Despite the fact that melanoma is a tumor of visual localization, mortality from skin melanoma remains one of the leading causes of mortality worldwide. Early metastasis of melanoma, even during the initial stages of the tumor process, indicates a high malignant potential of the tumor. Moreover, metastatic melanoma is resistant to current chemotherapy regimens, which is a significant problem today. Progression, resistance to drug therapy of skin melanoma is associated with a population of tumor stem cells, which are characterized by dysregulation of signaling pathways and aberrant phenotypes. The formation of tumor stem cells contributes to their microenvironment. Surface markers expressed by tumor stem cells include transporter proteins that mediate chemoresistance. The study of the microenvironment, the activity of the expressed antigenic determinants makes it possible to understand the processes of chemoresistance formation and to discover (develop) strategies for its overcoming. The article provides an analysis of the literature data on the significance of tumor stem cells in the development of drug resistance of melanoma.

Polymers have already been recognized as promising materials in many areas of life including pharmaceutical technology. A wide range of polymer properties such as providing controlled release of APIs, enhancing permeation and protection of APIs from mucosal enzymes is now successfully using worldwide in producing soft and solid dosage forms. It is now recognized that a significant portion of the polymer research ongoing in the world is related with a new group of polymer properties such as «shape memory system» and “self-folding”. This review focuses on “smart” – polymers properties that could be a promising tool in developing smart delivery systems.

Introduction . Inactive X chromosome (Xi) is associated with noncoding XIST RNA, series of proteins and contains multiple epigenetic modifications that altogether determine a silence of the most of X-linked genes. Recently the data were obtained that tumor suppressor BRCA1 is also associated with Xi. The purpose of this study was to reveal the colocalization of BRCA1 and XIST RNA and precise spatial organization on Xi with the high resolution of confocal microscopy.

Materials and methods . The object of the study is IMR90hTERT diploid immortalized fibroblast cell line. For BRCA1 and XIST RNA colocalization analysis on Xi the method of fluorescent hybridization in situ associated with immunofluorescent cell staining (immunoFISH) and confocal microscopy were used. For BRCA1 and heterochromatin protein-1 colocalization study the method of double immunofluorescent staining and common fluorescent microscopy were applied.

Results . The study using confocal fluorescent microscopy with higher resolution has demonstrated at first the colocalization of BRCA1 with XIST RNA region of Xi revealed with XIST RNA probes and with replicating Xi and autosomes revealed with BrdU in late S-phase of cell cycle. Altogether, the data obtained suggest the involvement of BRCA1 in the inhibition of gene expression on Xi due to the regulation of XIST RNA association with Xi. Moreover, according to the results of confocal microscopy, BRCA1 also colocalizes with replicating Xi and autosomes revealed with BrdU in late S-phase of cell cycle. This indicates a possible involvement of this protein in the replication of pericentromeric repeats in cellular chromosomes. Colocalization of BRCA1 with heterochromatin protein-1α presented in pericentromeric regions of all chromosomes supports this suggestion.

Conclusions . Altogether, the data obtained in this study suggest the involvement of BRCA1 in the inhibition of gene expression on Xi due to the association with noncoding inhibiting XIST RNA and in replication of heterochromatin regions. 

Introduction. Mammalian chitinase-like proteins are produced in the areas of inflammation and in tumors. Some members of chitinase-like proteins family are studied as potential biomarkers of tumors (glioma, prostate and ovary). YKL-39 also known as chitinase-3-like 2 (CHI3L2) is a secreted protein produced by chondrocytes. Its high expression is also found in synoviocytes, lung heart and macrophages.

The aim of this study was the development of highly specific monoclonal antibodies against human YKL-39.

Materials and methods. Using recombinant full-length human YKL-39 as immunogen using hybridoma technology we have generated monoclonal antibody 1B2G4, that specifically binds YKL-39 in ELISA.

Results and conclusion. Obtained antibody was successfully tested in Western blot, immunocytochemistry, immunofluorescence and immunohistochemistry on FFPE sections. It was shown that the antibody binds the full-length YKL-39 protein and does not interact with other chitinase-like proteins. 

Introduction . The report considers the prospect of rational approach to the new anticancer agents creation based on indolocarbazole derivatives.

