کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8456790 1548774 2018 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biologic Response of Colorectal Cancer Xenograft Tumors to Sequential Treatment with Panitumumab and Bevacizumab
ترجمه فارسی عنوان
واکنش زیستی تومورهای زنگ زده سرطان کولورکتال به درمان متوالی با پانیتومومب و بویازیوماب
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی
Recent studies in RAS wild-type (WT) metastatic colorectal cancer (mCRC) suggest that the survival benefits of therapy using anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies combined with chemotherapy are maximized when the anti-EGFR antibody is given as first-line, followed by subsequent anti-VEGF antibody therapy. We report reverse-translational research using LIM1215 xenografts of RAS WT mCRC to elucidate the biologic mechanisms underlying this clinical observation. Sequential administration of panitumumab then bevacizumab (PB) demonstrated a stronger tendency to inhibit tumor growth than bevacizumab then panitumumab (BP). Cell proliferation was reduced significantly with PB (P < .01) but not with BP based on Ki-67 index. Phosphoproteomic analysis demonstrated reduced phosphorylation of EGFR and EPHA2 with PB and BP compared with control. Western blotting showed reduced EPHA2 expression and S897-phosphorylation with PB; RSK phosphorylation was largely unaffected by PB but increased significantly with BP. In quantitative real-time PCR analyses, PB significantly reduced the expression of both lipogenic (FASN, MVD) and hypoxia-related (CA9, TGFBI) genes versus control. These results suggest that numerous mechanisms at the levels of gene expression, protein expression, and protein phosphorylation may explain the improved clinical activity of PB over BP in patients with RAS WT mCRC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 20, Issue 7, July 2018, Pages 668-677
نویسندگان
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