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悪性グリオーマの浸潤シグナルを狙った分子標的療法の確立
https://doi.org/10.24517/00051723
https://doi.org/10.24517/0005172343c09c54-883c-4f25-b197-436363da30f1
名前 / ファイル | ライセンス | アクション |
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ME-PR-NAKADA-M-kaken 2014-6p.pdf (399.7 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2018-07-20 | |||||
タイトル | ||||||
タイトル | 悪性グリオーマの浸潤シグナルを狙った分子標的療法の確立 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Molecular targeted therapy focusing invasion signaling in malignant glioma cell | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00051723 | |||||
ID登録タイプ | JaLC | |||||
著者 |
中田, 光俊
× 中田, 光俊 |
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著者別表示 |
Nakada, Mitsutoshi
× Nakada, Mitsutoshi |
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書誌情報 |
平成25(2013)年度 科学研究費補助金 基盤研究(C) 研究成果報告書 en : 2013 Fiscal Year Final Research Report 巻 2011-2013, p. 6p., 発行日 2014-05-21 |
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出版者 | ||||||
出版者 | 金沢大学医薬保健研究域医学系 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 本研究では膠芽腫に対するAkt阻害剤、Notch阻害剤の併用療法の有用性とGSK3β阻害によるテモゾロミド(TMZ)薬剤感受性亢進メカニズムを検討した。Akt阻害剤、Notch阻害剤両者の併用により細胞浸潤抑制効果は増強されたが、増殖抑制効果はAkt単独添加と同程度にとどまった。併用療法は増殖抑制には効果が少ないが浸潤抑制には効果的であることが示唆された。TMZとGSK3β阻害試薬の併用は相加的、相乗的な細胞増殖抑制効果を示した。GSK3β阻害によるTMZに対する膠芽腫細胞の感受性増強作用は、c-Mycを介してMGMT promoterのメチル化が促進されることを明らかにした。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | We assessed the therapeutic possibility of inhibiting Notch and Akt in gliomas using the clinically available, selective small molecule inhibitors. Additionally, we investigated the molecular mechanisms of sensitization of glioblastoma (GBM) cells to temozolomide (TMZ) by GSK3beta inhibition. Notch and Akt inhibitors significantly inhibited cell growth, migration, and invasion in a dose-dependent manner. However, the effect of combination treatment did not exceed that of Akt inhibitor monotherapy in proliferation assay. Inhibition of invasion, further enhanced by combination therapy. Therefore, combination therapy may be effective for inhibiting invasion but not proliferation. GSK3beta inhibition enhanced TMZ effect. c-Myc binds to the MGMT promoter with consequent recruitment of DNMT3A, regulating the levels of MGMT promoter methylation. Therefore, GSK3beta inhibition enhances TMZ effect by silencing MGMT expression via c-Myc-mediated promoter methylation. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:23592117, 研究期間(年度):2011-2013 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:研究課題「悪性グリオーマの浸潤シグナルを狙った分子標的療法の確立」課題番号23592117 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) (https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23592117/23592117seika/)を加工して作成 |
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著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/search/?qm=20334774 | |||||
関連名称 | https://kaken.nii.ac.jp/search/?qm=20334774 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592117/ | |||||
関連名称 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592117/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23592117/23592117seika/ | |||||
関連名称 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23592117/23592117seika/ |