Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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Биохимические критерии токсичности терапии высокими дозами метотрексата у детей с остеосаркомой
Get PDFНовое в изучении множественной лекарственной устойчивости клеток рака молочной железы
Get PDFBreast cancer (BC) is the most common cancer among women in Russia. One of the main treatment methods of BC is systemic chemotherapy. Multidrug resistance of tumor cells (MDR) is the important hindrance on the way to successful chemotherapy. The new data concerning molecular mechanisms of MDR will be presented in this review. The recent data concerning some new biological prognostic markers will be also discussed. There are data showing that transporters of ABC family (ABC transporters) influence tumor progression not only by MDR induction but also by the influence on the traits of malignancy in tumor cells. The results of the studies of ABC transporters, participation in the processes of accumulation of tumor stem cells under the influence of chemotherapy will be discussed. The problem of the participation of ABC transporters in the phenomenon of influence of PI3K/AKT/PTEN signal transduction pathway on the MDR regulation is discussed. The results of the studies of the role of microRNA deregulation in breast cancer drug resistance as well as studies of some epigenetic mechanisms of MDR regulation will be considered. Protein phosphatase 2A (PP2A, serine/threonine phosphatase), PTK7 (protein tyrosine kinase 7). fascin (an actin bundling cytoskeletal protein) multifunctional YB-1 protein will considered as new BC prognostic markers. The perspectives of MDR studies will be discussed as well
Endocytosis of the IFNAR1 chain of Type 1 interferon receptor is regulated by diverse E2 ubiquitin conjugation enzymes
Get PDFUbiquitination of signaling receptors triggers their endocytosis to restrict the extent of cell signaling. Type 1 interferon (IFN1) eliminates its receptor from cell surface via stimulating the ubiquitination of its IFNAR1 chain. While it was suggested that this ubiquitination aids IFNAR1internalization via relieving a steric hindrance of a linear motif within IFNAR1 from the endocytic machinery, the mechanisms involved remain poorly understood. Here we describe a specific role for two disparate ubiquitin acceptor sites within this receptor. These sites, Lys501 and Lys525 / 526, exhibit a preference for polyubiquitination via either Lys63- or Lys48‑linked chains (K63‑Ub and K48‑Ub, respectively). Whereas the SCFβTrcp E3 ubiquitin ligase controls either type of ubiquitination-dependent IFNAR1 endocytosis, the specificity of these processes is determined by two different E2 ubiquitin conjugating enzymes, Ubc13 and Cdc34. These enzymes can be directly used by SCFβTrcp E3 ubiquitin ligase to generate either K63‑Ub or K48‑Ub in vitro. Ubc13 is involved in IFNAR1 endocytosis driven by the K63‑Ub modification of Lys501, whereas the K48‑Ub-specific Cdc34 affects receptor endocytosis via ubiquitin conjugation that occurs on Lys525 / 526. Both types of linkages combine to maximize IFNAR1 endocytosis otherwise suppressed by unfavorable conformation dependent on the presence of a conserved Pro470 within the intracellular domain of IFNAR1. We propose a model where alternate utilization of both E2s to assemble diverse polyubiquitin linkages cooperates to achieve IFNAR1 intracellular domain conformations and spatial arrangements that favor a maximal rate of receptor endocytosis
Роль транскрипционного фактора Ikaros в нормальном гемопоэзе и лейкозогенезе: биологические и клинические аспекты
Get PDFЭпигенетическая регуляция экспрессии генов в вирус-ассоциированных опухолях человека
Get PDFViruses are associated with nearly 20 % of human cancers worldwide. Until recently genetic abnormalities generated by oncogenic virusesin cells were the main object of studies. Understanding of the importance of epigenetics in the regulation of gene expression prompted the investigation of virus and host interactions at the epigenetic level. We review aspects such as common futures of oncogenic virus interactions with cell epigenetic system and virus-specific peculiarities of these interactions. Knowledge of the regulation of virus genomes by cell epigenetic system and disturbances of this system by viruses should provide us with markers for following cancer progression, as well as new tools for cancer therapyОпухоли, ассоциированные с вирусами, составляют около 20 % всех опухолей человека. До недавнего времени при исследовании молекулярных механизмов вирусного канцерогенеза основные усилия были направлены на генетические нарушения, вызываемые онкогенными вирусами в клетке. Успехи, достигнутые в понимании механизмов эпигенетической регуляции экспрессии генов, стимулировали исследования взаимодействия вирусов и клетки-хозяина на эпигенетическом уровне. В обзоре рассмотрены общие закономерности взаимодействия онкогенных вирусов с эпигенетической системой регуляции функционирования генома и специфические для каждого вируса особенности этого взаимодействия в процессе установления латентной инфекции и опухолевой трансформации. Исследования регуляции экспрессии вирусного генома эпигенетической системой клетки и, с другой стороны, нарушений этой системы вирусами вносят вклад в понимание механизмов вирусного канцерогенеза, выявление новых маркеров прогрессии опухолей и мишеней для таргетной терапии
Иматиниб повышает чувствительность клеток гастроинтестинальных стромальных опухолей к ингибиторам топоизомераз II типа
Get PDFObjective: to study the sensitivity of gastrointestinal stromal tumors (GISTs) to the topoisomerases type II inhibitors and ability of imatinib to enhance GISTs sensitivity to the chemotherapeutic drugs indicated above.Subjects and Methods. We studied the sensitivity of gastrointestinal stromal tumors (GISTs) to the topoisomerases II inhibitors and ability of imatinib to enhance GISTs sensitivity to these chemotherapeutic agents. The expression of DNA damage and repair (DDR) markers was examined by western-blotting. Cleaved forms of poly (ADP-rybose) polymerase and caspase-3 were served as an apoptotic markers measured by western blotting. Amount of apoptotic cells was counted by flow cytometry analysis by using a propidium iodide DNA staining procedure and counting the numbers of hypodiploid cells.Results. We observed the sensitivity of GISTs to topoisomerase II inhibitors – doxorubicine and etoposide inducing DNA double-strand breaks and apoptotic cell death. Imatinib enhances GISTs sensitivity to topoisomerase II inhibitors. This might be due to reduced ability of GISTs to repair DNA damage by homologous recombination. Imatinib-induced reduction of Rad51 recombinase might be due to increased proteasome-dependent degradation.Conclusion. GIST cells are sensitive to topoisomerase II inhibitors (etoposide and doxorubicin) in vitro. Imatinib enhances GISTs sensitivity to the chemotherapeutic agents indicated above
Молекулярные особенности почечно-клеточного рака: ранняя диагностика и перспективы терапии
Get PDFKidney cancer (renal cell carcinoma) is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task