Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure.

Second Italian consensus conference on malignant pleural mesothelioma: state of the art and recommendations.

Malignant pleural mesothelioma (MPM) is a relevant public health issue. A large amount of data indicate a relationship between mesothelioma and asbestos exposure. MPM incidence has considerably and constantly increased over the past two decades in industrialized countries and is expected to peak in 2010-2020.

Immunohistochemistry and molecular diagnostics of pleural malignant mesothelioma.

Context: The pathologic approach to pleural-based lesions is stepwise and uses morphologic assessment, correlated with clinical and imaging data supplemented by immunohistochemistry (IHC), and more recently, molecular tests, as an aid for 2 main diagnostic problems: malignant mesothelioma (MM) versus other malignant tumors and malignant versus reactive mesothelial proliferations.

Objective: To present the current knowledge regarding IHC and molecular tests with respect to MM diagnosis, and in particular, the differentiation of the epithelioid type of MM from carcinoma metastatic to the pleural cavity.

Data Sources: A review of immunohistochemical features of 286 consecutive MMs from 459 cases of pleural pathology, diagnosed during routine practice from 2003 to 2009.

Antioxidants prevent the RhoA inhibition evoked by crocidolite asbestos in human mesothelial and mesothelioma cells.

Asbestos is a naturally occurring fibrous silicate, whose inhalation is highly related to the risk of developing malignant mesothelioma (MM), and crocidolite is one of its most oncogenic types. The mechanism by which asbestos may cause MM is unclear. We have previously observed that crocidolite in human MM (HMM) cells induces NF-κB activation and stimulates the synthesis of nitric oxide by inhibiting the RhoA signaling pathway.

Osteopontin plasma level does not detect prostate cancer in patients referred for diagnostic prostate biopsy.

Background: Prostate cancer is the second most frequent cause of tumor-related deaths in men in Western countries. The selection and evaluation of new markers might help to overcome the limits of the most widely used diagnostic tool, the prostate-specific antigen (PSA) test, often combined with digital rectal examination (DRE). Osteopontin (OPN) is an integrin-binding glycoprotein that has recently been shown to be related to tumor development, progression and metastasis in both experimental and clinical studies.

Expert opinions of the first italian consensus conference on the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a very important public health issue. A large amount of data indicates a relationship between mesothelioma and asbestos exposure. The incidence has both considerably and constantly increased over the past 2 decades in the industrialized countries and is expected to peak in 2010-2020.

In vitro anti-mesothelioma activity of cisplatin-gemcitabine combinations: evidence for sequence-dependent effects.

Purpose: The present study addresses the optimization of gemcitabine-cisplatin protocols currently adopted in the clinical management of malignant pleural mesothelioma (MPM), using cell lines derived from different histological subtypes of MPM as an in vitro model.

Methods: MPM cell lines were exposed either to single drugs or to their combinations, using a fixed dose ratio. Possible mechanisms for synergistic interactions were investigated by cell cycle analysis, western blot analysis of p53 phosphorylation status, and neutral comet assay to detect double strand breaks.

Spreading of mesothelioma cells is rapamycin-sensitive and requires continuing translation.

The interaction of cancer cells with extracellular matrix (ECM) is important in metastasization. Here we identified the molecules of the ECM expressed by sarcomatous malignant mesothelioma, and their effect on adhesion and spreading. In addition, by analyzing the relationship between translation and attachment to matrix, we found that mesothelioma cells rely on continuing translation to efficiently attach to matrix, and rapamycin inhibition affects spreading and migration of cancer cells.

Oxidative stress and total antioxidant capacity in human plasma.

While several tools are already available for the separate measurement of the oxidant and antioxidant pools, a single, quick and easy method for determining total oxidative stress would be advantageous. In the present study, we compare the plasma of untreated patients with leukemia/solid gynecological tumors (n = 50) and current regular smokers (n = 50) with a smoking history of >or=10 cigarettes per day to the plasma of healthy blood donors. Standard tools were used to measure total oxidant status, ceruloplasmin activity, total antioxidant capacity, uric acid content and oxidative stress index.

Enhanced antitumor therapy by inhibition of p21waf1 in human malignant mesothelioma.

Purpose: The p21 cyclin-dependent kinase inhibitor was frequently expressed in human malignant pleural mesothelioma (MPM) tissues as well as cell lines. Recent data indicate that p21 keeps tumor cells alive after DNA damage, favoring a survival advantage. In this study, we assessed the possibility of p21 suppression as a therapeutic target for MPM.

Asbestos induces nitric oxide synthesis in mesothelioma cells via Rho signaling inhibition.

We have observed that in three human malignant mesothelioma cell lines, crocidolite asbestos induced the activation of the transcription factor NF-kappaB and the synthesis of nitric oxide (NO) by inhibiting the RhoA signaling pathway. The incubation with crocidolite decreased the level of GTP-bound RhoA and the activity of Rho-dependent kinase, and induced the activation of Akt/PKB and IkBalpha kinase, leading to the nuclear translocation of NF-kappaB. The effects of crocidolite fibers on NF-kappaB activation and NO synthesis were mimicked by Y27632 (an inhibitor of the Rho-dependent kinases) and toxin B (an inhibitor of RhoA GTPase activity), while they were reverted by mevalonic acid, the product of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase.

Statins revert doxorubicin resistance via nitric oxide in malignant mesothelioma.

Human malignant mesothelioma (HMM) is resistant to many anticancer drugs, including doxorubicin. Mevastatin and simvastatin, 2 inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, potentiated the intracellular accumulation and the cytotoxicity of doxorubicin in HMM cells constitutively expressing P-glycoprotein and multidrug resistance-associated protein 3. This effect of statins was nitric oxide (NO)-dependent, since it was reverted by either an NO synthase inhibitor or an NO scavenging system.

Serum PDGF-AB in pleural mesothelioma.

Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls.

Aberrant E-cadherin and gamma-catenin expression in malignant mesothelioma and its diagnostic and biological relevance.

Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined and the role of the cadherin-catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and alpha-, beta- and gamma-catenins was studied in nine human MM cell lines and five human mesothelial cell lines.

The use of autologous platelet gel to treat difficult-to-heal wounds: a pilot study.

Background: Chronic ulcers can benefit from topical treatment with growth factors (GFs). PLT gel provides tissue regeneration-inducing GFs. The aim of this study was to verify the effectiveness of autologous PLT gel in the treatment of nonhealing skin lesions.

Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells.

The cytotoxic effects of asbestos are partly mediated by the production of free radicals, including nitric oxide (NO). SV40 has been suggested to synergize with asbestos in the pathogenesis of malignant mesothelioma. Crocidolite asbestos fibers induced in human mesothelial and malignant mesothelioma cells a significant increase of NO synthase activity and expression, which was absent in SV40-infected cells.

Synergistic effect of the anti-HER-2/neu antibody and cisplatin in immortalized and primary mesothelioma cell lines.

Malignant mesothelioma (MM) still remains a therapeutic and diagnostic problem to which new therapeutic perspectives are being continuously tried and tested. Three different primary cultures (MMGe-1, MES MM 98, and MES 1) and one immortalized cell line (MSTO 211 H) of human MM were studied in order to evaluate the HER-2/neu expression. Three out of four cell lines showed a different level of c-erbB-2 expression, the highest being detected on the MSTO 211 H cell line (fibroblastic phenotype), whereas MMGe-1 resulted negative.