Abstract
Tumor growth is dependent both on endothelial and tumor cells. The aim of this study was to investigate dynamically whether changes in tumor vasculature implicate tumor tissue degeneration during antiangiogenic therapies. In order to quantify intra-tumor vascularization and necrosis, we have used ultrasound technology. This study has identified essential parameters needed to quantify specifically and sensitively the number of microvessels and the extent of necrosis in xenografted human carcinomas during natural tumor evolution, using contrast-enhanced high-frequency ultrasonography with (HFCDUS) or without (HFUS) color Doppler. We showed that quantification of intra-tumor microvessels between HFCDUS and immunohistochemistry is correlated using an anti-CD31 antibody. Furthermore, quantification of tumor necrosis with HFUS was confirmed by histological examination of hematoxylin–eosin–saffranin-stained sections over the observation period. Subsequently, for the assessment of novel angiogenic inhibitors, HFCDUS and HFUS were used to elucidate the underlying dynamics linking vessel inhibition and tumor eradication. We describe a novel application for HFCDUS/HFUS that constitutes an effective, convenient, and non-invasive method for clinical assessment of angiogenic inhibitors. In conclusion, we showed that tumor cells abruptly became necrotic following an antivascular therapy, whereas untreated tumors were protected from degeneration by a significant blood supply.
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Abbreviations
- HFUS:
-
high-frequency ultrasonography
- HFCDUS:
-
high-frequency color Doppler ultrasonography
- IHC:
-
immunohistochemistry
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Acknowledgements
We sincerely thank the SCEA and specially Patrice Ardouin, Annie Rouches, Monique Stanciu, Jennifer Huard, and Désiré Challuau for animal care. We warmly acknowledge Dr Brian Mullan for critical reading. We thank Lorna Saint-Ange for editing. C Magnon and A Galaup were financially supported by the AP HP – INSERM – CEA and CNRS – Fondation Lefoulon Delalande Institut de France, respectively. This work was supported by the Centre National de la Recherche Scientifique, the Institut Gustave Roussy, the Ligue Nationale contre le Cancer, and the Association pour la Recherche sur le Cancer.
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Magnon, C., Galaup, A., Rouffiac, V. et al. Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration. Gene Ther 14, 108–117 (2007). https://doi.org/10.1038/sj.gt.3302849
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DOI: https://doi.org/10.1038/sj.gt.3302849