Introduction:Alcoholic hallucinosis (AH) is one of the severe complications of chronic alcoholism, characterized by psychotic symptoms such as auditory hallucinations and delusions. Haloperidol is widely used to treat AH; however, its therapy is often complicated by side effects. A personalized approach using pharmacogenetic testing (particularly the CYP2D6 polymorphism) allows individualization of haloperidol dosage, improving both safety and efficacy of therapy. Materials and Methods:The study included 100 men diagnosed with "psychotic disorder induced by alcohol use." Patients were randomized into two groups: the main group (45 patients) received haloperidol based on the results of pharmacogenetic testing, while the control group (55 patients) received standard dosing. Genotyping was conducted for the CYP2D6 1846G > A polymorphism. The effectiveness was assessed using the PANSS, UKU, and SAS scales. Results:Genotyping showed an even distribution of CYP2D6 polymorphisms in both groups. The main group demonstrated a significant reduction in side effects and improvement in psychotic symptoms compared to the control group. Differences on the UKU, SAS, and PANSS scales reached statistical significance on days 3-5 of treatment. Conclusion:Using pharmacogenetic testing to adjust haloperidol dosage improves therapy tolerability and accelerates the resolution of psychotic symptoms in patients with alcoholic hallucinosis, confirming the feasibility of a personalized approach in psychopharmacotherapy.

Gastric cancer if the 5th most common oncological disease in the world and one of the leading causes of death associated with this pathology. In clinical practice, the Lauren classification is widely used for gastric cancer characterization, but it does not provide accurate information on tumor progression and does not allow to select the optimal therapeutic approach. More modern tumor typologies, for example proposed by the The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG), are based on profiling of molecular changes in the tumor genome. Currently, several new classifications exist dividing gastric cancer into groups depending on response to different treatment, for example, checkpoint inhibitors or therapy based on activity of pathological pathways associated with immunity, DNA repair, oncogenic and stromal signatures. The proposed typologies improve diagnosis and treatment of this pathology. The review describes currently available classifications of gastric tumors and considers their practical potential.

Введение. Рак желудка (РЖ) является распространенным злокачественным заболеванием, оказывающим значительное влияние на качество жизни пациентов и уровень смертности. Микросателлитная нестабильность (MSI) – это генетическое изменение, которое может влиять на прогрессирование и прогноз рака. В настоящем исследовании изучаются частоты MSI при РЖ у российских пациентов, а также проводится анализ её прогностической значимости. Цель: определить частоту MSI у больных РЖ в России и проанализировать связь с клиническими параметрами, чтобы оценить прогностическую значимость. Методы. Материалом исследования служили 160 парных образцов опухолевой и неопухолевой ткани больных, оперированных по поводу РЖ. Определение MSI проводили путём фрагментного анализа ДНК с использованием пяти мононуклеотидных маркеров (NR21, NR24, NR27, BAT25 и BAT26). Образцы сравнивали с помощью точного критерия Фишера. Для сравнения более 3 групп использовали критерий хи-квадрат. Общая вероятность выживания рассчитывалась методом предельного произведения Каплана-Мейера. Результаты. По результатам исследования MSI была обнаружена у 28 из 160 пациентов, что составляет 17,5%. При анализе связи MSI с клинико–патологическими характеристиками пациентов выявлена достоверная ассоциация с возрастом старше 50 лет (p=0,038), размером опухоли (Т3-Т4) (р=0,017), метастазами в региональные лимфатические узлы (N1-N3) (p=0,028), отдаленными метастазами (М1) (p=0,009) и интестинальным типом по классификации Лорен (p=0,046). Introduction. Gastric cancer (GC) is a common malignant disease that has a significant impact on patients’ quality of life and mortality rate. Microsatellite instability (MSI) is a genetic change that can influence cancer progression and prognosis. This study examines the frequency of MSI in GC in Russian patients, as well as analyzes its prognostic significance. Aim: to determine the frequency of MSI in patients with gastric cancer in Russia and its relationship with clinical parameters and determine the prognostic significance. Methods. The study material included 160 paired samples of tumor and non-tumor tissue from patients undergoing surgery for gastric cancer. Microsatellite instability was determined by DNA fragment analysis using five mononucleotide markers (NR21, NR24, NR27, BAT25 and BAT26). Samples were compared using Fisher’s exact test. For comparisons of more than three groups, the chi-square test was used. Overall probability of survival (OS) was calculated by the Kaplan-Meier product limit method from the date of surgery to death from any cause and compared statistically using the Mantel-Haenszel test. Results. According to the study results, MSI was found in 28 out of 160 patients, representing 17.5%. When analyzing the associations of MSI with clinical and pathological characteristics of patients, a significant association was revealed with age over 50 years (p=0.038), tumor size (T3-T4) (p=0.017), metastases to regional lymph nodes (N1-N3) (p= 0.028), distant metastases (M1) (p=0.009) and intestinal type according to Lauren’s classification (p=0.046).

