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

Publication ,  Journal Article
Lilley, ER; Elion, GB; Dewhirst, MW; Schold, SC; Blum, MR; Savina, PM; Laskowitz, DT; Bigner, DD; Friedman, HS
Published in: Cancer Res
August 1, 1991

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 1, 1991

Volume

51

Issue

15

Start / End Page

3906 / 3909

Location

United States

Related Subject Headings

  • Rhabdomyosarcoma
  • Oxygen
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Methyltransferases
  • Melphalan
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lilley, E. R., Elion, G. B., Dewhirst, M. W., Schold, S. C., Blum, M. R., Savina, P. M., … Friedman, H. S. (1991). Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR. Cancer Res, 51(15), 3906–3909.
Lilley, E. R., G. B. Elion, M. W. Dewhirst, S. C. Schold, M. R. Blum, P. M. Savina, D. T. Laskowitz, D. D. Bigner, and H. S. Friedman. “Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR.Cancer Res 51, no. 15 (August 1, 1991): 3906–9.
Lilley ER, Elion GB, Dewhirst MW, Schold SC, Blum MR, Savina PM, et al. Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR. Cancer Res. 1991 Aug 1;51(15):3906–9.
Lilley, E. R., et al. “Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR.Cancer Res, vol. 51, no. 15, Aug. 1991, pp. 3906–09.
Lilley ER, Elion GB, Dewhirst MW, Schold SC, Blum MR, Savina PM, Laskowitz DT, Bigner DD, Friedman HS. Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR. Cancer Res. 1991 Aug 1;51(15):3906–3909.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

August 1, 1991

Volume

51

Issue

15

Start / End Page

3906 / 3909

Location

United States

Related Subject Headings

  • Rhabdomyosarcoma
  • Oxygen
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Methyltransferases
  • Melphalan