| Item type |
文献 / Documents(1) |
| 公開日 |
2021-10-13 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1111/cas.15041 |
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関連名称 |
10.1111/cas.15041 |
| 出版タイプ |
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出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
The BAFF/NFκB axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts |
| タイトル別表記 |
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その他のタイトル |
BAFF/NFκB経路はソラフェニブ耐性肝癌と癌関連線維芽細胞の相互作用に重要である |
| 著者 |
高, 露萍
森根, 裕二
山田, 眞一郎
齋藤, 裕
池本, 哲也
トクダ, カズノリ
宮崎, 克己
オキカワ, ショウヘイ
髙須, 千絵
島田, 光生
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| 抄録 |
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内容記述 |
The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7SR) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7SR-co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NFκB-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7SR cells, the previously increased malignancy and BAFF/NFκB axis in Huh7SR-co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NFκB pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NFκB axis in CAFs might be a potential therapeutic target in chemoresistance of HCC. |
| キーワード |
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|
主題 |
B-cell activating factor |
| キーワード |
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主題 |
cancer-associated fibroblasts |
| キーワード |
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|
主題 |
hepatocellular carcinoma |
| キーワード |
|
|
主題 |
drug resistance |
| キーワード |
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主題 |
sorafenib |
| 書誌情報 |
en : Cancer Science
巻 112,
号 9,
p. 3545-3554,
発行日 2021-06-22
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
13497006 |
| 出版者 |
|
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出版者 |
Wiley |
| 出版者 |
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出版者 |
Japanese Cancer Association |
| 備考 |
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|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Luping Gaoの学位論文として提出され，学位審査・授与の対象となっている。
学位授与者所属 : 徳島大学大学院医科学教育部（医学専攻） |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| EID |
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識別子 |
386674 |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3558号 |
| 学位記番号 |
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値 |
甲医第1511号 |
| 学位授与年月日 |
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学位授与年月日 |
2021-09-30 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関名 |
徳島大学 |
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