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Advances in Molecular Oncology

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Vol 5, No 2 (2018)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/2313-805X-2018-5-2

REVIEW ARTICLES

8-15 841
Abstract

MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.

16-23 1918
Abstract

The 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.

RESEARCH ARTICLES

24-30 2242
Abstract

Background. Cell cultures used as a models in studies of epithelial tumors, are obtained not only from solid tumors, but also from extracellular fluids. It is known that dissemination of ovarian cancer in the peritoneum and further growth of tumor cells in ascetic liquid is accompanied with the activation of epithelial-mesenchymal transition, and, therefore, cell cultures derived from extracellular fluids can have a distinct molecular phenotype from primary tumors.

Objective: evaluation the “persistence” of epithelial phenotype in breast and ovarian cancer cell cultures.

Materials and methods. The cells obtained from pleural fluid (MCF-7, T-47D), colostrum (HBL-100), solid tumors (BT-474, HCC1937) of patients with breast cancer and ascitic fluid (SCOV- 3) of patients with ovarian cancer. The expression of cytokeratins and vimentin was evaluated using a quantitative immunofluorescence method associated with flow cytometry.

Results. Vimentin expression in cells derived from extracellular fluids was not changed (line HBL-100), slightly decreased (SCOV-3 cells), or even was lost (MCF-7 and T-47D cells). HCC1937 cells obtained from solid tumor with expected low expression of vimentin acquired a molecular phenotype with a high expression of this mesenchymal marker. In breast cancer cells BT-474 derived from solid tumor a “persistence” of epithelial phenotype was discovered.

Conclusion. Quantitative assessment of the de novo expression of mesenchymal protein vimentin showed that the tumor phenotype within the organizm is not always realized in cells adapted to growth in culture, and is not always «strictly» epithelial, and this evidence must be considered with different kinds of molecular studies of epithelial cells in vitro.

31-41 687
Abstract

Background. 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.

42-49 646
Abstract

Background. Therapy with compounds potentially capable to block KRAS oncogene signaling pathway is perspective direction in modern oncopharmacology. The aim of current study was to investigate effects of the combined treatment with rapamycin (RAP) and paclitaxel (PAC) in transgenic zebrafish (Danio rerio) with constant expression of mutant KRASV12 oncogene conjugated to green fluorescent protein (GFP) in epidermal cells. This strain has a modified phenotype due to epidermal hyperplasia and expression of GFP reporter at skin of embryos and adult fish.

Materials and methods. Fish embryos 6 hpf were exposed to 0.1 % DMSO solution (control) and various doses of the drugs or combinations thereof. GFP expression in epidermal cells was morphometrically measured at 72 hpf.

Results. Dose-related decrease in phenotypic changes up to complete epidermal normalization under RAP 50–400 nM treatment was observed. Treatment with nontoxic for embryos doses of PAC 50–250 nM increased fluorescence level in a dose-dependent manner, indicating an activation of KRAS signaling. Using of lower doses of RAP (10 and 25 nM) or PAC (10 nM) had no statistically significant effect on expression of transformed phenotype. Whereas combined treatment (RAP 10–25 nM and PAC 10–50 nM) dramatically decreased level of epidermal fluorescence and completely normalized phenotype of transgenic fish.

Conclusions. Thus, mutual potentiating effect of RAP and PAC in low doses which leads to selective inhibition of the KRAS signaling pathway was revealed, indicating the prospect of further studies of these drugs combination for targeted cancer therapy.

50-61 1240
Abstract

The 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.

62-70 1178
Abstract

Objective: to study the prognostic significance of the expression of cancer-testis (CT) genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in patients with multiple myeloma (MM) and their influence on overall survival and relapse rate. To determine their effect on suсh clinical parameters as levels of lactate dehydrogenase, leucocytes, hemoglobin, calcium, albumen, creatinine, beta-2-microglobulin.

Materials and methods. Real-time polymerase chain reaction was performed on complementary DNA obtained from bone marrow of 77 patients with MM. The statistical analysis was performed using the Statistica 10.0 software package. To estimate prognostic values of the CT gene expression data were analyzed by the Kaplan – Meier method.

Results. The study was conducted to determine the level of expression of CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 in a group of patients with MM. The group included primary and receiving cancer treatment in MM patients. According to the log-rank criterion expression of any of the CT genes PRAME, NY-ESO1, GAGE1, MAGE A3, MAGE A6, MAGE A12, SSX1, SLLP1, PASD1 exerts a significant influence on overall survival and progression-free survival/relapse. It was also determined that providing expression of some CT genes, the levels of creatinine, calcium, beta-2-microglobulin were much higher to compare with patients without expression.



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ISSN 2313-805X (Print)
ISSN 2413-3787 (Online)