Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

Abstract

Vascular endothelial growth factor (VEGF) expression is elevated in a wide variety of solid tumours. Inhibition of VEGF activities is able to reduce angiogenesis and tumour growth. We have recently shown in vitro that carboxymethyl dextran benzylamide (CMDB7) prevents the binding of VEGF 165 to its cell surface receptors and thus inhibits VEGF activities on endothelial cells. In the present study, we explored the effects of CMDB7 on highly aggressive human epidermoid carcinoma A431 cells known to overexpress epidermal growth factor receptors (EGFRs) and produce a high amount of VEGF and a minor quantity of bFGF. In vitro, CMDB7 blocked the mitogenic activity of A431-conditioned medium on endothelial cells. Concerning A431 cells, CMDB7 inhibited their proliferation and the VEGF 165 binding to them. In vivo, administration of CMDB7 (10 mg kg À1 ) three times per week for 2 weeks inhibited the growth of A431 xenografts in nude mice by 73% as compared to the control group. Immunostaining of endothelial cells with mouse-specific GSL-1 lectin in tumour sections revealed that CMDB7 also inhibited the density of intratumour endothelial cells by 66%. These findings demonstrate that CMDB7 has an efficient antiangiogenic and antitumour action in vivo even when tumour cells produce a high level of VEGF and EGFRs.

A new dimethyl ester bisphosphonate inhibits angiogenesis and growth of human epidermoid carcinoma xenograft in nude mice

“…To visualize intratumor endothelial cells (ECs), sections of 5 mm were specifically stained with GSL-1 lectin (Vector, Burlingame, California, USA) as previously described [17][18][19]. To visualize intratumor endothelial cells (ECs), sections of 5 mm were specifically stained with GSL-1 lectin (Vector, Burlingame, California, USA) as previously described [17][18][19].…”

“…Image analysis was performed using the Image analysis NIH program as previously described [17][18][19]. Image analysis was performed using the Image analysis NIH program as previously described [17][18][19].…”

Comparative Studies on the Mechanisms of Action of Four Polysaccharides on Arterial Restenosis

“…Circulating heparin-like sulphated polysaccharides can bind to heparin-binding domains of ECM proteins. As reported for heparin or other polyaromatic heparin-mimicking compounds [19,[35][36][37], the binding of heparin-like polymers could locally modulate the bioavailability of key regulatory components such as heparin-binding growth factors present in the ECM [38][39][40]. Similarly to synthetic polysaccharides that exhibited in vivo affinity for damaged muscular tissue after systemic injection [4], the increasing concentration of LMW fucoidan at the damaged vascular wall may lead to reduction of the restenosis rate.…”

Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice

“…In recent years, it has been widely shown that activity of VEGF is a key feature during tumor growth and angiogenesis [28][29][30] . In the course of occurrence and development of gastric cancer, angiogenesis plays a crucial role in which VEGF is believed to be the most important factor in neovascularization [31] .…”