Advertisement

Tumor Growth Fraction Estimation, Perturbation, and Prognostication

  • Paul G. Braunschweiger
Protocol
Part of the Biological Methods book series (BM)

Abstract

The concept that solid tumors can be comprised of both actively cycling and noncycling cell populations was originally proposed by Mendelsohn (32) to account for the observation that after [3H]-TdR (tritiated thymidine) labeling in vivo, the fraction of labeled mitotic cells always exceeded that for interphase cells. Since the mitotic population can be considered a pure cycling cohort, it was concluded that a significant portion of the interphase population must be in a noncycling or quiescent (Q) configuration. The term “growth fraction (GF)” was thus coined to distinguish the cell population, in the tumor, that is actively engaged in cell cycle traverse (P cells) from that that is not (Q cells).

Keywords

Acridine Orange Growth Fraction Mammary Tumor Cell Pulse Label Cell Cycle Time 
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.

References

  1. 1.
    Barker, M., Hoshino, T., Gurcay, O., Wilson, C. B., Nielson, S. L., Downie, R., and Eliason, J. Development of an animal brain tumor model and its response to therapy with 1, 3-bis (2-chloroethyl 1)-1-nitrosourea. Cancer Res., 33: 976–986, 1973.PubMedGoogle Scholar
  2. 2.
    Barret, J. C. A mathematical model of the mitotic cycle and its application to the interpretation of percentage labeled mitosis data. J. Natl. Cancer Inst., 37: 443–950, 1966.Google Scholar
  3. 3.
    Barrett, J. C. Optimized parameters for the mitotic cycle. Cell Tissue Kinet., 3: 349–353, 1970.PubMedGoogle Scholar
  4. 4.
    Braunschweiger, P. G., Poulakos, L., and Schiffer, L. M. In vitro labeling and gold activation autoradiography for determination of labeling index and DNA synthesis time of solid tumors. Cancer Res., 36: 1748–1753, 1976.PubMedGoogle Scholar
  5. 5.
    Braunschweiger, P. G., Poulakos, L., and Schiffer, L. M. Cell kinetics in vivo and in vitro for C3H/He spontaneous mammary tumors. J. Natl. Cancer Inst., 59: 1197–1204, 1977.PubMedGoogle Scholar
  6. 6.
    Braunschweiger, P. G., Schenken, L. L., and Schiffer, L. M. The cytokinetic basis for the design of efficacious radiotheraphy protocols. Int. J. Radiat. Oncol. Biol. Phys., 5: 37–47, 1979.PubMedGoogle Scholar
  7. 7.
    Braunschweiger, P. G., Schenken, L. L., and Schiffer, L. M. Kinetically directed combination therapy with adriamycin and X-irradiation in a mammary tumor model. Int. J. Radiat. Oncol. Biol. Phys., 7: 747–753, 1981.PubMedCrossRefGoogle Scholar
  8. 8.
    Braunschweiger, P. G. and Schiffer, L. M. Nuclear DNA polymerase-α and replicative potential in mammalian cells. Eur. J. Cancer, 13: 775–779, 1977.PubMedGoogle Scholar
  9. 9.
    Braunschweiger, P. G. and Schiffer, L. M. PDP indices in human tumors: Evidence for proliferative correlations. Proc. Am. Soc. Clin. Oncol., 18: 276, 1977.Google Scholar
  10. 10.
    Braunschweiger, P. G. and Schiffer, L. M. Therapeutic implications of cell kinetic changes after cyclophosphamide treatment in “spontaneous” and “transplantable” mammary tumors. Cancer Treat. Rep., 62: 727–736, 1978.Google Scholar
  11. 11.
    Braunschweiger, P. G. and Schiffer, L. M. Cell kinetics after vin-cristine treatment of C3H/HeJ spontaneous mammary tumors: Implications for therapy. J. Natl. Cancer Inst., 60: 1043–1048, 1978.PubMedGoogle Scholar
