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Urothelial carcinomas (UCs), also known as transitional cell carcinomas, are the most common canine urinary tract neoplasms. Tyrosine kinases (TKs) are enzymes that tightly regulate cell growth and differentiation through phosphorylation. Receptor TK (RTK) inhibitors are currently used to treat UCs. Toceranib phosphate (Palladia; Pfizer) is an RTK inhibitor that blocks the activity of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor-alpha and -beta (PDGFR-α, -β), FMS-like tyrosine kinase 3, stem cell factor receptor (KIT, kinase inhibitor targeting), and colony stimulating factor receptor. To better understand UCs and validate treatment targets, we performed immunohistochemical staining for RTKs, as well as a novel target, cyclin-dependent kinase 4 (CDK4, a central regulator of the mammalian cell cycle), on formalin-fixed, paraffin-embedded tissues from bladder biopsies from 17 dogs with UCs, 17 dogs with cystitis (diseased controls), and 8 normal dogs (negative controls). Although immunohistochemical scores could not be extrapolated to prognostic value, response to treatment, and outcome of patients with UC, we demonstrated expression of PDGFR-β and VEGFR2 in UCs; all UC samples staining positively for VEGFR2. Minimal positive staining for KIT was noted in the tumor samples. CDK4 staining intensity was significantly weaker in UCs compared with normal and cystitis bladder samples. The intense staining of VEGFR2 in UC cells suggested that VEGFR2 may be of prognostic and/or therapeutic value in dogs with UC. Overexpression of VEGFR2 in UC cells validates this receptor as a treatment target in UC.

A Bourke's parrot ( Neopsephotus bourkii ) originating from an aviary in Australia, containing two species of parrots, five species of finch and a species of dove, was presented for necropsy. The Bourke's parrot died from gastritis caused by Macrorhabdus ornithogaster , but also had an interstitial nephritis and ureteritis with adenovirus-like inclusion bodies within collecting duct epithelial cells. The adenovirus causing the lesions was shown to be Psittacine adenovirus-2 (PsAdV-2) using a PCR assay specific for adenoviruses and sequencing of amplicons. A survey of droppings from other birds in the aviary using the same PCR assay with amplicon sequencing found a high prevalence of infection of PsAdV-2 in Bourke's and scarlet-chested parrots ( Neophema splendida ). PsAdV-2 was also present in droppings from a Namaqua dove ( Oena capensis ). Gouldian finches ( Erythrura gouldiae ), red-billed firefinches ( Lagonosticta senegala ), and red-throated parrot finches ( Erythrura psittacea ) were shedding Gouldian finch adenovirus-1 (GFAdV-1). Two novel adenoviruses, an atadenovirus and a siadenovirus, were detected in the droppings from long-tailed finches ( Poephila acuticauda ). Kidney tissue from three of four scarlet-chested parrots submitted for necropsy from a second aviary were also positive for PsAdv-2. These findings and previously reported findings of widespread PsAdv-2 infection in captive orange-bellied parrots ( Neophemia chrysogaster ) raise the possibility that PsAdV-2 is enzootic in Australian aviculture. This represents the first report of GFAdV-1 in Australia and first identification of infection in finch species other than the Gouldian finch. Identification of two novel adenoviruses in long-tailed finches suggests that other novel adenoviruses are circulating in other finch species. RESEARCH HIGHLIGHTS Psittacine adenovirus-2 was present in high prevalence in two Australian aviaries. Gouldian finch adenovirus-1 (GFAdV-1) was detected in Australia for the first time. The host range of GFAdV-1 host range was expanded to other finch species. Novel atadenovirus and siadenovirus were detected in Estrildid finches.