Background. An in-depth study of the participation of the microbiota in the pathogenesis of tumors has opened up new opportunities for the development of alternative approaches to the diagnosis, therapy and prevention of malignant neoplasms.

Aim. To summarize the data on the practical use of microbiota profile features as a marker of carcinogenesis and diagnosis, as well as to consider its participation in the combined treatment and prevention of cancer.

Materials and methods. A literature search was carried out in the databases NCBI MedLine (PubMed), Scopus, web of Science using keywords that determine the purpose of the study. Results from original studies, meta-analyses, randomized controlled clinical trials, and traditional, systematic, and umbrella reviews published in recent years were analysed.

Results. Qualitative and quantitative changes in the composition of the microbiota associated with the pathogenesis of oncological diseases make it possible to use them as markers for determining the risk of developing malignant neoplasms and predicting a wide range of tumors. The mechanisms that determine the use of the microbiota in anticancer therapy are diverse. The effect on the immune system is the most significant. Of great interest are artificially created hybrid nanoparticles covered with a membrane of bacterial vesicles and tumor cells to activate specific antitumor immunity. In terms of cancer prevention, the use of probiotics, prebiotics and synbiotics discovered by I.I. Mechnikov was fundamentally substantiated.

Conclusion. The complex of scientific genomic and epigenetic data obtained in mechanistic and epidemiological studies on the role of the microbiota in the pathogenesis of tumors is currently evaluated as the most significant result justifying its practical application as a component of cancer diagnosis, therapy and prevention.

Background. Skin melanoma (SM) is a malignant non-epithelial tumor of transformed melanocytes with predominant localization on the skin (more than 90 % of cases). According to statistics for 2021, SM in Russia accounted for 1.82 % of all malignant neoplasms of the adult population and 12.65 % of all skin tumors. There has been a steady and annual increase in the incidence of SM throughout the world, especially in countries with a predominantly Caucasian population. In Russia, over the past 10 years, mortality from SM has increased by 17.6 %. SM is a heterogeneous tumor with a high metastatic potential, because in addition to standard clinical and pathomorphological prognostic factors, the identification of additional factors of progression and unfavorable prognosis of the disease remains an urgent and unresolved problem of modern oncology.

Aim. To determine the role of spontaneous tumor regression in the occurrence of SM progression based on the analysis of literature data and their systematization.

Results. This literature review reflects various global research data on the role of spontaneous regression of SM in progression. Spontaneous regression of SM is an immunological process in which the disappearance of tumor cells is observed, which leads to the division of the tumor into separate islands with intermediate areas of non-tumor tissue. The mechanism of spontaneous regression of primary SM, as well as its prognostic significance, is not well understood and studied. Of course, most researchers primarily associate the occurrence of spontaneous regression of melanoma with an immune response, since lymphocytic infiltration of the tumor was noted in all cases of regression. The presence of lymphoid infiltration, as well as the quantitative and qualitative ratio of its cells, are important in the development of the tumor process, affect the effectiveness of immunotherapy and is to a greater extent a factor in a favorable prognosis.

Conclusion. The prognostic role of spontaneous melanoma regression is still an unresolved and controversial issue. Interestingly, a number of studies demonstrate that regression is an independent predictor of the progression of SM.

Background. In recent years, the availability of reconstructive plastic surgery has reached a new level. when performing an oncological operation, the question arises about choosing further reconstruction tactics: through one-stage or through delayed reconstruction. In the vast majority of cases, tissue expanders/implants are used for simultaneous breast reconstruction, but it is still unclear which allograft allows achieving the best aesthetic results of the operation without increasing the incidence of postoperative complications. In this review, we assessed the impact of the type of implant on aesthetic satisfaction with the result of reconstruction and the incidence of postoperative complications in patients with breast cancer.

Aim. To evaluate the impact of the type of implant during reconstruction on the risk of postoperative complications and quality of life in patients with breast cancer.

Materials and methods. A search for relevant sources was carried out in PubMed, MedLine, Cochrane Library, EMBASE, Global Health, Cyber Leninka, SpringerLink, e-Library, publications from 2010 to 2022 were studied, with an analysis of the evidence-based experimental and clinical base on the most modern issues breast reconstruction. Results. Having analyzed articles published over the past 15 years, we can clearly conclude that performing reconstructive plastic surgery in patients with breast cancer using various types of implants improves the quality of life and improves the aesthetic result of reconstruction according to the BREAST-Q questionnaire, regardless of the type and type of implant used.

