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Introduction: Malignant neoplasm of the endometrium is the most common malignant neoplasm of the female reproductive system. Toll Like Receptors (TLR) play a significant role in innate and late-immunity against infections or damaged tissues. TLRs are also involved in the development of tumors in their natural microenvironment. TLRs play an important role in angiogenesis, necessary for survival and growth of the tumor. Hypoxia playing a critical role in angiogenesis, carcinogenesis, tumor progression and distant metastasis is primarily mediated through hypoxia inducible factors (HIFs). Vascular endothelial growth factor family proteins (VEGF) are also strongly involved in tumor angiogenesis and their action is strongly associated with TLR receptors., Objectives: The aim of the study was to correlate the expression of selected TLRs and VEGFR's as well as HIF1α with clinicopathological data of endometrial cancer patients., Material and Methods: 123 neoplastic endometrial samples were included in the study. 51 samples of healthy endometrium served as control. The expression of TLR1, TLR2, TLR3, TLR4, VEGFR1 and VEGFR2, VEGF-A and HIF1α was examined after RNA isolation at the mRNA level by Real Time-PCR., Results: We have noted a significant correlation between the expression of selected TLR and VEGFR's and clinical stage as well as pathological grading of endometrial cancer., Conclusions: Received correlations confirm a significant contribution of some TLR expression and the receptor for VEGF in the pathogenesis of epithelial endometrial cancer.

Objectives: The aim of the study was to evaluate the cytotoxic effect of metformin on the ovarian cancer cells SKOV-3 and analyze the impact of this compound on the expression of genes coding for O-GlcNAc cycling enzymes, i.e. O-GlcNAc transferase (OGT) and -N-acetylglucosaminidase (OGA)., Materials and Methods: Viability and proliferation of control cells and cells treated with metformin were evaluated by MTT test and trypan blue staining. OGT and OGA mRNA expressions analysis was performed using real-time PCR method., Results: A metformin concentration-dependent decrease of SKOV-3 cell viability was observed. The IC50 parameter for metformin cytotoxicity was 14 mM. The SKOV-3 cell doubling time was 45 hours. The cell population treated with 10 mM metformin did not double even after 72 hours. There was no significant difference in mRNA level of OGA between control cells and cells treated with metformin. The OGT mRNA level was significantly higher in cells treated with metforrhin for 24 hours as compared to the control cells. The increase of OGT mRNA was dependent on time of incubation. Cells treated with metformin for 48 hour showed higher expression of OGT than cells treated for 24 hours., Conclusion: Antiproliferative activity of metformin suggests that this compound may be considered as a candidate for potential chemotherapeutic agent. However taking into account its impact on the expression of O-GlcNAc transferase, further studies on the molecular mechanism of metformin action are necessary

Objectives: The metastatic ability of tumors is characteristic for malignant neoplasms and constitutes the main cause of therapeutics failures. Metastasis formation involves the sequence of processes such as proteolytic degradation of the basement membrane, migration, intravasation, extravasation, proliferation and angiogenesis. Cadherins and integrins are groups of proteins directly involved in these processes. In the present study we analyzed the mRNA expression of CDH1 and ITGB1 genes by real-time polymerase chain reaction (RT-PCR). The study included 106 endometrial carcinomas. CDH1 and ITGB1 mRNA expression was found in all of the studied samples. Generally the CDH1 and ITGB1 mRNA expression was significantly higher in well-differentiated rather than poorly differentiated tumors., Materials and Methods: The mRNA expression levels of CDH1 and ITGB1 in series of 83 samples of endometrial carcinoma were studied by real time RT-PCR method. Statistical analysis of the obtained results was performed., Results: CDH1 and ITGB1 gene expression was observed in all examined tissues and was correlated with cancer malignancy (G). In high grade malignant tumors (G1), CDH1 and ITGB1 gene expression was the highest, in G2 and G3 tumors the expression of both genes was gradually lowering. Moreover the statistically significant correlation between CDH1 and ITGB1 gene expression was observed. (Spearman test, r=0.29, p

Breast cancer is the most common malignancy in women. Its estimated annual incidence is about one million cases worldwide. A number of risk factor have been identified, among them early menarche, late menopause, nulliparity and positive family history Moreover a number of highly penetrant breast and ovarian cancer susceptibility genes, such as BRCA 1 and BRCA2, have been identified. Recent findings suggest TopBP1 to be a breast and ovarian cancer susceptibility gene. Moreover; TopBPI protein may be an important prognostic marker of breast cancer TopBP1 protein is involved in DNA replication, mitosis and meiosis, as well as DNA repair Deregulation of these processes may have pathological implications in cancer

Breast and ovarian cancer are among the most common malignancies of women in the world. About 5 - 10% of the cases are considered familial. Germline mutations in the BRCA1 and BRCA2 genes are strong predictors of breast and/or ovarian cancer development. However currently known susceptibility genes including BRCA1, BRCA2, ATM, Chk2, PALB2, and BRIP1 explain less than 25% of familial breast and/ovarian cancers. Other genes, such as TopBP1 are also likely to be involved in hereditary predisposition to breast and/or ovarian cancer TopBP1 protein displays structural and functional similarities with BRCA1, and these two proteins have been suggested to function partially in the same cellular processes. TopBP1 protein is involved in DNA repair and cell cycle checkpoint control. Moreover TopBP1 interacts with transcription factors, such as E2F1, p53, Miz-1, HPV16 E2, and regulates their activity.

Objectives: O-GlcNAcylation is an abundant modification of cellular proteins which consist of single N-acetylglucosamine residues attached by O-linkage to serine or threonine residues. Abnormal O-GlcNAcylation seems to be a feature of malignant cancer cells. The aim of the present study was to determine the relationship between the expression of genes encoding O-GlcNAc cycling enzymes (OGT and MGEAS) and clinicopathological parameters of endometrial carcinomas., Materials and Methods: The mRNA expression levels of O-GlcNAc cycling enzymes in series of 76 samples of endometrial carcinoma were studied by real time RT-PCR method., Results: The OGT and MGEA5 mRNA expression was significantly higher in tumors of higher histological grade than in well-differentiated tumors. Statistically significant association was found between OGT and MGEA5 mRNA expression and depth of myometrial invasion. Both OGT and MGEA5 expression profiles showed no significant association with the clinical stage of endometrial cancer., Conclusion: O-GlcNAcylation may be an important regulatory modification involved in endometrial cancer pathogenesis but the actual significance of this modification for endometrial cancer progression needs to be investigated further.