THE MAIN PARAMETERS OF CELLULAR IMMUNITY IN PATIENTS WITH TRIPLE-NEGATIVE BREAST CANCER: RELATIONSHIP WITH EFFICIENCY OF CHEMOTHERAPY

Chemotherapy is among the primary methods of treating advanced breast cancer. It was shown that clinical efficacy of various chemotherapeutic agents in many cases depends not only on their direct cytostatic and/or cytotoxic effect upon tumor cells, but also on their ability to modulate phenotype of the tumor cells and to influence anti-tumor immune response. Initial state of the immune system and its response to treatment is crucial. Antitumor response involves cells of innate and adaptive immunity (NK, NKT, T cells). These populations are heterogeneous and contain, e.g., cells with antitumor activity and regulatory (suppressor) cells that suppress immune response and promote tumor progression. The aim of this work was to determine the relationship between the initial state of cellular immunity of patients suffering from locally advanced breast cancer with triple negative phenotype, and clinical effect of chemotherapy (cisplatin + doxorubicin/paclitaxel), and studying effects of the therapy upon subpopulation profiles of peripheral blood lymphocytes in the patients. We registered the terms of the disease progression as well as overall survival and progression-free survival. The disease progressed in 25 of 53 cases (47.2%) whereas 28 of 53 patients (52.8%) remained progression-free. The observation period was 35.5 months. Laboratory examination of the patients included immunophenotyping of peripheral blood lymphocytes and determination of NK cell cytotoxic activity before and after chemotherapy. Percentages of effectors and regulatory lymphocyte populations were determined. The results obtained showed that, for some lymphocyte subsets, the pre-treatment differences of cell percentage deviations from control were found between the progression-free groups and patients with progression of the disease. The differences in percentages of NKT cells and lymphocytes expressing CD25 activation marker proved to be most significant. Decreased number of NKT cells and activated CD25+ lymphocytes prior to chemotherapy was associated with increased probability of disease progression. Reduced percentage of NKT cells against control was observed in 56% of patients from the progression group (PD), and only 21.4% in the group free of disease progression (DF). [OR = 4.6 (95% CI 1.4 to 15.4)]. Percentage of CD25+ lymphocytes was decreased from 68.2% in the PD group, and 28.6% for DF patients [OR = 5.4 (95% CI 1.6-18.1)]. We studied relationships between the overall survival (OS) and percentage of perforin-containing NK, NKT, and T cells, and mean perforin fluorescence density (PFD) in these lymphocyte subsets in 26 of the 53 patients before treatment. A statistically significant positive correlation was revealed between OS and perforin PFD in all the three cell populations under study. Normalization of the parameters altered before treatment, and an increase of T cell numbers was observed in the disease-free patients

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10−8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5–18.2 mmHg, P = 2.22 × 10−126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54–9.70; P = 4.13 × 10−44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781–0.801) to 0.826 (95% CI, 0.817–0.836, ∆AUROC, 0.035, P = 1.98 × 10−34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research

Demographic potential of the Krasnoyarsk region in 1990–2000s

В статье анализируется в динамике система показателей, характеризующих демографический потенциал края. Все процессы рассмотрены в сравнении с аналогичными по России в целом, трактуются на основе теории демографической модернизации и конкретизирующей ее концепции второго демографического перехода.The article analyzes in dynamics the system of indicators characterizing the demographic potential of the region. All processes are considered in comparison with similar ones in Russia as a whole, are interpreted on the basis of the theory of demographic modernization and concretising the concept of the second demographic transition

Between Two «Russian Crosses»: the Reproduction of the Siberian Rural Population in the Post-Soviet Decades

Данной работе рассмотрены основные тенденции развития процесса воспроизводства населения в сибирской деревне в постсоветский период на примере населения Красноярского края. Цель исследования — выяснить, какой характер приобрел этот процесс в условиях радикальной трансформации сельского общества и какие особенности он имел в сибирских условиях. Выбор темы обусловлен ее недостаточной разработкой на общероссийском уровне и слабой изученностью в масштабах сибирских регионов. Все процессы красноярской деревне рассмотрены в сравнении с аналогичными в городах края и сельской местности России в целом. Информационную базу исследования составили итоги всеобщих переписей населения 1989, 2002 и 2010 гг., микропереписи 1994 г., текущая демографическая статистика. На основе статистического анализа динамики численности населения, уровня рождаемости и смертности показывается, что количественно демографический потенциал красноярских деревень с начала 1990-х гг. существенно уменьшился, утеряны положительные отличия половозрастной структуры населения. Исследование показало, что процесс воспроизводства сельского населения неустойчив и очень зависит от внешних условий. Их улучшение вызвало краткий рост рождений с начала реализации в 2007 г. национальных и краевых демографических проектов. Неустойчивость процесса воспроизводства обязывает отслеживать все его колебания, поскольку главным условием раз-работки эффективной демографической политики является знание всех тенденций рождаемости и смертности и определяющих их факторов в региональных масштабах.In this paper, the main trends in the development of the process of population reproduction in a Siberian village during the post-Soviet period are examined based on the example of the population of the Krasnoyarsk Territory. The purpose of the research is to find out what character this process acquired in the conditions of radical transformation of rural society and what features it had under Siberian conditions. The choice of the topic is due to its inadequate development at the all-Russian level and a weak study on the scale of the Siberian regions. All processes in the Krasnoyarsk village are considered in comparison with similar ones in the cities of the region and the countryside of Russia as a whole. The information base of the study was the data of 1989, 2002 and 2010 population censuses, the data of 1994 micro-census and the current demographic statistics. Based on the statistical analysis of population dynamics, level of fertility and mortality, it is shown that the demographic potential of the Krasnoyarsk villages has decreased significantly since the early 1990s, the positive differences in the age and sex structure of the population have been lost. Research has shown that the process of reproduction of the rural population is unstable and very dependent on external conditions. Their improvement has caused a short increase in births since the beginning of the implementation in 2007 year of national and regional demographic projects. The instability of the reproduction process requires that all its fluctuations be monitored, since the main condition for the development of an effective demographic policy is the knowledge of all the trends in the birth rate and mortality and the factors determining them on a regional scale