Physiology

Angiogenesis: Insights from a Systematic Overview by Gaetano Santulli

By Gaetano Santulli

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2, 117] Angiogenesis: Something Old, Something New 23 Results from Clinical Trials Clinical trials designed to test anti-angiogenic therapy have met with variable and rather disappointing success. In particular, not all tumor vessels appear equally susceptible to a single modality of anti-angiogenic therapy. The reasons for this outcome are likely multiple, one of them is the participation of tumor cells to the vascular wall (“vascular mimicry”). The molecular nature of tumor microvessels appears to be more variable than anticipated and differences in the tumor microenvironment will likely influence therapeutic outcome.

There does not appear to be ligand specificity between the ligands and receptors, however recent experimental evidence suggests that not all receptor/ligand pair results in signaling. Activation of Notch requires a series of proteolytic events that are trigged by binding to receptors. [12] 18 Evangeli Lampri and Elli Ioachim The Notch signaling also plays role in arterial phenotype. There is also ample evidence that the Notch pathway inhibits proliferation in endothelial cells. Suppression of Notch signaling results in increased endothelial cell proliferation in 3D sprouting assays in vitro.

Cell 1996;87:1161-9. [94] Thurston G, Rudge JS, Ioffe E et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000;6:460-3. [95] Xu Y, Yu Q. Angiopoietin-1, unlike angiopoietin-2, is incorporated into the extracellular matrix via its linker peptide region. J Biol Chem 2001;276:34990-8. [96] Carlson TR, Feng Y, Maisonpierre PC, Mrksich M, Morla AO. Direct cell adhesion to the angiopoietins mediated by integrins. J Biol Chem 2001;276:26516-25. [97] Gale NW, Yancopoulos GD.

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