Neuroendocrine tumors (NET) is a rare pathology characterized by dysfunction of the pituitary gland and endocrine glands. The survival prognosis depends on the stage of the disease at which the malignant growth was detected.

The study objective was to summarize information on the methods of early diagnosis of NETs and antitumor therapy using peptide hypothalamic hormone somatostatin analogues.

The review provides a chronological analysis of studies of the expression of somatostatin receptors (SSTRs) in different tissues and organs, methods of their visualization and quantitative determination over 50 years. The expression of SSTRs was revealed on NET cell membranes. The history of SSTRs study dates back to 1972, when somatostatin was first isolated and its structure established. Later, the peptide therapeutic activity in the treatment of NET, realized through somatostatin receptors, was discovered, and a number of somatostatin analogues were synthesized. Five main types of SSTRs are known, including subtypes which are expressed in characteristic volumes in the corresponding pathologies. Determining the expression of SSTRs provides diagnosis and staging of malignant neoplasms. Now the regulation of tumor growth is carried out by synthetic somatostatin analogues. SSTRs imaging is an important stage in planning NET therapy with drugs of this pharmacological group. Clinical studies of the therapy of tumors of various organs and tissues, in vitro and in vivo imaging are being carried out, methods for detecting SSTRs are being studied and compared.

A retrospective analysis of the methods used to visualize SSTRs and diagnose and treat NETs is presented. It has been shown that positron emission tomography combined with computed tomography, using SSTRs-binding radioligands is the safest and most accurate method for visualizing SSTRs and diagnosing NETs.

A special hypothetical mechanism of variable Individual Epitope Reverse Translation (at least 2 types) of eukaryotic cell is probably capable of reproducing primary linear (sens- / antisense-, CRISPR-, repeat-like, etc.) and secondary conformational (similar to quadruplexs, RNA-hairpins, RNA-ring-structures; etc.) oligonucleotide structures formed in the mitochondrial membrane-bound supramolecular and containing nanomolecular inclusions hypothetical particle of the retranslosome. This is the so-called nucleic acid equivalents of protein epitope, oligo-NEs, monomeric in ~15–30 and oligomeric in ~(15–30)n nucleotides, potentially capable of participating in the regulation of expression (activation, termination, switching) and modification of genes / genome, as well as in the creation protein / enzyme-containing nucleoprotein platform- / module- / complex-like formations in normal, pathologically altered (in particular, tumor) and virus-infected cells. Recently, in the GenBank databases, they are shown realistically and built / calculated bioinformatically in silico so-called minimum theoretical of 22 nucleotides and longer RNAring (stem-loop) structures, the composition of which depends, firstly, on constantly occurring chemical and enzymatic processes (including deamination mutations), and the properties of which, secondly, link, respectively, with the early (era of the so-called circular code) and later (era of modern universal coding, including the circular code as a component) evolutionary periods of the formation of the whole genetic code. It is generally accepted that the emergence and formation, respectively, of early evolutionary (proto-tRNA, proto-rRNA) and modern variants of molecules of the translational machine of mitochondria and cytoplasm is associated with stem-loop RNA-ring structures, similar to independently proposed oligo-NEs, such as tRNA, rRNA and gene products of ribosomal and other proteins.

Introduction. Numerous studies using multivariate analysis have confirmed the relationship between low hemoglobin and / or hypoxia of tumor tissue with a worsening prognosis.

The study objective was to assess the state of iron metabolism in breast cancer patients in the perioperative period, before conducting adjuvant chemotherapy for adequate administration of iron and recombinant erythropoietins preparations.

Materials and methods. The object of the study included 17 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, before the first course of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25), ferritin, soluble transferrin receptors, transferin, iron, erythropoietin, C-reactive protein and interleukin 6 indicators.

