Vol 18, No 6 (2020)

The review discusses the principles of predictive genetic testing and screening in the concept of personalized medicine. The criteria for screening developed by WHO in 1968, as well as modern supplemented and refined criteria for genetic testing for multifactorial diseases are presented. The methodology of the evaluation of genetic tests on analytical and clinical reliability, clinical significance, and ethical, legal, and social consequences is considered. The approaches of international organizations involved in the assessment of health technologies, including genetic tests, are demonstrated. The currently predictive genetic testing of multifactorial diseases is noted to be promising for diseases whose pathogenesis is associated with single genes that obey the Mendelian laws of inheritance. In this case, predictive genetic testing is of interest in terms of prevention of the disease, individual treatment, and disease prognosis. When considering the introduction of predictive genetic testing in the public health system, along with clinical and cost-effectiveness, public health risks should be taken into account. The benefits of genetic testing as a personalized health care service should prevail over the risks associated with it. The development of the methodology for assessing and predicting the risks associated with predictive genetic testing, as well as improving the methods of managing risks, will achieve the main goal - to improve the efficiency of the health system.

Ulcerative colitis and Crohn’s disease represent one of the most pressing problems of modern medicine. Even though much attention paid to the development and implementation of high-tech diagnostic methods, inflammatory bowel diseases (IBD) tend to increase in prevalence and incidence. The literature review presents data on the molecular genetic mechanisms of the formation of inflammatory bowel diseases (IBD), biochemical markers of IBD, and their prognostic value. An accurate understanding of the molecular basis for the development of IBD has been shown to be currently lacking, which complicates the development of pathogenetically reasoned methods for diagnosing and predicting the risk of the development and the clinicalfeatures of ulcerative colitis and Crohn’s disease. This leads to the occurrence of complications requiring surgical intervention as well as an unfavorable medical and social prognosis. Perhaps the mechanisms of the development of these diseases are caused by certain nucleotide polymorphisms of genes, with a certain combination of them with immunological, environmental factors and microbial flora. Moreover, the diagnostic and prognostic significance of genetic, biochemical, and environmental features associated with the risk of developing IBD, the clinical picture, and the effectiveness of therapy have significant differences in patients from various countries and regions, which, inter alia, prevents an adequate assessment of the results of molecular genetic testing in diagnostics and prediction of IBD.

Thyroid cancer (TC) is the most prevalent cancer among malignant neoplasms of the organs of the endocrine system. Cytological categories Bethesda III-V of TC are considered to be the most difficult for making a diagnosis. Molecular genetic tests can be a tool to complement routine cytopathological studies. The aim of the study. To develop a panel for detecting point mutations in the cytological material of thyroid tumors using the multi-target single-nucleotide elongation (MSE) method. Materials and methods. The studied group of patients included 52 cases with thyroid neoplasm. Patients were divided into subgroups under Bethesda category IV, V and VI. The first, second, and third subgroup consisted of 24, 7, and 21 patients correspondingly. Cytological material was obtained by fine-needle aspiration biopsy. Genetic testing was carried out using the MSE approach. There were created 3 panels included the most common mutations in thyroid cancer: mutations in the BRAF, KRAS, NRAS, HRAS genes. The obtained results of a postoperative histological examination included II samples of papillary thyroid cancer, 9 samples of the follicular variant of papillary cancer and 5 - follicular adenoma. Results. 39% of cytological samples showed mutations. The BRAFV600E mutation was revealed in 29% out of founding aberration, NRASQ6IR mutation in I0% of those. To verify the method, there were used positive and negative control samples confirmed by PCR. In all control samples, the results were completely consistent with the molecular genetic study by the MSE method. Conclusion. MSE is a highly sensitive and promising method for the detection of mutations in cytological samples in TC patients.

