Publications [#134074] of Mark W. Dewhirst

Papers Published

1. ER Lilley, GB Elion, MW Dewhirst, SC Schold, MR Blum, PM Savina, DT Laskowitz, DD Bigner, HS Friedman, Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR., Cancer research, UNITED STATES, vol. 51 no. 15 (August, 1991), pp. 3906-9, ISSN 0008-5472
   (last updated on 2004/03/30)

   Abstract:
   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.

   Keywords:
   Animals • Antineoplastic Agents • Antineoplastic Combined Chemotherapy Protocols • Drug Resistance • Drug Screening Assays, Antitumor • Etoposide • Female • Male • Melphalan • Methyltransferases • Mice • Mice, Inbred BALB C • Mice, Nude • Neoplasm Transplantation • O(6)-Methylguanine-DNA Methyltransferase • Oxygen • Rhabdomyosarcoma • administration & dosage • drug therapy* • enzymology • metabolism • pathology • pharmacology* • physiology • toxicity