Determinates of tumor response to radiation: Tumor cells, tumor stroma nd permanent local control

Wende Li, Peigen Huang, David J. Chen, Leo E. Gerweck

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA doublestrand break repair-defective (DNA-PKcs-/-) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose.

Original languageEnglish (US)
Pages (from-to)146-149
Number of pages4
JournalRadiotherapy and Oncology
Volume113
Issue number1
DOIs
Publication statusPublished - 2014

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Keywords

  • Intrinsic radiosensitivity
  • Predictive assays
  • Radiation
  • Tumor control dose
  • Tumor vasculature

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Hematology

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