Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.

ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN

Application of Upper Extremity Radionuclide Venography as a Diagnostic Approach for Port-A Catheter Thrombosis

To investigate the role of upper extremity radionuclide venography as a potential diagnostic modality in the assessment of venous thrombosis associated with a Port-A catheter. Methods: Fourteen symptomatic patients who had received Port-A catheter implantation were enrolled. A dynamic nuclear medicine flow study was performed with intravenous administration of Technetium-99m macroaggregated albumin to both upper extremities. Imaging patterns of the venous system were categorized as patency, partial obstruction, and total occlusion. Results: The findings of the dynamic images clearly demonstrated clinical problems. Three patients were free of a definite venous flow change. Three patients had partial obstruction of venous return. A significant cut-off of venous return was demonstrated in 8 patients, and total occlusions were hence diagnosed. All patients underwent this procedure smoothly without any complication. Conclusion: These results suggest that upper extremity radionuclide venography is an easily performed and effective method for diagnosing Port-A catheter thrombosis in clinical practice