{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:51:15Z","timestamp":1784771475464,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,20]],"date-time":"2016-06-20T00:00:00Z","timestamp":1466380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHD\/0191\/2552"],"award-info":[{"award-number":["PHD\/0191\/2552"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007469","name":"Higher Education Research Promotion","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007469","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,7]]},"abstract":"Expression of CD<\/jats:styled-content>44, especially the variant isoforms (CD<\/jats:styled-content>44v) of this major cancer stem cell marker, contributes to reactive oxygen species (ROS<\/jats:styled-content>) defense through stabilizing xCT<\/jats:styled-content> (a cystine\u2013glutamate transporter) and promoting glutathione synthesis. This enhances cancer development and increases chemotherapy resistance. We investigate the role of CD<\/jats:styled-content>44v in the regulation of the ROS<\/jats:styled-content> defense system in cholangiocarcinoma (CCA<\/jats:styled-content>). Immunohistochemical staining of CD<\/jats:styled-content>44v and p38MAPK<\/jats:sup><\/jats:styled-content> (a major ROS<\/jats:styled-content> target) expression in Opisthorchis viverrini<\/jats:italic>\u2010induced hamster CCA<\/jats:styled-content> tissues (at 60, 90, 120, and 180 days) reveals a decreased phospho\u2010p38MAPK<\/jats:sup><\/jats:styled-content> signal, whereas the CD<\/jats:styled-content>44v signal was increased during bile duct transformation. Patients with CCA<\/jats:styled-content> showed CD<\/jats:styled-content>44v overexpression and negative\u2010phospho\u2010p38MAPK<\/jats:sup><\/jats:styled-content> patients a significantly shorter survival rate than the low CD<\/jats:styled-content>44v signal and positive\u2010phospho\u2010p38MAPK<\/jats:sup><\/jats:styled-content> patients (P =<\/jats:italic> 0.030). Knockdown of CD<\/jats:styled-content>44 showed that xCT<\/jats:styled-content> and glutathione levels were decreased, leading to a high level of ROS<\/jats:styled-content>. We examined xCT<\/jats:styled-content>\u2010targeted CD<\/jats:styled-content>44v cancer stem cell therapy using sulfasalazine. Glutathione decreased and ROS<\/jats:styled-content> increased after the treatment, leading to inhibition of cell proliferation and induction of cell death. Thus, the accumulation of CD<\/jats:styled-content>44v leads to the suppression of p38MAPK<\/jats:sup><\/jats:styled-content> in transforming bile duct cells. The redox status regulation of CCA<\/jats:styled-content> cells depends on the expression of CD<\/jats:styled-content>44v to contribute the xCT<\/jats:styled-content> function and is a link to the poor prognosis of patients. Thus, an xCT<\/jats:styled-content> inhibitor could inhibit cell growth and activate cell death. This suggests that an xCT<\/jats:styled-content>\u2010targeting drug may improve CCA<\/jats:styled-content> therapy by sensitization to the available drug (e.g. gemcitabine) by blocking the mechanism of the cell's ROS<\/jats:styled-content> defensive system.<\/jats:p>","DOI":"10.1111\/cas.12967","type":"journal-article","created":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T15:34:53Z","timestamp":1463153693000},"page":"991-1000","source":"Crossref","is-referenced-by-count":59,"title":["CD44 variant\u2010dependent redox status regulation in liver fluke\u2010associated cholangiocarcinoma: A target for cholangiocarcinoma treatment"],"prefix":"10.1111","volume":"107","author":[{"given":"Malinee","family":"Thanee","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Khon Kaen University Khon Kaen Thailand"},{"name":"Liver Fluke and Cholangiocarcinoma Research Center Faculty of Medicine Khon Kaen University Khon Kaen 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