Vol 14, No 4 (2015)

Exosomes are small (80 - 130 nm) membrane vesicles secreted by virtually all cell types. The main physiological function of exosomes is considered to transfer substance and information from cell to cell. The biochemical composition of exosomes retains similarities with the cell of origin and reflects their endosomal biogenesis; moreover exosomes contain various signaling and regulatory molecules, components of the extracellular matrix and enzymes. Malignant transformation is associated with the activation of the exosomes secretion by cells. Cancer cell - derived exosomes are shown to play essential role in disease progression. The most significant effects of exosomes include suppression of anti-tumor immunity, stimulation of invasive growth and metastasis, the development of chemo- resistance. Tumor-derived exosomes can be detected in biological fluids, including blood. Exosomes are biochemically stable, their complex composition determines the possibility of comprehensive analysis. Thus, circulating exosomes have emerged as a promising source of cancer diagnostics material as it was demonstrated by number of studies. Although many substantial and methodological questions still remain to be addressed. This review briefly summarizes the current concepts of exosomes biology and discusses the main methodological aspects of exosomes research. Results of recent investigations aimed to develop new methods for cancer diagnosis and monitoring based on the analysis of exosomes and exosomal components are presented in great details.

Multiplexed suspension systems of anew generation are capable to provide precise quantitative profiling of mul- tipledisease-specific markers in human body fluids. We have developed suspension microarrays based on microbeads encoded with fluorescent nanociystals, that show undeniable advantages overavailable analogues in terms of improved multiplexing capabilities, physical and optical properties, low cost and simplicity of analysisperformance. We have adapted QD-encoded suspension microarrays for the simultaneous detection of two forms of prostate-specific antigen (PSA) in human serum by means of classical flow cytometiy. In the present study, we describe in detail the designed system properties including evaluation the microarray for quantitative analysis of serum markers in comparison to standard clinical approach ELISA, as well asestimation of the most important analytical characteristics, such as analytic sensitivity (limit of detection), reproducibility, reliability and accuracy of the analysis, the linear rangesfor detectable- marker concentrations. Experimental data suggested that the developed diagnostic system quantifies two forms of PSA in blood serum samples of patients with high accuracy, precision and reliability.

Исследована противоопухолевая активность и проведено доклиническое токсикологическое изучение фармацевтической композиции ЛХТА-1975, содержащей в качестве основного действующего компонента хлорид трис (1-пентил-ІН-индол-3-ил) метилия. Достоверный ростингибирующий эффект показан на мышах с лимфолейкозом Р-388, аденокарциномой молочной железы АК-755 и меланомой В-16. По данным токсикологических исследований препарат имеет значительный интервал между лечебными и токсическими дозами, что потенциально делает его интересным для дальнейшего изучения. При применении в дозах, в 5-10 раз превышающих терапевтические, композиция не вызывала токсических изменений в органах и тканях.

The research has been devoted to the study of acute toxicity of preparation based on derivative of indolocarba- zole - LCS-1208 in mice of both sexes and in rats of both sexes at intravenous and intraperitoneal administration of the drug. In the experiments the laboratory animals - outbred white rats and hybrid mice (C57Bl/6JxDBA2)Fl (B6D2F1) have been used. On the results of study has been obtained the calculated toxic doses of novel preparation based on derivative of indolocarbazole at intraperitoneal administration of the drug in mice of both sexes.

At present, the hormone somatostatin analogues is increasing interest in connection with their activity against hormone-dependent tumors, which leads to the need to develop domestic drugs belonging to this group. In the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin RCRC» synthesized new domestic pentapeptide somatostatin analogue of hypothalamic hormone (AGGS). In preliminary studies of this substance demonstrated sufficiently high antitumor activity AGGS on transplanted solid tumors of mice. Due to the insolubility of the substance in the water as an alternative liposomal formulation proposed, allowing to increase the bioavailability of the drag due to the possibility of intravenous administration, increased therapeutic efficacy and reduce side effects, by improving the selectivity of action against tumor cells. During experiments on the development of the liposomal formulation AGGS pre-established model containing as essential components of the liposomal bilayer and egg lecithin PEG-2000-DSPE in a molar ratio 72/1 and as a ciyo- protectant - sucrose. In developing the technological parameters of the process of obtaining dosage form (LF) found that for an acceptable size derived phosphohpid vesicles needs about 7 cycles extrusion. The lack of stability of liposomal dispersion selected composition during storage has led to this problem by means of freeze-drying, which kept the physico-chemical parameters LF at the initial level. The efficacy of the model LF on transplantable tumors of mice - breast adenocarcinoma Ca-755, which was more than 60 % of ITG at a dose of 5 mg / kg and more than 80 % ITG with 20 mg / kg. The findings of biological experiments indicate the prospects for further research and improvement liposomal LF to produce high-performance domestic anticancer drag from the group of somatostatin analogues.

A neutral photosensitizer, aminobutylamide chlorin e₆ with a terminal amino group (1), and its derivative, a cationic photosensitizer with a terminal trimethylammonium group (2) were synthesized. Spectral, photophysical and photobiological properties of compounds 1 and 2 were studied. An impact of a charge in molecule 2 on a photoinduced antitumor activity was evaluated in vitro. Relative coefficients of intracellular accumulation (K_rei) were determined for compounds 1 and 2 in human lung adenocarcinoma A549 and human glioblastoma U251 cells. The coefficients of intracellular accumulation of neutral chlorin 1 in both cell types are fivefold higher than those of cationic chlorin 2. As a consequence, compound 1 surpasses fifteen-fold compound 2 in photoinduced cytotoxicity.