  12. 12.
    Braunschweiger, P. G. and Schiffer, L. M. The effect of methylpred-nisilone on the cell kinetic response of C3H/HeJ mammary tumors to cyclophosphamide and adriamycin. Cancer Res., 39: 3812–3815, 1979.PubMedGoogle Scholar
  13. 13.
    Braunschweiger, P. G. and Schiffer, L. M. Cell kinetic directed sequential chemotherapy with cyclophosphamide and adriamycin in T1699 mammary tumors. Cancer Res., 40: 737–743, 1980.PubMedGoogle Scholar
  14. 14.
    Braunschweiger, P. G. and Schiffer, L. M. Effect of adriamycin on the cell kinetics of 13762 rat mammary tumors and implications for therapy. Cancer Treatments Rep., 64: 293–300, 1980.Google Scholar
  15. 15.
    Braunschweiger, P. G., Ting, H. L., and Schiffer, L. M. Receptor-dependent antiproliferative effects of corticosteroids in radiation-induced fibrosarcomas and implications for sequential therapy. Cancer Res., 42: 1686–1691, 1982.PubMedGoogle Scholar
  16. 16.
    Braunschweiger, P. G. and Schiffer, L. M. Response models for proliferative recovery in solid tumors after cyclophosphamide and adriamycin. Proc. AACR, 24: 262, 1983.Google Scholar
  17. 17.
    Braunschweiger, P. G. and Schiffer, L. M. The effect of Cisplatinol (D-DDp) on cell proliferation in solid tumor models. Cell Tissue Kinet., 17: 672, 1984.Google Scholar
  18. 18.
    Darzynkiewicz, Z. Cytochemical probes of cycling and quiescent cells applicable for flow cytometry. In: (J. W. Gray and Z. Darzynkiewicz, eds.), Techniques in Cell Cycle Analysis. New Jersey: Humana, 1986.Google Scholar
  19. 19.
    Darzynkiewicz, Z. Detection of DNA polymerase activity in fixed cells. Exp. Cell Res., 80: 483–486, 1973.PubMedCrossRefGoogle Scholar
  20. 20.
    Darzynkiewicz, Z., Traganos, F., Andreeff, M., Sharpless, T., and Melamed, M. R. Different sensitivity of chromatin to acid denaturation in quiescent and cycling cells as revealed by flow cytometry. J. Histochem. Cytochem., 27: 478–485, 1979.PubMedGoogle Scholar
  21. 22.
    Darzynkiewicz, Z., Traganos, F., and Melamed, M. R. New cycle compartments identified by multiparameter flow cytometry. Cytometry, 1: 98–108, 1980.PubMedCrossRefGoogle Scholar
  22. 22.
    Darzynkiewicz, Z., Traganos, F., Sharpless, T. R., and Melamed, M. R. Cell cycle related changes in nuclear chromatin of stimulated lymphocytes as measured by flow cytometry. Cancer Res., 37: 4635–4640, 1977.PubMedGoogle Scholar
  23. 23.
    Dethlefsen, L. A., Riley, R. M., and Roti Roti, J. L. Flow cytometric (FCM) analysis of adriamycin-perturbed mouse mammary tumors. J. Histochem. Cytochem., 37: 463–469, 1979.Google Scholar
  24. 24.
    Gerecke, D., Gegsen, A., and Gross, R. Continuous labeling method for autoradiographic analysis of cell cycle parameters in steady-state cell systems. Experientia, 32: 1088–1090, 1976.PubMedCrossRefGoogle Scholar
  25. 25.
    Hermens, A. F. and Barendsen, G. W. The proliferative status and clonogenic capacity of tumor cells in a transplantable rhabdomyosarcoma of the rat before and after irradiation with 800 rad of X-ray. Cell Tissue Kinet., 11: 83–100, 1978.PubMedGoogle Scholar
  26. 26.
    Houghton, P. J. and Taylor, D. M. Fractional incorporation of 3H-thymidine and DNA specific activity as assays of inhibition of tumor growth. Br. J. Cancer, 35: 68–77, 1977.PubMedCrossRefGoogle Scholar
  27. 27.
