Retraction: Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

University Hospitals, Case Western Reserve University School of Medicine, 11100 Euclid Avenue LKS Building 7th floor, Cleveland, OH, USA. .
Journal of Carcinogenesis 02/2008; 7:4. DOI: 10.1186/1477-3163-7-4
Source: PubMed
11 Reads
  • Source
    • "The EGFR is a transmembrane tyrosine kinase receptor that plays an important role in many tumorigenic processes, including cell growth, proliferation, invasion, and metastasis. These effects are mediated by activation of downstream signaling pathways , including RAS-RAF-mitogen-activated protein kinase and phosphatidylinositol-3 kinase (PI3K)-AKT pathways [1] [2]. Mutations in the tyrosine kinase (TK) domain of the EGFR gene are present in a subset of non-small cell lung cancers (NSCLCs), and those tumors with EGFR mutations have been reported to be highly sensitive to EGFR TK inhibitors [3]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The drug-dependent induction of premature senescence in neoplastic cells is considered per se an important tumor suppressive mechanism. DNA demethylating agents recently introduced in clinical trials, such as 5-aza-cytidine (Decitabine) and its derivatives, have been extensively characterized in recent years as antiproliferative compounds that act through multiple mechanisms, which have not yet been fully clarified. We recently analyzed the introduction of Decitabine in therapy for malignant pleural mesothelioma (MPM) observing that, despite the ability to induce profound biological effects in MPM cells, the drug failed to generate a massive apoptotic response. Since one of the most intriguing aspects of DNA demethylating agents is the possibility to accelerate the senescent response of tumor cells, we investigated the hypothesis of Decitabine inducing, in vitro, the premature aging of MPM cells.
    Lung cancer (Amsterdam, Netherlands) 01/2011; 71(1):113-5. DOI:10.1016/j.lungcan.2010.10.016 · 3.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the majority of mesothelioma cases worldwide, asbestos is a likely causal factor, but several alternative factors, such as ionizing radiation, have been recognized. We reviewed ionizing-radiation evidence from epidemiology studies of (1) patients exposed to the diagnostic X-ray contrast medium "Thorotrast," (2) patients undergoing radiation therapy (i.e., to treat cancer), and (3) atomic energy workers chronically exposed to lower levels of radiation. The results from these populations are also supported by case reports of mesothelioma following therapeutic radiation. Statistically significant associations were found in many, but not all, epidemiology studies (particularly those of Thorotrast- and radiation-treated patients). Given the low mesothelioma rate in the general population, the consistently increased risk among these radiation-exposed individuals is noteworthy. Many studies were limited by the lack of a uniform manner in which mesothelioma was reported prior to introduction of a uniform classification system (ICD-10). Future studies that rely on ICD-10 should have greater power to detect an association. While the evidence falls short of a definitive causal link, considering studies in which statistical significance was achieved, the case reports, and the plausible mode of action, we conclude that the evidence is supportive of a causal link between ionizing radiation exposure and mesothelioma risk.
    Cancer Causes and Control 06/2009; 20(8):1237-54. DOI:10.1007/s10552-009-9357-4 · 2.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate mortality among nuclear workers with potential internal exposure to uranium. The cohort included 2,709 workers employed at the AREVA NC Pierrelatte plant for at least 6 months (72,787 person-years). This plant processed uranium enrichment during the period 1960-1996 and chemical conversion since 1980. Mortality was compared to the national and regional mortality rates available for the period 1968-2005. For causes of death of interest with respect to occupational exposure, mortality trends according to occupational characteristics were assessed. As expected, an important healthy worker effect (all causes SMR = 0.55 (95% CI: 0.50-0.61), n = 411; all cancers SMR = 0.70 (95% CI: 0.60-0.81), n = 193) was observed. Among cancer sites a priori related to uranium exposure, only mortality for lymphatic cancer was increased among potentially exposed workers (SMR = 1.49 (95% CI: 0.68-2.82); n = 9). An important increase in mortality from pleural cancer was observed (SMR = 2.85 (95% CI: 0.93-6.66), n = 5); none of the deceased workers were exposed to radiation whereas all handled asbestos. In spite of limited statistical power, results show consistency with previous studies of nuclear workers potentially exposed to uranium. Further investigation based on more precise uranium exposure data should allow the estimation of uranium hazard effects among this cohort.
    International Archives of Occupational and Environmental Health 09/2009; 83(3):301-8. DOI:10.1007/s00420-009-0455-0 · 2.20 Impact Factor
Show more


11 Reads
Available from