Cleo Robinson1, Helman Alfonso2, Samantha Woo3, Nola Olsen2, A W Bill Musk4, Bruce W S Robinson3, Anna K Nowak3, Richard A Lake3. 1. National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia. Electronic address: cleo.robinson@uwa.edu.au. 2. Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway Crawley, WA 6009, Australia. 3. National Centre for Asbestos Related Diseases, University of Western Australia, Harry Perkins Institute for Medical Research, Nedlands, Perth, 6009 Western Australia, Australia. 4. Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway Crawley, WA 6009, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia 6009, Australia.
Abstract
OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma. MATERIALS AND METHODS: A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50mg/kg or 250 mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site). RESULTS: Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p<0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR=0.85; 95% CI=0.53-1.37, p=0.50), (HR=0.69; 95% CI=0.21-2.30, p=0.55) and (HR=0.43; 95% CI=0.16-1.13, p=0.087) respectively. CONCLUSION: We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.
OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors have been associated with lower incidence rates of some cancers. Because asbestos can cause chronic inflammation at the pleural and peritoneal surfaces we hypothesised that NSAID and COX-2 inhibitors would inhibit the development of asbestos-induced mesothelioma. MATERIALS AND METHODS: A murine model of asbestos-induced mesothelioma was used to test this hypothesis by providing the NSAID, aspirin, daily in the feed at 50mg/kg or 250 mg/kg. In a parallel study, the relationship between the use of NSAID and COX-2 inhibitors and mesothelioma was investigated in a human cohort of 1738 asbestos exposed people living or working in Wittenoom, Western Australia (a crocidolite mine site). RESULTS:Aspirin did not alter the rate of disease development or increase the length of time that mice survived. Aspirin had a small but significant effect on disease latency (the time between asbestos exposure and first evidence of disease; p<0.05) but disease progression was not affected by the continued presence of the drug. In the Wittenoom cohort, individuals who reported use of NSAIDs, COX-2 inhibitors or both did not have a lower incidence of mesothelioma (HR=0.85; 95% CI=0.53-1.37, p=0.50), (HR=0.69; 95% CI=0.21-2.30, p=0.55) and (HR=0.43; 95% CI=0.16-1.13, p=0.087) respectively. CONCLUSION: We conclude that NSAIDs and COX-2 inhibitors do not moderate mesothelioma development or progression in a human cohort exposed to asbestos and this result is confirmed in an autochthonous mouse model.
Authors: Yewei Liu; Ting Yin; Yuanbo Feng; Marlein Miranda Cona; Gang Huang; Jianjun Liu; Shaoli Song; Yansheng Jiang; Qian Xia; Johannes V Swinnen; Guy Bormans; Uwe Himmelreich; Raymond Oyen; Yicheng Ni Journal: Quant Imaging Med Surg Date: 2015-10
Authors: Cleo Robinson; Helman Alfonso; Samantha Woo; Amy Walsh; Nola Olsen; Arthur W Musk; Bruce W S Robinson; Anna K Nowak; Richard A Lake Journal: PLoS One Date: 2014-08-05 Impact factor: 3.240