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Busulfan therapy of central nervous system xenografts in athymic mice

  • Original Article
  • Busulfan, Xenografts, Brain Tumor
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Abstract

We evaluated the antitumor activity of busulfan against a panel of tumor cell lines and xenografts in athymic nude mice derived from childhood high-grade glioma, adult high-grade glioma, ependymoma, and medulloblastoma. Busulfan displayed similar activity against a panel of four medulloblastoma cell lines (D283 Med, Daoy, D341 Med, and D425 Med) and four corresponding sublines with laboratory-generated or clinically acquired resistance to 4-hydroperoxycyclophosphamide [D283 Med (4-HCR), Daoy (4-HCR), D341 Med (4-HCR), and D458 Med] and cross-resistance to melphalan. This is consistent with a nearly total lack of cross-resistance of busulfan to 4-hydroperoxycyclophosphamide. Busulfan was active in the therapy of all but one of the subcutaneous xenografts tested, with growth delays ranging from 14.3 days in D612 EP to 58.4 days in D528 EP. Busulfan produced statistically significant increases in the median survival of mice bearing intracranial D456 MG (66%–90%), D612 EP (18%–33%), and D528 EP (89%) xenografts. These studies suggest that busulfan may be active against medulloblastomas, highgrade gliomas, and ependymomas as well as against cyclophosphamide-resistant neoplasms.

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Authors and Affiliations

  1. Department of Pediatrics, Duke University Medical Center, 27710, Durham, NC, USA

    Rosemary H. Aaron, Michael Graham, Steven Keir & Henry S. Friedman

  2. Department of Pathology, Duke University Medical Center, 27710, Durham, NC, USA

    Darell D. Bigner & Henry S. Friedman

  3. Department of Pharmacology, Duke University Medical Center, 27710, Durham, NC, USA

    Gertrude B. Elion

  4. Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, 27710, Durham, NC, USA

    Darell D. Bigner & Henry S. Friedman

  5. The Johns Hopkins Oncology Center, The Johns Hopkins University, 21205, Baltimore, MD, USA

    O. Michael Colvin

Authors
  1. Rosemary H. Aaron
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  2. Gertrude B. Elion
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  3. O. Michael Colvin
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  4. Michael Graham
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  5. Steven Keir
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  6. Darell D. Bigner
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  7. Henry S. Friedman
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Additional information

This work was supported by National Institutes of Health grants NS 20023, NS 30245, CA 11898, and CA 56115 and American Cancer Society grant DHP-67E

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Aaron, R.H., Elion, G.B., Colvin, O.M. et al. Busulfan therapy of central nervous system xenografts in athymic mice. Cancer Chemother. Pharmacol. 35, 127–131 (1994). https://doi.org/10.1007/BF00686634

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  • DOI: https://doi.org/10.1007/BF00686634

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