Search for biomarkers of adverse events as skin reaction by molecular target drugs
| Project/Area Number |
24790156
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 分子標的治療薬 / 皮膚障害 / 手足症候群 / STAT3 / 角化細胞 |
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| Research Abstract |
This study aimed to examine whether the toxicity of molecular target drugs for human keratinocytes was associated with inhibiting signal transducer and activator of transcription 3 (STAT3). We studied whether STAT3 activity affects molecular target drugs-induced cell growth inhibition in HaCaT cells by WST-8 assay. Stattic enhanced the cell-growth inhibitory and apoptotic effects of molecular target drugs. HaCaT cells transfected with constitutively- active STAT3 (STAT3C) were resistant to the molecular target drugs-induced cell growth inhibition. STAT3 activity decreased after short-term treatment with sorafenib and sunitinib in a dose-dependent manner and recovered after long-term treatment with molecular target drugs at low doses. Moreover, HaCaT cells transfected with STAT3C showed high expression of apoptosis suppressors, e.g. bcl-2 and survivin. Thus, STAT3 activation mediating apoptosis suppressors may be a key factor in molecular target drugs-induced keratinocyte cytotoxicity.
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Report
(3 results)
Research Products
(23 results)
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[Presentation] ソラフェニブ・スニチニブによるアポトーシス制御機構を介した皮膚障害発症メカニズムの解明2014
Author(s)
山本和宏,水本篤志,西村幸治,宇田篤史,中川勉,久米学,槇本博雄,尾藤利憲,錦織千佳子,平野剛,平井みどり
Organizer
日本薬学会134年会
Place of Presentation
熊本
Year and Date
2014-03-30
Related Report
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[Presentation] ソラフェニブによる皮膚障害のビタミンC誘導体を用いた予防・治療法のメカニズム解析2014
Author(s)
小澤拓,山本和宏,久保萌子,賀来健太,水本篤志,宇田篤史,濱口常男,中川勉,尾藤利憲,錦織千佳子,平野剛,平井みどり
Organizer
日本薬学会134年会
Place of Presentation
熊本
Year and Date
2014-03-30
Related Report
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[Presentation] Dimension® Xpandを用いた血清リチウム濃度の院内測定2012
Author(s)
若松雄太,山下和彦,山本和宏,向井啓,瀬戸崇光,宇田篤史,平野剛,濱口常男,岩川精吾,太田光熙,棚橋孝雄,平井みどり
Organizer
第29回日本TDM学会学術大会
Place of Presentation
神戸
Year and Date
2012-06-17
Related Report
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