Objective . To conduct a comparative study of 12 domestic N-glycosides, indolo[2,3-a]pirrolo[2,3-a]carbazole derivatives in the course of “structure – activity” bond analysis.

Materials and methods . The investigation of influence of 12 carbohydrate – containing indolocarbazoles, synthesized in N. N. Blokhin Russian Cancer Research Center of the Ministry of Health of Russia, performed on models of solid transplantable mouse tumors: lung Lewis epidermoid carcinoma and B16 melanoma. The antitumor effect was assessed by Lewis epidermoid carcinoma and B16 melanoma tumor growth inhibition (TGI %) criterion.

Results . A variety of indolocarbazoles modifications allowed revealing the dependence of their antitumor properties on the structure of both, the aglycone and the glycoside residue. Imino-nitrogen interchange of atoms in upper heterocycle influences on indocarbazole derivatives antitumor activity change. During a comparative study of 12 N-glycosides indolocarbazole derivatives on lung Lewis epidermoid carcinoma and B16 melanoma models, 8 derivatives showed antitumor activity.

Conclusion . The formulated concepts on the modification features in indolocarbazole derivatives structure can be used for more active compounds creation with greater action selectivity. 

Introduction . The RHAMM (hyaluronan mediated mobility receptor) is overexpressed in many types of human cancer and increased synthesis of the RHAMM usually correlates with a poor prognostic factor. In this paper, we synthesized the peptide-RYQLHPYR modulating the activity of the RHAMM and examined the therapeutic potential of this RHAMM-targeting peptide as an antitumor agent.

Objective . Study the effect of the synthetic peptide RYQLHPYR on viability, apoptosis, necrosis, caspase-3 / 7 activity, and invasion of prostate cancer cells.

Materials and methods . The peptide RYQLHPYR was prepared by solid phase synthesis. Human prostate cancer cells (PC3 m-LN4), murine embryonic fibroblasts and murine embryonic fibroblasts (RHAMM- / -). To quantify the effect of the peptide on apoptosis and cell necrosis, ELISAPLUS was used. The activity of caspase-3 / 7 was determined by the colorimetric method. Evaluation of the anti-metastatic effect of the peptide in vitro was evaluated by invasion of cells by quantitative analysis of the area of degradation of fluorescent gelatin.

Results . It was found that the peptide RYQLHPYR inhibited the growth of tumor cells PC3 m-LN4 at a concentration of 10 μg / ml (2 × 10–7 M) after 24 h by ~80 %. It was shown that the peptide stimulated the level of apoptosis in cancer cells, approximately 10-fold. It was found that the peptide increased the necrotic death of tumor cells by 2.5 times. During the research it was revealed that the peptide increased the caspase-3 / 7 activity in tumor cells by 2 times. At the same time, it was shown that RHAMM-targeting peptide had no significant effect on apoptosis and necrosis of normal cells (fibroblasts) and fibroblasts (RHAMM- / -). It was found that the peptide inhibited invasion of tumor cells by ~99.86 % at a concentration of 10 μg / ml (2 × 10–7 M).

Conclusions . The obtained results indicate that the peptide RYQLHPYR has antitumor activity and, therefore, has a therapeutic potential for the treatment of prostate cancer. 

Introduction . Anthracycline antibiotic doxorubicin (DOX) is widely used in clinical oncology. It is known that hemin, endogenious compound, has the ability to modulate DOX cytotoxicity. We found that DOX toxicity against mammalian cancer cells can be decreased in vitro in the presence of teraftal (ТF), the component anticancer binaric catalytic system (TF + ascorbic acid).

Purpose . To study the influence of TF on anticancer effect of DOX.

Materials and methods . The mouse melanoma cell line B16 / F10 and mouse transplanted tumor B16 were used. The TF ability to protect from DOX-induced cell death were measured by MTT-assay, flow сytometry, light microscopy, cytochemical determination of ß-galactosidase expression, radiometric assay and tumor growth inhibition assay in vivo.

Results. The sensitivity of mouse melanoma cell line B16 / F10 to DOX decreased in the presence TF (10–20 mkM) in the mean by 4–6 fold. The same mechanism takes part into the decrease of DOX cytotoxicity at the presence of TF / hemin khown which connects with the cell ability to accumulate of drug. TF protect the mouse melanoma cells B16 / F10 from apoptosis, induced by DOX throwing switching on cell premature senescence programme. The antitumor effect of DOX against mouse transplanted melanoma B16 at presence of TF was the same as DOX alone.

