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

Thalidomide radiosensitizes tumors through early changes in the tumor
microenvironment.

Ansiaux R, Baudelet C, Jordan BF, Beghein N, Sonveaux P, De Wever J, Martinive
P, Gregoire V, Feron O, Gallez B.

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

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 - in process]