| ○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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| ○カテゴリ (推奨): |
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | 中川 忠彦
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| ○学籍番号 (推奨): | □ | ****
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| 2. | 佐藤 康史 ([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).地域消化器・総合内科学])
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| 3. | 棚橋 俊仁
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| 4. | 三井 康裕 ([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[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.消化器内科学])
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| ○学籍番号 (推奨): | □ | ****
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| 5. | 喜田 慶史 ([徳島大学.大学院医歯薬学研究部.医学域.先端臨床医学教育研究プロジェクト]/[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.消化器内科学])
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| ○学籍番号 (推奨): | □ | ****
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| 6. | 藤野 泰輝
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| ○学籍番号 (推奨): | □ | ****
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| 7. | (英) Hirata Misato (日) (読)
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| 8. | 北村 晋志
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| 9. | 宮本 弘志 ([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.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])
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| 10. | 岡本 耕一 ([徳島大学.病院.診療科.内科.消化器内科])
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| 11. | 六車 直樹
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| 12. | 坂東 良美 ([徳島大学.病院.診療科.病理診断科])
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| 13. | 高山 哲治 ([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.消化器内科学])
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| ○題名 (必須): | □ | (英) JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8. (日)
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| ○要約 (任意): | □ | (英) Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC. We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation. Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1. Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target. (日)
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| ○キーワード (推奨): |
| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Gastric Cancer (International Gastric Cancer Association/Japanese Gastric Cancer Association)
(pISSN: 1436-3291, eISSN: 1436-3305)
| ○ISSN (任意): | □ | 1436-3305
ISSN: 1436-3291
(pISSN: 1436-3291, eISSN: 1436-3305) Title: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer AssociationTitle(ISO): Gastric CancerPublisher: Springer (NLM Catalog)
(医中誌Web)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 23
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| ○号 (必須): | □ | 3
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| ○頁 (必須): | □ | 426 436
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2020年 5月 初日 (令和 2年 5月 初日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1007/s10120-019-01024-9 (→Scopusで検索)
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| ○PMID (任意): | □ | 31677131 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): |
| ○Scopus (任意): | □ | 2-s2.0-85074813194
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1007/s10120-019-01024-9 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) KeywordList.Keyword: Coiled-coil domain containing 8 (CCDC8) (日)
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| 4. | (英) KeywordList.Keyword: Drug resistance (日)
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| 5. | (英) KeywordList.Keyword: Gastric cancer (日)
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| 6. | (英) KeywordList.Keyword: Histone lysine demethylases (日)
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| 7. | (英) KeywordList.Keyword: Jumonji domain-containing protein 2A (JMJD2A) (日)
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