1150 ENHANCED ANTITUMOR EFFECT OF INTRAVESICAL BCG PLUS MMC THERAPY IN AN ORTHOTOPIC MURINE BLADDER CANCER MODEL

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20101150 ENHANCED ANTITUMOR EFFECT OF INTRAVESICAL BCG PLUS MMC THERAPY IN AN ORTHOTOPIC MURINE BLADDER CANCER MODEL Minoru Horinaga, Masashi Matsushima, Ryuichi Fukuyama, Hitoshi Yanaihara, Masahiro Iida, Yoko Nakahira, and Hirotaka Asakura Minoru HorinagaMinoru Horinaga Saitama, Japan More articles by this author , Masashi MatsushimaMasashi Matsushima Saitama, Japan More articles by this author , Ryuichi FukuyamaRyuichi Fukuyama Konan, Japan More articles by this author , Hitoshi YanaiharaHitoshi Yanaihara Saitama, Japan More articles by this author , Masahiro IidaMasahiro Iida Saitama, Japan More articles by this author , Yoko NakahiraYoko Nakahira Saitama, Japan More articles by this author , and Hirotaka AsakuraHirotaka Asakura Saitama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.649AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is currently the most successful adjuvant agent for the treatment and/or prophylaxis of superficial bladder tumors. However, superficial bladder tumors recur in 60 to 70% of all cases, and 30 % of these recurrent tumors present with a higher grade with invasive properties. We evaluated the combination of intravesical BCG plus MMC treatments against bladder tumors in a model of orthotopic murine bladder cancer. METHODS An orthotopic murine bladder cancer model was established using the simple instillation of one million MBT-2 cells into the lumen of the bladder of a female C3H/HeN mouse. To assess the antitumoral effect of MMC, intravesical MMC therapy was administered at various dose-escalating concentrations: 0ug(control: PBS), 25ug, 50ug, 100ug and 200ug (n = 8 for each group). Next, a comparative evaluation of tumor growth in a control group (PBS), a BCG-alone group(100ug), a MCC-alone group, and a combined BCG (100ug) plus MMC group was performed (n= 8 for each group; total 4 groups). Intravesical therapy was administered at 3-day intervals starting on day 5 and repeated 5 times. On day 60 after the initial implantation of the MBT-2 cells, all the surviving mice were sacrificed and necropsied. To evaluate the macrophage infiltration in the tumor and the proliferative activity among the different groups, CD-68 and Ki-67 staining of the tumor cells was performed in animal model. RESULTS In the MMC groups of 8 mice each treated with a dose of 0ug (survival; 26.4 days), 25ug (34.8 days) and 50ug (40.0 days), 0, 0 and 2 of the mice survived, respectively. In both the 100ug (survival;17.3 days) and 200ug (11.9 days) groups, all eight mice died from adverse events. A significant survival advantage was observed in the combined BCG (100ug) plus MMC (50ug) group (51.5 days), compared with that in the BCG-alone (100ug) group (33.4 days p = 0.03) and the MMC-alone (50ug) group (39.5 days p = 0.04). BCG significantly suppressed while MMC increased macrophage infiltration in the tumor, compared with in the control group. The Ki-67 expression level, which is regarded as a proliferation index, was significantly lower in the BCG plus MCC group (31.1 ± 5.2%) than in the BCG-alone group (50.9 ± 4.1%; p <0.001) and the MCC-alone group (39.2 ± 2.5%; p <0.05). CONCLUSIONS Combining BCG plus MMC treatment decreased the tumor appearance rate, improved the survival period, and reduced the proliferation rate in tumors, as compared with BCG-alone and MMC-alone treatment, possibly providing a greater therapeutic benefit over either agent alone. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e445 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Minoru Horinaga Saitama, Japan More articles by this author Masashi Matsushima Saitama, Japan More articles by this author Ryuichi Fukuyama Konan, Japan More articles by this author Hitoshi Yanaihara Saitama, Japan More articles by this author Masahiro Iida Saitama, Japan More articles by this author Yoko Nakahira Saitama, Japan More articles by this author Hirotaka Asakura Saitama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...