According to world Health Organization, breast cancer (BC) ranks first among cancer diseases in women in many developed countries of the world and in the Russian Federation. Over the past 20 years, the incidence of breast cancer in the world has increased and continues to increase. This phenomenon dictates the need for a more in-depth molecular biological, genetic and immunological study of the mechanisms of development and progression of this heterogeneous malignant tumor.

Recently, there has been increasing interest in the world not on lyin the direct causes of tumor development, but also in factors contributing to its progression, such as the cellular microenvironment of the tumor, the composition of which has a great influence on cancer development, treatment and prognosis. In the cellular microenvironment of the tumor, mononuclear cells are assessed, the proportion of which determines the severity and direction of the immuneresponse. Their importance for choosing the priority type of drug therapy and assessing its effectiveness is shown. The article provide scurrent data on subpopulations of T cells (CD8⁺, CD4⁺), B cells (CD20⁺), and natural killer. Their role in the development and progression of breast cancer is discussed depending on their phenotype. Modern research pays attention to a minor subpopulation of T lymphocytes – TCR-Vδ1⁺ cells. This subpopulation is represented predominantly in tumor tissue and has an immunosuppressive effect on T-effectors. At the present stage, inflammatory cells – macrophages and neutrophils – are of no less interest. Their role in tumor progression is widely debated. It is known that the differentiation of macrophages into M1 or M2 phenotypes is determined by the tumor microenvironment. The predominance of macrophages with protumor activity promotes tumor progression and cancer metastasis. Additionally, macrophages can stimulate the migration of neutrophils, which, in turn, support the metastasis of breast cancer through the production of matrix metalloproteinases. Matrix metalloproteinase 9 has been reported to promote the formation of vascular endothelial growth factor, which explains the protumor properties of neutrophils. In the context of growing tumor immunotherapy, assessment of tumor microenvironmental factors is promising both in relation to monitoring the effectiveness of breast cancer therapy and in relation to the search for potential therapeutic targets. The review systematizes and summarizes information on this issue to date.

Background. The development of polyneuropathy in the context of cytotoxic drug administration is a common neurological complication that can significantly impair patients’ quality of life and limit the use of chemotherapy. The difficulties in predicting the manifestations and severity of neurological complications are due to multiple factors, including individual patient characteristics, the type and dosage of the drug used, as well as the presence of comorbid conditions. In recent years, researchers have focused on identifying serum biomarkers that may aid in the early diagnosis and monitoring of Сhemotherapy-induced Peripheral Neuropathy. Understanding their role in the development of polyneuropathy may open new avenues for developing strategies for the prevention and treatment of this complication, which, in turn, could enhance treatment efficacy and improve patients’ quality of life. This review is dedicated to biomarkers and their clinical significance in the development of Сhemotherapy induced Peripheral Neuropathy.

Aim. To analyze and summarize the current understanding of serum biological markers of Chemotherapy-induced Peripheral Neuropathy based on literature data.

Materials and methods. The literature search was performed using the following databases: PubMed, Medline. Systematic reviews, publications of original studies and meta-analyses between 2000 and 2023 were included in the analysis.

Results. Over the past decades, new insights in to the role of biomarkers in the development of Chemotherapy-induced Peripheral Neuropathy have emerged, among which neurofilaments are more specific. The use of readily available and ultra-sensitive techniques for measuring biomarker concentrations will allow early prediction and prevention of this complication.

Conclusion. The analysis of literature data has shown the high relevance of the role of biomarkers in the damage of peripheral nervous system structures, which may in the near future affect the management tactics and in turn improve the quality of life of cancer patients.

Background. The variety of characteristics that should be taken into account in the clinical phenotyping of allergic diseases is currently being discussed. One of such characteristics is the individual spectrum of sensitization. An important stage in modern allergology has become the introduction of molecules / components for the detection of mediated reactions to specific class E immunoglobulins.

Aim. To determine the dominant phenotypes of sensitization in patients with severe atopic dermatitis and bronchial asthma based on the results of molecular diagnostics by the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) method using machine learning.

Materials and methods. The study included 100 patients who were candidates for genetically engineered biological therapy (n = 63), severe atopic dermatitis (n = 20), or their combination (n = 17) were included. Allergodiagnosis was performed by the ImmunoCAP ISAC method.