Results. In patients with breast cancer, even before adjuvant chemotherapy, a violation of iron metabolism was revealed. Anemic syndrome (AS) with iron deficiency erythroproiesis was diagnosed in 29.4 % of them. In most of them, AS was accompanied by a deficiency of endogenous erythropoietin. Iron deficiency anemia was more common; functional iron deficiency (FID) was found in some patients. In contrast to patients with iron deficiency anemia, patients with FID had a significant concentrations of GP25, C-reactive protein, and interleukin 6 and ferritin were within the upper limit of normal. It should be noted that GP25 hyperexression was observed not only in breast cancer patients with FID, but also in patients without laboratory signs of anemia, which did not exclude the latent stage of AS.

Conclusion. To achieve the effectiveness of the treatment of AS, a comprehensive and personalized approach is required. Iron preparations are prescribed to restore iron metabolism; recombinant erythropoietins preparations are used to increase the rate of erythrocyte formation during chemotherapy. The same treatment regimen is justified for the correction of AS with FID. However, the strategy for future treatment of FID is associated with the use of GP25 antagonists (in order to overcome the retention of iron in the reticuloendothelial system), hormones or cytokines that can effectively stimulate erythropoiesis in AS with impaired iron metabolism.

Introduction. Therapeutic advances in recent years, the appearance on the market each time of new drugs that allow patients to achieve complete remission, a long period without progression dictate the need to control treatment by monitoring residual disease in multiple myeloma. Monitoring of multiple myeloma is the detection of a small number of tumor cells after therapy in a patient, which may be the cause of recurrence of the disease – control of minimal residual disease (MRD). This article discusses the key diagnostic markers (CD45, CD56 and CD19) of minimal residual multiple myeloma disease at initial diagnosis and after induction therapy. There are various diagnostic methods of research that can reliably assess the response to therapy and predict the occurrence of relapse. The main methods for detecting MRD are allele-specific polymerase chain reaction, next-generation sequencing and multicolor flow cytometry. The diagnosis of MRD by flow cytometry is the most widely used quite fast, quantitative, sensitive and affordable method, it is used for the primary diagnosis of multiple myeloma, as well as for monitoring MRD. It is important to identify the aberrant immunophenotype during the initial diagnosis for the correct subsequent assessment of MRD. MRD of multiple myeloma is considered an important component in the course of patient therapy before hematopoietic stem cell autotransplantation to assess the effectiveness of therapy, control and prognosis of the disease.

The aim of the work MRD-study with the key diagnostic markers in multiple myeloma (CD45, CD56 and CD19).

Materials and methods. The study was carried out in 59 patients with multiple myeloma. For all patients, in addition to standard methods of diagnosis and staging of the disease, bone marrow morphology (myelogram) and immunophenotype were examined. Eight-color flow cytometry with a panel of monoclonal antibodies for the diagnosis of plasma cell tumors Euro-Flow 2012 was used to diagnose MRD.

Results. MRD was assessed by markers CD45, CD56 and CD19 in patients with multiple myeloma after induction therapy. The incidence of MRD-positivity for CD45 was 87.5 %, for CD56 – 97.5 %, for CD19 – 95.5 %. The incidence of MRD-negative status was for CD45 was 12.5 %, for CD56 – 2.5 % and for CD19 – 4,5 %.

Conclusion. The use of a complex of these markers allows the most accurate determination of the MRD-negative status, taking into account the primary immunophenotype of malignant plasma cells.

Introduction. Among the immunological prognostic factors in breast cancer, intratumoral lymphocytes play an important role. Pronounced infiltration of the tumor by CD8 lymphocytes is associated with a favorable prognosis. The expression of transferrin receptor (CD71) on tumor cells, on the contrary, is associated with an unfavorable prognosis. The bone marrow of breast cancer patients has been studied very little in terms of the prognostic role of hematopoietic cells and lymphocyte subpopulations.

The study objective was to investigate the bone marrow B-lymphocyte subpopulations of breast cancer patients and evaluate their prognostic value.

