Preliminary Study on Selected Markers of Oxidative Stress, Inflammation and Angiogenesis in Patients with Bladder Cancer.

In recent years, bladder cancer (BC) has been reported as one of the most commonly occurring cancers among older people, and its detection is still difficult. Therefore, there is a need to search for additional useful markers of disease. Some studies indicate the important roles of inflammation and oxidative stress (OS) in bladder tumour pathogenesis. The aim of this study was to examine the levels of selected markers of OS, inflammation and angiogenesis in blood plasma/serum samples derived from patients with BC, and a healthy control group. Moreover the degrees of change and strength of correlation between values of the analysed markers and tumour stage or grade were estimated. Concentrations of: malondialdehyde (MDA) and advanced oxidation protein products (AOPP), and total antioxidant status (TAS) divided into slow (TAS-s) and fast (TAS-f) antioxidants (spectrophotometric measurement), angiogenin (ANG) (immunoenzymatic method) and C-reactive protein (CRP) (immunoturbidimetric method) were determined in both the studied groups. The majority of values of the examined parameters were significantly higher among patients, while subfractions of TAS were significantly lower in comparison to the control group. Moreover, different values and different strengths of correlation between the examined parameters and cancer stage or grade were noticed. The most significant changes for CRP were observed in T2 and for MDA in G3, while the lowest TAS-f activity was revealed in G1 patients. Increased values of OS parameters, angiogenesis and inflammation markers, in combination with reduced TAS subfractions activity in BC are important in its pathogenesis and will be helpful in estimation of patients' condition.

The Diagnostic Value of Nuclear Matrix Proteins in Bladder Cancer in the Aspect of Environmental Risk from Carcinogens.

BACKGROUND: The interaction of environmental factors with genetic susceptibility and detoxification level seems to be an important causative factor in bladder cancer (BC). The aim of this study was to look for a BC marker panel which reflects the environmental risk. The nuclear matrix protein 22 (NMP22), bladder cancer-4 (BLCA-4), and total level proteins NMP22 and BLCA-4 (NMBL) in BC patients with genetic predisposition NAT2 (classified as slow acetylators, SA), DNA damage (8-OHdG), and detoxification by isoenzyme GSTπ activity were measured. MATERIALS AND METHODS: The urine and blood from 91 BC patients and controls were examined, also according to tumor stage (T) and grade (G). The participants completed a questionnaire in order to evaluate environmental risk. RESULTS: Most patients (75.3%) were previous or actual smokers. The levels of 8-OHdG, NMP22, BLCA-4, NMBL, and GSTπ were significantly higher in BC (p ≤ 0.001). The majority of patients (59.3%) were slow acetylators (SA). The highest BLCA-4/8-OHdG correlation was observed in total BC and SA smokers. CONCLUSIONS: The total pool of nuclear matrix proteins in the urine (NMBL) has a higher diagnostic value in bladder cancer than single proteins. The particular value of BLCA-4 and GSTπ in the aspect of environmental risk was noted.

The effects of coenzyme Q10 and baicalin in cisplatin-induced lipid peroxidation and nitrosative stress.

Cisplatin is the alkylating anticancer drug. These drugs show many side-effects including the damage of kidney. The nephrotoxicity of cisplatin is explained mainly by reactive oxygen species (ROS) generation. The increased level of lipids peroxidation was observed in patients treated with this drug. In the toxicity of cisplatin, are also involved reactive nitrogen species (RNS) such as nitric oxide (NO*) or peroxynitrite. The lack of cisplatin selectivity and its side effects tend to look for ways to reduce the toxicity in chemotherapy. Our previous studies demonstrated that oxidative stress caused by xenobiotics can sometimes be effectively inhibited by coenzyme Q10 and baicalin. The aim of our research was the evaluation of usefulness of two coenzyme Q10 forms: lipophilic, currently used (QA) and new, produced by nanotechnology, soluble in water, PureSorb-QTM40-P40 (QB). Also the utility of baicalin as free radicals scavenger in reducing the nephrotoxicity of cisplatin was examined. The study was performed on an in vitro model, human erythrocytes and serum. Oxidative stress was evaluated by the level of lipid peroxidation (TBARS method). The concentration of nitric oxide (NO*) and nitrate (NO3) was estimated in serum [Nitric Oxide Colorimetric Detection Kit (Cat. No. K023-H1) of Arbor Assays], based on reaction with Griess reagent. Cisplatin at concentration: 3.5, 10, 30 and 50 pg/mL significantly increased the level of TBARS in erythrocytes. All antioxidants: baicalin and two forms of coenzyme Q10 significantly inhibited TBARS compared to controls (p < 0.05). Both QA and QB studied in a wide range of concentrations (from 1.0 to 120.0 microg/mL) demonstrated their antioxidative effect. In all used doses they statistically significantly decreased TBARS level with the negative correlation (r = -0.751; p = 0.000). In the study of nitrosative stress, all doses of cisplatin increased NO* and NO3 level in serum (p < 0.05). Baicalin and QA showed no statistically significant influence on production of NO* and NO3 in serum, while QB unexpectedly increased these parameters. In joint exposure with cisplatin all three antioxidants, in the most of concentrations, decreased TBARS levels, elevated by cisplatin (p < 0.05). In nitrosative stress-induced by cisplatin, the most effective was QB, however, protective influence of all antioxidants varies and the results are ambiguous.