16 research outputs found

    Characterization and Study of Iron(III)-Released From Alginate/Zeolite/Fe Composite

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    Alginate is an organic polymer that is isolated from brown algae and bacteria, while the zeolite is an aluminosilicate mineral sample. The purpose of this study was to synthesize composite alginate / zeolite / Fe, characterize composite alginate / zeolite / Fe, and assessing the release properties of Fe (III) of the composite alginate / zeolite / Fe. Characterization of the composite is done by observing the color composite macroscopically, and observing the pattern of distribution of zeolite particles in composites using SEM (Scanning Electron Microscope). As for assessing the release of Fe (III) of the composite system made by soaking the composite in a solution of citric acid 0,33M for nine hours. Components of Fe (III) were dissolved in acid systems were analyzed using UV-Vis spectrophotometer.The results showed that the composite alginate / zeolite / Fe have colors that are significantly dependent on the component ratio of alginate and zeolitnya. SEM analysis provides information that the zeolites distributed evenly on alginate-Fe phase. The release profile of Fe (III) of the composite alginate / zeolite / Fe weight variation component alginate produced three mechanisms to increase and decrease the rate of release of Fe (III). While the release profile of Fe (III) of the composite alginate / zeolite / Fe by weight of the zeolite component generates two mechanisms that increase and decrease the rate of release of Fe (III)

    OX40L Inhibition suppresses KLH-driven immune responses in healthy volunteers: a randomized controlled trial demonstrating proof-of-pharmacology for KY1005

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    The safety, tolerability, immunogenicity, and pharmacokinetic (PK) profile of an anti-OX40L monoclonal antibody (KY1005, currently amlitelimab) were evaluated. Pharmacodynamic (PD) effects were explored using keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT) immunizations. Sixty-four healthy male subjects (26.5 +/- 6.0 years) were randomized to single doses of 0.006, 0.018, or 0.05 mg/kg, or multiple doses of 0.15, 0.45, 1.35, 4, or 12 mg/kg KY1005, or placebo (6:2). Serum KY1005 concentrations were measured. Antibody responses upon KLH and TT immunizations and skin response upon intradermal KLH administration were performed. PD data were analyzed using repeated measures analysis of covariances (ANCOVAs) and post hoc exposure-response modeling. No serious adverse events occurred and all adverse events were temporary and of mild or moderate severity. A nonlinear increase in mean serum KY1005 concentrations was observed (median time to maximum concentration (T-max) similar to 4 hours, geometric mean terminal half-life (t1/2) similar to 24 days). Cutaneous blood perfusion (estimated difference (ED) -13.4 arbitrary unit (AU), 95% confidence interval (CI) -23.0 AU to -3.8 AU) and erythema quantified as average redness (ED -0.23 AU, 95% CI -0.35 AU to -0.11 AU) decreased after KY1005 treatment at doses of 0.45 mg/kg and above. Exposure-response analysis displayed a statistically significant treatment effect on anti-KLH antibody titers (IgG maximum effect (E-max) -0.58 AU, 95% CI -1.10 AU to -0.06 AU) and skin response (erythema E-max -0.20 AU, 95% CI -0.29 AU to -0.11 AU). Administration of KY1005 demonstrated an acceptable safety and tolerability profile and PK analyses displayed a nonlinear profile of KY1005. Despite the observed variability, skin challenge response after KY1005 treatment indicated pharmacological activity of KY1005. Therefore, KY1005 shows potential as a novel pharmacological treatment in immune-mediated disorders.Drug Delivery Technolog

    IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

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    <p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p
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