Conclusions. The TF potency to decrease the sensitivity of cancer cells to DOX in vitro does not correlate with its ability to modulate аnthracycline antibiotics anticancer effect in vivo. 

The aim of this study was the morphological investigation of the CBA mice liver tissue at different stages of ontogenesis as well as during liquid form multifitoadaptogen therapeutic administration.

Materials and methods . The study objects are the liver samples of CBA male mice (subline CBA / LacY). Experimental animals received a 10 % solution of multifitoadaptogen from 6 months of age until natural death. Tissue samples were fixed in neutral buffered formalin and embedded in paraffin. Sections from paraffin blocks were stained with hematoxylin and eosin. The structure of the liver tumours was determined as well as the quantitаtive degree of leukocyte infiltration in the tumour tissue.

Results . The tumours morphologically structured as moderately differentiated trabecular hepatocarcinomas (at 8 months of age) and low differentiated trabecular-acinar hepatocarcinomas (aged 22 months) were revealed in CBA male mice. Higher lever of leukocyte infiltration in hepatocarcinomas of experimental animals was determined.

Conclusion . Leukocyte infiltration may be important for antitumour immune reaction as well as for reduction of the tumour formation incidence in high-cancer mice.

Introduction . In accordance with Russian Federal Program of import substitution of foreign medicines replacement for high-quality Russian drugs in Russia reproduced нydroxycarbamide (HC), which passed preclinical toxicological and pathomorphological testing in comparison with hydrea (HD), producted by Italy.

The aim . The aim of present study was the comparative evaluation of HC and HD effect on the internal organs of rats for the clearing up of their identity according to the morphological criterions.

Materials and methods. 70 non-inbred male rats, by 10 rats per group, were used. HC and HD were administered to rats oral daily for 5 days in the same total doses correspond with to the 2, 1 and 1 / 2 maximum tolerated dose. In the same regime control rats were oral administered with 1 % starch paste solution. Of animals were removed from the experience on days 3 and 30 after the end of the administration of the drugs. The macroscopic and histological examination of internal organs were perform by routine methods, including fixation of the material in 10 % formalin and staining of sections with hematoxylin and eosin. The histological preparations of the internal organs was analyzed in the light microscope at magnifications of 100, 400, 1000.

Results . HС, as well as HD, in total doses of 3000 and 1500 mg / kg at the 3 day after the end of the introduction caused different degrees of similar morphological changes in rat internal organs: moderate hypoplasia in the thymus, bone marrow and spleen, destructive and inflammatory changes in the stomach, duodenum and kidney. At the 30 day after the application of both drugs morphological changes in the thymus, the bone marrow and the spleen disappeared completely, residual morphological changes persisted in the duodenum and kidneys; in the testes of rats – moderate atrophic changes. HС, as well as HD in total dose 750 mg / kg did not cause changes in the internal organs of the rats.

Conclusion . Based on the results of macroscopic and histological examination the conclusion about of the identity of the influence of HC and HD on the internal organs of rats was made. 

The purpose of this work is to study of phenolic compounds in the dry extract of dandelion herb and large burdock leaf tea.

Materials and methods . The separation and identification of phenolic compounds of dry extract of dandelion herb and large burdock leaf tea by thin-layer chromatography and high-performance liquid chromatography with UV-detectionhas been carried out.

Results . As a result of research, it has been established that during TLC the optimal system for the separation of phenolic compounds is the ethyl acetate – formic acid – water system (10:2:3). On the chromatogram four spots were found corresponding to the value of Rf and fluorescence in UV-light to flavonoids of the flavone group and phenolic acids (chlorogenic and caffeic acids). For further identification of phenolic compounds using HPLC, eight peaks were found, which in terms of retention time and spectral characteristics correspond to phenologlycosides, chlorogenic acid, caffeic acid derivatives, ferulic acid, umbelliferone.

Conclusions . Thus, the dry extract of dandelion herb and large burdock leaf tea contains hydroxycinnamic acids and their derivatives, compounds of coumarin nature, phenologlycosides.