Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts

M. Eileen Dolan, Matthew J. Fleig, Burt G.F. Feuerstein, Hirak S. Basu, Gordon D. Luk, Robert A. Casero, Laurence J. Marton

Research output: Contribution to journalArticle

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Abstract

The polyamine analogue 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), 5 mg/kg i.p., was given twice daily on days 0-3 and 7-10 (cycle 1) to nude mice with human malignant gliomas (SF-767 and U-87 MG), lung adenocarcinoma (A549), and colon carcinomas (HCT116 and HT29). A second cycle of drug was given to mice with SF-767 and A549 tumors on days 42-45 and 49-52. The maximum animal weight loss varied between 4 and 12%, which was observed 10-15 days following the initiation of treatment, but no overt toxic reactions were noted. The SF-767 brain tumors were extremely responsive to BE-4-4-4-4 alone (3 of 8 complete regressions after 2 cycles); however, the growth of the U-87 MG brain tumor was only slightly inhibited by BE-4-4-4-4 treatment. There was significant inhibition of tumor growth after treatment with one cycle of BE-4-4-4-4 in animals carrying the A549, HCT116, and HT29 tumors. At day 73, the growth of the A549 tumor was inhibited by 78 and 89% following one or two cycles of BE-4-4-4-4, respectively. The mitotic index of A549 tumors was 18 times greater in control mice than in those treated with BE-4-4-4-4 for one or two cycles 99 days after initiation of treatment. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) was given to mice carrying the U-87 MG or A549 tumors on day 4 (cycle 1) and day 46 (cycle 2) in the maximal tolerated dose of 50 mg/kg for BCNU alone and 40 mg/kg for BCNU plus BE-4-4-4-4. BCNU alone significantly inhibited the growth of U-87 MG tumors but not the growth of A549 tumors. Treatment with the combination of BCNU and BE-4-4-4-4 was significantly better than BCNU alone for A549 tumors and better than BE-4-4-4-4 alone for U87 tumors. However, in both animal groups treated with the combination, there was a significant weight loss, which was not observed for animals treated with either agent alone. These data suggest a role for BE-4-4-4-4 in the treatment of brain, lung, and colon tumors.

Original languageEnglish (US)
Pages (from-to)4698-4702
Number of pages5
JournalCancer Research
Volume54
Issue number17
StatePublished - Sep 1 1994
Externally publishedYes

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Heterografts
Carmustine
Neoplasms
Growth
Brain Neoplasms
Weight Loss
Colon
BE 4-4-4-4
Mitotic Index
Maximum Tolerated Dose
Poisons
Polyamines
Nude Mice
Glioma
Carcinoma
Lung
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dolan, M. E., Fleig, M. J., Feuerstein, B. G. F., Basu, H. S., Luk, G. D., Casero, R. A., & Marton, L. J. (1994). Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts. Cancer Research, 54(17), 4698-4702.

Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts. / Dolan, M. Eileen; Fleig, Matthew J.; Feuerstein, Burt G.F.; Basu, Hirak S.; Luk, Gordon D.; Casero, Robert A.; Marton, Laurence J.

In: Cancer Research, Vol. 54, No. 17, 01.09.1994, p. 4698-4702.

