Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease.We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment.The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.
Purpose: to study the composition and content of proinflammatory cytokines, chemoattractant mediators, vascular growth factors in blood serum (SB) and lacrimal fluid (LF) in patients with KPHR. Materials and methods. A total of 106 patients with postinflammatory corneal spots and turbid transplant were examined. The control group consisted of 20 practically healthy donors. Cytokines: IL-2, IL-18, MCP-1 / CCL2, MIP-1β / CCL4, RANTES / CCL5, Eotaxin / CCL11, IP-10 / CXCL10, SDF-1α / CXCL12, VEGF-A, VEGF-D, PIGF-1, HGF / SF. Results. The study of the levels of systemic production of immunomodiators in the groups of patients revealed significant changes in the concentrations of MCP-1 / CCL2, RANTES / CCL5, Eotaxin / CCL11, IP-10 / CXCL10, SDF-1α / CXCL12, as well as angiogenic factors VEGF-A and HGF / SF compared to controls. In the group of primary KPHR in the presence of vascularization, an increase in the production of IL-18, RANTES / CCL5, Eotaxin / CCL11 was observed. 1 / CCL2, VEGF-A, PIGF-1 and HGF / SF (p<0.05). Graft vascularization in repeated (2 and higher) corneal transplants (group II) was associated with significant increases in SC IL-2, PIGF-1, and HGF/SF (p<0.05). Analysis of cytokine content in the LF of patients with repeated KPHR and vascularized graft showed a statistically significant increase in IP-10 / CXCL10, MIP-1β / CCL4, SDF-1α / CXCL12, and VEGF-A. A retrospective analysis of the content of cytokines in the SB, depending on the outcomes of keratoplasty, showed a significant increase in the concentration of 7 out of 11 studied cytokines in patients of the KPHR group with various complications in the postoperative period, including those with a developed graft rejection reaction. Conclusions. It has been shown that the formation of vascularized corneal spots is associated with a significant increase in systemic production of IL-18, an increase in the concentration of chemokines with angiogenic activity RANTES / CCL5 and Eotaxin / CCL11 in the blood of patients with KPHR. During vascularization of the graft with repeated KPHR in the SB and LF, a unidirectional increase in the levels of IL-2, MCP-1 / CCL2, growth of VEGF-A and HGF / SF is observed. A factor in the development of graft rejection is the initially high concentrations in the SB of patients with KPHR IL-2, IL-18, chemokines RANTES / CCL5, MIP1β / CCL4, VEGF-A, PLGF, HGF / SF (p<0.05), indicating about the activation of pathological angiogenesis against the background of inflammation and an activated adaptive immune response.
This work are devoted our experience with photodynamic therapy (PDT) with «Photosens»for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with «Photosens» (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser («Biospec», Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals.At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with «Photosens». 3Dmode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area.Photodynamic therapy with «Photosens» can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis. Downloaded From: http://proceedings.spiedigitallibrary.org/ on 06/24/2016 Terms of Use: http://spiedigitallibrary.org/ss/TermsOfUse.aspx SPIE-OSA/ Vol. 6632 663212-5 Downloaded From: http://proceedings.spiedigitallibrary.org/ on 06/24/2016 Terms of Use: http://spiedigitallibrary.org/ss/TermsOfUse.aspx
Background: The efficiency of treatment and prevention of retinopathy of prematurity (ROP) has improved. In addition, the development of a disease screening system to reduce the incidence of disability resulting from this pathology is important. Aim: This study aimed to determine new laboratory criteria for screening and predicting the ROP course through in-depth investigation of the molecules participating in the pathogenesis of ROP. Material and methods: A comprehensive clinical and experimental study was performed to assess the local and systemic levels of 49 cytokines with various biological effects, four monoamines, and angiotensin-II (AT-II) at different stages of the pathological process. In the clinical analysis, 165 preterm infants at risk of ROP development were examined. For the experimental part, the disease course of 145 Wistar infant rats in the developed model of experimental ROP was analyzed. Results: Among cytokines, the seven most promising potential laboratory markers of ROP development and adverse course were as follows: MCP1 95 pg/mL, IGF-II 140 pg/mL, TGFbeta1 18000 pg/mL, and IGF-I 24 pg/mL in the blood serum of preterm infants before the first signs of ROP and VEGF-A 108 pg/mL, TGF-beta2 100 pg/mL, and PDGF-BB 1800 pg/mL at ROP manifestation. Among monoamines, serotonin (17.0 pg/mL) and L-DOPA indicated their prognostic value in the clinical and experimental settings. Moreover, a possible prognostic role of AT-II was found. Conclusion: In this study, methods to improve the ROP screening system are outlined, but further work is necessary to assess the possibility of implementing the results in clinical practice
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