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.

Molecular genetic and molecular biology methods enable one to reveal pathogenetic basis of oncohematological diseases, they are particular useful for diagnostic purpouses, to control and evaluate treatment efficiency. In leukemia patients there are two different types of chromosomal anomalities: some of them give rise for chimeric oncogenes, others activate hyperexpression of regulatory genes. It is necessary to take into account this difference in order to proparely develop molecular genetic tests. Molecular tests are more sensitive to compare with other approaches, due to this fact they are especially useful to monitor residual leukemia cells and for early detection of relapse.

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. The disruption of BRCA1 function leads to the development of several cancers including breast cancer, ovarian cancer, non-small cell lung cancer, gastric cancer, pancreatic cancer. Recently it was demonstrated that BRCA1 protein as well as another DNA repair protein, ERCC1, could be prognostic markers of the course of the disease and predictive markers of platinum-based chemotherapy efficiency. Nevertheless, the obtained data are controversial. Aim. In current study the comparison of BRCA1 expression in breast cancer with favorable and unfavorable prognosis based on estrogen receptor status (ER+ and ER^- ) was carried out to evaluate its potential prognostic significance for subsets of breast cancer with different platinum chemotherapy sensitivity. Materials and methods. The estimation of BRCA1 expression was made in 50 samples of breast cancer tissue (40 ER+ and 10 ER^-) using the quantitative immunofluorescent method coupled with flow cytometry. Tumor cell suspensions were incubated with primary anti-BRCA1 antibodies (Abs) (SD118, Calbiochem) and secondary fluorescent Abs (DyLight650, ab98729). Cell fluorescence was measured at the Flow Cytometer FACSCanto II (Becton Dickinson, USA) using the program FACSDiva 6.0. The level of BRCA1 expression was analyzed using the program FlowJo 10.0 with statistical approach of Kolmogorov-Smirnov. The level of BRCA1 expression was determined as the ratio of specifically fluorescent cells to the total number of cells. Results. 1. The expression of BRCA1 was revealed in all breast cancer samples with mean expression level 36.8 ± 7.6 % and median 37 %. 2. Using the method of Student t-test statistically significant difference in mean value of BRCA1 expression level (p = 0.02) was revealed between ER+ and ER^- breast cancer groups (38.0 ± 7.5 % and 32.0 ± 6.3 %, respectively) 3. Comparison of BRCA1 expression level in ER+ and ER^- breast cancer groups using Mann - Whitney test also demonstrated statistically significant difference (p = 0.016). 4. These differences in mean value of BRCA1 expression level were especially prominent (p = 0.007) upon the comparison of ER+ and ER- breast cancer groups with BRCA1 expression levels below median (32.4 ± 5.0 % and 26.8 ± 2.9 %, respectively). 5. Comparison of BRCA1 expression levels in ER- breast tumors and the median for all studied breast cancer samples (37 %) demonstrated the correlation of decreased level of BRCA1 expression and negative ER status of the tumor. BRCA1 expression levels below the median were shown for 80 % of breast cancer patients with negative ER status in tumor, and over the median - in 2 0 % of cases, respectively. Conclusion. The results of current studies demonstrated that BRCA1 protein is expressed at different levels in the tumor tissue of all breast cancer patients. Lower level of BRCA1 expression in ER-negative as compared to ER-positive tumors, and established unfavorable prognostic value of ER-negative breast cancer status point to poor prognostic value of lower level of BRCA1 expression.

