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Type: Artigo de periódico
Title: Intravesical Bacillus Calmette-guerin Efficiently Reduces P70s6k1 But Not 4e-bp1 Phosphorylation In Nonmuscle Invasive Bladder Cancer
Author: Ferrari
Karen Linares; de Camargo
Juliana Alves; Rocha
Guilherme Zweig; Carvalheira
Jose B. C.; Saad
Mario J. A.; Billis
Athanase; Reis
Leonardo O.
Abstract: Purpose: We characterized the functional consequences of intravesical bacillus Calmette-Guerin on the molecular mechanism of the AKT/mTOR signaling pathway in nonmuscle invasive bladder cancer. To our knowledge this has not been reported previously. Materials and Methods: At age 7 weeks female Fischer 344 rats received 1.5 mg/kg MNU intravesically every other week for 6 weeks. They were randomized at 10 per group to MNU (0.2 ml vehicle), bacillus Calmette-Guerin (10(6) cfu Connaught strain), rapamycin (15 mu g/ml) and bacillus Calmette-Guerin plus simultaneous rapamycin, each intravesically for 6 weeks. At week 15 the bladders were collected for histopathology, immunohistochemistry and immunoblot to determine p-AKT, Rictor, Raptor, p-4E-BP1, p-p70S6K1, p-AMPK-alpha, p-mTOR and p-p53. Results: Papillary carcinoma (pTa) and high grade intraepithelial neoplasia (pTis) predominated in the MNU group while normal urothelium, papillary and flat hyperplasia were more common in treated groups. Nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin showed suppression of p70S6K1 but not 4E-BP1 phosphorylation. This suggests that 4E-BP1 is regulated differently than p70S6K1, escaping the bacillus Calmette-Guerin action that occurs in a mTOR independent manner. The association of bacillus Calmette-Guerin with rapamycin but not rapamycin monotherapy affected p70S6K1 and 4E-BP1 phosphorylation with no features of in situ carcinoma (pTis). Conclusions: The activation status of p70S6K1 and 4E-BP1 might be used to stratify patients who could benefit from targeting such molecular elements with multitarget/multidrug intravesical therapy. In the future 4E-BP1 might be a worthwhile new target for bacillus Calmette-Guerin refractory nonmuscle invasive bladder cancer.
Subject: Urothelial Carcinoma
Mammalian Target
Mouse Model
Country: NEW YORK
Citation: Intravesical Bacillus Calmette-guerin Efficiently Reduces P70s6k1 But Not 4e-bp1 Phosphorylation In Nonmuscle Invasive Bladder Cancer. Elsevier Science Inc, v. 193, p. 682-689 FEB-2015.
Rights: embargo
Identifier DOI: 10.1016/j.juro.2014.08.106
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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