Experimental Chemotherapy of Human Medulloblastoma Cell Lines and Transplantable Xenografts with Bifunctional Alkylating Agents

H. S. Friedman, O. M. Colvin, S. X. Skapek, S. M. Ludeman, G. B. Elion, S. C. Schold, P. F. Jacobsen, L. H. Muhlbaier, D. D. Bigner

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129 Scopus citations

Abstract

A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide, iphosphamide, phenylketocydophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitro- (in vivo) and busulfan (in vivo). Melphalan and phenylketocyclo-phosphamide were the most active agents in vitro with drug doses at which there is a 90% reduction in the number of colonies in comparison to controls of 2.13,5.29, and 4.72 μM for melphalan and 4.60,5.01, and 434 μM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cydophosphamide iphosphamide, phenylketocyclophosphamide and thiotepa produced significant growth delays against s.c. TE-671 and Daoy xenografts, while no activity could be demonstrated for 1,3-bis(2-chloroethyl)-l -nitrosourea or busuffan. Melphalan, cydophosphamide iphosphamide, and thiotepa also produced significant increases in median survival in mice bearing intracranial TE-671 and Daoy xenografts. These results extend our previous studies demonstrating the andtumor activity of nitrogen and phosphoramide mustard-based bifimctional alkylating agents in the treatment of human medulloblastoma continuous cell lines and transplantable xenografts, and support the continued use of these agents in clinical trials.

Original languageEnglish (US)
Pages (from-to)4189-4195
Number of pages7
JournalCancer research
Volume48
Issue number15
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Friedman, H. S., Colvin, O. M., Skapek, S. X., Ludeman, S. M., Elion, G. B., Schold, S. C., Jacobsen, P. F., Muhlbaier, L. H., & Bigner, D. D. (1988). Experimental Chemotherapy of Human Medulloblastoma Cell Lines and Transplantable Xenografts with Bifunctional Alkylating Agents. Cancer research, 48(15), 4189-4195.