Impact of estrogen receptor alpha on the tamoxifen resistance in breast cancer patients

Genetic aberrations and changes in the activity of estrogen receptors alpha (ERa[lpha]) play an important role in the endocrine sensitivity. The aim of this study was to examine the relationship between the ESR1 expression level, its polymorphic variants, and the distribution pattern of ER[alpha] expression with the prognosis and efficacy of tamoxifen treatment in breast cancer patients. Our data suggest that the ESR1 expression level, SNPs in the ESR1 gene and the distribution pattern of ERα expression can be a potential molecular marker of tamoxifen resistance in breast cancer patients

Геологическое строение, нефтегазоносность и подсчет запасов газа пласта ПК1 Антипаютинского газового месторождения (ЯНАО)

На основе комплексной интерпретации данных сейсморазведки 3D, данных ГИС и испытания пласта в разведочных скважинах обосновано геологическое строение газовой залежи пласта ПК1 Антипаютинского месторождения. Проведен обобщающий анализ результатов лабораторных исследований кернов, пластовых флюидов, промыслово-геофизических и газогидродинамических исследований изучаемого объекта. Построены карты кровли коллекторов пласта ПК1, поверхности межфлюидного контакта, эффективных газонасыщенных толщин пласта. Дано обоснование подсчётных параметров, определяемых по данным ГИС (коэффициенты пористости, газонасыщенности, эффективные газонасыщенные толщины). На основе построенной детальной геологической модели проведён дифференцированный подсчёт запасов газа.On the basis of complex interpretation this seismic exploration 3D, data of GIS and test of layer in prospecting wells the geological structure of a gas deposit of PK1 layer of the Antipayutinsky field is proved. The generalizing analysis of results of laboratory researches of cores, formation fluids, trade and geophysical and gas-hydrodynamic researches of the studied object is carried out. Cards of a roof of collectors of PK1 layer, a surface of interfluid contact, effective gas-saturated thickness of layer are constructed. Justification of the subcalculating parameters determined by data of GIS (coefficients of porosity, gas saturation, effective gas-saturated thickness) is given. On the basis of the constructed detailed geological model the differentiated calculation of reserves of ga

Voltammetric determination of indomenthyl

Cytokines are important mediators coordinating inflammation and wound healing in response to tissue damage and infection. Therefore, immobilization of cytokines on the surface of biomaterials is a promising approach to improve biocompatibility. Soluble cytokines signal through receptors on the cell surface leading to cell differentiation, proliferation, or other effector functions. Random immobilization of cytokines on surfaces will result in a large fraction of inactive protein due to impaired cytokine-receptor interaction. We developed a strategy that combined (i) directed covalent coupling of cytokines, (ii) quantification of coupling efficiency through fluorescence detection, and (iii) a reliable protease cleavage assay to control orientation of coupling. For this purpose, fusion proteins of the SNAP-tag followed by an enterokinase recognition site, yellow fluorescent protein (YFP), and the cytokine of interest being either interleukin-6 (IL-6) or oncostatin M (OSM) were generated. The SNAP-tag is a derivative of O6-alkylguanine-DNA alkyltransferase that couples itself covalently to benzylguanine. Bioactivities of the SNAP-YFP-cytokines were shown to be comparable with the nontagged cytokines. Efficient coupling of SNAP-YFP-cytokines to benzylguanine-modified beads was demonstrated by flow cytometry. The fact that enterokinase treatment released most of the fluorescence from the beads is indicative for directed coupling and only marginal adsorptive binding. Cellular responses to SNAP-YFP-cytokine beads were analyzed in cellular lysates and by confocal microscopy indicating that the directionally immobilized cytokines are fully signaling competent with respect to the activation of ERK and STAT3. The strategy presented here is generally applicable for the directed covalent immobilization of fluorescently labeled proteins including the convenient and reliable control of coupling efficiency and orientation

Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro

Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury

Ribonuclease 1 attenuates septic cardiomyopathy and cardiac apoptosis in a murine model of polymicrobial sepsis.

Septic cardiomyopathy is a life-threatening organ dysfunction caused by sepsis. Ribonuclease 1 (RNase 1) belongs to a group of host-defense peptides that specifically cleave extracellular RNA (eRNA). The activity of RNase1 is inhibited by ribonuclease-inhibitor 1 (RNH1). The role of RNase 1 in septic cardiomyopathy and associated cardiac apoptosis, however, is completely unknown. Here, we showed that sepsis resulted in a significant increase in RNH1 and eRNA serum levels compared to those of healthy subjects (p < 0.05). Treatment with RNase 1 resulted in a significant decrease of apoptosis, induced by the intrinsic pathway, and TNF expression in murine cardiomyocytes exposed to either necrotic cardiomyocytes or serum of septic patients for 16 h (p < 0.05). Furthermore, treatment of septic mice with RNase 1 resulted in a reduction in cardiac apoptosis, TNF expression and septic cardiomyopathy (p < 0.05). These data demonstrate that eRNA plays a crucial role in the pathophysiology of the organ (cardiac) dysfunction in sepsis and RNase and RNH1 may be new therapeutic targets/strategies to reduce the cardiac injury and dysfunction caused by sepsis