ABSTRACT. The medical records of 61 dogs with MCT at high risk for metastasis that were treated with prednisone and VBL following excision +/-radiation therapy were reviewed, and median disease-free interval (DFI), median overall survival time (OS) and prognostic factors assessed. Adverse effects, mostly mild, were noted in 26% of patients, usually after the first VBL dose. 6.5% experienced severe neutropenia. The DFI was 1305 days, and the OS was not reached, with 65% alive at 3 years. 100% of dogs with "high-risk" grade II MCT were alive at 3 years. The OS for dogs with grade III MCT was 1374 days. Histologic grade, location (mucous membrane vs. skin) and use of prophylactic nodal irradiation predicted outcome. Prednisone and VBL chemotherapy is well tolerated, and results in good outcomes following surgery in dogs with MCT at high risk for metastasis. High-grade and mucocutaneous tumors had a worse outcome, and the use of prophylactic nodal irradiation appeared to improve outcome in this group of dogs. KEY WORDS: canine, mastocytoma, Prednisone, vinblastine.J. Vet. Med. Sci. 68(6): 581-587, 2006 Mast cell tumour (MCT) represents the most common malignant cutaneous tumour in the dog [29]. High-grade or undifferentiated MCT (Patnaik grade III) comprise 29 to 40% of all MCT [2,14,22]. In addition to local infiltration, they have a reported metastatic rate of 55 to 96%, and are more likely to result in tumor-related death than are low-or intermediate-grade MCT [29]. While some discordance exists in the literature, patients with MCT of any grade involving the regional lymph node (LN) or arising from a mucous membrane (e.g. gingiva, perineum, prepuce, nailbed) may also be at higher risk for eventual death from MCT [1,10,[28][29][30]. Thus, local therapies alone may be suboptimal for tumour control in these patients.Survival times after surgery alone for high-grade MCT were reported in early studies as 15% at seven months, 6% at 48 months, and a median survival time (MST) of 13 weeks [2,3,22]. More recent studies have reported a MST of approximately 9 months with resection alone in dogs with high-grade MCT [20,25].Several studies have evaluated chemotherapy for the treatment of measurable MCT, and response rates from 7% to 78% have been documented [8,10,17,18,23,28]. However, few studies have evaluated the efficacy of chemotherapy as adjuvant treatment for MCT [7,28].Vinblastine (VBL) is an antimicrotubule alkaloid used in the treatment of hemolymphatic neoplasia in dogs [12], and various human malignancies [24]. We previously reported the results of a study employing prednisone/VBL for the treatment of dogs with gross, microscopic and "high-risk" MCT. An objective response rate of 44% was reported in dogs with gross disease, and there was suggestion that dogs receiving prednisone/VBL following surgery had a favorable clinical outcome compared with historical controls receiving local therapy alone [28]. However, the clinical characteristics of these patients were variable, and a relatively small number were treat...

The medical records of 15 dogs with anal sac adenocarcinoma (ASAC) treated with concurrent curative-intent radiotherapy and mitoxantrone (MX) after surgical removal of the primary tumour were reviewed retrospectively. Radiation was prescribed at 15 daily fractions of 3.2 Gy for a total dose of 48 Gy. MX was given intravenously at a dosage of 5 mg m(-2) every 3 weeks for five treatment sessions. Twelve dogs received pelvic irradiation to include the regional lymph nodes (LNs) and three received radiation only to the perineum. At the time of diagnosis, four dogs were hypercalcaemic and seven dogs presented with regional LN metastasis. All the dogs with regional LN metastasis received pelvic irradiation, and in three cases, metastatic LNs were treated in the macroscopic disease setting. The median event-free survival was 287 days, and the median overall survival was 956 days. Acute and chronic radiation complications were common and non-life threatening, although chronic complications contributed to the decision to euthanize two dogs. The results observed in this retrospective analysis compare favourably with cases of ASAC in the literature related to treatment with surgery and/or chemotherapy.

Intensity modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared to a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT treated and 2D treated dogs was 420 days and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in

AtPUB18 and AtPUB19 are homologous U-box E3 ubiquitin ligases in Arabidopsis (Arabidopsis thaliana). AtPUB19 is a negative regulator of abscisic acid (ABA)-mediated drought responses, whereas the role of AtPUB18 in drought responses is unknown. Here, loss-of-function and overexpression tests identified AtPUB18 as a negative regulator in ABA-mediated stomatal closure and water stress responses. The atpub18-2atpub19-3 double mutant line displayed more sensitivity to ABA and enhanced drought tolerance than each single mutant plant; therefore, AtPUB18 and AtPUB19 are agonistic. Stomatal closure of the atpub18-2atpub19-3 mutant was hypersensitive to hydrogen peroxide (H 2 O 2 ) but not to calcium, suggesting that AtPUB18 and AtPUB19 exert negative effects on the ABA signaling pathway downstream of H 2 O 2 and upstream of calcium. AtPUB22 and AtPUB23 are other U-box E3 negative regulators of drought responses. Although atpub22atpub23 was more tolerant to drought stress relative to wild-type plants, its ABA-mediated stomatal movements were highly similar to those of wild-type plants. The atpub18-2atpub19-3atpub22atpub23 quadruple mutant exhibited enhanced tolerance to drought stress as compared with each atpub18-2atpub19-3 and atpub22atpub23 double mutant progeny; however, its stomatal behavior was almost identical to the atpub18-2atpub19-3 double mutant in the presence of ABA, H 2 O 2 , and calcium. Overexpression of AtPUB18 and AtPUB19 in atpub22atpub23 effectively hindered ABA-dependent stomatal closure, but overexpression of AtPUB22 and AtPUB23 in atpub18-2atpub19-3 did not inhibit ABA-enhanced stomatal closure, highlighting their ABA-independent roles. Overall, these results suggest that AtPUB18 has a linked function with AtPUB19, but is independent from AtPUB22 and AtPUB23, in negative regulation of ABA-mediated drought stress responses.

The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.