dinoprost and Urinary-Bladder-Neoplasms

To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder.. GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls.. Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (P=0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (P=0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (P=0.044).. Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers, Tumor; Carcinoma, Transitional Cell; Case-Control Studies; Deoxyguanosine; Dinoprost; Female; Gene Frequency; Genetic Association Studies; Genotype; Glutathione Transferase; Heterozygote; Humans; Immunoenzyme Techniques; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Urinary Bladder Neoplasms

Prostaglandin F2 alpha can be measured as a stable degradation product, 13,14-dihydro-15-keto-prostaglandin F2 alpha (DHK-PGF2 alpha). Pathological serum levels of this lipid compound have been observed in prostate hyperplasia and treated testicular cancer patients. In renal cancer patients elevated DHK-PGF2 alpha shows a trend to normalize 12 months following nephrectomy in stage T0N0M0. Bladder cancer patients have slightly increased DHK-PGF2 alpha that differ in relation to preinvasive bladder cancer. In contrast serum haptoglobin levels were significantly pathological in patients with kidney and bladder cancer, suggesting involved cancer metabolism. Patients with prostate and testis cancer are without distinct relation to the tumour stage. After specification of haptoglobin types no coincidence to urogenital tumours could be detected. Correlated aberration of PGF2 alpha and haptoglobin displayed different patterns depending on the type of urogenital tumour.

Topics: Adult; Aged; Dinoprost; Female; Haptoglobins; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Staging; Prostaglandins F; Prostatic Hyperplasia; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms

13,14-Dihydro-15-keto-prostaglandin F2 alpha (13,14-DHK-PGF2 alpha) represents a stable product of degradation after pulmonary flow and it is shown to be reliably measured by radioimmunoassay. In patients with urogenital tumors, serum levels of 13,14-DHK-PGF2 alpha are distinctly elevated when compared to a control group. The rate of synthesis of this compound in urogenital tumors, however, appears to be different.

Topics: Adenocarcinoma; Dinoprost; Female; Humans; Kidney Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Prostaglandins F; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms