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• W2075489670 abstract "No AccessJournal of UrologyInvestigative Urology1 Apr 2013HMGB1 Release by Urothelial Carcinoma Cells is Required for the In Vivo Antitumor Response to Bacillus Calmette-Guérin Guangjian Zhang, Fanghong Chen, Yanli Cao, Bryon Johnson, and William A. See Guangjian ZhangGuangjian Zhang More articles by this author , Fanghong ChenFanghong Chen More articles by this author , Yanli CaoYanli Cao More articles by this author , Bryon JohnsonBryon Johnson More articles by this author , and William A. SeeWilliam A. See More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.09.123AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Prior series showed that a portion of urothelial carcinoma cells exposed to bacillus Calmette-Guérin undergoes nonapoptotic cell death and release of the chemokine HMGB1. We evaluated the role of tumor cell derived HMGB1 in mediating the in vivo antitumor effect of bacillus Calmette-Guérin. Materials and Methods: The murine urothelial carcinoma cell line MB49 was engineered to express a shRNA construct targeting HMGB1. The shRNA expressing cell line underwent characterization to ensure its comparability to the parental MB49 cell line. An orthotopic tumor model was used to compare the in vivo antitumor efficacy of bacillus Calmette-Guérin in the parental cell line (24 control and 24 bacillus Calmette-Guérin treated) vs the HMGB1 knockdown line (23 control and 21 treated). Results: Expression of the shRNA construct decreased HMGB1 expression and its release in response to bacillus Calmette-Guérin. The parental and shRNA cell lines showed similar in vitro doubling time and cytotoxicity in response to bacillus Calmette-Guérin. Treatment significantly decreased tumor volume vs controls in parental MB49 tumor bearing mice (p = 0.036). Tumor volume in treated mice inoculated with the shRNA cell line was higher than that in sham treated shRNA controls (p = 0.12). Of the bacillus Calmette-Guérin treated mice tumor volume was significantly lower in parental tumor bearing mice vs the shRNA group (p <0.00001). ANOVA revealed a significant interaction between the cell line (shRNA vs parental) and the bacillus Calmette-Guérin effect (p = 0.0076). Conclusions: The direct tumor response to bacillus Calmette-Guérin, culminating in HMGB1 release, may be an important contributor to the clinical efficacy of bacillus Calmette-Guérin. References 1 : EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol2011; 59: 997. Google Scholar 2 : Canadian guidelines for treatment of non-muscle invasive bladder cancer: a focus on intravesical therapy. Can J Urol2010; 4: 168. 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Link, Google Scholar Departments of Urology and Pediatrics (BJ), Medical College of Wisconsin, Milwaukee, Wisconsin© 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byShah G, Zhang G, Chen F, Cao Y, Kalyanaraman B and See W (2018) Loss of Bacillus Calmette-Guérin Viability Adversely Affects the Direct Response of Urothelial Carcinoma Cells to Bacillus Calmette-Guérin ExposureJournal of Urology, VOL. 191, NO. 3, (823-829), Online publication date: 1-Mar-2014.Zhang G, Chen F, Cao Y, Amos J, Shah G and See W (2018) HMGB1 Release by Urothelial Carcinoma Cells in Response to Bacillus Calmette-Guérin Functions as a Paracrine Factor to Potentiate the Direct Cellular Effects of Bacillus Calmette-GuérinJournal of Urology, VOL. 190, NO. 3, (1076-1082), Online publication date: 1-Sep-2013.Zhang G, Chen F, Cao Y and See W (2018) Contributors to HMGB1 Release by Urothelial Carcinoma Cells in Response to Bacillus Calmette-GuérinJournal of Urology, VOL. 190, NO. 4, (1398-1403), Online publication date: 1-Oct-2013. Volume 189Issue 4April 2013Page: 1541-1546 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsurinary bladderHMGB1 proteinBCG vaccinecarcinomaurotheliumAcknowledgmentsDr. Timothy Ratliff, Purdue University Center for Cancer Research, provided the MB49 cell line.MetricsAuthor Information Guangjian Zhang More articles by this author Fanghong Chen More articles by this author Yanli Cao More articles by this author Bryon Johnson More articles by this author William A. See More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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