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Tumor-Cell Survival

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Tumor Models in Cancer Research

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The development of assays for measuring the survival of individual tumor cells revolutionized the study of experimental cancer therapy by enabling researchers to move from assessing the gross responses of tumors to measuring the survival of cells in the critical, clonogenic tumor-cell populations (1). The development and use of these assays formed the basis for many of our modern concepts of tumor biology, from the concept of logarithmic cell kill to considerations of cell-proliferation kinetics. The first major step in this revolution in cancer biology was made by Puck and Marcus, who developed a cell-culture assay for cloning individual HeLa cells, derived from a human carcinoma of the cervix, and then used this assay to determine the changes in cell survival in cultures given graded doses of radiation (2,3). Assays for measuring the viability of cells suspended from tumors in vivo followed rapidly. The first cell-survival curve for tumors treated in vivo was obtained in 1959 Hewitt and Wilson, using a quantitative tumor transplantation assay (the TD50 assay) to measure the survival of cells harvested from leukemia infiltrates in the livers of mice after treatment with graded doses of radiation (4). Over the next few years, Hewitt’s TD50 assay was extended and used to study the quantitative transplantation and radiation responses of a wide variety of hematologic malignancies and solid tumors (5,6). The techniques were also refined and extended to produce true clonogenic assays for tumor-cell survival, in which the clonogenicity of individual tumor cells was tested by preparing tumor-cell suspensions, counting the tumor cells, and determining the ability of individual tumor cells to proliferate to form macroscopic clones (6). For some tumors, this can be done by injecting known numbers of tumor cells intravenously into recipient mice, allowing the cells to lodge in the spleen (7) or the lung (8), waiting for the individual cells to grow into macroscopic tumors, and counting the number of tumors. In a few tumor systems, the suspended cells can be plated at low densities in cell culture, so that individual tumor cells will grow into macroscopic colonies, allowing the measurement of cell survival by colony-formation assays analogous developed by Puck and Marcus (9,10). The final step in this revolution in cancer biology came in 1961, when Till and McCulloch (11) described their spleen-colony assay for measuring the survival of bone-marrow stem cells. Clonogenic assays for other normal cell populations followed (12), allowing the toxicities of antineoplastic agents to be evaluated in terms of the responses of the critical clonogenic stem-cell populations within the dose-limiting normal tissues.

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Authors
  1. Sara Rockwell PhD
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Editors and Affiliations

  1. Lilly Research Laboratories, Indianapolis, IN, USA

    Beverly A. Teicher

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© 2002 Springer Science+Business Media New York

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Rockwell, S. (2002). Tumor-Cell Survival. In: Teicher, B.A. (eds) Tumor Models in Cancer Research. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-100-8_32

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  • DOI: https://doi.org/10.1007/978-1-59259-100-8_32

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-6883-1

  • Online ISBN: 978-1-59259-100-8

  • eBook Packages: Springer Book Archive

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