Materials and methods. Detailed bone marrow studies were carried out in 107 patients who were treated in the department of mammary gland tumors mainly in the period 2013–2016. Thus, the duration of the follow-up period after surgical treatment was mainly from 5 to 8 years. W hen diagnosing patients, a standard study of the receptor status, Her2 / neu, Ki-67 expression, etc. was performed. Morphological examination of the bone marrow (myelogram) was performed in all patients. Clarification of the life expectancy of patients was carried out by personal surveys or through the Registry Office. If possible, the life expectancy of patients, the duration of the period without progression etc. were clarified.

Results. In cases with B-lymphocytes of more than 10 %, survival rates were more favorable (p = 0.019). Bone marrow B cells and, in particular, CD10‑positive B-linear precursors may have prognostic value in breast cancer. Thus, CD10 expression on 12 percent or more of bone marrow B cells of breast cancer patients was associated with a more favorable prognosis (p = 0.042). The prognostic role of the CD10 antigen was realized with a follow-up period of more than 5 years. The expression of CD38 on bone marrow B cells is a prognostically favorable factor (overall survival, p = 0.026), the role of which is realized within 5–10 days of follow-up after surgery. Bone marrow B1 lymphocytes had no association with breast cancer prognosis (overall survival), however, they were correlated (p = 0.07) with progression-free survival.

Conclusion. Total relative number of (more than 10 %) of bone marrow B-lymphocytes (CD19+) of breast cancer patients were significantly related to the more favorable prognosis (overall survival) primarily because of B-cell precursors (CD10+) CD38+ bone marrow cells were also associated with more favorable prognosis. Levels of B1‑lymphocytes (CD5+) in bone marrow lymphocytes were not related to the prognosis of breast cancer. Prognositic role of B-lineage precursors and CD38‑positive cells was noted in the periods of 5–10 years after operation.

Introduction. At present, in the light of impressive scientific achievements in tumor immunology, the question of the need for immunotherapeutic support in the treatment of cancer patients is especially relevant. Increasing attention is paid to the quality of life of patients receiving immunosuppressive therapy. However, the standards of immunotropic therapy in the complex and combined treatment of an oncological patient have not yet been developed. In the Russian Federation, more than 30 years ago, Timalin, a complex of peptides of thymic origin, was registered and approved for use in cancer patients.

The aim of the study was to evaluate the potential of Timalin to improve the quality of life of cancer patients during standard therapy.

Materials and methods. The study included 20 cancer patients, mostly with III–IV stages of the disease. All patients underwent a study of immunological status indicators before the start of therapy. The main indicators of cellular and humoral immunity were assessed: T-cells, B-cells, NKT-cells, activation markers, NK-cells, immunoregulatory index. All patients received Timalin. To assess the quality of life of patients, a questionnaire was used: EQ-5D before the start of Timalin immunotherapy, then once a week for one course lasting 1 month.

Results. After 1 month 9 patients responded that their health status increased by 20 points (on a 100‑point scale), 3 patients by 15 points, and 8 patients by 10 points. Against the background of immunotherapeutic support, all patients noted a decrease in the level of side effects in the process of special treatment for the underlying disease.

Conclusion. The article shows that before treatment, the indicators of the immune status and the condition of patients required immunocorrective therapy. Substantiated conclusions were made about the need to consider the inclusion of thymic peptides in the standards of care for cancer patients.

Introduction. Various scientific studies are carried out all over the world aimed at solving issues related to the availability and improvement of the quality of medical care to the population through various measures aimed at improving the integration and coordination of production and technological processes in medical organizations. In our previous works, the key methods for optimizing the operation of the operating unit were outlined, and efficiency was demonstrated with justification for the introduction of methods into the work of not only the operating unit, but also the unit involved in preoperative preparation, but the period for evaluating performance indicators was 1 year. Therefore, the study was continued in the period 2017–2021.

The purpose of the study is to evaluate the effectiveness of the practical implementation of the lean technology methodology in the operation of the operational unit.

