3-nitrotyrosine and Urinary-Bladder-Neoplasms

The epidemiological studies confirm that the overproduction of free radical is an important factor of cancer induction as well as development, and loss of antioxidant systems efficiency is associated with an increased risk of carcinogenesis. While bladder cancer is the fourth most common type of cancer all over the world, there is little evidence of the advancing changes in oxidative/nitrative stress during the progression of bladder cancer. Our study aimed to investigate the plasma levels of typical markers of oxidative/nitrative stress depending on the clinical classification of bladder cancer differentiation and infiltration degree. We examined 40 patients with newly diagnosed bladder cancer and 20 healthy volunteers as a control group. We analysed the plasma levels of protein carbonyls, thiol groups, 3-nitrotyrosine, lipid peroxidation, as well as non-enzymatic plasma antioxidant capacity using DPPH

Topics: Adult; Antioxidants; Biomarkers; Case-Control Studies; Disease Progression; Female; Free Radicals; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Sulfhydryl Compounds; Tyrosine; Urinary Bladder Neoplasms

Oxidative stress markers and peroxiredoxins are connected to cancer. A large set of urinary bladder carcinomas were studied for the expression of nitrotyrosine and 8-hydroxydeguanosine (8OHdG), two markers indicating oxidative damage. Serum and urine 8-OHdG were assessed in a subset of patients. We also analysed immunohisto-chemically the expression of nrf2, keap1, all six peroxiredoxins (prx) and thioredoxin (trx) in these tumors. 15 % of the cases showed 8OHdG and 36 % nitrotyrosine positivity. Expression of nitrotyrosine and 8OHdG associated with a poor prognosis (p=0.050, p=0.011, respectively). Peroxiredoxin positivity ranged from 39 % to 84 % lowest expression being for prx 4 and highest for prx 3. Prx 4 expression associated with a poor prognosis (p=0.025) with high grade (p=0.044) and larger tumors (p=0.023). Cytoplasmic trx positivity was seen in 91 % and nuclear in 59 % of tumors. Nuclear and cytoplasmic trx associated with each other (p<0.001), and nuclear trx associated with prx 6 (p=0.001), prx 2 (p<0.001), and prx 5 (p<0.001). 8OHdG associated with nuclear trx positivity (p=0.002), inversely with prx 1 (p=0.025) and with keap1 (p=0.020). Nuclear nrf2 was associated with nitrotyrosine (p=0.042). The results show that the amount of oxidative stress in urinary bladder tumors affects the prognosis of the patients. Of antioxidative enzymes, prx4 associated with an unfavourable prognosis. Selective inhibition of prx4 expression might then be one additional option of treatment of bladder cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; Carcinoma; Cell Nucleus; Cytoplasm; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Peroxiredoxins; Prognosis; Statistics, Nonparametric; Thioredoxins; Tyrosine; Urinary Bladder Neoplasms

Anatase particles of titanium dioxide (TiO2) absorb ultraviolet (UV) light which is shorter than 415 nm. Photoexcited TiO2, a strong oxidizer, is expected to inhibit malignant cell growth. Liposomes accelerate endophagocytosis to the cytoplasm of encapsulated materials. In this study, we examined anti-tumor effects of TiO2 and liposome-encapsulated TiO2 (LT) with UVA irradiation by an air pouch cancer model using NBT-II bladder cancer cells, which simulates bladder cancer. Injection of TiO2 or LT into the air pouch was followed by UVA irradiation via the opened pouch. Tumors of TiO2 + UVA and LT + UVA groups showed more pronounced necrotic areas, apoptotic indices, nitrotyrosine formation, tumor growth inhibition and increased survival compared with control groups. Especially the LT + UVA group showed more remarkable anti-tumoral effects than the TiO2 + UVA group, which was associated with higher TiO2 incorporation. These findings suggest that LT might be more effective than noncoated TiO2 in the treatment of bladder cancer.

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Liposomes; Male; Mice; Mice, Nude; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Titanium; Tyrosine; Urinary Bladder Neoplasms

DNA, protein oxidation and lipid peroxidation possess a major impact in carcinogenesis. Also, inflammatory and oxidative events have remarkable importance in bladder cancer. Thus, in this study total protein, protein carbonyl, nitrotyrosine, thiol residues, non-protein thiols, lipid peroxidation, and also, because of their relations to the above parameters, iron and iron binding levels have been investigated in patients with bladder cancer and in control group. Statistical evaluation of the results demonstrated significantly lower plasma protein levels in the patients with bladder cancer, as compared to the healthy control group. Serum iron levels in patients with invasive bladder cancer were found to be significantly lower when compared with non-invasive group. Protein carbonyl groups were remarkably higher in bladder cancer patients than in healthy controls. Patients with bladder cancer were demonstrated to have significantly lower levels of total thiol groups and protein-bound thiol groups as compared to healthy controls. Protein-bound thiol groups in patients with invasive bladder cancer revealed a more significant decline, than in non-invasive group.

Topics: Aged; Analysis of Variance; Biomarkers, Tumor; Blood Proteins; Carcinoma, Transitional Cell; Case-Control Studies; Humans; Iron; Lipid Peroxidation; Male; Middle Aged; Neoplasm Staging; Oxidation-Reduction; Oxidative Stress; Probability; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Sulfhydryl Compounds; Tyrosine; Urinary Bladder Neoplasms

Nitric oxide (NO) is produced by a group of synthase enzymes (NOS). By means of different pathways, NO exerts several functions in benign and malignant human bladder tissues. The current paper describes the NO/guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) and the NO/oxidative pathways in human bladder tissues.. Bladder carcinoma tissues were collected from 18 patients by transurethral resection procedures. Normal benign vesical tissue specimens from a further eight patients with benign diseases served as controls. Immunohistochemistry was conducted for localization of sGC, cGMP, and nitrotyrosine in benign and malignant vesical tissues, evaluating two-three tissue sections per patient.. Positive immunolabeling for sGC and cGMP was detected in vascular endothelial cells of normal and malignant vesical tissues. Those signals were most intense in bladder carcinoma tissues. Immunolabeling for sGC and cGMP was also detected in normal urothelial cells. In bladder carcinoma cells, a heterogeneous immunolabeling for sGC and cGMP was seen, with a wide spectrum of signal intensity. Positive immunostaining for sGC and cGMP was also observed in stromal round cells in benign and malignant bladder tissues. Immunolabeling for nitrotyrosine was mainly observed in endothelial cells, with a much stronger immunolabeling in bladder carcinoma tissues compared to normal benign controls. A weak immunolabeling for nitrotyrosine was also observed in bladder carcinoma cells. Normal urothelial cells did not show such nitrotyrosine expression.. The current report provides evidences that NO play several roles through different pathways in benign and malignant vesical tissues. The influences generated by NO molecules can be divided into cGMP-mediated effects (those resulting from the NO/sGC/cGMP pathway) and non-cGMP-mediated effects (those resulting from the NO/oxidative pathway). Increased angiogenesis is a cGMP-mediated effect, while nitrotyrosine production is a non cGMP-mediated oxidative effect. Such an NO/oxidative pathway is observed more often in bladder carcinoma.

Topics: Aged; Blotting, Western; Carcinoma; Cell Transformation, Neoplastic; Cyclic GMP; Free Radical Scavengers; Guanylate Cyclase; Humans; Immunohistochemistry; Neovascularization, Pathologic; Nitric Oxide; Nitric Oxide Synthase; Oxidation-Reduction; Tyrosine; Urinary Bladder Neoplasms