The aim of this study was to investigate COX-2 expression in squamous cell carcinoma of the oesophagus (SCC), and the potential of non-steroidal anti-inflammatory drugs, which inhibit the action of the enzyme, for chemoprevention of this cancer. The epidemiology of SCC and the outcome from surgery for this disease in Hebei Province, China, were reviewed. The rate of postoperative complications and deaths following oesophagectomy fell steadily over the last five decades, but the long-term survival remained disappointing. Improved survival is likely to be dependent on earlier diagnosis and better adjunctive therapies. Tissue was obtained from patients who had an oesophagectomy for SCC over 20 years earlier. The expression of COX-2 was elevated and correlated with TNM stage and lymph node metastases. Survival was longer in those patients whose tumours expressed lower levels of COX-2. The mechanism of action of aspirin, a non-selective COX inhibitor, and NS-398, a selective COX-2 inhibitor, was investigated in vitro. Both drugs inhibited the proliferation of and induced apoptosis in the SCC cell line TE-13. These changes correlated with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, inhibition of NF-KappaB nuclear translocation and an increase in cytoplasmic IKappaB. Similar changes were seen in tumour tissue resected from patients given the selective COX-2 inhibitor Mobic daily for 14 days before surgery. These results suggested that aspirin and similar drugs might have value in cancer therapy. A clinical trial was established to determine if treatment with aspirin post-operatively would improve survival of patients who had had an oesophagectomy for SCC. Preliminary results suggested that treatment had no effect on survival in patients operated on for SCC. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289296 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2007
| Identifer | oai:union.ndltd.org:ADTP/264549 |
| Date | January 2007 |
| Creators | Liu, Jun-Feng |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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