Vol 21, No 2 (2023)

Introduction. Overcoming resistance to anticancer drugs in the treatment of malignant neoplasms is an urgent problem of recent decades. Unfortunately, there is no single mechanism for the development of resistance. Alterations that occur in a normal cell during its transformation into a malignant one can lead to the development of primary resistance whereas secondary resistance occurs already as a result of treatment with anticancer drugs.

The purpose of the review. To summarize current data on the mechanisms of a drug resistance development to chemotherapeutic agents in order to select and implement possible ways to overcome it.

Material and methods. The materials were the results of research on this topic over the past 15 years, from 2007 to 2022. The publications included in the databases PubMed, Medline, EMBASE were analyzed.

Results. Analysis of the research results showed that among the mechanisms of a drug resistance development, there are changes in the activity of energy and metabolic processes, structural and/or functional alterations in the expression and function of cancer-related genes and proteins. All together it can lead to a disruption in the flow of the drug into the cancer cell, its active removal from the cell and the patient’s body, an insufficient, short-lived or perverted reaction of the malignant tumor to the drug. At the same time, the heterogeneity of primary tumor cells and metastatic cells leads to multiple mechanisms of drug resistance development in the same patient or in different patients with the same histological type of tumor. Overcoming or blocking some mechanisms of resistance can lead to the development of others.

Conclusion. The study of the cancer cell drug resistance will help to optimize pharmacotherapy and improve the quality and life expectancy of patients suffering from cancer.

The review is devoted to the analysis of modern ideas about the molecular mechanisms of the development of ferroptosis; the main conditions for the development of this type of cell death are described, and cell markers and targets for the induction of ferroptosis are characterized.

The aim of the study was to determine the current state of the issue and characterize the molecular markers of the induction of a decrease in the activity of glutathione peroxidase 4 (GPX4), lipid peroxidation caused by hyperproduction of ROS by excess iron-containing components.

Material and methods: the analysis and systematization of scientific literature over the past 10 years was carried out in the PubMed, Scopus and Google Scholar databases.

Results: The review focuses on two cellular components whose inhibition causes ferroptotic death: the cystine/glutamate antiporter xCT system and GPX4. This review describes in detail the disorders of iron metabolism. Iron can directly generate excess ROS through the Fenton reaction, thereby increasing oxidative damage. In addition, iron can increase the activity of lipoxygenase. In conclusion, attention is drawn to the unresolved issues of the mechanism of ferroptosis and the prospects for the induction and inhibition of ferroptosis for therapeutic purposes.

Introduction. Lung cancer and tuberculosis, make a significant affect to the morbidity and mortality of the population in Russia and in the world. Strategy of medication therapy has not been developed for cases when these diseases are combined.

The aim of the study was to investigate the effect of antitumor therapy on the course of pulmonary tuberculosis in an experiment. The research was supported by a grant from the Russian Science Foundation No. 22-15-00470 (https://rscf.ru/project/22-15-00470/)

Material and methods. The study was performed on 109 mice of the C57BL/6 line at the age of two months. The animals were infected with the reference strain of Mycobacterium tuberculosis (MTB) H37Rv. Antitumor drugs (that used in the treatment regimens of non-small cell lung cancer) were injected intraperitoneally in monotherapy mode. 10 groups were formed: 1 – intact mice 9 (n=10); 2 – mice infected with MTB, without treatment (n=19); 3 – mice infected with MBT + cisplatin injection 10 mg/kg (n=10); 4 – mice infected with MBT + carboplatin injection 100 mg/kg (n=10); 5 – mice infected with MTB + gemcitabine injection 300 mg/kg (n=10); 6 – mice infected with MTB + pemetrexed injection 167 mg/kg (n=10); 7 – mice infected with MTB + etoposide injection 40 mg/kg (n=10); 8 – mice, infected with MTB + paclitaxel injection 30 mg /kg (n=10); 9 – mice infected with MTB + docetaxel injection 30 mg/kg (n=10); 10 – mice infected with MTB + vinorelbin injection 10 mg/kg (n=10). Comparison of clinical, radiological, and laboratory parameters was performed using nonparametric statistics methods. The survival rate was analyzed using the Kaplan-Meyer method.

