We found that knockdown of FoxC1 reduced the expression of a number of metastasis-related genes. Among these genes, NEDD9 was the most down-regulated upon FoxC1 knockdown. Using serial deletion, site-directed mutagenesis, and ChIP, we showed that NEDD9 is a direct transcriptional target of FoxC1. Inhibition
of NEDD9 expression markedly decreased FoxC1-mediated HCC EGFR activity metastasis. Furthermore, FoxC1 expression was positively correlated with NEDD9 expression, and the coexpression of these genes was associated with poor prognosis in human HCC patients. Thus, FoxC1 promoted HCC metastasis by up-regulating NEDD9 expression. In conclusion, this study demonstrates that the overexpression of FoxC1 in HCC is a strong indicator of more-aggressive tumors and poor clinical outcome. FoxC1 promotes HCC metastasis through not only the induction of EMT, but also up-regulation of the adhesive molecule, NEDD9. Thus, FoxC1 may be a candidate biomarker for HCC prognosis and a target for new therapies. Additional Supporting Information may be found in the online version of this article. “
duct leaks can occur as a result of both acute and chronic pancreatitis or in the setting of pancreatic trauma. Manifestations SB203580 of leaks include pseudocysts, pancreatic ascites, high amylase pleural effusions, disconnected duct syndrome, and internal and external pancreatic fistulas. Patient presentations are highly variable and range from asymptomatic pancreatic cysts to patients with severe abdominal
pain and sepsis from infected fluid collections. The diagnosis can often be made by high-quality cross-sectional imaging or during endoscopic retrograde cholangiopancreatography (ERCP). Because of their complexity, pancreatic leak patients are best managed by a multidisciplinary team comprised of therapeutic endoscopists, interventional radiologists, and surgeons in the field of pancreatic interventions. Minor leaks will often resolve with conservative management while severe leaks will frequently require interventions. Endoscopic treatments for pancreatic duct leaks learn more have replaced surgical interventions in many situations. Interventional radiologists also have the ability to offer therapeutic interventions for many leak patients. The mainstay of endotherapy for pancreatic leaks is transpapillary pancreatic duct stenting with a stent that bridges the leak if possible, but varies based on the manifestation and clinical presentation. Fluid collections that result from leaks, such as pseudocysts, can often be treated by endoscopic transluminal drainage with or without endoscopic ultrasound or by percutaneous drainage. Endoscopic interventions have been shown to be effective and have an acceptable complication rate. Pancreatitis can be caused by multiple different types of insults to the pancreas.