Melanoma is considered to be the deadliest form of skin cancer. For years it has been accepted that all melanoma cells in tumor are capable of tumor formation and each of them has the ability to initiate the metastasis. At present a stem cell theory of cancer has been developed, which purports that a subpopulation of self-renewing tumor cells is responsible for tumorogenesis, neoangiogenesis and stroma building. In this review we will discuss the basic determinants of melanoma stem cell and melanoma stem cell targeting implications.

Metastatic melanoma is an aggressive skin cancer, which resistant to antitumor drugs. This review describes the different mechanisms of melanoma resistance and approaches to overcoming it.

Apoptosis can be triggered from external signals. Several homologous receptors transmit apoptotic signals from outside into the cell. For successful activation of apoptosis receptors should interact with their ligands. For example, FAS receptor must bind with FAS-ligand, TNFR1 with TNFα, TRAIL-R1 and TRAIL-R2 with TRAIL, DR3 - with TL1A, respectively. In majority of cases ligands should be anchoring in the cell membrane to perform their functions. FAS and TNFR1 receptors trigger apoptosis only when they are internalized into the cell’s cytoplasm. If FAS and TNFR1 are not internalized, then anti-apoptotic program won’t start. In contrast, TRAIL-R1, TRAIL-R2 and DR3 aren’t internalized during apoptotic signal transduction. Other receptors, TNFR2, TRAIL-R3 and TRAIL-R4 start an anti-apoptotic program. The apoptotic signal starts when DISC complex is formed on the inner side of the cell membrane. FADD, procaspase-8 and intracellular domain of receptor form together DISC complex. If the DISC complex wasn’t formed, signal is transmitted by the NFкB-way via MAP-kinase cascade. In such conditions anti-apoptotic program starts. A variety of receptors and ligands provides for multiple biological functions. For example, receptor-mediated apoptosis takes a part in elimination of infected or transformed cells, regulation of inflammation, modulation of ontogenesis, hematopoiesis and antibody production.

The analysis of CTG and CTA expression in malignant tumors described in this review has been showed that different types of tumors are significantly different from each other according to the frequency of CTA mRNA expression. Melanoma, ovarian cancer and lung cancer have a very high frequency of CTA expression. Lymphoma, kidney cancer, pancreatic cancer have a low frequency of CTA expression. Breast cancer, bladder cancer, prostate cancer demonstrate an intermediate level of CTA expression. High degree malignant tumors in late clinical stage with metastases showed a greater incidence of CTA -gene expression. CTA-genes are expressed together in tumor. If the tumor is positive for one CTA-gene then the expression of several genes is possible. Immunogenic CTA-s are a well object for anti-tumor vaccines creating.

Estrogen receptors are one of the major targets in cancer cells, acting on which it is possible not only to control the processes of carcinogenesis, but also to inhibit tumor cells growth. Brilliant confirmation of this is the results of long-term application of the first targeted therapy - antiestrogen tamoxifen - in breast cancer patients with positive hormonal status of the tumor. Being discovered in the 90s, estrogen receptor beta enhanced the understanding of estrogen-mediated signaling pathway and receptor-related interactions. This review of the literature presents data on the history of the discovery, structure and functional activity of selective estrogen receptor beta, and the results of existing clinical trials which have shown the predictive role of this marker.

The aim of this study was to investigate the relationship between the original amount of basic lymphocyte subpopulations in peripheral blood and the results of therapy in patients with HER2+ and triple negative breast cancer. Before treatment was conducted immunophenotyping of peripheral blood lymphocytes by flow cytometry using a panel of monoclonal antibodies to surface markers and intracellular lymphocyte antigen FOXP3 and determining the cytotoxic activity of NK-cells. Cytotoxic activity was determined with MTT colorimetric test against K-562 cells. Revealed some differences in the composition of the population of lymphocytes and the number of regulatory T cells in patients with HER2+ and triple negative breast cancer (BC). Discuss the relationship between the number of suppressor cells and the degree of therapeutic pathomorphosis of tumor.

