For clinical trials of therapeutic monoclonal antibodies (mAbs) to be successful, their efficacy needs to be adequately evaluated in preclinical experiments. However, in many cases it is difficult to evaluate the candidate mAbs using animal disease models because of lower cross-reactivity to the orthologous target molecules. In this study we have established a novel humanized Castleman's disease mouse model, in which the endogenous interleukin-6 receptor gene is successfully replaced by human IL6R, and human IL6 is overexpressed. We have also demonstrated the therapeutic effects of an antibody that neutralizes human IL6R, tocilizumab, on the symptoms in this mouse model. Plasma levels of human soluble IL6R and human IL6 were elevated after 4-week treatment of tocilizumab in this mouse model similarly to the result previously reported in patients treated with tocilizumab. Our mouse model provides us with a novel means of evaluating the in vivo efficacy of human IL6R-specific therapeutic agents.
Concentration and heterogeneity of CEA-like substance in gastric juice were studied using radioimmunoassay. Statistically significant increase of CEA-like substance in gastric juice was found in advanced atrophic gastritis (P less than 0.01), early gastric cancer (P less than 0.05) and advanced gastric cancer (P less than 0.01) as compared with normal subjects. In cases with atrophic gastritis with a high degree of intestinal metaplasia, the concentrations above 300 microgram/dl were noticed. The results indicate that increased concentrations of CEA-like substance in gastric secretions may strongly suggest the presence of a marked intestinal metaplasia and/or cancerous changes of gastric mucosae, including the early cancer. The distribution of CEA activity in gel filtration fractions of gastric juice was compared using kits of two different radioimmunoassay systems. The patterns of CEA activities were different between the two different kits used, but the main peaks were located in the fractions with the molecular weight of 20x10(4) daltons corresponding to that of serum CEA. It is considered, however, that the CEA-like substance in gastric juice specimens may be more or less heterogenous when any of the methods is used.
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