Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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Механизмы антиканцерогенного действия флавоноидов
Get PDFThe mechanisms of anticancerogenic effects of flavanoids and isocyanates from the plants widely consumed in the midland belt of Russia were reviewed. Data of studies both in vitro and in vivo were analyzed. Special attention was paid to inhibition of targets responsible for carcinogen metabolic activation, carcinogenesis promotion and tumor progression as well as neoangiogenesis. Besides that the antioxidant properties of flavonoids and their effects on cell cycle regulation, apoptosis initiation and cell mobility were considered.Целью представленного обзора является анализ механизмов антиканцерогенного действия флавоноидов и изоцианатов на примере ряда соединений, широко употребляемых в средней полосе. В обзоре приведены данные исследований антиканцерогенного действия этих соединений в экспериментах in vitro и in vivo, рассмотрены мишени ингибирования действия химических канцерогенов в цепи их метаболизма, антиоксидантные эффекты флавоноидов, влияние пищевых полифенолов на метаболизм канцерогенных соединений, процессы промоции канцерогенеза и прогрессии опухоли, регуляцию клеточного цикла, цитоскелет и подвижность трансформированных клеток, индукцию апоптоза и неоангиогенез
ЛИГАНД-РЕЦЕПТОРНАЯ СИСТЕМА RANK/RANKL/OPG И ЕЕ РОЛЬ ПРИ ПЕРВИЧНЫХ НОВООБРАЗОВАНИЯХ КОСТЕЙ (АНАЛИЗ ЛИТЕРАТУРЫ И СОБСТВЕННЫЕ РЕЗУЛЬТАТЫ)
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Современные представления о серологических опухолеассоциированных маркерах и их месте в онкологии
Get PDFThe paper reviews modern concepts of serological tumor markers and their place in oncology: using for differential diagnostics, in the prognosis of the tumor, follow-up and for preclinical revealing of relapses, as well as in the screening aimed at early detection of malignant neoplasms. Biochemical characteristics and functions of most informative tumor markers (CA125, PSA etc.) were described. Currently diagnostic indexes, obtained by the in vitro diagnostic multivariate index assay (IVDMIA), and algorithms using several serological markers begin to apply in laboratory practice to increase diagnostic accuracy. Also some promising new serological tumor markers were described in this review.Обзор посвящен современным представлениям о серологических опухолеассоциированных маркерах (ОМ) и их месте в онкологии: использовании для дифференциальной диагностики, в прогнозе течения опухолевого процесса, мониторинге и для доклинического выявления рецидивов болезни, а также в скрининге, направленном на раннее выявление злокачественных новообразований. Описаны биохимические характеристики и функции наиболее информативных ОМ (СА125, ПСА и др). В настоящее время с целью повышения диагностической точности в лабораторной практике начинают применяться диагностические индексы, полученные путем многопараметрического анализа in vitro (in vitro diagnostic multivariate index assay, IVDMIA), и алгоритмы с использованием нескольких серологических маркеров. Также в обзоре описаны некоторые новые перспективные серологические ОМ
Молекулярно-генетические особенности и маркеры гастроинтестинальных стромальных опухолей
Get PDFGastrointestinal stromal tumors (GISTs) are the most spread mesenchymal tumors located within the gastrointestinal tract that have particular clinico-morphological, immunohistochemical and molecular characteristics. The distinguishing mark of GISTs is the presence of the cell-surface antigen CD117 (KIT receptor tyrosine kinase), identified by immunohistochemistry. GISTs consist of tumors with various activating mutations in KIT (75–80 %) or PDGFRA (5–15 %) receptor tyrosine kinases. Numerous KIT and PDGFRA mutations are associated with specific GIST morphology, histologic phenotype, metastasizing and prognosis. 10–15 % of GISTs contain KIT and PDGFRA wild type genes, some of them have driver BRAF, IGF1R or PIK3CA mutations. The other GISTs patients have familial syndromes (neurofibromatosis type 1, Carney–Stratakis syndrome, Carney triad) and contain germline mutations of NF1 or the genes coding for the succinate dehydrogenase subunits SDHA, SDHB, SDHC, and SDHD. GISTs are first and the most studied model for development of principles and methods of personalized targeted therapy of solid tumors with tyrosine kinase inhibitors
