Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR.

Published

Journal Article

Investigations with the melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR were carried out to identify patterns of cross-resistance and collateral sensitivity and to define the mechanism(s) mediating melphalan resistance. TE-671 MR was cross-resistant to thio-TEPA, mitomycin, vincristine, and cisplatin, and partially resistant to chlorambucil and cyclophosphamide. TE-671 MR and the parent line TE-671 were both resistant to 1,3-bis(2-chloroethyl)-nitrosourea and expressed similar levels of O6-alkylguanine-DNA alkyltransferase. TE-671 MR retained full sensitivity to actinomycin D and demonstrated enhanced sensitivity to VP-16 compared to TE-671. Treatment of TE-671 MR with melphalan plus VP-16 resulted in greater than additive growth delays. The frequency of hypoxic regions was similar in TE-671 MR and TE-671, respectively. Measurement of tumor-to-plasma levels at 180 min following i.p. administration of melphalan at 0.5 of the 10% lethal dosage showed mean tumor-to-plasma ratios of 3.81 in TE-671 MR and 7.38 in TE-671, respectively. The lower drug levels in TE-671 MR may be contributing to the resistance to melphalan and thus indicate the need for further studies to define the reasons for these differences in tumor drug level.

Full Text

Duke Authors

Cited Authors

  • Lilley, ER; Elion, GB; Dewhirst, MW; Schold, SC; Blum, MR; Savina, PM; Laskowitz, DT; Bigner, DD; Friedman, HS

Published Date

  • August 1, 1991

Published In

Volume / Issue

  • 51 / 15

Start / End Page

  • 3906 - 3909

PubMed ID

  • 1855207

Pubmed Central ID

  • 1855207

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng

Conference Location

  • United States