    Kovacs, C. J., Hopkins, H. A., Simon, R. M., and Looney, W. B. Effects of 5-Fluorouracil on the cell kinetic and growth parameters of hepatoma 3924 A. Br. J. Cancer, 32: 42–50, 1975.PubMedCrossRefGoogle Scholar
  28. 28.
    Lange-Wantzin, G. Effect of cytosine arabinoside on nuclear labeling of leukemic myeloblasts with tritiated thymidine triphosphate. Leukemia Res., 3: 7–13, 1979.CrossRefGoogle Scholar
  29. 29.
    Lange-Wantzin, G., Rarle, H., and Killman, S. A. Nuclear DNA poly-merase estimation in human leukemic myeloblasts. Br. J. Hematol., 33: 329–334, 1976.CrossRefGoogle Scholar
  30. 30.
    Lange-Wantzin, G. Proliferation Characteristics of Human Leukemic Blast Cells In Vivo Before and After Cytostatic Drugs, p. 18, Copenhagen, Denmark: Villadsen and Christensen, 1981.Google Scholar
  31. 31.
    Looney, W. B., Hopkins, H. A., Grover, W. H., MacLeod, M. S., Ritenour, E. R., and Hobson, A. S. Solid tumor models for the assessment of different treatment modalities. XIII. Comparison of response and recovery of host and solid tumor to cyclophosphamide and radiation. Cancer, 45: 2793–2798, 1980.PubMedCrossRefGoogle Scholar
  32. 32.
    Mendelsohn, M. L. Autoradiographic analysis of cell proliferation in spontaneous breast cancer of C3H mouse. III. The growth fraction. J. Natl. Cancer Inst., 28: 1015–1029, 1962.PubMedGoogle Scholar
  33. 33.
    Mendelsohn, M. L. and Dethlefsen, L. A. Cell kinetics of breast cancer: The turnover of non-proliferating cells. Recent Results Cancer Res., 42: 73–86, 1973.Google Scholar
  34. 34.
    Moore, J. V. and Dixon, B. The gross and cellular response of a rat mammary tumor to single doses of cyclophosphamide. Eur. J. Cancer, 14: 91–95, 1978.PubMedGoogle Scholar
  35. 35.
    Nelson, J. S. R. and Schiffer, L. M. Autoradiographic detection of DNA polymerase containing nuclei in sarcoma 180 ascites cells. Cell Tissue Kinet., 6: 45–54, 1973.PubMedGoogle Scholar
  36. 36.
    Pallavicini, M. G., Gray, J. W., and Folstad, L. J. Quantitative analysis of cytokinetic response of KHT tumors in vivo to 1-beta-D-arafuranosylcytosine. Cancer Res., 42: 3125–3131, 1982.PubMedGoogle Scholar
  37. 37.
    Potmesil, M. and Goldfeder, A. Identification and kinetics of G1 phase confined cells in experimental mammary carcinomas. Cancer Res., 37: 857–864, 1977.PubMedGoogle Scholar
  38. 38.
    Potmesil, M. and Goldfeder, A. Nucleolar morphology and cell proliferation kinetics of thymic lymphocytes. Exp. Cell Res., 77: 31–90, 1973.PubMedCrossRefGoogle Scholar
  39. 39.
    Potmesil, M. and Goldfeder, A. Nucleolar morphology, nucleic acid synthesis and growth rates of experimental tumors. Cancer Res., 31: 789–797, 1971.PubMedGoogle Scholar
  40. 40.
    Potmesil, M., Ludwig, D., and Goldfeder, A. Cell kinetics of irradiated experimental tumors: Relationship between the proliferating and the non-proliferating pool. Cell Tissue Kinet., 8: 369–385, 1975.PubMedGoogle Scholar
  41. 41.
    Schenken, L. L. Proliferative character and growth modes of neo-plastic disease as determinants of chemotherapeutic efficacy. Cancer Treat. Rep., 60: 1761–1776, 1976.PubMedGoogle Scholar
  42. 42.
    Schiffer, L. M., Braunschweiger, P. G. and Stragand, J. J. Tumor cell population kinetics following non-curative treatment. Antibiot. Chemother., 23: 148–156, 1978.PubMedGoogle Scholar
  43. 43.