Conclusion. The use of anatomical implants in breast reconstruction compared to round ones reduces the risk of rupture, rippling, and the frequency of symmetrizing operations, but increases the risk of infectious complications and repeated operations to replace/remove the implant. The use of textured implants reduces the incidence of capsular contracture relative to smooth ones. High satisfaction with the aesthetic outcome of reconstruction, as measured by the BREAST-Q questionnaire in patients with silicone implants, is not equivalent to an improvement in general health status (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30).

Background. FCGR3A and FCGR3B messengers RNA (mRNA) translate the synthesis of membrane molecules of CD16A and CD16B, which are low-affinity immunoglobulin (Ig) G receptors bound to different cells of the immune system and involved in the immune response to tumors.

Aim. The aim of this study was to determine the level of FCGR3A and FCGR3B mRNA in the peripheral blood of patients with prostate cancer (PC).

Materials and methods. Blood samples from 47 prostate cancer patients and 31 healthy blood donors were examined. The relative level of FCGR3A and FCGR3B mRNA in the blood of patients and healthy donors was determined by reverse transcription polymerase chain reaction in real time (real-time RT-PCR).

Results. It has been shown that the relative level of FCGR3A and FCGR3B mRNA in the blood of PC patients exceeds the level evaluated in volunteers. The relative level of FCGR3A mRNA increases with age, with an increase in PSA concentration, prostate volume and stiffness, and in the presence of metastases. Differences in testosterone concentration, Gleason score, disease stage and tumor spread were not accompanied by changes in FCGR3A mRNA level. For FCGR3B mRNA, a different manner of its changes was revealed. As PSA concentration and prostate tissue stiffness increased, elevated FCGR3B mRNA level decreased, reaching normal levels. In the absence of metastases, it was higher than if they were present. In addition, trends towards an increase in the level of FCGR3B mRNA were revealed with an increase in the stage of the disease, the concentration of testosterone to 7 mmol / L and above, as well as the Gleason score to 7 and above.

Conclusion. Multidirectional changes in FCGR3A and FCGR3B mRNA levels were found with an increase in the severity of PC. Probably, the revealed nature of the change in the level of FCGR3A and FCGR3B mRNA associated with the dose-dependent effect of PSA on their level. The results indicate a possible monitoring value of FCGR3A mRNA and FCGR3B mRNA levels in the blood of PC patients.

Background. Pembrolizumab belongs to a fundamentally new class of antitumor agents with biological source – monoclonal antibodies. when creating generic biological medicinal products, it is necessary to assess the comparability of the pharmacokinetics of the developed drug and the original (reference) drug product in relevant animal species.

Aim. To compare the pharmacokinetics of two drugs with INN pembrolizumab, concentrate for solution for infusion, administered once intravenously to Macaca fascicularis.

Materials and methods. Biosimilar RPH-075 (INN pembrolizumab, JSC R-Pharm, Russia) and reference drug Keytruda® (INN pembrolizumab, MSD International GmbH) were administered once intravenously to male monkeys (2 groups of 4 males each) at a dose of 30 mg/kg. Macaque blood samples were collected for analysis before administration and at 1, 2, 4, 8, 24, 48, 72, 144, 312, 480, 648, 984, 1320 h after administration. Plasma concentrations of the active ingredient were determined by bridging ELISA using commercially available antibodies, followed by calculation of the main pharmacokinetic parameters (Cmax, AUC, MRT, Vss, T1/2, Cl).

Results. Using antibodies more available than commercial reagent kits, the pembrolizumab assay method recommended by the antibody manufacturer has been replicated. The method has been validated and applied to the analysis of biosamples obtained in the preclinical study. There was no effect of the test drug and the reference drug upon single intravenous administration to monkeys condition and animals body weigh; drugs were found to have comparable pharmacokinetic profiles.

Conclusion. The creation of a biosimilar drug in the Russian Federation will improve the treatment of patients with cancer, reduce the cost of treatment and increase the number of patients receiving high-quality medical care.

Background. Loss of heterozygosity, loss of the Y chromosome, and other types of genetic alterations are characteristic of tumor cell lines. Standard methods for detecting such changes are effortand time-consuming, and costly. Routine laboratory analysis of the authenticity and absence of intraspecific cell lines contamination using short tandem repeats (STR) profiling also allows for monitoring some genetic changes that cells undergo during the life cycle. The location of some potential STR loci is close to regulatory oncogenic loci, so many researchers note the prognostic and diagnostic utility of using STR profiling at the primary stage of genetic characterization of cell lines.

