318 ANTI-ANGIOGENIC EFFECTS OF THE SUPERANTIGEN STAPHYLOCOCCAL ENTEROTOXIN B (SEB) AND BACILLUS CALMETTE-GUERIN (BCG) IMMUNOTHERAPY IN THE SUPERFICIAL BLADDER CANCER (SBC)

Abstract

You have accessJournal of UrologyUrothelial Cancer: Medical & Surgical Therapy1 Apr 2010318 ANTI-ANGIOGENIC EFFECTS OF THE SUPERANTIGEN STAPHYLOCOCCAL ENTEROTOXIN B (SEB) AND BACILLUS CALMETTE-GUERIN (BCG) IMMUNOTHERAPY IN THE SUPERFICIAL BLADDER CANCER (SBC) Leonardo O. Reis, Valéria H.A. Cagnon, Ubirajara Ferreira, Athanase Billis, and Wagner J. Fávaro Leonardo O. ReisLeonardo O. Reis More articles by this author , Valéria H.A. CagnonValéria H.A. Cagnon More articles by this author , Ubirajara FerreiraUbirajara Ferreira More articles by this author , Athanase BillisAthanase Billis More articles by this author , and Wagner J. FávaroWagner J. Fávaro More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.382AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The angiogenic phenotype can be defined as an effect of balance between angiogenic and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is important regulator of cancer cell growth and metastases. Endostatin is one of angiogenic inhibitors which plays an important role in suppressing tumor growth. However, the endostatin anti-angiogenic mechanisms on urothelial tissue are unclear. Thus, the aim of this work was to characterize the anti-angiogenic effects of the BCG, SEB and BCG plus SEB treatments in the SBC of rats. METHODS Fifty 7-week-old female Fisher 344 rats were anesthetized and 10 of them received 0.3 ml dose of saline (Control group). Other 40 rats received 1.5 mg/kg dose of n-methyl-n-nitrosourea (MNU), intravesically every other week for 7 weeks. After MNU treatment, the 40 rats were divided into 4 groups: The MNU group; The SEB group received 10 μg/ml dose of SEB intravesically for 8 weeks; The BCG group received 106 UFC dose of BCG for 8 weeks; The BCG-SEB group received simultaneous BCG and SEB treatments. After 15 weeks, all bladders were collected for immunological analyses of the VEGF receptor (VEGFR), endostatin, matrix metalloproteinase 9 (MMP-9), insulin like growth factor receptor 1 (IGFR-1), Ki-67 (cellular proliferation) and apoptosis. RESULTS The apoptosis and cellular proliferation indexes were increased in all treatment groups. However, these processes were decreased in the BCG, SEB and BCG-SEB groups in relation to the MNU group. These indexes were similar to the normal status in the BCG-SEB group. Intensified VEGFR, IGFR-1 and MMP-9 immunoreactivities were verified in the MNU group; moderate in the BCG and SEB groups; and weak in the BCG-SEB and Control groups. Weak endostatin immunoreactivity was seen in the blood vessels of the MNU, BCG and SEB groups, moderate in the BCG-SEB group and intense in the Control group. CONCLUSIONS The associated BCG-SEB treatment was more effective in restoring apoptosis and cellular proliferation balance than BCG or SEB treatments. VEGFR, MMP-9 and IGFR-1 reactivities were an important pathway in cellular proliferation, and can be considered fundamental elements involved in bladder carcinogenesis. Furthermore, the decreased cellular proliferation and neoplastic features were correlated with increased endostatin and decreased VEGFR reactivities, mainly, in the BCG-SEB group. Finally, the association between BCG and SEB may be effective in treating bladder cancer focusing on angiogenic homeostasis. Campinas, Brazil© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e126 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Leonardo O. Reis More articles by this author Valéria H.A. Cagnon More articles by this author Ubirajara Ferreira More articles by this author Athanase Billis More articles by this author Wagner J. Fávaro More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...