Vol 15, No 4 (2016)

The basic problem in cancer treatment remains the identification of cells responsible for maintaining the whole population of cells in a tumor. For decades it has been considered that all transformed cells within a tumor have carcinogenic potential with unlimited proliferation capacity and metastases formation. At present, the concept of cancer stem cell was introduced indicating that tumor evolves from a small population of long-live and slow proliferating cells. These cells have the capacity to initiate the tumor formation in immunodeficient animals. Among their properties, resistance to standard oncology treatments leads to treatment failure and cancer recurrence. The management and eradication of different types cancer is completely depended on removal of this cell population. Current review presents basic information about cancer stem cell, particularly, the initiation of tumor, the peculiar properties of cancer stem cell, the role of cancer stem cell in metastasis formation and discusses therapeutic strategies targeted cancer stem cell.

Immune system plays a crucial role in tumor growth process. It exerts cancer surveillance function via innate and adaptive immune mechanisms, nonetheless tumor may exploit various immune cells to escape specific immune response. Dendritic cells are the primary antigen presenting cells, which mediate immune response against cancer cells. Dendritic cells are capable of processing and presenting tumor antigens to T cells, which results in tumor-specific T cell- mediated response. However, adoptive therapy with dendritic cells demonstrates poor clinical outcomes. Among a variety of factors, the impact of tumor microenvironment on dendritic cells may be the primary one. Therefore, tumor-derived factors, which lead to dendritic cells malfunction, may be the key target for improving dendritic cell - based therapy. Meanwhile, recovery of dendritic cell functions in cancer patients remains one of primary aims for cancer immunotherapy. This review outlines main types of tumor-induced dendritic cells dysfunctions in cancer.

Introduction. Governments around the world seek to reduce rapidly rising health care costs. Using the same high quality and often cheaper than the original brands, generics greatly reduces costs while providing an adequate quality of care. Therefore the development of generic medicines is an important task. The purpose of the study - the reproduction of the pharmaceutical dosage form for creation of national drug-generic epirubicin. Materials and methods. The study used a substance epirubicin (Ph. Eur current edition, Teva Pharmaceutical Industries Ltd., Israel); “Farmorubicin”, production “Pfizer Italia Srl” for “Pfizer Inc.”, Italy / US and excipients conforming to with relevant regulatory documents. Mice transplanted tumor: lymphocytic leukemia P388. Methods: technological, pharmaco-analytical, biological and pharmacological. Results. Pharmaceutical analysis of reproduced generic-drug “Epirubicin-RONC®” showed that itfully meets the requirements of manufacturer’s monograph. The results of “acute” toxicity study in rats and observations of the experimental animals within 30 days after a single administration suggest that both drugs have similar toxicological properties and are almost identical. Generic “Epirubicin RONC®” and “Farmorubicin” in lyophilized dosage form for injection 10.0 mg/vial, administered once, shows equal antitumor effect at two administration routes in mice with transplantable tumor: lymphocytic leukemia P-388. Conclusion. N.N. Blokhin Russian Cancer Research Center Ministry of Health of Russia has been reproduced generic - “Epirubi-cin-RONC®”, which is fully conform to the imported drug.

Background. The drug cyphetrylin, hypothalamic hormone somatostatin analogue, was developed in N.N. Blokhin Russian Cancer Research Center at the Ministry of Health of Russia. The basis of this work is the idea of using cyphetrylin as a specific carrier of cytotoxic groups. Objective. Synthesis of cytotoxic cyphetrylin analogues in order to study the effect of the presence of cytotoxic agents on its antitumor activity. Results. The classical methods of peptide chemistry were used for 5 the new cyphetrylin analogues synthesis. The compounds have been obtained by the addition to the cyphetrylin Na-group of the cysteine or lysine Ns-group chlorophenacyl or hydrolyzed сyphelin (cytotoxic agent). Purification of the peptides was performed by column chromatography on silica gel. The purity of the obtained compounds was confirmed by elemental analysis, TLC, optical rotation angle data and HPLC. Preliminary studies of anti-tumor activity were performed in mice transplanted tumors: adenocarcinoma Ca755 breast and melanoma B16. Conclusions. New peptides - analogues cyphetrylin containing cytotoxic fragment have been synthesized, their structure and purity have been confirmed.

