[Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Contributes to Tamoxifen Resistance in Estrogen-Positive Breast Cancer Patients].

Crosstalk between the estrogen receptors and the receptor tyrosine kinases, including vascular endothelial growth factor receptor type II (VEGFR2), is a key mechanism in breast cancer resistance to antiestrogen therapy with tamoxifen. A high level of VEGFR2 expression in a tumor serves as a marker of tamoxifen resistance. The tamoxifen efficacy prognostic value of functional polymorphisms in the VEGFR2/KDR gene has not been established. Using qRT-PCR, we detected the rs2071559 and the rs2305948 variants and the levels of KDR gene expression in 122 breast tumor tissue samples from cohorts of patients with progression (distant metastases or relapse) and patients with no progression during tamoxifen therapy. The expression levels of VEGFR2 protein were analyzed by immunohistochemistry. The frequency of heterozygous and mutant genotypes of the rs2305948 SNP was significantly higher in patients without progression than in the cohort with progression. KDR rs2305948 was associated with high survival rates in breast cancer patients. A correlation between the mRNA of the ESR1 and KDR genes in patients without progression was detected. The results indicate the prognostic value of rs2305948 and its potential contribution to the tumor phenotype sensitive to tamoxifen.

[Hormonal shifts in chronic hepatic diseases].

The authors offer quantitative evaluation of system cooperation of endocrine functions in healthy individuals, and apply a system approach to diagnostics of chronic liver diseases. The study included analysis of rectilinear and curvilinear correlations between endocrine system parameters in healthy individuals, and shifts in the levels of multilateral associations between the concentrations of various hormones in patients with different degree of the pathologic process in the liver. The study revealed system disintegration which occurs in the organism in cases of liver involvement and found that all liver diseases are associated with pronounced shifts in the condition of the hormonal system. The authors recommend distinguishing certain bands of the functional condition of the organism, which would allow determination of health status, risk groups, presence and prognosis of an illness. Analysis of hormonal status revealed elevation of excessiveness coefficient in liver diseases. The study established parameters that do not only allow quantitative evaluation of system disintegration of the endocrine system functioning, but differentiation of these diseases as well. The results suggest that cooperation of hormonal functions and their intermodal stability underlie the functional condition of both the endocrine system and the entire organism. Integral indices, unlike qualitative characteristics of individual functions, possess high diagnostic and prognostic relevance.