| Project/Area Number |
12671238
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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 |
Digestive surgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
TAKAO Sonshin Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80171411)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIZAWA Hidekazu Okayama University, Faculty of Environmental and technology, Associate Professor, 環境理工学部, 助教授 (20244262)
AIKOU Takashi Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (60117471)
NATSUGOE Shoji Kagoshima University, University Hospital, Faculty of Medicine, Assistant Professor, 医学部附属病院, 講師 (70237577)
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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 |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Gene therapy / Drug delivery system / microsphere / micrometastasis / Suppressor gene / liposome / Drug resistence / ドラッグ・デリバリー・システム / マイクロスフェアー / リンパ節転移 |
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| Research Abstract |
The purpose of the present study was to make the microsphere incorporated gene for micrometastasis in the gastrointestinal cancer. Chemotherapeutic agents with differentiating properties have been studied to increase sensitivity to anti-cancer drugs. We examined the ability of the novel histone deacetylase (HDAC) inhibitor, sodium butyrate (NaB), to modulate the expression of p53. In some cell lines which lacked p53 expression by western blot analysis, 1 mM NaB induced histone acetylation and p53 expression. Sensitivity to cis-platinum, 5-FU and SN-38 measured with the MTT assay, was markedly enhanced by NaB treatment. With a DNA laddering study, high frequencies of apoptosis were found in the NaB treated cells, compared with control cells. These in-vitro results suggest that NaB may be useful clinically for carcinomas that are not sensitive to anti-cancer drugs because of low expression of p53. We tried to adjust the microcapsule (MS) using mixed vitamins such as αG-lucin or αG-hesperizine as a drug carrier. The adjustment of MC was performed by vitamin added to glucose and PVA. Electron microscope revealed that the size of MC ranged 0.5〜2μm in size. We are now doing the experimental study on MC incorporated p53 plasmid. We also studied the specific liposome to lung resistance-related protein (LRP). We made a MCF-7AdVP3000/RzLRP cells which was induced to multi-drug resistant breast cancer cell (MCF-7AdVP3000). The LRP expression decreased in these cells and the sensitivity for adriamycin increased. In the present study, although the microsphere incorporated p53 gene could not be completely made, it is useful for further therapy to make MC or liposome which enhanced sensitivity for anticancer agents or decreased drug resistance factors.
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