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352 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D. 1980) from the Dept. of Psychiatry, University of Adelaide

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

Staphylococcal tenosynovitis and osteomyelitis are world-wide problems of broilers and broiler breeders caused by staphylococci. Pathogenesis of the disease is ill defined. Avian heterophils are analogous to mammalian neutrophils but the granules appear to be different. The first chemotactic study was done on heterophils from chickens having natural staphylococcal infection brought from a commercial broiler flock and on the heterophils obtained from healthy 6-8 weeks old chickens brought from a local hatchery as one day old chicks. In the second study, a chemotactic study was done with three different staphylococci on heterophils obtained from healthy 6-8 weeks old chickens brought from a local hatchery as one day old chicks. Results for the first study showed a decreased chemotactic response in the heterophils of chickens naturally infected with staphylococcus compared to healthy chicken heterophils in response to minimum essential medium, pooled normal chicken serum and E. coli endotoxin with normal chicken serum used as chemoattractants. Second study results showed that pathogenic capsule type 5 and type 8 Staphylococcus aureus isolates both induced chemotaxis in heterophils from healthy chickens to a significantly greater degree than did a non-pathogenic Staphylococcus xylosus. The Staphylococcus aureus isolate with capsule type 5 induced heterophil chemotaxis more than the capsule type 8 isolate. / Graduation date: 1993

Cisplatin is one of the most widely used chemotherapeutic anti-cancer drugs due to its ability to effectively damage DNA and cause cell death. Despite this, cisplatin still suffers from two main drawbacks: toxicity and drug resistance. Many cisplatin-like compounds have been synthesized via traditional methods of drug design but very few have been able to enter clinical trials or even be approved for clinical use. The reason why so many compounds have been rejected is that their reaction mechanisms are rarely understood. By observing and studying the reaction mechanisms of a drug at the molecular level, the reaction can be optimized to enhance its therapeutic effects. The powerful technique of time-resolved pump-probe femtosecond laser spectroscopy was performed by Lu et al. to reveal the extremely high reactivity of cisplatin with weakly-bound electrons, thus providing a deeper understanding of this drug’s therapeutic effects. Taking advantage of this reaction mechanism, a molecular promoter can be identified to amplify the therapeutic efficacy of cisplatin by combination in a synergistic manner. Through cell survival rate measurements, fluorescence microscopic studies to view cell death, cell cycle analysis and DNA fragmentation measurements via flow cytometry, as well as absorption spectroscopic studies, the synergistic effects between cisplatin and a new molecular promoter (PM2A) were measured. This new chemotherapeutic regimen, which was designed based on the electron-transfer reaction mechanism of cisplatin, can be used to decrease the required doses of cisplatin used in the clinic (to effectively reduce its toxic side effects), to circumvent the drug resistance and to improve targeting to cancer cells.

abstract / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Master / Doctor of Medicine

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