В исследовании The Cancer Genome Atlas (TCGA) с учетом выявляемых методом полноэкзомного секвенирования изменений копийности хромосомных локусов, экспрессии генов, метилирования ДНК и активности белков предложена молекулярная классификация рака желудка на четыре подтипа: подтип, ассоциированный с вирусом Эпштейна-Барр (EBV+), подтип, ассоциированный с микросателлитной нестабильностью (MSI), хромосомно-нестабильный подтип (CIN) и геномно стабильный подтип (GS). Однако в настоящее время подтип CIN недостаточно охарактеризован и не имеет эффективных и удобных маркеров для диагностики, молекулярной и гистологической верификации. Подтип CIN характеризуется наличием хромосомной нестабильности, которая проявляется повышенной частотой анеуплоидий и/или структурных хромосомных перестроек в опухолевых клетках. Структурные перестройки при раке желудка CIN являются неслучайными и выявляются в определенных хромосомных локусах, которые часто подвергаются перестройкам в результате определенной структурной организации. В обзоре рассмотрены молекулярные механизмы и возможные причины, приводящие к появлению хромосомной нестабильности в опухолях желудка, представлены характерные перестройки хромосомных локусов и их влияние на развитие и клиническое течение заболевания, а также перечислены драйверные гены, их функции и возможности их таргетирования. The Cancer Genome Atlas (TCGA), using approaches based on the analysis of full-exome sequencing, changes in the copy of chromosomal loci, gene expression, DNA methylation and protein activity, proposed a molecular classification of gastric cancer into four subtypes: the subtype associated with Epstein-Barr virus (EBV+), the subtype associated with microsatellite instability (MSI), chromosomally unstable subtype (CIN) and genomically stable subtype (GS). However, the subtype of GC with chromosomal instability is still insufficiently described and does not have effective and convenient markers for diagnosis, molecular and histological verification. The CIN subtype of GC is characterized by the presence of chromosomal instability, which is manifested by an increased frequency of aneuploidies and/or structural chromosomal rearrangements in tumor cells. Structural rearrangements in CIN subtype of GC are not accidental and are detected in certain chromosomal loci, which are often subject to rearrangements as a result of a certain structural organization. The review considers the molecular mechanisms and possible causes leading to the appearance of chromosomal instability in GC, presents the common rearrangements of chromosomal loci and their impact on the development and clinical course of the disease, as well as lists the driver genes, their functions and the possibilities of targeting them in CIN subtype of GC.

To date, haloperidol has been widely used to treat patients with acute alcoholic hallucinosis. There is strong evidence that haloperidol therapy is commonly associated with adverse drug reactions (ADRs). The 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) is known to affect the metabolism rates of haloperidol; hence it correlates with both therapy efficacy and safety parameters. Objective:The study objective was to investigate the effect of 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) on the efficacy and safety profiles of haloperidol in patients with acute alcoholic hallucinosis. Methods:This study enrolled 100 male patients suffering from acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile of haloperidol was assessed using the PANSS (Positive and Negative Syndrome Scale) validated psychometric scale. The safety profile of therapy was assessed with the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Results:There were no statistically significant results for the efficacy rates (dynamics of the PANSS score: AA genotype -14.00 [-16.00; -12.00], AG genotype -13.00 [-14.00; -10.50], p = 0.306). Similarly, there was no statistically significant difference in the safety profiles (dynamics of the UKU score: AA genotype - 9.00 [7.00; 13.00], AG genotype - 8.50 [7.25; 10.50], p = 0.620; dynamics of the SAS score: AA genotype -12.00 [10.00; 16.75], AG genotype - 10.00 [10.00; 12.25], p = 0.321). Conclusion:The study demonstrated that the 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) in patients with acute alcoholic hallucinosis does not affect the efficacy and safety rates of haloperidol therapy.

