E- and P-selectin are inflammation-induced cell adhesion molecules that mediate leukocyte-endothelial cell and leukocyte-platelet interactions. Monoclonal antibodies (MoAbs) specific for either E-selectin or P-selectin are protective in several animal models of inflammatory disease. To generate an MoAb with broader therapeutic potential, MoAbs that bind to both E- and P-selectin were generated ...

We recently generated a monoclonal antibody that disrupted the association of endothelial cells with their target location during kidney development. Here, we purified the antigen of this monoclonal antibody to homogeneity using rat mesangial cell cytosol. Sequence revealed that it is a previously identified protein, termed the "laminin receptor precursor" (LRP). We found that this protein is e...

Current studies of tumor angiogenesis rely on the concept that endothelium proliferates 30-40 times faster in tumors than in normal tissues. This evidence is based on histological autoradiographic data largely from animal studies. To assess endothelial cell proliferation in human cancer we used the more sensitive and specific technique of immunohistochemistry. We measured the frequency and dist...

When tumours outgrow their vascular supply, they become hypoxic because of nutrient deficiency. This increases the expression and secretion of proangiogenic factors, like vascular endothelial growth factor (VEGF), leading to the activation of endothelial cells. The activated endothelial cells migrate, proliferate and form new blood vessels, resulting in increased tumour growth. This process is ...

The treatment of colorectal cancer has undergone enormous changes in the past decade. From a disease with a single treatment option (ie, fluorouracil, a modestly effective drug), the treatment options have evolved to include at least five new classes of antineoplastic agents. Among the considerable number of recently approved drugs, two are monoclonal antibodies and are the testing ground for o...

Cell-cell adhesion is controlled by many molecules found on the cell surface. In addition to the constituents of well-defined junctional structures, there are the molecules that are thought to play a role in the initial interactions of cells and that appear at precise times during development. These include the cadherins and cell adhesion molecules (CAMs). Representatives of these families of a...

Background: One area of nanoscience deals with nanoscopic interactions between nanostructured materials and biological systems. To elucidate the effects of the substrate surface morphology and viscoelasticity on cell proliferation, fractal analysis was performed on endothelial cells cultured on nanocomposite samples based on silicone rubber (SR) and various concentrations of organomodified nano...

Background: Vascular endothelial growth factor-A (VEGF-A), an endothelial cell-specific mitogen produced by various cell types, plays important roles in cell differentiation and proliferation. In this study we investigated the effect of recombinant VEGF-A on differentiation of mesenchymal stem cells (MSCs) to endothelial cells (ECs). Methods: VEGF-A was expressed in E. coli BL21 (DE3) and BL21...

Agonist monoclonal antibodies (mAb) to the immune costimulatory molecule CD137, also known as 4-1BB, are presently in clinical trials for cancer treatment on the basis of their costimulatory effects on primed T cells and perhaps other cells of the immune system. Here we provide evidence that CD137 is selectively expressed on the surface of tumor endothelial cells. Hypoxia upregulated CD137 on m...

OBJECTIVE Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these studies. METHODS AND RESULTS Using human embryonic stem cells as a model system, we were ...