Search

Autophagy and epithelial-to-mesenchymal transition (EMT) are the main biological processes involved in tumor progression, and are closely linked. On the one hand, activation of autophagy provides energy and essential nutrients for EMT during the metastases spreading, which is required for tumor cells survival in adverse environmental conditions. On the other hand, autophagy, acting as a tumor suppressor, tends to inhibit metastasis by selectively suppressing the transcription factors of EMT in the early stages. Therefore, inhibition of EMT by inhibitors or inducers of autophagy may be a new strategy for antitumor therapy. Thus, the aim of this review is to highlight current knowledge about the crosstalk between autophagy and EMT processes in tumor progression and to summarize data supporting the necessity of parallel regulation of two processes through signaling pathways.

During cancer progression Notch signaling pathway and its components could demonstrate oncogenic and tumor-suppressive properties depending on tissue type and cellular microenvironment. However, until recently, very little was known about Notch role in bladder cancer (BC). According to recent studies it was revealed that loss of copy number and decreased expression of NOTCH1 is the hallmark of BC cell lines; and NOTCH1 activation in vitro reduces cell proliferation, suggesting that NOTCH1 acts as a tumor suppressor in BC. Furthermore, BC could be promoted by bladder-specific inactivation of a component of y-secretase complex, which is directly involved in Notch signaling, in vivo. By contrast, further studies have demonstrated that NOTCH2 acts as an oncogene which could promote cell proliferation and metastasis through induction of epithelial-to-mesenchymal transition and maintaining stemness. Studies indicating that NOTCH1 and NOTCH2 have opposite effects on BC progression could give rise to novel therapeutic approaches aimed at impact on Notch activity.

Understanding genetic mechanisms and detection of biological markers of tumor growth forms an individual molecular phenotype of transformed cells that characterizes stage of tumor, the ability to metastasize, hormonal sensitivity, chemotherapyefficiencyetc. Mutations in proto- and anti-oncogenes controlling mitotic activity of cells and their ability to DNA reparation are often found in tumor cells in patients with cancer. Defects of classical tumor suppressor genes (BRCA1/2, CHEK2, ATM, PALB2, NBS1, TP53, etc.) determine the hereditary predisposition to breast cancer caused by genomic instability and appearance of «chimeric» genes, aneuploidies and chromosomal aberrations. Breast cancer is a genetically heterogeneous disease with various molecular, biological and clinical features. Identificationof the molecular phenotype of breast carcinomas is an important prognostic factor of the disease, and it helps to individualize the therapeutic approach for patients.

Для сокрытия преступлений, предусмотренных ст. 258 Уголовного кодекса Российской Федерации «Незаконная охота», зачастую преступники устанавливают на нарезное огнестрельное оружие различные дульные устройства, снижающие звук выстрела, тогда как их продажа и установка на гражданском и служебном оружии запрещена Федеральным законом от 13 декабря 1996 г. № 150-ФЗ «Об оружии». При производстве судебно-баллистических экспертиз вызывает затруднение криминалистическая оценка «саундмодераторов» («суппрессоров»). В статье приводятся конструктивные характеристики данных устройств. В результате сравнительного анализа авторы приходят к выводу, что «саундмодераторы» по конструкции и целевому назначению являются глушителями звука выстрела. Следовательно, их продажа и установка на оружие на территории Российской Федерации является незаконной. Данная работа предназначена для экспертов-криминалистов, проводящих судебно-баллистические экспертизы, а также будет полезна курсантам и слушателям вузов МВД России при изучении дисциплины «Судебная баллистика и судебно-баллистическая экспертиза»., To cover up crimes stipulated by Article 258 of the Criminal Code of the Russian Federation «Illegal Hunting», criminals often attach to rifled firearms various muzzle devices reducing the sound intensity of a shot. However, according to the Federal Law No. 150-FZ of December 13, 1996 «On Weapons» it is prohibited to sell and attach them to civilian and service weapons. When conducting forensic ballistic examinations the forensic evaluation of sound moderators (suppressors) causes certain difficulties. The article represents design characteristics of these devices. As a result of the comparative analysis, the authors come to the conclusion that sound moderators by their design and designated purpose are considered to be suppressors. Therefore, it is illegal to sell and attach them to weapons in the territory of the Russian Federation. This article is intended for forensic experts conducting forensic ballistic examinations as well as for cadets and trainees of higher education institutions of the Ministry of Interior of Russia studying Forensic Ballistics and Forensic Ballistic Examination., №2(54) (2018)

Present work aims to investigate functioning of the regulatory T-cells with suppressor activity in surgical sepsis. It has been shown that the septic patients with decreased T cell proliferation are characterized by enhanced relative contents of СD4+СD25+ lymphocytes, including СD4-CD25high. Moreover, a reverse correlation has been revealed between СD4+CD25+high and anti-CD3-induced proliferative response of mononuclear cells (MNC). Increased ratio of СD4+СD25+ cells is associated with arising suppressive activity of MNC, which is partially abrogated by addition of rIL-2. It should be noted that the depletion of CD25+ subpopulation is accompanied by increased T cell proliferation. Hence, a decrease in T cell proliferative activity in surgical sepsis is coupled with naturally occurring СD4+СD25+ regulatory T-cells (Trn). Furthermore, it has been demonstrated that the suppressive activity of MNCs in septic patients is mediated by soluble factors, in particular, IL-10. Indeed, septic patients are characterized by increased level of IL-10 production and enhanced number of CD4+IL-10+ T-cells. Addition of neutralizing anti-IL-10 antibody partially abrogated the suppressive activity of MNC supernatants. Thus, our study demonstrated that inducible regulatory T cells (Tr1) coupled to the naturally occurring СD4+СD25+ regulatory T-cells (Trn) actively contribute to genesis of immune pathology in sepsis.