СТРУКТУРНО-ФУНКЦИОНАЛЬНЫЙ АНАЛИЗ ОПУХОЛЕВЫХ ГЕНОМОВ И РАЗРАБОТКА ТЕСТ-СИСТЕМ ДЛЯ РАННЕЙ ДИАГНОСТИКИ, ПРОГНОЗА ТЕЧЕНИЯ И ОПТИМИЗАЦИИ ТЕРАПИИ ЗЛОКАЧЕСТВЕННЫХ НОВООБРАЗОВАНИЙ

The article discusses results of the structural and functional analysis of molecular genetic abnormalities in various malignant tumors. Investigations have discovered more than 20 new markers for sporadic breast cancer. Several of them formed the test system, allowing the diagnosis with a specificity of 100%. Appearance of TMPRSS2/ERG4 chimeric gene is a frequent tumor-specific event, its expression is correlated with more aggressive forms of prostate cancer, may serve as a molecular marker for tumor cells and androgen assessment of tumor response to hormonal therapy. The effective systems for the early diagnosis of cervix and endometrium cancer were developed as well. Mutations in the VHL, deletions of chromosome 3 and methylation of several genes can predict the course and selection of effective therapy of clear cell kidney cancer. a number of molecular markers were identified for early diagnosis and prognosis of recurrence of bladder cancer. For diagnosis, prognosis and treatment of brain tumors we developed an effective complex system of markers. Protocol of molecular genetics investigation reveals the cause of the disease by more than 90% of patients with retinoblastoma. In order to study abnormal methylation in tumor genomes an innovative technology AFLOAT has been developed that allows to efficiently identify new markers with diagnostic value. Test systems of molecular genetic and epigenetic markers for early diagnosis and prognosis as well as for cancer therapy optimization have shown to be effective, have been approved for use in clinical practice and are being introduced into practical healthcare.Рассматриваются результаты структурно-функционального анализа молекулярно-генетических нарушений при различных злокачественных опухолях. Исследования позволили обнаружить более 20 новых маркеров для спорадического рака молочной железы, из которых сформированы тест-системы, позволяющие проводить диагностику со специфичностью 100%. Образование химерного гена TMPRSS2/ERG4 является частым опухоль-специфическим событием, его экспрессия коррелирует с более агрессивными формами рака предстательной железы может служить молекулярным маркером  андрогенчувствительности опухолевых клеток и оценки ответа опухоли на гормональную терапию. Разработаны эффективные системы для ранней диагностики рака шейки матки и эндометрия. Мутации гена VHL, делеции хромосомы 3 и метилирование ряда генов позволяет прогнозировать течение и подбор эффективной терапии светлоклеточного рака почки. Для ранней диагностики, прогноза течения и рецидивирования рака мочевого пузыря определен целый ряд молекулярных маркеров. Для диагностики, прогноза и лечения опухолей мозга разработана эффективная комплексная система маркеров. Протокол молекулярно-генетического  исследования позволяет обнаружить причину заболевания более чем у 90% пациентов с ретинобластомой.  Для исследования аномального метилирования в опухолевых геномах разработана инновационная технология AFLOAT, позволяющая эффективно выявлять новые маркеры, имеющие диагностическое значение. Тест-системы молекулярно-генетических и эпигенетических маркеров для ранней диагностики, прогноза течения и оптимизации терапии злокачественных новообразований показали свою эффективность, получили разрешение на использование в клинической практике и в настоящее время активно внедряются в практическое здравоохранение.

РЕЗУЛЬТАТЫ ЭКПЕРТИЗЫ КАЧЕСТВА МЕДИЦИНСКОЙ ПОМОЩИ ПРИ СОЧЕТАННОЙ ПОЗВОНОЧНО-СПИННОМОЗГОВОЙ ТРАВМЕ

Medical care quality assessment for patients with vertebro-spinal-cord injury at different stages in St.-Petersburg during year was performed. The first aid in the most cases (74,8%) was rendered by emergency service. A vertebro-spinal-cord injuries were not diagnosed by a staff of line and special medical aid brigades in 31,6-51,9%. The causes of incorrect diagnostics at hospital stage: insufficient and delayed patient examination, underestimation of injury severity in consequence of delayed use of neuro-imaging methods. Surgical operations for vertebro-spinal-cord injuries were performed in 59 (8%) cases. 43 (73%) patients needed in vertebral fixation.Проведена оценка качества медицинской помощи на различных ее этапах пациентам с сочетанной позвоночно-спинномозговой травмой в Санкт-Петербурге за год. Большинству пострадавших (74,8%) первая помощь была оказана службой скорой медицинской помощи. На догоспитальном этапе персоналом линейных и специализированных бригад позвоночно-спинномозговая травма не была диагностирована в 31,6-51,9% наблюдений. Причины дефектов диагностики на госпитальном этапе - недостаточное и несвоевременное обследование пациентов, недооценка тяжести травмы позвоночника и спинного мозга, что обусловлено поздним применением нейровизуализационных методов. Операции по поводу позвоночно-спинномозговой травмы проведены в 59 (8%) наблюдениях, из которых в 43 (73%) потребовалась фиксация позвоночника

DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues

Extracellular glycoproteins of the laminin family are essential components of basement membranes involved in a number of biological processes, including tissue differentiation, wound healing, and tumorigenesis. We present the first comprehensive study of promoter methylation status of the genes encoding laminin chains in normal tissues (peripheral blood leucocytes, buccal epithelial cells, autopsy breast tissue samples) and in breast carcinoma samples. Based on the results of this study, we divide laminin genes into three categories. Genes, constitutively methylated in breast tissues include LAMA3A, LAMB2, LAMB3, and LAMC2. Genes prone to abnormal methylation in breast carcinoma include LAMA1, LAMA2, LAMA3B, LAMA4, LAMB1, and LAMC3. Genes that are rarely if ever methylated in breast carcinoma include LAMA5 and LAMC1. The constitutively methylated group includes all of the genes that encode subunits of laminin-5 (the historical name of laminin 332), the promoters of which were previously considered unmethylated in normal tissues and prone to abnormal methylation in breast cancer. © 2015, Pleiades Publishing, Inc

DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues

Extracellular glycoproteins of the laminin family are essential components of basement membranes involved in a number of biological processes, including tissue differentiation, wound healing, and tumorigenesis. We present the first comprehensive study of promoter methylation status of the genes encoding laminin chains in normal tissues (peripheral blood leucocytes, buccal epithelial cells, autopsy breast tissue samples) and in breast carcinoma samples. Based on the results of this study, we divide laminin genes into three categories. Genes, constitutively methylated in breast tissues include LAMA3A, LAMB2, LAMB3, and LAMC2. Genes prone to abnormal methylation in breast carcinoma include LAMA1, LAMA2, LAMA3B, LAMA4, LAMB1, and LAMC3. Genes that are rarely if ever methylated in breast carcinoma include LAMA5 and LAMC1. The constitutively methylated group includes all of the genes that encode subunits of laminin-5 (the historical name of laminin 332), the promoters of which were previously considered unmethylated in normal tissues and prone to abnormal methylation in breast cancer. © 2015, Pleiades Publishing, Inc

Mass spectrometric study of ring-substituted secondary and tertiary γ-aminopiperidines

Fragmentation of secondary and tertiary γ-aminopiperidines proceeds via elimination of γ-amino radicals and the ring substituents of piperidine, and is accompanied by their cleavage. High-resolution mass spectral data, DADI spectra, and fragmentation of deutero analogs confirm this decomposition. On the basis of quantum chemical MNDO calculations the most probable alternate structures have been proposed for a number of typical ions. From the features of dissociative ionization we can determine the kind and location of substituents in the piperidine ring. © 1990 Plenum Publishing Corporation

Abnormal hypermethylation of CpG dinucleotides in promoter regions of matrix metalloproteinases genes in breast cancer and its relation to epigenomic subtypes and HER2 overexpression

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) substantially contribute to the regulation of intercellular interactions and thereby play a role in maintaining the tissue structure and function. We examined methylation of a subset of 5'-cytosine-phosphate-guanine-3' (CpG) dinucleotides in promoter regions of the MMP2, MMP11, MMP14, MMP15, MMP16, MMP17, MMP21, MMP23B, MMP24, MMP25, MMP28, TIMP1, TIMP2, TIMP3, and TIMP4 genes by methylation-sensitive restriction enzyme digestion PCR. In our collection of 183 breast cancer samples, abnormal hypermethylation was observed for CpGs in MMP2, MMP23B, MMP24, MMP25, and MMP28 promoter regions. The non-methylated status of the examined CpGs in promoter regions of MMP2, MMP23B, MMP24, MMP25, and MMP28 in tumors was associated with low HER2 expression, while the group of samples with abnormal hypermethylation of at least two of these MMP genes was significantly enriched with HER2-positive tumors. Abnormal methylation of MMP24 and MMP25 was significantly associated with a CpG island hypermethylated breast cancer subtype discovered by genome-wide DNA bisulfite sequencing. Our results indicate that abnormal hypermethylation of at least several MMP genes promoters is a secondary event not directly functional in breast cancer (BC) pathogenesis. We suggest that it is elevated and/or ectopic expression, rather than methylation-driven silencing, that might link MMPs to tumorigenesis. © 2020 by the authors