FT1276 showed reduced number of ACF in a dose dependent manner. Treatment with 70mg/kg significantly reduced the number of ACF. Treatment with GGT1297 showed similar tendency. There was a synergistic inhibitory effect in FTI-276 and GGTI-297 treatment in the rats model of colon carcinogenesis. The adverse effects of FTI-276 and GGTI-297 were negligible. Conclusion : It was suggested that FTI and GGTI are useful chemopreventive agents targeting mutated K-ras in ACF of colorectal carcinogenesis.
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