| Project/Area Number |
12671679
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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 |
Otorhinolaryngology
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| Research Institution | Jichi medical School |
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Principal Investigator |
NISHINO Hiroshi Jichi Medical School Assistant Profeddor, 医学部, 講師 (50245057)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIMURA Keiichi Jichi Medical School Professor, 医学部, 教授 (00010471)
ISHIKAWA Kazuhiro Jichl Medical School Assistant, 医学部, 助手 (40296083)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | IL-6 / IL-6 receptor / RT-PCR / cell growth / cell invasion / G-CSF / 頭頸部癌 / γ線 / 自殺遺伝子 / アデノ随伴ウイルス / 単純ヘルペスチミジンキナーゼ / ガンシクロビル / MMP-2 / MMP-9 |
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| Research Abstract |
We established NKO-1, a SCC cell line that produces high levels of G-CSF and IL-6, from a metastatic lymph node obtained from a patient with a poorly differentiated maxillary SCC. We studied the in vitro effect of G-CSF and IL-6 on the growth of NKO-1, the in vitro effect of neutralizing G-CSF on the growth of NKO-1 normally enhanced by rhG-CSF, and invasion assay. The in vitro growth of NKO-1 cells was enhanced by high concentrations of G-CSF, but not by any concentration of hIL-6. The effect of G-CSF on NKO-1 cell growth was reduced by antibody to G-CSF in a dose-dependent manner. Compared with other cell lines, which produce low levels of G-CSF and IL-6, NKO-1 cells showed strong invasiveness.
Cancer cells of head and neck cancer cell lines have IL-6 receptors (RT-PCR). The levels of those IL-6 receptors were reduced by antibody to IL-6 receptors in a dose-dependent manner. The in vitro growth rates of cancer cells of head and neck cancer cells lines were reduced by IL-6. We studied the invasiveness of cancer cells of head and neck cancer cell lines with IL-6 in an extracellular matrix membrane system. The degree of invasiveness was enhanced by incubating cells with IL-6. In addition G-CSF enhanced the invasiveness of tumor cells that produced large amounts of G-CSF.
Low efficiency of transgene expression can be a problem in some applications that require potent gene expression such as antitumor applications. We demonstrate that AAV vector harbouring the HSVtk is able to kill cancer cells more efficiently when used in combination with γ-ray irradiation. γ-rays enhance rAAV-mediated transegene expression.
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