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ALDH-Dependent Glycolytic Activation Mediates Stemness and Paclitaxel Resistance in Patient-Derived Spheroid Models of Uterine Endometrial Cancer
http://hdl.handle.net/10191/00051797
http://hdl.handle.net/10191/000517978385a513-5069-47ff-88dd-702722bfd9c6
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本文 (7.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-08-31 | |||||
| タイトル | ||||||
| タイトル | ALDH-Dependent Glycolytic Activation Mediates Stemness and Paclitaxel Resistance in Patient-Derived Spheroid Models of Uterine Endometrial Cancer | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | ALDH依存性の解糖活性化は子宮内膜がんの患者由来スフェロイドモデルにおいて幹細胞性およびパクリタキセル抵抗性を媒介する | |||||
| 著者 |
Mori, Yutaro
× Mori, Yutaro |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 177998 | |||||
| 姓名 | 森, 裕太郎 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Uterine endometrial cancer is associated with poor survival outcomes in patients with advanced-stage disease. Here, we developed a three-dimensional cell cultivation method of endometrioid cancer stem-like cells with high aldehyde dehydrogenase (ALDH) activity from clinical specimens. ALDH inhibition synergized with paclitaxel to block cancer proliferation. In the clinical setting, high ALDH1A1expression was associated with poor survival. A high level of ALDH correlated with an increase of glucose uptake, activation of the glycolytic pathway, and elevation of glucose transporter 1 (GLUT1). Blockade of GLUT1 inhibited characteristics of cancer stem cells. Similarly to ALDH inhibition, GLUT1 inhibition synergized with paclitaxel to block endometrial cancer proliferation. Our data indicated that ALDH-dependent GLUT1 activation and the resulting glycolytic activation are of clinical importance for both prognostic evaluation and therapeutic decision-making in endometrial cancer patients. In addition, the synergistic effects of taxane-compounds and ALDH or GLUT1 inhibitors may serve as a new clinical treatment option for endometrial cancer. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Stem Cell Reports. 2019, 13(4), 730-746. | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1016/j.stemcr.2019.08.015 | |||||
| 権利 | ||||||
| 権利情報 | 【○!C】 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-03-23 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4674号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博(医)甲第908号 | |||||