Introduction. PRAME protein is a promising target for cancer immunotherapy. PRAME is not expressed in normal tissues, but active in number of the tumor types. We have developed the mouse monoclonal antibodies 5D3F2 and 6H8F12 against PRAME epitopes. Aim. To determine the effects provided by the monoclonal antibodies 5D3F2 and 6H8F12 against the cells with different levels of PRAME gene expression. Materials and methods. We used different cell lines: NOMO-1 and WI-38 with low levels of expression PRAME; THP-1 with intermediate level of PRAME expression; K562 and WI-38-PRAME with high level of PRAME expression. We incubated these cell lines in the presence of monoclonal antibodies 5D3F2 and 6H8F12. The final concentration of monoclonal antibodies in culture varied from 6 pg/ml to 120 mcg/ml. The live cells were counted at the 24, 48 and 72 hours after incubation. The number of dead cells was evaluated by the MTT-test after 24 hours. Results. Cell growth rate is significanely decreased during incubation with monoclonal antibodies. This effect is correlated with increase of monoclonal antibody concentrations (Pearson coefficient 0,67;p = 0,0219). K562 growth rate was much less compared to the THP-1’s rate (p = 0,0061), NOMO-1 (p = 0,0005) and WI-38 (p = 0,0002) in the presence of the same amount of monoclonal antibody 6H8F12. K562 cell growth rate was lower than the WI-38-PRAME’s rate (p = 0,0027), despite the comparable level of PRAME expression. Effects of monoclonal antibody 5D3F2 and 6H8F12 were similar (p = 0,3946). According to the MTT-test, the comparable number of death cells in K562 and WI-38-PRAME was observed (p = 0,8405). Under the same conditions the amount of death cells in THP-1 was smaller than K562 (p = 0,6335). To compare with K562, fewer cells died in NOMO-1 and WI-38 (p = 0,0026 and p = 0,0005, respectively). Conclusion. It was shown that monoclonal antibody 5D3F2 and 6H8F12 exhibit a significant cytotoxic effect against PRAME-express-ing cells. In case of higher levels of PRAME expression the cytotoxic effect was stronger.

Introduction. Among the variety forms of inflammation, many of which contribute to the growth of tumors, classical inflammation reaction - delayed type hypersensitivity is able to eliminate. Artificially induced intratumoral it can be used successfully in immunotherapy. As the level of antitumor immunity correlates with the intensity of the reaction, we used the results of our preliminary research, which helped to increase the level of delayed type hypersensitivity several times. 0ur earlier experiments indicated a paradoxical mechanism of bi-directional control of delayed type hypersensitivity reactions at various stages by antigens class IIMHC I-A-molecules, expressed on the surface of antigen-presenting cells. This fact must be strictly taken into account when designing schemes of immunotherapy. The purpose of the research is development of effective methods for experimental immunotherapy on the basis of delayed type hypersensitivity with the use of means and methods of its regulation. Materials and methods. The above-described phenomenon was used in the development of 2 methods experimental immunotherapy of carcinoma Lewis in mice BDF1. Delayed type hypersensitivity to laboratory antigen ovalbumin induced intratumoral and stimulated point based bi-directional development of reaction or aspirin in the induction stage (indirectly increasing the expression of I-A-anti-gens), or (overpowering her) nicotinamide in the effector phase of the reaction. Results. It is shown that delayed type hypersensitivity to ovalbumin induced intratumoral and stimulated by aspirin or nicotinamide, provides inhibition of tumor growth at 81.5 % and 86.5 % compared with the control, respectively. Conclusion. It is demonstrated 2 ways of experimental immunotherapy of tumors based on delayed type hypersensitivity, with strict regard to bi-directional control reaction by I-a-antigens. According to the literature in a number of agents capable of altering the expression of I-A-molecules, in addition to aspirin and nicotinamide are a well known, widely used in the clinic drugs. The irregularity of bi-directional development of delayed type hypersensitivity during their appointment subsequently leads not only to the weak therapeutic effect, but may cause increased tumor growth. Probably this is the reason for the observed unpredictability in immunotherapy. Obviously, to develop appropriate treatment regimens need careful, targeted intervention in the specific protective immune response in accordance with its molecular mechanism of regulation. In summary, the results presented here can be the basis for the testing of these methodological approaches in the clinic.

