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25/12/2002 THE USE OF NSAIDS IN CHEMOTHERAPEUTIC TREATMENT Author-Zahi even-zoor Instructor- Dr. Gillian dank
NSAIDs are group of drugs effective in the relief of pain, inflammation, and fever. The pharmacologic action of NSAIDs is to inhibit the enzyme Cyclooxygenase (Cox). Cox is the initial step in the metabolism of archidonic acid into prostaglandin. Prostaglandin modulates many functions of cells and tissues in the body. There are two kinds of isoenzyms to Cox: Cox 1- expressed constitutively in most tissues of the body. It has a role in gastric cytoprotection, platelet aggregation, contribute to vascular dilatation and renal sodium and water balance. Cox 2- is not expressed regularly, but is up regulated by inflammatory cytokines, growth factors and tumor promoters. Most NSAIDs inhibits both Cox 1 & Cox 2 , but there are Cox 2 selective drugs.
Many studies have shown that NSAIDs inhibits cancer development by inhibition of Cox, in animal models and tissue cultures. Most of the research on chemotherapeutic treatment with NSAIDs has been done on human colorectal cancer or colorectal adenomatous polyps. Cox is also expressed in tumors of the stomach, esophagus, head and neck, liver, pancreas and lungs.
Mechanism of action of Cox 2 inhibitors- over expression of Cox in cancer tissue cause a reduction in the normal apoptosis and increase in angiogenesis. Cox 2 inhibitors suppress this processes and by that control tumor behavior and invasiveness.
Transitional cell carcinoma (TCC) is the most common tumor in canine urinary bladder. In the study of Sulma I.M. et. al 2002 , treatment of TCC with Piroxicam (non selective NSAID) cause a reduction in pgE2 concentration in the tumor tissue, increase the apoptotic index of the tumor and cause a reduction in the tumor proliferation. In another study of Bredley R. et. al 2001, treatment of squamous cell carcinoma (SCC) with piroxicam causes a remission of the tumor in 18% of the dogs, and stable disease in 29%of the dogs.
References: 1. Small animal clinical oncology: Stephen J. withrow , E. Gregory macewen p.110-111, 490-499. 2. Cancer chemotherapy and biotherapy, third edition: Bruce A. chabner, Dan L. longo p. 601-610. 3. Sulma I. mohammed: Effects of piroxicam, on tumor response, apoptosis and angiogenesis in a canine model of human invasive urinary bladder cancer; cancer research 62, 356-358, January 15, 2002. 4. Bradley R. Schmidt: Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs; javma 2001; 218: 1783-1786. 5. Textbook of veterinary internal medicine: Stephen J. Ettinger, Edward C. Feldman P.541-542.
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