Skip to main content
Log in

The effect of the anti-angiogenic agent TNP-470 on tumor growth and vascularity in low passaged xenografts of human gliomas in nude mice

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The effect of the anti-angiogenic agent TNP-470 on tumor growth, vascular area, vascular density and tumor perfusion of two different subcutaneously implanted human glioma xenografts (E98 and E106) in nude mice was evaluated. Vascular parameters were investigated with an image analysis system. For both tumor lines a small but significant tumor growth suppression was observed. However, no differences in vascular parameters between TNP-470 treated tumors and controls could be found after 6 weeks of treatment. It is concluded that although TNP-470 is a promising anti-angiogenic agent in many tumor types, at least 2 glioma lines seem to be partly resistant to its anti-angiogenic effects. Further evaluation of the effects of combination of TNP-470 and cytostatic agents or radiotherapy in human glioma xenografts are required to determine the place of anti-angiogenic therapy in general and treatment with the anti-angiogenic agent TNP-470 more specifically in the treatment of human gliomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Folkman J: Clinical applications of research on angiogenesis. N Engl J Med 333: 1757–1763, 1995

    Google Scholar 

  2. Auerbach W, Auerbach R: Angiogenesis inhibition. A review. Pharm Ther 63: 265–311, 1994

    Google Scholar 

  3. Fan TP, Jaggar R, Bicknell R: Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy. Trends Pharmacol Sci 16: 57–66, 1995

    Google Scholar 

  4. Ingber D, Fujita T, Kishimoto S, Sudo K, Kanamaru T, Brem H, Folkman J: Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature 348: 555–557, 1990

    Google Scholar 

  5. Yanase T, Tamura M, Fujita K, Kodama S, Tanaka K: Inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of human cell lines in vitro and in vivo. Cancer Res 53: 2566–2567, 1993

    Google Scholar 

  6. Abe J, Zhou W, Takuwa N, Kurokawa K, Kumada M, Takuwa Y: A fumagillin derivative angiogenesis inhibitor, AGM 1470, inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation or protooncogen expression in vascular endothelial cells. Cancer Res 54: 3407–3412, 1994

    Google Scholar 

  7. Takamiya Y, Brem H, Ojeifo J, Mineta T, Martuza RL: AGM-1470 inhibits the growth of human glioblastoma cells in vitro and in vivo. Neurosurgery 34: 869–875, 1994

    Google Scholar 

  8. Takechi A, Uozumi T, Kawamoto K, Ito A, Kurisu K, Sudo K: Inhibitory effect of TNP-1470, a new anti-angiogenic agent, on estrogen induced rat pituitary tumors. Anticancer Res 14: 157–162, 1994

    Google Scholar 

  9. Isobe N, Uozumi T, Kurisu K, Kawamoto K: Antitumor effect of TNP-470 on glial tumors transplanted in rats. Anticancer Res 16: 71–76, 1996

    Google Scholar 

  10. Westphal JR, van' t Hullenaar RGM, van der Laak JAWM, Cornelissen IMHA, Schalkwijk LJM, van Muijen GNP, Wesseling P, de Wilde PCM, Ruiter DJ, de Waal RMW: Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential. Br J Cancer, in press

  11. Rijken PFJW, Bernsen HJJA, van der Kogel AJ: Application of an image analysis system for the quantitation of the tumor perfusion and vascularity in human glioma xenografts. Microvasc Res 50: 141–153, 1995

    Google Scholar 

  12. Wilson JT, Penar PL: The effect of AGM-1470 in an improved intracranial 9L-gliosarcoma rat model. Neurol Res 16: 121–124, 1994

    Google Scholar 

  13. Konno H, Tanaka T, Matsuda I, Kanai T, Maruo Y, Nishino N, Nakamura S, Baba S: Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP-470, and mitomycin C on the growth and liver metastasis of human colon cancer. Int J Cancer 61: 268–271, 1995

    Google Scholar 

  14. Konno H, Tanaka T, Kanai T, Maruyama K, Nakamura S, Baba S: Efficacy of an angiogenesis inhibitor, TNP-470, in xenotransplanted human colorectal cancer with high metastatic potential. Cancer 77: 1736–1740, 1996

    Google Scholar 

  15. Mcleskey SW, Zhang L, Trock BJ, Kharbanda S, Liu Y, Gottardis MM, Lippman ME, Kern FG: Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells. Br J Cancer 73: 1053–1062, 1996

    Google Scholar 

  16. Yamamoto T, Sudo K, Fujita T: Significant inhibition of endothelial cell growth in tumor vasculature by an angiogenesis inhibitor, TNP-470 (AGM-1470). Anticancer Res 14: 1–4, 1994

    Google Scholar 

  17. Kusaka M, Sudo K, Matsutani E, Kozai Y, Marui S, Fujita T, Ingber D, Folkman J: Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor TNP-470 (AGM 1470). Br J Cancer 69: 212–216, 1994

    Google Scholar 

  18. Hori A, Ikeyama S, Sudo K: Suppression of cyclin D1 mRNA expression by the angiogenesis inhibitor TNP-470 (AGM 1470) in vascular endothelial cells. Biochem Biophys Res Commun 204: 1067–1073, 1994

    Google Scholar 

  19. Kim KJ, Li B, Winer J, Armanini M, Gillet N, Phillips HS, Ferrara N: Inhibition of VEGF-induced angiogenesis suppresses tumor growth in vivo. Nature 362: 841–844, 1993

    Google Scholar 

  20. Millauer B, Longhi MP, Plate KH, Shawver LK, Risau W, Ullrich A, Strawn LM: Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. Cancer Res 56: 1615–1620, 1996

    Google Scholar 

  21. Bernsen HJJA, Rijken PFJW, Peters H, Bakker H, van der Kogel AJ: The effect of anti-VEGF treatment on growth of human glioma xenografts in nude mice and vascular changes following anti-angiogenic therapy. Submitted for publication

  22. Teicher BA, Holden SA, Ara G, Sotomayor EA, Huang ZD, Chen YN, Brem H: Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti-angiotoxic cancer therapies by TNP-470 alone and with other anti-angiogenic agents. Int J Cancer 57: 920–925, 1994

    Google Scholar 

  23. Teicher BA, Holden SA, Ara G, Dupuis NP, Liu F, Yuan J, Ikebe M, Kakeij Y: Influence of an anti-angiogenic treatment on 9L gliosarcoma: Oxygenation and response to cytotoxic therapy. Int J Cancer 61: 732–737, 1995

    Google Scholar 

  24. Yanai S, Okada H, Saito K, Kuge Y, Ogewa Y, Toguchi H: Optimal formulation of an angiogenesis inhibitor, TNP-470, for arterial injection determined by in vitro drug release and stability, and in vivo antitumor activity. Int J Pharmaceutics 123: 237–245, 1995

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernsen, H., Rijken, P., Peters, H. et al. The effect of the anti-angiogenic agent TNP-470 on tumor growth and vascularity in low passaged xenografts of human gliomas in nude mice. J Neurooncol 38, 51–57 (1998). https://doi.org/10.1023/A:1005957201431

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005957201431

Navigation