The main goal of our study is to provide clinical and biological assessment of MMP14 as gene that causes recurrent glioblastoma. We analyzed expression of MMP14 in 108 and 129 samples represented by Rembrandt 8РOncomine databases. The biological significance was done is based on genetic knockdown and rescuing of MMP14 attenuated U87 and U251 glioma cells followed by cytofluorimetry and array gene expression. As expected, genetic silencing of MMP14 led to accumulation cells in the “G₂” phase of cell divisions which correlates to cell kinase’s expression. Furthermore, exposure of MMP14 to ionizing radiation and temozolomidt treatments prolongs glioma cell proliferation and increase the anti-glioma effect of temozolomide-ionizing radiation therapeutic combination. Our data suggest that most of the neoplastic glioma cells express significantly MMP14.Therefore, alteration of MMP14, improves anti-tumor effect.

An open-label, retrospective comparative clinical trial evaluated the efficacy of Temobel (RUP Belmedpreparaty) and Temodal (Schering-Plough, the Office of the Joint-Stock Company «Schering-Plough Central East AG») in 90 patients with high-grade (III-IV) glial brain tumors within a postoperative chemoradiotherapy course (a total target dose of 50-60 Gy). The compared groups, 45 patients in each, were fully matchable in prognostic factors affecting treatment outcomes. Median survival, 1- and 3-year overall survivals with Temobel in the combination treatment scheme were 20 months, 72.7±6.7% and 23.7±9.5%, whereas with Temodal they were 17 months, 77.8±6.2% and 30.3±7.0% respectively (P=0.935). Meanwhile, progressive-free median survival and progressive-free 1- and 3-year survival with Temobel and Temodal were 12 months, 51.0±7.5%, 21.3±6.4% and 11 months, 49.3±7.6%, 15.5±5,7% respectively (P=0.814). No statistically significant differences were found in the survival of patients in the compared groups.

It is already established that verapamil inhibits Pgp expression in the brain tumor cancer cells such as medulloblastoma. The aim of this study is to investigate the sensitivity of glioblastoma cancer cells to verapamil and its combination with oncolytic adenoviral victor CRAd-S-pK7. In vitro using U87 and U251 human glioblastoma cell lines, we obtained experimental data suggesting a therapeutic effect of verapamil and CRAd-S-pK7. Moreover, we established that verapamil improves anti-glioma effect of oncolytic adenoviral vector in the presence of ionizing radiation, which results into more suppression of U251 cancer cells via inhibition of their proliferation.

This article presents the results of preclinical study of antitumor activity of indolo[2,3-a]carbazoles N-glycosides derivative (LCS-1208) in pharmaceutical dosage form for intravenous administration - lyophilisate for injection. LCS-1208 high antitumor efficiency has been shown by different regimens of administration on tumors of diverse histogenesis: LCS-1208 exhibited increase of life span (ILS) 76% on lympoblastosis P-388 and ILS 76 % and 33 % recovery of Fisher lympadenosis L5178Y by 25 mg/kg daily intravenous administration during 5 days. Whereas LCS-1208 demonstrated high antitumor efficiency on solid tumors by 150 mg/kg single intravenous dosing: on LLC - tumor growth inhibition (TGI) 95% - 81% during 9 days and on RShM-5 (TGI 74% - 56% during 9 days). LCS-1208 appeared statistically significant TGI 51 % and 47 % on 3rd and 7th days after 150 mg/kg single intravenous dosing on established tumor. Comparative study of LCS-1208 substance and dosage form by intraperitoneal injection has shown that decrease of therapeutic dose to 110 mg/kg, which doesn’t induce death of animals, resulted only in dosage form antitumor effect (TGI 74-75 % during 8 days after the end of treatment).

