Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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Тканеспецифичность экспрессии протеогликанов в различных типах опухолей человека
Get PDFBackground. Proteoglycans (PGs) are complex glycosylated molecules playing an important role in cell-cell and cell-matrix interactions and signaling. Expression of PGs and their expression pattern change considerably during malignant transformation of mammalian cells and tissues.Objective. The aim of our work was to investigate tissue-specificity of main PGs expression (glypican-1, perlecan, syndecan-1, aggrecan, versican, CSPG4/NG2, brevican, decorin, lumican) in normal cells (fibroblasts and normal epithelial prostate cells PNT2) and in different human cancer cell lines (prostate, breast, lung, brain, kidney). Expression patterns of main PGs were determined in these cells using reverse transcription polymerase chain reaction analysis and immunocytochemical staining.Results. It was shown that fibroblasts actively expressed PGs, and PNT2 cells had lower (5–6-fold) expression levels of a limited set of PG. In different cancer cell lines, overall transcriptional activities of PGs varied up to 10-fold, although their expression patterns had tissue-specific properties (for example, expression of syndecan-1 is more specific for prostate cancer cells, while perlecan is typical for lung cancer cell lines).Conclusions. Along with this, variability of the PG expression patterns in cell lines of the same tissue of origin was shown, suggesting a possible contribution of the variable PGs expression to intratumoural heterogeneity of cancer cells and their potential as perspective biomarker (s) for personalised cancer diagnostics
Экспрессия iNOS и биосинтез метаболитов оксида азота при росте опухолей различного гистогенеза
Get PDFThe dynamics of the production of nitric oxide (NO) metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs
Изучение новых систем доставки противоопухолевых препаратов на основе наночастиц нитрида бора
Get PDFThe main problem in the treatment of many cancers is multidrug resistance due to tumor progression. Using nanosized drug delivery systems allows to overcome the mechanisms of multidrug resistance of cancer, in this case, chemotherapeutic agents can effectively introduce into cancer cells by endocytosis and accumulate near the nucleus and far from ATP-binding cassette transporters. Creation of boron nitridebased drug delivery nanocarriers with high chemical and oxidative stability is one of the perspective ways. Using chemical vapor deposition spherical boron nitride particles,100–150 nm in diameter (BNNPs), with peculiar petal-like surfaces or smooth surfaces were fabricated. BNNPs were loaded with doxorubicin. Drug loading efficacy of BNNPs-DOX was about 0.095 mg/mg of particles. BNNPs-DOX were relatively stable at neutral pH, whereas DOX is effectively released from the BNNPs at acidic pH (pH 4.5–5.5). Using confocal microscopy, the uptake of BNNPs-DOX by IAR-6-1, KB-3-1, К562 cells and multidrug resistant КВ-8-5 и IS-9 cells was studied. Most of BNNPs-DOX had been co-localized with LysoTracker, indicating that BNNPs-DOX are located in the endosomes/lysosomes after intracellular delivery
Вторые первичные опухоли у онкологических больных: лекарственный канцерогенез в онкологии
Get PDFCytostatic drugs used in chemotherapy cause secondary tumors in some patients cured of the antecedent neoplasm. Thus the incidence of second neoplasia for cancer survivors compared with the general population represents a 4-fold to 6-fold increased risk.The review presents recent data on the mechanisms of malignant transformation of cells by cytostatics, on the characteristics of high- risk groups associated with congenital polymorphisms of xenobiotic metabolizing enzymes and DNA repair systems. Increased risk of drug-related cancer was observed in patients with high activity of P450 isoforms, transforming cytotoxic prodrugs into the active electrophilic metabolites and low level of detoxifying enzymes. All things being equal the risk of therapy related neoplasia is higher in patients with low activity of DNA repair enzymes. It is evaluated the possibility of experimental study of new targeted drugs carcinogenic potential in order to minimize the future risk of secondary malignancies.Цитостатики, используемые в химиотерапии, вызывают образование вторых первичных опухолей у некоторых больных, излеченных от первого новообразования. При этом риск возникновения вторых опухолей после излечения от первых повышается в 4–6 раз по сравнению с общей популяцией. В обзоре приведены современные данные о механизме злокачественной трансформации клеток цитостатиками, группах повышенного риска, связанного с врожденным полиморфизмом систем метаболизма ксенобиотиков и репарацией повреждений ДНК. Наибольший риск лекарственных опухолей отмечен у пациентов с высокой активностью изоформ цитохрома Р450, превращающего транспортные формы цитостатиков в активные электрофильные метаболиты, и с низким уровнем детоксицирующих ферментов. При прочих равных условиях в группу повышенного риска входят больные с низкой активностью ферментов репарации ДНК. Рассматриваются возможности исследования канцерогенного потенциала новых таргетных препаратов в эксперименте в целях минимизации риска возникновения вторых опухолей, обусловленных лечением
Аллель-специфическая экспрессия генов при канцерогенезе