Chromatin remodeling is the one of the main epigenetic ways of gene expression regulation both in normal cells and in oncological diseases. Genes encoding protein subunits of SWI/ SNF remodeling complexes often mutate and/or change their expression in human tumors, affecting the expression programs of many genes during carcinogenesis, which is associated with the occurrence and progression of cancer. Today, there are no therapeutic drugs that could directly change the structure of chromatin because of complexity of this process with involvement of a large number of genes, proteins, non-coding transcripts and other intermediary molecules. However, the chromatin remodeling complexes can be affected by consistent influence on the subunits and the genes encoding them, as well as the non-coding RNAs that regulate the operation of these complexes and direct them to the target gene regions. Today, several successful strategies have been proposed to influence epigenetic regulators associated with chromatin in order to cause synthetic lethality of cancer cells and block tumor growth. To influence the processes of chromatin remodeling, various strategies and mechanisms are being investigated, from inhibitors of bromodomains of individual subunits to direct effects on the function of SWI/ SNF by destroying its main adenosine triphosphatase subunit. In our review, we analyze the ways and mechanisms of influencing the SWI/ SNF chromatin remodeling complex in order to obtain a stable antitumor effect, from experiments on tumor cells and animal models to the combined use of clinical drugs for the treatment of cancer patients.

Haloperidol is currently used in addictology for the treatment of acute psychotic disorders, including acute alcoholic hallucinosis. The use of haloperidol is often accompanied by the occurrence of adverse drug reactions (ADRs). There is evidence that CYP2D6 isoenzyme is involved in the biotransformation of haloperidol. Aim:The study aimed to evaluate the relationship of 1846G > A polymorphism of the CYP2D6 gene to the equilibrium concentration levels of haloperidol in patients with acute alcoholic hallucinosis. Material and Methods:The study was conducted on 100 male patients with acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile was evaluated using the PANSS (Positive and Negative Syndrome Scale) scale. The safety of therapy was assessed using the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Equilibrium plasma concentration levels of haloperidol were investigated using the high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS). Results:No statistically significant results were obtained during the therapy efficacy assessment (dynamics of the PANSS score: GG genotype (-13.00 [-16.00; -16.00; -11.00]), GA genotype (-15.00 [-16.75; -13.00], p = 0.728). There was a statistically significant difference in safety assessment scores (dynamics of the UKU score: GG genotype (8.00 [7.00; 10.00]), GA genotype (15.00 [9.25; 18.00], p < 0.001); dynamics of the SAS score: GG genotype (11.00 [9.00; 14.00]), GA genotype (14.50 [12.00; 18.00], p < 0.001). The pharmacokinetic study results showed a statistically significant difference: GG (3.13 [2.32; 3.95]), GA (3.89 [2.92; 5.26], p = 0.010). Thus, a study conducted on a group of 100 patients with acute alcoholic hallucinosis demonstrated an association between the 1846G > A polymorphism of the CYP2D6 gene (rs3892097) and the safety profile of haloperidol therapy. We also revealed the presence of statistically significant difference in the equilibrium concentration levels of haloperidol in patients with the GG and AG genotypes. Conclusion:It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients carrying the GG genotype. It is shown that 1846G > A polymorphism of the CYP2D6 gene (rs3892097) has a statistically significant effect on the equilibrium concentration levels of haloperidol.

