| Project/Area Number |
07457397
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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 |
Otorhinolaryngology
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| Research Institution | Fukui Medical University |
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Principal Investigator |
SAITO Hitoshi Fukui Medical University, Medical department, Professor, 医学部, 教授 (90079898)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Chizuru Fukui Medical University, University Hospital, Assistant, 医学附属病院, 助手 (80283183)
TSUZUKI Hideaki Fukui Medical University, University Hospital, Assistant, 医学部附属病院, 助手 (90236927)
NODA Ichiro Fukui Medical University, Medical department, Assistant, 医学部, 助手 (60283181)
FUJIEDA Shigeharu Fukui Medical University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (30238539)
OHTSUBO Toshio Fukui Medical University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (10223877)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Head and neck cancer / Anticancer drug sensitivity / Chemoresistance / Hyperthermia / Apoptosis / P-glycoprotein / MRP / Glutathione / アンチセンス / CDDP / 頭頸部癌 / ATP法 / LAK細胞 |
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| Research Abstract |
1995 : The chemosensitivity test by ATP method was applied to 139 cases of head and neck cancer. The evaluated rate was 95%, and the chemosensitive rate was in the order of 5-FU (27%) >CDDP=CBDCA>MTX>PEP (23%). This results indicate that the rest of about 25% show the natural resistance. The expression of P-glycoprotein as one of the cause of chemoresistance appeared in about 60% of them, and showed significant correlation with ADM-resistance. When the content of glutathione (GSH) in squamous cell carcinoma increased, the sensitivity to CDDP decreased. It was proved that the LAK activity increased with hyperthermic condition.
1996 : The relationship between the intracellular GSH content and CDDP sensitivity was investigated. The result showed that the decreased level of GSH induced necrotic cell death, while the increased GSH induced apoptosis. The 4 main resistant factors, drug influx, efflux, DNA-Pt adducts and DNA repair, were investigated concerning CDDP sensitivity using several ca
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ncer cell lines. The result showed the heterogeneity among the cell lines. The cases stained with apoptosis-inducing genes, Fas (+) and Bcl-2 (-), showed good chemosensitivity. The cancer cell lines having G-CSF receptors increased the cell invasion by rG-CSF stimulation. This fact should be bore in mind for clinical use.
1997 : The expression of multidrug resistance-associated protein (MRP) in 115 cases of head and neck carcinomas was investigated by immunohistochemistry, and 30% of them showed positive staining without any clinical correlation and anticancer drug resistance. The synergistic effects of H-7, a protein kinase inhibitor (PKC), on CDDP cytotoxicity to KB cells, a human pharyngeal carcinoma cell line, was investigated. The treatment with H-7 markedly decreased PKC activity and significantly sensitized the cells to CDDP.The treatment of KB cells with H-7 induced a dose-dependent depletion of intracellular GSH levels. A low hyperthermia at 40ﾟC increased accumulation of platinum of CDDP into cancer cells. As a result, CDDP sensitivity was hyperthermically chemopotentiated in CDDP-resistant variants even at low hyperthermia. A combination with CDDP and bcl-2 antisense therapy increased CDDP sensitivity, and thus a possibility of gene chemotherapy was introduced. The expression of bax, a gene inducing apoptosis, was immunohistchemically examined. The positive expression was significantly more observed in the early stage I and II than the late stage. Less
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