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Inhibition of Cell Signalling in Neoplastic Canine Mast Cells

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Title: Inhibition of Cell Signalling in Neoplastic Canine Mast Cells
Author: Masson, Sean
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Coomber, Brenda
Abstract: Canine mast cell tumours (MCTs) are a common skin malignancy in dogs, largely driven by dysregulated activity of KIT and VEGFR2. High grade/metastatic MCTs are resistant to conventional chemotherapeutics, thus canine MCT cells represent a valuable model for KIT dysregulation in human cancers. Canine MCTs are currently treated with the TKIs toceranib (Palladia) or masitinib (Kinavet), with mixed results. Itraconazole, an anti-fungal agent shown to interfere with VEGFR2 glycosylation and hence signalling, may also affect KIT in these cells. The effect of itraconazole on two canine MCT cell lines (MCT1 and MCT2) was evaluated individually and in combination with RTK inhibitors. Cell proliferation and receptor phosphorylation and glycosylation were examined after treatment. Combination itraconazole and toceranib treatment for 48 hours generally decreased proliferation rates and disrupted RTK phosphorylation and glycosylation. These data demonstrate that novel anti-cancer drugs such as itraconazole warrant further investigation as inexpensive and less toxic alternatives to traditional chemotherapeutics.
Date: 2014
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