В основе инвазии и метастазирования опухолевых клеток лежит эпителиально-мезенхимальный переход (ЭМП). При этом состоянии происходит потеря связи между эпителиальными клетками и появляется подвижный фенотип, характерный для мезенхимальных клеток. Важную роль в процессе ЭМП играет белок Е-кадгерин, который устанавливает и поддерживает межклеточные взаимодействия и позволяет эпителиальным клеткам формировать клеточный пласт. Частичная или полная потеря экспрессии E-кадгерина, происходящая при ЭМП, опосредована механизмами, которые блокируют экспрессию активаторов белка и связанных с ним транскрипционных факторов. Напротив, происходит гиперэкспрессия генов его блокаторов SNAIL1/2, ZEB, TWIST1, GRHL2, OVOL1/2 и PRRX1. E-кадгерин задействован в различных онкогенных сигнальных путях, таких как Wnt/β-catenin, Rho GTPase и EGF/EGFR, благодаря чему он способствует развитию многих опухолей, включая рак желудка (РЖ). Важнейшие компоненты эпигенетического контроля экспрессии генов при канцерогенезе - микроРНК и длинные некодирующие РНК - участвуют в регуляции функции Е-кадгерина. Они действуют непосредственно или опосредованно, через многочисленные факторы, контролирующие транскрипцию гена, и таким образом влияют на пролиферацию и метастазирование опухолевых клеток. Этот обзор посвящен роли E-кадгерина в опухолевой прогрессии, а также участию некодирующих РНК в механизмах его экспрессионного контроля при канцерогенезе желудка. Epithelial-mesenchymal transition (EMT) is the basis of tumor invasion and metastasis. It is characterized by the loss of communication between epithelial cells, which lead to the appearance of a motile phenotype of mesenchymal cells. The E-cadherin protein plays an important role in the EMT process, establishing and maintaining intercellular interactions and allowing epithelial cells to form a cell layer. The partial or complete loss of E-cadherin expression that occurs during EMT is mediated by mechanisms that block the expression of activators of this protein and related transcription factors. In contrast, the inhibitors of E-cadherin SNAIL1/2, ZEB, TWIST1, GRHL2, OVOL1/2, and PRRX1 are overexpressed. E-cadherin is involved in various oncogenic signaling pathways such as Wnt/β-catenin, Rho GTPase and EGF/EGFR. Therefore it contributes to many tumors, including gastric cancer (GC). MicroRNAs and long noncoding RNAs as important epigenetic regulators of gene expression in carcinogenesis are also involved in the regulation of E-cadherin function. They act directly or indirectly, through multiple factors controlling gene transcription, and thus influence tumor cell proliferation and metastasis. This review is focused on the role of E-cadherin in tumor progression and the involvement of non-coding RNAs in the mechanisms controlling its expression in gastric carcinogenesis.

Introduction. Gastric cancer remains one of the most common cancers and has a high mortality rate worldwide. Epigenetic alternations of non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs can contribute to its pathogenesis and progression, and could be potent diagnostic and prognostic biomarkers.Aim. Estimation of PROX1‑AS1 and miR-647 expression in gastric cancer and investigation of its clinical significance. Materials and methods. Tumor and adjacent normal tissues (n = 62), and sectional normal tissue samples (n = 5) were included in the study. The expression of the ncRNAs was quantified by reverse transcription-polymerase chain reaction assay.Results. We have reviled the significant difference in the PROX1‑AS1 expression in tumor (p = 0.002) and non-tumor tissues (p <0.001) obtained from gastric cancer patients in comparison with sectional gastric tissues without pathology. Pearson correlation analysis confirmed a negative correlation between PROX1‑AS1 and miR-647 in gastric cancer both in tumor (р <0,001) and adjacent normal tissues (р <0.001). Besides, expression of PROX1‑AS1 and miR-647 was associated with the size and extent of the primary tumor.Conclusion. The obtained results allow to suggest a potential prognostic value of PROX1‑AS1 and miR-647 in gastric cancer.

Background. Bladder cancer (BC) is a common urological cancer, 75 % of which are non-muscle invasive BC. After removal of the primary tumor, the adequate classification of malignancy and the defining of tumor progression risk remains an important issue, since it is associated with frequency of cystoscopy and choice of the BCG- or chemotherapy management.Objective: improve the algorithms of prognosis in intermediate-risk patients with non-muscle-invasive bladder cancer with the consideration of molecular characteristics of the primary tumor.Materials and methods. We studied 125 BC samples; mutations in the FGFR3, PIK3CA, TERT, and TP53 genes were determined by polymerase chain reaction and Sanger sequencing, as well as the expression of the FGFR3, EGFR, ERBB2, FOXA1, and GATA3 genes using realtime polymerase chain reaction.Results. Somatic mutations in the studied loci were detected in 65.6 % of the samples, five new mutations were identified. A decrease of the mutation frequency in the FGFR3 and TERT genes was shown, an increase — TP53 in order (Ta—T1/low G) > (T1/high G) > (>T2/any G). The largest area under the ROC curve (0.807 ± 0.092, р = 0.004) was demonstratedfor the prognostic classifier with the independent variables: mutation in FGFR3 and/or TERT; mutation TP53; overexpression of the FGFR3 gene. The FGFR3, TERT mutations and/or FGFR3 overexpression in the absence of TP53 mutation indicates minimally invasive primary tumor. On the contrary, harboring TP53 mutation indicate the features of muscle-invasive BC at the genetic level. Using this algorithm, we reclassified 21 of T1G3 BC cases as having characteristics associated with non-invasive tumor in 43 %, and invasive BC in 57 % of patients.Conclusion. The aforementioned prognostic model could be used as additional laboratory test in assessing the malignancy and progression risk of non-muscle invasive BC.

