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, Paul Modrich

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2933-2936
Number of pages4
JournalCancer Research
Volume57
Issue number14
StatePublished - Jul 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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