This literature review provides basic information about the role of hematopoietic stem cell transplantation in the treatment of myelodysplastic syndromes, acute myeloid leukemia, acute lymphoblastic leukemia. The recommendations for the use of stem cell transplantation are indicated. Conditioning regimens (myeloablative, non-myeloablative, reduced intensity), their advantages and disadvantages are considered. The issues of prevention and treatment of graft-versus-host disease, including graft preparation (T-cell depletion), extracorporeal photopheresis and mechanisms of graft-versus-tumor (-leukemia) reaction are highlighted. The historical milestones of theimmunotherapy development, the creation of therapeutic monoclonal antibodies, the development of targeted therapy, for example, conjugates of monoclonal antibodies with cytostatic drugs and radionuclides (targeted radionuclide therapy) are reported. Information about radioimmunotherapy as a method used for treatment of solid tumors and non-Hodgkin’s lymphoma, and information on the use of mesenchymal stem cells for the treatment and prevention of the graft-versus-host reaction are presented.

Ovarian cancer of epithelial origin is the most common type of oncological process in this organ and is characterized by a high probability of fatal outcome. It is believed that this is due to insufficiently effective diagnosis of the prevalence and severity of this disease. This review presents data on the development of disease recurrence in a significant number of patients after cytoreductive surgery. According to some authors, the reason for the high risk of recurrence is the insufficient information content of the method of studying histological preparations of regional lymph nodes after staining with hematoxylin and eosin to detect small-sized metastases, including isolated tumor cells and micrometastases. To improve the accuracy of such diagnostics, it is recommended to supplement the study of multilevel sections of lymph nodes using routine staining with the use of immunohistochemistry and other methods using various antibodies to cytokeratins, along with other epithelial markers. The review provides an analysis of the opinions of various researchers on the prognostic significance of the detection of micrometastases in the lymph nodes, which can increase the effectiveness of therapy due to a more accurate assessment of the prevalence of the disease and correction of the tactics of treating patients with various oncological diseases.

Pancreatic cancer (PC) is a malignant highly aggressive tumor that arises and grows under conditions of inflammation and tissue hypoxia. In PC, one of the key processes in progression is epithelial-mesenchymal transition, which leads to early dissemination and rapid realization of metastatic disease, which accounts for low overall survival rates. The tumor, by releasing a wide range of different molecules (circulating DNA, exosomes, proteins and lipids), allows to identify and use them as potential, diagnostic and prognostic biomarkers.

This review introduces readers to the liquid biopsy technique. The main applications of the technique in patients with ductal adenocarcinoma of the pancreas are shown. Liquid biopsy is a modern diagnostic method of molecular oncology, the principle of which is to detect circulating tumor cells, DNA, exosomes in biological fluids. Publications evaluating the potential of the method to assess minimal residual disease, evaluate tumor response to systemic therapy, and determine prognosis are discussed. Liquid biopsy is particularly relevant in cases of malignant tumors of difficult localization, in particular, PC. Modern methods of morphological verification of pancreatic tumors (fine needle biopsy under endosonographic control and percutaneous biopsy) have essential disadvantages: low information value, multiple repeated interventions, postmanipulative complications (pancreatitis, bleeding, etc.). Taking into consideration obvious advantages and perspectives of this method over traditional methods of morphological verification, liquid biopsy seems to be a promising diagnostic tool in personalized oncology for pancreatic cancer.

Primary-multiple malignant neoplasms develop in about 9 % of cancer patients in the Russian Federation, while synchronous tumors are detected in a quarter of them, which dictates the need for a mandatory multidisciplinary approach to the choice of treatment. Localization of synchronous primary-multiple tumors in one anatomical zone requires a qualitative interpretation of instrumental diagnostic methods and morphological analysis after biopsy of each tumor. Along with this, there is a possibility of an erroneous opinion about the presence of different histological structures of the detected tumors and the data of visual assessment methods are interpreted in favor of a single disease.

