Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer

Abstract

Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators.

Glyceraldehyde-3-phosphate dehydrogenase is overexpressed in colorectal cancer onset

“…Under mild oxidative stress conditions, such as the one that is induced by the repression of mitochondrial β-F1-ATPase, GAPDH is strongly hyperactivated, while apoptogenic stress levels inhibit GAPDH activity [26,27]. In advanced stages of tumour progression, oxidative stress is higher than in early phases of carcinogenesis [28][29][30], which can explain the increased levels of GAPDH in stage I in comparison with later stages of progression. In addition, overexpression of GAPDH has two cooperative roles in protection towards caspase-independent cell death; a high glycolytic ATP production and the induction of autophagy-mediated clearance of damaged mitochondria [6,7], both of which favour tumour onset.…”

Iron-enhanced coagulation is attenuated by chelation A thrombelastographic and ultrastructural analysis

“…Using deferoxamine-mediated chelation, appropriate temperature, and sufficient incubation time, it will be potentially possible to assess the impact of iron with thrombelastography, thromboelastimetry, or SEM. Thus, as reviewed [1], the role of ferritin and free iron excess in chronic diseases such as diabetes mellitus, rheumatoid arthritis, or perhaps cancer [19] can be assessed. Perhaps the degree of iron-specific hypercoagulability could be correlated with clinical disease, and in turn, such diagnostics could be used to assess the effectiveness of therapy targeted at diminishing circulating iron concentrations or interventions that diminish inflammatory processes that result in iron overload.…”

Determination of common urine substances as an assay for improving prostate carcinoma diagnostics

“…Several studies have reported that the uric acid level is depleted during tumor development (47,48). In contrast, uric acid may be increased due to cancer therapy, such as by chemotherapy or irradiation during treatment.…”