His study objective has been to develop optimal composition of Cifelin sterically stabilized liposomal formulation. The substance of Cifelin synthesized in chemical synthesis laboratory FSBNI «N.N. Blokhin RCRC». All used excipients and reagents conform to the standard documentation. Method of obtaining liposomes includes: a method of obtaining Cifelin multilamellar and unilamellar liposomes dispersions. Liposomal dispersion has been lyophilized on freeze-dryer Edwards Minifast DO.2. Liposomes size has been measured by light diffusion dynamic spectrums copy on Nicomp 380 Submicron Particle Sizer. Quantitative measurement has been conducted by spectrometry in ultraviolet area. Crystals of unenclosed into lipid bilayer Cifelin have been separated by filtration through filter with pore diameter of 0,22 μm. Lipids peroxidation has been estimated by concentration of oxidation final product - MDA. MTT-test has been used to estimate Cifelin LF cytotoxic activity in vitro. In this study the optimum molar ratio of components has been found for liposomal membrane composed of phosphatidylcholine, cholesterol and DSPE-PEG-2000. Composition with lipids molar ratio 165 : 8 : 1 and “lipid: Cifelin” ratio 12 : 1 has been chosen as optimal by entrapment efficiency and appearance, encapsulated API value in this composition has been 98±1 %, liposomal size has been 136±12 nm. On cell line SKOV-3 and Jurkat in vitro cytotoxic effect of Cifelin liposomal drug form has been highly increased. As a result of the study drug product “Cifelin lyophilized liposomal for injections 17 mg” has been developed.

The article presents the results of high-cancer CBA inbred mice liver morphological research while using multiphytoadaptogene early postnatal ontogenesis administration. Moderate and pooly differentiated trabecular and trabecular-acinar hepatocarcinomas were determined. Lymphocytes infiltration and destructive features were microscopically visible in hepatocarcinomas at the age of 22 months. Infiltrated lymphocytes and destructive features in control mouse hepatocarcinomas were not detected.

In this study we first identified role of small GTPase Arf6 in stimulation of proliferation and autonomous growth of human glioblastoma cells. We revealed that Arf6 activates the mTOR complex 1 (mTORCl) and this process is appeared to be an alternative mechanism of mTORC1-signaling activation, independent of PI3K/Akt-signaling pathway. We also showed that Arf6 is a negative regulator of protein kinase ERK1/2 in glioblastoma cells.

MAb against the antigen CD117 - stem marker of human tumor cells. Strain 406 PPI prepared by cell fusion of mouse myeloma NS-1 cells with spleen mice BALB/ C, pre-immunized three times at an interval of two weeks, the cells of the cell line of human melanoma melKor. Merging conducted using a solution of PEG/DMSO. For screening received mAb 406 used human melanoma cell lines which differed in the expression of CD117 antigen FSBSI "N.N. Blokhin RCRC" collection. N.N Blokhin. Antigen expression was studied in immunofluorescence and evaluated on a flow cytometer BD FACS CantoTMII. ICA IC0-406 was compared with commercial ICA against antigen CD 117 (Germany). The results indicated the identity of the frequency of antigen-positive cases and the percentage of antigen cells. ICA IC0-406 block binding to cells melKor ICA anti-CD117. Linking ICA IC0-406 antigen-positive cells causes modulation of antigen CD 117.

Pharmaceuticals derived from plants, have become one of the leading commercial directions in modern biotechnology. The benefits that offer these technologies, cannot be matched with any other modern technology for producing drugs from recombinant proteins. Main advantages of plant technologies for production of proteins are easy scalability, efficiency, bio-safety, ease of cultivation and collection of biological material. This approach promises to be the most perspective for production of a wide range of drug substances and vaccines. In current investigation we have analyzed in vitro and in vivo biological activity of plant-derived anti-HER2 recombinant antibodies - phytotrastuzumab. Phytotrastuzumab and trastuzumab have similar activity in grows suppression of breast cancer cells overexpressing HER2 in-vitro and were active in suppression of xenografted tumors SK-BR-3 in-vivo.