UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at http://www.ucl.ac.uk/finance/research/post_award/post_award_contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
IFN-beta restricts tumor growth and sensitizes alveolar rhabdomyosarcoma to ionizing radiation
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Sims TL, McGee M, Williams RF, Myers AL, Tracey L, Hamner JB, Ng C, Wu J, Gaber MW, McCarville B, Nathwani AC, Davidoff AM
  • Publication date:
    03/2010
  • Pagination:
    761, 771
  • Journal:
    Mol.Cancer Ther.
  • Volume:
    9
  • Issue:
    3
  • Keywords:
    Animals, blood supply, Cell Line,Tumor, Cell Proliferation, drug effects, Humans, Interferon-beta, Male, Mice, Mice,Scid, Neovascularization,Pathologic, Oxygen Consumption, pathology, pharmacology, Radiation Tolerance, Radiation,Ionizing, Radiation-Sensitizing Agents, radiotherapy, Recombinant Proteins, Rhabdomyosarcoma,Alveolar, therapy, Tumor Burden, Xenograft Model Antitumor Assays
  • Author URL:
  • Notes:
    DA - 20100311 IS - 1538-8514 (Electronic) IS - 1535-7163 (Linking) LA - eng PT - Journal Article RN - 0 (Radiation-Sensitizing Agents) RN - 0 (Recombinant Proteins) RN - 77238-31-4 (Interferon-beta) SB - IM
Abstract
Ionizing radiation is an important component of multimodal therapy for alveolar rhabdomyosarcoma (ARMS). We sought to evaluate the ability of IFN-beta to enhance the activity of ionizing radiation. Rh-30 and Rh-41 ARMS cells were treated with IFN-beta and ionizing radiation to assess synergistic effects in vitro and as orthotopic xenografts in CB17 severe combined immunodeficient mice. In addition to effects on tumor cell proliferation and xenograft growth, changes in the tumor microenvironment including interstitial fluid pressure, perfusion, oxygenation, and cellular histology were assessed. A nonlinear regression model and isobologram analysis indicated that IFN-beta and ionizing radiation affected antitumor synergy in vitro in the Rh-30 cell line; the activity was additive in the Rh-41 cell line. In vivo continuous delivery of IFN-beta affected normalization of the dysfunctional tumor vasculature of both Rh-30 and Rh-41 ARMS xenografts, decreasing tumor interstitial fluid pressure, increasing tumor perfusion (as assessed by contrast-enhanced ultrasonography), and increasing oxygenation. Tumors treated with both IFN-beta and radiation were smaller than control tumors and those treated with radiation or IFN-beta alone. Additionally, treatment with high-dose IFN-beta followed by radiation significantly reduced tumor size compared with radiation treatment followed by IFN-beta. The combination of IFN-beta and ionizing radiation showed synergy against ARMS by sensitizing tumor cells to the cytotoxic effects of ionizing radiation and by altering tumor vasculature, thereby improving oxygenation. Therefore, IFN-beta and ionizing radiation may be an effective combination for treatment of ARMS
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Research Department of Haematology
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by