Aim. Control of cell identity and genetic variability during the establishment of a stable cell line.

Materials and methods. Profiling was carried out for primary cell cultures, for xenografts samples mel Lap nude, mel Kas nude and mel Pet nude, as well as during cell culture at 8^th, 10^th, 20^th passages of the mel Lap, at 10th, 20^th passages of the mel Kas and at 5^th, 10^th, 20^th, 49^th passages of the mel Pet, as well as after defrosting archived samples.

Results. For the mel Lap culture, by passage 8, a loss of heterozygosity was observed at the SE33 locus, and then the genetic profile remained stable. By passage 10, mel Kas cells lost heterozygosity for two loci SE33 and D6S1043, and in the CSF1PO locus at passage 0, amplification of three alleles was observed – 11, 12, 13. Subsequently, the culture maintained a stable STR profile. By the 5th passage, the mel Pet cell culture lost heterozygosity for almost all the studied loci, but then its STR profile remained unchanged throughout 49 passages and in the xenograft material.

Conclusion. The STR profiling method allows not only to monitor genetic stability in a cell line and the absence of intraspecific contamination during cultivation, but also, being fast and cheap, can be used as an additional primary test for significant genetic changes in cells.

Background. In the experimental study of potential medicines, animal studies are of the greatest prognostic importance. Domestic authors performed most of the experimental toxicological work on rats of outbred colonies (mongrel (albino) and wistar). The variability of numerous literature data obtained over a long time range on the physiological parameters of mongrel rats and wistar rats indicates the need for their comparative characteristics in one study.

Aim. To evaluate the main indicators for wistar and albino rats used in assessing the acute and chronic toxicity of pharmaceutical compounds and to determine the physiological characteristics of the animals in these colonies.

Materials and methods. Female albino and wistar rats of the same age were used in the experiment. The animals were kept in the same conditions according to international ethical standards. The condition, behavior, body weight, peripheral blood parameters, feed intake, daily diuresis, neurological reactions, mass coefficients of internal organs were evaluated.

It was found that in wistar rats, body weight increases significantly more slowly, its weekly increase is ≈4–5 %, in Albino ≈10 %. The number of red blood cells and hemoglobin levels are significantly lower, the volume of red blood cells is larger, and the hemoglobin content is higher for Albino rats. For wistar, an increased level of anxiety in the open field test and a lower variability of the arithmetic mean error were demonstrated.

Conclusion. The features of the physiological parameters of the studied colonies of mongrel rats are within the reference intervals. The choice in favor of Albino rats or wistar rats in modeling preclinical experiments depends on the type and objectives of the study. when studying the neurotoxicity of drugs, the increased anxiety level of wistar rats should be taken into account.

Background. Lipophilicity is a fundamental physicochemical property that determines the solubility and transport of a drug through biological membranes, as well as its behavior in the body. Lipophilicity also affects the ability of a drug to bind to plasma proteins and reach the corresponding receptors. The standard for drug lipophilicity experimental study is measuring the distribution between two immiscible phases – aqueous (water and buffer solutions) and hydrophobic (most often octanol).

Aim. The experimental study of somatostatin analogue cyphetrylin lipophilicity in octanol/water system distribution test.

Materials and methods. The lipophilicity of cyphetrylin, synthesized in the Laboratory of Chemical Synthesis of the N.N. Blokhin National Medical Research Center for Oncology of the Russian Ministry of Health, was studied in the octanol/water system; ethanol was used to study cyphetrylin spectral characteristics and its quantitative determination; shake flask method, UV-spectrometry.

Results. The experimental assessment of cyphetrylin lipophilicity was carried out by shake flask method in a system of mutually saturated water and octanol 1:1. Since cyphetrylin is practically insoluble in water, the concentration of the drug in the octanol phase was determined by UV-spectrometry and the concentration in water was calculated by mass balance. Lipophilicity was expressed as the decimal logarithm of the concentration of cyphetrylin in the octanol phase to its concentration in the aqueous phase (logPo/w) ratio. The experimentally determined value of logPo/w was 1.14.

Conclusion. The lipophilicity of cyphetrylin was studied experimentally by shake flask method as a parameter that determines the molecule probability to reach the biological target. The logPo/w value 1.14 in decimal logarithmic form indicates moderate lipophilicity of cyphetrylin, which exhibits antitumor activity when interacting with somatostatin receptors.