PAUF promotes adhesiveness of pancreatic cancer cells by modulating focal adhesion kinase

Pancreatic cancer is a notorious disease with a poor prognosis and low survival rates, which is due to limited advances in understanding of the molecular mechanism and inadequate development of effective treatment options over the decades. In previous studies, we demonstrated that a novel soluble protein named pancreatic adenocarcinoma up-regulated factor (PAUF) acts on tumor and immune cells and plays an important role in metastasis and progression of pancreatic cancer. Here we show that PAUF promotes adhesiveness of pancreatic cancer cells to various extracellular matrix (ECM). Our results further support a positive correlation of activation and expression of focal adhesion kinase (FAK), a key player in tumor cell metastasis and survival, with PAUF expression. PAUF-mediated adhesiveness was significantly attenuated upon blockade of the FAK pathway. Moreover, PAUF appeared to enhance resistance of pancreatic cancer cells to anoikis via modulation of FAK. Our results suggest that PAUF-mediated FAK activation plays an important role in pancreatic cancer progression.

NADPH Oxidase and Mitochondrial ROS are Involved in the TNF-alpha-induced Vascular Cell Adhesion Molecule-1 and Monocyte Adhesion in Cultured Endothelial Cells

Atherosclerosis is considered as a chronic inflammatory process. However, the nature of the oxidant signaling that regulates monocyte adhesion and its underlying mechanism is poorly understood. We investigated the role of reactive oxygen species on the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion in the cultured endothelial cells. TNF-alpha at a range of 1~30 ng/ml induced VCAM-1 expression dose-dependently. BCECF-AM-labeled U937 cells firmly adhered on the surface of endothelial cells when the endothelial cells were incubated with TNF-alpha (15 ng/ml). Ten micromol/L of SB203580, an inhibitor of p38 MAPK, significantly reduced TNF-alpha-induced VCAM-1 expression, compared to the JNK inhibitor (40micromol/L of SP60015) or ERK inhibitor (40micrommol/L of U0126). Also, SB203580 significantly inhibited TNF-alpha-induced monocyte adhesion in HUVEC. Superoxide production was minimal in the basal condition, however, treatment of TNF-alpha induced superoxide production in the dihydroethidine-loaded endothelial cells. Diphenyleneiodonium (DPI, 10micromol/L), an inhibitor of NADPH oxidase, and rotenone (1micromol/L), an inhibitor of mitochondrial complex I inhibited TNF-alpha-induced superoxide production, VCAM-1 expression and monocyte adhesion in the endothelial cells. Taken together, our data suggest that NADPH oxidase and mitochondrial ROS were involved in TNF-alpha-induced VCAM-1 and monocyte adhesion in the endothelial cells.

Clinical Evaluation of Risk Factors in Elderly patients with Reflux Esophagitis / 대한소화관운동학회지

BACKGROUND/AIMS: The elderly patients with reflux esophagitis are less likely to feel or report their symptoms than the younger patients, even though they are more prone to complications such as bleeding, stricture or Barrett's esophagus. In this study we tried to investigate risk factors in the elderly patients who had endoscopically diagnosed reflux esophagitis. METHODS: Clinical data of six hundred and eighty seven patients with reflux esophagitis were reviewed. RESULTS: Among the 687 patients with reflux esophagitis, two hundred and thirteen (31%) were 60 or more than 60 years old. The frequency of accompanying hiatal hernia in the elderly group (age>or=60) was significantly higher than the younger group (age<60) (16.9%, 36/213 vs. 3.4%, 16/474, p<0.05). There was significant difference according age in the female group (0.9%, 1/114 vs. 22.7%, 22/97, p<0.05). The frequency of atropic gastritis was significantly higher in the elderly group than in the younger group , while other factors such as smoking, H. pylori and peptic ulcer disease were not different between the two groups. CONCLUSION: Among the risk factors of reflux esophagitis, the existence of hiatal hernia seems to be suggested more relevant to the development of this condition in the elderly group.

Clinical Evaluation of Risk Factors in Elderly patients with Reflux Esophagitis / 대한소화관운동학회지

BACKGROUND/AIMS: The elderly patients with reflux esophagitis are less likely to feel or report their symptoms than the younger patients, even though they are more prone to complications such as bleeding, stricture or Barrett's esophagus. In this study we tried to investigate risk factors in the elderly patients who had endoscopically diagnosed reflux esophagitis. METHODS: Clinical data of six hundred and eighty seven patients with reflux esophagitis were reviewed. RESULTS: Among the 687 patients with reflux esophagitis, two hundred and thirteen (31%) were 60 or more than 60 years old. The frequency of accompanying hiatal hernia in the elderly group (age>or=60) was significantly higher than the younger group (age<60) (16.9%, 36/213 vs. 3.4%, 16/474, p<0.05). There was significant difference according age in the female group (0.9%, 1/114 vs. 22.7%, 22/97, p<0.05). The frequency of atropic gastritis was significantly higher in the elderly group than in the younger group , while other factors such as smoking, H. pylori and peptic ulcer disease were not different between the two groups. CONCLUSION: Among the risk factors of reflux esophagitis, the existence of hiatal hernia seems to be suggested more relevant to the development of this condition in the elderly group.