Introduction. Revealing the relationship between the severity of oxidative stress and the activity of cathepsins in tissues (plasma and blood cells) readily available for the diagnosis of Alzheimer’s disease can be useful for understanding the pathogenesis of the disease, early diagnosis, and monitoring the course of pathology. The aim of the study: identification of correlations between the level of oxidative modification of proteins and the activity of lysosomal cysteine proteinases in plasma and leukocytes in patients with Alzheimer’s disease in comparison with similar indices in patients without signs of neurodegeneration. Methods. Spectrophotometric determination of the level of carbonyl derivatives of proteins, spectrofluorometric determination of the activity of lysosomal cysteine cathepsins, analysis of correlations between indices in plasma and leukocytes (polymorphonuclear and mononuclear) both in patients with Alzheimer’s disease, and patients without signs of neurodegeneration. Results. In leukocytes in Alzheimer’s disease, a moderate negative correlation was found between the activity of cathepsin H and the level of products of oxidative protein modification. In patients with vascular dementia, a pronounced negative correlation between cathepsin B and L in polymorphonuclear leukocytes was found. A similar trend was observed in the comparison group (patients without signs of dementia and neurodegeneration). Also, in this group, a moderate positive correlation was found between the activity of cathepsin L and the level of markers of oxidative stress in blood plasma. Based on the results were made the following conclusions: • Between the activity of cathepsin H and the level of oxidative modification of proteins, a moderate negative correlation was revealed in leukocytes of patients with Alzheimer’s disease. • The activity of cathepsins B and L negatively correlates with the level of oxidative modification of proteins in polymorphonuclear leukocytes of patients with vascular dementia and cases ts without signs dementia and neurodegeneration. • The activity of cathepsin L is in direct proportion to the level of oxidative modification of the protein in the blood plasma of patients without signs of dementia and neurodegeneration.

Introduction. The molecular mechanisms of the development of tumor pathology of the thyroid gland are associated with the activation of angiogenesis and the development of hypoxia, which contributes to the proliferation, invasion, and progression of the disease. However, the biological characteristics of the development of the disease associated with the involvement of regional lymph nodes are still unknown. The aim of the study. To investigate the transcription factors HIF-1, HIF-2, VHL, growth factors VEGF, CAIX, VEGFR2 expression both in the benign and malignant tumors of the thyroid gland, as well as in the metastatic sites. Material and methods. The study included 40 patients with thyroid pathology who received treatment in the Tomsk National Research Medical Center of the Russian Academy of Science. Stage T1-2N0-2M0 was observed in 18, T3-4N0-2M0 in 22 patients. Regional metastases were diagnosed in 19 patients; the group without regional metastases included 21 patients. The level of gene expression of transcription factors HIF-1, HIF-2, VHL, growth factors VEGF, CAIX, VEGFR2 receptor was evaluated using quantitative reverse transcriptase real-time PCR (RT-qPCR). Results. The work revealed an increase in the level of HIF-1, HIF-2 in the tissue of a malignant thyroid tumor compared with patients with benign tumors. The expression of molecular markers in the tissue of papillary thyroid cancer was not associated with clinical and morphological indices of the disease. In the tissue of thyroid metastases, a decrease in the level of VHL B VEGF mRNA was noted in comparison with the primary tumor. In patients with papillary thyroid cancer with an increased level of VHL mRNA (>1), the expression of HIF-1, HIF-2, and VEGF, CAIX is higher compared with patients with a reduced level of VHL (<1). Moreover, the distribution frequency, depending on the level of expression of the VHL protein, does not practically differ in groups of patients with a tumor of various sizes and the spread of the disease to regional lymph nodes. Conclusion. There was reveled significance of molecular markers associated with angiogenesis: transcription factors HIF-1, HIF-2, VEGF, VEGFR2 and CAIX in the development of benign and malignant thyroid tumors, as well as in the spread of the disease. The formation of metastases in regional lymph nodes is determined by a change in the expression of the VHL protein, which is accompanied by an increase in the expression of angiogenic factors.