2003 Fiscal Year Final Research Report Summary
Chemoprevention of colorectal cancer targeting mutated K-ras in ACF
| 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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| 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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[Publications] Sagawa T, Takayama T, Oku T, Hayashi T, Ohta H, Okamoto T, Muramatsu H, Katsuki 5, Sato Y, Kato J, Niitsu Y.: "Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invation."Gut.. 52. 334-339 (2003)
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[Publications] Terui T, Murakarni K, Takimoto R, Takahashi M, Takada K, Murakami T, Minami S, Matsunaga T, Takayama T, Kato I, Niitsu Y.: "Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors."Cancer Res.. 63. 8948-8954 (2003)
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[Publications] Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, Akiyama T, Kuroda H, Kawano Y, Kobune M, Kato J, Hirayama Y, Sakamaki S, Kohda K, Miyake K, Niitsu Y.: "Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia."Nat Med.. 9. 1158-1165 (2003)
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[Publications] Yamauchi A, Ito Y, Morikawa M, Kobune M, Huang I, Sasaki K, Takahashi K, Nakamura K, Dehari H, Niitsu Y, Abe T, Hamada H.: "Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model."J Gene Med.. 5. 994-1004 (2003)
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