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KAKEN_24591850seika.pdf
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Title |
Title |
PI3K/Akt/mTOR経路を標的とする放射線増感剤の開発 : 胃癌細胞での検討
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Kana |
PI3K/Akt/mTOR ケイロ オ ヒョウテキ ト スル ホウシャセン ゾウカンザイ ノ カイハツ : イガン サイボウ デノ ケントウ
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PI3K / Akt / mTOR keiro o hyoteki to suru hoshasen zokanzai no kaihatsu : igan saibo deno kento
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Radiosensitization in gastric cancer cell lines using different PI3K/AKT/mTOR inhibitors
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茂松, 直之
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シゲマツ, ナオユキ
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Shigematsu, Naoyuki
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 30178868
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深田, 淳一
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フカダ, ジュンイチ
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Fukada, Junichi
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 50338159
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西村, 修一
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ニシムラ, シュウイチ
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Nishimura, Shuichi
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慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 40571138
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2015
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科学研究費補助金研究成果報告書
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2014
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Abstract |
進行胃癌の治療成績は未だ十分といえず, 集学的治療の充実が望まれる。PI3K/AKT/mTOR シグナル経路は様々な成長因子の受容体により活性化され細胞増殖に関与する。胃癌培養細胞に対しPI3K/AKT/mTOR経路の阻害剤投与, 放射線照射, 照射と薬剤投与併用を行い, 細胞生存率, アポトーシスの比率, 細胞周期の変化について測定し, 有効な放射線増感剤を探索した。
薬剤と照射同時投与を行うことで最も高い殺細胞効果が得られ, アポトーシスも多く観察された。細胞周期の検討では, NVP-BEZ235と照射の同時併用においてのみG2/M期とG1期の比が上昇しており, 有効な放射線増感剤と考えられた。
Treatment of gastric cancer in advanced stages is still challenging. More effective anti-tumor radiosensitizing drug is desired to manage systemic disease. PI3K/AKT/ mTOR pathway is one of the important signal cascades which are activated by various growth factor receptors. We selected three PI3K/AKT/ mTOR pathway inhibitors. Treatment effectiveness is assessed by irradiation, drug exposure alone and combination of irradiation and drug in human gastric cell lines. Cell survival was evaluated with colony formation. Apoptosis was evaluated with flow cytometric analyses using AnnexinV-FITC/PI stain. Cell cycle distribution was evaluated using flow cytometric analyses. Concurrent exposure showed larger cytotoxic effect and higher apoptotic rate than the other exposure. The G2/G1 ratio was exclusively increased by concurrent exposure with irradiation and NVP-BEZ235 after 48-hours. NVP-BEZ235 seems to be a promising radiosensitizing drug in terms of arresting cell cycle in G2/M phase.
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研究種目 : 基盤研究(C)
研究期間 : 2012~2014
課題番号 : 24591850
研究分野 : 医学
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