Heterogeneity and Variability of Test Results as Limiting Factors for Predictive Assays

  • P. Schlag
  • D. Flentje
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 94)


A number of different human neoplasms have been postulated to arise from more than one single cell of origin (Ohno 1971; Petersen et al. 1979; Siracky 1979), whereas there is evidence that myelomas and some hematological malignancies may be monoclonal (Fialkow 1976). The question arises whether the wellknown morphologically different cell types found in many tumors point to a multicellular origin or whether these phenotypes only represent differentiation levels or directions of cells which have developed from a single stem cell (Nowell 1976).


Clonogenic Assay Cloning Efficiency Predictive Assay Single Stem Cell Tumor Cell Subpopulation 
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  1. Barranco SC, Ho DHW, Drewinko B (1972) Differential sensitivities of human melanoma cells grown in vitro to arabinosyl-cytosine. Cancer Res 32: 2733–2736PubMedGoogle Scholar
  2. Buick RN, Fry SE, Salmon SE (1980) Effect of host-cell interactions on clonogenic carcinoma cells in human malignant effusions. Br J Cancer 41: 695–704PubMedCrossRefGoogle Scholar
  3. Dexter DL, Spremulli EN, Fligid Z, Barbosa JA, Vogel R, Van Voorhees A, Calabresi P (1981) Heterogeneity of cancer cells from a single human colon carcinoma. Am J Med 71: 949–956PubMedCrossRefGoogle Scholar
  4. Epstein LB, Jen-Ta Sehn, Abele JS, Reese CC (1980) Further experience in testing the sensitivity of human ovarian carcinoma cells to interferon in an in vitro semisolid agar culture system: comparison of solid and ascites forms of the tumor. In: Salmon SE (ed) Cloning of human tumor stem cells. Liss, New York, pp 277–290Google Scholar
  5. Fialkow PJ (1976) Clonal origin of human tumors. Biochim Biophys Acta 458: 283–291PubMedGoogle Scholar
  6. Fidler IJ, Kripke ML (1980) Tumor cell antigenicity, host immunity and cancer metastasis. Cancer Immunol Immunother 7: 201–205CrossRefGoogle Scholar
  7. Fidler IJ, Gersten DM, Budmen MB (1978) The biology of cancer invasion and metastasis. Adv Cancer Res 28: 149–250PubMedCrossRefGoogle Scholar
  8. Heppner GH, Dexter DL, DeNucci T, Müller FR, Calabresi P (1978) Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor. Cancer Res 38: 3758–3768PubMedGoogle Scholar
  9. Kerbel RS (1979) Implications of immunological heterogeneity of tumors. Nature 280: 358–360PubMedCrossRefGoogle Scholar
  10. Mackillop WJ, Stewart SS, Buick RN (1982) Density/volume analysis in the study of cellular heterogeneity in human ovarian carcinoma. Br J Cancer 45: 812–820PubMedCrossRefGoogle Scholar
  11. Meyskens FL (1980) Human melanoma colony formation in soft agar. In: Salmon SE (ed) Cloning of human tumor stem cells. Liss, New York, pp 85–100Google Scholar
  12. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194: 23–28PubMedCrossRefGoogle Scholar
  13. Ohno S (1971) Genetic implication of karyologic instability of malignant somatic cells. Physiol Rev 51: 496–526Google Scholar
  14. Petersen SE, Bichel P, Lorentzen M (1979) Flow cytometric demonstration of tumor cell subpopulations with different DNA content in human colorectal carcinoma. Eur J Cancer 15: 383–386PubMedGoogle Scholar
  15. Rosenblum ML, Ferosa MA, Dougherty DV (1981) Influence of tumor heterogeneity on chemosensitivity testing on human brain tumors. Stem Cells 1: 279Google Scholar
  16. Salmon SE, Hamburger AW, Soehnlen BS, Durie BGM, Alberts DS, Moon TE (1978) Quantitation of differential sensitivity of human-tumor stem cells to anti-cancer drugs. N Engl J Med 298: 1321–1327PubMedCrossRefGoogle Scholar
  17. Sanfilippo O, Silvestrini RS, Zaffaroni N, Piva L (1983) Potentiality of an in vitro chemosensitivity assay for human germ cell testicular tumors (GCTT). Proceedings ASCO, 19th Annual Meeting 2: C-145Google Scholar
  18. Schlag P, Schreml W (1982) Heterogeneity in growth pattern and drug sensitivity of primary tumor and metastases in the human tumor colony-forming assay. Cancer Res 42: 4086–4089PubMedGoogle Scholar
  19. Selby PJ, Thomas JM, Peckham MJ (1979) A comparison of the chemosensitivity of a primary tumor and its metastases using a human tumor xenograft. Eur J Cancer 15: 1425–1429PubMedGoogle Scholar
  20. Siracky J (1979) An approach to the problem of heterogeneity of human tumor cell subpopulations. Br J Cancer 39: 570–577CrossRefGoogle Scholar
  21. Vindelov LL, Hansen HH, Christensen IJ, Spang-Thomsen M, Hirsch FR, Hansen M, Nissen NJ (1980) Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis. Cancer Res 40: 4295–4300PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1984

Authors and Affiliations

  • P. Schlag
    • 1
  • D. Flentje
    • 1
  1. 1.Sektion Chirurgische OnkologieChirurgische UniversitätsklinikHeidelbergGermany

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