[Modern methods of immunotherapy for metastatic melanoma].

Over the past five years drug therapy of disseminated melanoma took a giant step forward. In clinical practice there are several fundamentally new classes of drugs: inhibitors of the individual components of MAPK-signaling pathway and modulators of a work of immunological synapse (inhibitor of CTLA4 ipilimumab, inhibitors of PD1 nivolyumab and pem- brolizumab).Here are presented features of the mechanism of action of new immunotherapeutic agents, the review of results of their clinical use, the description of the main treatment- related adverse events. The interaction of new approaches with other methods of systemic treatment and an algorithm for per- sonalized use of these methods is regarded. Modern means of therapy allow achieving expressed and long effects giving pos- sibility in some cases to cure a patient. Rational sequential and combined use of different variants of systemic treatment for disseminated melanoma, appropriate diagnosis and treatment of treatment-related adverse events can significantly increase the length and quality of life of patients.

Polymorphisms of the anti-inflammatory IL-10 gene associated with malignancy in female reproductive system.

Association of three polymorphisms (1082G/A, 819C/T, and 592C/A) of the promotor region of the anti-inflammatory IL-10 gene with malignancy of female reproductive organs was revealed by SNP (single nucleotide polymorphism) method in ethnic groups of Adygei Republic. Breast cancer, cervical cancer, and cancer of the uterine corpus are associated with allele 592A (р=0.042) in Circassians and with polymorphism 819T in Russians (р=0.046). Irrespective of the ethnicity, allele 819T was signifi cantly more often (р<0.05) detected in prevalent forms of breast cancer involving regional lymph nodes. 1082G polymorphism is associated with low-differentiated adenocarcinoma. In women of Adygei Republic, ATA/GCA gaplotypes are associated with high risk factors for breast cancer.

[Changes of oxidative and antioxidative properties of blood under the action of perftoran in patients with acute sensorineural loss of hearing].

The authors report the results of examination and treatment of 100 patients presenting with acute sensorineural loss of hearing using audiological and biochemical methods. General oxidative (GO) and antioxidative (GAO) activities, malonic dialdehyde (MDA) and catalase (C) levels in blood plasma were measured in 60 patients given original perftoran-based therapy and in 40 patients receiving traditional treatment. Management of acute sensorineural loss of hearing with the use of perftoran proved efficacious in 95% of the cases compared with 80% using traditional therapy. Plasma oxidative activity decreased and antioxidative activity increased within 1 week after infusion of perftoran. These changes correlated with positive functional outcomes of the treatment.

Mechanisms of regulation of transcription factor HIF under hypoxia.

The importance of transcription factor HIF in cellular response to hypoxia and various regulatory levels determining its functioning within cells are considered. Special attention is paid to important links of the hypoxia-triggered HIF-mediated mechanism. The review contains retrospective analysis of the search for cellular primary oxygen sensors and their interactions with HIF. It also deals with the interrelation of HIF-mediated and other hypoxia-activated mechanisms and outlines importance of HIF subunits in the cell.

Resistance of rat bone marrow mesenchymal stromal precursor cells to anoxia in vitro.

We studied the effect of significantly reduced oxygen content (0% O(2)in gaseous phase) in culture medium on rat bone marrow mesenchymal stromal precursor cells. The cells retained their morphology and expression of characteristic markers during several days under these conditions; they were viable, proliferated, and some cultured cells were even capable of realizing the initial stages of osteogenic and adipogenic differentiation. Further culturing of precursor cells under conditions of anoxia led to activation of apoptosis in cultures and to progressive necrosis.

[Mesenchymal stromal progenitor cells: general characteristics and functional state in low oxygen tension].

The promising use of multipotent mesenchymal stromal cells (MSC) in regenerative technologies accounts for necessity of detailed study and analysis of their physiology. Along with searching for MSC specific immunophenotype markers and factors that affect MSC heterogeneity, proliferative activity, self-renewal capacity and differentiation potential, progenitor, the cells functioning in low oxygen tension present one the open-ended problems. The specific response of progenitor cells to hypoxia seems to depend on many factors including their commitment and differentiation status, tissue type as well as the nature of the hypoxic impact. Interestingly, it was shown that low oxygen tension can be used as a factor regulating MSC proliferation, viability and differentiation.

[Heterogeneity of stromal precursor cells isolated from rat bone marrow].

Bone marrow stroma contains mesenchymal stem cells (MSC) which are precursor for at least mesenchyma-derived cells. Recent investigations revealed a lot of questions concerning MSC biology that should be further refined. The aim of this study was the comparative analysis of rat bone marrow stroma cells cultures. Mesenchymal precursor cells isolated from rat bone marrow were passed up to 50 times. Comparative morphological and immunophenotypical analysis of these cultures was carried out as well as their ability to osteogenic differentiation was studied. The isolated cultures contained morphologically different types of cells and thus showed a high heterogenity level. Morphology of these cell types was described. The heterogeneity level was reported to decrease over time. It was found out that subcultures isolated from different rats shared the same immunophenotype characteristics (CD90+, CD44+, CD54+, CD 106+, CD45-, CD11b-), but differed in their morphology as well as in ability to osteogenic differentiation. Thus MSC identification requires more specific marker and functional tests to be used.