Introduction:Phenazepam is commonly administered to patients diagnosed with major depressive disorder. Some proportion of such patients do not show adequate response to treatment regimen containing phenazepam, whereas many of them experience type A adverse drug reactions. Previous studies showed that CYP2D6 IS involved in the biotransformation of phenazepam, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective. The objective of the study was to evaluate the impact of 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of phenazepam, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from major depressive disorder. Material and methods:The study enrolled 191 patients with recurrent depressive disorder (age -40.0 ± 16.3 years). Treatment regimen included phenazepam in an average daily dose of 6.0 ± 2.3 mg per day. Treatment efficacy was assessed using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels we performed the real-time polymerase chain reaction (PCR Real-time). The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6M-THBC/pinoline). Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results:Our findings didn't reveal the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 6.0 [4.0; 8.0] and (GA) 6.0 [5.0; 7.8], p > 0.999; the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 4.0] and (GA) 3.0 [3.0; 3.0], p > 0.999. We didn't reveal a statistical significance for concentration/dose indicator of phenazepam in patients with different genotypes: (GG) 0.812 [0.558; 1.348] and (GA) 0.931 [0.630; 1.271], p = 0.645). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 22.5 [16.9; 29.8], (GA) 22.7 [15.7; 31.5], p = 0.695. At the same time, correlation analysis didn't reveal a statistically significant relationship between the phenazepam efficacy profile evaluated by changes in HAMA scale scores and the hsa-miR-370-3p plasma concentration: rs = -0.01, p = 0.866. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.07, p = 0.348. Also we did not reveal the relationship between the CYP2D6 enzymatic activity (as evaluated by 6M-THBC/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.14, p = 0.056. At the same time, correlation analysis did not reveal a statistically significant relationship between the phenazepam concentration and the hsa-miR-370-3p plasma concentration: rs = -0.05, p = 0.468. Conclusion:The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of phenazepam was not demonstrated in a group of 191 patients with recurrent depressive disorder. At the same time, hsa-miR-370-3p does not remain a promising biomarker for assessing the level of CYP2D6 expression, because it does not correlate with encoded isoenzyme activity.

Breast cancer (BC) resistance to antiestrogens is one of the main problems that limit the efficacy of chemotherapy. Exosomes, microvesicles secreted and absorbed by cells, play an important role in the development and transmission of resistance of tumor cells. Exosomes are enriched with microRNAs taking part in the regulation of target genes. The aim of this work was to identify the microRNAs involved in the development of resistance and to study the effects of their transfection into BC cells. Experiments were performed on the in vitro cultured estrogen-dependent MCF-7 cells and tamoxifen-resisitant MCF-7/T subline. Exosomes were prepared by ultracentrifugation. Data on microRNA expression in exosomes were obtained by NGS. Transient multiple transfections of microRNAs were performed in the cells. Protein expression was determined by immunoblotting, reporter analysis was used to study the transcriptional activity of estrogen receptor (ERa). Cells growth rates were assessed by MTT test. The microRNAs profile of the MCF-7 and MCF-7/T exosomes was studied, and 6 microRNAs - ERa suppressors were found to be overexpressed in the exosomes of resistant cells. It was revealed that the transfection of identified microRNAs into MCF-7 cells causes a slight decrease in ERa transactivation and practically does not affect the expression of ERa protein. At the same time, transient multiple transfection (totally, 20 rounds of transfection) of one of these microRNAs, miR-181a-2, into MCF-7 cells induces the tamoxifen resistance in the latter. The transfected cells maintained the resistance to tamoxifen within at least 3 months of cultivation after the last transfection. The acquired tamoxifen resistance was associated with the alteration of DNA methylation as well as with a decrease in the expression of DNMT3, an important methylation regulator, the suppression of which may be characteristic of resistant cells. The transient multiple transfection of miR-181a-2 into MCF-7 cells induces the irreversible tamoxifen resistance demonstrating the important role of this microRNA in the formation of the resistant phenotype.

