Combined Detection of Serum Matrix Metalloproteinase 9,Acetyl Heparinase and Cathepsin L in Diagnosis of Ovarian Cancer

Objective： To investigate the clinic values of combining test of serum matrix metalloproteinase 9 （MMP-9）, acetyl heparinase （Hpa） and Cathepsin L （CL） in diagnosis of ovarian cancer. Methods： Serum levels of MMP-9, Hpa and CL were detected in a total of 418 cases, including 217 cases with ovarian malignant tumor, 100 cases with ovarian benign tumor and 101 healthy controls, by using enzyme-linked immunosorbent assay （ELISA）. Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic （ROC）. The combined diagnosis model was established by logistic regression analysis. Results： The serum levels of MMP-9, Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control, the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor, and MMP-9, Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage. The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL, Hpa and MMP-9, and the specificity was MMP-9, CL and Hpa. The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%, respectively, which were significantly higher than a single tumor marker. Conclusion： Serum MMP-9, Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.

Inhibition of Sanggenon G Isolated from Morus alba on the Metastasis of Cancer Cell

Objective An organic layer prepared from the cortex of Morus alba(Moraceae)was studied in order to identify the active compounds for heparinase.Methods Bioassay-guided fractionation resulted in the isolation of sanggenon G.Results The compound showed inhibitory activity with IC50 of 3.7μmol/L on heparinase in vitro as well as 24μmol/L in invasion assay using MDA-MB231 cells.Sanggenon G also had the moderate cytotoxicity at SW 620(colon)and ACHN(kidney)cancer cell lines with IC50 of 10.96 and 13.44μmol/L,respectively.Conclusion This is the first time that prenylated flavonoid sanggenon G is described as heparinase inhibitor.Besides,this flavonoid would be expected to be a metastasis inhibitor of cancer cells and also a valuable reagent to explore the mechanism of heparinase/heparanase-mediated metastasis.

Structural basis of heparan sulfate-specific degradation by heparinase Ⅲ

Heparinase Ⅲ(HepⅢ)is a 73-kDa polysaccharide lyase(PL)that degrades the heparan sulfate(HS)polysaccharides at sulfate-rare regions,which are important co-factors for a vast array of functional distinct proteins including the well-characterized antithrombin and the FGF/FGFR signal transduction system.It functions in cleaving metazoan heparan sulfate(HS)and providing carbon,nitrogen and sulfate sources for host microorganisms.It has long been used to deduce the structure of HS and heparin motifs;however,the structure of its own is unknown.Here we report the crystal structure of the HepⅢ from Bacteroides thetaiotaomicron at a resolution of 1.6Å.The overall architecture of HepⅢ belongs to the(α/α)5 toroid subclass with an N-terminal toroid-like domain and a C-terminal β-sandwich domain.Analysis of this high-resolution structure allows us to identify a potential HS substrate binding site in a tunnel between the two domains.A tetrasaccharide substrate bound model suggests an elimination mechanism in the HS degradation.Asn260 and His464 neutralize the carboxylic group,whereas Tyr314 serves both as a general base in C-5 proton abstraction,and a general acid in a proton donation to reconstitute the terminal hydroxyl group,respectively.The structure of HepⅢ and the proposed reaction model provide a molecular basis for its potential practical utilization and the mechanism of its eliminative degradation for HS polysaccarides.

Severe preeclampsia cured by heparin in a patient with twin-twin transfusion syndrome

Heparin therapy for preeclampsia has been reported .frequently. Most of the authors used heparin toprevent thrombosis and achieved good results. But its mechanism is not clear. Here we describe a case of severe early-onset preeclampsia complicated with hypercoagulable state, fetal growth restriction, and twin-twin transfusion syndrome, that responded well to heparin.