Of 1146 caprine necropsy or biopsy specimens submitted from 1987 through 2011 to the Veterinary Diagnostic Laboratory at Oregon State University, 100 goats (8.7%) had 102 tumors. Detailed records were available for 89 cases. Fifty-five goats were female, 17 were castrated males, and 12 were intact males. Breeds included 21 Nubian, 16 Pygmy, 10 Pygora, 8 Alpine, 4 Angora, 4 Saanen, 2 Toggenburg, and 9 crossbred goats. Dwarf, Nubian, and Saanen goats were overrepresented and Alpine and Boer goats underrepresented among cases with neoplastic disease in comparison to submissions overall. Age ranged from 7 months to 19 years (median, 7 years). Histopathology was performed on 97 tumors. Lymphoma (n = 17) was the most common tumor, followed by cutaneous squamous cell carcinoma (n = 10) and thymoma (n = 9). Most lymphomas were multicentric. All 7 mammary neoplasms were adenocarcinomas. Five of 7 vascular proliferations were hemangiosarcomas. All 4 melanocytic tumors were classified as (malignant) melanoma. Rarely reported caprine tumors included a choroid plexus carcinoma, 2 rhabdomyosarcomas, and 3 pheochromocytomas. Cutaneous round cell tumors were provisionally diagnosed as 2 histiocytomas and 5 mast cell tumors. Single cases of previously unreported caprine tumors included amyloid-producing odontogenic tumor, myxosarcoma, sebaceous carcinoma, apocrine sweat gland adenoma, and thyroid carcinoma. Nonneoplastic entities included 2 cases of mammary fibroadenomatous hyperplasia and single cases of vascular hamartoma, cervical adenomatous hyperplasia, and cervical leiomyofibromatosis. The results of this 25-year retrospective study indicate that lymphoma in particular and tumors in general are common in goats.

A novel swine-origin H1N1 influenza A virus has been identified as the cause of the 2009 influenza pandemic in humans. Since then, infections with the pandemic (H1N1) 2009 influenza virus have been documented in a number of animal species. The first known cases of lethal respiratory disease associated with pandemic (H1N1) 2009 influenza virus infection in house pets occurred in domestic cats in Oregon. A 10-year-old neutered domestic shorthair and an 8-year-old spayed domestic shorthair died shortly after developing severe respiratory disease. Grossly, lung lobes of both cats were diffusely firm and incompletely collapsed. Histologically, moderate to severe necrotizing to pyonecrotizing bronchointerstitial pneumonia was accompanied by serofibrinous exudation and hyaline membranes in the alveolar spaces. Influenza A virus was isolated from nasal secretions of the male cat and from lung homogenate of the female cat. Both isolates were confirmed as pandemic (H1N1) 2009 influenza virus by real-time reverse transcriptase polymerase chain reaction. With immunohistochemistry, influenza A viral antigen was demonstrated in bronchiolar epithelial cells, pneumocytes, and alveolar macrophages in pneumonic areas. The most likely sources of infection were people in the household with influenza-like illness or confirmed pandemic (H1N1) 2009 influenza. The 2 cases reported here provide, to the best of the authors’ knowledge, the first description of the pathology and viral antigen distribution of lethal respiratory disease in domestic cats after natural pandemic (H1N1) 2009 influenza virus infection, probably transmitted from humans.

Aryl hydrocarbon receptor (AhR) activation by high-affinity ligands mediates immunosuppression in association with increased regulatory T cells (Tregs), making this transcription factor an attractive therapeutic target for autoimmune diseases. We recently discovered 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ), a nanomolar affinity AhR ligand with immunosuppressive activity and favorable pharmacologic properties. In this study, we tested the consequences of AhR activation in the NOD model. Oral 10-Cl-BBQ treatment prevented islet infiltration without clinical toxicity, whereas AhR-deficient NOD mice were not protected. Suppression of insulitis was associated with an increased frequency, but not total number, of Foxp3⁺ Tregs in the pancreas and pancreatic lymph nodes. The requirement for Foxp3⁺ cells in AhR-induced suppression of insulitis was tested using NOD.Foxp3^DTR mice, which show extensive islet infiltration upon treatment with diphtheria toxin. AhR activation prevented the development of insulitis caused by the depletion of Foxp3⁺ cells, demonstrating that Foxp3⁺ cells are not required for AhR-mediated suppression and furthermore that the AhR pathway is able to compensate for the absence of Foxp3⁺ Tregs, countering current dogma. Concurrently, the development of disease-associated CD4⁺Nrp1⁺Foxp3⁻RORγt⁺ cells was inhibited by AhR activation. Taken together, 10-Cl-BBQ is an effective, nontoxic AhR ligand for the intervention of immune-mediated diseases that functions independently of Foxp3⁺ Tregs to suppress pathogenic T cell development.

The c-MYC (MYC) oncoprotein is often overexpressed in human breast cancer; however, its role in driving disease phenotypes is poorly understood. Here, we investigate the role of MYC in HER2⁺ disease, examining the relationship between HER2 expression and MYC phosphorylation in HER2⁺ patient tumors and characterizing the functional effects of deregulating MYC expression in the murine NeuNT model of amplified-HER2 breast cancer. Deregulated MYC alone was not tumorigenic, but coexpression with NeuNT resulted in increased MYC Ser62 phosphorylation and accelerated tumorigenesis. The resulting tumors were metastatic and associated with decreased survival compared with NeuNT alone. MYC;NeuNT tumors had increased intertumoral heterogeneity including a subtype of tumors not observed in NeuNT tumors, which showed distinct metaplastic histology and worse survival. The distinct subtypes of MYC;NeuNT tumors match existing subtypes of amplified-HER2, estrogen receptor–negative human tumors by molecular expression, identifying the preclinical utility of this murine model to interrogate subtype-specific differences in amplified-HER2 breast cancer. We show that these subtypes have differential sensitivity to clinical HER2/EGFR–targeted therapeutics, but small-molecule activators of PP2A, the phosphatase that regulates MYC Ser62 phosphorylation, circumvents these subtype-specific differences and ubiquitously suppresses tumor growth, demonstrating the therapeutic utility of this approach in targeting deregulated MYC breast cancers.