OP1-03 INTRAVESICAL BACILLUS CALMETTE-GUERIN (BCG) EFFICIENTLY TACKLES S6K1 BUT NOT 4E-BP1 PHOSPHORYLATION IN NON-MUSCLE INVASIVE BLADDER CANCER

Abstract

You have accessJournal of UrologyOutstanding Posters: Research1 Apr 2014OP1-03 INTRAVESICAL BACILLUS CALMETTE-GUERIN (BCG) EFFICIENTLY TACKLES S6K1 BUT NOT 4E-BP1 PHOSPHORYLATION IN NON-MUSCLE INVASIVE BLADDER CANCER Karen Ferrari, Juliana A. de Camargo, Guilherme Z. Rocha, José B.C. Carvalheira, Athanase Billis, Mário J.A. Saad, and Leonardo O. Reis Karen FerrariKaren Ferrari More articles by this author , Juliana A. de CamargoJuliana A. de Camargo More articles by this author , Guilherme Z. RochaGuilherme Z. Rocha More articles by this author , José B.C. CarvalheiraJosé B.C. Carvalheira More articles by this author , Athanase BillisAthanase Billis More articles by this author , Mário J.A. SaadMário J.A. Saad More articles by this author , and Leonardo O. ReisLeonardo O. Reis More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.611AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bacillus Calmette-Guérin (BCG) is the gold standard treatment of non-muscle invasive bladder cancer (NMIBC). We aimed to characterize the functional consequences of intravesical BCG on the molecular mechanism of the PI3K/AKT/mTOR signaling pathway in NMIBC, never reported to date. METHODS Female (Fischer 344) rats, 6 weeks old, received 1.5 mg/kg MNU (N-methyl-n-nitrosourea) intravesically every other week for 6 weeks and were randomly divided into 2 groups: - MNU tumor group (n=10) received 0.3 ml saline and - BCG treatment group (n=10) received 106 cfu of BCG intravesically for 6 weeks. At week 15 all bladders were collected for histopathology, immunohistochemistry, proliferation index (Ki-67), and immunoblotting (pAKT, pAMPK, pp53, pp70S6K, RICTOR, RAPTOR, mTOR, p4EBP1). Student’s t-test was used to compare groups. Two tailed p<0.05 was considered statistically significant. RESULTS Papillary carcinoma (pTa) and high-grade intraepithelial neoplasia (carcinoma in situ) predominated in the MNU group while normal urothelium, papillary and flat hyperplasia were more common in BCG treatment. NMIBC treated with BCG exhibited suppression of S6K1 (Figure 1 B) but not 4E-BP1 phosphorylation (Figure 1 A), suggesting that 4E-BP1 is regulated differently that S6K1, escaping the BCG action. The cellular proliferation index decreased in the BCG treatment compared to MNU (Figure 1 C). Table 1 shows the mammalian target of rapamycin pathway phosphorylation status of BCG treatment compared to MNU. CONCLUSIONS 4E-BP1 might be a worthwhile new target for BCG refractory NMIBC. In the future, activation status of S6K1 and 4E-BP1 might stratify patients that could benefit from targeting such molecular elements. This is the first study to explore the mammalian target of rapamycin pathway in the intravesical BCG treatment of NMIBC. Table 1. Mammalian target of rapamycin pathway phosphorylation status of BCG treatment compared to MNU Immunoblotting BCG/MNU (%) p values mTOR 66.84 0.5299 pAKT 56.74 0.3278 pAMPK 121.33 0.6399 pp53 73.40 0.5166 RICTOR 80.28 0.6448 RAPTOR 88.62 0.8867 p4EBP1 140.16 0.5069 pp70S6K 17.08 0.0034 © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e162-e163 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Karen Ferrari More articles by this author Juliana A. de Camargo More articles by this author Guilherme Z. Rocha More articles by this author José B.C. Carvalheira More articles by this author Athanase Billis More articles by this author Mário J.A. Saad More articles by this author Leonardo O. Reis More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...