Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Research into this process not only offers new insights in...
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Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Research into this process not only offers new insights into tumour biology but is also leading to the development of realistic novel and minimally toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines and pathways have been characterized and their interrelationships are becoming increasingly complex as new findings are made. This article reviews the current understanding of tumour angiogenesis, the basic mechanisms involved and the more important and investigated pathways and proteins involved.
The accelerated formation of advanced glycation end products (AGEs) is implicated in diabetic microvascular and macrovascular complications. The binding of AGEs to their cellular surface receptor (RAGE) induces vascul...
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The accelerated formation of advanced glycation end products (AGEs) is implicated in diabetic microvascular and macrovascular complications. The binding of AGEs to their cellular surface receptor (RAGE) induces vascular dysfunction and in particular an increase in vascular permeability. We previously demonstrated that rat recombinant RAGE (rR-RAGE)produced in insect cells corrected the hyperpermeability due to RAGE AGE interaction and that pharmacokinetic properties of rR-RAGE after i.v. administration in rats were compatible with a potential therapeutic use. In the present study, we showed that recombinant human RAGE (rH-RAGE) had a similar efficacy in inhibiting AGE-induced endothelial, alteration and in reducing the hyperpermeability observed in streptozotocin-induced diabetic rats. I-125-rH-RAGE elimination half-life! after i.v. administration was similar in diabetic and normal rats (53.7 +/- 7.6 and 45.3 +/- 4.0 h, respectively). The presence of AGEs is responsible for a higher distribution volume in diabetic rats compared with normal rats (15.3 +/- 2.7 and 7.7 +/- 0.7 l/kg, respectively). Immunoreactive I-125-rH-RAGE decreased move rapidly than did immunoreactive I-125-rR-RAGE. The differences between I-125- rH-RAGE and I-125-rR-RAGE pharmacokinetics in rat may be related to differences in potential O-glycosylation and protease cleavage sites between the two RAGE molecules.
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