| ○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): |
| ○学究種別 (推奨): |
| ○組織 (推奨): | 1. | 徳島大学.医学部.医学科.生体防御腫瘍医学講座.呼吸器・膠原病内科学分野
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| ○著者 (必須): | 1. | (英) Kuramoto Takuya (日) (読)
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| 2. | 後東 久嗣
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| 3. | (英) Mitsuhashi Atsushi (日) (読)
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| 4. | (英) Tabata Sho (日) (読)
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| 5. | 小川 博久 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.疾患病理学])
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| 6. | 上原 久典 ([徳島大学.病院.診療科.病理診断科])
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| 7. | 西條 敦郎
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| 8. | 柿内 聡司
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| 9. | 前川 洋一
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| 10. | 安友 康二 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.生体防御医学])
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| ○貢献度 (任意): |
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| 11. | 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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| 12. | 秋山 伸一
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| 13. | 曽根 三郎
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| 14. | 西岡 安彦 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.呼吸器・膠原病内科学])
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| ○題名 (必須): | □ | (英) Dll4-Fc, an inhibitor of Dll4-Notch signaling, suppresses liver metastasis of small cell lung cancer cells through down-regulation of NF-kappa-B activity (日)
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| ○副題 (任意): |
| ○要約 (任意): | □ | (英) Notch signaling regulates cell-fate decisions during development and postnatal life. Little is known, however, about the role of Delta-like-4 (Dll4)-Notch signaling between cancer cells, or how this signaling affects cancer metastasis. We, therefore, assessed the role of Dll4-Notch signaling in cancer metastasis. We generated a soluble Dll4 fused to the IgG1 constant region (Dll4-Fc) that acts as a blocker of Dll4-Notch signaling and introduced it into human small cell lung cancer (SCLC) cell lines expressing either high levels (SBC-3 and H1048) or low levels (SBC-5) of Dll4. The effects of Dll4-Fc on metastasis of SCLC were evaluated using a mouse model. Although Dll4-Fc had no effect on the liver metastasis of SBC-5, the number of liver metastasis inoculated with SBC-3 and H1048 cells expressing Dll4-Fc was significantly lower than that injected with control cells. To study the molecular mechanisms of the effects of Dll4-Fc on liver metastasis, a PCR array analysis was conducted. Because the expression of NF-κB target genes was affected by Dll4-Fc, we conducted an electrophoretic mobility shift assay and observed that NF-κB activities, both with and without stimulation by TNF-α, were downregulated in Dll4-Fc-overexpressing SBC-3 and H1048 cells compared with control cells. Moreover, Dll4-Fc attenuates, at least in part, the classical and alternative NF-κB activation pathway by reducing Notch1 signaling. These results suggest that Dll4-Notch signaling in cancer cells plays a critical role in liver metastasis of SCLC by regulating NF-κB signaling. (日)
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| ○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | アポトーシス (apoptosis)
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| 3. | (英) Cell Growth Processes (日) (読)
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| 4. | (英) Cell Movement (日) (読)
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| 5. | (英) Down-Regulation (日) (読)
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| 6. | (英) Humans (日) (読)
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| 7. | (英) Liver Neoplasms, Experimental (日) (読)
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| 8. | (英) Lung Neoplasms (日) (読)
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| 9. | (英) Male (日) (読)
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| 10. | (英) Mice (日) (読)
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| 11. | (英) Mice, SCID (日) (読)
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| 12. | (英) NF-kappa B (日) (読)
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| 13. | (英) Receptors, Notch (日) (読)
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| 14. | (英) Recombinant Fusion Proteins (日) (読)
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| 15. | シグナル伝達 (signal transduction)
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| 16. | (英) Small Cell Lung Carcinoma (日) (読)
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| 17. | (英) Transfection (日) (読)
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| 18. | (英) Xenograft Model Antitumor Assays (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Molecular Cancer Therapeutics ([American Association for Cancer Research])
(pISSN: 1535-7163, eISSN: 1538-8514)
| ○ISSN (任意): | □ | 1538-8514
ISSN: 1535-7163
(pISSN: 1535-7163, eISSN: 1538-8514) Title: Molecular cancer therapeuticsTitle(ISO): Mol Cancer TherPublisher: American Association for Cancer Research (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 11
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| ○号 (必須): | □ | 12
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| ○頁 (必須): | □ | 2578 2587
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2012年 9月 18日 (平成 24年 9月 18日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1158/1535-7163.MCT-12-0640 (→Scopusで検索)
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| ○PMID (任意): | □ | 22989420 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): | □ | 000312012800004
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| ○Scopus (任意): |
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| ○指導教員 (推奨): |
| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1158/1535-7163.MCT-12-0640 (日)
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| 2. | (英) Article.Affiliation: Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan. (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 4. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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