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Radio-sensitization by 17AAG in human tumor cells

https://repo.qst.go.jp/records/69026
https://repo.qst.go.jp/records/69026
46ec66b9-e236-40a7-ba79-5dc2dd0fe32c
Item type 会議発表用資料 / Presentation(1)
公開日 2007-07-17
タイトル
タイトル Radio-sensitization by 17AAG in human tumor cells
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Yu, Dong

× Yu, Dong

WEKO 677442

Yu, Dong

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Sekine, Emiko

× Sekine, Emiko

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Sekine, Emiko

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Ninomiya, Yasuharu

× Ninomiya, Yasuharu

WEKO 677444

Ninomiya, Yasuharu

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Fujimori, Akira

× Fujimori, Akira

WEKO 677445

Fujimori, Akira

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Okayasu, Ryuichi

× Okayasu, Ryuichi

WEKO 677446

Okayasu, Ryuichi

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et.al

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et.al

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于 冬

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en 于 冬

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関根 絵美子

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en 関根 絵美子

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二宮 康晴

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en 二宮 康晴

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藤森 亮

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en 藤森 亮

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岡安 隆一

× 岡安 隆一

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en 岡安 隆一

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抄録
内容記述タイプ Abstract
内容記述 Heat-shock protein 90 (Hsp90) is a ubiquitous molecular chaperone protein, which is related to the stabilization and activation of various cell cycle checkpoints and signal transduction proteins. An effective Hsp90 inhibitor 17-AAG has now entered clinical trials. Insulin-like growth factor I receptor (IGF-IR) over-expressed HeLa cells (HeLa-IGF-IR) exhibit a radioresistant phenotype and are difficult to be treated with radio-therapy. We studied the radio-sensitization effects of 17-AAG in HeLa-IGF-IR cells. After pretreatment with 17-AAG for 24 hours, characteristics of irradiated cells were examined by colony-forming assay, MTT assay, western blotting, and immunostaining. 150nM of 17-AAG pretreatment significantly radio-sensitized HeLa-IGF-IR cells, but this sensitization was not observed with non-transfected HeLa cells. The protein expression of PARP after irradiation was reduced with 17-AAG pretreatment, indicating an increase in apoptosis formation. Irradiation with 17-AAG pretreatment in HeLa-IGF-IR cells led to reduction in cell growth kinetics when compared to HeLa cells. The downstream pathways of IGF-IR (PI3-K/Akt and Raf/MEK/ERK pathways, proliferation signal pathways) were inhibited by 17-AAG treatment, and more cells were led to apoptosis. We also used the tumor xenografts model using SQ5 lung carcinoma cells to examine the antitumor effect of 17-AAG in vivo. The combined treatment with 17-AAG (80mg/kg, 1-3 times/week, i.p.) and 8 Gy gamma-rays significantly inhibited tumor growth. 17AAG treatment would be a useful method for certain radio-resistant tumor cells.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 13th International Congress of Radiation Research
発表年月日
日付 2007-07-12
日付タイプ Issued
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