@article{e1bf83adb8fa4a2fad06c46ecb3aa39d,
title = "High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma",
abstract = "Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells{\textquoteright} stemness properties in vitro and in vivo. Results: The authors{\textquoteright} data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo. Conclusions: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient{\textquoteright}s clinical outcomes in the future.",
author = "Lin, {Cheng Han} and Li, {Hao Yi} and Liu, {Yu Peng} and Kuo, {Pei Fung} and Wang, {Wen Ching} and Lin, {Forn Chia} and Chang, {Wei Lun} and Sheu, {Bor Shyang} and Wang, {Yi Ching} and Hung, {Wan Chun} and Cheng, {Hui Chuan} and Yao, {Yun Chin} and Calkins, {Marcus J.} and Michael Hsiao and Lu, {Pei Jung}",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by the Ministry of Science and Technology, R.O.C. (MOST 105-2320-B-006-054, MOST 106-2320-B-006-066-MY3) to Pei-Jung Lu, and supported by Academia Sinica and Ministry of Science and Technology [MOST 106-0210-01-15-02, MOST 107-0210-01-19-01] to Michael Hsiao. Funding Information: Cheng-Han Lin and Hao-Yi Li contributed equally to this work. We thank the proteomics core facility of the Clinical Medicine Research Center at National Cheng Kung University Hospital for assisting with protein expression experiment processing. We are also grateful to Dr. Kuen-Jer Tsai and Ya-Chun Hsiao for the services of the image acquiring and analyzing in the Center of Clinical Medicine, National Cheng Kung University Hospital. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by the Ministry of Science and Technology, R.O.C. (MOST 105-2320-B-006-054, MOST 106-2320-B-006-066-MY3) to Pei-Jung Lu, and supported by Academia Sinica and Ministry of Science and Technology [MOST 106-0210-01-15-02, MOST 107-0210-01-19-01] to Michael Hsiao. Publisher Copyright: {\textcopyright} The Author(s), 2019.",
year = "2019",
doi = "10.1177/1758835919875324",
language = "English",
volume = "11",
journal = "Therapeutic Advances in Medical Oncology",
issn = "1758-8340",
publisher = "SAGE Publications Inc.",
}