Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder.

OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder. PROCEDURES-Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d (1.36 mg/lb/d) as a single-agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Toxic effects of deracoxib administration in dogs were assessed through clinical observations and hematologic and biochemical analyses. RESULTS-Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC.

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs.

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.

Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. DESIGN: Prospective nonrandomized clinical trial. ANIMALS: 25 dogs. PROCEDURE: Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. RESULTS: 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. CONCLUSIONS AND CLINICAL RELEVANCE: Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

Esophageal achalasia and secondary megaesophagus in a dog.

A 5-year-old, castrated male, golden retriever was presented with a history of regurgitation. An esophagram revealed normal peristalsis with failure of the lower esophageal sphincter to open, supporting the diagnosis of esophageal achalasia. Prior to surgery, the dog developed megaesophagus. Heller's esophagomyotomy resolved the clinical signs and the esophageal dilation.

S-adenosylmethionine and cAMP confer differential cytoprotection against bile acid-induced apoptosis in canine renal tubular cells and primary rat hepatocytes.

Cholestasis results in the accumulation of cytotoxic bile acids in the body. The cytoprotective effect of S-adenosylmethionine (SAMe) and cAMP were compared in two in vitro models of bile acid-induced apoptosis. Primary cultures of rat hepatocytes and canine renal tubular cells (Madin-Darby canine kidney [MDCK] cells stably transfected with the conjugated bile salt transporter, sodium [Na+]/taurocholate cotransporting polypeptide [Ntcp]) were treated with conjugated bile acids and monitored for apoptosis. Glycine-conjugated bile acids caused similar amounts of apoptosis, whereas taurine-conjugated bile acids were five to 10 times more toxic in MDCK-Ntcp cells than in hepatocytes. Treatment with the 1,4-butanedisulfonate salt of SAMe (500 microM) or the stable chlorophenylthio-cAMP analogue (100 microM) inhibited bile acid-induced apoptosis in hepatocytes by 70% and 40%, respectively. In MDCK-Ntcp cells, SAMe inhibited apoptosis by 20%, but cAMP was without effect. Immunoblotting for activation of putative survival kinases in cAMP-treated cells (phosphorylated protein kinase B [Akt] or mitogen-activated protein kinase [MAPK]) was done using phosphospecific antibodies. cAMP increased Akt phosphorylation threefold in hepatocytes but not in MDCK-Ntcp cells. Activation of p42/p44 MAPK was inhibited by cAMP in both cells. SAMe protects against bile acid-induced apoptosis in hepatocytes and MDCK-Ntcp cells. The cytoprotective effect of cAMP is seen only in hepatocytes and may reflect tissue-specific activation of Akt.