| Project/Area Number |
12672139
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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 |
Biological pharmacy
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| Research Institution | KOBE PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
OKANO Toshio KOBE PHARMACEUTICAL UNIVERSITY, DEPARTMENT OF HYGIENIC SCIENCES, PROFESSOR, 薬学部, 教授 (20131542)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kimie KOBE PHARMACEUTICAL UNIVERSITY, DEPARTMENT OF HYGIENIC SCIENCES, ASSISTANT, 薬学部, 助手 (90309435)
KAMAO Maya KOBE PHARMACEUTICAL UNIVERSITY, DEPARTMENT OF HYGIENIC SCIENCES, ASSISTANT, 薬学部, 助手 (40299087)
TSUGAWA Naoko KOBE PHARMACEUTICAL UNIVERSITY, DEPARTMENT OF HYGIENIC SCIENCES, ASSISTANT PROFESSOR, 薬学部, 講師 (30207352)
竹内 敦子 神戸薬科大学, 薬学部, 講師 (80154970)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | ACTIVE VITAMIN D ANALOGS / CANCER CELLS / STRUCTURE AND ACTIVITY / CELL DIFFERENTIATION - PROLIFERATION / GENE REGULATION / APOPTOSIS / CELL CYCLE / VITAMIN D RECEPTOR / 癌細胞 / 活性ビタミンD誘導体 / 遺伝子転写調節 |
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| Research Abstract |
It has been well documented in vitro and in vivo that 1a, 25-dihydroxyvitamin D3 (1a, 25(OH)2D3), an active form of vitamin D3, exhibits a variety of anti-tumor activities including inhibition of proliferation, induction of cell differentiation and apoptosis towards breast, prostate, lung and colon cancer cell lines. These effects are extremely strong when compared to those of other natural compounds and theft clinical applications are anticipated. However, there are still lots of issues regarding the efficacy and safety of these analogs. To address these issues, we performed this project from 2000 to 2001 and our results were as follows.
(1) The insertion of a methyl group into the C-2 position of the A-ring of the active form of vitamin D extremely enhanced its biological activity.
(2) The epimerization of the hydroxy group at the C-1 and C-3 positions of the A-ring induced the selective activity of cell differentiation and apoptosis.
(3) The hybrid analogs with the above two characteristics were found to be a promising candidate for the treatment of cancer.
In 2002, we tried to clarify the structure motifs related to the efficacy and safety of vitamin D analogs, especially a non-calcemic analog OCT at the gene, cell, and human levels. The results were as follows.
1) OCT is metabolized via two major pathways, dehydration and epimerization.
2) The enzymes responsible for the above two metabolic pathways are thought to be different from the known enzymes involved in the hydroxylation of vitamin D.
3) The regulatory mechanism to control the above two pathways seems to exist.
4) We confirmed that the CYP24 and CYP27A1 expression vector systems using E-Coli are powerful tools for screening general biological activity of vitamin D analogs.
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