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Hyperthermia-induced enhancement of melphalan activity against a melphalan-resistant human rhabdomyosarcoma xenograft.

Publication ,  Journal Article
Laskowitz, DT; Elion, GB; Dewhirst, MW; Griffith, OW; Savina, PM; Blum, MR; Prescott, DM; Bigner, DD; Friedman, HS
Published in: Radiat Res
February 1992

The effects of regional hyperthermia (42 degrees C for 70 min) on the antitumor activity of melphalan were examined in athymic mice bearing melphalan-resistant human rhabdomyosarcoma (TE-671 MR) xenografts growing in the right hind limb, and results were compared with similar studies of melphalan-sensitive (TE-671) parent xenografts. Melphalan alone at a dose of 36 mg/m2 (0.5 of the 10% lethal dose) produced growth delays of 4.1 to 10.2 days in TE-671 MR xenografts and 21.8 to 28.7 days in TE-671, respectively. Hyperthermia alone produced growth delays of 0.9 days in TE-671 MR xenografts and 0.8 days in TE-671. Combination therapy with melphalan and hyperthermia produced growth delays of 7.2 to 13.3 days in TE-671 MR xenografts and 34.3 to 42.8 days in TE-671, respectively, representing a mean thermal enhancement ratio of 1.7 in TE-671 MR and 1.5 in TE-671. Measurement of glutathione levels in TE-671 MR xenografts following treatment with melphalan, hyperthermia, or melphalan plus hyperthermia revealed significant reductions in glutathione content with the nadir (60% of control values) seen 6 h following treatment. Glutathione levels in TE-671 xenografts following identical therapy revealed no differences from control values. Hyperthermia plus melphalan did not result in a higher tumor-to-plasma melphalan ratio compared with treatment with melphalan alone in either TE-671 MR or TE-671 xenografts. These studies suggest that heat-induced alterations in tumor glutathione or melphalan levels are not responsible for the increase in melphalan activity produced by hyperthermia. Combination therapy with melphalan plus regional hyperthermia offers promise for treatment of melphalan-resistant neoplasms.

Duke Scholars

Published In

Radiat Res

ISSN

0033-7587

Publication Date

February 1992

Volume

129

Issue

2

Start / End Page

218 / 223

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Rhabdomyosarcoma
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Melphalan
  • Male
  • Hyperthermia, Induced
 

Citation

APA
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ICMJE
MLA
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Laskowitz, D. T., Elion, G. B., Dewhirst, M. W., Griffith, O. W., Savina, P. M., Blum, M. R., … Friedman, H. S. (1992). Hyperthermia-induced enhancement of melphalan activity against a melphalan-resistant human rhabdomyosarcoma xenograft. Radiat Res, 129(2), 218–223.
Laskowitz, D. T., G. B. Elion, M. W. Dewhirst, O. W. Griffith, P. M. Savina, M. R. Blum, D. M. Prescott, D. D. Bigner, and H. S. Friedman. “Hyperthermia-induced enhancement of melphalan activity against a melphalan-resistant human rhabdomyosarcoma xenograft.Radiat Res 129, no. 2 (February 1992): 218–23.
Laskowitz DT, Elion GB, Dewhirst MW, Griffith OW, Savina PM, Blum MR, et al. Hyperthermia-induced enhancement of melphalan activity against a melphalan-resistant human rhabdomyosarcoma xenograft. Radiat Res. 1992 Feb;129(2):218–23.
Laskowitz, D. T., et al. “Hyperthermia-induced enhancement of melphalan activity against a melphalan-resistant human rhabdomyosarcoma xenograft.Radiat Res, vol. 129, no. 2, Feb. 1992, pp. 218–23.
Laskowitz DT, Elion GB, Dewhirst MW, Griffith OW, Savina PM, Blum MR, Prescott DM, Bigner DD, Friedman HS. Hyperthermia-induced enhancement of melphalan activity against a melphalan-resistant human rhabdomyosarcoma xenograft. Radiat Res. 1992 Feb;129(2):218–223.

Published In

Radiat Res

ISSN

0033-7587

Publication Date

February 1992

Volume

129

Issue

2

Start / End Page

218 / 223

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Rhabdomyosarcoma
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Melphalan
  • Male
  • Hyperthermia, Induced