Background Urothelial carcinoma (UC) accounts for > 90% of canine tumors occurring in the urinary bladder. Toceranib phosphate (TOC) is a multi-target receptor tyrosine kinase (RTK) inhibitor that exhibits activity against members of the split kinase family of RTKs. The purpose of this study was to evaluate primary UC tumors and UC cell lines for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, and KIT to assess whether dysregulation of these RTKs may contribute to the observed biological activity of TOC. Results Transcript for VEGFR2, PDGFRα, PDGFRβ, and KIT was detected in all UC tissue samples and UC cell lines. The Proteome Profiler™ Human Phospho-RTK Array Kit (R & D Systems) provided a platform to assess phosphorylation of 42 different RTKs in primary UC tumors and UC cell lines. Evidence of PDGFRα and PDGFRβ phosphorylation was present in only 11% or 33% of UC tumors, respectively, and 25% of UC cell lines. Treatment of UC cell lines with TOC had no significant impact on cell proliferation, including UC cell lines with evidence of PDGFRβ phosphorylation. Conclusions Phosphorylation of several key RTKs targeted by TOC is present in a small subset of primary UC tumors and UC cell lines, suggesting that these RTKs do not exist in a state of continuous activation. These data suggest that activation of RTKs targeted by TOC is present in a small subset of UC tumors and UC cell lines and that treatment with TOC at physiologically relevant concentrations has no direct anti-proliferative effect on UC cells.
Salad vegetables purchased from farmer's markets and grocery stores in central Ohio during the summers of 2015 and 2016 were tested for the presence of Enterobacteriaceae resistant to extended-spectrum cephalosporins and carbapenems, Salmonella contamination, and coliform bacterial counts. A total of 364 samples were collected from 36 farmers' markets and 33 grocery stores. Using selective media, we found 23 (6.3%) samples that produced Enterobacteriaceae expressing an AmpC β-lactamase phenotype, with 11 (3.0%) confirmed to contain blaCMY and 6 (1.6%) that produced Enterobacteriaceae with an extended-spectrum β-lactamase (ESBL) phenotype, 1 (0.3%) of which was confirmed to contain blaCTX-M. All blaCMY and blaCTX-M strains were isolated from leafy greens. No Salmonella spp. or carbapenem-resistant Enterobacteriaceae were recovered from fresh produce samples. Adjusting for year, the geometric mean coliform count differed (P < 0.05) between produce types, with the count in tomatoes (15 CFU/mL) being lower than those in cucumbers (77.4 CFU/mL) and leafy greens (75.0 CFU/mL). The coliform counts also differed (P < 0.05) between years, with 19.6 CFU/mL in 2015 and 96.0 CFU/mL in 2016. There was no difference in coliform counts or the prevalences of Enterobacteriaceae expressing AmpC or ESBL phenotypes in produce purchased from farmers' markets and grocery stores. HIGHLIGHTS
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