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Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):743-50.

Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment.

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  • 1Laboratories of Biomedical Magnetic Resonance, Université Catholique de Louvain, Avenue E. Mounier 73-40, B-1200 Brussels, Belgium.

Abstract

PURPOSE:

The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible "normalization" of the tumor vasculature that could be exploited to improve radiotherapy.

EXPERIMENTAL DESIGN:

Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO(2)) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrast-enhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a "wick-in-needle" technique.

RESULTS:

Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling.

CONCLUSIONS:

In summary, the microenvironmental changes induced by thalidomide were sufficient to radiosensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization.

PMID:
15701864
[PubMed - indexed for MEDLINE]
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