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British Journal of Cancer logoLink to British Journal of Cancer
. 1989 Feb;59(2):206–209. doi: 10.1038/bjc.1989.42

Effect of human recombinant tumour necrosis factor and rat gamma interferon on nitrosomethylurea-induced mammary tumours.

P Shah 1, P H van der Meide 1, T Borman 1, N Schroeder 1, J M Bliss 1, R C Coombes 1
PMCID: PMC2246997  PMID: 2495016

Abstract

We have used the nitrosomethylurea-induced rat mammary tumour model to study the effects of parenteral administration of human recombinant tumour necrosis factor (rHu-TNF) and rat gamma interferon (IFN-gamma). An inbred strain of tumour bearing female Ludwig/Wistar/Olac rats were randomised to either treatment or control groups. Two independent studies showed that combined treatment with rHu-TNF and rat IFN-gamma induced significant tumour regression over 4 weeks (P = 0.004, P = 0.005 respectively). Treatment with either rHu-TNF or rat IFN-gamma given individually did not affect the overall rate of tumour growth (P = 0.157 and 0.40 respectively) although an initial reduction in tumour size was observed during the first few days after injection. Measurement of circulating oestradiol levels in groups in which maximum tumour regression was observed showed no statistically significant difference when compared to the control group. Similarly, measurement of oestrogen receptor content showed no statistically significant difference between rHu-TNF-gamma or rat-IFN-gamma treatment or combined treatment of rHu-TNF and IFN-gamma with the control group. We conclude from these observations that combined therapy with rHu-TNF and rat IFN-gamma may prove to be useful new forms of treatment for human breast cancer.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aggarwal B. B., Eessalu T. E., Hass P. E. Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon. Nature. 1985 Dec 19;318(6047):665–667. doi: 10.1038/318665a0. [DOI] [PubMed] [Google Scholar]
  2. Aggarwal B. B., Kohr W. J., Hass P. E., Moffat B., Spencer S. A., Henzel W. J., Bringman T. S., Nedwin G. E., Goeddel D. V., Harkins R. N. Human tumor necrosis factor. Production, purification, and characterization. J Biol Chem. 1985 Feb 25;260(4):2345–2354. [PubMed] [Google Scholar]
  3. Balkwill F. R., Goldstein L., Stebbing N. Differential action of six human interferons against two human carcinomas growing in nude mice. Int J Cancer. 1985 May 15;35(5):613–617. doi: 10.1002/ijc.2910350508. [DOI] [PubMed] [Google Scholar]
  4. Balkwill F. R., Lee A., Aldam G., Moodie E., Thomas J. A., Tavernier J., Fiers W. Human tumor xenografts treated with recombinant human tumor necrosis factor alone or in combination with interferons. Cancer Res. 1986 Aug;46(8):3990–3993. [PubMed] [Google Scholar]
  5. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Creasey A. A., Reynolds M. T., Laird W. Cures and partial regression of murine and human tumors by recombinant human tumor necrosis factor. Cancer Res. 1986 Nov;46(11):5687–5690. [PubMed] [Google Scholar]
  7. Dowsett M., Goss P. E., Powles T. J., Hutchinson G., Brodie A. M., Jeffcoate S. L., Coombes R. C. Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Res. 1987 Apr 1;47(7):1957–1961. [PubMed] [Google Scholar]
  8. Fransen L., Van der Heyden J., Ruysschaert R., Fiers W. Recombinant tumor necrosis factor: its effect and its synergism with interferon-gamma on a variety of normal and transformed human cell lines. Eur J Cancer Clin Oncol. 1986 Apr;22(4):419–426. doi: 10.1016/0277-5379(86)90107-0. [DOI] [PubMed] [Google Scholar]
  9. Gullino P. M., Pettigrew H. M., Grantham F. H. N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst. 1975 Feb;54(2):401–414. [PubMed] [Google Scholar]
  10. Haranaka K., Satomi N., Sakurai A. Antitumor activity of murine tumor necrosis factor (TNF) against transplanted murine tumors and heterotransplanted human tumors in nude mice. Int J Cancer. 1984 Aug 15;34(2):263–267. doi: 10.1002/ijc.2910340219. [DOI] [PubMed] [Google Scholar]
  11. McGuire W. L., DeLaGarza M. Improved sensitivity in the measurement of estrogen receptor in human breast cancer. J Clin Endocrinol Metab. 1973 Dec;37(6):986–989. doi: 10.1210/jcem-37-6-986. [DOI] [PubMed] [Google Scholar]
  12. Männel D. N., Moore R. N., Mergenhagen S. E. Macrophages as a source of tumoricidal activity (tumor-necrotizing factor). Infect Immun. 1980 Nov;30(2):523–530. doi: 10.1128/iai.30.2.523-530.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Satomi N., Haranaka K., Kunii O. Research on the production site of tumor necrosis factor (TNF). Jpn J Exp Med. 1981 Dec;51(6):317–322. [PubMed] [Google Scholar]
  14. Sugarman B. J., Aggarwal B. B., Hass P. E., Figari I. S., Palladino M. A., Jr, Shepard H. M. Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science. 1985 Nov 22;230(4728):943–945. doi: 10.1126/science.3933111. [DOI] [PubMed] [Google Scholar]
  15. Sugarman B. J., Lewis G. D., Eessalu T. E., Aggarwal B. B., Shepard H. M. Effects of growth factors on the antiproliferative activity of tumor necrosis factors. Cancer Res. 1987 Feb 1;47(3):780–786. [PubMed] [Google Scholar]
  16. Travers M. T., Barrett-Lee P. J., Berger U., Luqmani Y. A., Gazet J. C., Powles T. J., Coombes R. C. Growth factor expression in normal, benign, and malignant breast tissue. Br Med J (Clin Res Ed) 1988 Jun 11;296(6637):1621–1624. doi: 10.1136/bmj.296.6637.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wilkinson J. R., Williams J. C., Singh D., Goss P. E., Easton D., Coombes R. C. Response of nitrosomethylurea-induced rat mammary tumor to endocrine therapy and comparison with clinical response. Cancer Res. 1986 Sep;46(9):4862–4865. [PubMed] [Google Scholar]
  18. Williams J. C., Gusterson B. A., Coombes R. C. Spontaneously metastasizing variants derived from MNU-induced rat mammary tumour. Br J Cancer. 1982 Apr;45(4):588–597. doi: 10.1038/bjc.1982.96. [DOI] [PMC free article] [PubMed] [Google Scholar]

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