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Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

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.
AuthorsH S Friedman, S P Johnson, Q Dong, S C Schold, B K Rasheed, S H Bigner, F Ali-Osman, E Dolan, O M Colvin, P Houghton, G Germain, J T Drummond, S Keir, S Marcelli, D D Bigner, P Modrich
JournalCancer research (Cancer Res) Vol. 57 Issue 14 Pg. 2933-6 (Jul 15 1997) ISSN: 0008-5472 [Print] United States
PMID9230204 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Melanocyte-Stimulating Hormones
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
Topics
  • Animals
  • DNA Methylation
  • DNA Repair
  • Drug Resistance
  • Glioblastoma (drug therapy, genetics)
  • Humans
  • Melanocyte-Stimulating Hormones (analysis)
  • Methyltransferases (metabolism)
  • Mice
  • Mice, Inbred BALB C
  • Microsatellite Repeats
  • Neoplasm Transplantation
  • O(6)-Methylguanine-DNA Methyltransferase
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

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