MP39-16 GENE THERAPY AGAINST BLADDER CANCER IN VIVO: A NEW STRATEGY TO FIGHT THE UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2014MP39-16 GENE THERAPY AGAINST BLADDER CANCER IN VIVO: A NEW STRATEGY TO FIGHT THE UROTHELIAL CARCINOMA Eduardo Landerer, Maximiliano Bendek, Lorena Lobos, Miguel Ávila, Alexis Rivas, Vincenzo Borgna, Luis O. Burzio, Carlos González, Octavio Castillo, and Jaime Villegas Eduardo LandererEduardo Landerer More articles by this author , Maximiliano BendekMaximiliano Bendek More articles by this author , Lorena LobosLorena Lobos More articles by this author , Miguel ÁvilaMiguel Ávila More articles by this author , Alexis RivasAlexis Rivas More articles by this author , Vincenzo BorgnaVincenzo Borgna More articles by this author , Luis O. BurzioLuis O. Burzio More articles by this author , Carlos GonzálezCarlos González More articles by this author , Octavio CastilloOctavio Castillo More articles by this author , and Jaime VillegasJaime Villegas More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1331AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In the early 2000s, our laboratory described the existence of a new family of non-coding mitochondrial RNAs (ncmtRNAs) named sense (S-ncmtRNA) and antisense (AS-ncmtRNA), which exhibits a differential pattern of expression depending on the malignant potential and the proliferative state of cells, observing a selective repression of the expression of the antisense molecule in tumour cells. Lipofection of antisense oligodeoxynucleotides (AS-ODN) complementary to the AS-ncmtRNA (UAB1) in tumour cell lines of bladder cancer, in vitro, induces cell death. When it is applied to primary cultures of normal murine urothelial cells, they are not affected. Objective To evaluate the antineoplastic effect of the AS-ODNs complementary to ASncmtRNA in a model of bladder cancer in vivo. METHODS We implemented the immunocompetent syngeneic orthotopic murine bladder cancer model: MB49 C57BL/6. We performed a tumour growth curve and a study of local and systemic toxicity. Bladder cancer cells were instilled on 10 mice, separating them into two groups: Group 1 treated with UAB1; Group 2, treated with AS-ODN control, on days 3, 4, 5, 8, 9 and 10 at a dosis of 300 ng/ul of full-phosphorothioate ODN, assessing tumour progression and survival of animals. RESULTS 100% of mice developed superficial bladder tumours with a tumour growth curve in log phase since the third day of evolution, which showed a direct relationship with the presence of tumour cells in urine and subsequently, with clinical evidence of gross haematuria. The toxicity study showed a local and systemic biosafety in 100% of animals. The mice of group 1 (AS-ODN UAB1) evolved with an increase of 500% in the survival time compared to control group. The necropsy demonstrated evidence of invasive bladder cancer in all mice of control group unlike of no one of mice of case group. CONCLUSIONS Antisense therapy against AS-ncmtRNA on a model of bladder cancer in vivo, avoids the tumour progression and increases significantly the survival time when compared to a control group. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e432 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Eduardo Landerer More articles by this author Maximiliano Bendek More articles by this author Lorena Lobos More articles by this author Miguel Ávila More articles by this author Alexis Rivas More articles by this author Vincenzo Borgna More articles by this author Luis O. Burzio More articles by this author Carlos González More articles by this author Octavio Castillo More articles by this author Jaime Villegas More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...