Results. Based on the results of the study, 6 phenotypes were identified. In phenotype 1, pollen molecules (Amb a1, Phl p4) and crossed reactive food molecules (Mal d1, Ara h8, Gly m4, Act d8, Pru p3) are the leading, among epidermal molecules only Fel d1 (epidermal allergen) and Asp f6 (fungal allergen) are found. For phenotype 2, the significant allergens were fungal (Asp f6), epidermal (Can f1, Can f5, Can f6, Fel d1), food (Gad c1) and cross reactive food molecules (Mal d1, Pru p1. Ara h8, Cor a1.0401). In phenotype 4, only 3 allergen groups are present:

epidermal (Fel d1, Fel d2, Can f5, Can f6, Can f3), fungal (Asp f6), and cross food allergy (Jug r3, Pru p3). Phenotype 5 and 6 are dominated by epidermal molecules (Can f1 and Fel d1), true food allergies allergens (Gad c1 and Gal d1 and Gad c1, Gal d1, Gal d3, respectively). In phenotype 3, a combination of the previously labeled molecules is noted.

Conclusion. Each of the identified phenotypes reveals a different set of molecules that can be used in real clinical practice to develop reduced panels, making them more accessible.

Background. Currently, the search for circulating immunological and inflammatory markers that play a significant role in the pathogenesis of uterine fibroids (UF) is relevant.

Aim. Changes in the serum levels of soluble molecules CD50 (sCD50), CD54 (sCD54) and CD95 (sCD95) in patients with UF depending on the characteristics of the disease.

Materials and methods. The study involved 78 patients with UF aged 31–59 years and 45 clinically healthy women of comparable age. The patients were divided into the following groups depending on the localization of the myomatous node: interstitial-subserous localization (n = 17), subserous localization (n = 16), submucosal localization (n = 15), interstitial-submucosal localization (n = 15), interstitial localization (n = 15). In 34.6 % patients, the number of myoma nodes was 4–6, in 46.2 % women there were 2–3 nodes, in 19.2 % – 1 node.

Determination of the serum concentration of sCD50, sCD54 and sCD95 molecules was performed using a two-site enzyme immunoassay and expressed in conventional units (U / ml).

Results. The average serum concentration of sCD95, sCD54 and sCD50 in all patients with UF was significantly higher than in the control group (p <0.05). The maximum level of the tested molecules was found in UF patients with submucosal localization and the presence of one myomatous node.

Conclusions. The detected increase in sCD50, sCD54 and sCD95 levels in UF patients indicates the participation of these proteins in the immunopathogenesis of this pathology. The imbalance in studied proteins levels is most pronounced in submucosal localization of fibroids, which may indicate an unfavorable course of the disease and serve as an additional criterion for selecting patients in the preoperative period.

Background. Among all the new methods and approaches, virotherapy with oncolytic viruses, both in combination with immunotherapy and without it, shows high efficiency in various phases of clinical trials and good tolerance by patients.

Aim. To study the sensitivity of some immortalized cancer cell lines to the R-92 strain of human reovirus with cell characteristics at the ultrastructural level.

Materials and methods. The study was carried out on cell lines of HeLa, A549, U87MG. Cells were planted in an amount of 15 thousand per well of a 96-well plate and after adhesion, the virus was inoculated by adding a medium containing virus particles in 4 tenfold dilutions (approximately 10 9 –106 particles per ml). Next, the cells were cultured for 24 h, after which the number of living cells in the wells was determined indirectly using the methyl tetrazolium test, which was carried out according to standard methods. To study the ultrastructure of infected cells, cells were seeded into a T25 flask and inoculated with the virus at the maximum concentration. After 24 h of cultivation, the cells were fixed in a 2.5 % glutaraldehyde solution in phosphate buffer for 1 h, after which they were washed three times in phosphate buffer and samples were processed for TEM according to standard methods.

Results. Diluting the virus 1000 times led to a decrease in the cytostatic effect in all three cultures to a level practically no different from the control. HeLa turned out to be the most sensitive culture to reovirus. In the experiment, the number of living cells decreased to 60.4 ± 10.2 % compared to the control during incubation with the maximum number of viral particles and to 63.7 ± 16.2 % with a tenfold dilution of the virus. This indicator was significantly lower than in the other two studied cultures under these cultivation conditions (p <0.001).

