title: Inhibition of nitric oxide is a good therapeutic target for bladder tumors that express iNOS.
abstract: Bladder cancer is the second cause of death for urological tumors in man. When the tumor is nonmuscle invasive, transurethral resection is curative. On the other hand, radical cystectomy is the treatment chosen for patients with invasive tumors, but still under treatment, these patients have high risk of dying, by the development of metastatic disease within 5 years. It is therefore important to identify a new therapeutic target to avoid tumor recurrences and tumor progression. Nitric oxide (NO) is an important biological messenger known to influence several types of cancers. In bladder cancer, production of NO and expression and activity of inducible NO synthase was associated to recurrence and progression. The objective of this work was to analyze if inhibition of nitric oxide production could be considered a therapeutic target for bladder tumors expressing iNOS. Using a bladder cancer murine model with different invasiveness grade we have demonstrated that NO inhibition was able to inhibit growth of bladder tumors expressing iNOS. Furthermore, invasive properties of MB49-I orthotopic growth was inhibited using NO inhibitors. This paper also shows that levels of NO in urine can be correlated with tumor size. In conclusion, inhibition of NO could be considered as a therapeutic target that prevents tumor growth and progression. Also, urine NO levels may be useful for measuring tumor growth.
authors.affiliation: Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
authors.forename: Denise
authors.initials: D
authors.lastname: Belgorosky
authors.affiliation: Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Langle
authors.affiliation: Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Prack  Mc Cormick
authors.affiliation: Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
authors.forename: Lucas
authors.initials: L
authors.lastname: Colombo
authors.affiliation: Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sandes
authors.affiliation: Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina. Electronic address: anamariaeijan@gmail.com.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Eiján
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000737:chemistry; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: 4′,6-diamino-2-phenylindole; BC; Bladder cancer; CM; DAPI; L-NAME; MMP; N-nitro-L-arginine-methyl-esterHCl; NMI; NO; Nitric oxide; Orthotopic murine model; bladder cancer; conditioned medium; eNOS; endothelial nitric oxide synthase; iNOS; inducible nitric oxide synthase; matrix metalloproteinase; nNOS; neuronal nitric oxide synthase; nitric oxide; nonmuscle invasive; uPA; urokinase-type plasminogen activator