Effect of hypoxia on stromal precursors from rat bone marrow at the early stage of culturing.

We studied the effect of hypoxia on stromal precursors from rat bone marrow. Under hypoxic conditions the cultures were characterized by low heterogeneity, the percent of large spread morphologically different cells decreased. Hypoxia increased proliferative activity of cells, had no adverse effect, and decreased the percent of cells expressing hemopoietic markers.

A new quasi-one-dimensional niobium oxychloride cluster compound Cs2Ti4Nb6Cl18O6: structural effects of ligand combination.

The new niobium oxychloride cluster compound, Cs2Ti4Nb6Cl18O6, was obtained by solid-state synthesis techniques in the course of our systematic investigation of metal oxychloride systems aimed at the preparation of low-dimensional cluster compounds. Cs2Ti4Nb6Cl18O6 crystallizes in the trigonal system, with unit cell parameters a= 11.1903(7), c = 15.600(2) A, space group P3bar1c, Z = 2. Its crystal structure was determined by single-crystal X-ray diffraction techniques. The full-matrix least-squares refinement against F(2) converged to R(1) = 0.048 (F(o) > 4sigma(F(o))), wR(2) = 0.069 (all data). The structure is based on an octahedral cluster unit (Nb6Cl(i)6O(i)6)Cl(a)6 in which the six edge-bridging oxide ligands are arranged in two sets of three on opposite sides of the Nb6 octahedron. Ti(3+) ions link the clusters through O(i) and Cl(a) ligands to form linear chains running along the c axis. The location of titanium ions correlates with the arrangement of oxide ligands around the Nb6 metal core. The chains interact with each other through additional Ti(3+) and Cs(+) ions. Interchain interactions are significantly weaker than intrachain interactions, resulting in a quasi-one-dimensional character of the overall structure.

Structural studies of indium and thallium insertion into the framework of the cluster compound Ti2Nb6Cl14O4.

We have investigated the possibility of altering the electronic configuration of the niobium oxochloride cluster compound Ti2Nb6Cl14O4 (I) by doping this material with monovalent cations that can fit into cavities present in its cluster framework. The doping of I with In+ and Tl+ ions resulted in the formation of MxTi2Nb6Cl14-xO4+x (M = In, x = 0.10, 0.20, 0.27; M = Tl, x = 0.10, 0.20) in which the M+ ions partially occupy these cavities. The crystal structure analysis indicated that the additional charge provided by M+ ions is compensated by substitution of chlorine by oxygen, which leads to the cluster electronic configuration being intact. Crystal data: In0.272Ti2Nb6Cl13.728O4.272, space group C2/c (No. 15), a = 12.679(2) A, b = 14.567(2) A, c = 12.632(3) A, beta = 95.26(2) degrees, Z = 4; Tl0.196Ti2Nb6Cl13.804O4.196, space group C2/c (no. 15), a = 12.732(1) A, b = 14.607(2) A, c = 12.662(2) A, beta = 95.28(1) degrees, Z = 4.

[Effect of the antioxidant dibunol on hemostatic parameters in patients with non-healing ulcers]. / Vliianie antioksidanta dibunola na otdel'nye pokazateli gemostaza y bol'nykh iazvennoi bolezn'iu s dlitel'no nerubtsuiushchimisia iazvami.

Dibunol, antioxidant drug, made in Russia was given to 42 patients aged 18-59 with unhealing ulcer 0.64 c 0.06 cm in diameter treated previously without effect for 99.74 +/- 30.6 days. Scarring came in 99.6% of cases on treatment day 15.9 +/- 1.23 without appearance of a rough scar. Recurrences occurred 6 months later in 7.1% of patients. Dibunol did not suppress antioxidant system of the serum, lowered serum level of lipid hydroperoxides, stimulated activity of natural antioxidants in the mucous gastroduodenal zone, had no effect on hormonal homeostasis and blood coagulation.

[Glycoproteins from the African swine fever virus]. / Glikoproteiny virusa afrikanskoi chumy svinei.

The composition of African swine fever virus (ASFV) glycoproteins was studied. Isolate-specific major gp 110-140 was identified by radioimmunoprecipitation in lysate of porcine bone marrow cells infected with hemadsorbing virus strains. Carbohydrates constitute about 50% of the total mass of gp 110-140. A quantitative method is proposed for identification of the serologic relationships between ASFV hemadsorbing strains. A possible role of ASFV glycoprotein carbohydrates in the hemadsorption, virulence, and immunogenicity is discussed.