Materials. Statistical data on the results of work of surgical departments of the Research Institute of Clinical Oncology of N. N. Blokhin National Research Medical Center of the Ministry of Health of the Russia for 2017–2021.

Results. The expansion of the staff, the active use of all operating rooms, the rational distribution of medical equipment and instruments, the change in the work plan of departments and the routing of surgical patients allowed not only to increase the flow of patients, but also to achieve world standards when planning the operation of the operating unit. Using the example of a progressive increase in the number of operations at the Research Institute of Clinical Oncology from 10 470 in 2017 to 15 140 in 2021, as well as the example of individual surgical departments (surgery departments No. 15, plastic surgery departments), it is possible to trace the process of successful optimization.

Conclusion. An example of the development and application of lean technologies in the operating unit of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia makes it possible to conclude that a competent approach to optimizing the unit is necessary, which can be achieved in a relatively short time by increasing productivity. Lean technologies have helped to significantly reduce the preoperative bedday, significantly increase the productivity of the operating unit, and as a result, increase the number of surgical interventions performed at the center.

Introduction. Sonodynamic therapy is a topical research area in experimental oncology. The method is based on the combined use of photosensitizing agents with ultrasonic radiation with certain parameters. The result of this interaction is the induction of sonochemical reactions and the effect of cavitation in the tumor cell. The consequence is its death (apoptosis, autophagy).

The study objective is to investigate the antitumor efficacy of sonodynamic therapy with a chlorine-based photosensitizer (PS) in an experiments on laboratory animals with transplantable tumors.

Materials and methods. The experimental study was performed on 50 white outbred rats weighing 250 ± 50 grams. Subcutaneously transplanted Pliss lymphosarcoma (PLS) and alveolar liver cancer RS1 (RS1) were used as tumor models. Chlorine-based PS (Belmedpreparaty, Republic Belarus) was injected intravenously at a dose of 2.5 mg / kg. The ultrasound sessions (US) were carried out 2.5–4 hours (depending on the tumor strain) after the administration of the PS using the device Phyaction U (Gymna Yniphy, Belgium) with frequencies of 1.04 and 3 MHz, intensity of 2 W / cm2 and duration of 10 minutes in continuous mode. For each of the tumor model the study was performed on 25 laboratory animals subdivided into groups of 5 individuals: intact control, US 1.04 MHz; US 3 MHz; PS + US 1.04 MHz and PS + US 3 MHz. The criteria for assessing the antitumor efficacy were indicators of the dynamics of the growth of transplanted tumors: аverage volume of tumors (Vav, cm3), the coefficient of tumor growth inhibition (TGI, %), coefficient of absolute growth of tumors (K) and the frequency of complete regressions 60 days after treatment (%).

Results. For PLS Vav in groups were 32.72 ± 7.23; 26.81 ± 1.06; 14.80 ± 5.08; 9.37 ± 6.05 and 22.25 ± 4.91 cm3, respectively (p ˂0.05). The coefficients TGI in the experimental groups were 20.27; 54.77; 71.36 and 31.99 %, respectively. Indicators K in groups were 21.64; 14.52; 6.12; 4.91 and 15.34, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0, 20, 20, 40 and 0 %, respectively. For RS1 Vav in groups were 23.29 ± 5.11; 6.22 ± 2.22; 11.78 ± 4.57; 6.38 ± 2.57 and 13.06 ± 3.53 cm3, respectively (p ˂0.05). The coefficient of TGI in the experimental groups were 73.25; 49.42; 72.60 and 43.92 %, respectively. Indicators K in groups were: 8.34; 1.11; 3.39; 2.91 and 5.05, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0, 0, 0, 40 and 0 %, respectively.

Conclusions. The data obtained indicate a trend towards an increase in the antitumor effectiveness of the combined use of PS and sonodynamic therapy on various histological structures and growth patterns of transplanted tumors, as well as the prospects for further studies of the sonosensitizing properties of photosensitizing agents.