Advertisement

The Therapeutic Response of a Variety of Human Tumour Xenografts

  • G. G. Steel
  • M. J. Peckham
Part of the ESO Monographs book series (ESO MONOGRAPHS)

Abstract

This paper reviews a research programme on human tumour xenografts that has been under way since around 1975. Its objectives have been to establish xenografts that are representative of a number of tumour types, to investigate their biological characteristics and to evaluate their therapeutic response. We have been interested in the evaluation of response both to chemotherapy and radiotherapy. During the period 1975–1983 our major effort was on response to cytotoxic drugs. At that time it was recognised that chemotherapeutic agents are more selective than radiation in killing tumour cells, for instance, the range of sensitivities observed for different tumour cell types treated with a particular drug is much wider than for radiation (26). We reasoned that since human tumours no doubt change their biological characteristics to some degree during transplantation from man to mouse, it was more likely that the ranking of chemotherapeutic response would be maintained than that response to radiation would do so, especially since in vivo radiation response is so dependent on conditions of local oxygenation.

Keywords

Human Tumour Xenograft Carcinoma Xenograft Volume Doubling Time Cell Survival Curve Clonogenic Cell Survival 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bailey MJ, Gazet JC and Peckham MJ: Human breast cancer xenografts in immune-suppressed mice. Br J Cancer 1980 (42): 524–529PubMedCrossRefGoogle Scholar
  2. 2.
    Bailey MJ, Gazet JC, Smith IE, Steel GG: Chemotherapy of human breast-carcinoma xenografts. Br J Cancer 1980 (42): 530–536PubMedCrossRefGoogle Scholar
  3. 3.
    Bailey M, Jones A, Raghavan D, Selby P, Shorthouse A, Gibbs J, Peckham MJ: Limitations of human tumour xenografts in individual patient drug-sensitivity testing (Abstract). Br J Cancer 1981 (43): 725CrossRefGoogle Scholar
  4. 4.
    Berman R, Gusterson B and Steel GG: Resistance to alkylating agents and tumour differentiation in xenografts of small cell lung cancer. Br J Cancer 1985 (51): 653–658PubMedCrossRefGoogle Scholar
  5. 5.
    Berman R and Steel GG: Induced and inherent resistance to alkylating agents in human small-cell bronchial carcinoma xenografts. Br J Cancer 1984 (49): 431–436PubMedCrossRefGoogle Scholar
  6. 6.
    Courtenay VF, Mills J: An in vitro colony assay for human tumours grown in immune-suppressed mice and treated in vivo with cytotoxic agents. Br J Cancer 1978 (37): 261–268PubMedCrossRefGoogle Scholar
  7. 7.
    Courtenay VD, Mills J, Steel GG: The spectrum of chemosensitivity of two human pancreatic carcinoma xenografts. Br J Cancer 1982 (46): 436–439PubMedCrossRefGoogle Scholar
  8. 8.
    Deacon J, Peckham MJ and Steel GG: The radioresponsiveness of human tumours and initial slope of the cell survival curve. Radiother and Oncol 1984 (2): 317–323CrossRefGoogle Scholar
  9. 9.
    Deacon JM, Wilson PA and Peckham MJ: The radiobiology of human neuroblastoma. Radiother and Oncol 1985 (3): 201–209CrossRefGoogle Scholar
  10. 10.
    Deacon JM, Wilson PA and Steel GG: Radiosensitivity of neuroblastoma. Advances in Neuroblastoma Research 1985: 525–531Google Scholar
  11. 11.
    Duchesne G, Peacock J and Steel GG: The acute in vitro and in vivo radiosensitivity of human lung tumour lines. Radiother and Oncol 1986 (7): 353–361CrossRefGoogle Scholar
  12. 12.
    Fertil B and Malaise EP: Inherent radiosensitivity as a basic concept for human tumour radiotherapy. Int J Radiat Oncol Biol Phys 1981 (7): 621–629PubMedCrossRefGoogle Scholar
  13. 13.
    Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE: Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Rep 1966 (50): 219–234PubMedGoogle Scholar
  14. 14.
    Gibbs J, Peckham MJ and Steel GG (unpublished)Google Scholar
  15. 15.
    Jones AC, Wilson PA, and Steel GG: Cell survival in four ovarian carcinoma xenografts following in vitro exposure to melphalan, cisplatin and JM8. Cancer Chemother Pharmacol 1984 (13): 109–113PubMedCrossRefGoogle Scholar
