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Christophe Borg, Magali Terme, Julien Taïeb, Cédric Ménard, Caroline Flament, Caroline Robert, Koji Maruyama, Hiro Wakasugi, Eric Angevin, Kris Thielemans, Axel Le Cesne, Véronique Chung-Scott, Vladimir Lazar, Isabelle Tchou, Florent Crépineau, François Lemoine, Jacky Bernard, Jonhantan A. Fletcher, Ali Turhan, Jean-Yves Blay, Alain Spatz, Jean-François Emile, Michael C. Heinrich, Salah Mécheri, Thomas Tursz, Laurence Zitvogel
Published in Volume 114, Issue 3
J Clin Invest. 2004; 114(3):379–388 doi:10.1172/JCI21102
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Figure 1

Gleevec prevented tumor progression in vivo in tumor models resistant to the Gleevec antiproliferative effects in vitro. (A) Mouse tumor models resistant to Gleevec in vitro. AK7, B16F10 (B16), RMA-S, MCA 102, or BAF3p210 cells (bearing the BCR/ABL translocation) were incubated for 24 hours with the indicated doses of Gleevec, and the absolute number of surviving cells was determined by trypan blue exclusion assay. Proliferation indexes are shown. The Wilcoxon two-sample rank sum test was used to compare the proliferation indexes (*P < 0.05). (B) Gleevec prevents establishment of B16F10 lung metastases. We injected 5 × 105 B16F10 tumor cells in the tail vein at day 0. Oral feeding with Gleevec (150 mg/kg bid) or H2O (200 μl) was administered on days 5–11 and mice were sacrificed for the enumeration of lung metastases on day 11. The data from 3 independent experiments, each including 5–7 mice per group, were pooled and are depicted. The Wilcoxon two-sample rank sum test was used to compare the number of lung metastases (**P < 0.05, Gleevec versus H2O). (C) FL and Gleevec synergize to eradicate AK7. We inoculated 3 × 106 AK7 tumor cells in the abdominal flank of C57BL/6 mice on day 0. FL was started at day 11 when AK7 tumors reached a diameter of 20 ± 20 mm2. FL was continued for 10 days and combined with Gleevec the day before FL arrest and for 8 consecutive days (same doses as in B). Each experiment included 5–7 mice/group and was repeated twice with similar results. The Kruskal Wallis multiple comparison test was used for statistical analyses and significant effects are signified by triple asterisks.