Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer.
Introduction
The study aims to determine whether body mass index (BMI), metabolic syndrome (MS) or its individual components (primary hypertension, type 2 diabetes mellitus and dyslipidemias) are risk factors for common urological diseases.
Materials and methods
Cross-sectional study with data collected on February 28, 2022 from the TriNetX Research Network. Patients were divided in cohorts according to their BMI, presence of MS (BMI > 30 kg/m
2
, type 2 diabetes mellitus, primary hypertension and disorders of lipoprotein metabolism) and its individual components and its association with common urological conditions was determined. For each analysis, odds ratio (OR) with 95% confidence intervals were calculated. Statistical significance was assessed at
p
< .05.
Results
BMI > 30 kg/m
2
was associated with increased risk of lithiasis, kidney cancer, overactive bladder, male hypogonadism, benign prostatic hyperplasia, and erectile dysfunction (
p
< .05). On the contrary, BMI was inversely associated with ureteral, bladder and prostate cancer (
p
< .05). In all urological diseases, MS was the strongest risk factor, with prostate cancer (OR = 2.53) showing the weakest and male hypogonadism the strongest (OR = 13.00) associations.
Conclusions
MS and its individual components were significant risk factors for common urological conditions. Hence holistic approaches with lifestyle modification might prevent common urological disease.
Key messages
Overall, metabolic syndrome is the strongest risk factor for all the analysed urological diseases.
Abnormally high body mass index can be a risk or protective factor depending on the threshold and urological disease that are being evaluated.
Metabolic syndrome and increased BMI should be considered important factors associated to the prevalence of common urological diseases.
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