5 research outputs found
Quality of reporting of cranial irradiation techniques in randomized controlled trials of primary brain tumors: A systematic review
10.1371/journal.pone.0241566PLoS ONE1511-Nove024156
Management of locally advanced synchronous colorectal and prostate cancers: A case report
10.1097/MD.0000000000020336Medicine9922e2033
Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: A systematic review and meta-analysis
10.18632/oncotarget.21019Oncotarget865109712-10972
Adoption of prophylactic cranial irradiation (PCI) for extensive stage small cell lung cancer (ES-SCLC): A population based outcome study
10.1186/s13014-018-1184-xRadiation Oncology13124
Supplementary Material for: Prevention of Venous Neointimal Hyperplasia by a Multitarget Receptor Tyrosine Kinase Inhibitor
<b><i>Background/Aims:</i></b> Venous neointimal hyperplasia (NH) is the predominant cause of stenosis in hemodialysis arteriovenous grafts (AVG), but there is currently no clinically used therapy to prevent NH. <b><i>Methods:</i></b> A porcine AVG model was used to identify potential pharmacological targets to prevent NH. Sunitinib, a broad-spectrum tyrosine kinase inhibitor, was examined as a potential anti-NH drug utilizing in vitro and ex vivo models. <b><i>Results:</i></b> In an in vivo porcine model, PDGF, VEGF and their receptors PDGFR-α and VEGFR-2 were upregulated at the venous anastomosis within 2 weeks after AVG placement, with NH development by 4 weeks. Sunitinib inhibited PDGF-stimulated proliferation, migration, phosphorylation of MAPK and PI3K/Akt proteins and changes in the expression of cell-cycle regulatory proteins in vascular smooth-muscle cells as well as VEGF-stimulated endothelial cell proliferation in vitro. In an ex vivo model, significant NH was observed in porcine vein segments perfused for 12 days under pathological shear stress. Sunitinib (100 nM) inhibited NH formation, with the intima-to-lumen area ratio decreasing from 0.45 ± 0.25 to 0.04 ± 0.02 (p < 0.05) with treatment. <b><i>Conclusion:</i></b> These findings demonstrate sunitinib to be a potential NH-preventive drug as well as the utility of an ex vivo model to investigate pharmacotherapies under pathophysiological flow conditions