Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
Research Area from the Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, CP 1417 DTB Buenos Aires, Argentina.
Nitric Oxide. 2014 Jan 30;36:11-8. doi: 10.1016/j.niox.2013.10.010. Epub 2013 Nov 6.
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.
膀胱癌是男性泌尿系统肿瘤中第二大致死原因。当肿瘤是非肌肉浸润性的时,经尿道切除是一种有效的治疗方法。另一方面,对于浸润性肿瘤患者,根治性膀胱切除术是首选的治疗方法,但在治疗过程中,这些患者仍有很高的死亡风险,因为在 5 年内会发生转移性疾病。因此,确定新的治疗靶点以避免肿瘤复发和进展非常重要。一氧化氮(NO)是一种重要的生物信使,已知它会影响多种类型的癌症。在膀胱癌中,NO 的产生以及诱导型一氧化氮合酶的表达和活性与复发和进展有关。本研究的目的是分析抑制一氧化氮的产生是否可以被认为是表达 iNOS 的膀胱癌的治疗靶点。我们使用具有不同侵袭性等级的膀胱癌小鼠模型证明了,抑制 NO 的产生可以抑制表达 iNOS 的膀胱癌的生长。此外,NO 抑制剂还可以抑制 MB49-I 原位生长的侵袭性。本文还表明,尿液中的 NO 水平可以与肿瘤大小相关。总之,抑制 NO 可以被认为是一种治疗靶点,可防止肿瘤的生长和进展。此外,尿液中的 NO 水平可能有助于测量肿瘤的生长。