The purpose of this retrospective study was to provide additional data on the use of toceranib in a wide variety of tumor types in small breed dogs, especially < 8 kg (except 5 dogs). This was a retrospective study of 31 dogs with malignant tumors treated with a 2.5 mg/kg median dose of toceranib (Palladia; Zoetis, USA) on a Monday-Wednesday-Friday schedule. Clinical benefit was observed in 13 of 15 dogs (86.7%, 3 with complete response, 4 with partial response, 6 with stable disease) with gross disease. Distant metastasis, response to treatment, and treatment setting were significantly associated with survival time. Negative prognostic factors were multiple chemotherapy and distant metastasis (affecting progression-free survival [PFS]), surgery, regional enlarged lymph nodes, underlying disease, and toxicity (affecting median survival time [MST]). Positive prognostic factors were epithelial and round cell tumor (affecting PFS), epithelial tumor, microscopic disease, no evidence of disease response, and stable disease (MST). In conclusion, a clinical benefit from toceranib treatment was noted in most of the dogs with gross disease in our study. This study suggested that the toceranib is probably selective treatment to various tumor types in small breed dogs.

OBJECTIVE To determine the in vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in blood from healthy dogs. SAMPLES Blood samples from 9 healthy dogs. PROCEDURES Blood samples were incubated with LPS from Escherichia coli O127:B8 or PBSS (control) for 1 hour. Afterward, the samples were incubated with 10μM epinephrine, norepinephrine, or dobutamine or with saline (0.9% NaCl) solution (control) for 23 hours. Leukocyte viability was assessed by use of trypan-blue exclusion in blood from 2 dogs to ensure cell viability was not altered by the catecholamines. Tumor necrosis factor-α, IL-6, and IL-10 concentrations were measured in the supernatant in duplicate with a canine-specific multiplex bead-based assay. Blood samples from 2 dogs were used to create dose-response curves to evaluate whether the observed cytokine modulation was dependent on catecholamine concentration. RESULTS Incubation of blood with epinephrine and norepinephrine significantly increased LPS-stimulated production of IL-10, compared with the control. Epinephrine and norepinephrine significantly decreased LPS-stimulated production of TNF-α, compared with the control. Epinephrine and norepinephrine did not significantly alter LPS-stimulated production of IL-6. Dobutamine did not alter catecholamine production. CONCLUSIONS AND CLINICAL RELEVANCE Epinephrine and norepinephrine, but not dobutamine, had immunomodulatory effects on LPS-stimulated TNF-α and IL-10 production in blood from healthy dogs in this in vitro model of sepsis. Data suggested that dobutamine may have immune system-sparing effects in dogs with sepsis.

Although glucocorticoid administration has produced impressive results in treating canine mast cell tumors (MCTs), in some cases, glucocorticoids fail to reduce the tumor volume, leading to tumor relapse even after treatment. To date, mechanisms involved in glucocorticoid resistance in canine MCTs remain poorly defined. The objective of this study was to establish glucocorticoid-resistant canine MCT cell lines derived from glucocorticoid-sensitive cell lines after prolonged treatment with dexamethasone (Dex). Real-time polymerase chain reaction (RT-PCR) revealed that elevation of glucocorticoid receptor (GR)-regulated gene expression was suppressed in Dex-resistant cell lines after Dex stimulation compared with parent Dex-sensitive cell lines. This indicated that GR-regulated transcription was suppressed in Dex-resistant cell lines. Insufficient expression of GRs was not detected in Dex-resistant cell lines. Possible inhibitors of GR-regulated transcription were increased in mRNA expression in Dex-resistant cell lines. In addition, it was determined that mRNA expression of drug efflux pumps and anti-apoptosis factors was higher in Dex-resistant cell lines. In conclusion, glucocorticoid-resistant canine MCT cell lines have been established that are derived from glucocorticoid-sensitive cell lines. These cell lines suggest that multiple mechanisms contribute to glucocorticoid resistance in canine MCT cells. The mechanisms of glucocorticoid resistance after long-term treatment can be further investigated using these cell lines and a novel therapeutic strategy for glucocorticoid-resistant canine MCT cells can be developed.

Factors such as location, volume, and the type of neoplasm complicate achieving tumor control. Electrochemotherapy (ECT) is a supplementary treatment for inoperable neoplasms in veterinary patients. Three dogs were diagnosed with a tumor. Two were squamous cell carcinoma (SCC), and the other was liposarcoma, each with a single tumor with the size range of 1 to 5 cm. The tumor locations were the cervical, oral, and abdominal cavity. ECT was selected as a treatment. Bleomycin was injected intratumorally at the dose of 0.5 to 1.0 mg/cm³. Five minutes after the injection, electric pulses applied in a sequence of eight pulses lasting 100 µsec each, were delivered in 1,000 V/cm. An evaluation was performed after 1 week, and the next session was administered 2 weeks later. In a patient with oral SCC, the tumor was in partial remission after two sessions of ECT. Another patient with SCC on her neck was showed complete remission after 2 weeks of ECT administration. A third patient showed stable disease for 8 weeks. Complications were mild and transient and included skin necrosis, edema, local pain, and gait disturbance. ECT is a valid adjuvant, especially for inoperable, cutaneous, or accessible intra-abdominal tumors.

A 1-year-old, castrated male mixed-breed dog presented with diffuse, purple lesions arranged in an irregular patchy pattern, with a slight elevation on the right hindlimb extending from the tarsus joint to the upper region of the thigh. Dermatological examinations and fungal and bacterial cultures revealed no infectious agents. The therapeutic response to antibiotics and antifungal agents was negative. A histopathology examination of the lesion revealed vascular proliferation with vasodilation and numerous varying-sized vessels. Mast-cell-dominated perivascular cuffing was also noted. The dog was diagnosed with cutaneous angiomatosis due to diffuse lesions and the histopathology findings of hemangioma.

The objective of this retrospective study was to evaluate the expression of receptor tyrosine kinases (RTKs) in canine adrenal tumors and correlate this expression with features of tumor aggressiveness and survival in dogs undergoing adrenalectomy. Forty-three canine adrenal tumors were evaluated for expression of c-kit, fms-like tyrosine kinase 3 (flt-3), platelet-derived growth factor receptor-β (PDGFR-β), and vascular endothelial growth factor receptor 2 (VEGFR2) using immunohistochemistry. Tumor RTK staining characteristics were compared to normal adrenals. Medical records were reviewed for data regarding patient outcome and tumor characteristics. Expression of c-kit, flt-3, PDGFR-β, and VEGFR2 was detected in 26.9%, 92.3%, 96.2%, and 61.5% of cortical tumors and 0%, 63.2%, 47.4%, and 15.8% of pheochromocytomas, respectively. Expression of RTKs was not significantly increased when compared to normal adrenals and did not correlate with survival after adrenalectomy. Receptor tyrosine kinases are not overexpressed in canine adrenal tumors compared to normal adrenal tissue. Therapeutic inhibition of these receptors may still represent an effective approach in cases where receptor activation is present.