Fast Traveling-Wave Reactor of the Channel Type

The main aim of this paper is to solve the technological problems of the TWR based on the technical concept described in our priority of invention reference, which makes it impossible, in particular, for the fuel claddings damaging doses of fast neutrons to excess the ~200 dpa limit. Thus the essence of the technical concept is to provide a given neutron flux at the fuel claddings by setting the appropriate speed of the fuel motion relative to the nuclear burning wave. The basic design of the fast uranium-plutonium nuclear traveling-wave reactor with a softened neutron spectrum is developed, which solves the problem of the radiation resistance of the fuel claddings material.Comment: 18 pages, 5 figures, 2 table

Immunohistochemical evaluation of Ki-67, Cyclin D1 and β-catenin expression in the subtypes of triple negative breast cancer

Aim. To evaluate the expression levels of Ki-67 and cyclin D1 and β-catenin in the subtypes of triple negative breast cancer. Methods. The study was conducted on the surgical material from 60 patients of clinical stage 2A (T1N1M0 or T2N0M0) who were treated at the Rostov Research Institute of Oncology from 2012 to 2015. For immunohistochemistry, antibodies to estrogen and progesterone receptors, cytokeratins 5/6, Ki-67, cyclin D1, β-catenin, HER2/neu and EGFR proteins were used. Results. Triple negative breast cancer with the signs of basal epithelium was found to have a significantly higher expression level of Ki-67 compared to non-basal-like one. In some part of triple negative breast cancer samples overexpression of cyclin D1 was observed. The high level of cyclin D1 in the basal-like subtype was less common than in the subtypes without the signs of basal epithelium, but its average value was significantly higher. In triple negative cancer with cyclin D1 overexpression, the loss of β-catenin on the cell membrane and its abnormal accumulation in the cytoplasm was significantly more frequent. β-catenin translocation into the cell nucleus was observed only in basal-like triple negative cancer, and 2 times more often in case of cyclin D1 overexpression. Conclusion. In triple negative breast cancer tumors with overexpression of cyclin D1 and abnormal expression of β-catenin are observed in some cases; these biomarkers can be considered as potential therapeutic targets for this group of tumors

INTRATUMORAL AMPLIFICATION HETEROGENEITY IN HER2/neu-POSITIVE BREAST CANCER MOLECULAR-GENETIC SUBTYPES

The defining feature of HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtype breast cancer is HER2/neu gene amplification and protein overexpression on cancer cell membrane. The HER2-targeted therapy is nowadays available for patients with HER2-positive breast cancer However, a significant fraction of HER2+ tumors acquire or possess intrinsic mechanisms of resistance, based on multiple factors, and genetic heterogeneity among them. The aim of our study was to quantify the heterogeneity of HER2/neu amplification in HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtypes of breast cancer. Material and methods. A retrospective analysis of 210 cases referred for dual probe fluorescence in situ hybridization (FISH) confirmation of an immunohistochemical equivocal 2+ result was performed. Results. Our results demonstrated a heterogeneous amplification pattern of HER2/neu gene, whose expression is a substantial cause of HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtypes of breast cancer, in 31 % of invasive breast cancer cases. As heterogeneous, we interpreted tumors containing cells with HER2/CEP17 ratio < 2 and gene copies 4 ≤ HER2/neu < 6, that is, those without HER2/neu amplification. The amount of heterogeneous tumors between HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtypes was not statistically significant. ROC analyses identified optimal cutoff point for HER2/CEP17 ratio as 2.6 for distinguishing heterogeneous tumors. Conclusion. The heterogeneity of HER2/neu amplification is determined by FISH in 31 % of cases and is independent of molecular breast cancer subtype. If a HER2/neu-positive breast cancer has HER2/CEP17 ratio ≤ 2,6, it contains minor subclones without HER2/neu amplification with a probability of 95 %. Our results demonstrated that HER2/neu amplification heterogeneity may be important for prognosis of survival and treatment decisions

Achievements and prospects of cellular technologies based on the activated lymphocytes in the treatment of malignant tumors

