Overexpression and altered glycosylation of MUC1 in malignant mesothelioma

Current interest in the MUC1/EMA mucin relates to its role in malignancy, and its potential as a therapeutic target. MUC1/EMA expression has been observed in the majority of epithelioid mesotheliomas. However, little is known of the characteristics of MUC1/EMA in mesothelioma. Herein, we studied the cell surface and soluble expression of the MUC1/EMA glycoprotein, and determined the mRNA and genomic expression profiles in mesothelioma. We found that the anti-MUC1 antibody, E29, was the most diagnostically useful of seven antibody clones examined with a sensitivity of 84% (16 out of 19 cases) and no false positive results. MUC1 mRNA expression was significantly higher in mesothelioma samples than in benign mesothelial cells. No amplification of the MUC1 gene was observed by FISH. Seven of 9 mesothelioma samples expressed MUC1-secreted mRNA isoform in addition to the archetypal MUC1/transmembrane form. CA15.3 (soluble MUC1) levels were significantly higher in the serum of mesothelioma patients than in healthy controls but were not significantly different to levels in patients with benign asbestos-related disease. CA15-3 in effusions could differentiate malignant from benign effusions but were not specific for mesothelioma. Thus, as in other cancers, alterations in MUC1 biology occur in mesothelioma and these results suggest that specific MUC1 characteristics may be useful for mesothelioma diagnosis and should also be investigated as a potential therapeutic target

Toxicity of environmental lead and the influence of intestinal absorption in children

© Freund Publishing HouseExposure to metals, particularly lead, remains a widespread issue that is associated with historical and current industrial practices. Whereas the toxic properties of metals are well described, exposure to metals per se is only one of many factors contributing to elevated blood metal concentrations and their consequent health effects in humans. The absorbed dose of metal is affected by geochemical, biochemical, and physiological parameters that influence the rate and extent of absorption. In children, the interplay among these factors can be of critical importance, especially when biochemical and physiological processes might not have matured to their normal adult status. Such immaturity represents an elevated risk to metal-exposed children because they might be more susceptible to enhanced absorption, especially via the oral route. This review brings together the more recent findings on the physiological mechanisms of metal absorption, especially lead, and examines several models that can be useful in assessing the potential for metal uptake in children.L.M. Heath, K.L. Soole, M. McLaughlin, G.T.A. McEwan, J.W. Edwardshttp://www.scopus.com/scopus/record/display.url?eid=2-s2.0-1242345171&view=basic&origin=inward&txGid=sYXEr2JmKUC1bUgWZ7-G6e7%3a