Intramural coronary artery and myocardial pathology in captive tigers (Panthera tigris) and African lions (Panthera leo).

There is limited published data regarding cardiovascular disease in nondomestic felid populations. To address this knowledge gap, necropsy cases of tigers and lions with representative myocardial samples submitted to a diagnostic laboratory were histologically assessed with hematoxylin and eosin and Sirius red stains. A total of 32 submissions (15 tigers, 17 lions) were identified in a 4-year period. All tigers and lions had some degree of coronary artery lesions in the left ventricle and/or interventricular septum. Major findings included moderate to marked arteriosclerosis in 8 tigers (53%) and 4 lions (24%) and moderate to marked perivascular fibrosis in 10 tigers (67%) and 9 lions (53%). Moreover, 10 tigers (67%) and 8 lions (47%) had coronary artery lesions with variable degrees of perivascular cardiomyocyte degeneration and/or loss. To our knowledge, this is the first report describing coronary artery pathology in captive tigers and lions.

Characterization of WWOX expression and function in canine mast cell tumors and malignant mast cell lines.

BACKGROUND: The WW domain-containing oxidoreductase (WWOX) tumor suppressor gene is frequently lost in a variety of solid and hematopoietic malignancies in humans. Dysregulation of WWOX has been implicated as playing a key role in tumor cell survival, DNA damage repair, and genomic stability. The purpose of this study was to characterize WWOX expression in spontaneous canine mast cell tumors (MCTs) and malignant cell lines and investigate the potential contribution of WWOX loss on malignant mast cell behavior. METHODS/RESULTS: WWOX expression is decreased in primary canine MCTs and malignant mast cell lines compared to normal canine bone marrow-cultured mast cells. In transformed canine mastocytoma cell lines, overexpression of WWOX or WWOX knockdown had no effect on mast cell viability. Inhibition of WWOX enhanced clonogenic survival following treatment with ionizing radiation in the C2 mast cell line. Lastly, immunohistochemistry for WWOX was performed using a canine MCT tissue microarray, demonstrating that WWOX staining intensity and percent of cells staining for WWOX is decreased in high-grade MCTs compared to low-grade MCTs. CONCLUSIONS: These data suggest that WWOX expression is attenuated or lost in primary canine MCTs and malignant mast cell lines. Given the observed increase in clonogenic survival in WWOX-deficient C2 mast cells treated with ionizing radiation, further investigation of WWOX and its role in mediating the DNA damage response in malignant mast cells is warranted.

Reprogramming the Canine Glioma Microenvironment with Tumor Vaccination plus Oral Losartan and Propranolol Induces Objective Responses.

Purpose: Malignant gliomas have a highly immune suppressive tumor microenvironment (TME) which renders them largely unresponsive to conventional therapeutics. Therefore, the present study evaluated a therapeutic protocol designed overcome the immune barrier by combining myeloid cell targeted immunotherapy with tumor vaccination. Experimental Design: We utilized a spontaneously occurring canine glioma model to investigate an oral TME modifying immunotherapy in conjunction with cancer stem cell (CSC) vaccination. Dogs were treated daily with losartan (monocyte migration inhibitor) and propranolol (myeloid-derived suppressor cell depleting agent) plus anti-CSC vaccination on a bi-weekly then monthly schedule. Tumor volume was monitored by MRI and correlated with patient immune responses. Results: Ten dogs with histologically confirmed gliomas were enrolled into a prospective, open-label clinical trial to evaluate the immunotherapy protocol. Partial tumor regression was observed in 2 dogs, while 6 dogs experienced stable disease, for an overall clinical benefit rate of 80%. Overall survival times (median = 351 days) and progression-free intervals (median = 163 days) were comparable to prior studies evaluating surgical debulking followed by immunotherapy. Dogs with detectable anti-CSC antibody responses had an increased overall survival time relative to dogs that did not generate antibody responses (vaccine responder MST = 500 days; vaccine non-responder MST = 218 days; p = 0.02). Conclusions: These findings suggest that combining myeloid cell targeted oral immunotherapy with tumor vaccination can generate objective tumor responses, even in the absence of conventional therapy. Overall, this approach has promise as a readily implemented therapeutic strategy for use in brain cancer patients.

Myxedema Coma and Acute Hepatopathy in a Dog with Severe Atherosclerosis.

A 9-year-old male intact mixed-breed dog was presented to The Ohio State University Veterinary Medical Center for evaluation of two days' duration of weakness, lethargy, inappetence, and one episode of vomiting the day of presentation. On presentation, the dog was depressed and tetraparetic. He was noted to be icteric and dehydrated. Obesity and truncal alopecia with a "rat tail" appearance were observed. Diagnostic testing revealed evidence of an acute hepatopathy and peritonitis. Given the dog's neurologic status, physical examination abnormalities, including a "tragic facial expression", and hyperlipidemia, there was concern for possible myxedema coma. A thyroid panel was consistent with hypothyroidism. The dog experienced respiratory arrest prior to initiation of therapy, and an autopsy confirmed the presence of subacute necrotizing cholangiohepatitis, marked atherosclerosis, and severe thyroid atrophy. These clinical and pathologic changes were supportive of myxedema coma.