In addition, at the maximum virus concentration, the A549 culture was less sensitive than the U87MG culture (p <0.01). At lower concentrations of viral particles, the average viability of the studied cell lines did not differ significantly from each other. Analysis of electron diffraction patterns showed that the virus successfully replicates in the cytoplasm of the studied cultures, but is not released from the cell, which is apparently due to the short incubation period. TEM also showed cell damage characteristic of apoptosis or necroptosis, uniformly expressed in all studied cultures.

Conclusion. Cell lines A549, HeLa and U87MG, according to the results of the methyl tetrazolium test, demonstrate different sensitivity to the human reovirus strain P-92. The TEM picture of cells from infected cultures showed signs of the development of apoptosis or necroptosis.

Background. Expanding the list of safe and effective medicines are the main directions of development of modern medicine and pharmacy. Acridine derivatives are an interesting object of study due to their proven antitumor effect on leukemia and lymphoma. The mechanism of their antitumor effect is the ability to intercalate DNA, as well as to inhibit topoisomerases and telomerase, initiate ROS-mediated oxidative stress, arrest the cell cycle, and interact with glycoprotein-P.

Aim. To develop the composition and technology for obtaining a model pharmaceutical form (PF) for parenteral use of a new compound a pyrrolo [3,2-l] acridinone derivative with antitumor activity.

Materials and methods. Substance MOB 265 S (Institute of Technical Chemistry of Ural Branch of Russian Academy of Sciences – Perm Federal Research Center, Ural Branch of Russian Academy of Sciences, Russia), polyvinylpyrrolidone (PVP, Kollidon® 17PF, BASF, Germany), polyoxyl-35-castor oil (Cremophor® ELP, BASF, Germany), macrogol (15) – hydroxystearate (Cremophor® ELP, BASF, Germany), water for injection. Technological (solubilization, dissolution, filtration, lyophilization), analytical (spectrophotometry, potentiometry) and biological (in vitro) methods were used in the experimental work. Cytotoxic activity was determined on cell lines of T-cell lymphoblastic leukemia Jurkat, PC-3 prostate carcinoma, A549 lung carcinoma, colon carcinoma HCT-116, breast adenocarcinoma MCF-7.

Results. In the course of experimental studies using various solubilizers, model compositions of a PF based on MOB 265 S were obtained, in which water for injection was used as a solvent. The formation of a clear solution was observed only in the model with PVP, which was characterized by basic pharmaceutical parameters and studied in vitro. The inhibitory concentration causing 50 % cell death on various cell lines was 29.6–65.5 μM.

Conclusion. Model of the PF a new domestic compound (pyrrolo [3,2-l] acridinone derivative) in the form of a lyophilisate with a mass ratio of MOB 265 S: PVP – 1:5, as well as a technology for its production in 5 stages. The main quality indicators of the resulting model were selected. The results of cytotoxic activity showed that the composition is effective in all used cell cultures, with maximum cytotoxicity observed in the Jurkat leukemia cell line, which coincides with literature data on the cytotoxic activity of acridine derivatives on leukemia and malignant lymphomas. The new PF is promising for further research as an import substitution, due to the lack of acridinone derivative drugs in Russia.

Background. Iron oxide nanoparticles (NP) represent a promising theranostic platform for combined radiotherapy: the reactivity of iron oxide enhances oxidative stress of tumor cells associated with irradiation while magnetic properties may provide additional feature as controlled delivery.

Aim. To study the potency of heparinized iron oxide NP in experimental antitumor therapy.

Materials and methods. The synthesis of iron oxide NP was carried out by chemical precipitation followed by magnetic separation, the resulting sol was stabilized with heparin. For each batch of newly synthesized particles, the hydrodynamic diameter was determined, IR spectrometry, X-ray diffraction analysis, and scanning electron microscopy were performed. The MX-7 tumor model of rhabdomyosarcoma chosen for the study was transplanted into female C3HA mice; NP were administered intratumorally or intravenously, once a day, according to the “5–2–5” scheme. Fractional irradiation (1–2 Gy / fraction; 1.3±0.15 Gy / min) was carried out after NP administration.

Increasing life expectancy (ILE), the degree of tumor growth inhibition (TGI), a pathomorphological assessment of the lung, liver, spleen and tumor node was carried out for all experimental mice.

