Advances in molecular oncology (E-Journal) / Успехи молекулярной онкологии
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Экзосомальные протеины – потенциальные маркеры для диагностики множественной миеломы
Get PDFBackground. Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. EXs as a source of markers for MM diagnostics are also not studied.Objective: to use proteomic profiling of EXs as a tool to identify circulating tumor associated markers in MM patients.Results. The proteome composition of EXs obtained from plasma of patients with MM and multiple sclerosis was studied for the first time. nano-HPLC–MS/MS analysis identified a total of 332 proteins in the EXs of both groups of patients and determined the proximity of their qualitative composition. For the first time, 12 differentially expressed proteins were detected, the levels of which were significantly increased in EXs from patients with MM. This allowed us to consider them as potential markers of the disease.Conclusion. Proteomic analysis of EXs obtained from plasma of patients with MM is an important method for finding disease markers
Цитотоксичные катионные пептиды как лиганды рецепторного нуклеолина
Get PDFBackground. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the сell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides – expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43–100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins
Протеогликаны в нормальной физиологии и канцерогенезе
Get PDFMalignant transformation of any cell is associated with numerous physiological and morphological disorders at both genomic and protein levels, a variety of macromolecules being involved in. However, the tumour development and metastasis depends on not only the molecular characteristics of the tumour cell but also its interaction with the surrounding extracellular matrix (ECM), which is an important and necessary part of any tissue. An important role in this process belongs to the complex protein-carbohydrate molecules – proteoglycans (PG), which are one of the main component of ECM and cell surface of any tissue and are tightly involved in cell-cell and cell-matrix interactions and signaling. During carcinogenesis, significant changes in the PG structure and composition occur both at the surface of tumour cells and surrounding ECM, resulting in the transformation of normal ECM into a tumour microenvironment and deterioration of cell-cell and cell-matrix communication. Further, the tumorigenic niche contributes to active proliferation of the cancer cells, tumour development and metastasis. At present, many key PG are identified as possible diagnostic and prognostic molecular markers and target molecules for the creation of new antitumor drugs.The review describes the main PG types, their structure, localisation, functional role in normal cell and tissue physiology and participation in molecular mechanisms of carcinogenesis
Таргетная жидкостная биопсия посредством «обогащенной» полимеразной цепной реакции и анализа плавления ДНК
Get PDFObjective: to evaluate the possibility of using a highly sensitive method of “enriched” polymerase chain reaction followed by DNA melting analysis (PCR-DMA) for target liquid biopsy of cancer patients.Materials and methods. The “enriched” PCR-DMA was used for mutation scanning of KRAS (codons 12 and 13) in tumor and blood plasma of 20 patients with colorectal cancer.Results. Activated oncogene was found in tumor tissue of 16 patients and in blood plasma of 5 patients (confirmed by sequencing). Mutant KRAS alleles were also found in tumor and plasma of another 2 patients, but in very low concentrations that did not allow their validation by Sanger sequencing. Thus, in our study the target liquid biopsy was successful in ~35 % patients. Since the plasma tests were carried out after repeated medical procedures causing mass death of tumor cells, the actual efficiency of this approach may appear significantly higher
ВЛИЯНИЕ ПРОПИОНАТА НА СПЕКТР ВЫСШИХ ЖИРНЫХ КИСЛОТ В КЛЕТКАХ ШЕЙКИ МАТКИ ПРИ ДИС- И НЕОПЛАСТИЧЕСКОЙ ТРАНСФОРМАЦИИ
Get PDFBackground. Metabolic reprogramming of tumor cells is one of the leading links in carcinogenesis. The objective to confirm the hypothesis of a propionate pathway for the synthesis of long-chain acids with an odd number of carbon atoms in cervical cancer.Materials and methods. As samples for the study were biopsies of the colli uteri, from which a suspension of tumor cells was obtained (20 – cervical cancer, 20 – cervical intraepithelial neoplasia III grade, 18 – endocervical scraping from healthy women). The spectrum of fatty acids (FA) was analyzed before, after 24 hours incubation without and with 50 μmol/l propionic acid by the gas chromatography method.Results. Metabolism of FA is multidirectional in different locus in cervical cancer. In the locus of cervical cancer, most likely, there is a propionic pathway for the synthesis of FA using palmitate. In cervical intraepithelial neoplasia III grade, the metabolism of FA is another. Palmitic acid was used for synthesis stearate, which was metabolized to oleic acid.Сonclusion. The specificity of biochemical changes within one organ and one pathology has been revealed, which reflects the stage-by-stage development of the oncological process
ИССЛЕДОВАНИЕ УРОВНЯ ЖИРНЫХ КИСЛОТ МЕМБРАН ЭРИТРОЦИТОВ И СЫВОРОТКИ КРОВИ У ПАЦИЕНТОВ С КОЛОРЕКТАЛЬНЫМ РАКОМ Г. НОВОСИБИРСКА
