Analysis of the Polymorphisms and Expression Levels of the BCL2, BAX and c-MYC Genes in Patients with Ovarian Cancer.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile.

Ovarian cancer is a common cause of death among women worldwide. The current diagnostic and prognostic procedures available for the treatment of ovarian cancer are either not specific or are very expensive. Gene expression profiling has proved to be a very effective tool in the exploration of new molecular markers in patients with ovarian cancer, although the link between such markers and patient survival and clinical outcomes is still elusive. We are looking for genes that may function in the development and progression of ovarian cancer. The aim of our study was to evaluate the expression of selected suppressor genes (ATM, BRCA1, BRCA2), proto-oncogenes (KRAS, c-JUN, c-FOS), pro-apoptotic genes (NOXA, PUMA), genes related to chromatin remodeling (MEN1), and genes related to carcinogenesis (NOD2, CHEK2, EGFR). Tissue samples from 30 normal ovaries and 60 ovarian carcinoma tumors were provided for analysis of the gene and protein expression. Gene expression analysis was performed using the real-time PCR method. The protein concentrations from tissue homogenates were determined using the ELISA technique according to the manufacturers' protocols. An increase in the expression level of mRNA and protein in women with ovarian cancer was observed for KRAS, c-FOS, PUMA, and EGFR. No significant changes in the transcriptional levels we observed for BRCA1, BRCA2, NOD2, or CHEK2. In conclusion, we suggest that KRAS, NOXA, PUMA, c-FOS, and c-JUN may be associated with poor prognosis in ovarian cancer.

Ozonation of Whole Blood Results in an Increased Release of Microparticles from Blood Cells.

Autohemotherapy with ozonated blood is used in the treatment of a broad spectrum of clinical disorders. Ozone demonstrates strong oxidizing properties and causes damage to cell membranes. The impact of whole-blood ozonation on the release of microparticles from blood and endothelial cells and the concentration of selected markers in the hemostatic system (APTT, PT, D-dimer, fibrinogen) were investigated. Venous blood, obtained from 19 healthy men, was split into four equal parts and treated with air, 15 µg/mL ozone, or 30 µg/mL ozone, or left untreated. The number and types of microparticles released were determined using flow cytometry on the basis of surface antigen expression: erythrocyte-derived microparticles (CD235+), platelet-derived microparticles (CD42+), leukocyte-derived microparticles (CD45+), and endothelial-derived microparticles (CD144+). The study is the first to demonstrate that ozone induces a statistically significant increase in the number of microparticles derived from blood and endothelial cells. Although statistically significant, the changes in some coagulation factors were somewhat mild and did not exceed normal values.