Reduction in Basic Fibroblast Growth Factor Mediated AngiogenesisIn Vivoby Linomide

Abstract

Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxoquinoline-3-carboxa mide) is a novel immunomodulator with a potent anti-tumoral activity. This study was undertaken to test the effect of Linomide on basic fibroblast growth factor (bFGF) induced angiogenesis in vivo, which manifests itself in an increased number of blood vessels per unit of cell infiltrated area. Subcutaneously implanted polyvinyl alcohol sponges (PVS) in guinea pigs were used as a model system to quantitate angiogenesis in vivo. Oral treatment with Linomide was able to reduce significantly the bFGF induced blood vessel growth and proliferation within the implanted PVS, relative to untreated controls. In addition, Linomide significantly reduced the bFGF mediated augmentation of protein and collagen content in the implanted PVS, indicating an inhibition in the deposition of extracellular matrix (ECM). We conclude that the potent inhibition of bFGF induced angiogenesis by Linomide in vivo in addition to immunomodulatory effects may have potentially important clinical applications.