Get PDFThe objective is to measure the level of fatty acids in erythrocyte membranes and serum of patients with colorectal cancer.Materials and methods. The study group included 100 patients with diagnosed colorectal cancer (57 men and 43 women). The control group included 24 reasonably healthy people (14 men and 10 women) matched for age and sex, without malignant cancers or manifested pathology of the internal organs.Results. Decreased levels of saturated, monounsaturated fatty acids and increased levels of polyunsaturated fatty acids (PUFAs) in erythrocyte membranes and serum (p <0.0001–0.05) were observed. The levels of omega-3 PUFAs in colorectal cancer exceeded the levels in healthy individuals both in erythrocyte membranes and in serum; for omega-6 PUFAs only a trend was observed. At the same time, the ratio of omega-6/omega-3 PUFAs in colorectal cancer was lower than in control (p <0.0001–0.002). The state of erythrocyte membranes more significantly and for more parameters characterized differences between the groups than serum. The most discriminating parameters between patients with colorectal cancer and healthy individuals both in erythrocyte membranes and serum were the levels of C20:2;11,14 (eicosadienoic), C20:3;8,11,14 (dihomo-γ-linolenic), C20:4;5,8,11,14 (eicosatetraenoic, arachidonic), C22:5;7,10,13,16,19 (docosapentaenoic), and C22:6;4,7,10,13,16,19 (docosahexaenoic) PUFAs
Взаимосвязь компонентов EGFR/PI3K/Akt-сигнального пути с эффективностью терапии тамоксифеном у больных эстрогензависимым раком молочной железы
Get PDFИММУНОТЕРАПИЯ НА ОСНОВЕ ДЕНДРИТНЫХ КЛЕТОК В ЛЕЧЕНИИ РАКА МОЧЕВОГО ПУЗЫРЯ
Get PDFThe development of an antitumor vaccine based on autologous dendritic cells (DCs) for bladder cancer treatment is extremely relevant today due to the proven high immunological potency of this type of tumor. Vaccination with DCs-based drugs as a monotherapy or in combination with other methods of treatment has shown to be effective in cancer therapy. The vaccine administration is considered to be safe, the associated side effects are insignificant and can be characterized as undesirable phenomena of 1st or 2nd degree. There are a number of issues that arise while creating DCs vaccines that need to be carefully resolved. Among them, the problem of selecting potential targets for the vaccine treatment, the ways to enhance the potency of the vaccine, and the selection of technology for obtaining a sufficient number of functional DCs should be specifically mentioned. The review focuses on the use of autoantigen or alloantibody material for the activation of DCs, and the results of experimental and clinical studies of DCs vaccines in bladder cancer
Молекулярно-генетическая гетерогенность меланомы глаза
Get PDFBackground. Ocular melanoma is the most common cancer of adult eye and is represented by two main subtypes of uveal (UM) and conjunctival (CM) melanoma with distinct clinical (frequency, localization, histology) and genomic features. The objective is to compare molecular and genetic characteristics of tumors in patients with melanoma of the eye. Materials and methods. In this study molecular profiling of 78 tumors including 73 UM (choroidea, ciliar body and iris) and 5 СM, was evaluated. DNA was isolated from tumor cells collected by macrodissection of FEPE sections of tumor biopsies using proteinase K. The following genes were studied by Sanger sequencing: GNAQ, GNA11, KIT, BRAF, NRAS. Results. Mutations in GNAQ and GNA11 were found in 81 % (59/73) of UM, in 42 % (31/73) and 38 % (28/73) of cases correspondently. GNAQ mutations were more frequent in primary UM (63 %), while GNA11 mutations dominated in metastatic UM (42 %). There was а correlation between frequency of GNAQ/GNA11 mutations and histologic type of UM. GNAQ mutations were identified in 55 % of spindle cell UM, while GNA11 mutations were more frequent in epithelioid cell UM (42 %). There were no differences in frequency of GNAQ/GNA11 mutations in UM of patients of different age (younger and elder 50 years). There was no statistically difference in UM patient outcome with GNAQ or GNA11 mutations. We also detected 3 UM with KIT mutations and 2 UM with BRAF mutations. There was no big difference in frequency of «driver mutations» in UM of choroidea, ciliar body and iris. Molecular profiling of conjunctival melanoma (CM) resembles that of cutaneous melanoma of skin: in 3 (60 %) CM BRAF V600E was identified and in 1 (20 %) – NRAS Q61K. Conclusion. Genetic analysis reveals wide diversity of melanoma of eye and is important for it characterization and treatment
Клинико-морфологические и молекулярно-генетические предикторы метастатического поражения регионарных лимфатических узлов при раке молочной железы
Get PDFDespite the sufficient amount of data accumulated in the literature, there are still no factors, on the basis of which it would be possible to estimate the regional lymph nodes status in breast cancer with a high degree of accuracy. The review presents literature data relating to the influence of clinicopathological, molecular-biological and genetic characteristics of primary tumor on lymph node metastases. Data of 66 foreign and Russian articles are included.Несмотря на достаточное количество накопленных данных, все еще не выделены факторы, на основании которых можно было бы с высокой степенью достоверности судить о статусе регионарных лимфатических узлов при раке молочной железы. В обзоре представлены данные литературы, касающиеся влияния клинико-морфологических, молекулярно-биологических и генетических характеристик первичной опухоли на метастатическое поражение регионарных лимфатических узлов. В работу включены данные 66 зарубежных и отечественных статей