The review discusses the functional features of the dopaminergic system. Dopamine synthesis is carried out both in the сentral nervous system and in the gastrointestinal tract. The first part of the review is devoted to the data of modern literature on the role of dopamine in the mechanisms of aging. At the same time, the processes underlying the depressive disorder in terms of the dopaminergic system participation integrating monoaminergic, epigenetic, inflammatory, neurotrophic and antiapoptic concepts are described.

The review considers and analyzes the literature data on the functions of the toll-like receptor family (TLR) in the development of malignant process. The structure of TLR, mechanisms of intracellular signal transduction, specific ligands antagonists and agonists of TLR are briefly reflected. Effects of various TLR from the point of view of influence on tumor growth and reactions of cellular immunity are given. The ambiguous results of experimental and clinical application of agonists and antagonists of TLR are compared. It is concluded that it is necessary to obtain additional information with the agonists of TLR at the stages of preclinical study.

Introduction. One of the promising approaches to cancer immunotherapy is the generation of personal antitumor vaccines that provides immune system recognition of mutant tumor neoantigenes.

The aim of this study was to develop bioinformatic approaches for melanoma NGS-sequencing data analysis. On the basis of data obtained, to predict the peptides capable of inducing an immune response against B16F10 mouse melanoma.

Materials and methods. Exom and transcriptom of B16/F10 melanoma tumor tissue and normal tissue of C57BL/6 mice were sequenced. Library sequencing procedure was performed on Illumina HiSeq 2500platform, quality analysis of all obtained libraries was performed using FastQC and MultiQC. The obtainedfiles were usedfor further bioinformatics analysis. The GATKMuTect2 and Strelka were used for searching the mutations in tumor samples.

Results. Identification of somatic mutations specific for tumor was based on the analysis of few mice tumors. Here we show that mutations in different tumor samples significantly overlap, but are not identical. Prediction of short peptides affinity to the mouse main histocompatibility complex (MHC) H2 was performed using netMHCpan version 3.0. Mutations such as missense and frameshift were used to predict short peptides that could trigger an immune response. Transcriptome data confirm that mutated alleles are expressed in tumors. Vaxrank pipeline predicted immunogenic peptides with a length of25—27. We also present the synthesis and solubility of these peptides.

Conclusion. A bioinformatic approach has been developed to predict peptides capable of increasing immune response of mouse melanoma B16/F10.

Introduction. In recent years, the creation and use of drugs for antitumor therapy, which have improved the quality of life and survival of cancer patients, has become a crucial event in the development of oncology. It is known that urea derivatives are included in the class of drugs with anti-angiogenic properties. The addition of a carbohydrate residue to urea derivatives helps to improve the solubility, targeted drug deliveiy in the body (targeting), and the elimination of side effects. In order to search for new compounds with anti-angiogenic properties, we have synthesized a number of compounds, some of which are previously unknown urea derivatives.

Purpose of the study — synthesis of urea derivatives based on sugary nitrosocarbamidetransamidation. To evaluate using in silico and in vitro methods, there is the ability to create new anticancer drugs based on new glycosidic urea derivatives.

Materials and methods. Pre-experimental prediction of biological activity was performed using a computer system PASS. Cytotoxic activity was determined by the MTT method. For the MTT assay, cells were dropped into 198 µl of RPMI-1640 complete medium in 96-well plates. After one day, the test compounds were added to each well in concentration 100 µmol. After 72 hours, 20 µl of MTT solution was added to each well. The intensity of the medium staining was measured on a Multiskan EX photometric immunoassay analyzer at λ= 540 nm.

Results. From the number of virtual compounds studied, for 5 compounds a high probability of antineoplastic activity and a low probability of cytotoxic activity in silico are predicted. Compounds were synthesized: N-(β-D-galactopyranosylcarbamoyl-l)-2-isonicotin-semicarbazide, l-[(N-β -D-galactopyranosyl)-carbamoyl]-3,5-dimethylpyrazoIe, N-(β -D -galactopyranosylcarbamoyl)-p-bromophenylurea, N-(β -D -galactopyranosyl)-p-chlorophenylurea, N-(β -D -glucopyranosyl)-p-chlorophenylurea. The compounds did not show cytotoxic activity in vitro.

Conclusion. For the studied compounds, a tow probability of cytostatic activity manifestation (as confirmed experimentally) and a high probability of antitumor activity manifestation are virtually predicted.

Introduction. Fluorescent probes based on monoclonal antibodies (MAb) are widely used in scientific and clinical research in the field of oncology, hematology, immunology, epidemiology. The unique spectral properties of the natural protein, phycoerythrin (PE), made it the dominant dye widely used for the preparation of fluorescent probes based on MAb.

Objective. To create of fluorescent probes based on the MAb and the fluorescent dye PE by two alternative methods of protein synthesis.

Materials and methods. MAb to T lymphocyte antigen (clone ICO-86, clone ICO-31), fluorescent dye PE and bifunctional agents SPDP and SMCC were used in the work. Liquid chromatography methods were used for isolation and purification of MAb: in the first step, affinity isolation of immunoglobulins on the immobilized protein G or anion exchange column chromatography. Gelfiltration on a PD-10 column was used to purify the conjugates (immunofluorescent probes, IFP) in the second step, the concentration and labeling density of the IFP were determined spectrophotometrically.

