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Experimental Therapeutics

Methylator Resistance Mediated by Mismatch Repair Deficiency in a Glioblastoma Multiforme Xenograft

Henry S. Friedman, Stewart P. Johnson, Qing Dong, S. Clifford Schold, B. K. Ahmed Rasheed, Sandra H. Bigner, Francis Ali-Osman, Eileen Dolan, O. Michael Colvin, Peter Houghton, Glen Germain, James T. Drummond, Stephen Keir, Susan Marcelli, Darell D. Bigner and Paul Modrich
Henry S. Friedman
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Stewart P. Johnson
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Qing Dong
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S. Clifford Schold
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B. K. Ahmed Rasheed
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Sandra H. Bigner
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Francis Ali-Osman
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Eileen Dolan
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O. Michael Colvin
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Peter Houghton
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Glen Germain
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James T. Drummond
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Stephen Keir
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Susan Marcelli
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Darell D. Bigner
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Paul Modrich
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DOI:  Published July 1997
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Abstract

A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.

Footnotes

  • ↵1 This work was supported by NIH Grants CA 23099, CA 16783, CA 71627, NS 30245, NS 20034, and GM 45190.

  • ↵2 To whom requests for reprints should be addressed, at Duke University Medical Center, Department of Pediatrics, Box 3624, Durham, NC 27710, Phone: (919) 684-8722; Fax: (919) 684-8918.

  • Received January 23, 1997.
  • Accepted May 7, 1997.
  • ©1997 American Association for Cancer Research.
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July 1997
Volume 57, Issue 14
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Methylator Resistance Mediated by Mismatch Repair Deficiency in a Glioblastoma Multiforme Xenograft
Henry S. Friedman, Stewart P. Johnson, Qing Dong, S. Clifford Schold, B. K. Ahmed Rasheed, Sandra H. Bigner, Francis Ali-Osman, Eileen Dolan, O. Michael Colvin, Peter Houghton, Glen Germain, James T. Drummond, Stephen Keir, Susan Marcelli, Darell D. Bigner and Paul Modrich
Cancer Res July 15 1997 (57) (14) 2933-2936;

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Methylator Resistance Mediated by Mismatch Repair Deficiency in a Glioblastoma Multiforme Xenograft
Henry S. Friedman, Stewart P. Johnson, Qing Dong, S. Clifford Schold, B. K. Ahmed Rasheed, Sandra H. Bigner, Francis Ali-Osman, Eileen Dolan, O. Michael Colvin, Peter Houghton, Glen Germain, James T. Drummond, Stephen Keir, Susan Marcelli, Darell D. Bigner and Paul Modrich
Cancer Res July 15 1997 (57) (14) 2933-2936;
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