Značaj oksidativnog stresa i poremećaja metabolizma arginina kao markera metastaziranja tumora debelog creva

Abstract

Colorectal cancer is one of the most frequent human malignant diseases and one of the most common causes of malignant diseases death. Oxidative and nitrosative stress have an important role in cancer initiation and propagation. That is why this study is focused on the determination of oxidative and nitrosative stress markers in tumor, adjacent and health tissue, which are important for estimation of tumor proliferative and angiogenic potential and assessment of their validity in identification of patients’s risk for tumor process promotion and distant metastasis development. The study encompassed 50 patients who underwent surgery due to colorectal cancer. In the tissue samples from resected preparation (tumor, adjacent and healthy tissue, at least 10 cm distant from tumor), oxidative and nitrosative stress markers, malondyaldehyde and nitric oxide (NO), as well as superoxide dismutase activity, were determined. Also, arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethylarginines, as potent modulators of NO synthesis, were determined. The biochemical parameters were correlated with the tumor recurrence, metastasis and three year- and five year survival. The results of this multidsiciplinary study prove the presence of oxidative stress in tumor tissue. Lower NO concentrations in tumor tissue compared to the adjacent tissue point out high angiogenic potential, which could have clinical importance in the assessment of the probability of local recurrence. Increased ADMA and SDMA concentrations in tumor tissue associated with low NO levels, make the basis for the new therapeutic strategies directed to the use of inhibitors of their synthesis as ideal candidates for molecular threrapy of colorectal cancer. ADMA concentration in adjacent tissue was proved to be an independent predictor of distant metastasis. The obtained results point out that determination of examined biomarkers in colorectal cancer tissue samples, after surgery, could give useful informations about tumor proliferative and angiogenic potential in patients, which could enable individualization of therapy and the choice of adequate adjuvant therapy.