• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Apr 26, 1994; 91(9): 4082–4085.
PMCID: PMC43727

Thalidomide is an inhibitor of angiogenesis.

Abstract

Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • CAHEN R, SAUTAI M, MONTAGNE J. RECHERCHE DE L'EFFET T'ERATOG'ENE DE LA 2-DI'ETHYLAMINOPROPIOPH'ENONE. Med Exp Int J Exp Med. 1964;10:201–224. [PubMed]
  • Helm F. Tierexperimentelle Untersuchungen und Dysmeliesyndrom. Arzneimittelforschung. 1966 Sep;16(9):1232–1244. [PubMed]
  • Sterz H, Nothdurft H, Lexa P, Ockenfels H. Teratologic studies on the Himalayan rabbit: new aspects of thalidomide-induced teratogenesis. Arch Toxicol. 1987 Jul;60(5):376–381. [PubMed]
  • Stephens TD. Proposed mechanisms of action in thalidomide embryopathy. Teratology. 1988 Sep;38(3):229–239. [PubMed]
  • Seifert R, Zhao B, Christ B. Cytokinetic studies on the aortic endothelium and limb bud vascularization in avian embryos. Anat Embryol (Berl) 1992 Dec;186(6):601–610. [PubMed]
  • Auerbach R, Kubai L, Knighton D, Folkman J. A simple procedure for the long-term cultivation of chicken embryos. Dev Biol. 1974 Dec;41(2):391–394. [PubMed]
  • Crum R, Szabo S, Folkman J. A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science. 1985 Dec 20;230(4732):1375–1378. [PubMed]
  • Folkman J, Szabo S, Stovroff M, McNeil P, Li W, Shing Y. Duodenal ulcer. Discovery of a new mechanism and development of angiogenic therapy that accelerates healing. Ann Surg. 1991 Oct;214(4):414–427. [PMC free article] [PubMed]
  • Bogman MJ, Cornelissen IM, Berden JH, De Jong J, Koene RA. A comparative study of total body irradiation as a method of inducing granulocyte depletion in mice. J Immunol Methods. 1984 May 11;70(1):31–38. [PubMed]
  • Bigelow CL, Adler LT, Appelbaum FR. Allogeneic bone marrow transplantation in irradiated adult rabbits. Transplantation. 1987 Sep;44(3):351–354. [PubMed]
  • Helm FC, Frankus E, Friderichs E, Graudums I, Flohé L. Comparative teratological investigation of compounds structurally and pharmacologically related to thalidomide. Arzneimittelforschung. 1981;31(6):941–949. [PubMed]
  • Gordon GB, Spielberg SP, Blake DA, Balasubramanian V. Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2545–2548. [PMC free article] [PubMed]
  • Kocher-Becker U, Kocher W, Ockenfels H. Thalidomide-like malformations caused by Tween surfactant in mice. Z Naturforsch C. 1981 Sep-Oct;36(9-10):904–906. [PubMed]
  • SHESKIN J. THALIDOMIDE IN THE TREATMENT OF LEPRA REACTIONS. Clin Pharmacol Ther. 1965 May-Jun;6:303–306. [PubMed]
  • Field EO, Gibbs JE, Tucker DF, Hellmann K. Effect of thalidomide on the graft versus host reaction. Nature. 1966 Sep 17;211(5055):1308–1310. [PubMed]
  • Lim SH, McWhannell A, Vora AJ, Boughton BJ. Successful treatment with thalidomide of acute graft-versus-host disease after bone-marrow transplantation. Lancet. 1988 Jan 16;1(8577):117–117. [PubMed]
  • McCarthy DM, Kanfer EJ, Barrett AJ. Thalidomide for the therapy of graft-versus-host disease following allogeneic bone marrow transplantation. Biomed Pharmacother. 1989;43(9):693–697. [PubMed]
  • Saurat JH, Camenzind M, Helg C, Chapuis B. Thalidomide for graft-versus-host disease after bone marrow transplantation. Lancet. 1988 Feb 13;1(8581):359–359. [PubMed]
  • McCarthy DM, Kanfer EJ, Barrett AJ. Thalidomide for the therapy of graft-versus-host disease following allogeneic bone marrow transplantation. Biomed Pharmacother. 1989;43(9):693–697. [PubMed]
  • Keenan RJ, Eiras G, Burckart GJ, Stuart RS, Hardesty RL, Vogelsang G, Griffith BP, Zeevi A. Immunosuppressive properties of thalidomide. Inhibition of in vitro lymphocyte proliferation alone and in combination with cyclosporine or FK506. Transplantation. 1991 Nov;52(5):908–910. [PubMed]
  • Ausprunk DH, Falterman K, Folkman J. The sequence of events in the regression of corneal capillaries. Lab Invest. 1978 Mar;38(3):284–294. [PubMed]
  • Jurand A. Early changes in limb buds of chick embryos after thalidomide treatment. J Embryol Exp Morphol. 1966 Oct;16(2):289–300. [PubMed]
  • Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med. 1991 Mar 1;173(3):699–703. [PMC free article] [PubMed]
  • Sunderkötter C, Roth J, Sorg C. Immunohistochemical detection of bFGF and TNF-alpha in the course of inflammatory angiogenesis in the mouse cornea. Am J Pathol. 1990 Sep;137(3):511–515. [PMC free article] [PubMed]
  • Fràter-Schröder M, Risau W, Hallmann R, Gautschi P, Böhlen P. Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5277–5281. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...