This paper presents a clinical observation of a rare combination of gastric adenocarcinoma and peritoneal mesothelioma. The case was discussed at a multidisciplinary consultation with the participation of a surgeon, a chemotherapist and a radiologist. Taking into account the clinical stage of gastric body cancer c T3N1M0, III stage, it was decided to conduct preoperative polychemotherapy at the first stage. Repeated diagnostic laparoscopy revealed no negative dynamics, multiple small dropouts in the peritoneum persisted. Subsequently, the operation was performed in the volume of gastrectomy, total parietal peritectomy and appendectomy without macroscopic signs of a residual tumor. It was decided to refrain from intra-abdominal chemoperfusion with hyperthermia due to the large volume of surgery and the previous 8 courses of polychemotherapy. Microscopic examination of the altered part of the stomach wall revealed residual adenocarcinoma (type according to Lauren – intestinal) with signs of therapeutic pathomorphosis G3 (according to Mandard), which had grown into the subserous layer and the fiber of the small omentum, with signs of perineural invasion, in the absence of vascular invasion; resection edges – R0. On the surface of the removed fragments of the peritoneum, various foci of malignant epithelioid mesothelioma were found. At the control examination a year later, according to computed tomography and esophagogastroduodenoscopy, there were no signs of progression, the patient’s condition was satisfactory.

Background. Individuals with increased expression of components of the IGF/INS system, are more likely to develop various malignancies. And in the case when the components of the IGF/INS system are overexpressed in tumors, this adversely affects the prognosis of the disease, including leading to a decrease in relapse-free survival. A characteristic feature of the IGF/INS system is the ability of the same ligands to bind to different receptors and vice versa (cross interactions) and activate different signaling pathways in the cell. This feature of the system requires an integrated approach to the study of the expression of its components, namely, the study of the quantitative ratio of the expression of individual components. The result obtained will make it possible to determine possible combinations of ligand-receptor bonds and, ultimately, will have both prognostic and evaluative value: in terms of a therapeutic target.

Aim. To establish the quantitative ratio of mRNA expression of the IGF/INS system receptors: IR-A, IR-B, IGF-1R, and IGF-2R in the IM9 lymphoblastoid cell line and in three myeloma cell lines: RPMI1640, RPMI8226, H929, and to identify frequency of expression of these receptors in the mononuclear fraction of bone marrow aspirates obtained from treated patients with multiple myeloma.

Materials and methods. We used human lymphoblastoid cells and 3 types of human myeloma cells, differing in the degree of differentiation and, as well as bone marrow aspirates obtained from 19 treated patients with stage III multiple myeloma. Expression of mRNA in cells was studied by quantitative real-time reverse transcription polymerase chain reaction and in bone marrow aspirate samples by semi-quantitative reverse transcription polymerase chain reaction.

Results. During the study, we found that within each cell line, the receptor IR-A is predominant compared to the receptor IR-B. Patients with MM have a high frequency of IR-A expression compared to IR-B. The minimum ratio of IGF-1R:IR-A and IGF-1R:IR-B mRNA is in IM9 lymphoblastoid cells, and for myeloma cells these ratios are high. The ratio of IGF-2R:IR-A is maximum for IM9 lymphoblastoid cells, and for myeloma cells this ratio is three or more times less.

Conclusion. Based on the study of the quantitative ratio of receptor mRNA, we state that in myeloma cells there is a high probability of the presence of IGF-1R/IGF-1R and IR-A/IR-A homodimers, and an IGF-1R/IR-A heterodimer. These data have both prognostic and evaluative value, since these combinations of receptors suggest a significant increase in the mitogenic effect due to activation by three ligands: IGF-1, IGF-2 and INS, which is an unfavorable factor, especially when a patient with multiple myeloma with concomitant Diabetes mellitus was prescribed insulin therapy along with chemotherapy. Based on our findings, we recommend simultaneously inhibiting both the IGF-1R receptor and the IR-A receptor as a therapeutic target.

Background. Despite the significant clinical efficacy of current treatment protocols for acute lymphoblastic leukemia (ALL) in children, high-dose methotrexate demonstrates significant interindividual variability in drug toxicity and disease outcomes due to polymorphisms of drug transporter genes and genes responsible for cytostatic metabolism, which makes pharmacogenetic studies increasingly relevant.

Aim. To evaluate the association of ABCB1 (C3435T rs1045642, rs1128503, rs2032582, rs4148738), SLCO1B1 T521C rs4149056 gene polymorphisms with the main types of methotrexate toxicity and the onset of clinical events (death, recurrence, progression) during the treatment of childhood ALL.