Research output: Contribution to journalArticle

Dolan, ME, Fleig, MJ, Feuerstein, BGF, Basu, HS, Luk, GD, Casero, RA & Marton, LJ 1994, 'Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts', Cancer Research, vol. 54, no. 17, pp. 4698-4702.
Dolan ME, Fleig MJ, Feuerstein BGF, Basu HS, Luk GD, Casero RA et al. Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts. Cancer Research. 1994 Sep 1;54(17):4698-4702.
Dolan, M. Eileen ; Fleig, Matthew J. ; Feuerstein, Burt G.F. ; Basu, Hirak S. ; Luk, Gordon D. ; Casero, Robert A. ; Marton, Laurence J. / Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts. In: Cancer Research. 1994 ; Vol. 54, No. 17. pp. 4698-4702.
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abstract = "The polyamine analogue 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), 5 mg/kg i.p., was given twice daily on days 0-3 and 7-10 (cycle 1) to nude mice with human malignant gliomas (SF-767 and U-87 MG), lung adenocarcinoma (A549), and colon carcinomas (HCT116 and HT29). A second cycle of drug was given to mice with SF-767 and A549 tumors on days 42-45 and 49-52. The maximum animal weight loss varied between 4 and 12{\%}, which was observed 10-15 days following the initiation of treatment, but no overt toxic reactions were noted. The SF-767 brain tumors were extremely responsive to BE-4-4-4-4 alone (3 of 8 complete regressions after 2 cycles); however, the growth of the U-87 MG brain tumor was only slightly inhibited by BE-4-4-4-4 treatment. There was significant inhibition of tumor growth after treatment with one cycle of BE-4-4-4-4 in animals carrying the A549, HCT116, and HT29 tumors. At day 73, the growth of the A549 tumor was inhibited by 78 and 89{\%} following one or two cycles of BE-4-4-4-4, respectively. The mitotic index of A549 tumors was 18 times greater in control mice than in those treated with BE-4-4-4-4 for one or two cycles 99 days after initiation of treatment. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) was given to mice carrying the U-87 MG or A549 tumors on day 4 (cycle 1) and day 46 (cycle 2) in the maximal tolerated dose of 50 mg/kg for BCNU alone and 40 mg/kg for BCNU plus BE-4-4-4-4. BCNU alone significantly inhibited the growth of U-87 MG tumors but not the growth of A549 tumors. Treatment with the combination of BCNU and BE-4-4-4-4 was significantly better than BCNU alone for A549 tumors and better than BE-4-4-4-4 alone for U87 tumors. However, in both animal groups treated with the combination, there was a significant weight loss, which was not observed for animals treated with either agent alone. These data suggest a role for BE-4-4-4-4 in the treatment of brain, lung, and colon tumors.",
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N2 - The polyamine analogue 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), 5 mg/kg i.p., was given twice daily on days 0-3 and 7-10 (cycle 1) to nude mice with human malignant gliomas (SF-767 and U-87 MG), lung adenocarcinoma (A549), and colon carcinomas (HCT116 and HT29). A second cycle of drug was given to mice with SF-767 and A549 tumors on days 42-45 and 49-52. The maximum animal weight loss varied between 4 and 12%, which was observed 10-15 days following the initiation of treatment, but no overt toxic reactions were noted. The SF-767 brain tumors were extremely responsive to BE-4-4-4-4 alone (3 of 8 complete regressions after 2 cycles); however, the growth of the U-87 MG brain tumor was only slightly inhibited by BE-4-4-4-4 treatment. There was significant inhibition of tumor growth after treatment with one cycle of BE-4-4-4-4 in animals carrying the A549, HCT116, and HT29 tumors. At day 73, the growth of the A549 tumor was inhibited by 78 and 89% following one or two cycles of BE-4-4-4-4, respectively. The mitotic index of A549 tumors was 18 times greater in control mice than in those treated with BE-4-4-4-4 for one or two cycles 99 days after initiation of treatment. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) was given to mice carrying the U-87 MG or A549 tumors on day 4 (cycle 1) and day 46 (cycle 2) in the maximal tolerated dose of 50 mg/kg for BCNU alone and 40 mg/kg for BCNU plus BE-4-4-4-4. BCNU alone significantly inhibited the growth of U-87 MG tumors but not the growth of A549 tumors. Treatment with the combination of BCNU and BE-4-4-4-4 was significantly better than BCNU alone for A549 tumors and better than BE-4-4-4-4 alone for U87 tumors. However, in both animal groups treated with the combination, there was a significant weight loss, which was not observed for animals treated with either agent alone. These data suggest a role for BE-4-4-4-4 in the treatment of brain, lung, and colon tumors.

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