A mesothelioma epidemic in Cappadocia: Scientific developments and unexpected social outcomes

Cancer Research Center of Hawaii, Thoracic Oncology Program, Honolulu, Hawaii 96816, USA.
Nature reviews. Cancer (Impact Factor: 37.4). 03/2007; 7(2):147-54. DOI: 10.1038/nrc2068
Source: PubMed

ABSTRACT In Cappadocia, Turkey, an unprecedented mesothelioma epidemic causes 50% of all deaths in three small villages. Initially linked solely to the exposure to a fibrous mineral, erionite, recent studies by scientists from Turkey and the United States have shown that erionite causes mesothelioma mostly in families that are genetically predisposed to mineral fibre carcinogenesis. This manuscript reports, through the eyes of one of the researchers, the resulting scientific advances that have come from these studies and the social improvements that were brought about by both the scientists and members of the Turkish Government.

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    • "A naturally occurring zeolite mineral also exists in a fi brous form. It has been implicated as a potent cause of mesothelioma in humans and animals (Wagner et al. 1985, Baris et al. 1981, 1987, Baris and Grandjean 2006, Carbone et al. 2007, Ryan et al. 2011). "
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    ABSTRACT: Airborne fibers, when sufficiently biopersistent, can cause chronic pleural diseases, as well as excess pulmonary fibrosis and lung cancers. Mesothelioma and pleural plaques are caused by biopersistent fibers thinner than ∼0.1 μm and longer than ∼5 μm. Excess lung cancer and pulmonary fibrosis are caused by biopersistent fibers that are longer than ∼20 μm. While biopersistence varies with fiber type, all amphibole and erionite fibers are sufficiently biopersistent to cause pathogenic effects, while the greater in vivo solubility of chrysotile fibers makes them somewhat less causal for the lung diseases, and much less causal for the pleural diseases. Most synthetic vitreous fibers are more soluble in vivo than chrysotile, and pose little, if any, health pulmonary or pleural health risk, but some specialty SVFs were sufficiently biopersistent to cause pathogenic effects in animal studies. My conclusions are based on the following: 1) epidemiologic studies that specified the origin of the fibers by type, and especially those that identified their fiber length and diameter distributions; 2) laboratory-based toxicologic studies involving fiber size characterization and/or dissolution rates and long-term observation of biological responses; and 3) the largely coherent findings of the epidemiology and the toxicology. The strong dependence of effects on fiber diameter, length, and biopersistence makes reliable routine quantitative exposure and risk assessment impractical in some cases, since it would require transmission electronic microscopic examination, of representative membrane filter samples, for determining statistically sufficient numbers of fibers longer than 5 and 20 μm, and those thinner than 0.1 μm, based on the fiber types.
    Critical Reviews in Toxicology 08/2014; 44(8). DOI:10.3109/10408444.2014.928266 · 5.10 Impact Factor
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    • "Genetic factors can play a role in the development and progression of MM as depicted in a study on the population in parts of Cappadocia, Turkey exposed to erionite (a fiber found in the volcanic rock of this area that shares many similar properties with crocidolite asbestos). Erionite related MM reached epidemic proportions, but only in families that passed on a predisposition to MM by erionite exposure in an autosomal‐dominant manner [Carbone et al., 2007] "
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    ABSTRACT: Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 01/2014; 115(1). DOI:10.1002/jcb.24642 · 3.26 Impact Factor
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    • "This tumor is characterized by long latency period (20–30 years) and slow growth which cause late diagnosis, poor prognosis, and limited effective therapies. It has also been suggested that additional factors besides asbestos may play a role in the tumor pathogenesis, such as SV40 infection [1] and genetic predisposition [2]. "
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug). In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.
    PLoS ONE 03/2013; 8(3):e58051. DOI:10.1371/journal.pone.0058051 · 3.23 Impact Factor
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