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Purpose: Genomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in “intermediate” clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients. Methods: This multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes. Results: One third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2–42.4). Chemotherapy was withdrawn in 57 cases (28.4% [22.2–34.8]) and added in 15 (7.5% [3.8–11.2]. 6 changes (8%) were based on patients’ decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p

The oncogenic process leading to nasopharyngeal carcinoma (NPC) requires the combination of genetic and epigenetic alterations, latent infection by the Epstein-Barr virus and local inflammation. A transcriptome analysis of NPC xenografts identified the gene encoding the cellular inhibitor of apoptosis protein 2 (c-IAP2) among the top five most intensely expressed. Consistently, the very high levels of the c-IAP2 protein were detected in 11 of 13 NPC biopsies. RMT 5265, a structural analog of second mitochondria-derived activator of caspase (SMAC), induced the rapid degradation of c-IAP2 in nasopharyngeal epithelial cells, whether malignant or not, but blocked clonal cell growth in NPC cells only. In short-term experiments, RMT 5265 induced apoptosis in a fraction of NPC cells, and this apoptosis was dramatically enhanced when RMT 5265 was combined with Toll-like receptor 3 (TLR3) stimulation. By contrast, the cooperative effect with tumor necrosis factor α was only marginal. The apoptosis induced by the combination of RMT 5265 and TLR3 stimulation was mediated by caspase-8 and associated with a decrease in the cellular content of the long isoform of FLICE-like inhibitory protein. Similar caspase-8 activation was obtained when siRNA knockdown of c-IAP2 was combined with TLR3 stimulation. In conclusion, c-IAP2 has a specific protective function in NPC cells challenged by TLR3 agonists. This protective function is probably important to make NPC cells tolerant to their own production of small viral RNAs, which are potential agonists of TLR3. Our data will help to design a rational use of IAP inhibitors in NPC patients.

BACKGROUND: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. METHODS: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. RESULTS: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with ≥10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival. CONCLUSIONS: Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC.

Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the absence of contamination of tumor DNA from maternal DNA. Three cell lines, BeWo, JAR, JEG were also studied by this high resolution pangenomic technique. According to aCGH analysis, the de novo choriocarcinomas exhibited simple chromosomal rearrangements or normal profiles. The cell lines showed various and complex chromosomal aberrations. 23 Minimal Critical Regions were defined that allowed us to list the genes that were potentially implicated. Among them, unusually high numbers of microRNA clusters and imprinted genes were observed.

Based on Greek and Latin epigraphy, the article examines the main features of civil ideology associated with the concept of “love of the fatherland” ( philopatria , amor patriae and their derivatives). The corresponding categories, often emotionally colored, were widely used to characterize the virtues and behavioral motives of urban elites who acted as euergetai . The lexical and contextual analysis of the inscriptions shows that the civic patriotism of the Greek cities coexisted quite well with the political loyalty to the Roman authorities and ruling emperors. In both Greek and Latin inscriptions, there is an explicit or implicit imperial context. In the former, it is especially emphasized by title names indicating “love” for emperors and Rome (φιλόκαισαρ, φιλοσέβαστος, φιλορώμαιος). In the western provinces and Italy, there was obviously no particular need for such direct references. It is reasonable to believe that there, in urban communities consisting of Roman citizens, a sense of belonging to two homelands, as Cicero defined them, remained: Rome as communis patria / patria civitatis (iuris) and the fatherland by nature and locality ( patria naturae / loci patria ). In other aspects, however, a comparison of the discourses of Greek and Latin inscriptions reveals direct parallels and coincidences in the basic value orientations, due to the remaining civil-communal (polis) character of the cities of the Roman Empire.

Introduction: Liver plays an essential role in the metabolism, synthesis, transport and clearance of lipids and lipoproteins, therefore, changes in the lipid profile in liver pathology reflects the degree of its dysfunction. Leading role in the development of atherosclerosis belongs to lipid spectrum disorders in the form of hyperlipidaemia and dyslipidaemia, associated with an increased cardiovascular risk in liver cirrhosis. Aim: To study the relationship between violations of lipid profile of blood with the features and the clinical picture of Liver Cirrhosis (LC). Materials and Methods: The study was an open prospective and comparative analysis of patients with LC, conducted at Stavropol State Medical University (Stavropol State, Russia). Research was conducted from June till August 2020. In 108 patients with LC, blood concentration of total cholesterol, triglycerides, High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were studied in association with manifestations of the disease. Control group constituted of 45 healthy individuals, comparable in sex, age and ethnicity. Two sample student’s t-test, Newman Keuls test, chi-square test with Yates’s correction and Pearson’s linear correlation coefficient (r) were calculated. Receiver Operating Characteristic (ROC) analysis was used, the Odds Ratio (OR) and its 95% Confidence Interval (CI), sensitivity, specificity, positive and negative predictive value and accuracy were determined. Differences were considered statistically significant at p≤0.05. Results: Regardless of gender and age of patients, decrease of serum levels of total cholesterol (p