Introduction. Development of new models of a human disseminated skin melanoma of the with molecular-genetic targets for specific therapy increases productivity of the preclinical researches new the anti-melanoma drugs or their combinations in vitro and in vivo. Such opportunity is realized by adaptation in vivo of the original human pigmented skin melanoma cell line mel Cher and receiving subcutaneous (s. c.) xenograft under monitoring of transplant, morphological, molecular-genetic (V600E BRAF mutation) and chemotherapeutic (sensitivity for the inhibitor of BRAF kinases to a vemurafenib) characteristics. Objective: receiving from the cell line mel Cher s. c. xenogratft of the human pigmented skin melanoma with V600E BRAF mutation and sensitive to specific target therapy. Materials and methods. Human pigmented skin melanoma cell line mel Cher from the Collection of Russian Cancer Research Center and immunodeficient Balb/c nude female mice cultivated in Russian Cancer Research Center was used. Required characteristics are defined by multiple s. c. transplanting in vivo by methods of transplant biology, a light microscopy, molecular-genetics and the experimental chemotherapy. Sensitivity to a BRAF kinase inhibitor to a vemurafenib was estimated under monitoring of the tumor growth rate (Vt/V0) on indexes, adequate for patients: existence of the complete remission and possibility of recurrence. Results. When s. c. transplantation of 107 cell of mel Cher line cytological identical intertwined s. c. xenografts with a stable growth kinetics on 4-9 passages (a latent phase 8 days, exponential - to 14 days, stationary - to 24 days) and existence of a mutation of V600E BRAF have been recieved. Vemurafenib in a single dose of 75 mg/kg caused the complete remission during a 15-day course and within 7 days after its cancellation - with the subsequent recurrence. Conclusion: receiving from the cell line mel Cher s. c. xenogratft of a human pigmented melanoma of skin with a mutation of V600E BRAF and sensitive to specific target therapy is suitable for preclinical studying of the new anti-melanoma drugs specific for this target.

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. In connection with the prospect of the use of an analog of the hypothalamic hormone somatostatin synthesized by the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin Russian Cancer Research Center» and showed a high anti-tumor activity as a drug arises a need to establish an optimal technology of its receipt. In preliminary studies in a modelformulation for an analog of the hypothalamic hormone somatostatin selected liposome technological process of which has a series of specific steps comprising. Objective. Development of technology for obtaining liposomal formulation hypothalamic hormone somatostatin analogue. Materials and methods. Liposomes analog of the hypothalamic hormone somatostatin obtained by method Bengema in modification for hydrophobic substances. To reduce the diameter of the liposome are used methods extrusion, homogenization and ultrasonic. Analysis of the size of the liposomes was performed by correlation spectroscopy light scattering using nanosizer. The pH of the liposomal dispersion was determined by potentiometry. The quantitative content of the drug substance was determined by spectrophotometry using a standard sample with X (282 ± 3) nm and an alcoholic solution of empty liposomes as a reference solution. Amount of incorporated drug was calculated as the ratio of the concentration of drug in the liposome dispersion after filtration to the concentration of drug in the dispersion after preparation. Results and Conclusion. The hydrophobic nature of the substance causes an analog of the hypothalamic hormone somatostatin technological features of obtaining liposomal formulation. Since the step of forming a film of the lipid substance is dissolved in an organic solvent together with lipids, film is hydrated by a solution of cryoprotectant. Grinding liposomes an analog of the hypothalamic hormone somatostatin appropriate to be carried out using homogenization or extrusion methods, due to the high efficiency of these methods, the preservation stability of the liposomes and a high percentage of inclusion an analog of the hypothalamic hormone somatostatin, included in the liposomal bilayer. At the stage of separating the non-inclusion of substance an analog of the hypothalamic hormone somatostatin due to the insolubility of the substance in the water, you can use the filtering method, without the need for complicated procedures gel filtration, dialysis, etc. Furthermore the process of separating a substance not included can be combined with the sterilization of the liposome dispersion by selecting a particular filter material.

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.

