02522-A: The Investigation of Lypoxigenase-5 Expression in Canine Normal, Hyperplastic and Neoplastic Urinary Bladder Epithelium
Grant Status: Closed
Transitional Cell Carcinoma (TCC) is the most common tumor of the canine urinary tract, causing nonresolving urinary signs (i.e., straining, hematuria) after it invades a large portion of the bladder and/or neighboring structures. Surgery may not be an option and chemotherapy represents the most common treatment; however, significant tumor reduction rarely occurs, resulting in a poor long-term outcome. Piroxicam, a non-steroidal anti-inflammatory drug, is one of the most effective compounds used to slow TCC progression. Piroxicam may also potentiate the effect of conventional chemotherapeutics, which are largely unrewarding when administered alone. Piroxicam targets cyclooxygenases (COX; proinflammatory enzymes), constitutively expressed by the bladder (COX-1) and overexpressed by the cancer (COX-2). Other inflammatory markers such as Lipoxigenase-5 (LOX-5) have been investigated in human TCCs, and found to be overexpressed compared to normal tissue. Importantly, in vitro studies have revealed that treating cancer cells with LOX-5 inhibitors can lead to 30% tumor reduction. The investigators will evaluate the expression of LOX-5 in canine TCCs, cystitis and normal bladder samples. COX-1&2 expression will be also analyzed in relationship to LOX-5. The demonstration of LOX-5 expression in canine TCC would open the possibility of using lipoxygenase inhibitors together with cyclooxygenase inhibitors to provide better treatment strategies for dogs. These inhibitors are safe and have shown stronger anti-inflammatory effect than piroxicam alone in dogs with other inflammatory disorders including uveitis and osteoarthritis.
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