СHANGES OF TLR GENE EXPRESSION IN CERVICAL EPITHELIUM FROM THE PATIENTS WITH UROGENITAL INFLAMMATORY DISEASES

Toll-like receptors (TLR) are involved into innate immune recognition of microorganisms, including pathogenic bacteria. The aim of this work is to assess relative levels of TLR2 and TLR9 expression in cervical epithelial cells of women with inflammatory diseases of pelvic organs. The total group of patients consisted of 47 persons, including 20 women with urogenital infections, and 27 women comprised a control group. Using real-time PCR, we identified the opportunistic pathogens and gene expression levels of TLR2, TLR9 in the cervix epithelial cells. It was shown that expression of TLR9 in the group with urogenital infections was 13.7-fold higher than in control group. We have revealed that a significant increase of TLR9 expression in the mucosal epithelium from cervical canal correlated with detection of infectious pathogens in the samples

ABOUT ANTI-RECESSIONARY STRATEGY OF REGIONAL SPONTANEOUS SOCIAL AND ECONOMIC SYSTEMS

There are the results of the research, directed on revealing of conditions of steady regional development and specification on this basis of the general principles of formation of regional anti-recessionary programs, presented. The synergetic analysis and social and economic modeling were as a methodical basis of the presented work of steel

Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma

The disialoganglioside GD2 is a well-established target antigen for passive immunotherapy in neuroblastoma (NB). Despite the recent success of passive immunotherapy with the anti-GD2 antibody ch14.18 and cytokines, treatment of high-risk NB remains challenging. We expanded the approach of GD2-specific, antibody-based immunotherapy to an application of a GD2-specific natural killer (NK) cell line, NK-92-scFv(ch14.18)-zeta. NK-92-scFv(ch14.18)-zeta is genetically engineered to express a GD2-specific chimeric antigen receptor generated from ch14.18. Here, we show that chimeric receptor expression enables NK-92-scFv(ch14.18)-zeta to effectively lyse GD2(+) NB cells also including partially or multidrug-resistant lines. Our data suggest that recognition of GD2 by the chimeric receptor is the primary mechanism involved in NK-92-scFv(ch14.18)-zeta-mediated lysis and is independent of activating NK cell receptor/ligand interactions. Furthermore, we demonstrate that NK-92-scFv(ch14.18)-zeta is able to mediate a significant anti-tumor response in vivo in a drug-resistant GD2(+) NB xenograft mouse model. NK-92-scFv(ch14.18)-zeta is an NB-specific NK cell line that has potential for future clinical development due to its high stability and activity toward GD2(+) NB cell lines

Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Combining passive immunotherapy with an antibody to the disialoganglioside GD2 (ch14.18/SP2/0) and cytokines with 13-cis-retinoic acid for post-myeloablative maintenance therapy increased survival in high-risk NB, but the overall prognosis for these children is still in need of improvement. Fenretinide (4-HPR) is a synthetic retinoid that has shown clinical activity in recurrent NB and is cytotoxic to a variety of cancer cells, in part via the accumulation of dihydroceramides, which are precursors of GD2. We investigated the effect of 4-HPR on CHO-derived, ch14.18-mediated anti-NB effector functions, complement-dependent cytotoxicity (CDC), and antibody-dependent and antibody-independent cellular cytotoxicity (ADCC and AICC, respectively). Here, we demonstrate for the first time that pretreatment of fenretinide-resistant NB cells with 4-HPR significantly enhanced ch14.18/CHO-mediated CDC and ADCC and AICC by both human natural killer cells and peripheral blood mononuclear cells. Treatment with 4-HPR increased GD2 and death receptor (DR) expression in resistant NB cells and induced an enhanced granzyme B and perforin production by effector cells. Blocking of ganglioside synthesis with a glucosylceramide synthase inhibitor abrogated the increased ADCC response but had no effect on the AICC, indicating that GD2 induced by 4-HPR mediates the sensitization of NB cells for ADCC. We also showed that 4-HPR induced increased GD2 and DR expression in a resistant NB xenograft model that was associated with an increased ADCC and AICC response using explanted tumor target cells from 4-HPR-treated mice. In summary, these findings provide an important baseline for the combination of 4-HPR and passive immunotherapy with ch14.18/CHO in future clinical trials for high-risk NB patients

Conceptual approach to innovational development of the university through the prism of a faculty

В статье обоснован подход к инновационному развитию университета через реорганизацию деятельности факультета как основной структурной единице вуза. Рассмотрены новые формы и условия организации партнерства университета и бизнеса по основным видам деятельности. Сформулированы концептуальные идеи и методические решения, направленные на сближение университетского обучения с кадровыми потребностями промышленности, а также вузовской науки с проблемами технологического развития предприятий.The article specifies the approach to innovational development of the university by reorganizing the faculty activity as it is the main structural unit of any educational establishment. New forms and conditions to organize partnership of university and business along the main lines of activity are considered. Conceptual ideas and methodical decisions aimed at bringing university education closer to industrial personnel requirements and university science closer to the issues of technological development of enterprises are formulated

Conceptual approach to innovational development of the university through the prism of a faculty

В статье обоснован подход к инновационному развитию университета через реорганизацию деятельности факультета как основной структурной единице вуза. Рассмотрены новые формы и условия организации партнерства университета и бизнеса по основным видам деятельности. Сформулированы концептуальные идеи и методические решения, направленные на сближение университетского обучения с кадровыми потребностями промышленности, а также вузовской науки с проблемами технологического развития предприятий.The article specifies the approach to innovational development of the university by reorganizing the faculty activity as it is the main structural unit of any educational establishment. New forms and conditions to organize partnership of university and business along the main lines of activity are considered. Conceptual ideas and methodical decisions aimed at bringing university education closer to industrial personnel requirements and university science closer to the issues of technological development of enterprises are formulated