The usage of reovirus has reached phase II and III clinical trials in human cancers. However, this is the first study to report the oncolytic effects of reovirus in veterinary oncology, focusing on canine mast cell tumor (MCT), the most common cutaneous tumor in dogs. As human and canine cancers share many similarities, we hypothesized that the oncolytic effects of reovirus can be exploited in canine cancers. The objective of this study was to determine the oncolytic effects of reovirus in canine MCT in vitro, in vivo and ex vivo. We demonstrated that MCT cell lines were highly susceptible to reovirus as indicated by marked cell death, high production of progeny virus and virus replication. Reovirus induced apoptosis in the canine MCT cell lines with no correlation to their Ras activation status. In vivo studies were conducted using unilateral and bilateral subcutaneous MCT xenograft models with a single intratumoral reovirus treatment and apparent reduction of tumor mass was exhibited. Furthermore, cell death was induced by reovirus in primary canine MCT samples in vitro. However, canine and murine bone marrow-derived mast cells (BMCMC) were also susceptible to reovirus. The combination of these results supports the potential value of reovirus as a therapy in canine MCT but warrants further investigation on the determinants of reovirus susceptibility.

ABSTRACT. The importance of CD4 + CD25 + Foxp3 + regulatory T cells (Treg cells) in immune response is increasingly being recognized. However, to date, only a few studies on these cells have been conducted in canine species, partly because of the unavailability of appropriate antibodies to detect this cell population. In this study, the crossreactivities of anti-human CD25 antibody (clone ACT-1) and antimouse Foxp3 antibody (clone FJK16s) to canine CD25 and Foxp3, respectively, were confirmed using cell lines overexpressing either of these genes. By using these antibodies, we determined if CD4

Reovirus is a potent oncolytic virus in many human neoplasms that has reached phase II and III clinical trials. Our laboratory has previously reported the oncolytic effects of reovirus in canine mast cell tumour (MCT). In order to further explore the potential of reovirus in veterinary oncology, we tested the susceptibility of reovirus in 10 canine lymphoma cell lines. Reovirus-induced cell death, virus replication and infectivity were confirmed in four cell lines with variable levels of susceptibility. The level of Ras activation varied among the cell lines with no correlation with reovirus susceptibility. Reovirus-susceptible cell lines underwent apoptosis as proven by propidium iodide (PI) staining, Annexin V-FITC/PI assay, cleavage of PARP and inhibition of cell death by caspase inhibitor. A single intratumoral injection of reovirus suppressed the growth of canine lymphoma subcutaneous tumour in NOD/SCID mice. Unlike canine MCT, canine lymphoma is less susceptible to reovirus.

ABSTRACT. Five novel, canine lymphoma cell lines (Ema, CLC, CLK, Nody-1 and UL-1) were established from dogs suffering from lymphoma and characterized in vitro and in vivo. All cell lines, except CLC, were characterized with T-cell phenotypes, by flow cytometric analysis and polymerase chain reaction for antigen receptor rearrangement. Cell proliferation rates and transcriptional levels of MYC, PTEN, KIT and FLT3 varied between each cell line. Intraperitoneal xenotransplantation of Ema, CLC, Nody-1 and UL-1 lymphoma cell lines into NOD/SCID mice induced ascites, intraperitoneal tumors and severe infiltration of lymphoma cells into the pancreas and mesentery. Establishment of novel canine lymphoma cell lines with different characteristics is critical for elucidating the pathophysiology of canine lymphoma and improving current therapies.

ABSTRACT. A 6-month-old miniature Schnauzer presented with hypernatremia and clinical signs of vomiting, diarrhea, inappetence, and lethargy. The dog did not consume water on its own. Hypernatremia and the related clinical signs were resolved by fluid administration. Endocrinological investigations and urinalysis excluded the possibility of diabetes insipidus and hyperaldosteronism. Therefore, the dog was diagnosed with hypodipsic hypernatremia. Magnetic resonance imaging revealed dysgenesis of the corpus callosum and other forebrain structures. On the basis of these findings, congenital brain malformation associated with failure of the osmoreceptor system was suspected.KEY WORDS: dysgenesis of corpus callosum, hypodipsic hypernatremia, magnetic resonance imaging, miniature Schnauzer.J. Vet. Med. Sci. 71(10): 1387-1391, 2009 Hypernatremia is uncommon in conscious animals that have free access to water [6]. If chronic and recurrent hypernatremia is identified in fully conscious animals that have access to water and do not have polyuria, the cause of hypernatremia is almost certainly the abnormal osmoregulation of antidiuretic hormone (ADH) release and/or hypodipsia resulting from hypothalamic lesions [1,3,4,17]. Although hypodipsic hypernatremia has been documented as a congenital disorder of young miniature Schnauzers [5,13,20,22,23], the magnetic resonance imaging (MRI) findings in miniature Schnauzers with hypodipsic hypernatremia have not yet been reported. This report describes a case of hypernatremia secondary to hypodipsia in a miniature Schnauzer and the MRI findings in this case.A 6-month-old, female miniature Schnauzer was referred to Yamaguchi University Animal Medical Center because of a history of repeated episodes of elevated plasma sodium ion concentration, as determined using laboratory tests. The dog had a 1.5-month history of intermittent vomiting, diarrhea, inappetence, and lethargy. These clinical signs improved when balanced electrolyte solutions were administered intravenously or subcutaneously. The laboratory findings recorded by the referring veterinarian consisted of marked hypernatremia and hyperchloremia (Table 1).At the time of referral, the dog had a body weight of 3.6 kg and was small for its age and breed. Initial physical examination revealed that the capillary refilling time and visible mucous membranes were normal, and the dog was considered to be hydrated. Laboratory findings revealed macrocytic hypochromic anemia (hematocrit, 33.0% Table 1). The calculated plasma osmolality was remarkably increased (344 mOsm/kg). The findings of thoracic and abdominal radiography and abdominal ultrasonography were unremarkable. Additional investigations were performed to determine the cause of hypernatremia (Table 1). The plasma cortisol concentrations before and after the administration of adrenocorticotropic hormone (ACTH) were 0.82 and 14.24 g/dl, respectively. The blood aldosterone level was normal (148 pg/ml) and arginine vasopressin (AVP) level was appropriate (6.41 pg/ml). The dog did ...