Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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    Секция IV. СИГНАЛЬНЫЕ КАСКАДЫ В ОПУХОЛЕВЫХ КЛЕТКАХ

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    О НОВЫХ ДИАГНОСТИЧЕСКИХ ВОЗМОЖНОСТЯХ CD138 (СИНДЕКАНА-1) ПРИ МНОЖЕСТВЕННОЙ МИЕЛОМЕ

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    Syndecan-1 (CD138) is one of the main cell markers used in flow cytometric analysis of multiple myeloma (MM) cells. CD138 and several other markers – CD19, CD45, CD56 – which are often used in order to characterize MM and give the possibility to differentiate MM cells from the normal plasmocytes are described. Only CD138-expressing MM plasma cells are usually taken into account in MM analysis. The current literature data point out that CD138-negative MM plasma cells could be important for MM prognosis, as well. This cell population demonstrates certain properties that are typical to the cancer stem cells. CD138-negative cell population is characterized by higher proliferation, clonogenicity, engraftment in immunodeficient mice as compared to CD138 expressing plasma cells. Besides that, CD138-negative cells were more resistant than CD138-positive cells to the drugs that are used in MM chemotherapy. CD138-negative plasma cells are able to produce CD138 expressing cells upon a long-term culture in vitro and thus to reproduce the heterogenic in CD138 expression population of MM plasma cells. The results of these investigations, as well as statistical data indicating the worse overall survival of CD138 low expressing MM patients point out that CD138-negative population of MM plasma cells should be taken into consideration in MM analysis. Thus, it could be important to find the new markers distinguishing the plasma cell population differing in CD138 expression. Vascular endothelial growth factor receptor VEGFR3 was found to be a new marker with such properties

    Протеомика в открытии маркеров рака предстательной железы

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    Prostate cancer (PC) represents the second most frequent type of tumor in men worldwide. Proteomics represents a promising approach for the discovery of new biomarkers able to improve the management of PC patients. Markers more specific and sensitive than prostate-specific antigen are needed for PC diagnosis, prognosis and response to treatment. Moreover, proteomics could represent an important tool to identify new molecular targets for PC tailored therapy. Now several possible PC biomarkers sources, each with advantages and limitations, are under investigation, including tissues, urine, serum, plasma and prostatic fluids. Innovative high-throughput proteomic platforms are now identifying and quantifying new specific and sensitive biomarkers for PC detection, stratification and treatment. Nevertheless, many putative biomarkers are still far from being applied in clinical practice.This review aims to discuss the recent advances in PC proteomics, emphasizing biomarker discovery and their application to clinical utility for diagnosis and patient stratification

    Сигнальные пути, регулируемые эстрогенами, и их роль в опухолевой прогрессии: новые факты и направления поиска

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    Over the last forty years antiestrogen tamoxifen belongs to the most effective antitumor drugs widely used in the treatment of breast cancer, however, the efficiency of tamoxifen therapy is often limited by development of tumor hormonal resistance. The study of the mechanism of hormonal resistance led to the significant progress in the insight in signaling pathways respondent for the cancer cell growth in the absence of estrogen. In the review we have analyzed the recent data including our results obtained in the N. N. Blokhin RCRC, concerned with the study of the new aspects of hormonal resistance – the involvement of hypoxia-dependent HIF-1α / VEGF pathway, epithelial-mesenchymal transition and mTOR / AMPK in the formation of estrogen-independent phenotype. Some of the signaling proteins are considered as the potential targets for the therapy of the estrogen-resistant breast cancer.Более сорока лет антиэстроген тамоксифен успешно применяется в терапии рака молочной железы, но основной проблемой в его применении до настоящего времени остается развитие у больных гормональной резистентности, существенно ограничивающей эффективность антиэстрогеновой терапии. За последние годы достигнут значительный прогресс в понимании механизмов формирования гормональной резистентности и выявлены новые молекулярные пути, поддерживающие рост опухоли в условиях «выключения» рецепторов эстрогенов. В обзоре проанализированы результаты исследований, в том числе выполненных в ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, посвященных новым аспектам этой тематики – активности сигнальных путей HIF-1α / VEGF, эпителиально-мезенхимального перехода и mTOR / AMPK; показано, как на молекулярном уровне формируется устойчивость опухоли к действию гормональных цитостатических препаратов. Некоторые из сигнальных белков рассмотрены в качестве показателей прогноза и / или перспективных мишеней таргетной терапии резистентных форм рака молочной железы

    Факторы роста, их рецепторы и нижележащие сигнальные белки: от эксперимента к клинике

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    The basic contemporary data and the results of authors’ long-term personal research devoted to the role of auto / paracrine growth factors, their receptors and some down-stream signaling proteins (PI3K, Akt, NF-κB) in clinical course, prognosis and development of hormonal and drug sensitivity of various human tumors are reviewed. The data on the key targeted drugs suppressing various growth factor signaling pathways components are summarized with special attention to the criteria of assessment of individual sensitivity to these drugs including those based on modern molecular biologic technologies.В обзоре представлены основополагающие данные современной литературы и результаты собственных многолетних исследований роли ауто / паракринных факторов роста, их рецепторов и некоторых нижележащих сигнальных белков (PI3K, Akt, NF-κB) в клиническом течении, прогнозе и формировании гормональной и / или лекарственной чувствительности различных опухолей человека. Суммированы также данные о ключевых таргетных препаратах, направленных на подавление различных компонентов сигнальных путей факторов роста; критериях оценки индивидуальной чувствительности к этим препаратам, в том числе с использованием современных молекулярно-биологических технологий

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    Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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