Get PDFRecent large-scale genomic studies established the occurrence of multiple DNA sequence variants in genomes of healthy individuals that differ from the reference sequence. Among these variants mostly represented by germline single nucleotide polymorphisms disease-related alleles are detected including alleles which are associated with monogenic disorders, and putative deleterious genetic variants. Apart from functional significance of a particular variant and of a gene harboring it, the penetrance of these allelic variants depends on their expression level and can be determined by preferential expression of a particular allele, or allele-specific expression. It is estimated that 20–30 % of genes present in the human genome display allelic bias in a tissue-specific manner. Allele-specific expression is defined by a range of genetic and epigenetic mechanisms including cis-regulatory polymorphisms, allele-specific binding of transcription factors, allele-specific DNA methylation and regulation through non-coding RNA.Although the data on the issue are scarce, allele-specific expression has been reported to be implicated in several hereditary disorders including benign and malignant tumors of the large intestine. Recent studies that estimate allele-specific expression incidence in tumors and identify wide range of genes displaying allelic imbalance indicate that allele-specific expression might play a significant role in carcinogenesis. Eventually, estimation of transcriptional rate of allelic variants which cause dysfunction of oncogenes and tumor suppressors may prove to be essential for rational choice of antitumor therapeutic strategy. In this review, we outline the main concepts and mechanisms of allele-specific expression and the data on allelic imbalance in tumors
Морфологическая классификация нэйроэндокринных новообразований пищеварительной системы: современное состояние проблемы и нерешенные вопросы
Get PDFNeuroendocrine tumors comprise the heterogeneous group of malignant epithelial neoplasms, the diagnosis of which is based on their histopathologic features and immunohistochemical profile. For neuroendocrine tumors of the digestive system in the World Health Organization (2010) classification were introduced main categories, the nomenclature, criterions for grading and staging. However, accumulating evidence demonstrates actual controversies in the histopathology of neuroendocrine neoplasms and unreserved problems in their classification. In this review we focus on some of the common features of neuroendocrine neoplasms, their classification, and differences in pathology, biology of the main categories, and the most important immunohistochemical markers.Нейроэндокринные опухоли образуют разнородную группу злокачественных эпителиальных новообразований, диагностика которых основывается на особенностях гистологической структуры и иммуногистохимического профиля. В классификации Всемирной организации здравоохранения (2010) для нейроэндокринных новообразований пищеварительной системы были определены основные категории, номенклатура, критерии градации и стадирования. При этом накопленные данные демонстрируют ряд важных патоморфологических противоречий в подходе к классификации. В данном обзоре мы остановимся на некоторых общих особенностях нейроэндокринных новообразований, их классификации, морфологических и биологических различиях основных категорий, наиболее важных иммуногистохимических маркерах
Феномен РНК-интерференции в онкологии: достижения, проблемы и перспективы
Get PDFReview describes the phenomenon of RNA interference – the recently discovered biological mechanism of the negative regulation of gene expression. The mechanism is based on the block of the translation and/or degradation of messenger RNA under short non-coding RNA, among them: microRNA and small interfering RNA. The paper reviews the molecular processes of the formation of small RNA, the mechanism of their action and the feasibility of small RNA implementation in the anti-tumor therapy. Specially, we analyze the approaches to in vivo delivery of small RNA, in particular – the liposome and exosome constructs, and perspectives of the involvement of such constructs in the cancer treatment.Обзор посвящен РНК-интерференции – сравнительно недавно открытому биологическому механизму негативной регуляции экспрессии генов. В основе этого механизма лежит блок трансляции и/или деградация информационной матричной РНК под действием малых некодирующих РНК, наиболее известными представителями которых являются микроРНК и короткие интерферирующие РНК. В обзоре рассматрены молекулярные процессы образования малых РНК, механизм действия и возможность их использования в качестве противоопухолевых терапевтических препаратов. Особое внимание отведено проблеме доставки малых РНК in vivo, в том числе с помощью липосом и экзосом, и перспективам использования таких препаратов в клинической практике
Вторые первичные опухоли у онкологических больных: эпидемиология, роль противоопухолевой терапии
Get PDFThe recent years have seen considerable advancement in the therapy of oncology patients and hence better survival and longer lifespan. Thus, studies on the distant effects of antitumor therapy have become increasingly important. That particularly concerns the risk of development of the second primary tumors. The patients that received therapy for the first malignant neoplasm become a higher-risk group for the development of a second tumor for their entire subsequent life. The review represents the data of analytical epidemiological studies on the second leukemia and solid tumors caused by the aftereffects of antitumor therapy using alkylating agents. Data are also considered on the risk of the second tumors that developed upon transplantation of stem cells. The second tumor etiology includes other significant risk factors such as genetic predisposition, smoking, alcohol consumption, imbalanced diet, etc. In combination with the aftereffects of antitumor therapy they may influence significantly the probability of the development of the second tumors in cancer patients, which should be considered in developing preventive measures. The review data suggest the need for cooperation of specialists in various fields and the use of clinical, epidemiological and molecular approaches to study the carcinogenesis of the first and second tumors, the choice of efficient and the safest methods of antitumor therapy to reduce the risk of the development of distant aftereffects and their prevention
