521 ENHANCED ANTITUMOR EFFECT OF INTRAVESICAL BCG PLUS DOCETAXEL THERAPY IN AN ORTHOTOPIC BLADDER CANCER MODEL

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 2011521 ENHANCED ANTITUMOR EFFECT OF INTRAVESICAL BCG PLUS DOCETAXEL THERAPY IN AN ORTHOTOPIC BLADDER CANCER MODEL Minoru Horinaga, Ryuichi Fukuyama, Masahiro Iida, Masashi Matsushima, Hitoshi Yanaihara, Yoko Nakahira, Munehisa Ueno, and Hirotaka Asakura Minoru HorinagaMinoru Horinaga Saitama, Japan More articles by this author , Ryuichi FukuyamaRyuichi Fukuyama Konan, Japan More articles by this author , Masahiro IidaMasahiro Iida Saitama, Japan More articles by this author , Masashi MatsushimaMasashi Matsushima Saitama, Japan More articles by this author , Hitoshi YanaiharaHitoshi Yanaihara Saitama, Japan More articles by this author , Yoko NakahiraYoko Nakahira Saitama, Japan More articles by this author , Munehisa UenoMunehisa Ueno 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.2011.02.1217AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intravesical BCG therapy is currently the most successful adjuvant agent for patients with non-muscle invasive bladder cancer (NMIBC). However, little progress in the management of NMIBC has been made. We explored the combination of intravesical BCG + Docetaxel(Doc) in an orthotopic bladder cancer model. METHODS An orthotopic murine bladder cancer model was used. To assess the antitumoral effect of Doc, intravesical Doc therapy was administered at various dose-escalating concentrations: 0μg (control: PBS), 25μg, 50μg and 100μg (n = 12 for each group; total of 4 groups). Next, a comparative evaluation of tumor growth among the control, the BCG-alone group(100μg), the Doc-alone group, and three combined BCG (100μg) + Doc group (a coincident(CO) and two sequential groups) was performed (n= 12 ; total of 6 groups). The sequential combined groups consisted of SA group (SA; Doc administration followed by BCG administration on the next day) and SB group (SB; BCG administration followed by Doc administration on the next day). Therapy was administered at 3-day intervals starting on day 5 and was repeated 5 times. To evaluate proliferation, T cell infiltration and apoptosis among the different groups, the tumor cells in the animal model were stained for Ki-67, CD8 and Cleaved caspase 3 after 4 instillations performed every 3 days. (n = 5). RESULTS In the Doc groups treated with a dose of 0 μg(survival; 32.3 ± 9.4 days), 25μg (36.8 ± 11.4), 50μg (38.1 ± 11.0) or 100μg (40.0 ± 12.7) one, two, two and three of the mice survived, respectively. Significant survival advantages were observed in the combined BCG + Doc group (CO: 50.7 ± 9.0, SA: 51.5 ± 6.9) compared with that in the BCG-alone group (33.1 ± 10.4) and the Doc-alone group (38.8 ± 11.5). The Ki-67 index of the cancer cells was significantly lower in the combined group, compared with that in the BCG-alone group (p < 0.0001), the Doc-alone group (p < 0.05) and the control(p < 0.0001). BCG-alone significantly increased the number of CD8+ T cells (p < 0.05), while Doc-alone reduced the CD8+ T cells (p < 0.05), compared with that in the control. Apoptosis was significantly increased when Doc was administrated to the animals irrespective of the presence (p < 0.05) or absence (p < 0.05) of BCG instillation. CONCLUSIONS Our results suggested that the combination of BCG + Doc treatment decreased the tumor appearance rate and improved the survival period. The enhancement in tumor growth inhibition enabled by combination regimens was presumably associated with a reduction in the tumor proliferation rate and might not depend on either CD8+ T cells or apoptosis. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e212 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Minoru Horinaga Saitama, Japan More articles by this author Ryuichi Fukuyama Konan, Japan More articles by this author Masahiro Iida Saitama, Japan More articles by this author Masashi Matsushima Saitama, Japan More articles by this author Hitoshi Yanaihara Saitama, Japan More articles by this author Yoko Nakahira Saitama, Japan More articles by this author Munehisa Ueno Saitama, Japan More articles by this author Hirotaka Asakura Saitama, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...