Development of anti-cancer reagent utilizing cytotoxic potential of human ribonucleases
| Project/Area Number |
09555255
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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 | 展開研究 |
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| Research Field |
生物・生体工学
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| Research Institution | Okayama University |
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Principal Investigator |
YAMADA Hidenori Okayama University, Faculty of Engineering, Professor, 工学部, 教授 (80037613)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Hiroko Okayama University, Faculty of Engineering, Assistant Professor, 工学部, 助手 (60271061)
SENO Masaharu Okayama University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (90243493)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | RNase / Anti-cancer agent / Growth factor / Growth inhibition / 細胞成長因子 / 細胞増殖阻害 |
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| Research Abstract |
Pancreatic-type RNases are considered to have cytotoxic potential, because they can degrade RNA molecules when enter the cytosol. However, most of these RNases are virtually little toxic because cells have no active uptake mechanism for these RNases and because ubiquitous cytoplasmic RNase inhibitor is considered to play protective role against endocytotic leak of RNases from outside of cells. To study the cytotoxic potential of RNase toward malignant cells targeting growth factor receptors, the carboxyl terminus of human RNase 1 was fused to the amino terminus of human basic fibroblast growth factor (bFGF). This RNase-FGF fused protein was found to effectively inhibited the growth of mouse melanoma cell line B 16/BL6 with the high level of cell surface FGF receptor.
This effect appeared to result from prolongation of overall cell cycle rather than killing cells or specific arrest in a particular phase of cell cycle. Thus human RNase 1 fused to a ligand of cell surface molecules such as FGF receptor is shown to be an effective candidate for selective cell targeting agent toward malignant cells with low toxic effects on normal cell types.
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Report
(3 results)
Research Products
(19 results)
