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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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, phenylketocyclophosphamide, thiotepa, 1,3-bis(2-chloroethyl)-1-nitrosourea (in vivo), and busulfan (in vivo). Melphalan and phenylketocyclophosphamide 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 4.34 μM for phenylketocyclophosphamide against TE-671, D283 Med, and Daoy, respectively. Melphalan, cyclophosphamide, 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)-1-nitrosourea or busulfan. Melphalan, cyclophosphamide, 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 antitumor activity of nitrogen and phosphoramide mustard-based bifunctional 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 - 1988

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Medulloblastoma
Melphalan
Alkylating Agents
Heterografts
Thiotepa
Ifosfamide
Drug Therapy
Cell Line
Cyclophosphamide
Carmustine
Busulfan
Nude Mice
Pharmaceutical Preparations
Nitrogen
Clinical Trials
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Friedman, H. S., Colvin, O. M., Skapek, S. X., Ludeman, S. M., Elion, G. B., Schold, S. C., ... Bigner, D. D. (1988). Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents. Cancer Research, 48(15), 4189-4195.

Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents. / 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.

In: Cancer Research, Vol. 48, No. 15, 1988, p. 4189-4195.

Research output: Contribution to journalArticle

Friedman, HS, Colvin, OM, Skapek, SX, Ludeman, SM, Elion, GB, Schold, SC, Jacobsen, PF, Muhlbaier, LH & Bigner, DD 1988, 'Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents', Cancer Research, vol. 48, no. 15, pp. 4189-4195.
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. / Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents. In: Cancer Research. 1988 ; Vol. 48, No. 15. pp. 4189-4195.
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AU - Elion, G. B.

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