[Methylation profiles of genes in breast cancer luminal HER2-negative primary tumor during regional lymphnode metastasis]. / Profil' metilirovaniia genov pervichnoi opukholi u bol'nykh liuminal'nym HER2-negativnym rakom molochnoi zhelezy pri metastazirovanii v regionarnye limfaticheskie uzly.

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene - p=0.009 (AUC (95%CI) = 0.76 (0.59-0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6-0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.

[The content of cytokines IL-6, IL-8, TNF-α, IL-4 and the level of expression in macrophages CD86 and CD163 in peritoneal fluid has a reverse correlation with the degree of severity of external genital endometriosis]. / Soderzhanie tsitokinovIL-6, IL-8, TNF-α, IL-4 i uroven' ékspressii makrofagami CD86 i CD163 v peritoneal'noi zhidkosti imeet obratnuiu korreliatsiiu so stepen'iu tiazhesti naruzhnogo genital'nogo éndometrioza.

Concentrations of eight different cytokines and the level of expression of CD86 and CD163 macrophages were studied in peritoneal fluid in women with endometriosis. It was found that the concentration of both inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) as well as the level of macrophage expression of the proinflammatory marker CD86 and anti-inflammatory marker CD163 increased in women with mild external genital endometriosis (1-2 stage), and did not differ from the control group in women with severe endometriosis (3-4 stage). The content of IL-2, IL-10, CM-CSF and IFN-γ in the peritoneal fluid of women with endometriosis did not differ significantly from the control group. The results of the study indicate that the development of external genital endometriosis may be based on insufficient both inflammatory and anti-inflammatory activity of macrophages in the peritoneal fluid.

Complex Analysis of Total and Fetal DNA and Cytokines in Blood Plasma of Pregnant Women with Preeclampsia.

We performed a complex analysis of total and fetal extracellular DNA, 8 cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage CSF, IFNγ, and TNFα) in blood plasma obtained from women with preeclampsia prior to labor onset. Total (sensitivity 89.47%, specificity 93.75%) and fetal extracellular DNA (sensitivity 73.68%, specificity 87.5%) were the most accurate parameters determining preeclampsia. We revealed a high correlation (p=3×10-6) between total and fetal extracellular DNA levels in the group of preeclampsia. Preeclampsia significantly increased the levels of macrophage factors IL-10 and IL-6. These cytokines significantly correlated with the levels of total and fetal extracellular DNA in the preeclampsia group. In the control group, such correlations were not observed. These findings obtained suggest that preeclampsia develops upon increased macrophage activity, leading to destruction of the placenta trophoblast cells.