TOWARDS THE ISSUE ON DEMAND GENERATION IN THE SERVICE MARKET

The features of supply and demand in the service market, the main trends in the market of household services, its dynamics for the period from 2010 to the present in the Russian Federation have been considered. The level of influence of marketing tools on the customer’s perception (collaboration, full information about the service, advertising campaign, employee motivation, presentation of new products, etc.) has been studied, the results of the study have been given, the main measures for creating demand for a company providing consumer services, event budget have been defined. An economic assessment of the effectiveness of the proposed measures in the form of an expected increase in revenue and payback periods has been given. Using the proposed set of measures will allow you to actively influence the process of forming the company’s demand in the market of household services

Влияние стрессоустойчивости на экспрессию проаутофагического белка Beclin-1 в миокарде после экспериментального ушиба сердца

Objective. Evaluation of myocardial expression of the pro-autophagic protein Beclin-1 after cardiac contusion in experimental animals with different stress resistance.Materials and methods. The study included 68 white mongrel male rats weighing 250–300 g. After ranking for extreme variants of stress resistance, moderately stress-resistant rats (N=36) were excluded from the study. The remaining animals were split into the control (N=16) and study (N=16) groups, each group composed of 8 high stress resistant and 8 low stress resistant rats. In the study group, 24 hours after inflicted cardiac contusion, 5×5 mm myocardial tissue specimens were sampled from the intraventricular septum, anterior walls of the left and right ventricles, histological sections were made, and a reaction with primary polyclonal Anti-Beclin-1 antibodies was performed. Beclin-1 expression was evaluated under the microscope.Results. Immunohistochemical evaluation revealed a statistically significant increase in Beclin-1 protein expression (P=0.0002) in the cytoplasm of cardiomyocytes in the study group vs the control group, regardless of animals’ baseline stress resistance. However, expression of Beclin-1 protein in the myocardium of highly stress-resistant rats (Me=4.3; LQ=4.0; HQ=4.3) was significantly higher versus low-resistant animals (Me=3.6; LQ=3.3; HQ=3.6) (P=0.0009).Conclusion. Increased expression of Beclin-1 protein in the post-traumatic period of experimental cardiac contusion indicates autophagic flux activation. Intensity of autophagy varied depending on the animal’s stress resistance.Цель исследования. Оценка выраженности экспрессии проаутофагического белка Beclin-1 в миокарде при различной стрессоустойчивости после экспериментального ушиба сердца.Материалы и методы. В исследование включили 68 белых беспородных крыс-самцов массой 250–300 г. Животных ранжировали по крайним вариантам стрессоустойчивости. Среднестрессоустойчивых крыс (n=36) исключили из исследования. Затем сформировали контрольную (n=16) и опытную (n=16) группы. В каждой группе выделили подгруппы, включавшие крыс с высокой и низкой стрессоустойчивостью, по 8 животных в каждой. В опытной группе через 24 ч после моделирования ушиба сердца из межжелудочковой перегородки, передних стенок левого и правого желудочков иссекали фрагменты миокарда 5×5 мм, изготавливали гистологические срезы, проводили реакцию с первичными поликлональными антителами Anti-Beclin-1. Полученные образцы исследовали под микроскопом.Результаты. Иммуногистохимическое исследование выявило статистически значимое увеличение (p=0,0002) экспрессии белка Beclin-1 в цитоплазме кардиомиоцитов в опытной группе по сравнению с контрольной вне зависимости от исходной стрессоустойчивости. Однако в миокарде высокоустойчивых к стрессу травмированных крыс наблюдали более выраженный уровень экспрессии белка Beclin-1 (Me=4,3; LQ=4,0; HQ=4,3) в сравнении с низкоустойчивыми особями (Me=3,6; LQ=3,3; HQ=3,6) (p=0,0009).Заключение. Выявленное увеличение экспрессии белка Beclin-1 в посттравматическом периоде экспериментального ушиба сердца свидетельствует об активации процессов аутофагии. Выраженность аутофагии различалась в зависимости от стрессоустойчивости организма животного

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Molecular and cellular basis in prediction of gastric cancer: a multidisciplinary research experience

A self-review of the results of multidisciplinary studies on the development of a predictive system for intestinal type gastric cancer (adenocarcinoma) is present. The authors' studies carried out in 2007-2017 in light of recent concepts of prediction and prevention of gastric cancer are discussed. The predictive model for gastric cancer is proposed. This includes an evaluation of inflammatory cytokine genes nucleotide polymorphisms, aberrant expression of microRNA, detection of tissue patterns of gastric atrophy and intestinal metaplasia (metaplastic atrophy), principles and possibilities of pathomorphological monitoring.Представлен самообзор результатов мультидисциплинарных исследований по разработке предиктивной системы в отношении рака желудка кишечного типа (аденокарциномы). Обсуждаются исследования авторов, выполненные в 2007-2017 годах в аспекте современных концепций предикции и превенции рака желудка. Предложена модель предикции рака желудка, включающая оценку нуклеотидных замен в генах воспалительных цитокинов, аберрантную экспрессию микроРНК, детекцию тканевых паттернов атрофии и метапластической атрофии слизистой оболочки желудка, принципы и возможности патоморфологического мониторинга

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types