Homocysteine (Hcy) is an endogenous, non-structural protein, a sulfur-containing amino acid emerging on the pathway of methionine and cysteine, actively involved in numerous biochemical reactions. Total concentration of homocysteine in plasma of healthy humans is low and its level is between 5.0 and 15.0 mmol/l, assessed with the use of HPLC, or 5.0-12.0 mmol/l, using immunoassay methods. Higher concentration of this amino acid in blood is called hyperhomocysteinemia. Hyperhomocysteinemia is significantly correlated with cardiovascular disease and its complications: heart attacks and strokes. It is believed that hyperhomocysteinemia damages endothelial cells, reduces the flexibility of vessels, and adversely affects the process of hemostasis. In addition, hyperhomocysteinemia enhances the adverse effects of risk factors such as hypertension, smoking, and impaired glucose, lipid and lipoprotein metabolism, as well as promoting the development of inflammation. The concentration of homocysteine can be effectively lowered by supplementation with folic acid and vitamins B12 and B6. However, intervention studies conducted in the past decade did not confirm the clinical benefit of vitamin therapy lowering the level of homocysteine in blood of patients with cardiovascular disease. Moreover, there is not clear evidence from genetic studies that the presence of the gene for MTFHR polymorphism 677C>T, which is one of the most common causes of hyperhomocysteinemia, is also associated with the development of cardiovascular disease. These results led the researchers to discuss the role of homocysteine in the development and treatment of cardiovascular disease as well as the need for further research on this issue.
It is widely accepted that endothelial dysfunction is the basis of the development of cardiovascular diseases, including hypertension. With regard to hypertension, endothelial dysfunction is concerned mainly with impaired vascular expansion; however, it is also related to the intensity of the development of atherosclerosis and thrombosis. Among the factors that cause damage to the endothelium, along with classic risk factors, is hyperhomocysteinemia. Hyperhomocysteinemia promotes the formation of oxygen radicals, lowering the oxidation-reduction potential, adversely affects the biosynthesis and function of vasodilator factors in the vascular wall, contributes to the inhibition of endothelial cell division with intense myocyte proliferation and migration, and impairs production of extracellular matrix components in the vascular wall. In addition, high levels of homocysteine and its derivatives contribute to the modification of LDL and HDL particles, inflammation and disorders in coagulation and fibrinolysis. Biochemical effects of the impact of hyperhomocysteinemia on endothelium can lead to damage of endothelial cells, dysfunction of diastolic function of vessels and reduction of their flexibility through its influence on vascular wall remodeling. These changes lead to an increase in blood pressure, strengthening the development of hypertension and target organ damage in patients with this disease.
Aim of the studyAssessment of the concentrations of the soluble forms of the cell adhesion molecules sVCAM-1 and sICAM-1 in serum of female breast cancer patients. These concentrations were assessed in relation to factors such as: age, clinical stage of disease, histological grade of malignancy, the status of the local axillary lymph nodes, and the size of the primary tumour.Material and methodsA total of 103 patients with primary breast cancer, aged 29 to 89 years, were investigated. The control group consisted of 40 healthy women. The concentration of sVCAM-1 and sICAM-1 was assessed using an enzyme-linked immunosorbent assay (ELISA).ResultsThe results of the study suggest that the level of sVCAM-1 and sICAM-1 in the serum of women with breast cancer was significantly higher than that seen in the serum of healthy women. A relationship between the level of adhesion molecules and the stage of clinical disease advancement was discovered. There was a correlation between the increasing concentrations of sVCAM-1 and sICAM-1 and with the aggressiveness of the disease. Significant differences were also found in the group of women with metastases to the axillary lymph nodes and women with no metastasis. Similar correlations were found between sVCAM-1 and sICAM-1 levels and the size of primary tumour.ConclusionsThe results obtained suggest that the assessment of the soluble forms of sVCAM-1 and sICAM-1 may be useful indicators in the assessment of the clinical advancement of breast cancer.
The purpose of the study was to ascertain the value of assessment of vascular endothelial growth factor (VEGF) levels and microvessel density, and to search for correlations between them, in women with breast cancer. The assessment considered factors such as the stage of clinical disease advancement--according to International Union Against Cancer, the grade of histological malignancy, status of axillary lymph nodes and the size of the primary tumour. The concentration of VEGF was assessed in the plasma of 103 women with breast cancer, using an immunoenzymatic method (Quantikine test of R&D Systems). Assessment of microvessel density was performed using histopathological immunoperoxidase methods, using an anti-von Willebrand factor antibody (DAKO A/S). A statistically significant relationship was found between rising VEGF levels and microvessel density in women with breast cancer, when compared to values from a control group. A correlation was found between VEGF concentration and microvessel density (MVD) values. Statistically significant differences were found between VEGF levels of patients in stages I, II and III of clinical disease advancement. For MVD, differences were found only between stages I and III. A statistical relationship was also found between VEGF and MVD and tumour size. Similar results were found between VEGF concentrations in women with metastases to the axillary lymph nodes and cytokine levels in women with no metastases. The results of the study suggest that the degree of tumour vascularization and the concentration of VEGF may represent valuable indicators for the assessment of the angiogenic process in women with breast cancer.
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