Introduction:Mirtazapine is commonly administered to patients with recurrent depressive disorder. Some of these patients do not show adequate response to the therapy with mirtazapine, whereas many of them experience dose-dependent adverse drug reactions. Previous research revealed that CYP2D6 is involved in the metabolism of mirtazapine, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective:The objective of this study was to investigate the effect of polymorphisms of the CYP3A4, CYP2C9, CYP3A5, ABCB1, CYP2C19, SCL6A4, and 5-HTR2A genes on the concentration/dose indicator of mirtazapine and on the CYP3A expression level obtained by measuring the miR-27b plasma concentration levels in patients suffering from a recurrent depressive disorder. Material and Methods:Our study included 108 patients with recurrent depressive disorder (average age - 35.2 ± 15.1 years). The treatment regimen included mirtazapine in an average daily dose of 45.0 [30.0; 60.0] mg per week. Therapy efficacy was assessed using the international psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6b-HC/cortisol). Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results:Our study didn't reveal any statistically significant results in terms of the treatment efficacy and safety of the therapy. We also didn't reveal a statistical significance for the concentration/dose indicator of mirtazapine in patients with different genotypes. Analysis of the results of the pharmacotranscriptomic part of the study didn't demonstrate the statistically significant difference in the miR-27b plasma levels in patients with different genotypes. At the same time, correlation analysis didn't reveal a statistically significant relationship between the mirtazapine efficacy profile evaluated by changes in HAMD scale scores and the miR-27b plasma concentration: rs = -0.2, p = 0.46. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.029, p = 0.93. In addition, we didn't reveal the relationship between the CYP3A enzymatic activity and the miR-27b plasma concentration: rs = -0,188, p = 0.85. However, the difference in the CYP3A enzymatic activity in carriers of AG and GG genotypes of the 6986A > G polymorphism of CYP3A5 gene has been revealed: (AG) 4.75 [1.28; 7.34] vs (GG) 8.83 [4.73; 13.62], p-value = 0.023. Conclusion:Thus, the effect of genetic polymorphism of the CYP3A4, CYP2C9, CYP2C9, CYP3A5, ABCB1, CYP2C19, CYP2C19, CYP2C19, SCL6A4, 5-HTR2A gene on the efficacy and safety profiles of mirtazapine was not demonstrated in a group of 108 patients with depressive disorder and alcohol use disorder.

Аnxiety disorders are considered a serious problem of psychiatry being comorbid with other states. In this context investigation of factors responsible for unequal drug efficiency and safety in different patients is needed. Among these factors, genetics is considered to be one of the most important. This study assessed the role of CYP2D6 gene polymorphism 1846G>A in Lexotan efficiency and safety in patients with anxiety disorders comorbid with alcoholism.

Эпигенетические механизмы регулируют структуру хроматина и создают устойчивые закономерности экспрессии генов в процессе жизни клеток. Нарушение эпигенетической регуляции играет значительную роль в канцерогенезе, инвазии, рецидивировании и метастазировании опухолей и может служить полезным клиническим маркером. Мутационное профилирование генов эпигенетической регуляции в опухолевых образцах рака желудка позволит определить новые клинические и прогностические маркеры и дополнительные таргеты для лечения пациентов. В статье представлены первые результаты исследования соматических мутаций в генах эпигенетической регуляции, проведенного методом NGS. Epigenetic mechanisms regulate chromatin structure and create stable patterns of gene expression during cell life. Violation of epigenetic regulation plays a significant role in carcinogenesis, invasion, recurrence and metastasis of tumors, and can serve as a useful clinical marker. Mutational profiling of epigenetic regulation genes in tumor samples of gastric cancer will allow us to identify new clinical and prognostic markers and additional targets for the treatment of patients with gastric cancer. This article presents the first results of a study of somatic mutations in the epigenetic regulation genes carried out using NGS.

Aims: This letter to the editor features a selection of possible miRNAs to be included into further development of smart diagnostic systems for clopidogrel resistance testing. Materials and methods: The PharmGKB (www.pharmgkb.org), TargetScanHuman 7.2 (www.targetscan.org/vert_72/) databases were scanned for a selection of relevant miRNAs. The designed graph includes the miRNAs that cover most of the genes responsible for clopidogrel resistance. Results: Twenty-three miRNAs were selected to be included into the smart clopidogrel resistance testing systems: miR-15 (9/132 cases, 6.8%), miR-16, miR-195, miR-203, miR-424, miR-497 (8/132 cases, 6.0%, each), miR-30 (6/132, 4.5%), miR-19, miR-155 (4/132 cases, 3.0% each), miR-26, miR-27, miR-223 (3/132 cases, 2.3% each), miR-31, miR-96, miR-101, miR-128, miR-129, miR-137, miR-138, miR-143, miR-200, miR-455, miR-1271, (2/132 cases, 1.5% each). Conclusion: This miRNAs selection can be used for scientific needs for further development of clopidogrel resistance testing systems.