| Project/Area Number |
16591718
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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 | Department of Biology and Function in the Head and Neck Yokohama City University Graduate School of Medicine |
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Principal Investigator |
TSUKUDA Mamoru Yokohama City University, Graduate School of Medicine, Dept. of Biology and Function in the Head and Neck, Professor, 大学院・医学研究科, 教授 (70142370)
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| Co-Investigator(Kenkyū-buntansha) |
MIKAMI Yasukazu Yokohama City University, Graduate School of Medicine, Dept. of Biology and Function in the Head and Neck, Associate Professor, 医学部, 準教授 (10322356)
HORIUCHI Choichi Yokohama City University, Graduate School of Medicine, Dept. of Biology and Function in the Head and Neck, Assistant Professor, 医学部, 助手 (40295499)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Head and Neck Cancer / Growth Factor / Epidermal Growth Factor / Angiogenesis Factor |
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| Research Abstract |
The prognosis of advanced head and neck cancer is still poor. Conventional definitive treatments, i.e., surgical resection and/or radiotherapy have not improved the outcome because of locoregional relapses and distant metastases. It is indispensable to improve the outcome by examining biological characteristics of squamous cell carcinoma (SCC) cells which pathologically account for 90% of head and neck carcinomas in the head and neck. Based on this reason, we examined biological characteristics, e.g., growth and metastatic factors, of head and neck SCC cell lines established in our institute and anti-tumor effects of molecular targeted agents against these cell lines.
In these SCC cell lines, hetero- type mutation (2361 G to A) on exon 20 was found and IC_<50> of cell lines with the mutation in a sensitivity assay using gefitinib was significantly lower than that of cell lines without the mutation. This result indicates that the examination on gene mutation of EGFR on SCC cells might be useful to expect the effectiveness of gefitinib in patients with SCC of the head and neck.
Furthermore anti-tumor effects of bevacizumab, an inhibitor of VEGF pathway, and ZD6474 showing both inhibitory actions in VEGFR-2 and EGFR pathways were examined. A suppressive effect of bevacizumab in vitro was not observed, however bevacizumab showed an anti-tumor effect in vivo through induction of apoptosis and anti-angiogenesis. On the other hand, ZD6474 showed a suppressive effect on cell growth in vitro through inhibitions on phosphorylation of VEGFR-2,EGFR and MAPK. ZD6474 showed anti-tumor effects in vivo through induction of apoptosis and anti-angiogenesis. These results showed that ZD6474 had anti-tumor effects by two mechanisms, e.g., an inhibition on VEGFR-2 pathway resulting in anti-angiogenesis and an inhibition on EGFR pathway resulting in induction of apoptosis.
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