Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary leaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E2 (PGE2) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified. Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 month intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable disiroxicam (Feldene) is a nonsteroidal anti-inflammatory P drug primarily used to treat arthritis in humans.' It has also been reported to have antitumor activity in chemically inducal2-' and transplanted* tumors in rodents and in metastatic tumors in people.' We previously reported a phase I clinical trial of piroxicam in 62 dogs with naturally occurring tumors and identified dose-related gastrointestinal toxicity and subclinical renal toxicity.'o Antitumor activity was observed in this phase 1 trial in dogs with transitional cell carcinoma (TCC) of the urinary bladder." To hrther investigate the antitumor activity of piroxicam, we conducted a phase I1 clinical trial in 25 dogs with TCC of the bladder. The study reported here includes 9 dogs from the phase I trial and 25 dogs from the phase I1 trial. Although the purpose of a phase I trial is to evaluate drug doses and toxicity, useful information on tumor response and survival was available in the dogs with TCC in the phase I trial we conducted." Therefore, these dogs were included in this report. Materials and Methods Clinical Trial DesignEntry requirements for this study included the presence of measurable (by cystography), histopathologically confirmed TCC of the urinary bladder, performance status consistent with expected minimum survival of6 weeks, and informed consent by the owner. Dogs that had previously received chemotherapy had evidence of tumor progression on that therapy, and a minimum of 3 weeks was required between the last chemotherapy and entry into this trial.Dogs were evaluated at the Purdue University Veterinary Teaching Hospital on days 0, 28, and 56. These evaluations included physical examination, complete blood count, serum biochemistry profile, urinalysis, thoracic radiography, and cystography (pneumocystography or double contrast cystography). Care was taken to perform the cystography in the same manner (same radiographic technique, same amount of contrast material) for each evaluation of a patient. Piroxicam was administered orally at a dose of 0.3 mg/kg sid. This dose was established based on a previous phase I clinical trial." When secondary bacteria...

Transitional cell carcinoma (TCC) of the urinary bladder, the most common malignancy of the urinary tract in dogs, is challenging to both diagnose and treat effectively. The prevalence of this disease may be increasing. The etiology of canine TCC is likely multifactorial. Epidemiological studies of TCC in the dog have revealed a number of risk factors, including breed and female gender, as well as environmental factors, such as insecticide exposure. This tumor is difficult to remove surgically and responds poorly to chemotherapy. The efficacy of radiotherapy and other treatment modalities needs further investigation. Cyclooxygenaseinhibiting drugs have some activity against TCC, and studies to further define these effects are ongoing. Use of the tumor/node/ metastasis (TNM) classification scheme for bladder cancer has allowed for the identification of prognostic factors. Urinary tract obstruction and metastatic disease remain challenges to treat. Work with canine TCC has demonstrated how closely this disease resembles human invasive urinary bladder cancer. Therefore, future research has the potential to benefit both dogs and humans with TCC.Key words: Animal models; Bladder cancer; Chemotherapy; Cyclooxygenase; Piroxicam; Risk factors.U rinary bladder cancer in dogs is a challenging disease to diagnose, stage, and treat. Fortunately, urinary bladder cancer is uncommon in the dog, comprising Ͻ2% of all reported canine malignancies. 1 Transitional cell carcinoma (TCC) is the most common neoplasm affecting the urinary bladder of dogs. In this article, we review current knowledge of canine TCC with regard to frequency, etiology, histopathological characteristics, cellular and molecular features, response to therapy, and prognostic factors. We also discuss why canine TCC is a good model of human invasive bladder cancer. FrequencyAlthough the true prevalence of canine TCC is not known, it is the most common form of urinary tract cancer in the dog and comprises 1.5-2% of all canine cancers. 2,3 The hospital prevalence, or proportionate morbidity, of bladder cancer at university-based veterinary hospitals appears to be increasing. 4 A search of the Veterinary Medical Data Base (VMDB) 5 from 1975 to 1995 showed a continuous increase in the prevalence of bladder cancer, with prevalence defined as the number of dogs with bladder cancer divided by the total number of individual dogs seen for any reason at the same participating university veterinary hospitals. 4 Etiology and Risk FactorsThe etiology of canine TCC is most likely multifactorial. Risk factors that have been identified include exposure to topical insecticides for flea and tick control, exposure to marshes that have been sprayed for mosquito control, obe- University, West Lafayette, IN. Reprint requests: Deborah W. Knapp, DVM, MS, DACVIM, Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907-1248; e-mail: knappdw@purdue.edu. Submitted December 28, 2001; Revised April 23, 2002; Accepted June 17, 2002. Copyright ᭧ 2003 sity, ...

Objective. To determine whether overexpression of the high-affinity folate receptor (FR) on activated macrophages can be exploited to selectively target imaging agents to sites of inflammation in rats with adjuvant-induced arthritis (AIA).Methods. Folic acid was conjugated to a 99m Tc chelator (the complex termed EC20), and its distribution was visualized using gamma scintigraphy in healthy rats, rats with AIA, and arthritic rats that had been depleted of macrophages. To confirm that uptake was mediated by the FR, excess folic acid competition studies were conducted, and tissue FR levels were quantitated using a radioligand binding assay. Flow cytometry was also used to investigate uptake of folate conjugates into macrophages of both arthritic and healthy rats.Results. EC20 concentrated in the arthritic extremities of diseased rats but not in the extremities of healthy rats. The intensity of images of affected tissues was greatly reduced in the presence of excess competing folic acid. The livers and spleens of arthritic animals also showed enhanced uptake of EC20 and increased levels of FR. Depletion of macrophages from arthritic animals reduced tissue FR content and concomitantly abolished uptake of EC20. In addition, macrophages isolated from livers of rats with AIA exhibited a significantly higher binding capacity for folate conjugates than did macrophages obtained from healthy rats.Conclusion. Although EC20 is currently undergoing clinical evaluation for use in the imaging of ovarian carcinomas, the present results suggest that it may also be useful for assaying the participation of activated macrophages in inflammatory processes such as rheumatoid arthritis.

Radiographic evaluation of navicular syndrome is problematic because of its inconsistent correlation with clinical signs. Scintigraphy often yields false positive and false negative results and diagnostic ultrasound is of limited value. Therefore, we assessed the use of computed tomography and magnetic resonance imaging in a horse with clinical and radiographic signs of navicular syndrome. Cadaver specimens were examined with spiral computed tomographic and high-field magnetic resonance scanners and images were correlated with pathologic findings. Radiographic changes consisted of bony remodeling, which included altered synovial fossae, increased medullary opacity, cyst formation and shape change. These osseous changes were more striking and more numerous on computed tomographic and magnetic resonance images. They were most clearly defined with computed tomography. Many osseous changes seen with computed tomography and magnetic resonance imaging were not radiographically evident. Histologically confirmed soft tissue alterations of the deep digital flexor tendon, impar ligament and marrow were identified with magnetic resonance imaging, but not with conventional radiography. Because of their multiplanar capability and tomographic nature, computed tomography and magnetic resonance imaging surpass conventional radiography for navicular imaging, facilitating earlier, more accurate diagnosis. Current advances in imaging technology should make these imaging modalities available to equine practitioners in the future.

Cisplatin/piroxicam induced remission more frequently than cisplatin alone in a canine model of human invasive TCC. Strategies to reduce renal toxicity need to be developed prior to evaluation of cisplatin/piroxicam in humans or general use of this treatment in pet dogs.