RESUMEN
Many studies have drawn attention to the possible association between occupational exposure to asbestos and tumours of the urinary apparatus. Besides the main etiological agents recognised today--such as smoking, obesity and hypertension--experimental and epidemiological evidence converges on the view that tumours of the kidney and bladder are largely due to occupational exposure to industrial agents: these and their transformation products linger in the body and are eventually eliminated by those organs. That one such agent targeting the urinary system is asbestos has found confirmation in the discovery of asbestos fibres in the urine of populations at risk. We here present 23 cases of work exposure to asbestos in a range of exposure scenarios where the workers developed tumours of the kidney and bladder. The cases came to the attention of the Ramazzini Institute casually.
Asunto(s)
Amianto/efectos adversos , Exposición Profesional/efectos adversos , Neoplasias Urológicas/etiología , Academias e Institutos , Humanos , Italia , Neoplasias Urológicas/epidemiologíaRESUMEN
Nowadays tumours represent one of the major problems of public health, both for their epidemiological dimension as for the causes that are at their origin, represented by three important factors: people ageing, general and occupational environmental pollution, including incongruous individual behaviour, and individual genetic susceptibility. The strategies followed till today in order to check tumours have privileged the role of therapeutic interventions: the results achieved show the great limits. On the contrary, current scientific experiences indicate the need to re-orientate present strategies, developing prevention programmes for the identification of carcinogenic risks (primary prevention), and early diagnosis of preneoplastic and neoplastic lesions (secondary prevention). In this review we discuss the importance of primary prevention in tumour control and specifically we present: - the role of long-term carcinogenic bioassays on rodents (rats and mice) in order to identify and predict the carcinogenic risks and then the great value that these studies have for public health; - the two major programmes of carcinogenic bioassays: the National Toxicological Program (NTP) of the US government, and the one performed by the European Ramazzini Foundation (ERF), in Italy; - the importance of observing the experimental animals until spontaneous death in order to improve the sensitivity and specificity of the assays, a way of working followed by ERF from the beginning.
Asunto(s)
Carcinógenos , Neoplasias/prevención & control , Enfermedades Profesionales/prevención & control , Animales , Bioensayo , Europa (Continente) , Fundaciones , Humanos , Italia , Ratones , Neoplasias/mortalidad , Enfermedades Profesionales/mortalidad , Prevención Primaria , Salud Pública , Ratas , Ratas Sprague-Dawley , Prevención Secundaria , Estados UnidosRESUMEN
Chemotherapy, as generally available, is of a limited value in curing malignant brain tumors (gliomas), which often develop resistance to drugs, becoming completely unresponsive to any standard therapeutic approach. Camptothecins, a family of topoisomerase I inhibitor drugs, represent a new promising treatment strategy and are currently under evaluation for testing the clinical efficacy. We selected a CPT-resistant sub-line (U87CPT-R) from U87-MG grade III-IV astrocytoma cells, and compared the expression profile of the two cell lines by cDNA-microarray, as a preliminary screening of the molecular mechanisms involved in the acquisition of CPT resistance in glioma cells. The relevant role of IL-1 beta overproduction as well as a generalised up-regulation of genes implicated in angiogenesis and inflammatory response are discussed in details.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Encefálicas/patología , Camptotecina/farmacología , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/patología , Perfilación de la Expresión Génica , Humanos , Inflamación , Neovascularización Patológica , Análisis de Secuencia por Matrices de Oligonucleótidos , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
OBJECTIVE: To develop a multiple-endpoint monitoring system in order to assess and minimize long term risks in hospital nurses exposed to antiblastic drugs. DESIGN: Molecular epidemiology study. SETTING: S. Orsola-Malpighi Hospital in Bologna, Italy: nurses exposed to antiblastic drugs. PARTICIPANTS: 50 exposed subjects (8 males and 42 females) and 50 unexposed individuals (8 males and 42 females) matched for age and smoking habits. MAIN OUTCOME MEASURES: Urinary markers of exposure, Heat Shock Proteins (HSPs) 27, 70, 90, 110, immunologic biomarkers in peripheral blood lymphocytes: apoptosis, cell-cycle analysis G1-S-G, typization of Natural Killer cells (NK) and receptors micronuclei; frequency in peripheral blood lymphocytes and in exfoliated buccal mucosa cells; activation ofspecific oncogenes (bax, bcl2). RESULTS: 19/50 subjects showed urinary antiblastic drug levels (3 subjects MTX, 11 subjects CP, 5 subjects MTX and CP). No statistically significant differences were observed in all the considered biomarkers between the exposed and control groups. CONCLUSION: This biomonitoring study doesn't evidence any early significant effect associated to the exposure to antiblastic drugs.
Asunto(s)
Antineoplásicos/orina , Monitoreo del Ambiente , Enfermeras y Enfermeros , Exposición Profesional/análisis , Adulto , Femenino , Humanos , MasculinoRESUMEN
The question of whether the distinct isoforms of the family of enzymes phosphoinositide 3-kinases (PI3Ks) play redundant roles within a cell or whether they control distinct cellular processes or distinct steps within the same cellular process has gained considerable importance in the recent years due to the development of inhibitors able to selectively target individual isoforms. It is important to understand whether inhibition of one PI3K can result in compensatory effect from other isoform(s) and therefore whether strategies aimed at simultaneously blocking more than one PI3K may be needed. In this study we investigated the relative contribution of distinct PI3K isoforms to endothelial cells (EC) functions specifically regulated by the sphingolipid sphingosine-1-phosphate (S1P) and by high density lipoproteins (HDL), the major carrier of S1P in human plasma. Here we show that a co-ordinated action of different PI3Ks is required to tightly regulate remodelling of EC on Matrigel, a process dependent on cell proliferation, apoptosis and migration. The contribution of each isoform to this process appears to be distinct, with the class II enzyme PI3K-C2ß and the class IB isoform p110γ mainly regulating the S1P- and HDL-dependent EC migration and PI3K-C2α primarily controlling EC survival. Data further indicate that PI3K-C2ß and p110γ control distinct steps involved in cell migration supporting the hypothesis that different PI3Ks regulate distinct cellular processes.