کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4308316 | 1289277 | 2010 | 9 صفحه PDF | دانلود رایگان |
BackgroundB-RafV600E is a frequent mutation in anaplastic thyroid cancers and is a novel therapeutic target. We hypothesized that PLX4720 (an inhibitor of B-RafV600E) and thyroidectomy would extend survival and would decrease tumor burden in a mouse model.MethodsOrthotopic anaplastic thyroid tumors were induced in severe combined immunodeficient mice. Mice were treated with PLX4720 or vehicle after 7 days of tumor growth, and thyroidectomy or sham surgery was performed at day 14. The neck space was re-explored, and tumor volume was measured at day 35. Mice were sacrificed when they lost >25% of their initial weight.ResultsAll 5 mice that received the vehicle developed cachexia, had invasive tumors (average 61 mm3)and were sacrificed by day 35. All 6 mice receiving PLX4720 + sham had small tumors (average 1.3 mm3) and maintained their weight. Three out of 6 mice receiving PLX4720+thyroidectomy had no evidence of tumor at 35 days; the other 3 mice had small tumors (average 1.4 mm3) and showed no signs of metastatic disease. All mice treated with PLX4720 were alive and well-appearing at 50 days.ConclusionThyroidectomy with neoadjuvant PLX4720 could be an effective therapeutic strategy for early anaplastic thyroid cancers that harbor the B-RafV600E mutation and are refractory to conventional therapeutic modalities.
Journal: Surgery - Volume 148, Issue 6, December 2010, Pages 1154–1162