کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4156765 1273780 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rapamycin-induced tumor vasculature remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پریناتولوژی (پزشکی مادر و جنین)، طب اطفال و بهداشت کودک
پیش نمایش صفحه اول مقاله
Rapamycin-induced tumor vasculature remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation
چکیده انگلیسی

PurposeRapamycin inhibits vascular endothelial growth factor expression. Vascular endothelial growth factor is a tumor-elaborated protein that stimulates neovascularization. This inhibition can cause transient “normalization” of the generally dysfunctional tumor vasculature, resulting in improved tumor perfusion and oxygenation. We hypothesized that this may potentiate the antitumor effects of adjuvant ionizing radiation.MethodsMice bearing orthotopic Rh30 alveolar rhabdomyosarcomas were treated with rapamycin (5 mg/kg intraperitoneally daily ×5). Tumors were then evaluated for changes in intratumoral oxygenation, perfusion, vessel permeability, and microvessel density. Additional tumor-bearing mice were treated with 5 doses of rapamycin, irradiation (4 Gy), or 5 doses of rapamycin with irradiation administered on the first or sixth day of rapamycin treatment.ResultsAlthough tumor vessel permeability changed only minimally, microvessel density decreased (3153 ± 932 vs 20,477 ± 3717.9 pixels per high-power field), whereas intratumoral oxygenation increased significantly (0.0385 ± 0.0141 vs 0.0043 ± 0.0023 mm Hg/mm3) after 5 doses of rapamycin. Contrast-enhanced ultrasound demonstrated a significantly increased rate of change of signal intensity after 5 days of rapamycin, suggesting improved intratumoral perfusion. Tumor volume 14 days after treatment was smallest in mice treated with the combination of rapamycin given before irradiation.ConclusionCombination therapy with rapamycin given before irradiation to normalize the tumor vasculature, thereby improving tumor oxygenation, increased the sensitivity of alveolar rhabdomyosarcoma xenografts to adjuvant irradiation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pediatric Surgery - Volume 47, Issue 1, January 2012, Pages 183–189
نویسندگان
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