Detection and Genotyping of Human Papillomavirus (HPV16/18), Epstein-Barr Virus (EBV), and Human Cytomegalovirus (HCMV) in Endometrial Endometroid and Ovarian Cancers.

The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.

Evaluation of Variances in VEGF-A-D and VEGFR-1-3 Expression in the Ishikawa Endometrial Cancer Cell Line Treated with Salinomycin and Anti-Angiogenic/Lymphangiogenic Effect.

BACKGROUND: In cancer, an excessive and uncontrolled process of creating new blood and lymphatic vessels that play a key role in the metastasis process can be observed. The Vascular Endothelial Growth Factor (VEGF-A,-B,-C,-D) family together with their specific receptors (VEGFR-1,-2,- 3) plays a key role in these processes, therefore, it would be reasonable to determine the correct pattern of their expression. OBJECTIVES: The study aimed to assess the use of salinomycin as an anti-angiogenic and anti-lymphangiogenic drug during endometrial cancer by examining changes in the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3 depending on the treatment period of the Ishikawa endometrial cancer cells with salinomycin in comparison to the control culture. MATERIALS AND METHODS: To determine how influential salinomycin was on the expression of both mRNAs, 1 µM of the drug was added to the cell culture and then it was cultured all together for 12, 24 and 48 hour periods. The cells that made up the control culture were not treated with salinomycin. To determine the changes in the expression profile of the selected genes, we used the microarray, techniques: RTqPCR and ELISA (p<0.05). RESULTS: For all isoforms of VEGF-A-D as well as receptors of VEGFR-1-3, a decrease in expression under the influence of salinomycin was noted. For VEGF-A and VEGFR-1, the difference in the expression between the culture treated with salinomycin in comparison to the control was statistically significant (p=0.0004). In turn, for VEGF-B, the difference between the culture exposed for 24 hours in comparison to the control (p=0.00000) as well as the comparison between H48 vs. C (p=0.00000) was statistically significant. In reference to VEGF-C, VEGFR-2 and VEGFR-3, the statistical analysis showed the significant difference in expression between the culture incubated with the drug for 12, 24 and 48 hours in comparison to the control as well as between the selected times. For all of these comparisons, p=0.00000 was utilized. CONCLUSION: Salinomycin changes the expression pattern of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3 in endometrial cancer cells. The obtained results suggest that salinomycin might exert the effect via VEGF signaling pathways.

Cisplatin Changes Expression of SEMA3B in Endometrial Cancer.

BACKGROUND: Semaphorin 3B (SEMA3B) is characterized as a strong suppressing factor of the proliferation of cancerous cells and also by its anti-angiogenic effect. However, the knowledge on the changes in the expression profile of SEMA3B under the influence of cisplatin in endometrial cancer remains fragmented. The aim of this work was to note the changes in expression of SEMA3B when under the influence of cisplatin in the endometrial cancer cell line. METHODS: Ishikawa cell line cells were exposed to three different concentrations of cisplatin: 2.5µM; 5µM; 10µM for 12, 24 and 48 hours and were compared to cells untreated by the drug. Changes in the expression profile of SEMA3B were determined based upon RtqPCR (mRNA) alongside the ELISA assay (protein). The Statistica 13.0 PL program was used for statistical analysis (p<0.05). RESULTS: Changes on the transcriptome level seem to be more dynamic than on the proteome level. Regardless of the concentration given or the exposition period, the expression of semaphorin 3B was, in fact, higher in cells exposed to cisplatin. Statistically substantial differences (p<0.05) in the expression of SEMA3B mRNA and protein were seen for all incubation periods at the given cisplatin level when compared to the control. CONCLUSION: Cisplatin causes a growth in the expression of SEMA3B in an endometrial cancer cell culture, this results in the restoration in the state of cell homeostasis and shows the effectiveness of pharmacotherapy, including a low risk of drug resistance.

Variances in the Level of COX-2 and iNOS in Different Grades of Endometrial Cancer.

BACKGROUND: Many experimental studies have demonstrated the importance of COX-2 in the tumor angiogenesis. Inducible iNOS is responsible for a high and stable level of nitric oxide and is expressed in response to pro-inflammatory factors. OBJECTIVE: The aim of this study was to evaluate the expression of COX-2 and iNOS at the protein level and to assess their potential prognostic significance in patients with endometrial cancer. METHODS: The study group consisted of 45 women with endometrial cancer divided according to the degree of histological differentiation i.e. G1, 17; G2, 15; G3, 13. The control group consisted of 15 women without neoplastic changes. The expression of studied proteins was determined immunohistochemically with specific polyclonal antibodies. RESULTS: Analysis of the COX-2 expression showed that the optical density of the reaction product in G1 reached 186% in the control group, while the values in G2 and G3 reached 243% and 293%, respectively. In the case of iNOS, the optical density of the reaction product reached the following percentages in the control group: 147% in G1, 243% in G2, and 241% in G3. CONCLUSION: Our findings suggest that changes in the expression of COX-2 and iNOS may be potentially useful in predicting the progression of endometrial cancer and treatment effectiveness.