Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve.

Published

Journal Article

We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.

Full Text

Duke Authors

Cited Authors

  • Celik, I; Sürücü, O; Dietz, C; Heymach, JV; Force, J; Höschele, I; Becker, CM; Folkman, J; Kisker, O

Published Date

  • December 1, 2005

Published In

Volume / Issue

  • 65 / 23

Start / End Page

  • 11044 - 11050

PubMed ID

  • 16322254

Pubmed Central ID

  • 16322254

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-05-2617

Language

  • eng

Conference Location

  • United States