| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○招待 (推奨): |
| ○審査 (推奨): |
| ○カテゴリ (推奨): |
| ○共著種別 (推奨): | □ | 徳島大学以外での国際共著 (徳島大学以外での複数の国の研究機関による共同研究)
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Ho Jeong Lee (日) (読)
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| 2. | 埴淵 昌毅 ([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域呼吸器・血液・代謝内科学])
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| 3. | (英) Sun-Jin Kim (日) (読)
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| 4. | (英) Yu Hyunkyung (日) (読)
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| 5. | (英) Mark Seungwook Kim (日) (読)
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| 6. | (英) Junqin He (日) (読)
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| 7. | (英) Robert R. Langley (日) (読)
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| 8. | (英) Francois Lehembre (日) (読)
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| 9. | (英) Urs Regenass (日) (読)
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| 10. | (英) Isaiah J. Fidler (日) (読)
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| ○題名 (必須): | □ | (英) Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel (日)
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| ○副題 (任意): |
| ○要約 (任意): | □ | (英) We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. (日)
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| ○キーワード (推奨): |
| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Neuro-Oncology (Society for Neuro-Oncology)
(pISSN: 1522-8517, eISSN: 1523-5866)
| ○ISSN (任意): | □ | 1523-5866
ISSN: 1522-8517
(pISSN: 1522-8517, eISSN: 1523-5866) Title: Neuro-oncologyTitle(ISO): Neuro OncolPublisher: Oxford University Press (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 18
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| ○号 (必須): | □ | 4
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| ○頁 (必須): | □ | 486 496
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2016年 4月 初日 (平成 28年 4月 初日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1093/neuonc/now037 (→Scopusで検索)
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| ○PMID (任意): | □ | 26995790 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS : | □ | 000372503100005
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| ○Scopus (任意): | 1. | 2-s2.0-84966533797
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1093/neuonc/now037 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, N.I.H., Extramural (日)
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| 4. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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| 5. | (英) OtherID: PMC4799693 [Available on 04/01/17] (日)
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| 6. | (英) KeywordList.Keyword: astrocytes (日)
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| 7. | (英) KeywordList.Keyword: brain metastases (日)
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| 8. | (英) KeywordList.Keyword: endothelial cells (日)
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| 9. | (英) KeywordList.Keyword: endothelin (日)
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| 10. | (英) KeywordList.Keyword: macitentan (日)
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