Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a glioblastoma model

The receptor protein tyrosine phosphatase beta (RPTPbeta) is a functional biomarker for several solid tumor types. RPTPbeta expression is largely restricted to the central nervous system and overexpressed primarily in astrocytic tumors. RPTPbeta is known to facilitate tumor cell adhesion and migration through interactions with extracellular matrix components and the growth factor pleiotrophin. Here, we show that RPTPbeta is expressed in a variety of solid tumor types with low expression in normal tissue. To assess RPTPbeta as a potential target for treatment of glioblastoma and other cancers, antibodies directed to RPTPbeta have been developed and profiled in vitro and in vivo. The recombinant extracellular domain of human short RPTPbeta was used to immunize mice and generate monoclonal antibodies that selectively recognize RPTPbeta and bind to the antigen with low nanomolar affinities. Moreover, these antibodies recognized the target on living tumor cells as measured by flow cytometry. These antibodies killed glioma cells in vitro when coupled to the cytotoxin saporin either directly or via a secondary antibody. Finally, in vivo studies showed that an anti-RPTPbeta immunotoxin (7E4B11-SAP) could significantly delay human U87 glioma tumors in a mouse xenograft model. Unconjugated 7E4B11 provides a modest but statistically significant tumor growth delay when delivered systemically in mice bearing U87 glioma tumors.     

G-CSF administration is neuroprotective following transient cerebral ischemia even in the absence of a functional NOS-2 gene

Granulocyte colony-stimulating factor (G-CSF) is a candidate neuroprotective factor following cerebral ischemia. To determine whether G-CSF acts partly through the inhibition of nitric oxide synthase (NOS)-2 expression, we administered G-CSF to male NOS-2−/− mice after cerebral ischemia. Although male NOS-2−/− mice exhibit resistance to the gross effects of cerebral ischemia, they display neuronal loss and skilled motor deficits following cerebral ischemia. Administration of G-CSF during reperfusion reduced motor deficit and neuronal loss. Thus, G-CSF is still effective in NOS-2 gene-deficient mice, suggesting that part of the mechanism of action is independent of NOS-2.     

Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis

Background  

Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs). This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events.     

Tetralogy of Fallot: MR findings

Surgical treatment of patients with tetralogy of Fallot requires accurate definition of all anatomic structures, particularly the central pulmonary arteries. Magnetic resonance (MR) images of 22 patients with tetralogy of Fallot were studied to assess their usefulness in providing information regarding the spectrum of anatomic abnormalities in this condition. MR findings were compared with information obtained at catheterization (in 16 patients) and at surgery (in nine patients), both of which were performed within 3 months of MR imaging. Ventricular chamber enlargement and wall hypertrophy were clearly delineated in most of the 17 patients who were examined before definitive surgical repair, and ventricular septal defects were visualized in all 17. Palliative systemic-to-pulmonary shunts were visualized in 11 patients and could be evaluated for patency. Most important, the morphology and size of the right ventricular outflow tract and central pulmonary arteries could be accurately assessed. Pulmonary artery measurements obtained from MR images demonstrated excellent correlation with angiographic measurements. In six patients examined after complete surgical repair, MR images accurately reflected changes in pulmonary artery outflow tract morphology and complications, such as residual pulmonary artery stenosis and thrombosis. The findings suggest that MR imaging can complement or obviate catheterization in the evaluation of tetralogy of Fallot with regard to suitability for definitive surgical repair.