Современные стратегии исследования маркеров опухолевого роста в клинической практике
Get PDFImportance of molecular genetics-based essays in clinical oncology is now unquestionable due to the fact that all oncological diseases and their progression are based on cascading accumulation of genetic aberrations involving more than 20 different genes. Essentially new capacities of clinical oncology are uncovered with the help of modern molecular biology methods that allow to determine structural and functional changes of genes and their products. This review examines approaches to improve criteria for creating diagnostic essays, evaluation of treatment efficiency and molecular factors of clinical course. In order to determine relevant markers, special consideration should be given to the research of signal transduction pathways involving key genes responsible for tumor growth and their partners. The correct formation of patient’s groups and selection of samples is very important. It is emphasized that integrated clinical programs should combine traditional methods of diagnostics and treatment with modern molecular testing and bioinformatics methods
МЕХАНИЗМЫ ПРОТОНИРОВАНИЯ МЕЖКЛЕТОЧНОГО ПРОСТРАНСТВА В ОПУХОЛЯХ
Get PDFOne of the differences between normal and tumor cells is more intensive acidification of the extracellular area in tumor cells compare with intracellular area. Low pH in extracellular region stimulates invasion and metastatic process. This effect of low pH is not fully understood. There are some mechanisms of maintenance of low pH in extracellular region of tumor. In tumor some cells exist in hypoxic state. It is accepted that invasion and metastatic process occur at hypoxic area of tumor. During hypoxia due to activation of transcription factor HIF-1α the tumor cells turn to glycolysis and the end point of glucose oxidation is lactate. The formation of lactate from pyruvate is catalyzed by HIF-1α-dependent lactate dehydrogenase isoform. Accumulation lactate with pK 3.9 is dangerous for cells and monocarboxilate transporters which transport lactate and proton from cytosol are activated. The other mechanism of extracellular protonation is realized by functioning of HIF-1α-dependent carbonic anhydrase (СА IX). СА IX catalyzed the proton formation by interaction of carbonate dioxide with water. СА IX is situated in cell membrane in such manner, that active centre is directed in extracellular matrix. The function of other transmembrane proton pomp is not associated with hypoxia. The activation of Na+/H+ exchanger occur by stress, like osmotic chock or proliferation stimuli. In would be reviewed here the mechanisms of activation of proton pumps. It is shown the results of experiments devoted the effects of different types of inhibitors on tumor growth in cell culture and in vivo. It is suggest that proton pump inhibitors could be in complex with “classical” antineoplastic compounds perspective in cancer treatment
Влияние полиморфизма геномов онкогенных вирусов на риск возникновения опухолей человека и их специфическая профилактика
Get PDFNumerous studies have shown that approximately 20 % of all human tumors are neoplasms of an infectious nature. This review is an attempt to summarize the current understanding of the role of known human oncogenic viruses and their genetic variants on the risk of the human cancers development, as well as to show the existing measures of specific prevention of virus-induced tumors. It was paid also attention to the interaction between viral and cellular proteins, including tumor suppressors, and to the evaluation the significance of this interaction for specific oncogenic viruses and virus-associated tumors.Многочисленными исследованиями доказано, что примерно 20 % всех опухолей человека являются новообразованиями инфекционной природы. Данный обзор представляет собой попытку суммировать современные представления о роли известных онкогенных вирусов и их генетических вариантов в риске возникновения опухолей человека, а также показать существующие меры специфической профилактики вирус-индуцированных опухолей. Уделено также внимание вопросам взаимодействия между вирусными белками и клеточными белками, включая опухолевые супрессоры, и оценена значимость такого взаимодействия для конкретных опухолеродных вирусов и ассоциированных с ними опухолей
