Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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ЭКСПРЕССИЯ РАКОВО-ТЕСТИКУЛЯРНЫХ ГЕНОВ PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 У БОЛЬНЫХ МНОЖЕСТВЕННОЙ МИЕЛОМОЙ, ИХ ВЛИЯНИЕ НА ПОКАЗАТЕЛИ ОБЩЕЙ ВЫЖИВАЕМОСТИ И СКОРОСТЬ ВОЗНИКНОВЕНИЯ РЕЦИДИВА
Get PDFoai:oai.umo.elpub.ru:article/149Objective: to study the prognostic significance of the expression of cancer-testis (CT) genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in patients with multiple myeloma (MM) and their influence on overall survival and relapse rate. To determine their effect on suсh clinical parameters as levels of lactate dehydrogenase, leucocytes, hemoglobin, calcium, albumen, creatinine, beta-2-microglobulin.Materials and methods. Real-time polymerase chain reaction was performed on complementary DNA obtained from bone marrow of 77 patients with MM. The statistical analysis was performed using the Statistica 10.0 software package. To estimate prognostic values of the CT gene expression data were analyzed by the Kaplan – Meier method.Results. The study was conducted to determine the level of expression of CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in a group of patients with MM. The group included primary and receiving cancer treatment in MM patients. According to the log-rank criterion expression of any of the CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 exerts a significant influence on overall survival and progression-free survival/relapse. It was also determined that providing expression of some CT genes, the levels of creatinine, calcium, beta-2-microglobulin were much higher to compare with patients without expression
Экспрессия мРНК гена BRCA1 в опухолях молочной железы как предиктор ответа на неоадъювантную химиотерапию
Get PDFМеханизмы приобретенной резистентности к анти-EGFR-препаратам при немелкоклеточном раке легкого, не связанной с мутацией Т790М, и их значение в клинической практике
Get PDFThe prospects of treatment strategies for patients with non-small cell lung cancer (NSCLC) featuring the acquired resistance to tyrosine kinase inhibitors, not associated with the Т790М mutation, are quite vast from a scientific point of view, but in routine clinical practice they are not yet available in full. Understanding the mechanisms of acquired resistance to tyrosine kinase inhibitors is important for clinicians from the perspective of the possibility of forming more effective options for the second and subsequent treatment of NSCLC. The most studied and frequent mechanism causing the formation of the acquired resistance is the appearance of the Т790М mutation in 20 exons of the EGFR gene. This article describes the current understanding of the mechanisms of acquired resistance to tyrosine kinase inhibitors not associated with the mutation of T790M, the evolution of views concerning the treatment of NSCLC, progressing in the course of the treatment by this group of drugs. Taking into account the diversity of unresolved issues and directions of further scientific research, we should not forget about the available research results and the ability to use the described options in routine clinical practice in a proper way
Распределение генов HLA II у больных раком носоглотки, ассоциированным с вирусом Эпштейна–Барр, и другими опухолями ротовой полости в России
Get PDFЭКСПРЕССИЯ ВИМЕНТИНА В КУЛЬТУРАХ КЛЕТОК ЭПИТЕЛИАЛЬНЫХ ОПУХОЛЕЙ ЧЕЛОВЕКА
Get PDFBackground. Cell cultures used as a models in studies of epithelial tumors, are obtained not only from solid tumors, but also from extracellular fluids. It is known that dissemination of ovarian cancer in the peritoneum and further growth of tumor cells in ascetic liquid is accompanied with the activation of epithelial-mesenchymal transition, and, therefore, cell cultures derived from extracellular fluids can have a distinct molecular phenotype from primary tumors.Objective: evaluation the “persistence” of epithelial phenotype in breast and ovarian cancer cell cultures.Materials and methods. The cells obtained from pleural fluid (MCF-7, T-47D), colostrum (HBL-100), solid tumors (BT-474, HCC1937) of patients with breast cancer and ascitic fluid (SCOV- 3) of patients with ovarian cancer. The expression of cytokeratins and vimentin was evaluated using a quantitative immunofluorescence method associated with flow cytometry.Results. Vimentin expression in cells derived from extracellular fluids was not changed (line HBL-100), slightly decreased (SCOV-3 cells), or even was lost (MCF-7 and T-47D cells). HCC1937 cells obtained from solid tumor with expected low expression of vimentin acquired a molecular phenotype with a high expression of this mesenchymal marker. In breast cancer cells BT-474 derived from solid tumor a “persistence” of epithelial phenotype was discovered.Conclusion. Quantitative assessment of the de novo expression of mesenchymal protein vimentin showed that the tumor phenotype within the organizm is not always realized in cells adapted to growth in culture, and is not always «strictly» epithelial, and this evidence must be considered with different kinds of molecular studies of epithelial cells in vitro
СЕЛЕКТИВНОЕ ИНГИБИРОВАНИЕ KRAS-СИГНАЛЬНОГО КАСКАДА ПРИ КОМБИНИРОВАННОМ ВОЗДЕЙСТВИИ НИЗКИХ ДОЗ РАПАМИЦИНА И ПАКЛИТАКСЕЛА IN VIVO
