Purpose: Epithelial to mesenchymal transitions are vital for tumor growth and metastasis.Several inducers of epithelial to mesenchymal transition are transcription factors that repress E-cadherin expression, such as Snail, Slug, and Twist. In this study, we aimed to examine the expression of these transcription factors in pancreatic cancer. Experimental Design: The expression of Snail, Slug, and Twist was detected by immunohistochemistry in tissue samples from patients with pancreatic ductal adenocarcinoma. Five human pancreatic cancer cell lines (AsPC-1, Capan-1, HPAF-2, MiaPaCa-2, and Panc-1) were analyzed by reverse transcription-PCR, real-time PCR, and Western blotting. An orthotopic nude mouse model of pancreatic cancer was applied for in vivo experiments. Results: Seventy-eight percent of human pancreatic cancer tissues showed an expression of Snail, and 50% of the patients displayed positive expression of Slug. Twist showed no or only weak expression. Snail expression was higher in undifferentiated cancer cell lines (MiaPaCa-2 and Panc-1) than in more differentiated cell lines (Capan-1, HPAF-2, AsPC-1). Expression of Slug was detected in all cell lines with different intensities. Twist was not expressed. After exposure to hypoxia, theTwist gene was activated in all five pancreatic cancer cell lines. Conclusions:The transcription factors Snail and Slug are expressed in pancreatic cancer but not in normal tissue, suggesting a role in the progression of human pancreatic tumors.Twist, activated by hypoxia, may play an important role in the invasive behavior of pancreatic tumors.Pancreatic cancer is the fifth leading cause of cancer-related death in industrial western countries. It is an aggressive disease with <5% survival after 5 years (1, 2). This is largely attributable to late clinical presentation and limitations in diagnostic methods. More than 80% of patients are diagnosed with pancreatic cancer at a locally advanced or metastatic stage, which excludes a curative surgical resection (3). The response to conventional therapies, such as radiotherapy and chemotherapy, is poor and has little effect on the natural progress of this malignancy (4). Understanding the molecular biology of pancreatic cancer and metastasis may provide insight for the development of novel tumor markers or new therapeutic strategies.Epithelial to mesenchymal transition (EMT) is a key step during embryonic morphogenesis and is involved in the progression of primary tumors toward metastasis (5). During EMT, cells undergo a developmental switch from a polarized, epithelial phenotype to a highly motile fibroblastoid or mesenchymal phenotype (6). Tumor cells begin to grow invasive, enter into systemic circulation (''intravasation''), move from the circulatory system into a new host tissue (''extravasation''), and proliferate and grow to a secondary tumor. The cell adhesion molecules E-cadherin and N-cadherin, members of the classic cadherin family, are regarded as inducers of EMT (7,8). E-cadherin is required for the formation o...

Smoking and coronary heart disease are important risk factors for anastomotic leakage and postoperative mortality after elective resection for rectal cancer.

Orthotopic implantation of donor tumor fragments into nude mice is technically feasible and is superior to the cell injection technique. It results in reproducible local and systemic development of pancreatic cancer that mimics the human disease. A dissemination score may help to better quantify therapeutic effects in future studies.

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Background-Capillary leakage with fluid loss into the third space contributes to many of the early systemic complications in severe acute pancreatitis. There has been increasing interest in endothelin as one of the factors aVecting capillary permeability. Aim-To elucidate further the role of endothelin in the development of capillary leakage in acute pancreatitis by investigating the eVect of exogenous endothelin administration and endothelin receptor blockade in sham operated animals and two models of acute pancreatitis. Methods-Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. Results-Pancreatic and colonic capillary permeability increased stepwise from mild to severe acute pancreatitis. Endothelin increased pancreatic and colonic capillary permeability in healthy animals and animals with mild acute pancreatitis but had no additional adverse eVect in severe acute pancreatitis. Endothelin receptor blockade decreased pancreatic capillary permeability in sham operated rats but had no eVect on the colon. In mild and severe acute pancreatitis, endothelin receptor blockade stabilised increased capillary permeability in both the pancreas and colon. Conclusions-Endothelin plays an important role in mediating capillary permeability in the pancreas. In severe pancreatitis, it increases capillary permeability even outside the pancreas, thereby contributing to capillary leakage. Endothelin receptor blockade significantly reduces capillary permeability in acute pancreatitis both in and outside the pancreas, suggesting a therapeutic approach to counteract capillary leakage in severe acute pancreatitis. (Gut 2000;46:390-394)