The initial levels of soluble Fas antigen (sFas), leptin, and vascular endothelium growth factor (VEGF) were measured in the sera of 100 patients with ovarian cancer and benign tumors and in 60 healthy women aged 28-65 years. Serum levels of sFas and VEGF were elevated in the total group of patients with ovarian tumors, while leptin levels were the same as in healthy women. The studied parameters did not depend on the age of patients and healthy women. The levels of sFas and leptin were virtually the same in benign and malignant ovarian tumors, while VEGF concentration was higher in patients with ovarian cancer. The mean serum levels of sFas, VEGF, and leptin in patients with poorly and moderately differentiated serous ovarian cancer were 2-fold higher than in well-differentiated tumors (p<0.05), while serum concentrations of sFas and leptin increased with the disease stage progress in patients with ovarian cancer (p<0.05). According to the data of unifactorial analysis, the increase in serum levels of sFas and VEGF in ovarian cancer patients correlated with short duration of the relapse-free period. Multifactorial analysis showed that the disease stage (p=0.006), presence of ascites (p=0.03), VEGF concentration (p=0.02), and the sFas/leptin coeffi cient (p=0.045) are highly signifi cant independent factors for predicting the relapse-free survival of patients with serous ovarian cancer.Ovarian cancer ranks fi rst in the structure of mortality from malignant tumors of the female reproductive sys tem [2]. Analysis of the Russian and foreign publications showed unsatisfactory results of treatment of patients with ovarian cancer, because by the moment of diagnosis about 70% patients have advanced stages of the tumor process [3]. In addition, ovarian cancer unites the histogenetic variants of tumors, the majo rity of which are characterized by aggressive clinical course and are liable to early metastasizing. The aggressive nature of the tumor manifests by its capacity to invasion and metastasis development. This can be due to histogenesis, differentiation degree, and genome damage, all this leading to activation of the factors closely related to "biological" behavior of the tumor.Studies of biological factors essential for tumor growth and metastasizing will lead to better understanding of some stages in the pathogenesis of ovarian tumors. Inhibition of Fas-dependent apoptosis is an important component in the system of transformed cell defense from antitumor immunity. The Fas receptor triggers apoptosis in the target cell after interactions with its ligand (FasL). Soluble Fas (sFas) distantly
A test system developed by the authors was used to measure serum concentrations of soluble Fas in patients with malignant and benign tumors of different location and morphology. Relationships between soluble Fas levels and the main clinical and morphological characteristics of cancer were evaluated. It is proven that the concentrations and incidence of detection of soluble Fas in the sera of patients with tumors are significantly higher than in normal subjects. No appreciable differences in the concentrations of soluble Fas were detected in malignant and benign tumors of the mammary gland, bones, ovaries, and adrenals. In thyroid cancer, soluble Fas levels were higher than in benign and hyperplastic processes in this organ. High level of soluble Fas is associated with late stages of the disease (ovarian cancer, cancer of the corpus uteri, adrenocortical and colorectal cancer) and with poor differentiation of the tumor (ovarian cancer and cancer of the corpus uteri), with local metastases (colorectal and adrenocortical cancer), and with tumor invasion into the myometrial tissue, intestinal wall, and adjacent tissues (cancer of the corpus uteri and colorectal cancer). A significantly high level of soluble Fas was detected in colorectal and adrenocortical cancer in the presence of at least 2 local metastases. Soluble Fas levels depended on tumor histogenesis in malignant and benign ovarian tumors. High concentration of soluble Fas was detected in large tumors in patients with ovarian cancer, cancer of the corpus uteri, colorectal cancer, thyroid cancer and adenoma, and in adrenocortical cancer. Initially high levels of soluble Fas are characteristic of patients whose tumors are little sensitive to nonadjuvant radiotherapy. The overall 5-year survival of patients with low levels of soluble Fas is better in osteosarcoma, cancer of the corpus uteri, ovarian and adrenocortical cancer.
Here we present the results of evaluation of the expression of neural cell adhesion molecules CD56 (NCAM) in serous ovarian adenocarcinoma. The expression was detected in 48.5% cases. Infiltration of tumor stroma and parenchyma with CD8+ and CD4+ lymphocytes was significantly less pronounced in tumors expressing neural cell adhesion molecules; CD3+CD4+CD25+ predominate among CD4+ lymphocytes in CD56+ tumors. CD56+ tumors were lower in size (5.2±0.6, 7.9±0.8 and 10.3±1.5 cm in monomorphic, mosaic, and negative phenotypes, respectively (p=0.05) and were characterized by the absence of cystic component (p=0.012), larger disseminations in the peritoneum (4.2±1.1 and 2.7±0.5 cm; p=0.05), and larger volume of the residual tumor (p=0.018) after surgical treatment. NCAM phenotype of the tumor does not correlate with the stage and differentiation degree of serous ovarian adenocarcinoma.
The main biologically significant molecular markers of human tumors are discussed on the basis of modern published data and author's findings of many-year studies: steroid hormone receptors, growth factors and underlying signal proteins, tumor-associated proteases, and angiogenesis markers. Methodological aspects, progress in preclinical studies, international recommendations on the use of these parameters for prediction of the disease course and prescription of effective therapy are analyzed. Latest data on the potentialities and limitations of modern highly productive technologies (microchips) as an alternative to studies of individual molecular markers are presented.
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