Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers.

Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans, which participate in cell proliferation, cell migration and cell-matrix interactions. Decreased expression of syndecan-1 has been observed in some gastrointestinal malignancies, and it is thought that high levels of syndecan-1 correlate with the maintenance of epithelial morphology and inhibition of invasiveness. In our study, we characterized the expression of syndecan-1 in normal, chronic pancreatitis and primary and metastatic human pancreatic cancer tissues, in cultured pancreatic cancer cell lines and in esophageal, gastric, colon, and liver cancers. Pancreatic cancer cell lines expressed syndecan-1 mRNA and protein at variable levels. In addition, these cells also released syndecan-1 into the culture medium. Pancreatic cancer tissues markedly over-expressed syndecan-1 mRNA in comparison with both chronic pancreatitis (2.4-fold increase, p < 0.01) and normal pancreatic samples (10.6-fold increase, p < 0.01). There was no difference in syndecan-1 mRNA expression between early and advanced tumors. By in situ hybridization and immunohistochemistry, syndecan-1 expression was evident at relatively low levels in the ductal cells and less frequently in acinar cells of the normal pancreas. In chronic pancreatitis, syndecan-1 was present at low to moderate levels in areas with atrophic acinar cells and ductular complexes. In contrast, in pancreatic cancer tissues, syndecan-1 was present at moderate to high levels in the majority of the cancer cells within the tumor mass and also in metastatic lesions of pancreatic tumors. Syndecan-1 mRNA levels in other gastrointestinal malignancies (esophageal, gastric, colon and liver cancers) were not significantly different from the levels observed in the corresponding normal samples. Together, our findings suggest that syndecan-1 expression by pancreatic cancer cells may be of importance in the pathobiology of this disorder and that its role in pancreatic cancer seems to be different from that in other gastrointestinal malignancies.

Cyclosporine increases local glomerular synthesis of reactive oxygen species in rats: effect of vitamin E on cyclosporine nephrotoxicity.

BACKGROUND: We report an investigation of the effects of cyclosporine (CsA) on kidney function, the glomerular synthesis of reactive oxygen species, the peroxidation of lipids, and the levels of thromboxane B2 (TXB2). The effect of the simultaneous administration of the antioxidant vitamin E (Vit E) and CsA in rats was also evaluated. METHODS: Adult male Wistar rats were treated for 30 days with CsA (30 mg/kg/day), with Vit E (0.05 mg/ml), with CsA plus Vit E, or with the vehicle used for administration of CsA, namely 12.6% ethanol. RESULTS: CsA induced kidney failure and increased the glomerular synthesis of superoxide anion, H2O2, malonyldialdehyde, and TXB2. Vit E minimized the adverse effects of CsA on kidney function and the glomerular synthesis of these compounds. CONCLUSIONS: Our results suggest that the acute decrease in glomerular filtration rate induced by CsA might be mediated by the synthesis of reactive oxygen species and subsequent peroxidation of lipids, which increases the levels of TXB2. Treatment with Vit E prevented these effects, suggesting a possible role for antioxidants in the prevention of CsA nephrotoxicity.

Diagnostic value of three tumor markers determined in pleural effusions.

In order to discriminate between malignant and benign effusions, the values of tissue polypeptide specific antigen,carcinoembryonic antigen and squamous cell carcinoma associated antigen were measured in the pleural fluid of 30 patients with neoplasm, 10 with tuberculous pleurisy, 10 with transudates due to congestive heart failure or cirrhosis, 29 with parapneumonic effusions and 23 with benign diseases other than tuberculosis and pneumonia. Carcinoembryonic antigen and tissue poly-peptide specific antigen levels in effusions due to neoplasms were significantly higher than those in effusions due to other diseases. The areas under Receiver Operating Characteristic curves for carcinoembryonic antigen and tissue polypeptide specific antigen determinations were 0.69 and 0.67, respectively. No significant differences were found in the pleural fluid squamous cell carcinoma associated antigen levels between neoplasms and other diseases. The ability of tissue polypeptide specific antigen and carcinoembryonic antigen to discriminate between benign and malignant effusions may be considered comparable. Although both carcinoembryonic antigen and tissue polypeptide specific antigen showed a low accuracy (the number of undiagnosed pleural effusions is considerably high), both tissue polypeptide specific antigen and carcinoembryonic antigen determinations may contribute to a correct diagnostic classification. Moreover, the combination of these markers provides a specificity of 97.2%. However, the low number of positivities obtained for tissue polypeptide specific antigen and carcinoembryonic antigen together (13 cases in our series) reveals the need for further investigations.