This article reviews the immune system and its role in the relationship between the tumor and the body of a patient with tumor diseases. It is about controlling homeostasis by recognizing and eliminating genetically alien substances (antigens). Antitumor treatment is now not only considered as an “instrument” for eliminating and destroying tumor cells, but also its ability to change/restore impaired functions of the immune system attracts attention. The used antitumor treatment is widely known to be immunosuppressive, stress and radiation effects also cause and/or enhance immunosuppression. In this work, the authors provide literature data demonstrating current status and problems of cellular immunotherapy of malignant tumors with the use of activated lymphocytes, and the role of antigen-specific T-lymphocytes as one of its most important agents is reviewed. Currently, among the immunotherapeutic methods, a special place is occupied by approaches involving the use of autologous or allogenic ex vivo stimulated immunocompetent cells (adoptive immunotherapy). The importance of complex influence on various links (T-, B-, NK-cell) and stages (presentation, recognition, proliferation, differentiation, migration, activation, effector functions) of the immune response is considered. The emergence of targeted drugs based on antibodies, as well as vaccines, especially dendritic cells, has provoked the emergence of a new wave of interest in the formation of specific antitumoral immune response mediated by T lymphocytes, so the introduction of the latter can be classified as a kind of targeted therapy. The value of antigen-specific T-lymphocytes in the formation of antitumor immunity is shown, which emphasizes the importance not only of CD8+, but also of CD4+ T-lymphocytes. In addition, there are suggestions of the possible significance of both T- and B-cells for developing a strategy of cellular immunotherapy. The literature data suggest that not only cytotoxic lymphocytes, but also T-helpers and even B-lymphocytes can be effective as antigen-specific lymphocytes as a component of antitumor treatment. The authors consider the possibility of obtaining antigen-specific T cells, as well as their further storage. The possibility of elimination or selective inhibition of regulatory T-cells during adoptive immunotherapy aimed at removing the suppressor effect on cytotoxic lymphocytes is studied. Various strategies for the use of cell therapy are also discussed

Six-month therapy of CGRP monoclonal antibodies in real-world clinical practice: an interim analysis of efficacy and safety data

Introduction. Migraine is one of the most common disabling neurological disorders. Recently developed monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor are the first targeted medication for preventive therapy of both episodic and chronic migraine. They have been thoroughly investigated in clinical trials; however, there is little data from real-world clinical practice available to date. The aim of this study is to assess the efficacy and safety of 6 months of treatment with erenumab in real-world clinical practice and investigate the effect of the drug on the patients’ sensitivity to medicines for migraine headaches relief and patient satisfaction after treatment.Materials and methods. Our observational cohort prospective study included patients in our Headache Clinic prescribed monoclonal antibodies blocking the  CGRP-receptor  – erenumab. During the  investigation, we evaluated the  previous preventive therapy and its efficacy, the number of days with migraine per month, adverse events occurring during the erenumab treatment, depression and anxiety (HADS), migraine disability (MIDAS), the presence of allodynia (ACS-12) and improved response to acute therapy after treatment. A total of 42 patients participated in the study: 6 men, 36 women, the average age was 43.9 ± 12.2. Of them, 38 patients (90%) had chronic migraine. Thirty-two patients (76%) had previously been prescribed preventive therapy, which proved ineffective, and 10 patients (24%) had not once received any type of migraine prevention.Results. Among our patients, we identified 11 patients with resistant migraine and one patient with refractory migraine. During the study, two patients dropped out due to adverse events (constipation). Thirty patients continued the administration of erenumab 70 mg for at least six months. The average number of migraine days per month before treatment was 22.8, and after six months of treatment, it dropped to 7.3. Twenty-nine patients (72.5%) also noted that the response to acute headache treatment improved after the therapy.Conclusion. The results of our study are consistent with the international experience of using erenumab and confirm its effectiveness for migraine preventive therapy, including difficult-to-treat migraine cases. However, further studies with more participants and evaluation of predictors of successful monoclonal antibody therapy are still needed

Status and Objectives of the Dedicated Accelerator R&D Facility "SINBAD" at DESY

We present a status update on the dedicated R\&D facility SINBAD which is currently under construction at DESY. The facility will host multiple independent experiments on the acceleration of ultra-short electron bunches and novel, high gradient acceleration methods. The first experiment is the ARES-experiment with a normal conducting 100\,MeV S-band linac at its core. We present the objectives of this experiment ranging from the study of compression techniques to sub-fs level to its application as injector for various advanced acceleration schemes e.g. the plans to use ARES as a test-site for DLA experiments in the context of the ACHIP collaboration. The time-line including the planned extension with laser driven plasma-wakefield acceleration is presented. The second initial experiment is AXSIS which aims to accelerate fs-electron bunches to 15\,MeV in a THz driven dielectric structure and subsequently create X-rays by inverse Compton scattering.Comment: EAAC'17 conference proceeding

Intermolecular interactions of decamethoxinum and acetylsalicylic acid in systems of various complexity levels

Intermolecular interactions between decamethoxinum (DEC) and acetylsalicylic acid (ASА) have been studied in the phospholipid-containing systems of escalating complexity levels. The host media for these substances were solvents, L-α-dipalmitoylphosphatidylcholine (DPPC) membranes, and samples of human erythrocytes. Peculiar effects caused by DEC-ASА interaction have been observed in each system using appropriate techniques: (a) DEC-ASА non-covalent complexes formation in DPPC-containing systems were revealed by mass spectrometry with electrospray ionization; (b) joint DEC-ASА action on DPPC model membranes led to increasing of membrane melting temperature Tm, whereas individual drugs caused pronounced Tm decreasing, which was demonstrated by differential scanning calorimetry; (c) deceleration of DEC-induced haemolysis of erythrocytes under joint DEC-ASА application was observed by optical microscopy