In vitro functional similarity assessment of a proposed biosimilar BAT1706 to bevacizumab / 药学学报

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.

Role of adiponectin in diabetes myocardial ischemia-reperfusion injury and ischemic postconditioning

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.

Expression of Platelet Membrane Glycoprotein Ib/IX/V Complex, a Receptor of Thrombin, in Patients with Hemorrhagic Thrombopathy / 华中科技大学学报（医学）（英德文版）

To investigate the role of platelet membrane glycoprotein (GP) Ib/Ⅸ/Ⅴ complex and its subunit GP Ibа in patients with hemorrhagic thrombopathy (HT), the expressions of GP lb/Ⅸ/Ⅴ complex and GP Ibа, defined as mean fluorescence intensity (MFI), were assessed by flow cytometry.The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP lblIX/V complex and GP Ibct was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant (P<0.05). There was no significant difference in the expressions of GP lb/Ⅸ/Ⅴ complex and GP lbа between well-controlled HT patients and normal healthy subjects (P>0.05). It was concluded that the expression of GP Ib/Ⅸ/Ⅴ complex, the receptor of thrombin and yon Willebrand factor, was down-regulated in HT patients with current hemorrhage,which might result in the dysfunction of platelet aggregation and recurrence of HT.