  16. 16.
    Kelland LR, Burgess L, and Steel GG: Characterisation of four new cell lines derived from human squamous carcinomas of the uterine cervix. Cancer Res 1987 (47): 4947–4952PubMedGoogle Scholar
  17. 17.
    Millar JL, Blackett NM, Hudspith BN: Enhanced postirradiation recovery of the haemopoietic system in animals pretreat-ed with a variety of cytotoxic agents. Cel Tiss Kinet 1978 (11): 543–553Google Scholar
  18. 18.
    Nowak K, Peckham MK, Steel GG: Variation in response of xenografts of colo-rectal carcinoma to chemotherapy. Br J Cancer 1978 (37): 576–584PubMedCrossRefGoogle Scholar
  19. 19.
    Peacock JH (unpublished)Google Scholar
  20. 20.
    Phelps, TA: Cytarabin (Ara-C) induced radioresistance of mouse jejunal stem cells following single or fractionated doses of radiation. Int J Radiat Oncol Biol Phys 1980 (6): 1671–1677PubMedCrossRefGoogle Scholar
  21. 21.
    Pickard RG, Cobb LM, Steel GG: The growth kinetics of xenografts of human colorectal tumours in immune-deprived mice. Br J Cancer 1975 (31): 36–45PubMedCrossRefGoogle Scholar
  22. 22.
    Selby PJ, Courtenay VD, McElwain TJ, Peckham MJ and Steel GG: Colony growth and clonogenic cell survival in human melanoma xenografts treated with chemotherapy. Br J Cancer 1980 (42): 438–447PubMedCrossRefGoogle Scholar
  23. 23.
    Selby PJ and Thomas JM: Clonogenic cell survival curves for human melanoma xenografts using agar diffusion chamber and lung colony assays. Br J Cancer 1980 (41 Suppl IV): 150–153Google Scholar
  24. 24.
    Shorthouse AJ, Carter SM, Ellison ML: Tumour marker production in human bronchial carcinoma xenografts. Oncodevelop Biol Med 1982 (3): 273–281Google Scholar
  25. 25.
    Shorthouse AJ, Jones JM, Steel GG and Peckham MJ: Experimental combination and single-agent chemotherapy in human lung-tumour xenografts. Br J Cancer 1982 (46): 35–44PubMedCrossRefGoogle Scholar
  26. 26.
    Steel GG: The growth kinetics of tumours. Oxford University Press, London 1977, pp 255–265Google Scholar
  27. 27.
    Steel GG: Therapeutic response of human tumour xenografts in immune-suppressed mice. In: Sordat B (ed) Immune-deficient animals in experimental research. Karger AG, Basel 1984, pp 395–404Google Scholar
  28. 28.
    Steel GG: How well do xenografts maintain the therapeutic characteristics of the source tumour in the donor patient? In: RF Kallman (ed) Rodent tumours in experimental cancer therapy. 1987 pp 205–208Google Scholar
  29. 29.
    Steel GG, Courtenay VD and Peckham MJ: The immune-suppressed mouse as an alternative host for heterotransplantation. In: Fogh J and Giovanella BC (eds) The nude mouse in experimental and clinical research, Vol. 2. Academic Press Inc 1982, pp 207–227Google Scholar
  30. 30.
    Steel GG, Courtenay VD and Peckham MJ: The response to chemotherapy of a variety of human tumour xenografts. Br J Cancer 1983(47): 1–13PubMedCrossRefGoogle Scholar
  31. 31.
    Steel GG, Courtenay VD, Phelps TA and Peckham MJ: The therapeutic response of human tumour xenografts. In: Sparrow S (ed) Symposium on immuno-deficient animals in cancer research. McMillan, London 1980, pp 179–189Google Scholar
  32. 32.
    Steel GG, Deacon JM, Duchesne GM, Horwich A, Kelland LR and Peacock JH: The dose-rate effect in human tumour cells. Radiother and Oncol 1987. Radiother and Oncol 1987 (9): 299–310Google Scholar
  33. 33.
    Steel GG, Down JD, Peacock JH and Stephens TC: Doserate effects and the repair of radiation damage. Radiother and Oncol 1986 (5): 321–331CrossRefGoogle Scholar
  34. 34.
    Thomas JM: A lung colony clonogenic cell assay for human malignant melanoma in immune-suppressed mice and its use to determine chemosensitivity, radiosensitivity and the relationship between tumour size and response to therapy. Br J Surg 1979 (66): 696–700PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • G. G. Steel
    • 1
  • M. J. Peckham
    • 1
  1. 1.Radiotherapy Research UnitInstitute of Cancer ResearchSutton, SurreyUK

Personalised recommendations