Results. There was a decrease in body weight in all groups of mice infected with MTB compared to intact animals. The lowest body weight gain was observed in group 8, and the greatest increase in group 3. Infiltrative-focal changes in the lungs were detected during computed tomography less frequently in groups 3, 4, 9, 10 in comparison with the control (group 2). The lowest total lung lesion index was recorded in groups 10, 9 and 4 (less than in infection control group). In groups 3, 6, 7, 8 tuberculous lung lesions were more common than in group 2. The most common exudative changes were recorded in groups 3 and 7, and productive changes in groups 6 and 7. The highest level of mycobacterial load was recorded in the lungs of mice in group 7 after etoposide injection. Low survival was observed in groups 3, 5, 10. The highest survival rates were recorded in groups 4, 6, 8.

Conclusion. The results of the complex analysis allow us to consider carboplatin and docetaxel as the most promising drugs for the treatment of malignant lung tumors in patients with combined pathology.

Introduction. Primary immunodeficiency states (PIDs) are a heterogeneous group of innate immune disorders. A feature of the clinical manifestations of PID is that they are nonspecific for specific clinical forms. With untimely diagnosis and the absence of pathogenetic therapy for immunodeficiencies, an unfavorable outcome is likely. From these positions, a modern method for diagnosing PID using multiplex analysis of the amount of TREC and KREC in dry blood spots in newborns and young children is relevant.

The purpose of the study: a comparative analysis of the amount of TREC and KREC in dry blood spots in children at risk for primary immunodeficiency (PID) under the age of 2 years as markers of T- and B-cell immune defects.

Methods. Markers of T-cell (TREC) and B-cell (KREC) immunodeficiencies were identified in 112 children from the PID risk group under the age of 2 years. The number of copies of TREC and KREC was determined by real-time PCR. Phenotyping of lymphocytes was carried out by flow cytometry.

Results. In 98 children (87.5%) out of 112 examined, the levels of TREC and KREC did not differ from the reference values. In 14 (12.5%) of children, a decrease in the level of TREC compared with the norm (p<0.05) was detected, regardless of gestational age: 87 copies /10⁵ cells [27–217] in 5 full-term children and 140 copies /10⁵ cells (51–338) in 9 premature babies. The number of copies of TREC in the retest after 4 months reached the reference values in children with different gestational age. A decrease in the absolute and relative values of CD19+lym (B-cell) was found in two children of 2B group.

Conclusion. The obtained results allow us to consider the quantitative analysis of TREC and KREC as an effective method for screening for immune defects, especially T-cell deficiency, in children, regardless of gestational age.

Introduction. There is take place increasing in the incidence of obesity among children and adolescents in the world. However, until now there are not exist clear views about mechanisms of that phenomenon.

The aim of study. The purpose of that work is comparative analysis of metabolic status, as well as content of adipokines, myokines and some hormones in the blood of children and adolescents with obesity, dependent of gender.

Methods. Quantification of the adipokines, myokines and hormones was carried out using multiplex ELISA.

Results. Studies have revealed gender differences in the level of certain hormones, adipokines, and myokines, suggesting the appearance of features in the development of obesity in boys and girls. Obese girl experience compensatory changes that help limit manifestation of insulin resistance and lipotoxicity, as well as cardioprotective and neuroprotective effects. This prevents them from serious complications from the cardiovascular and central nervous system in obesity. In boy, due to the formation of gender peculiarities in the production of hormones, adipokines, and myokines, with obesity there are propose for appearance of a number of complications that worse the prognosis of disease in terms of development of its complications – type II diabetes mellitus and atherosclerosis.

Conclusion. The development of obesity in children and adolescents is accompanied by the appearance of gender peculiarities on the part of the endocrine function of mesenchymal tissues.