Reactive oxygen species and vascular endothelial growth factor (VEGF) in ovarian cancer patients
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In 41 stage II–IV epithelial ovarian cancer patients, markers of oxidative stress (malondialdehyde, ceruloplasmin) were elevated, decreased across chemotherapy cycles, were higher with residual disease, and correlated with elevated VEGF levels.
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Abstract
Background: Hypoxia plays an important role in ovarian cancer and understanding the role of reactive oxygen species and VEGF may identify patients who benefit the most from targeted therapies. The aims of the study were to determine the intensity of oxidative stress in ovarian cancer patients and to establish a connection between the presence of the reactive oxygen species (ROS) and VEGF. Methods: Forty-one patients diagnosed with epithelial ovarian carcinoma stage II-IV between 2010 and 2017, who underwent multimodality treatment (surgery and chemotherapy) were included in the study. ROS measured in dynamic (four determinations between every cycle) were malondialdehyde to evaluate the lipid peroxidation, ceruloplasmin, SH- albumin thiols groups and total antioxidants. Results: There was an increase in the value of ROS: malondialdehyde mean value was 8.5 μmol/100 ml (normal value 4 μmol/100 ml); ceruloplasmin mean value was 147.8U.I. (normal value 120U.I), both showing an active oxidative process in patients with ovarian cancer. A small decrease of the value of thiols (397 vs. 450 μmol/l) and a small increase of total antioxidants was noticed (1.45 vs. 1.4 μmol). All four compounds decreased between the first determination and the fourth one. There was a strong correlation between lipid peroxides levels and ceruloplasmin (Pearson correlation 0.315 p = 0.005) and between lipid peroxides and thiols groups (Pearson correlation 0.23 p = 0.039). There was a correlation between thiols and antioxidants (Pearson correlation 0.33 p = 0.003). Lipid peroxidation and ceruloplasmin were significantly higher in patients with residual disease (p = 0.039, p = 0.046) emphasizing that the tumor is a generator of oxidative stress. Mean VEGF levels were elevated 983.42 pg/ml, and VEGF levels statistically significant corelates with malondialdehyde (Pearson correlation 0.439, p = 0.036). Conclusions: Tumours produce ROS in excess in patients with advanced ovarian adenocarcinoma. Those ROS are corelated between each other and with VEGF and act as signalling molecules. Legal entity responsible for the study: National Institute of Oncology Al. Treistioreanu. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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