The arylhydrocarbon receptor (AhR) was initially identified as a member of the adaptive metabolic and toxic response pathway to polycyclic aromatic hydrocarbons and to halogenated dibenzo-p-dioxins and dibenzofurans. In the present study, we sought to determine the functional significance of the AhR pathway in pancreatic carcinogenesis. AhR expression was analysed by Northern blotting. The exact site of AhR expression was analysed by in situ hybridization and immunohistochemistry. The effects of TCDD and four selective AhR agonists on pancreatic cancer cell lines were investigated by growth assays, apoptosis assays, and induction of the cyclin-dependent kinase inhibitor p21. There was strong AhR mRNA expression in 14 out of 15 pancreatic cancer samples, weak expression in chronic pancreatitis tissues, and faint expression in all normal pancreata. In pancreatic cancer tissues, AhR mRNA and protein expression were localized in the cytoplasm of pancreatic cancer cells. TCDD and the four AhR agonists inhibited pancreatic cancer cell growth in a dose-dependent manner, and decreased anchorage-independent cell growth. DAPI staining did not reveal nuclear fragmentation and CYP1A1 and was not induced by TCDD and AhR agonists. In contrast, TCDD and AhR agonists induced the expression of the cyclindependent kinase inhibitor p21. In conclusion, the relatively non-toxic AhR agonists caused growth inhibition in pancreatic cancer cells with high AhR expression levels via cell cycle arrest. In addition, almost all human pancreatic cancer tissues expressed this receptor at high levels, suggesting that these or related compounds may play a role in the therapy of pancreatic cancer in the future.

Background-Nerve growth factor (NGF), a target derived factor for survival and maintenance of peripheral and central neurones, has been implicated in several chronic inflammatory processes. Aims-To analyse the concomitant presence of NGF and its high aYnity receptor TrkA in patients undergoing surgery for Crohn's disease (CD) and ulcerative colitis (UC). Patients-CD

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. Int. J. Cancer 88:12–20, 2000. © 2000 Wiley‐Liss, Inc.