The aim of this study was to examine the anticancer activity of rare earth elements complexes with antipirin. Materials and methods. We have studied the cytotixic activity of in vitro and antineoplastic activity in vivo of 28 iodides and perchlorates containing as a ligand antipirine. Results. Here we show, that non of tested compounds exert cytotoxic action on 5 human cancer cell lines of different histogenesis at a concentration of 100 ßM. However, we observe that two complexes of antipirine derivatives with iodides of gadolinium and neodymium possess anti-tumor activity in experiments with transplantable solid tumors. Conclusion. The data obtained indicate the feasibility of further studies of these two complexes on a larger number of mice, with changing doses and routes of administration. We also suggest the investigation of these compounds on ascites tumors.

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. BCR-ABL gene mutations are the main course of tyrosine kinase 1^st generation inhibitor (TKI-1) imatinib resistance in chronic myelogenous (CML) patients. Some of them are resistant both for imatinib and TKI-2. The nilotinib and dasatinib mutation spectra are not the same. To ensure a correct choice of TKI-2 for imatinib CML resistant patient treatment it is necessary to investigate frequency of BCR-ABL gene mutations. Aim. To evaluate BCR-ABL gene mutation frequency in imatinib resistant CML patients. Materials and methods. Peripheral blood of imatinib resistant CML patients were studied by means of direct PCR product Sanger sequencing in order to reveal BCR-ABL gene mutations. Results. BCR-ABL gene mutations were found in 31 % (n=262/846) imatinib resistant patients. Proportion of resistant mutations were 40,3 % for nilotinib and 21 % for dasatinib. Conclusion. More than a halve of BCR-ABL mutations resistant for imatinib were resistant either against nilotinib or dasatinib. Consequently, prior to replace imatinib for nilotinib or dasatinib it is necessary to perform BCR-ABL mutational analysis. If to prescribe TKI-2 blindly there may be high risk that nilotinib or dasatinib would be ineffective due to improper mutation in BCR-ABL gene.

Introduction. Bone marrow is one of the most common sites of involvement in follicular lymphoma (70 % of cases). Comparison of bone marrow lymphocyte subpopulations with the immunophenotype of primari tumor ant its microinvirement has not been done. Matherials and methods. Study has been done in 78 patients with follicular lymphoma. Diagnosis in each case was verified according to criteria of WHO classification (2008). Objective - to compare subpopulation composition of lymphocytes in bone marrow of patients with follicular lymphoma with immunophenotype of the primary tumor and the characteristics of the non-tumor microenvironment. Results. Histological detection of bone marrow involvement was associated with significant elevation of mature B-cells (CD19+, CD20+) as well as CD10+ lymphovytes in bone marrow aspiration biopsy specimens. In CD10-negative follicular lymphoma T-cell content (CD5+CD19-) was higher than in CD10+ cases (32.2 ± 7.6 % и 13.5 ± 3.4 %; р = 0.021). Oppositively, number of B-cells in bone marrow (CD19+CD5-, CD10+) was higher in CD10+ cases (p < 0.05). Intensive infiltration of primary tumor with T-cells was associated with lower number of bone marrow B-cells with specific follicular lymphoma phenotype - CD10+, CD19+CD23+ - (р = 0.001 and 0.048, correspondingly). Elevation of bone marrow lymphocytes was associated with higher number of mature T-cells in bone marrow - CD3, CD5, CD7, CD4, CD8. Number of B-cells (CD20+, CD22+) and (CD19+, CD19+CD5-), as well as B-cells expressing HLA-DR, CD23, CD10, CD38 was either equal or even higher in group of patients without lymphocytosis in bone marrow. In the gruop of normal level of oxyphilic normoblasts in bone marrow higher level of mature bone marrow B-cells (CD19, CD20, CD22) was noted. Conclusion. Our data confirm that verification of bone marrow involvement in follicular lymphoma should be immunological. T-cell microinvirement in primary tumor prevents of follicular lymphoma dissemination to bone marrow. Subpopulations of bone marrow lymphocytes are related to the immunophenotype of primary tumor (CD10). Bone marrow microenvironment (CD8+ lymphocytes) correlates with the absense of specific bone marrow involvement according to histology of bone marrow trephine biopsy.

