PURPOSE: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. METHODS AND MATERIALS: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. RESULTS: SU5416, when combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. CONCLUSIONS: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.
PURPOSE: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a humanglioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. METHODS AND MATERIALS: A humanglioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. RESULTS:SU5416, when combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. CONCLUSIONS: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.
Authors: Satoshi Itasaka; Ritsuko Komaki; Roy S Herbst; Keiko Shibuya; Tomoaki Shintani; Nancy R Hunter; Amir Onn; Corazon D Bucana; Luka Milas; K Kian Ang; Michael S O'Reilly Journal: Int J Radiat Oncol Biol Phys Date: 2007-03-01 Impact factor: 7.038
Authors: Saskia E Rademakers; Paul N Span; Johannes H A M Kaanders; Fred C G J Sweep; Albert J van der Kogel; Johan Bussink Journal: Mol Oncol Date: 2008-03-27 Impact factor: 6.603
Authors: Elizabeth W Newcomb; Yevgeniy Lukyanov; Michelle Alonso-Basanta; Mine Esencay; Iva Smirnova; Tona Schnee; Yongzhao Shao; Mary Louise Devitt; David Zagzag; William McBride; Silvia C Formenti Journal: Int J Radiat Oncol Biol Phys Date: 2008-08-01 Impact factor: 7.038