Beneficial effect of an antibody against interleukin-2 receptor (daclizumab) in an experimental model of hepatocyte xenotransplantation.

AIM: To investigate the use of Daclizumab (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte xenotransplantation (XenoTx) in rats with fulminant hepatic failure (FHF). METHODS: Two white male New Zealand rabbits were used as donors and 68 Wistar rats as recipients. FHF was induced by intravenous application of dimethylnitrosamine (DMNA). The isolated hepatocytes of the rabbits were xenotransplanted into the spleen of the rats 24 h after FHF induction. Group A (n = 13): no treatment; Group B (n = 14): FHF and XenoTx; Group C (n = 14): FHF and XenoTx and cyclosporin (CsA); Group D (n = 14): FHF and XenoTx and Dmab; Group E (n = 13): FHF and XenoTx and CsA and Dmab. The rats were followed for 15 d. RESULTS: Statistical analysis showed better survival among groups D (92.86%) and E (76.92%) compared to group A (all rats died after 72 h), group B (28.57%) or group C (71.43%), although the differences were not statistically significant. Biochemical evaluation of the liver enzymes and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model has shown the safe, effective and beneficial use of Dmab in a xenotransplantation model of rabbit hepatocytes in rats.

Pancreatic-polypeptide in the human pancreas: expression and quantitative variation during development and in ductal adenocarcinoma.

AIM: To determine the immunoreactivity of pancreatic-polypeptide (PP) during the development of the human fetal pancreas and ductal pancreatic adenocarcinoma, given that, PP positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. METHODS: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed. RESULTS: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal - endocrine) and pure ductal type (p1 = 0.001, p2 < 0.0005, p3 = 0.046 and p4 < 0.0005 respectively). The above values were estimated during the 10th to 12th week. There was no significant difference in the density of positive cells in the mantle zone of the islets from the 13th to the 24th week, and the neoplastic tissue of mixed (p5 = 0.11) and pure ductal type (p6 = 0.23). CONCLUSION: The immunostaining for PP identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component, initially considered as pure ductal tumors, and mixed ductal and neuroendocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, raising the question of therapeutic efficacy of PP and analogues as potential adjuvant treatment of pancreatic cancer.

Does neoplastic cholecystokinin expression reflect the embryonal pattern of the protein? A study in human pancreas.

AIM: To determine the immunoreactivity of cholecystokinin (CCK) during the development of the human fetal pancreas and pancreatic adenocarcinoma, given that, CCK positive cells were demonstrated either in its embryonic anlage or in pancreatic cancer. In order to obtain possible parallels in the expression pattern of neoplastic cells in adults (well--moderately--poorly differentiated), we investigated the pattern of CCK expression in the pancreatic tissue during the various stages of development and compared these with the proliferation of tissue assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. EXPERIMENTAL DESIGN: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed using immunohistochemical methods for CCK. RESULTS: The density of positive cells in the primitive exocrine ductal walls and outgrowing buds was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (p1=0.004, p2 < 0.0005, p3 < 0.0005 and p4=0.023 respectively). The above values were estimated from 20th to 22nd weeks of gestation. There was no significant difference in the density of positive cells in the islet cell epithelium from 25-30 weeks, and the neoplastic tissue of mixed (p5=0.10) and pure ductal type (p6=0.15). CONCLUSIONS: The immunostaining for CCK identifies a sub-group of pancreatic ductal adenocarcinomas with a neuroendocrine component (initially considered as pure ductal tumors), and mixed ductal-endocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, and may be important for the development of new therapeutic approaches with eventual clinical utility.