| ○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. | (英) Kubo Tomohiro (日) (読)
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| 2. | (英) Kawano Yutaka (日) (読)
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| 3. | (英) Himuro Nobuaki (日) (読)
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| 4. | (英) Sugita Shintaro (日) (読)
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| 5. | 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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| 6. | (英) Ishikawa Kazuma (日) (読)
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| 7. | (英) Takada Kohichi (日) (読)
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| 8. | (英) Murase Kazuyuki (日) (読)
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| 9. | (英) Miyanishi Koji (日) (読)
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| 10. | (英) Sato Tsutomu (日) (読)
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| 11. | (英) Takimoto Rishu (日) (読)
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| 12. | (英) Kobune Masayoshi (日) (読)
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| 13. | (英) Nobuoka Takayuki (日) (読)
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| 14. | (英) Hirata Koichi (日) (読)
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| 15. | 高山 哲治
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| 16. | (英) Mori Mitsuru (日) (読)
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| 17. | (英) Hasegawa Tadashi (日) (読)
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| 18. | (英) Kato Junji (日) (読)
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| ○題名 (必須): | □ | (英) BAK is a predictive and prognostic biomarker for the therapeutic effect of docetaxel treatment in patients with advanced gastric cancer. (日)
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| ○要約 (任意): | □ | (英) Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes. Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed. BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values 3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002). BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy. (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): | □ | 1436-3291
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)
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(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 19
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| ○号 (必須): | □ | 3
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| ○頁 (必須): | □ | 827 837
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2016年 6月 初日 (平成 28年 6月 初日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1007/s10120-015-0557-1 (→Scopusで検索)
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| ○PMID (任意): | □ | 26486506 (→Scopusで検索)
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| ○CRID (任意): |
| ○Scopus (任意): | 1. | 2-s2.0-84944937274
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| ○備考 (任意): | 1. | (英) Article.PublicationTypeList.PublicationType: JOURNAL ARTICLE (日)
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| 2. | (英) KeywordList.Keyword: BAK (日)
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| 3. | (英) KeywordList.Keyword: BH3 (日)
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| 4. | (英) KeywordList.Keyword: Docetaxel (日)
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| 5. | (英) KeywordList.Keyword: Gastric cancer (日)
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