Somatic cells can be chemically reprogrammed into a pluripotent stem cell (CiPSC) state, mediated by an extraembryonic endoderm- (XEN-) like state. We found that the chemical cocktail applied in CiPSC generation initially activated a plastic state in mouse fibroblasts before transitioning into XEN-like cells. The plastic state was characterized by broadly activated expression of development-associated transcription factors (TFs), such as Sox17, Ascl1, Tbx3, and Nkx6-1, with a more accessible chromatin state indicating an enhanced capability of cell fate conversion. Intriguingly, introducing such a plastic state remarkably improved the efficiency of chemical reprogramming from fibroblasts to functional neuron-like cells with electrophysiological activity or beating skeletal muscles. Furthermore, the generation of chemically induced neuron-like cells or skeletal muscles from mouse fibroblasts was independent of the intermediate XEN-like state or the pluripotency state. In summary, our findings revealed a plastic chemically activated multi-lineage priming (CaMP) state at the onset of chemical reprogramming. This state enhanced the cells’ potential to adapt to other cell fates. It provides a general approach to empowering chemical reprogramming methods to obtain functional cell types bypassing inducing pluripotent stem cells.

The pancreas arises from a small population of cells but how individual cells contribute to organ formation is unclear. Here, the authors deconstruct pancreas organogenesis into clonal units, showing that single progenitors give rise to heterogeneous multi-lineage and endocrinogenic single-lineage clones.

The relevance of the work is caused by the necessity to develop a new anti-corrosion paints, with increased resource exploitation to protect gas pipelines and wellhead equipment of oil wells from corrosion. The main aim of the study is to increase the service life of silicone coatings based on the study of the influence of nitrogen-containing surfactants on wetting of aluminum and steel substrates in silicon-organic paint materials. The methods used in the study: analysis of surface tension in static mode on the device Rehbinder, on the border of phases - solution of polyphenylsiloxane/water and polyphenylsiloxane/air solution and the contact angle of wetting on the border - solution of polyphenylsiloxane/aluminum/water and polyphenylsiloxane/steel/water solution; photographing the surfaces of the coatings and electrochemical determination of coating porosity. The paper introduces the results of the study of nitrogen-containing surfactants effect on wetting of aluminum and steel substrates with solutions of polyphenylsiloxane. The authors have calculated the change in wetting and shown their influence on porosity of coatings. Introduction of surfactants improves wetting of metal substrates in solutions of polyorganosiloxanes, which is expressed in the change of wetting angle. It is to 22° for aluminum substrate and 32,5° for steel one. Analysis of changes in wetting functioning allows supposing that polyethylenpolyamines demonstrate the greatest wetting activity (if their content in the solution is to 0,5 g/dm3), and low molecular weight amines in more concentrated solutions (with added content more than 0,5 g/dm3). The authors derived the equations describing the effect of additives and polyphenylsiloxane contents on wetting angles and developed the nomograms. The introduction of surfactants causes decrease in porosity and roughness of the surfaces (in 2,5 times).

The relevance of the work is caused by the necessity to develop a new anti-corrosion paints, with increased resource exploitation to protect gas pipelines and wellhead equipment of oil wells from corrosion. The main aim of the study is to increase the service life of silicone coatings based on the study of the influence of nitrogen-containing surfactants on wetting of aluminum and steel substrates in silicon-organic paint materials. The methods used in the study: analysis of surface tension in static mode on the device Rehbinder, on the border of phases - solution of polyphenylsiloxane/water and polyphenylsiloxane/air solution and the contact angle of wetting on the border - solution of polyphenylsiloxane/aluminum/water and polyphenylsiloxane/steel/water solution; photographing the surfaces of the coatings and electrochemical determination of coating porosity. The paper introduces the results of the study of nitrogen-containing surfactants effect on wetting of aluminum and steel substrates with solutions of polyphenylsiloxane. The authors have calculated the change in wetting and shown their influence on porosity of coatings. Introduction of surfactants improves wetting of metal substrates in solutions of polyorganosiloxanes, which is expressed in the change of wetting angle. It is to 22° for aluminum substrate and 32,5° for steel one. Analysis of changes in wetting functioning allows supposing that polyethylenpolyamines demonstrate the greatest wetting activity (if their content in the solution is to 0,5 g/dm3), and low molecular weight amines in more concentrated solutions (with added content more than 0,5 g/dm3). The authors derived the equations describing the effect of additives and polyphenylsiloxane contents on wetting angles and developed the nomograms. The introduction of surfactants causes decrease in porosity and roughness of the surfaces (in 2,5 times).