| Project/Area Number |
17590118
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
ENDO Yoshio Cancer Research Institute, Associate Professor, がん研究所, 助教授 (30211783)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Takuma School of Pharmacy, Aichi Gakuin University, Professor, 薬学部, 教授 (90109976)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Antitumor nucleoside / chemosensitivity / gemcitabine / CNDAC / ribonucleotide reductase / deoxycytidine kinase / nucleoside transporter / ヌクレオシド / デオキシシチジンキナーゼ / シチジンデアミナーゼ / リボヌクレオチドリダクター / リボヌクレオチドリダクターゼ |
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| Research Abstract |
Antitumor 2'-deoxycytidine analogues such as gemcitabine (dFdC) and 2'-C-cyano-2'-deoxy-1-β-D-arabinofuranosylcytosine (CNADC) are enzymatically activated by intracellular deoxycytidine kinase (dCK), while cytidine deaminase (CDA) inactivates them by converting each into its uracil form. Triphosphates of dFdC and CNDAC effectively induce cell-cycle arrest and cell death by inhibiting DNA polymerases. The diphosphate of dFdC also inhibits ribonucleotide reductase (RR). In order to elucidate the determinants of chemosensitivity to dFdC and CNDAC, we examined the protein expression levels of equilibrative nucleoside transporter-1 (ENT1), dCK, CDA, and the RRM1 subunit in 40 clinical specimens of lung cancer using specific antibodies. The chemosensitivity of the clinical specimens was determined using the collagen gel matrix assay. The dFdC sensitivity of the clinical specimens was found to be significantly correlated with the protein levels of CDA and the RRM1 subunit. Interestingly, the protein level of the RRM1 subunit was also correlated with CNDAC sensitivity. The ratios of dCK/RRM1 and dCK/CDA were associated with chemosensitivity to both analogues. These results indicate that the protein expression levels of CDA, dCK, and RRM1 are useful markers to predict chemosensitivity to dFdC and CNDAC.
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