Cancer Chemotherapy and Pharmacology

, Volume 35, Issue 2, pp 115–120 | Cite as

Effects of neocarzinostatin upon the development of tumors from murine neuroblastoma cells

  • Patricia Will
  • Kathleen A. Guger
  • Nina Felice Schor
Original Article Neuroblastoma, Differentiation, Enediyne

Abstract

The use of differentiation-inducing agents has been proposed for the purging of bone marrow and for the treatment of minimal residual disease prior to autologous bone marrow transplantation in patients with metastatic neuroblastoma. The present studies examine the effects of the enediyne differentiation inducer neocarzinostatin (NCS) on tumor development from subcutaneous implants of murine (Neuro-2A) neuroblastoma cells. Prior in vitro treatment with NCS results in a concentration- and drug exposure time-dependent decrease in the incidence of tumors from subcutaneously implanted cells. In vivo treatment results in a dose-dependent decrease in the rate of tumor growth. These results imply that enediynes such as NCS may be useful in ex vivo purging regimens and in in vivo treatment of microscopic residual disease in patients with neuroblastoma.

Key words

Neuroblastoma Differentiation Enediyne 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cornaglia-Ferraris P, Ponzoni M, Montaldo P, Mariottini GL, Donti E, Di Martino D, Tonini GP (1990) A new human highly tumorigenic neuroblastoma cell line with undetectable expression of N-myc. Pediatr Res 27: 1Google Scholar
  2. 2.
    Falcione M, Milligan KD, Schwartz MC, Schor NF (1993) Prevention of neocarzinostatin-induced cell death and morphologic change in SK-N-SH human neuroblastoma cells by continuous exposure to nerve growth factor. Biochem Pharmacol 46: 731Google Scholar
  3. 3.
    Geran RI, Greenberg NH, MacDonald MM, Schumacher AM, Abbott BJ (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep 3: 1Google Scholar
  4. 4.
    Goldberg IH (1991) Mechanism of neocarzinostatin action: role of DNA microstructure in determination of chemistry of bistranded oxidative damage. Acc Chem Res 24: 191Google Scholar
  5. 5.
    Guger KA, Schor NF (1992) Neocarzinostatin produces loss of tumorigenicity in murine neuroblastoma cells. Ann Neurol 32: 472Google Scholar
  6. 6.
    Maeda H, Ueda M, Morinaga T, Matsumoto T (1985) Conjugation of poly(styrene-co-maleic acid) derivatives to the antitumor protein neocarzinostatin: pronounced improvements in pharmacological properties. J Med Chem 28: 455Google Scholar
  7. 7.
    Nicolaou KC, Dai W-M, Tsay S-C, Estevez VA, Wrasidlo W (1992) Designed enediynes: a new class of DNA-cleaving molecules with potent and selective anticancer activity. Science 256: 1172Google Scholar
  8. 8.
    Pearson ES, Hartley HO (1976) Biometrika tables for statisticians. Biometrika Trust, Cambridge, EnglandGoogle Scholar
  9. 9.
    Prasad KN, Kumar S (1975) Role of cyclic AMP in differentiation of human neuroblastoma cells in culture. Cancer 36: 1338Google Scholar
  10. 10.
    Schor NFT (1987) Adjunctive use of Ethiofos (WR2721) with free radical-generating chemotherapeutic agents in mice: new caveats for therapy. Cancer Res 47: 5411Google Scholar
  11. 11.
    Schor NF (1989) Neocarzinostatin induces neuronal morphology of mouse neuroblastoma in culture. J Pharmacol Exp Ther 249: 906Google Scholar
  12. 12.
    Schor NF (1992) Targeted enhancement of the biological activity of the antineoplastic agent, neocarzinostatin: studies in murine neuroblastoma cells. J Clin Invest 89: 774Google Scholar
  13. 13.
    Seeger RC, Siegel SE, Sidell N (1982) Neuroblastoma: clinical perspectives, monoclonal antibodies, and retinoic acid. Ann Intern Med 97: 873Google Scholar
  14. 14.
    Seeger RC, Matthay KK, Villasblanca JG, Harris R, Feig SA, Selch M, Stram D, Reynolds CP (1991) Intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT) for high risk neuroblastoma. Proc Am Soc Clin Oncol 251: A1089Google Scholar
  15. 15.
    Siegel S (1956) Nonparametric statistics. McGraw-Hill, New YorkGoogle Scholar
  16. 16.
    Sokal RR, Rohlf FJ (1981) Biometry. W.H. Freeman, San FranciscoGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Patricia Will
    • 1
  • Kathleen A. Guger
    • 1
  • Nina Felice Schor
    • 1
    • 2
  1. 1.Departments of Pediatrics, Neurology, and PharmacologyUniversity of PittsburghPittsburghUSA
  2. 2.Division of Child NeurologyChildren's Hospital of PittsburghPittsburghUSA

Personalised recommendations