Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site

Background. An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environ-mental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated. Methods. The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed. Results. Mesothelioma incidence in the study area was increased: 46 cases were ob-served with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age- classes below 55 years. Conclusions. The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks

Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site

Background. An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environ-mental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated.Methods. The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed. Results. Mesothelioma incidence in the study area was increased: 46 cases were ob-served with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age-classes below 55 years.Conclusions. The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks

Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry.

BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs

Global Gene Expression Profiling Of Human Pleural Mesotheliomas: Identification of Matrix Metalloproteinase 14 (MMP-14) as Potential Tumour Target

BACKGROUND:The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY:We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). CONCLUSIONS:Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

Abstract BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs

Pleural mesothelioma incidence in the population resident close to an asbestos-cement industry located in an Italian polluted site

BACKGROUND. The industrial area of "Bagnoli Coroglio" in Naples municipality was defined as a "polluted site of national concern for remediation" in 2000. A steel and a cement plants and an asbestos-cement (Eternit) and a chemical industries operated in the area. AIMS. To estimate pleural mesothelioma incidence in the districts of Naples around the industrial area. METHODS. The area potentially affected by the industrial emissions was identified by modelling; environmental asbestos exposure was categorized in two levels: higher in subarea 2 and lower in subarea 1. Cases of pleural mesothelioma (2001-2007) were mapped according to residence at diagnosis; those included in the occupational cohorts of the asbestos-cement and steel plants and those with ascertained occupational exposure in the Mesothelioma Registry were excluded. Standardized Incidence Ratios (SIRs) were computed for overall area and subareas with respect to municipal rates. RESULTS. At 2001 census 157,495 subjects lived in the study area; 12 women and 34 men of them had a diagnosis of pleural mesothelioma (2001-2007). A significant increase was observed among men in the overall study area (SIR=1.89) and in subarea 1 (SIR=2.04). Among women in both subareas the increases were not significant. A not significant Risk Rate of 1.15 was observed in women of subarea 2 with respect to subarea 1. CONCLUSIONS. In the territory close to the industrial area increased pleural mesothelioma incidence (statistically significant among men and not significant in women) was found. In the subarea with a higher estimated asbestos exposure, SIR was not significantly increased, but a risk ratio higher than 1, based on 3 observed cases, was found in women with respect to the other subarea. Two of these 3 women were less than 50 years old. Despite the low power, the study indicates a possible impact of environmental asbestos exposure in the population resident close to an asbestos-cement industry

Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability-0

Ed by cell counts and was expressed as percent of control (untreated cells). Experiments were repeated in triplicate and media values were calculated and indicated in the upper table. P values at the different points of the treatments respect to the control and of the combined treatment (P+C) respect to the single drugs treatment were indicated in the lower tables. CTRL = control; P = piroxicam; C = CDDP.<p><b>Copyright information:</b></p><p>Taken from "Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability"</p><p>Journal of Translational Medicine 2008;6():27-27.</p><p>Published online 22 May 2008</p><p>PMCID:PMC2412853.</p><p></p