Study on growth suppression of lung cancer by the inhibition of COX2,LOX, and EGFR for clinical application
| Project/Area Number |
15590835
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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 |
Respiratory organ internal medicine
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
HIDA Toyoaki Aichi Cancer Center Research Institute, Molecular Oncology, Researcher, 分子腫瘍学部, 研究員 (80250249)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Takahiko Aichi Cancer Center Research Institute, Research Institute, Researcher, 研究所, 研究員 (50117826)
TAKAHASHI Takashi Aichi Cancer Center Research Institute, Molecular Oncology, Chief, 分子腫瘍学部, 部長 (50231395)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Lung cancer / LOX inhibitor / EGFR inhibitor / COX2 inhibitor / Growth suppression / Combination / Gene mutation / Anti-cancer agent / COX-2阻害剤 / EGFR / HER2 / HER3 / HER4 / K-ras変異 |
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| Research Abstract |
This study showed that lipoxygenase inhibitors can inhibit proliferation of lung cancer cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis. Moreover, we found that lipoxygenase inhibitors reduced the IC50 values of various anticancer agents, suggesting that the use of lipoxygenase inhibitors may be a promising therapeutic approach. Using a panel of 19 lung cancer cell lines, we observed the lack of association of gefitinib sensitivity with the expression of EGFR, HER2, HERS, and HER4. Our results also showed no apparent association between K-ras mutations and sensitivity to gefitinib. These data suggest that tumor EGFR expression is not clinically relevant for predicting response to gefitinib. In clinical studies, we found that about 40 % of Japanese patients with non-small cell lung cancer had EGFR mutations. The mutations were deletions or point mutations. EGFR mutations were significantly frequent in female, adenocarcinomas, and in never smokers, and EGFR mutations showed good -correlation with gefitinib effectiveness. These data suggest that EGFR mutations may help to define the patient population likely to benefit most from EGFR-targeted therapies.
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Report
(3 results)
Research Products
(14 results)