    Schiffer, L. M., Markoe, A. M., and Nelson, J. S. R. Estimation of tumor growth fraction in murine tumors by the primer-dependent available DNA-dependent polymerase assay. Cancer Res., 36: 2415–2418, 1976.PubMedGoogle Scholar
  44. 44.
    Schiffer, L. M., Markoe, A. M., and Nelson, J. S. R. Evaluation of the PDP index as a monitor of growth fraction during tumor therapy. In: The Cell Cycle in Malignancy and Immunity, 13th Annual Hanford Biology Symposium, pp. 459–472, US Energy Research and Development Administration, 1975.Google Scholar
  45. 45.
    Schiffer, L. M., Markoe, A. M., Wenkelstein, A., Nelson, J. S. R., and Mikulla, J. M. Cycling characteristics of human lymphocytes in vitro. Blood, 44: 99–107, 1974.PubMedGoogle Scholar
  46. 46.
    Schuartzendruber, D. E. A bromodeoxyuridine (BUdR)-mithramycin technique for detecting cycling and non-cycling cells by flow cytometry. Exp. Cell. Res., 109: 439–445, 1977.CrossRefGoogle Scholar
  47. 47.
    Shackney, S. A cytokinetic model for heterogeneous mammalian cell populations. II. Tritiated thymidine studies: The percent labeled mitosis (PLM) curve. J. Theor. Biol., 44: 4990, 1974.CrossRefGoogle Scholar
  48. 48.
    Shackney, S. and Ritch, P. Percent labeled mitosis curve analysis. In: (J. W. Gray and Z. Darzynkiewicz, eds.), Techniques in Cell Cycle Analysis. New Jersey: Humana, 1986.Google Scholar
  49. 49.
    Simpson-Herren, L., Sanford, A. H., and Holmquist, J. P. Cell population kinetics of transplanted and metastatic Lewis lung carcinoma. Cell Tissue Kinet., 7: 349–361, 1974.PubMedGoogle Scholar
  50. 50.
    Simpson-Herren, L. L., Sanford, A. H., Holmquist, J. P., Springer, T. A., and Lloyd, H. H. Ambiguity of the thymidine index. Cancer Res., 36: 4705–4709, 1976.PubMedGoogle Scholar
  51. 51.
    Skipper, H. E. and Schabel, F. M. Quantitative and cytokinetic studies in experimental tumor models. In: (J. F. Holland and E. Frei, III, eds.), Cancer Medicine. Philadelphia: Lea and Febiger, 1973.Google Scholar
  52. 52.
    Steel, G. G. Cell loss in experimental tumors. Cell Tissue Kinet., 1: 193–207, 1968.Google Scholar
  53. 53.
    Steel, G. G. Delayed uptake by tumors of tritium from thymidine. Nature (Lond.), 210: 806–808, 1966.CrossRefGoogle Scholar
  54. 54.
    Steel, G. G. Growth Kinetics of Tumors. Oxford: Oxford University, 1977.Google Scholar
  55. 55.
    Stragand, J. J., Bergerat, J.-P., White, R. A., Hokanson, J., and Drewinko, B. Biological and cell kinetic properties of a human colonic adenocarcinoma (LoVo) grown in athymic mice. Cancer Res., 40: 2846–2852, 1980.PubMedGoogle Scholar
  56. 56.
    Tannock, I. F. The relationship between cell proliferation and the vascular system in a transplanted mouse mammary tumor. Brit. J. Cancer, 22: 258, 1968.PubMedCrossRefGoogle Scholar
  57. 57.
    Takahashi, M., Hogg, G. D., and Mendelsohn, M. L. The automated analysis of FLM curves. Cell Tissue Kinet., 4: 505–518, 1971.PubMedGoogle Scholar
  58. 58.
    Twentyman, P. R., Brown, J. M., Gray, J. W., Franks, A. J., Scoles, M. A., and Kallman, R. F. A new mouse tumor model system (RIF-1) for comparison of end-point studies. J. Natl. Cancer Inst., 64: 595–604, 1980.PubMedGoogle Scholar

Copyright information

© The Humana Press Inc. 1987

Authors and Affiliations

  • Paul G. Braunschweiger
    • 1
  1. 1.Department of Experimental TherapeuticsAMC Cancer Research Center and HospitalLakewood

Personalised recommendations