Vaccinated animals produced high-titer antibodies that neutralize

Vaccinated animals produced high-titer antibodies that neutralized all four serotypes of dengue viruses in vitro. The ability of the vaccine to induce rapid, as well as sustained, protective immune responses was examined with two separate live-virus challenges administered at 4 and 24 weeks after the final vaccination. For both of these virus challenge studies, significant protection from viremia was demonstrated for all four dengue virus serotypes in vaccinated

animals. Viremia from dengue-1 and dengue-3 challenges was completely blocked, whereas viremia from dengue-2 and dengue-4 was significantly reduced, as well as delayed, compared to that of control-vaccinated animals. These results demonstrate NVP-BGJ398 that the tetravalent dengue vaccine formulation provides significant protection in rhesus macaques against challenge with all four dengue virus serotypes.”
“Introduction: Our objective was to define the relationships RNA Synthesis inhibitor between tumor uptake of [In-111]-IGF-1 and [In-111]-IGF-1 (E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression

on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, Ag1024.

Methods: The tumor and normal tissue uptake of [In-111]-IGF-1 and [In-111]-IGF-1

(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5 x 10(4), 1.4 x 10(4),4.0 x 10(4) and 1.0 x 10(5) IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 mu g) or IGFBP-3 (2 or 25 mu g) was studied. The relationship between tumor uptake of [In-111]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [In-111]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 mu g/ml) in the absence/presence of IGFBP-3 (1 mu g/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 mu g/ml), was determined.

Results: Sinomenine [In-111]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9 +/- 0.1 vs. 1.0 +/- 0.1 % 1D/g). Co-injection of IGBP-3 decreased kidney uptake of [In-111]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r(2)=0.99) between the tumor uptake of In-111-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4 +/- 0.05 % 1D/g for H2N to 2.5 +/- 0.5 % 1D/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT.

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