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• W2503089356 abstract "// Wei Chen 1, 2, * , Jiancheng Zhou 3, * , Kaijie Wu 1 , Jun Huang 1 , Ye Ding 4 , Eun-Jin Yun 2 , Bin Wang 1, 2 , Chunyong Ding 4 , Elizabeth Hernandez 2 , John Santoyo 2 , Haiying Chen 4 , Ho Lin 5 , Arthur Sagalowsky 2 , Dalin He 1 , Jia Zhou 4 , Jer-Tsong Hsieh 2, 6 1 Department of Urology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710049, China 2 Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 3 Department of Urology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China 4 Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA 5 Department of Life Sciences, National Chung Hsing University, Taichung 40705, Taiwan 6 Graduate Institute of Cancer Biology, China Medical University Hospital, Taichung 40447, Taiwan * These authors have contributed equally to this work Correspondence to: Jer-Tsong Hsieh, email: jt.hsieh@utsouthwestern.edu Jia Zhou, email: jizhou@utmb.edu Dalin He, email: dalinhe@yahoo.com Keywords: Oridonin, Wnt pathway, β-catenin, XBP1, transitional cell carcinoma Received: May 11, 2016      Accepted: July 01, 2016      Published: July 27, 2016 ABSTRACT Conventional chemotherapy is commonly used for advanced stages of transitional cell carcinoma (TCC) with modest success and high morbidity; however, TCC eventually develops resistance. Muscle invasive bladder cancer (MIBC) is recognized as a lethal disease due to its poor response to traditional chemotherapy. Numerous studies have implicated β-catenin, a critical effector in Wnt–mediated pathway associated with epithelial-mesenchymal transition and cancer stem cell, is involved in TCC progression, and furthermore closely associated with chemo-resistance. In this study, we discovered a novel natural product analogue CYD 6-17 that has a potent inhibitory effect on TCC cells exhibiting drug resistance to various chemotherapeutics, with an IC 50 at nM range. Delivery of CYD 6-17 significantly inhibited the tumor growth using xenograft model but without detectable side effects. Mechanistically, it targeted β-catenin gene transcription by decreasing the binding of XBP1 to the promoter region, which appeared to be a new regulatory mechanism for β-catenin gene expression. Clinically, XBP1 expression correlated with the poor overall survival of patients. Overall, this study unveils unique mechanism of β-catenin gene regulation in advanced TCC and also offers a potential rational therapeutic regimen to MIBC." @default.
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• W2503089356 date "2016-07-27" @default.
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• W2503089356 title "Targeting XBP1-mediated β-catenin expression associated with bladder cancer with newly synthetic Oridonin analogues" @default.
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• W2503089356 doi "https://doi.org/10.18632/oncotarget.10863" @default.
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