Effect of tyrosine kinase inhibition by imatinib mesylate on mast cell tumors in dogs

BACKGROUND: Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT. HYPOTHESIS: Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit. ANIMALS: Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment. METHODS: Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks. RESULTS: Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission). CONCLUSIONS AND CLINICAL IMPORTANCE: Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.     

Integrated field- and model-based study of hydro-environmental aspects of a small, endangered wetland in eastern Hokkaido, Japan

The hydro-environmental aspects of a small, endangered wetland (Totsuru wetland), located in eastern Hokkaido, Japan, are investigated, and the efficacy of a proposed engineering strategy for restoring the wetland is examined. Taking ²²²Rn as a target tracer and building a static ²²²Rn mass balance equation, the share of groundwater-genetic surface water in yielding the entire surface water in the wetland is appraised. The share is also appraised by using a different approach based on a non-static, site-specific water balance model. Both approaches yielded nearly the same percentage share, and therefore, it is concluded that 70% or more of the surface water entering the Totsuru swamp through the natural rivers is groundwater genetic. Using the water balance model, it is deduced that the reverse flow from the Uenbetsu drainage river is not less than 30% of the entire surface water flow entering the swamp, and therefore contributes considerably to mitigating the shrinkage of the swamp. Finally, through numerical experiments, it is shown that raising the water level of the Uenbetsu drainage river with a constructed weir to enhance the reverse flow is efficacious for restoring the wetland.