The Nitric Oxide Pathway Provides Innate Antiviral Protection in Conjunction with the Type I Interferon Pathway in Fibroblasts

The innate host response to virus infection is largely dominated by the production of type I interferon and interferon stimulated genes. In particular, fibroblasts respond robustly to viral infection and to recognition of viral signatures such as dsRNA with the rapid production of type I interferon; subsequently, fibroblasts are a key cell type in antiviral protection. We recently found, however, that primary fibroblasts deficient for the production of interferon, interferon stimulated genes, and other cytokines and chemokines mount a robust antiviral response against both DNA and RNA viruses following stimulation with dsRNA. Nitric oxide is a chemical compound with pleiotropic functions; its production by phagocytes in response to interferon-γ is associated with antimicrobial activity. Here we show that in response to dsRNA, nitric oxide is rapidly produced in primary fibroblasts. In the presence of an intact interferon system, nitric oxide plays a minor but significant role in antiviral protection. However, in the absence of an interferon system, nitric oxide is critical for the protection against DNA viruses. In primary fibroblasts, NF-κB and interferon regulatory factor 1 participate in the induction of inducible nitric oxide synthase expression, which subsequently produces nitric oxide. As large DNA viruses encode multiple and diverse immune modulators to disable the interferon system, it appears that the nitric oxide pathway serves as a secondary strategy to protect the host against viral infection in key cell types, such as fibroblasts, that largely rely on the type I interferon system for antiviral protection

Морфологические и иммунологические особенности стимулированного Г-КСФ аутологичного и аллогенного костного мозга, применяемого для трансплантации в клинической онкологии

58 samples of stimulated bone marrow (39 – oncology patients, 19 healthy donors) obtained for transplantation in cancer patients were analysed and compared to control group (13 bone marrow samples from women with mastopathies). It was noted the significant increase of blast cells in cancer patients compared to donors and control group (p<0.037). Neutrophyl maturation index was higher in stimulated bone marrow (p<0.001) and decrease of lymphocyte percentage (p<0.008) compared to control group: elevation of CD3+ and CD8+ lymphocytes (p<0.0001) as well as decrease of NK-cells CD56+ CD3-  and/ or CD16+ CD3-).При анализе 58 образцов стимулированного костного мозга (39 онкологических больных и 19 здоровых доноров), полученного для трансплантации онкологическим больным, и сопоставлении основных показателей с исторической нормой и 13 образцами костного мозга больных контрольной группы (мастопатия) выявлен ряд особенностей стимулированного костного мозга. Показано достоверное увеличение количества бластных клеток костного мозга у онкологических больных в сравнении с донорами и группой контроля (р<0,037). В образцах стимулированного костного мозга (онкологические больные и доноры) выявлен более высокий индекс созревания нейтрофилов (р<0,001) и снижение процента зрелых лимфоцитов (p<0,008) в сравнении с контрольной группой. Среди лимфоцитарных популяций под влиянием ГКСФ как у онкологических больных, так и у доноров отмечено нарастание суммарного числа зрелых CD3+ Т-клеток и CD8+ Т-киллеров (p<0,0001), а также снижение количества субпопуляций NK-клеток CD56+ CD3–  и/или CD16+ CD3– (р<0,006) в сравнении с группой контроля

Lipegfilgrastim in patients with chemotherapy-induced neutropenia

The development of dose-limiting toxicities, including myelotoxicity, can significantly limit cytostatic therapy of malignant tumors. Neutropenia associated with high risk of febrile neutropenia (FN) and infectious complications that may interfere with therapy intensity and significantly increases the cost of diagnosis and treatment. With the development of recombinant forms of human granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, therapy of iatrogenic neutropenia has undergone significant changes. The use of G-CSF (filgrastim, lenograstim, pegfilgrastim) reduces FN incidence in patients receiving myelosuppressive chemotherapy. Until recently, the only original preparation of G-CSF with prolonged action was pegfilgrastim. Lipegfilgrastim (Lonquex, Teva) is a new highly effective long-acting pegylated G-CSF, which has been approved by European Medicines Agency experts for FN prevention in patients receiving chemotherapy. This review summarizes the characteristics of chemical structure, pharmacokinetics, safety and efficacy of lipegfilgrastim

Autologous hematopoietic stem cell transplantation in remission consolidation of acute myeloid leukemia with initially unfavorable prognostic factors

Introduction. The role of autologous hematopoietic stem cell transplantation (autoHSCT) in adult patients with acute myeloid leukemia (AML) with poor prognosis factors is not completely defined.Purpose: to present the results of a multicenter prospective study of autoHSCT efficacy in AML patients with initially unfavorable prognostic factors.Materials and methods. From 2007 to 2014, 42 patients with primary AML with one or more poor prognosis factors were included in the study. AutoHSCT was performed in 16 patients (9 women) aged 20–57 years (median 38 years) without available compatible allogeneic (related or unrelated) donor. In order to identify the role of different prognostic factors the long-term results were analyzed.Results. With a median follow up of 49 months (range 5–86 months) 5-years overall survival, event-free survival and relapse-free survival were 47, 47 and 51 %, respectively. Rate of mortality associated with transplantation in 100 days and 2 years after autoHSCT reached 0 and 6 %, respectively. AML relapse was observed in 44 % of patients. Favorable prognostic influence of total body irradiation in conditioning regimens on the overall survival has been identified (р = 0.045).Conclusion. AutoHSCT in AML patients with initially poor prognosis factors has a long-term anti-tumor effect. In the absence of a fully compatible allogeneic donor, autoHSCT may be considered as an alternative treatment