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スニチニプ耐性腎細胞癌に対する新世代mTOR阻害剤Rapalink-1の新規治療効果の可能牲
http://hdl.handle.net/10232/00031724
http://hdl.handle.net/10232/00031724fb40f2cf-5d7b-4f19-bde6-4146fdd109fb
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Diss_黒島_和樹_ISK591_2020 (2.0 MB)
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Result_Kuroshima_Kazuki_isk_591 (223.3 kB)
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Comments_Kuroshima_Kazuki_isk_591 (99.8 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-04-14 | |||||
| タイトル | ||||||
| タイトル | Potential new therapy of Rapalink-1, a new generation mTOR inhibitor, against sunitinib-resistant renal cell carcinoma. | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| タイトル | スニチニプ耐性腎細胞癌に対する新世代mTOR阻害剤Rapalink-1の新規治療効果の可能牲 | |||||
| タイトル言語 | ja | |||||
| 著者 |
黒島, 和樹
× 黒島, 和樹 |
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| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | mTOR inhibitor | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Rapalink-1 | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | renal cell carcinoma | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | sunitinib resistance | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | temsirolimus | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Sunitinib, a multitargeted receptor tyrosine kinase inhibitor including vascular endothelial growth factor, has been widely used as a first-line treatment against metastatic renal cell carcinoma (mRCC). However, mRCC often acquires resistance to sunitinib, rendering it difficult to treat with this agent. Recently, Rapalink-1, a drug that links rapamycin and the mTOR kinase inhibitor MLN0128, has been developed with excellent therapeutic effects against breast cancer cells carrying mTOR resistance mutations. The aim of the present study was to evaluate the in vitro and in vivo therapeutic efficacy of Rapalink-1 against renal cell carcinoma (RCC) compared to temsirolimus, which is commonly used as a small molecule inhibitor of mTOR and is a derivative of rapamycin. In comparison with temsirolimus, Rapalink-1 showed significantly greater effects against proliferation, migration, invasion and cFolony formation in sunitinib-naïve RCC cells. Inhibition was achieved through suppression of the phosphorylation of substrates in the mTOR signal pathway, such as p70S6K, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and AKT. In addition, Rapalink-1 had greater tumor suppressive effects than temsirolimus against the sunitinib-resistant 786-o cell line (SU-R 786-o), which we had previously established, as well as 3 additional SU-R cell lines established here. RNA sequencing showed that Rapalink-1 suppressed not only the mTOR signaling pathway but also a part of the MAPK signaling pathway, the ErbB signaling pathway and ABC transporters that were associated with resistance to several drugs. Our study suggests the possibility of a new treatment option for patients with RCC that is either sunitinib-sensitive or sunitinib-resistant. Kazuki Kuroshima, Hirofumi Yoshino, Shunsuke Okamura, Masafumi Tsuruda, Yoichi Osako, Takashi Sakaguchi, Satoshi Sugita, Shuichi Tatarano, Masayuki Nakagawa, Hideki Enokida Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against sunitinib-resistant renal cell carcinoma Cancer Science 2020 111(5) p.1607-1618 https://doi.org/10.1111/cas.14395 |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2021-03-10 | |||||
| 日付タイプ | Collected | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| NDC | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 490 | |||||
| ファイル（説明） | ||||||
| 内容記述 | 博士論文全文, 最終試験結果の要旨, 論文審査の要旨 | |||||
| 公開者・出版者 | ||||||
| 出版者 | Wiley | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 公開者・出版者 | ||||||
| 出版者 | カゴシマ ダイガク | |||||
| 出版者言語 | ja-Kana | |||||
| 備考 | ||||||
| 備考 | 【指導教員:中川昌之】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2020-08-05 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 学位授与機関名 | 鹿児島大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2021-03-17 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲総研第591号 | |||||