Results. Conjugation of MAb with PE was carried out at a molar ratio of components of 1: 2. For this both components of the conjugation reaction (PE and MAb) were separately modified. For the creation of IFP on the basis of the MAb of the ICO series, both methods of conjugation of Mab with PE are applicable, but method II, in which the chemical modification by the bifunctional SMCC agent is exposed only to the PE molecule by its free amino groups, and the immunoglobulin molecule is conserved in the maximally native state is preferred.

Conclusion. The methods described in the article allow to obtain immunofluorescent probes based on antibodies of the ICO series that are comparable in their analytical characteristics to foreign commercial analogs.

Introduction. Beta-III tubulin (TUBB3), the structural protein of microtubules, is not expressed in normal epithelium, but is frequently present in different epithelial tumors. We suggested that the screening for TUBB3 in morphologically normal tissue outside the tumor may be used for the molecular diagnostics of the local spread of cancer, which is particularly significant in case of the tumors with a high rate of local recurrence, like esophageal cancer.

Objective. The quantitative assessment of TUBB3 expression in tumor and morphologically normal esophageal tissue adjacent and remote from the tumor.

Materials and methods. The expression of TUBB3 in surgical biopsy specimens of tumor and morphologically normal tissue derived from 40patients after radical surgery for esophageal cancer was measured by immunocytometry.

Results. TUBB3 expression was detected in 35 out of 40 studied samples of esophageal cancer, as well as in 10 out of 13 samples of morphologically normal esophagus tissue adjacent to the tumor, and in 25 out of 40samples of esophagus tissue most distant from the tumor near the resection edge. It was shown that the expression of TUBB3 in tissue specimens increases as follows: “normal tissue → adjacent normal tissue → tumor”, which basically means the existence of a positive gradient of TUBB3 expression level and intensity towards the tumor.

Conclusion. The expression of TUBB3, a protein associated with tumor growth, outside the primary tumor may indicate that the tissue appearing to be normal is already affected by the malignancy. It can be used as an additional factor in tumor staging and post-operative patient management.

Introduction. In N. N. Blokhin National Medical Research Center of Oncology were made preclinical toxicological studies of drmustine, a new antitumor drug from the class of nitrosoureas. The paper presents some results of study the subchronic toxicity ofdrmustine in dogs. Objective. The objective of the present study was to investigate the subchronic toxicity of оrmustine on dogs with a daily intravenous administration during 3 days.

Materials and methods. The study was performed in 12 dogs of the English beagle breed of males and females. Ormustine was adminis¬tered intravenously daily during 3 days in total doses of 1, 5, 10, 20 and 30 mg/kg. During the experiment, to study the damaging effect of ormustin on organs and tissues, clinical and lab tests andpathomorphological examinations were performed.

Results. Ormustin in doses of 20 and 30 mg/kg caused the death of animals on the 7th and 8th day of observation against the background of severe hemato-and gastrointestinal toxicity. In dogs receiving the drug in all doses, there were external manifestations of intoxication and changes in behavioral reactions, weight loss during the entire observation period. It was found that the drug had a dose-related myelosuppressive effect. Ormustin caused pronounced morphological changes of varying degrees of reversibility in the small intestine, kidneys, thyroid gland, liver, lymph nodes, spleen, heart and gonads; less pronounced — in the large intestine, stomach and bladder. Conclusion. According to the study, the total doses of ormustin 20 and 30 mg/kg were characterized as lethal, 5 and 10 mg/kg — high toxic, 1 mg/kg — low toxic dose.

Background. Pediatric skin melanoma is very rare, it differs in a number of features from adult skin melanoma. Early diagnostics of this highly malignant tumor is a key prerequisite for effective treatment. The same methods are commonly used which are applied for diagnostics of adult melanoma in the course of diagnostics of skin melanoma in children. Appropriateness of this approach deserves validation.

The aim of this work is to describe procedures of diagnostics of a pigment skin malformation in a child.

Case report. Girl aged 5 months entered pediatric clinic of the FSBI “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation with inborn tumor in a wrist joint area. Hemangioma had been suggested formerly at residence place. In the course of diagnostics in N.N. Blokhin National Medical Research Center of Oncology the following complex of approaches was used: ultrasound scanning, magnetic resonance imaging, trepanobiopsy, open biopsy. Tissues from the latter were examined histologically on hematoxylin and eosin — stained slides. Immunohistochemical study was also done by means of revelation of determinants of cell proliferation, antigens of melanocytic differentiation, proteins commonly used as strictly melanoma markers as well as antigens of tissue compatibility. The conclusion was done about nodular pigment cell skin melanoma. Excision of the tumor was carried out. Relapse-free period lasts for 12 months at present.

Conclusion. Procedures are described of diagnostics and treatment of a 5-month-old girl with skin melanoma in a wristjoint area. In the course of diagnostics approaches were used which are commonly applied when identifying a more frequent and better explored adult skin melanoma. Prolongation of studies is desirable to validate these approaches for diagnostics of pediatric pigment skin tumors.