MicroRNA expression as a diagnostic parameter in early endometrial cancer.

OBJECTIVES: MicroRNAs (miRNAs) have emerged as biomarkers that showed strong diagnostic potential in various diseases, including cancer. This study aimed to estimate the expression and diagnostic potential of miRNAs (miR-200a, miR-21, miR-210, miR-126, and miR-130a) in endometrial cancer samples. The DICER1 and AGO2 genes were also analysed. METHODS: The expression of miRNAs, DICER1, and AGO2 was quantified using the quantitative real-time PCR method in 40 tissue samples with early-stage endometrial cancer and 16 normal controls. RESULTS: All tested miRNAs showed significantly higher expression in endometrial cancer compared with the control group, while DICER1 was significantly downregulated. The expression levels of miR-200a, miR-21, and miR-210 were negatively correlated with DICER1 expression. Individually, miR-200a, miR-21, miR-210, and DICER1 showed the best diagnostic performance in distinguishing patients with endometrial cancer from normal controls, whereas a combination of all biomarkers resulted in an even higher area under the curve. CONCLUSIONS: Our study showed that a panel of selected biomarkers (miR-200a, miR-21, miR-210, miR-126, miR-130a, DICER1, and AGO2) may be candidates for the detection of early-stage endometrial cancer.

Potential of Orlistat to induce apoptotic and antiangiogenic effects as well as inhibition of fatty acid synthesis in breast cancer cells.

Breast cancer as most often women's cancer is the second cause of mortality worldwide. Research interest increased in testing non-standard drugs to suppress breast cancer progression and become significant supplements in anticancer therapy. The anti-obesity drug Orlistat showed significant ability for modulation of cancer cell metabolism via antiproliferative, proapoptotic, antiangiogenic, antimetastatic, and hypolipidemic effects. The anticancer potential of Orlistat was evaluated by cytotoxicity (MTT assay), type of cell death (AO/EB double staining), determination of redox status parameters (superoxide, hydrogen peroxide, lipid peroxidation, reduced glutathione), and total lipid levels with colorimetric methods, as well on angiogenesis-related (VEGF, MMP-9, CXCR4/CXCL12) and fatty acid synthesis-related (ACLY, ACC, FASN) parameters on gene and protein levels (immunocytochemistry and qPCR). Based on obtained results Orlistat induces significant cytotoxic, proapoptotic, and anti-angiogenic effects in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells, without significant cytotoxic effects on normal MRC-5 cells. It decreased total lipid levels and changed redox status parameters and cancer cell metabolism via suppression of genes and proteins involved and fatty acid synthesis. Based on showed, Orlistat may be an important supplement in antiangiogenic therapy against breast cancer with no side effects on normal cells, making it a good candidate for future clinical trials.

L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.

This study evaluated the potential of antitumor activity of snake venom from Vipera ammodytes and L-amino acid oxidase from Crotalus adamanteus on different colorectal cancer cell lines through determination of cytotoxic activity by MTT assay, pro-apoptotic activity by acridine orange/ethidium bromide staining, and concentrations of redox status parameters (superoxide, reduced glutathione, lipid peroxidation) by colorimetric methods. The expression of genes involved in the biotransformation process and metabolite efflux was determined by qPCR method, while protein expression of glutathione synthetase and P-glycoprotein were analysed by immunocytochemistry. The analysis of cell death shows that snake venom dominantly leads cells to necrosis. Induction of apoptosis by L-amino acid oxidase was in correlation with oxidative disbalance in cancer cells. Gene expression profile of membrane transporters and CYP genes were different in each cell line and in correlation with their sensitivity of treatment. Our results show that L-amino acid oxidase from snake venom is a potent cytotoxic substance with pronounced pro-apoptotic activity. The inhibition of P-glycoprotein suggests that L-amino acid oxidase is a good substance for furter research of antitumor effect, with unexpressed potential for occurrence of drug resistance in vitro.

Correlation of elongation factor 1A accumulation with photosynthetic pigment content and yield in winter wheat varieties under heat stress conditions.

Heat stress is one of the most important environmental factors that influences wheat growth and development, leading to significant losses in grain yield and has become a significant detrimental factor for worldwide wheat production. In recent years, several studies suggested that eukaryotic elongation factor 1A (eEF1A), may contribute to heat tolerance in plants, therefore the aim of this study was: to investigate the accumulation of eEF1A in wheat under conditions of moderate and high air temperatures; to determine the amount of photosynthetic pigments and to determine the yield traits; and to examine whether there is a correlation between eEF1A accumulation, photosynthetic pigments, and yield in different wheat varieties. The results showed that heat stress induced accumulation of eEF1A significantly different among wheat varieties and showed that varieties with a higher accumulation of eEF1A under heat stress are characterized by a smaller decrease in the photosynthetic pigments. A correlation between higher accumulation of eEF1A under heat stress and yield traits was found. Analyzed parameters from two growing seasons, indicated that the higher accumulation of eEF1A and a smaller decrease in photosynthetic pigments distinguishes the varieties more resistant to heat stress. The analysis of the molecular mechanisms by immunoblot, under conditions of high and moderate air temperatures in two growing seasons, aims to develop agricultural strategy and develop wheat varieties tolerant to heat stress.