Italy was the second main asbestos producer in Europe, after the Soviet Union, until the end of the 1980s, and raw asbestos was imported on a large scale until 1992. The Italian pattern of asbestos consumption lags on average about 10 years behind the United States, Australia, the United Kingdom and the Nordic countries. Measures to reduce exposure were introduced in the mid-1970s in some workplaces. In 1986, limitations were imposed on the use of crocidolite and in 1992 asbestos was definitively banned. We have used primary pleural cancer mortality figures (1970 -1999) to predict mortality from mesothelioma among Italian men in the next 30 years by age-cohort-period models and by a model based on asbestos consumption figures. The pleural cancer/mesothelioma ratio and mesothelioma misdiagnosis in the past were taken into account in the analysis. Estimated risks of birth cohorts born after 1945 decrease less quickly in Italy than in other Western countries. The findings predict a peak with about 800 mesothelioma annual deaths in the period 2012-2024. Results estimated using ageperiod-cohort models were similar to those obtained from the asbestos consumption model.

Sperm DNA damage may have adverse effects on reproductive outcome. Sperm DNA breaks can be detected by several tests, which evaluate DNA integrity from different and complementary perspectives and offer a new class of biomarkers of the male reproductive function and of its possible impairment after environmental exposure. The remodeling of sperm chromatin produces an extremely condensed nuclear structure protecting the nuclear genome from adverse environments. This nuclear remodeling is species specific, and differences in chromatin structure may lead to a dissimilar DNA susceptibility to mutagens among species. In this study, the capacity of the comet assay in its two variants (alkaline and neutral) to detect DNA/chromatin integrity has been evaluated in human, mouse, and bull sperm. The hypothesis that chromatin packaging might influence the amount of induced and detectable DNA damage was tested by treating sperm in vitro with DNAse I, whose activity is strictly dependent upon its DNA accessibility. Furthermore, hydrogen peroxide (H 2 O 2 ) was used to assess whether spermatozoa of the three species showed a different sensitivity to oxidative stress. DNAse I-induced damage was also assessed by the sperm chromatin structure assay and the TUNEL assay, and the performances of these two assays were compared and correlated with the comet assay results. Results showed a different sensitivity to DNAse I treatment among the species with human sperm resulting the most susceptible. On the contrary, no major differences among species were observed after H 2 O 2 treatment. Furthermore, the three tests show a good correlation in revealing sperm with DNA strand breaks.

Purpose:The CXC chemokine receptor-4 (CXCR4)/stromal-derived factor-1and c-Met/hepatocyte growth factor axes promote the metastatic potential of rhabdomyosarcoma cell lines in experimental models, but no data are available on their role in rhabdomyosarcoma tumors. The expressions of CXCR4 and c-Met were evaluated in primary tumors and isolated tumor cells in marrow, and were correlated with clinicopathologic variables and survival. Experimental Design: Forty patients with recently diagnosed rhabdomyosarcoma were retrospectively enrolled. CXCR4 and c-Met expression was investigated in primary tumors by immunohistochemistry, in isolated marrow-infiltrating tumor cells using double-label immunocytology. Results were expressed as the mean percentage of immunostained tumor cells. Results: CXCR4 and c-Met were expressed in z5% of tumor cells from 40 of 40 tumors, with14 of 40 cases showing z50% of immunostained tumor cells (high expression). High CXCR4 expression correlated with alveolar histology (P = 0.006), unfavorable primary site (P = 0.009), advanced group (P < 0.001), marrow involvement (P = 0.007), and shorter overall survival and event-free survival (P < 0.001); high c-Met expression correlated with alveolar histology (P = 0.005), advanced group (P = 0.04), and marrow involvement (P = 0.02). In patients with a positive diagnosis for isolated tumor cells in marrow (n = 16), a significant enrichment in the percentage of CXCR4-positive (P = 0.001) and c-Met^positive (P = 0.003) tumor cells was shown in marrow aspirates compared with the corresponding primary tumors. Conclusions: CXCR4 and c-Met are widely expressed in both rhabdomyosarcoma subtypes and, at higher levels, in isolated marrow-infiltrating tumor cells. High levels of expression are associated with unfavorable clinical features, tumor marrow involvement and, only for CXCR4, poor outcome. In rhabdomyosarcoma, CXCR4 and c-Met represent novel exploitable targets for disease-directed therapy.

No abstract

Amyotrophic lateral sclerosis (ALS) is a rare and devastating neurological disorder of the adult age with a prognosis of about 2-3 years from the onset of the disease. No clear cause has been identified but it seems to be a multifactorial disease with genetic and environmental components involved. Increments of mortality rates were observed since 1980 both in Italy and in many other countries. The objective of the present study is to describe the distribution of ALS mortality in Italy in the period 1980-2001 detecting single municipalities or clusters with high mortality levels for motor neuron disease (MND). ALS represents the main part (85%) of the MND group which is globally identified by the IX ICD (International Classification of Diseases and Causes of Death) 335.2 code. Death numbers and standardized mortality ratios (SMR) for MND were calculated for all Italian municipalities through the ENEA mortality database system (data source: National Institute of Statistics-ISTAT), using national mortality rates as reference. Subsequently, in order to detect municipal clusters, spatial analysis was performed. Out of the 8,099 Italian municipalities, 132 where characterized by SMR values higher than expected. Moreover 16 clusters with significant high relative risk values (RR) were identified, 12 out of them including only a single municipality. Only 22 of the municipalities with high SMR were included in the clusters. In conclusion, the two different epidemiological methodologies demonstrated to be widely complementary in detecting the geographical distribution of the disease in terms of risk for populations. A first selection of the priority areas where analytical studies should be carried on, in order to identify risk factors associated to ALS, is tentatively suggested.