Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model
| Autor: | Heijmen, L., Voert, E.G.W. ter, Punt, C.J.A., Heerschap, A., Oyen, W.J.G., Bussink, J., Sweep, C.G.J., Laverman, P., Span, P.N., Geus-Oei, L.F. de, Boerman, O.C., Laarhoven, H.W.M. van |
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| Přispěvatelé: | Cancer Center Amsterdam, Oncology, Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2014 |
| Předmět: |
Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2]
genetic structures Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15] Nanomedicine Radboud Institute for Health Sciences [Radboudumc 19] Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] eye diseases Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] |
| Zdroj: | Contrast Media and Molecular Imaging, 9, 3, pp. 237-45 Contrast media & molecular imaging, 9(3), 237-245. John Wiley and Sons Ltd Contrast Media and Molecular Imaging, 9, 237-45 |
| ISSN: | 1555-4309 |
| Popis: | Contains fulltext : 137470.pdf (Publisher’s version ) (Open Access) The purpose of this study was to assess the effect of bevacizumab on vasculature and hypoxia in a colorectal tumor model. Nude mice with subcutaneous LS174T tumors were treated with bevacizumab or saline. To assess tumor properties, separate groups of mice were imaged using (18) F-Fluoromisonidazole (FMISO) and (18) F-Fluorodeoxyglucose (FDG) positron emission tomography or magnetic resonance imaging before and 2, 6 and 10 days after the start of treatment. Tumors were harvested after imaging to determine hypoxia and vascular density immunohistochemically. The T2 * time increased significantly less in the bevacizumab group. FMISO uptake increased more over time in the control group. Vessel density significantly decreased in the bevacizumab-treated group. The Carbonic anhydrase 9 (CAIX) and glucose uptake transporter 1 (GLUT1) fractions were higher in bevacizumab-treated tumors. However, the hypoxic fraction showed no significant difference. Bevacizumab led to shorter T2 * times and higher GLUT1 and CAIX expression, suggesting an increase in hypoxia and a higher glycolytic rate. This could be a mechanism of resistance to bevacizumab. The increase in hypoxia, however, could not be demonstrated by pimonidazole/FMISO, possibly because distribution of these tracers is hampered by bevacizumab-induced effects on vascular permeability and perfusion. Copyright (c) 2014 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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