ABSTRACT
Objective To investigate the expression of GRP78 in breast cancer,the relationships among the expression and the clinicopathological characteristics,prognosis were also investigated.Methods The expression of GRP78 was detected in 172 paraffin-embedded breast cancer samples with immunohistochemistry Envision method,the relationships among the expression and the clinicopathological characteristics,prognosis were investigated.Results Positive expression of GRP78 is common in breast cancer.Strong expression of GRP78 was detected in 71 cases (41.28％),and weak expression was detected in 101 cases (58.72％).GRP78 expression wasn't associated with the clinicopathological characterristics except T stage and Her-2 status.Univariate analysis (log-rank test) showed that GRP78 expression correlated with disease free survival and overall survival significantly.Patients with strong GRP78 expression had poorer prognosis compared to those with weak GRP78 expression(P ＜ 0.05).Multivariate analysis utilizing Cox regression analysis showed that GRP78 is an independent biomarker of disease free survival (P ＜ 0.05),but not an independent biomarker of overall survival (P ＞ 0.05).Conclusions Positive expression of GRP78 is common in breast cancer and strong expression is associated with poorer survival.
ABSTRACT
Aim To investigate whether melatonin ( MT) can alleviate endoplasmic reticulum( ER) stress at an early stage of bleomycin( BLM)-induced lung fi-brosis in mice. Methods Adult healthy male ICR mice were divided randomly into control group, MT group, BLM group and MT + BLM group. In MT group, mice had saline treatment 30 minutes after hav-ing the intraperitoneal injection of MT (10 mg·kg-1 ) and had been intraperitoneally injected with MT once in the following every 24 hours. In BLM group, mice were intratracheally injected with a single dose of BLM (5 mg·kg-1). In MT+BLM group, mice had been intraperitoneally injected with BLM 30 minutes after having MT and had been injected with MT once in the following every 24 hours. In control group, mice re-ceived the same level of saline treatment in the same manner. All mice were dissected for collecting the tis-sue of lungs at different time points (24h, 72h) after BLM treatment. Inflammatory cell infiltration of lungs was determined by HE staining. The level of ER stress related proteins ( GRP78 , p-eIF2α, p-IRE1α) in lungs was determined using Western blot. The distribu-tion of ER stress related proteins ( GRP78 , p-IRE1α, ATF6α, p-PERK) in lungs was detected by immuno-histochemistry. Results The model of BLM-induced acute inflammation of lung fibrosis in mice had been successfully constructed. After BLM treatment, lung weight, lung weight ratio and inflammatory cell infiltra-tion were significantly increased with a significant cor-relation between time and effectiveness. After MT treatment, lung weight, lung weight ratio and inflam-matory cell infiltration were significantly reduced. The results of Western blot showed that MT pretreatment not only prevented the increase of BLM-induced GRP78 protein significantly, but also restrained the phosphorylation of eIF2α and IRE1α in mouse lungs. Immunohistochemistry also showed that MT pretreat-ment reduced the expression of GRP78 , p-IRE1α, ATF6α and p-PERK. Conclusion MT alleviates ER stress effectively at an early stage of BLM-induced lung fibrosis in mice.