Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: Experimental and clinical evidence
Abstract Purpose This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT). Methods Tumor-perfusion parameters and hypoxia were monitored after rh-Endo t...
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Veröffentlicht in: | Radiotherapy and oncology 2013-01, Vol.106 (1), p.130-137 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Abstract Purpose This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT). Methods Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 non-small cell lung-cancer (NSCLC) patients. Eight-week female C57BL/6J mice were randomized to receive rh-Endo or control (saline) once daily for 12 days when Lewis lung carcinoma (LLC) reached approximately 100–150 mm3 . On planned days, tumors were measured for cell apoptosis, microvessel density, pericytes, blood-vessel morphology, and tumor hypoxia. The tumor response under different combinations of rh-Endo and RT schedules was evaluated. Results Tumor hypoxia was significantly reduced 5 days after rh-Endo in NSCLC patients, and a similar result was found in the LLC mouse model. The anti-tumor effect was markedly enhanced when RT was administered within the remodeling period compared to any other treatment schedule. rh-Endo treatment remodeled the tumor vasculature after 5 days by reducing microvessel density and increasing pericytic coverage of the vessel endothelium. Conclusion This study demonstrated decreased hypoxia in animals and patients upon rh-Endo treatment, which also enhanced the radioresponse within the vasculature-remodeling period. The optimal clinical combination of rh-Endo and RT warrants further investigation. |
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ISSN: | 0167-8140 1879-0887 |
DOI: | 10.1016/j.radonc.2012.10.022 |