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dc.contributor.authorKijima, Takashi
dc.contributor.authorNakagawa, Hiroshi
dc.contributor.authorShimonosono, Masataka
dc.contributor.authorChandramouleeswaran, Prasanna M.
dc.contributor.authorHara, Takeo
dc.contributor.authorSahu, Varun
dc.contributor.authorKasagi, Yuta
dc.contributor.authorKikuchi, Osamu
dc.contributor.authorTanaka, Koji
dc.contributor.authorGiroux, Veronique
dc.contributor.authorMuir, Amanda B.
dc.contributor.authorWhelan, Kelly A.
dc.contributor.authorOhashi, Shinya
dc.contributor.authorNaganuma, Seiji
dc.contributor.authorKlein-Szanto, Andres J.
dc.contributor.authorShinden, Yoshiaki
dc.contributor.authorSasaki, Ken
dc.contributor.authorOmoto, Itaru
dc.contributor.authorKita, Yoshiaki
dc.contributor.authorMuto, Manabu
dc.contributor.authorBass, Adam J.
dc.contributor.authorDiehl, J. Alan
dc.contributor.authorGinsberg, Gregory G.
dc.contributor.authorDoki, Yuichiro
dc.contributor.authorMori, Masaki
dc.contributor.authorUchikado, Yasuto
dc.contributor.authorArigami, Takaaki
dc.contributor.authorAvadhani, Narayan G.
dc.contributor.authorBasu, Devraj
dc.contributor.authorRustgi, Anil K.
dc.contributor.authorNatsugoe, Shoji
dc.contributor.alternative貴島, 孝
dc.contributor.alternative下之薗, 将貴
dc.contributor.alternative原, 豪男
dc.contributor.alternative菊池, 理
dc.contributor.alternative田中, 晃司
dc.contributor.alternative大橋, 真也
dc.contributor.alternative長沼, 誠二
dc.contributor.alternative新田, 吉陽
dc.contributor.alternative佐々木, 健
dc.contributor.alternative尾本, 至
dc.contributor.alternative喜多, 芳昭
dc.contributor.alternative武藤, 学
dc.contributor.alternative土岐, 祐一郎
dc.contributor.alternative森, 正樹
dc.contributor.alternative内門, 泰斗
dc.contributor.alternative有上, 貴明
dc.contributor.alternative夏越, 祥次
dc.date.accessioned2020-03-26T02:29:52Z-
dc.date.available2020-03-26T02:29:52Z-
dc.date.issued2019
dc.identifier.issn2352-345X
dc.identifier.urihttp://hdl.handle.net/2433/246431-
dc.description.abstractBackground & 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.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherElsevier BV
dc.rights© 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/).
dc.subject3D Organoids
dc.subjectAutophagy
dc.subjectCD44
dc.subject5-Fluorouracil
dc.titleThree-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells
dc.type.niitypeJournal Article
dc.identifier.jtitleCellular and Molecular Gastroenterology and Hepatology
dc.identifier.volume7
dc.identifier.issue1
dc.identifier.spage73
dc.identifier.epage91
dc.relation.doi10.1016/j.jcmgh.2018.09.003
dc.textversionpublisher
dc.identifier.pmid30510992
dc.identifier.kaken17H04285 / 15K10108
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