4.6 Article

The hollow fiber assay for drug responsiveness in the Ewing's sarcoma family of tumors

期刊

JOURNAL OF PEDIATRICS
卷 149, 期 1, 页码 103-111

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MOSBY-ELSEVIER
DOI: 10.1016/j.jpeds.2006.02.042

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  1. National Centre for the Replacement, Refinement and Reduction of Animals in Research [G0400043/1] Funding Source: Medline
  2. National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [G0400043/1] Funding Source: researchfish

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Objective: To investigate the use of the National Cancer Institutes hollow fiber assay (HFA) to evaluate and prioritize novel treatment strategies for clinical trials in the Ewings sarcoma family of tumors (ESFT). Study design: The growth and morphology of ESFT cell lines in hollow fibers (HFs) vas characterized in vitro and in vivo. Reliability and reproducibility were evaluated using doxorubicin. Results: The numbers of viable cells in all 6 ESFT ceU lines increased with time in vitro (0 to 96 hours). The SKES-1 and A673 cell lines grew exponentially after implantation of HFs in node mice at subcutaneous and intraperitoneal sites. ESFT cells formed highly organized distinctive morphology within the HFs in vitro and in vivo. The number of viable ESFT cells within the HFs decreased in a time-dependent (24 to 96 hours) and dose-dependent (1 to 10 mg/kg) manner after treatment with doxorubicin in vivo. Conclusions: The HFA is a versatile short-term in vivo model that may be exploited to predict efficacy of potential anticancer agents in ESFT cells. Tumor markers and pharmacodynamic endpoints may be quantified in the pure population of ESFT cells from within the HFs.

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