Objective To investigate the expression level of hypoxia-inducible factor-lot (HIF-1ot) in gastric cancer and its relationship with clinicopathological characteristics and prognosis of patients with gastric cancer.Methods From March 3,2011 to September 28,2012,49 patients with gastric adenocarcinoma tissue chips were selected from pathology department of our hospital.They were matched with paracancerous tissues.The expression levels of HIF-1α were measured by immunohistochemistry method in gastric cancer tissues and paracancerous tissues chips.Kaplan-Meier was used to evaluate the progression-free survival (PFS) and overall survival (OS),and the Cox proportional hazards model was used to analyze whether HIF-1α was a prognostic factor.Results The high expression rate of HIF-1α protein in gastric cancer was significantly higher than that in paired para-carcinoma group (42.9％ vs.4.1％,x2 =20.509,P ＜ 0.001).The expression of HIF-1 α protein was related to TNM stage (x2 =4.601,P =0.032),vascular invasion (x2 =6.766,P =0.009) and degree of differentiation (x2 =7.969,P =0.005).Compared with patients with low expression of HIF-1α,the median PFS (16.2 months vs.27.3 months) and median OS (34.8 months vs.43.8 months) were shorter in the patients with high expression of HIF-1 α,and the differences were statistically significant (median PFS:x2 =4.661,P =0.002;median OS:x2 =6.903,P =0.009).The results of single factor analysis showed that overexpre-ssion of HIF-1α was correlated with PFS and OS (PFS:HR =4.461,95％ CI:1.969-10.802,P ＜0.001;OS:HR =3.109,95％CI:1.274-7.588,P =0.013).The results of Cox multivariate analysis showed that overexpression of HIF-1α was the independent risk factor that affected the survival and prognosis of patients with gastric cancer (PFS:HR =4.747,95％ CI:2.175-10.230,P ＜0.001;OS:HR =3.171,95％ CI:1.358-7.404,P =0.008).Conclusion The high expression rate of HIF-1α protein in gastric cancer tissues is significantly higher than that in paracancerous tissues.The expression of HIF-1α is associated with TNM stage,vascular invasion,degree of differentiation in patients with gastric cancer.The high expression of HIF-1α is associa-ted with the shorter median OS and PFS.The high expression of HIF-1α is an independent risk factor for the survival and prognosis of patients with gastric cancer,which is expected to be an independent marker of poor prognosis.

Protein tyrosine phosphatase 1B (PTP1B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii (Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1B inhibitory ursane-type triterpenes: ursolic acid (1), 2-oxopomolic acid (2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Kinetics analyses revealed that 1 was a non-competitive PTP1B inhibitor, and 2 and 3 were mixed type PTP1B inhibitors. Compounds 1-3 and structurally related triterpenes (4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases (TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxy-urs-12-ene-28-oic acid (5), and pomolic acid-3β-acetate (6) bound at the allosteric site including α3, α6, and α7 helix of PTP1B.
Enzyme Inhibitors ; chemistry ; metabolism ; Fruit ; chemistry ; Humans ; Kinetics ; Methanol ; chemistry ; Molecular Docking Simulation ; Molecular Structure ; Plant Extracts ; chemistry ; Protein Binding ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; metabolism ; Protein Tyrosine Phosphatases ; antagonists & inhibitors ; Rubus ; chemistry ; Structure-Activity Relationship ; Triterpenes ; chemistry ; metabolism