| ○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): | □ | 学内共著 (徳島大学内研究者との共同研究 (学外研究者を含まない))
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| ○学究種別 (推奨): |
| ○組織 (推奨): |
| ○著者 (必須): | 1. | 友成 哲 ([徳島大学.病院.先端医科医療開発研究プロジェクト]/[徳島大学.病院.診療科.内科.消化器内科])
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| ○学籍番号 (推奨): |
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| 2. | 武石 俊作
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| 3. | 谷口 達哉
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| 4. | (英) Tanaka Takahiro (日) (読)
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| 5. | (英) Tanaka Hironori (日) (読)
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| 6. | (英) Fujimoto Shota (日) 藤本 将太 (読) ふじもと しょうた
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| ○学籍番号 (推奨): | □ | ****
| [ユーザ] |
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| 7. | 木村 哲夫
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| 8. | 岡本 耕一 ([徳島大学.病院.診療科.内科.消化器内科])
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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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| ○学籍番号 (推奨): |
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| 10. | 六車 直樹
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| 11. | 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) MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma (日)
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| ○副題 (任意): |
| ○要約 (任意): | □ | (英) The mechanism of resistance of hepatocellular carcinoma (HCC) to sorafenib is unknown and no useful predictive biomarker for sorafenib treatment has been reported. Accordingly, we established sorafenib-resistant HCC cells and investigated the underlying mechanism of resistance to sorafenib. Sorafenib-resistant cell lines were established from the HCC cell line PLC/PRF5 by cultivation under continuous exposure to increasing concentration of sorafenib. The IC50 values of the 2 resistant clones PLC/PRF5-R1 and PLC-PRF5-R2 were 9.2±0.47 M (1.8-fold) and 25±5.1 M (4.6-fold) respectively, which were significantly higher than that of parental PLC/PRF5 cells (5.4±0.17 M) (p < 0.01 respectively), as determined by MTT assay. Western blot analysis of signal transduction-related proteins showed no significant differences in expression of AKT/pAKT, mTOR/pmTOR, or ERK/pERK between the 2 resistant clones versus parent cells, suggesting no activation of an alternative signal transduction pathway. Likewise, when expression of membrane transporter proteins was determined, there were no significant differences in expression levels of BSEP, MDR1, MRP2, BCRP, MRP4 and OCT1 between resistant clones and parent cells. However, the expression levels of MRP3 in the 2 resistant clones were significantly higher than that of parent cells. When MRP3 gene was knocked down by siRNA in PLC-PRF5-R2 cells, the sensitivity of the cells to sorafenib was restored. In the analysis of gene mutation, there was no mutation in the activation segment of Raf1 kinase in the resistant clones. Our data clearly demonstrate that the efflux transporter MRP3 plays an important role in resistance to sorafenib in HCC cells. (日)
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| ○キーワード (推奨): |
| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Oncotarget (Impact Journals)
(eISSN: 1949-2553)
| ○ISSN (任意): | □ | 1949-2553
ISSN: 1949-2553
(eISSN: 1949-2553) Title: OncotargetTitle(ISO): OncotargetPublisher: Impact Journals LLC (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 7
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| ○号 (必須): | □ | 6
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| ○頁 (必須): | □ | 7207 7215
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2016年 1月 12日 (平成 28年 1月 12日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.18632/oncotarget.6889 (→Scopusで検索)
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| ○PMID (任意): | □ | 26769852 (→Scopusで検索)
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| ○CRID (任意): |
| ○WOS (任意): | □ | 000376123100061
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| ○Scopus (任意): | □ | 2-s2.0-84981164782
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| ○機関リポジトリ : | □ | 113043
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| ○評価値 (任意): |
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| ○指導教員 (推奨): |
| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.18632/oncotarget.6889 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) KeywordList.Keyword: MRP3 (日)
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| 4. | (英) KeywordList.Keyword: hepatocellular carcinoma (日)
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| 5. | (英) KeywordList.Keyword: resistance (日)
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| 6. | (英) KeywordList.Keyword: sorafenib (日)
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| 7. | (英) KeywordList.Keyword: transporter (日)
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