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アポトーシス抵抗性に起因する変異型選択的EGFR-TKI耐性克服治療の開発
https://doi.org/10.24517/00057539
https://doi.org/10.24517/00057539cde6e481-df02-4f86-8b68-080666dc0ba3
名前 / ファイル | ライセンス | アクション |
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HO-PR-TAKEUCHI-S-kaken 2021-10p.pdf (545.3 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2022-02-28 | |||||
タイトル | ||||||
タイトル | アポトーシス抵抗性に起因する変異型選択的EGFR-TKI耐性克服治療の開発 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Development of therapy for overcoming resistance to mutant selective EGFR-TKI due to persistance of apoptosis | |||||
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 | 10.24517/00057539 | |||||
ID登録タイプ | JaLC | |||||
著者 |
竹内, 伸司
× 竹内, 伸司 |
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著者別表示 |
Takeuchi, Shinji
× Takeuchi, Shinji |
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書誌情報 |
令和2(2020)年度 科学研究費補助金 基盤研究(B) 研究成果報告書 en : 2020 Fiscal Year Final Research Report 巻 2017-04-01 – 2021-03-31, p. 10p., 発行日 2021-06-21 |
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出版者 | ||||||
出版者 | 金沢大学附属病院がんセンター | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | EGFR変異肺癌において、BIM遺伝子多型を有するとEGFR-TKIによるアポトーシスに抵抗性を示す。本研究では、変異型選択的EGFR-TKIであるOsimertinibの耐性にBIM遺伝子多型が影響するか検討し、HDAC阻害薬であるVorinostatの併用効果について解析を行った。BIM遺伝子多型を有するEGFR変異肺癌細胞はOsimertinibによるアポトーシス誘導に抵抗性を示し、Vorinostat併用によりアポトーシスが誘導されることが明らかになった。さらに、このVorinostatの効果にはHDAC3阻害活性が重要であり、HDAC3選択的阻害薬の開発が有望であることが示唆された。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The BIM deletion polymorphism is associated with apoptosis resistance to EGFR-TKIs, such as gefitinib, in NSCLC harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a mutant selective EGFR-TKI. EGFR-mutated NSCLC cell lines with the BIM deletion polymorphism exhibited apoptosis resistance to osimertinib and this resistance was overcome by combined use with vorinostat in vitro and in vivo. Experiments with homozygous BIM deletion-positive EGFR-mutated NSCLC cells revealed that vorinostat increased the expression of active BIM protein and induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating EGFR-mutated lung cancers carrying the BIM deletion polymorphism. |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:17K09649, 研究期間(年度):2017-04-01 – 2021-03-31 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:「アポトーシス抵抗性に起因する変異型選択的EGFR-TKI耐性克服治療の開発」研究成果報告書 課題番号17K09649 (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-17K09649/17K09649seika/)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=90565384 | |||||
関連名称 | https://kaken.nii.ac.jp/search/?qm=90565384 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K09649/ | |||||
関連名称 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K09649/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K09649/17K09649seika/ | |||||
関連名称 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K09649/17K09649seika/ |