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The Clinical Significance Of Expression Of Cyclooxygenase-2 In Human Breast Cancer

Posted on:2006-03-02Degree:MasterType:Thesis
Country:ChinaCandidate:M XuFull Text:PDF
GTID:2144360155952647Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Cyclooxygenase (COX) is a rate-limiting enzymethat converts arachidonic acid to prostaglandin, COX exists in twoisoforms, Cox-1 and COX-2. Cox-1 is a constitutive enzyme thatproduces PGs for maintaining physiological functions, such asgastric cytoprotection, vascular homeostasis, and renal function.COX-2 is an inducible enzyme that produces PG involedinflammation and cell growth. Cox-2 is express in normal brain andkidney. COX-2 expression is stimulated by a number ofinflammation, growth factors, oncogenes, lipopolysaccharides, andtumor promoters. Results of several studies using mose models ofcolon cancer and the results of clinical trails have shown COX-2 tobe useful target for the prevent and treatment of cancer. studieswith several other epithelial cancers involving different organ site,e.g. breast prostate, bladder, lung, suggest that Cox-2 plays animportant role in the pathogenesis of these cancers. Recent reportshave demonstrated that the use of NSAIDs is associated with areduction in human breast cancer risk and that breast cancer riskdeclines with increasing NSAID exposure.。Studies from mouse ofmammary tumorigenesis and from human breast cancer cell linesprovide evidence that COX-2 overexpression plays an importantrole in the pathogenesis of malignant breast cancer in humans. Thisstudy was designed to investigate the role of COX-2 in thedevelopment and progression of breast cancer through examing theexpress of COX-2 and pathophysiological features in patients withbreast cancer. Because of availability of effective and relativelysafe COX-2 inhibitors, it should be soon possible to evaluate theireffectiveness in the clinic for the prevention and treastment ofbreast cancer. It is likely the COX-2 inhibitors will be effective inthe treastment regimens involving combination chemotherapies. Methods: Expression of COX-2 protein was detected in 40case if breast cancinoma tissues ang 18 case of paracancerous byimmunohistochemistry method (Steptavidin —biotinimmunoperoxidase method ) ,the relationship between COX-2expression level and cancer pathologic parameters was analyzed . Results : Positive expression of COX-2 was detected in 52.5%of the breast cancerous tissues and in 11.11% of paracanceroustissues and there was significant diffrence in expression of COX-2between cancer tissues and paracancerous tissues (P﹤0.005) . Theexpression of COX-2 was correlation with the metastatic lymphnodes and HER-2/neu-overexpression (P﹤0.05) but there was nocorrelation with age,pathologic stage and tumor size (P﹥0.05). Conclusions: COX-2 might play important role in theproliferation of breast cancer cells .Recently many of reserchesshowed that COX-2 plays a key role in tumorigenesis throughstimulating epithelial cell preliferation, stimulating angiogenesis,enhancing cell invasiveness, mediating immune suppression, andby increasing the production of mutagens, inhibition of tumor cellsapoptosis . Accoding to our study, a high level of COX-2 protein wasdetected in21 of 40 breast cancer samples .as only 2 of 18 ofparacancerous samples for a lower level of COX-2 protein .There isincreasing evidence that COX-2 is more upregulated in humantumors than in adjacent normal tissue . The exepression of COX-2had no association with pathologic stage, We belivedoverexpression of COX-2 in early breast cancer. The expression ofCOX-2 was correlation with the metastic lymph nodes (P﹤0.05).It is possible that this indicate mediatly infiltrating mammarycarcinona expressed significant levels of COX-2. Because of themore of infiltration ductal carcinomas and the lower of otherpathologic type carcinomas in this trial, we had no conclusion therelationship between infiltration of breast cancer. This is illustratedby the study in which COX-2 overexpression protein was detectedin 8 of 10 breast cancer samples that were positive forHER-2/neu-overexpression ., the level and frequency of COX-2expression were singnificantly lower in HER-2/neu-overexpression,...
Keywords/Search Tags:Cyclooxygenase-2
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