The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.

Background: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures.

The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.

Introduction: The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.

Methods: Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM.

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues.

Introduction: Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure.

Methods: The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines.

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.

Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers.

Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression-based classification and established prognostic markers.

Experimental Design: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4 × 44 K microarrays. Classification models were built using 75 tumors with contrasting courses of disease.

High genomic instability predicts survival in metastatic high-risk neuroblastoma.

We aimed to identify novel molecular prognostic markers to better predict relapse risk estimate for children with high-risk (HR) metastatic neuroblastoma (NB). We performed genome- and/or transcriptome-wide analyses of 129 stage 4 HR NBs. Children older than 1 year of age were categorized as "short survivors" (dead of disease within 5 years from diagnosis) and "long survivors" (alive with an overall survival time ≥ 5 years).

Tools and collaborative environments for bioinformatics research.

Advanced research requires intensive interaction among a multitude of actors, often possessing different expertise and usually working at a distance from each other. The field of collaborative research aims to establish suitable models and technologies to properly support these interactions. In this article, we first present the reasons for an interest of Bioinformatics in this context by also suggesting some research domains that could benefit from collaborative research.

3-Methyl-3-deazaadenine, a stable isostere of N3-methyl-adenine, is efficiently bypassed by replication in vivo and by transcription in vitro.

The goal of the present work was to determine the impact of N3-methyladenine (3-mA), an important lesion generated by many environmental agents and anticancer drugs, on in vivo DNA replication and in vitro RNA transcription. Due to 3-mA chemical instability, the stable isostere 3-methyl-3-deazaadenine (3-m-c(3)A) was site specifically positioned into an oligodeoxynucleotide. The oligomer was, then incorporated into a vector system that is rapidly converted to ssDNA inside yeast cells and requires DNA replication opposite the lesion for plasmid clonal selection.

Chromosome 9q and 16q loss identified by genome-wide pooled-analysis are associated with tumor aggressiveness in patients with classic medulloblastoma.

Medulloblastoma (MB) is one of the most aggressive pediatric brain tumor. We report genome-wide pooled-analysis of classic MB variant of patients over 3 years of age at diagnosis. We combined array comparative genomic hybridization (aCGH) results from experimental analysis (31 cases) with two public databases (55 cases) in a final evaluation of 86 MBs.

Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes.

Germline TP53 mutations result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni-like, and nonsyndromic predisposition with or without family history. To explore genotype/phenotype associations, we previously adopted a functional classification of all germline TP53 mutant alleles based on transactivation. Severe deficiency (SD) alleles were associated with more severe cancer proneness syndromes, and a larger number of tumors, compared with partial deficiency (PD) alleles.

PRIMA-1 cytotoxicity correlates with nucleolar localization and degradation of mutant p53 in breast cancer cells.

PRIMA-1 has been identified as a compound that restores the transactivation function to mutant p53 and induces apoptosis in cells expressing mutant p53. Studies on subcellular distribution of the mutant p53 protein upon treatment with PRIMA-1Met, a methylated form of PRIMA-1, have suggested that redistribution of mutant p53 to nucleoli may play a role in PRIMA-1 induced apoptosis. Here, we specifically investigated the influence of PRIMA-1 on cellular localization of mutated p53-R280K endogenously expressed in tumour cells.

Transcribed-ultra conserved region expression profiling from low-input total RNA.

Background: Ultra Conserved Regions (UCRs) are a class of 481 noncoding sequences located in both intra- and inter-genic regions of the genome. The recent findings that they are significantly altered in adult chronic lymphocytic leukemias, carcinomas, and pediatric neuroblastomas lead to the hypothesis that UCRs may play a role in tumorigenesis.

Results: We present a novel application of Ribo-SPIA isothermal linear amplification of minute RNA quantities for quantifying Transcribed-UCR (T-UCR) expression by quantitative PCR.

Transcribed-Ultra Conserved Region expression is associated with outcome in high-risk neuroblastoma.

Background: Neuroblastoma is the most common, pediatric, extra-cranial, malignant solid tumor. Despite multimodal therapeutic protocols, outcome for children with a high-risk clinical phenotype remains poor, with long-term survival still less than 40%. Hereby, we evaluated the potential of non-coding RNA expression to predict outcome in high-risk, stage 4 neuroblastoma.

Mutagenicity of N3-methyladenine: a multi-translesion polymerase affair.

We recently demonstrated that Polzeta and Rev1 contribute to alleviate the lethal effects of Me-lex, which selectively generates 3-methyladenine, by error prone lesion bypass. In order to determine the role of Poleta in the biological fate of Me-lex induced lesions, the RAD30 (Poleta) gene was deleted in the yIG397 parental strain and in its rev3 (Polzeta) derivative, and the strains transformed with plasmid DNA damaged in vitro by Me-lex. While deletion of RAD30 increased the toxicity of Me-lex, the impact on mutagenicity varied depending on the concentration of Me-lex induced DNA damage and the overall TLS capacity of the cells.

