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O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials.

Publication ,  Journal Article
Keir, ST; Dolan, ME; Pegg, AE; Lawless, A; Moschel, RC; Bigner, DD; Friedman, HS
Published in: Cancer Chemother Pharmacol
2000

PURPOSE: To evaluate the role of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus O6-benzylguanine (O6-BG) in the treatment of both Mer+ and Mer- tumors. METHODS: The effect of pretreatment with O6-BG on the activity of BCNU against Mer- human central nervous tumor xenografts D-54 MG and D-245 MG was evaluated in athymic nude mice. RESULTS: BCNU (1.0 LD10; dose lethal to 10% of treated animals) produced growth delays of 8.9 days and 7.5 days and tumor regressions in six of ten and one of nine animals against D-54 MG, which was derived from a human malignant glioma xenograft. Dose reduction of BCNU to 0.38 LD10 eliminated antitumor activity. The combination of BCNU (0.38 LD10) plus O6-BG produced growth delays of 8.8 days and 7.9 days, with tumor regressions in four of ten and two of nine animals, respectively. BCNU (1.0 LD10) produced a growth delay of 49.8 days and ten of ten tumor regressions against D-245 MG, which was derived from a glioblastoma multiforme. BCNU (0.38 LD10) produced a growth delay of 19.4 days, with nine of ten tumor regressions. The combination of BCNU (0.38 LD10) plus O6-BG produced a growth delay of 65.7 days and seven of eight tumor regressions. CONCLUSION: These results suggest that the combination of BCNU plus O6-BG may be a rational intervention for both Mer+ as well as Mer- tumors.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

2000

Volume

45

Issue

6

Start / End Page

437 / 440

Location

Germany

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Humans
  • Guanine
 

Citation

APA
Chicago
ICMJE
MLA
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Keir, S. T., Dolan, M. E., Pegg, A. E., Lawless, A., Moschel, R. C., Bigner, D. D., & Friedman, H. S. (2000). O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials. Cancer Chemother Pharmacol, 45(6), 437–440. https://doi.org/10.1007/s002800051016
Keir, S. T., M. E. Dolan, A. E. Pegg, A. Lawless, R. C. Moschel, D. D. Bigner, and H. S. Friedman. “O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials.Cancer Chemother Pharmacol 45, no. 6 (2000): 437–40. https://doi.org/10.1007/s002800051016.
Keir ST, Dolan ME, Pegg AE, Lawless A, Moschel RC, Bigner DD, et al. O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials. Cancer Chemother Pharmacol. 2000;45(6):437–40.
Keir, S. T., et al. “O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials.Cancer Chemother Pharmacol, vol. 45, no. 6, 2000, pp. 437–40. Pubmed, doi:10.1007/s002800051016.
Keir ST, Dolan ME, Pegg AE, Lawless A, Moschel RC, Bigner DD, Friedman HS. O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials. Cancer Chemother Pharmacol. 2000;45(6):437–440.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

2000

Volume

45

Issue

6

Start / End Page

437 / 440

Location

Germany

Related Subject Headings

  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • O(6)-Methylguanine-DNA Methyltransferase
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Humans
  • Guanine