Introduction: EGFR-activating overexpression or somatic mutations are common in different human cancers. In this regard, the search for promising ways to control the carcinogenic transformation of tumor cells and the progression of malignant tumors expressing EGFR seems to be one of the most promising and developing areas of modern molecular pathology and pharmacology. Material and Methods: An antitumor activity of a novel compound, a pyridine carboxylic acid derivative LHT-17-19, was studied. The molecule was developed and synthesized at the Department of Chemistry, Drug Design and Technology of All-Russian Research Center for Biological Active Compounds Safety (Russia). The study was carried out in cell cultures of stomach cancer (Hs746T, AGS and MKN1) and patient-derived organoid (PDO) model of breast cancer (BC) expressing wild-type EGFR. Results: It was shown that LHT-17-19 induced concentration-dependent cytotoxicity of EGFR-expressing gastric cancer cells of all the aforementioned cultures. Pathomorphological, immunohistochemical and molecular validation of BC organoids derived from ductal breast carcinoma cells of a 68-year-old patient was done. PDOs were established as ER-negative, PR-negative, Her2/neu-negative, EGFR-positive with 35% of the Ki-67 expression index. In addition, the tumor cells translocation was resulted in a loss of ER expression and PDOs molecular pattern conversion towards a more aggressive triple negative type. PDOs incubation with 0.5-60.0 µM LHT-17-19 was accompanied not only by inhibition of their growth and proliferation, but also by significant cytoreduction. Conclusion: Thus, in two-dimensional and three-dimensional tumor cell cultures, the possibility of controlling the oncogenic expression of EGFR with the acridone compound 9-ammonium-3,3-dimethyl-3,4-dihydroacridine-1(2H)-OH L-2-hydroxybutanedivacate (LHT-17-19) was shown.

The study involved a newovel compound, a benzoxazinone derivative Rog014. QSAR analysis was performed using the PASSonline software. The ADME methodology was used to predict pharmacokinetic parameters. Screening for antitumor activity of the compound included in the A549 tumor culture (human non-small cell lung adenocarcinoma); non-tumor human fetal lung fibroblasts MRC-5 were used for the primary safety assessment of the compound. As a result of bioinformatics prediction of biological activity of benzoxazine-2-thione compound Rog014, biological targets and types of action were established, which determine the possibility of implementing substances with antitumor activity. According to its physicochemical properties, the limiting substance has moderate lipophilicity, can be absorbed from the gastrointestinal tract, is able to penetrate the blood-brain barrier and, for determining the characteristics, can be considered as a candidate for drugs. When incubating A549 cell culture with benzoxazine-2-thione compound Rog014, IC50 was measured at 4.1 × 10-5 M; while incubation of human fibroblast culture during the study does not lead to an additional cellular side. Compound Rog014 can be considered as a candidate for an antitumor drug.

The global task of modern Russian society is to improve demographic indicators by increasing the birth rate. The introduction of patient-centered programs in obstetric institutions is aimed at the formation of a favorable psycho-emotional state in a couple expecting a child and motivation for childbearing. Objective. Dynamic evaluation of the performance of the third level obstetric institution after the introduction of medical-social-psychological projects. Material and methods. Statistical analysis of the performance indicators of the state budgetary health care institution of the Moscow region «Naro-Fominsk Perinatal Center» for 2018-2022. Results. The article presents the data of the analysis of the performance indicators of the third group obstetric institution for 2018-2022, the dynamics of the total number of births, the number of premature births, cesarean sections, births in women with uterine scar, perinatal mortality was considered. A set of measures aimed at creating a positive attitude in women towards pregnancy and preparation for childbirth was described. Conclusion. The positive dynamics of the most significant indicators after the introduction of medical-social-psychological programs that allow women and their family members to actively participate in decision-making regarding pregnancy management and delivery is shown.