Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for ...TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the
genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high
expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the
and
genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4,
= 2.6 × 10
; R = -0.21,
= 0.015) and cg21886367 (R = -0.45,
= 7.3 × 10
; R = -0.24,
= 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated
. To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated
genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating
hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.
Abstract
The results of an experimental study of the adiabatic wall temperature for a supersonic air flow across the cylinder are presented. The temperature was measured contactlessly using an ...InfraTEC ImageIR 8855 thermal imager through a ZnSe infrared illuminator. The freestream Mach number was 3.0, input flow total temperature was 295 K, and the total pressure 615 kPa. The Reynolds number calculated from the cylinder diameter (30 mm) was about 10
6
. It is shown that it is possible in principle to determine the high-speed flow total temperature by defining the maximum temperature of a cylindrical probe at the front critical point. Thermograms of the wall temperature distribution along the profile of the cylinder were obtained. The research was performed at the experimental facilities of the Institute of Mechanics of Lomonosov Moscow State University.
The article puts forward a modified finite element method based on decomposition and analytical solution techniques. The algorithm is as follows. A complex structure is divided into simple form ...sub-regions which involve partial differential equations. Next, the equations are decomposed. The decomposed equation solutions are written using analytical solution formulae. Meanwhile, the finite element size of the method proposed is defined only by the value of an averaging interval of required functions, since ordinary differential equation formulae are analytical. The algorithm has been tested by solving rectangular plate and bicurved shallow shell bending problems. The results proved proper convergence to precise values with increasing number of finite elements.
The active centers of carbon catalysts doped with cobalt, nickel, copper, manganese, zinc, and chromium were modeled by density functional theory methods. Likewise, the thermodynamics of the oxygen ...reduction reaction (ORR) on model catalysts were determined. The features of the chemical properties of chromium-containing material, namely its spontaneous oxidation into the hydroxo form, were revealed. In addition, it was established that among the studied catalysts, graphene doped with cobalt showed the best properties.
The results of an experimental study of the thermal parameters of a supersonic flow around a flat wall in the presence of finely divided water droplets are presented. The relative mass flow rate of ...the liquid (mass concentration) varied in the range 0.05-0.5%. Liquid (distilled water) was sprayed through centrifugal nozzles into the air flow in the prechamber of the supersonic wind tunnel. Next, the adiabatic wall temperature for the given flow conditions was measured with the use of infrared thermal imager. The input flow Mach number was 2.5, the Reynolds number based on the dynamic boundary layer length from the nozzle throat was at least 2·107 at the nozzle exit section. The research was performed at the experimental facilities of the Institute of Mechanics of Lomonosov Moscow State University.
The results of an experimental study of heat transfer for a supersonic flow behind a backward-facing step are presented. Input flow Mach number was 2.2, Reynolds number was over 20 million when ...calculated with the use of the dynamic boundary layer length from the critical section to the exit section of the nozzle. The height of the step ranged from 8 to 14 mm. The thickness of dynamic boundary layer for plane model flow was about 6 mm in the region of nozzle exit section. The heat transfer coefficient and adiabatic wall temperature for the wake flow behind the step have been analysed in comparison with the plane model flow. The experiment was made with the use of chromel-kopel thermocouples with thermal compensation of cold junction, stagnation and static pressure meters, NI LabView powered programs of experimental automation. The graphs of the wall temperature, stagnation flow temperature, adiabatic wall temperature, the stagnation and static pressure, the distribution of the temperature recovery coefficient and the relative Stanton number along the model length are presented.
The results of an experimental study of heat transfer for supersonic flow around plane surface in the wake of a rib are presented. The study was conducted on unsteady regime during the launching ...supersonic wind tunnel before reaching the equilibrium thermal state. The initial flow Mach number was 2.2, Reynolds number based on the length of the dynamic boundary layer from the nozzle throat was over 20 million at the nozzle exit section. The rib height was varied from 2 to 10 mm while boundary layer thickness for smooth model flow in the region of rib placement was about 6 mm. Recovery temperature and the coefficient of heat transfer enhancement for flow past the rib are presented in comparison with the regime of a smooth model flow. The research was carried out with the use of thermocouples with thermal compensation, total and static pressure probes, LabView automation programs.
Despite the advantages of neoadjuvant chemotherapy (NACT), associated toxicity is a serious complication that renders monitoring of the patients' response to NACT highly important. Thus, prediction ...of tumor response to treatment is imperative to avoid exposure of potential non-responders to deleterious complications. We have performed genome-wide analysis of DNA methylation by XmaI-RRBS and selected CpG dinucleotides differential methylation of which discriminates luminal B breast cancer samples with different sensitivity to NACT. With this data, we have developed multiplex methylation sensitive restriction enzyme PCR (MSRE-PCR) protocol for determining the methylation status of 10 genes (SLC9A3, C1QL2, DPYS, IRF4, ADCY8, KCNQ2, TERT, SYNDIG1, SKOR2 and GRIK1) that distinguish BC samples with different NACT response. Analysis of these 10 markers by MSRE-PCR in biopsy samples allowed us to reveal three top informative combinations of markers, (1) IRF4 and C1QL2; (2) IRF4, C1QL2, and ADCY8; (3) IRF4, C1QL2, and DPYS, with the areas under ROC curves (AUCs) of 0.75, 0.78 and 0.74, respectively. A classifier based on IRF4 and C1QL2 better meets the diagnostic panel simplicity requirements, as it consists of only two markers. Diagnostic accuracy of the panel of these two markers is 0.75, with the sensitivity of 75% and specificity of 75%.
Experimental results for artificially initiated shock wave influence on machineless gas flow energy separation effect are presented. The working principle of the technique is based on interaction of ...supersonic and subsonic flows through the heat-conducting wall. In result at output there are two flows with different temperature - heated supersonic air flow and cooled subsonic one. Shock waves were initiated by conic ribs placed along the supersonic channel. During the research varied parameters included uni-flow and counter-flow air moving direction in subsonic and supersonic channels, subsonic flow rate divided by supersonic one (from 0 to 0.9), stagnation flow temperature (298, 313 and 343K) and initial Mach number (1.9, 2.5). The research was carried out with the use of infrared thermal imaging, thermocouples, total and static pressure probes, National Instruments automation equipment. Energy separation effect is increasing with the growth of Mach number and stagnation flow temperature. Rib placement in supersonic channel causes rise of static pressure and wall temperature and results in decreasing of energy separation effect at output of the device by less than 12%. Operability of the device with shock wave generation is remained.
In this Letter, comprehensive results on π±, K±, KS0, p(p¯) and Λ(Λ¯) production at mid-rapidity (0<yCMS<0.5) in p–Pb collisions at sNN=5.02 TeV, measured by the ALICE detector at the LHC, are ...reported. The transverse momentum distributions exhibit a hardening as a function of event multiplicity, which is stronger for heavier particles. This behavior is similar to what has been observed in pp and Pb–Pb collisions at the LHC. The measured pT distributions are compared to d–Au, Au–Au and Pb–Pb results at lower energy and with predictions based on QCD-inspired and hydrodynamic models.
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