8-oxo-7-8-dihydrodeoxyguanine and Ovarian-Neoplasms

Potential tissue and serum biomarkers were assessed for predicting efficacy of bevacizumab in ovarian cancer (OC).. Twenty patients with OC received chemotherapy alone (control group) or in combination with bevacizumab (study group) in this non-randomised study. Pre- and post-treatment serum concentrations of vascular endothelial growth factor (VEGF), 8-hydroxydeoxyguanosine (8-OHdG) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in all patients. In addition, immunohistochemical expressions VEGF receptors (R1, R2), hypoxia-inducible factor 1alpha (HIF-1 alpha), matrix metalloproteinases (-2, -9) and TIMP-2 were analysed in tumours from bevacizumab-treated patients.. 8-OHdG and HIF-1alpha immunostainings were more highly expressed among patients with progression-free survival (PFS) >23 months than in patients with PFS <12 months. Similarly, MMP-9 was more frequently highly expressed in those with long versus short PFS. Serum VEGF concentrations decreased substantially in all bevacizumab-treated patients versus only 20% of the control group.. Our results indicate differences in MMP-9 and HIF-1alpha expression in relation to duration of PFS and effects on serum VEGF when bevacizumab is used in combination with chemotherapy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Carboplatin; Female; Guanine; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Middle Aged; Ovarian Neoplasms; Paclitaxel; Receptors, Vascular Endothelial Growth Factor; Tissue Inhibitor of Metalloproteinase-1; Vascular Endothelial Growth Factor A

Previous studies have suggested the importance of reactive oxygen species in all the steps of carcinogenesis. Antioxidant enzymes are considered as the most specific and efficient way to protect cells from reactive oxygen species. The purpose of the current study was to identify the role of oxidative stress and major antioxidant enzymes in ovarian carcinomas.. The material consisted of 68 invasive ovarian carcinomas which were studied by immunohistochemistry with antibodies to antioxidant enzymes peroxiredoxins (Prxs) I-VI and thioredoxin and oxidative stress markers nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG). Both the intensity and the extent of the stainings were assessed, and the nuclear and cytoplasmic expressions were evaluated separately.. The study revealed the hydroxyl radical-derived oxidative stress marker in DNA, 8-OHdG, to be a powerful prognostic factor in ovarian carcinoma (Kaplan-Meier survival log-rank-analysis P = 0.003; risk of death to ovarian carcinoma 2.69; 95% confidence interval 1.35-5.35. 8-OHdG was also associated with poor differentiation (P = 0.053), higher stage (P < 0.001), and non-optimal surgical outcome (P = 0.002). High cytoplasmic Prx IV immunostaining was associated with a better prognosis (P = 0.024), and elevated cytoplasmic expression rates of Prxs V (P = 0.043) and VI (P = 0.032) were associated with a higher stage.. To conclude, it appears that hydroxyl radical-derived oxidative stress, but not nitric oxide radical-derived oxidative stress, plays a significant role in ovarian carcinogenesis. Immunohistochemical assessment of 8-OHdG could provide a useful prognostic marker in ovarian cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Biomarkers, Tumor; Carcinoma; Cell Nucleus; Cytoplasm; DNA Adducts; Female; Guanine; Humans; Immunohistochemistry; Neoplasm Staging; Ovarian Neoplasms; Oxidative Stress; Prognosis; Survival Analysis; Tyrosine