Introduction. About 25 % of patients at diagnosis of follicular lymphoma have intoxication symptoms, which are probably induced by endogeneous cytokines. Production of several cytokines may be followed by temperature, lypogenesis disturbances, anorexia, body weight loss and so on. The pathogenesis of intoxication symptoms and its clinical significance are not completely understood in follicular lymphoma. Objective - to investigate the clinical and prognostic significance of presence of intoxication symptoms at the opening stages of follicular lymphomas. Matherials and methods. We’ve characterized a group of 74 follicular lymphoma patients, which had at time of diagnosis B-symptoms. Comparison group included 207 patients without intoxication symptoms. Results. In patients with B-symptoms we noted higher estimation according to ECOG scale, more fequent of haemoglobin diminution less than 120 g/l. It was more frequently noted elevation of LDH levels and diminution of serum total protein concentration. Presense of intoxication symptoms usually indicated the more turmor burden in patients: in 90,5 % advanced disease stages, in 75,7 % involvement of more than 4 nodal zones, in 81,1 % peripheral lymph nodes above diaphragm were involved, in 35,1 % mediastinal lymph nodes, and in 74,3 % of patients retroperitoneal lymph nodes were involved. More frequently in patients with intoxication symptoms more than one extranodal zone was ivolved, especially spleen and hepar. According to FLIPI 64,2 % of follicular lymphoma patients with B-symptoms were of high risk group, and they had worse quality of treatment response: in 25 % of cases progression during or soon after treatment was noted. Intoxication symptoms negatively influensed on overall survival, but not on the duration of treatment response. Conclusion. Intoxication symptoms significantly affects overall survival and survival without progression in follicular lymphoma patients. Key words: follicular lymphoma, intoxication symptom

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.

Objecive. The investigation is devoted to study subpopulation structure of lymphocytes from peripheral blood of patients, suffering from breast cancer. Materials and methods. Peripheral blood of 70 patients with breast cancer and 39 healthy women was analyzed using the flow cytometry method with monoclonal antibodies to CD3, CD4, CD8, CD16, CD56, CD19, CD45 antigens. Results. Statistically significant disturbance of linear structure of lymphocytes (T-cells CD45+/CD3+/CD19-; B-cells CD45+/CD3-/ CD19+; NK-cells CD45+CD3-CD16+56+) detected only in the analysis of individual immunograms, but not in analysis of whole group of breast cancer patients. Conclusion. Based on analysis of frequence of occurrence of disturbances of cancer breast patients with low values of ratio CD4/CD8, it was detected 4 different variants of disturbance.

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.

Bakground. Monoclonal antibodies are reliable and convenient tool for the diagnosis of human pathologies. Most often they are used as conjugates with fluorescent or other labels. The classical approach of creating such conjugates reduces chemical reactions using monoclonal antibodies protein base. However, for a number of manufacturing monoclonal antibodies conjugate followed by embedding tags in the antigen binding site, which leads to reduction or complete loss of specific activity of the conjugate. The way out of this situation could be the synthesis of fluorescent conjugates, methods of carbohydrate chemistry through spatially distant from the active site of the antibody oligosaccharides. The purpose of the study - to show the fundamental possibility of chemical modification of the oligosaccharides monoclonal antibodies ICO series and get to their base fluorescent conjugates. Materials and methods. We used monoclonal antibodies panel ICO series of high purity. Oligosaccharides monoclonal antibodies oxidized to aldehyde groups, is reacted with a hydrazine derivative of biotin and streptavidin-conjugated flyuoristsiinom. The resulting complex was used for the direct reaction immunofluorescence. Results. All modified monoclonal antibodies retain binding specificity to target cells inherent to native antibodies. Conclusions. This may be an alternative method for conjugating a fluorescent label with monoclonal antibodies to protein synthesis methods which lead to loss of activity of the conjugate.