High frequency of genomic deletions induced by Me-lex, a sequence selective N3-adenine methylating agent, at the Hprt locus in Chinese hamster ovary cells.

We have investigated the mutagenicity induced at the Hprt locus in Chinese hamster ovary (CHO) cells treated with increasing concentrations of Me-lex, a minor groove selective methylating agent that efficiently generates more than 90-95% of 3-MeA DNA adducts. Me-lex treatment was cytotoxic but weakly mutagenic, resulting in up to 7-fold induction above background in the Hprt mutation frequency. The molecular nature of 43 Hprt mutations induced by Me-lex was determined by sequence analysis of the Hprt cDNA and genomic analysis of the gene locus.

Survival of pleural malignant mesothelioma in Italy: a population-based study.

A median survival time of about 9 months is generally reported among malignant pleural mesothelioma cases. Recently, better results in terms of survival and performance status have been reported in clinical trials that included highly selected patients. We describe the survival of pleural mesothelioma patients and the factors predictive of survival in an unselected, population-based setting.

PRIMA-1 synergizes with adriamycin to induce cell death in non-small cell lung cancer cells.

p53-dependent apoptosis is important for the efficacy of cancer treatment, and tumors carrying mutant p53 are often resistant to chemotherapy. Non-small cell lung cancer (NSCLC) cells generally exhibit resistance to apoptosis following treatment with many cytotoxic drugs. The new molecule PRIMA-1 appears to kill human tumor cells by restoring the transcriptional activity to mutated p53.

SWS: accessing SRS sites contents through Web Services.

Background: Web Services and Workflow Management Systems can support creation and deployment of network systems, able to automate data analysis and retrieval processes in biomedical research. Web Services have been implemented at bioinformatics centres and workflow systems have been proposed for biological data analysis. New databanks are often developed by taking into account these technologies, but many existing databases do not allow a programmatic access.

Reanalysis of updated mortality among vinyl and polyvinyl chloride workers: Confirmation of historical evidence and new findings.

Background: The production of vinyl chloride (VC) and polyvinyl chloride (PVC) involves the use of various chemicals, some known to be toxic and potentially or definitely carcinogenic. The related potential risk often has not been properly investigated. Updated cancer mortality among different subgroups of workers employed in a VC-PVC production plant located in Porto Marghera (Italy) was re-analyzed using an internal reference group of workers with low (or null) exposure to VC.

Rev1 and Polzeta influence toxicity and mutagenicity of Me-lex, a sequence selective N3-adenine methylating agent.

The relative toxicity and mutagenicity of Me-lex, which selectively generates 3-methyladenine (3-MeA), is dependent on the nature of the DNA repair background. Base excision repair (BER)-defective S. cerevisiae strains mag1 and apn1apn2 were both significantly more sensitive to Me-lex toxicity, but only the latter is significantly more prone to Me-lex-induced mutagenesis.

Biowep: a workflow enactment portal for bioinformatics applications.

Background: The huge amount of biological information, its distribution over the Internet and the heterogeneity of available software tools makes the adoption of new data integration and analysis network tools a necessity in bioinformatics. ICT standards and tools, like Web Services and Workflow Management Systems (WMS), can support the creation and deployment of such systems. Many Web Services are already available and some WMS have been proposed.

The kinetics of p53-binding and histone acetylation at target promoters do not strictly correlate with gene expression after UV damage.

We have addressed the correlation between sequence-specific DNA binding by the tumor suppressor p53 and transactivation of various target genes, in the context of UV irradiation responses. In A549 cells (p53WT), p53 occupancy at the p21, mdm2, and puma promoters increased significantly after UV irradiation. In contrast, p21 mRNA levels did not change, mdm2 mRNA decreased and both p21 and mdm2 proteins were downregulated shortly after UV.

Trends in incidence rates of oesophagus and gastric cancer in Italy by subsite and histology, 1986-1997.

Objective: Population-based studies in Western countries suggest that the incidence of oesophageal adenocarcinoma (OA) and gastric cardia adenocarcinoma (GCA) is increasing, whereas the incidence of distal gastric carcinoma and oesophageal squamous cell carcinoma (OSCC) is declining. This is the first population-based study carried out in a southern European region to evaluate the time trends in incidence rates of oesophageal and gastric tumours according to subsite and histology over the period 1986-1997.

Methods: Cancer cases were drawn from seven registries of the Italian Network of Cancer Registries, which covers approximately 9% of the Italian population (annual average 5 027 944).

Web services and workflow management for biological resources.

Background: The completion of the Human Genome Project has resulted in large quantities of biological data which are proving difficult to manage and integrate effectively. There is a need for a system that is able to automate accesses to remote sites and to "understand" the information that it is managing in order to link data properly. Workflow management systems combined with Web Services are promising Information and Communication Technologies (ICT) tools.