Aims and objectives. During regional intraperitoneal chemotherapy cytostatics in prolonged dosage form, in particular, on the basis of various biodegradable hydrogels, such as dextran phosphate are applied. Aim of the study - a comparative evaluation of the antitumor activity ofcisplatin and cisplatin in prolonged dextran phosphate hydrogel form on Zajdel ascites hepatoma. Materials and methods. On 49 white no inbreed rats (n = 7) with implanted intraperitoneal Zajdel ascites hepatoma the antitumor activity of cisplatin in prolonged dextran phosphate hydrogel form with single intraperitoneal injection of the dosage from 3 to 8 mg/kg (≈ maximum tolerated dose, MTD) was evaluated in comparison with officinal cisplatin. The treatment efficacy was assessed by a statistically significant standard criteria: the absence of ascites by 32nd day of the experiment (complete remission) and an increase in life span of rats with ascites (T/C >_125 %, «treatment/control») in comparison with the rats without treatment (tumor growth control, where T/C = 100 %) or treated with officinal cisplatin. Macroscopic, pathomorphological and statistical analysis of the results were used. Results. It has been shown that hydrogel form of cisplatin compared to cisplatin was significantly more effective: complete remission 4/7-6/7 vs 0/7, T/C = 140-188 % vs 91-101 %, the volume of ascites 13,6 ± 6,6 ml vs 50,0 ± 7,9 ml (p = 0,004) because of a better tolerance. Regression analysis confirms that hydrogel form of cisplatin in used dose range significantly improves the rats survival with Zajdel ascites hepatoma, reducing the risk of death from tumor in 7-35 times and the relative risk with the dose of 5,5 mg/kg in 36 times (95 % CI3,86 + 327,60) (p = 0,002-0,005). Conclusions. The data obtained allow considering the hydrogel form of cisplatin as a promising prolonged this drug form of cisplatin by the intraperitoneal therapy and recommending it to preclinical study.

Background. A search for pathogenetically grounded approaches to the treatment of non-small cell lung cancer is undoubtedly one of the top priorities, because of the results of its treatment cannot be regarded as satisfactory. Discovery of a new type of receptors, estrogen receptors ß, that expressed in non-small cell lung cancer, created the preconditions for the development of a new treatment strategy for non-small cell lung cancer, namely antiestrogen therapy. Objective was to answer to the clinically significant question of how many patients with non-small cell lung cancer and lung metastases are potential candidates for antiestrogen treatment. Materials and methods. A comparative quantitative estimation of the level and frequency of the estrogen receptors ß expression in non-small cell lung cancer tissues and also in lung metastases (74 in total) was carried out by flow cytometry. Results. The estrogen receptors ß expression was detected in the majority of the investigated tumors and lung metastases, in 92 and 86 % of patients, respectively. The average level of estrogen receptors ß expression in non-small cell lung cancer tissue was higher then in metastases (42 % and 34.6 % respectively). The differences was statistically significant (p = 0.03). Primary tumors with a high and low+moderate estrogen receptors ß expression levels were detected in 35 % and 65 % of cases respectively and metastases with such expression levels - in 14 % and 86 % of cases respectively. Conclusion. 1. The estrogen receptors ß expression in the tumor predicts a more favorable course of the disease. One of the reasons for this may be a greater metastatic potential of tumor cells with low estrogen receptors ß expression. 2. The group of potential candidates for carrying out the adjuvant antiestrogen therapy comprises about 70 % of patients with primary lung tumors and with metastatic lesions of lung.

Aim of this work was the synthesis of REDOX-dendrimer core, which is tetraglycidyl ether of pentaerythritol, and a dendron, which is a derivative of anthraquinone. Materials and methods. Analytical and preparative chromatography was carried out on a liquid chromatograph SP 8000 (Spectra-Physics (USA)). Chromatograms were recorded using a UV-detector (Spectra-Physics (USA)) and refractive index detector (Jobin-Ivon (France)). The structure was confirmed by PMR (Bruker WH-360 (Germany)) with an operating frequency of 360 MHz. Monitoring of reactions conducted using HPLC. Results. Derivatives of 2-methylanthraquinone were synthesized and isolated by use of preparative HPLC. Their structure was determined by PMR-spectroscopy. They were used as a dendron in the synthesis of dendrimer. Its toxicity was studied in male mice ВDF1. Redox dendrimers containing methylanthraquinone derivatives in its structure were synthetized. Low toxicity of obtained REDOX-dendrimer was shown. Conclusion. The similarity of REDOX-dendrimer structure with doxorubicin and its low toxicity provides background for further study of its antitumor activity.