Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure

Neri, Monica; Filiberti, Rosangela; Taioli, Emanuela; Garte, Seymour; Paracchini, Valentina; Bolognesi, Claudia; Canessa, Pier Aldo; Fontana, Vincenzo; Ivaldi, Giovanni Paolo; Verna, Anna; Bonassi, Stefano; Puntoni, Riccardo

doi:10.1016/j.mrfmmm.2005.06.003

Cited by 39 publications

(41 citation statements)

References 31 publications

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“…29,30 MM traditionally is associated with occupational exposure to asbestos fibers. 31,32 However, recent reports suggest that genetic susceptibility and Simian virus 40 infections also cause the modifications in cell signaling events, particularly the induction of cell survival pathways and inhibition of apoptosis that favors the growth of MM. 33,34 Activation of caspases is 1 of the key events in the process of initiation of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells

Nasreen

Mohammed

Antony

2006

Cancer

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BACKGROUND.The over‐expression of the ephrin‐A1 ligand receptor EphA2 is associated with the growth and metastatic potential of tumors. Although EphA2 is expressed in a variety of tumors, its expression and function in malignant mesothelioma (MM) remain unknown. The authors hypothesized that expression of the receptor EphA2 in MM cells (MMCs) plays a key role in the growth and haptotactic migration of MM. They also hypothesized that silencing EphA2 expression by using small‐interfering RNA (siRNA) inhibits the proliferation and haptotaxis of MMCs and induces apoptosis in MMCs.METHODS.The expression of EphA2 in MMCs and in normal pleural mesothelial cells (PMCs) was studied by using real‐time quantitative polymerase chain reaction analysis and Western blot analysis. The growth of MMCs was determined with the WST‐1 cell‐proliferation assay. The haptotactic migration of MMCs and PMCs was determined with a Boyden chamber assay. Expression of caspases was determined with calorimetric assays.RESULTS.The results demonstrated that silencing the receptor EphA2 by siRNA significantly reduced the proliferation and haptotactic migration of MMCs compared with controls. Over‐expression of EphA2 with plasmid pcDNA/EphA2 enhanced the proliferation and haptotaxis of MMCs significantly. Knocking down EphA2 expression initiated caspase‐9–mediated apoptosis in MMCs.CONCLUSIONS.The current results suggested that constitutive expression of EphA2 may contribute to the aggressive behavior and cellular survival of MMCs. EphA2 may be an effective therapeutic target in patients with mesothelioma. Silencing the receptor EphA2 gene is a novel approach for the containment of growth and migration of tumor in patients with malignant mesothelioma. Cancer 2006. © 2006 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells

Nasreen

Mohammed

Antony

2006

Cancer

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“…This indicates that factors other than asbestos play a role in the genesis of the tumor 63) . A body of evidence suggest that individual differences in metabolic genes, involved in detoxification, might partly explain the difference in susceptibility to mesothelioma 64) . The occurrence of more mesothelioma cases among members of the same family has attracted some attention [65][66][67][68] .…”

Section: Co-factorsmentioning

confidence: 99%

Malignant Mesothelioma: Global Incidence and Relationship with Asbestos

2007

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Mesothelioma incidence varies markedly from one country to another. The highest annual crude incidence rates (about 30 cases per million) are observed in Australia, Belgium, and Great Britain. A lot of data indicate a relationship between mesothelioma and asbestos. The hot areas for mesothelioma exactly correspond to the sites of industries with high asbestos use, such as shipbuilding and asbestos-cement industry. However, in many countries with high asbestos consumption, mesothelioma incidence is low. The reasons for this fact are not clear. The latency periods elapsing between first exposure to asbestos and development of mesothelioma are mostly longer than 40 yr. An inverse relationship exists between intensity of asbestos exposure and length of the latency period. Mesothelioma generally develops after long-time exposures to asbestos. Some recent studies show that the risk increases with the duration of exposure. Possible co-factors in the pathogenesis of asbestos-related mesothelioma include genetic predisposition, diets poor in fruit and vegetables, viruses, immune impairment, recurrent serosal inflammation. The study of co-morbidity in mesothelioma could give an insight into the pathogenesis of the tumor. While a levelling-off in mesothelioma incidence has been registered in some countries, a worsening of the epidemic is predictable in large parts of the world.

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“…6,7 A study indicate a possible role of individual susceptibility to mesothelioma in subject with lower asbestos exposure. 8 The availability of genetic markers of individual susceptibility could help to identify the subjects at higher risk of mesothelioma within a population exposed to asbestos fibres.…”

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confidence: 99%

Polymorphisms of glutathione‐S‐transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma

Landi

Gemignani

Neri

et al. 2007

Intl Journal of Cancer

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Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR 5 1.69, 95% CI 5 1.04-2.74; p 5 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR 5 3.07, 95% CI 5 1.55-6.05; p 5 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM. ' 2007 Wiley-Liss, Inc.

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Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure

Cited by 39 publications

References 31 publications

Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells

Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells

Malignant Mesothelioma: Global Incidence and Relationship with Asbestos

Polymorphisms of glutathione‐S‐transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma

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