Autophagy Enhances the Aggressiveness of Human Colorectal Cancer Cells and Their Ability to Adapt to Apoptotic Stimulus

Objective To investigate LC3B-Ⅱand active caspase-3 expression in human colorectal cancer to elucidate the role of autophagy and to explore the relationship of autophagy with apoptosis in human colorectal cancer. Methods LC3B expression was detected by immunohistochemistry in 53 human colorectal cancer tissues and 20 normal colon tissues.The protein levels of LC3B-Ⅱand active caspase-3 were also determined by Western blot analysis in 23 human colorectal cancer tissues and 10 normal colon tissues. Results LC3B was expressed both in cancer cells and normal epithelial cells.LC3B expression in the peripheral area of cancer tissues was correlated with several clinicopathological factors,including tumor differentiation(P=0.002),growth pattern of the tumor margin (P=0.028),pN(P=0.002),pStage(P=0.032),as well as vessel and nerve plexus invasion(P=0.002).The protein level of LC3B-Ⅱin cancer tissue was significantly higher than in normal tissue(P=0.038),but the expression of active forms of procaspase-3 in cancer tissue was lower(P=0.041).There was a statistically significant positive correlation between the expression levels of LC3B-Ⅱand the active forms of procaspase-3(r=0.537,P=0.008). Conclusions Autophagy has a prosurvival role in human colorectal cancer.Autophagy enhances the aggressiveness of colorectal cancer cells and their ability to adapt to apoptotic stimulus.

Relationship between the Plasma Fibulin-1 Levels,Pulse Wave Velocity,and Vascular Age in Asymptomatic Hyperuricemia

Fibulin-1(FBLN-1),an elastin-associated extracellular matrix protein,has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease(CVD).We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity(baPWV)in patients with asymptomatic hyperuricemia(AHU).In total,66 patients with AHU and 66 gender-and age-matched healthy individuals were enrolled.The plasma fibulin-1 levels were measured by immunochemistry.Patients with AHU presented significantly higher vascular age[median(interquartile range):54(22)vs.48(14)years,P=0.01]and baPWV[mean±SD:1373±223 vs.1291±177 cm/s,P=0.02]than the healthy subjects;however,no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects[median(interquartile range):4018(3838)vs.3099(3405)ng/mL,P=0.31].A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU(r=0.29,P=0.02);and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age(r=0.22,P=0.08).However,these associations were rendered insignificant after adjustments for potential confounders.In healthy subjects,no correlation was observed between fibulin-1 levels and CVD risk.This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU,but the relationship is not robust.