Materials and methods. The study enrolled 103 patients diagnosed with ALL who received therapy according to BFM group protocols (2002/2009), using high-dose (2000 and 5000 mg/m²) methotrexate. Laboratory methods using NCI toxicity scales (CTCAE v5.0 2018) were used to assess adverse reactions. Real-time polymerase chain reaction method was used to study ABCB1 and SLCO1B1 gene polymorphisms. The study material was peripheral blood. Material was sampled once, regardless of the duration of methotrexate therapy. SPSS Statistics 21.0 software was used for statistical processing of the results. Analysis of associations was performed using the χ2 criterion and Fisher’s exact test.

Results. Development of infectious complications, oropharyngeal mucositis, delayed MTX elimination, events were significantly associated with polymorphisms of the studied genes: SLCO1B1 T521C rs4149056, ABCB1 rs4148738, ABCB1 rs1128503, which correlates with the data of world scientific literature.

Conclusion. Determination of polymorphisms of genes responsible for the transport and metabolism of methotrexate is a promising and dynamically developing area of clinical oncology.

Background. β2‑microglobulin is a low molecular weight glycoprotein that is part of the major histocompatibility complex. The concentration of β2‑microglobulin in the blood serum of patients increases with various oncohematological pathologies, including multiple myeloma. One of the methods for detecting membrane β2‑microglobulin is flow cytometry. This article discusses the expression of β2‑microglobulin and key markers on the membrane of malignant cells in patients with multiple myeloma at the onset of the disease.

Aim. To study the expression of β2‑microglobulin and markers CD45, CD56 and CD19 on the membrane of tumor plasma cells in the primary diagnosis of multiple myeloma.

Materials and methods. The study of β2‑microglobulin and CD45, CD56 and CD19 was carried out in 37 patients with multiple myeloma by 8‑color flow cytometry using a panel of monoclonal antibodies for the diagnosis of plasma cell tumors (EuroFlow, 2012).

Results. The expression of β2‑microglobulin in combination with markers CD45, CD56 and CD19 on tumor plasma cells was assessed, illustrations of the expression of these markers are presented. Out of 37 patients with multiple myeloma, hyperexpression of β2‑microglobulin was noted in 23 (62.2 %), in other cases there were normal or reduced levels of this protein in other cases.

Conclusion. Tumor plasma cells overexpress β2‑microglobulin in a significant percentage of cases (62.2 %). This allows further assessment of the clinical significance of such aberrant expression and its relationship with serum levels of β2‑microglobulin.

Background. The search for technology or the use of excipients for the development of drugs containing poorly soluble pharmaceutical substances is an urgent task of pharmacy. According to the biopharmaceutical classification system, resveratrol belongs to group 4: the substance has low solubility and low permeability. Therefore, one of the priorities in the development of drugs with resveratrol is to increase its solubility and, as a result, increase its permeability. The article presents the results of physicochemical studies of resveratrol compositions with solubilizers (poloxamer 407, polysorbate 80, methyl-beta-cyclodextrin) after dissolution in a common solvent followed by evaporation.

Aim. Obtaining compositions of resveratrol with solubilizers and auxiliary formations with an exclusive study of their properties for the development of solid dosage forms.

Materials and methods. Trans-resveratrol, poloxamer 407, polysorbate 80, methyl-beta-cyclodextrin, citric and ascorbic acids, glycerin, methanol; high performance liquid chromatography, differential scanning calorimetry.

Results. Physical and chemical studies of the obtained compositions of resveratrol with excipients were carried out. Excipients used: citric and ascorbic acids for all compositions, as well as glycerin for compositions with tween 80. Stability studies were carried out under conditions of «accelerated aging», as a result of which a noticeable decrease in the amount of resveratrol was found (80 % of the original). Studies of the stability of resveratrol have shown that at low pH, inherent in the stomach, its content remains practically unchanged for two days. And at pH close to neutral, the content of resveratrol is reduced to 90 % of the original amount. The obtained results indicate the feasibility of developing drugs that promote the absorption of resveratrol in the stomach and are stored at low temperatures (in the refrigerator).

Conclusion. Compositions of resveratrol with solubilizers were obtained and the choice of excipients for the development of solid dosage forms was substantiated. Recommendations are given for obtaining solid dosage forms for each of the developed formulations and storage conditions are determined.