Get PDFBackground. Therapy with compounds potentially capable to block KRAS oncogene signaling pathway is perspective direction in modern oncopharmacology. The aim of current study was to investigate effects of the combined treatment with rapamycin (RAP) and paclitaxel (PAC) in transgenic zebrafish (Danio rerio) with constant expression of mutant KRASV12 oncogene conjugated to green fluorescent protein (GFP) in epidermal cells. This strain has a modified phenotype due to epidermal hyperplasia and expression of GFP reporter at skin of embryos and adult fish.Materials and methods. Fish embryos 6 hpf were exposed to 0.1 % DMSO solution (control) and various doses of the drugs or combinations thereof. GFP expression in epidermal cells was morphometrically measured at 72 hpf.Results. Dose-related decrease in phenotypic changes up to complete epidermal normalization under RAP 50–400 nM treatment was observed. Treatment with nontoxic for embryos doses of PAC 50–250 nM increased fluorescence level in a dose-dependent manner, indicating an activation of KRAS signaling. Using of lower doses of RAP (10 and 25 nM) or PAC (10 nM) had no statistically significant effect on expression of transformed phenotype. Whereas combined treatment (RAP 10–25 nM and PAC 10–50 nM) dramatically decreased level of epidermal fluorescence and completely normalized phenotype of transgenic fish.Conclusions. Thus, mutual potentiating effect of RAP and PAC in low doses which leads to selective inhibition of the KRAS signaling pathway was revealed, indicating the prospect of further studies of these drugs combination for targeted cancer therapy
Взаимосвязь ВПЧ-инфицирования карциномы эндометрия с ее клинико-морфологическими особенностями
Get PDFBackground. There are contradictory data on the detection of human papillomavirus (HPV) in the tumor tissue in endometrial cancer (EС). Objective: to assess HPV infection rates in EC tumor tissues and to establish the relationship between the status of HPV infection and tumor morphological characteristics. Materials and methods. 57 formalin-fixed paraffin-embedded (FFPE) tissue samples of EC patients aged 47–78 years were studied. HPV DNAs were found in 54.4 % of samples. Results and conclusion. We did not reveal an association between the HPV tumor status and age, metastasis or invasion depth. However, there was an interdependence between HPV infection and some morphological characteristics of the tumor: its histological type (adenocarcinomas with squamous cell differentiation were HPV-positive 1.8 times more frequent compared to adenocarcinomas without one; in the first case, tumor tissues were more often infected with HPV 16, and in the second case with HPV 18); tumor grade (in the total cohort and in serous-papillary adenocarcinomas, tumors with higher grades were more often HPV-infected: from 0 to 81.8 % and from 0 to 100 % respectively); disease stage (in the total cohort the percentage of HPV-positive tumors in stage II was 2.4 times and in stage III – 1.6 times higher than in stage I, and stage IA tumors were HPV-positive 2.3 times more often than IB tumors); type of tumor growth (tumors with infiltrative growth type were HPV-positive 1.7 times more often than with exophytic growth, and 2.2 times more often than with mixed growth). The achieved results do not allow us to conclude with confidence that HPV is the main tumor forming factor in EC
Асинхронная репликация у онкологических больных
Get PDFEpigenetics is a science studying mechanisms of heritable changes in gene function that occur without a change in the DNA sequence. One of the most important marks of epigenetic misbalance of cell genome is an replication asynchrony of genes with biallelic expression. Interphase fluorescence in situ hybridization (I-FISH) in phytohaemagglutinin-stimulated lymphocytes of peripheral blood is a proper method of estimation of aberrant DNA replication time e. g. DNA replication asynchrony. In this review we analyzed reports referring to asynchronous DNA replication of biallelically expressed genes in lymphocytes of peripheral blood of cancer patients. Analysis shows the DNA replication asynchrony is a nonspecific tumor marker observing both in tumor cells and lymphocytes of peripheral blood in oncohematological patients and patients with solid tumors. It’s stated the frequency of lymphocytes with asynchronous DNA replication of studied genes in cancer patients is increased significantly compares with healthy donors and is enhanced during malignance process. It gives the opportunity of potential using asynchronous replication as molecular genetic marker for cancer patients early revealing
Медицинские работники: профессиональные канцерогенные факторы и онкологический риск
Get PDFThe number of healthcare workers is over two million in Russia. Many of them are exposed to hazardous physical, chemical and biological occupational factors acting along with psychological strain. The results of large epidemiological studies carried out in various countries revealed greater cancer risk in physicians and nurses: cancer of the breast, skin, brain and other sites. Higher cancer risk of lung, breast, uterine, ovary, brain is considered to be associated with ionizing radiation. The female healthcare workers who handle antineoplastic drugs showed a greater risk of birth defects in offspring, spontaneous abortions and breast cancer. In Russia, the growing number of accidents among healthcare workers following transmission of infection by carcinogenic biological factors such as HBV and HIV is observed. Higher risk of reproductive impairments, hyperplasia of the breast and uterine tissues, breast cancer are revealed in nurses working the night shift. In Russia, there is lack of epidemiological studies of cancer risk among healthcare workers, the number of medical personal exposed to occupational carcinogens is unknown. That all does not show the actual situation in our country and does not allow setting priorities in cancer prevention among medical workers