Results. As a result of the study, it was found that when administered intratumorally, heparinized iron oxide NP are retained inside the tumor, providing a moderate additive effect, compared with isolated radiotherapy in the first week of irradiation (TGI = 40 % (day 6), TFD = 10 Gy, p <0.05), however, with an increase in tumor volume by the end of the second week, the treatment regimen was not more effective than radiotherapy. with a combination of radiotherapy and intravenous administration of NP, the effect was observed within two weeks (TGI = 43 % (day 6), TGI = 29 % (day 14), TFD = 10 Gy; p <0.05; ILE = 54 %, TFD = 20Gy; p <0.05).

Conclusion. The studied iron oxide nanopreparation enhanced capacity of radiation therapy to inhibit tumor growth when administered intravenouslyin experimental mice with rhabdomyosarcoma and irradiated subsequently.

Background. One of the important areas of pharmaceutical research is the creation of new, as well as improvement of existing, in-demand dosage forms, using already known drugs as active substances. Current issues are the development of drugs that activate the integrative properties and functions of the brain, as well as increase the body’s resistance to aggressive influences. Nootropics, namely piracetam and its analogues, are successfully used in neurological, psychiatric and drug treatment practice. At the same time, the intranasal route of administration is attractive for combined and longterm therapy of these diseases. when developing new intranasal compositions, the issues of choosing the optimal combination of excipients that allow the dosage form to be easily distributed in the nasal cavity must be resolved. The selection of optimal compositions based on consistency properties is possible on the basis of rheological research data, which allows not only to predict the properties of the dosage form being developed, but also to select the required composition and ratio of components. In addition, an important indicator of the quality of soft dosage forms that affects consumer properties is their stability during transportation and storage, as well as such an indicator as spreadability.

Aim. Selection of the optimal composition of the gel with piracetam based on rheological characteristics and predicting the thermal and colloidal stability of the gel structure.

Materials and methods. Carboxymethyl cellulose, chitosan and carbopol were chosen as the gel base. The rheological characteristics of the samples were studied by rotational viscometry on a Fungilab Premium viscometer (Spain). Data were obtained and collected using Fungilab Data Boss software; additional data processing was carried out using Microsoft Excel.

Results. The gelling agent was selected and its rheological characteristics were determined.

Conclusion. The optimal composition of excipients piracetam gel was selected taking into account the basic rheological parameters.

Background. For in vivo determination of size and metabolic characteristics of model tumors in laboratory animals, it is recommended to use imaging methods: positron emission tomography (PET), single-photon emission computed tomography (SPECT), computed tomography (CT) and magnetic resonance imaging (MRI). Due to the limited availability of hybrid scanners, it is necessary to investigate the feasibility of obtaining tomograms on separate devices with subsequent geometric comparison of images.

Aim. To investigate the feasibility of multimodal imaging of mice with subcutaneous melanoma B16F10.

Materials and methods. PET, SPECT and CT were performed using a preclinical VECTor 6 tomograph (MILabs, the Netherlands), MRI was performed using a preclinical nanoScan^® 3T tomograph (Mediso, Hungary). The following modality combinations were studied: MRI and PET / CT with ¹⁸F-fluorodeoxyglucose; MRI and PET / CT with ¹⁸F-boronphenylalanine; MRI and PET / SPECT / CT with ¹⁸F-fluoroethyltyrosine (¹⁸F-FET) and ¹⁷⁷lutetium – prostate-specific membrane antigen (¹⁷⁷Lu-PSMA). Mice were immobilized in a custom-made device during scanning and during movement between tomographs. PET and MRI, SPECT and MRI images were fused in the program InterView FUSION 3.09.008.0000 through an intermediate stage of fusion with CT.

Results. Multimodal PET / CT / MRI and PET / SPECT / CT / MRI images of tumor-bearing mice were obtained for the first time in Russia. PET / MRI data confirmed development of the tumor from 6 × 4 × 4 mm in size. PET / SPECT / CT / MRI enabled to image visceral organs with high accumulation of radionuclide tracers: pancreas with ¹⁸F-FET (standardized uptake value 2.6) and kidneys with ¹⁷⁷Lu-PSMA (standardized uptake value 4.4), while the obtained images of organs did not merge and did not overlap.

Conclusion. Multimodal imaging enables the selection of experimental animals with tumors of specific size and metabolic activity for the study of new radiopharmaceuticals, including those with vector delivery.