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j.jcmgh.2018.09.003.pdf | 4.81 MB | Adobe PDF | 見る/開く |
タイトル: | Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells |
著者: | Kijima, Takashi Nakagawa, Hiroshi Shimonosono, Masataka Chandramouleeswaran, Prasanna M. Hara, Takeo Sahu, Varun Kasagi, Yuta Kikuchi, Osamu https://orcid.org/0000-0001-5012-5897 (unconfirmed) Tanaka, Koji Giroux, Veronique Muir, Amanda B. Whelan, Kelly A. Ohashi, Shinya Naganuma, Seiji Klein-Szanto, Andres J. Shinden, Yoshiaki Sasaki, Ken Omoto, Itaru Kita, Yoshiaki Muto, Manabu https://orcid.org/0000-0002-3127-8203 (unconfirmed) Bass, Adam J. Diehl, J. Alan Ginsberg, Gregory G. Doki, Yuichiro Mori, Masaki Uchikado, Yasuto Arigami, Takaaki Avadhani, Narayan G. Basu, Devraj Rustgi, Anil K. Natsugoe, Shoji |
著者名の別形: | 貴島, 孝 下之薗, 将貴 原, 豪男 菊池, 理 田中, 晃司 大橋, 真也 長沼, 誠二 新田, 吉陽 佐々木, 健 尾本, 至 喜多, 芳昭 武藤, 学 土岐, 祐一郎 森, 正樹 内門, 泰斗 有上, 貴明 夏越, 祥次 |
キーワード: | 3D Organoids Autophagy CD44 5-Fluorouracil |
発行日: | 2019 |
出版者: | Elsevier BV |
誌名: | Cellular and Molecular Gastroenterology and Hepatology |
巻: | 7 |
号: | 1 |
開始ページ: | 73 |
終了ページ: | 91 |
抄録: | Background & Aims: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas. Methods: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo. Results: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment. Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine. |
著作権等: | © 2019 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
URI: | http://hdl.handle.net/2433/246431 |
DOI(出版社版): | 10.1016/j.jcmgh.2018.09.003 |
PubMed ID: | 30510992 |
出現コレクション: | 学術雑誌掲載論文等 |
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