EFFECTS OF ACETYLIC SALICYLIC ACID AND PENTOXIFYLLINE ON THE EFFICACY OF INTRAVESICAL BCG THERAPY IN ORTHOTOPIC MURINE BLADDER CANCER (MB49)

Abstract

No AccessJournal of UrologyInvestigative Urology1 May 1999EFFECTS OF ACETYLIC SALICYLIC ACID AND PENTOXIFYLLINE ON THE EFFICACY OF INTRAVESICAL BCG THERAPY IN ORTHOTOPIC MURINE BLADDER CANCER (MB49) J-H. GUNTHER, M. FRAMBACH, I. DEINERT, S. BRANDAU, D. JOCHAM, and A. BOHLE J-H. GUNTHERJ-H. GUNTHER , M. FRAMBACHM. FRAMBACH , I. DEINERTI. DEINERT , S. BRANDAUS. BRANDAU , D. JOCHAMD. JOCHAM , and A. BOHLEA. BOHLE View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)69008-8AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), which has become the gold standard in the adjuvant treatment of superficial bladder cancer, is hampered by local side effects. Anti-inflammatory drugs may be helpful, but as an undesired side effect, therapeutic efficacy of BCG might be impaired. Therefore, we investigated the effects of anti-inflammatory drugs on the efficacy of intravesical BCG in an animal model. Materials and Methods: Syngenic tumor cells were implanted into the bladders of 75 mice according to our modification of the method. Mice were randomized to 5 groups with 15 animals each and treated with phosphate buffered saline (PBS), group 1; BCG, group 2; BCG + acetylic salicylic acid (ASA), group 3; BCG + pentoxifylline (POF), group 4; autoclaved BCG (aBCG), group 5. Intravesical instillation of 1.35 mg. BCG was initiated one day after tumor inoculation and repeated in weekly intervals for 4 instillations altogether. ASA and POF in doses of 200 mg./kg. and 150 mg./kg., respectively, were given continuously with the drinking water starting at the first instillation. Autoclaved BCG served as control for the importance of viability and was given at the same dose as viable BCG. Mice were monitored for survival, gross hematuria and body weight and after 28 days evaluated for bladder weight and tumor occurrence. Results: Autoclaved BCG and PBS had no effect on tumor growth, whereas animals treated with viable BCG alone and in combination with POF and ASA, respectively, showed a significant reduction in bladder weight: PBS, 248 mg.; BCG, 140 mg. (p = 0.0009); BCG + ASA, 123 mg. (p = 0.0001); BCG + POF, 145 mg. (p = 0.0004); autoclaved BCG, 283 mg. (p = 0.21). Mice treated with BCG, BCG + ASA and BCG + POF showed a significantly higher proportion of survival until day 28 as compared to PBS alone. Autoclaved BCG had no therapeutic efficacy (Kaplan-Meier method/log rank test: BCG, p = 0.0053; BCG + ASA, p = 0.0044; BCG + POF, p = 0.0027; aBCG, p = 0.33). No significant differences among the 3 groups treated with viable BCG, with or without anti-inflammatory drugs, regarding bladder weight and survival were detectable. 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Google Scholar From the Department of Urology, Medical University of Lubeck, and the Department of Immunology and Cell Biology, Research Center Borstel, Germany(Bohle) Requests for reprints: Department of Urology, Medical University of Lubeck, Ratzeburger Allee 160, D-23538 Lubeck, GermanySupported by Deutsche Forschungsgemeinschaft SFB 367, project C7.© 1999 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byNoguera-Ortega E, Rabanal R, Secanella-Fandos S, Torrents E, Luquin M and Julián E (2015) γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live MycobacteriaJournal of Urology, VOL. 195, NO. 1, (198-205), Online publication date: 1-Jan-2016.Secanella-Fandos S, Noguera-Ortega E, Olivares F, Luquin M and Julián E (2013) Killed but Metabolically Active Mycobacterium bovis bacillus Calmette-Guérin Retains the Antitumor Ability of Live bacillus Calmette-GuérinJournal of Urology, VOL. 191, NO. 5, (1422-1428), Online publication date: 1-May-2014.Shah G, Zhang G, Chen F, Cao Y, Kalyanaraman B and See W (2013) 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.Durek C, Jurczok A, Werner H, Jocham D and Böhle A (2018) Optimal Treatment of Systemic Bacillus Calmette-Guerin Infection: Investigations in an Animal ModelJournal of Urology, VOL. 168, NO. 2, (826-831), Online publication date: 1-Aug-2002.DUREK C, RICHTER E, BASTECK A, RÜSCH-GERDES S, GERDES J, JOCHAM D and BÖHLE A (2018) THE FATE OF BACILLUS CALMETTE-GUERIN AFTER INTRAVESICAL INSTILLATIONJournal of Urology, VOL. 165, NO. 5, (1765-1768), Online publication date: 1-May-2001. Volume 161Issue 5May 1999Page: 1702-1706 Advertisement Copyright & Permissions© 1999 by American Urological Association, Inc.Metrics Author Information J-H. GUNTHER More articles by this author M. FRAMBACH More articles by this author I. DEINERT More articles by this author S. BRANDAU More articles by this author D. JOCHAM More articles by this author A. BOHLE More articles by this author Expand All Advertisement PDF downloadLoading ...