Asbestos-Induced Mesothelioma

Size: px
Start display at page:

Download "Asbestos-Induced Mesothelioma"

Transcription

1 2 Asbestos-Induced Mesothelioma Maria E. Ramos-Nino, Marcella Martinelli, Luca Scapoli, and Brooke T. Mossman Asbestos, a group of chemically and physically distinct fibers, is one of the most notorious carcinogens in the lung and pleura. The National Institutes of Health in 1978 estimated that approximately 11 million individuals had been exposed to asbestos in the United States since 1940 (1). Although widely employed in World Wars I and II, the use of asbestos has undergone major changes in recent decades, with severe restrictions in most countries on amphiboles. In developed countries, with the exception of Japan, asbestos production is controlled or banned, while in developing countries, consumption has leveled off or increased (2). Between the 1940s and 1970s, asbestos was utilized extensively in insulation applications (primarily in the building construction industry), and in asbestos-cement pipes. Current usage is generally confined to chrysotile in four products: asbestos cement, friction materials, roof coating and cements, and gaskets. In 1992 approximately 28 million tons of asbestos-cement products were produced in approximately 100 countries (3). Properties of Asbestos Fibers Asbestos is a naturally occurring group of fibers, each with its own unique structure and chemical composition (Table 2.1). There are two subgroups: (1) the serpentine group, consisting of chrysotile; and (2) the amphiboles, a group of rod-like fibers including crocidolite, amosite, tremolite, anthophyllite, and actinolite (4). Asbestos fibers are ubiquitous in certain geographic areas and become problematic to human health when they are inhaled. It is unclear how they get to the pleura to cause mesothelioma. Epidemiology of Asbestos-Induced Mesotheliomas The most important causal factor for the development of human mesothelioma is exposure to asbestos, primarily the amphiboles crocidolite and amosite. Malignant mesothelioma is presently a worldwide 21

2 22 Chapter 2 Asbestos-Induced Mesothelioma Table 2.1. Types, composition and characteristics of asbestos fibers Type Composition Source Morphology Chrysotile* Mg 6 Si 4 O 10 (OH) 8 Northern hemisphere (U.S. and Curly, pliable Canada) Crocidolite Na 2 (Fe 3+ ) 2 (Fe 2+ ) 3 Si 8 O 22 (OH) 2 South Africa, Western Australia Rodlike, durable Amosite (Fe, Mg) 7 Si 8 O 22 (OH) 2 South Africa Rodlike, durable Anthophyllite (Mg, Fe) 7 Si 8 O 22 (OH) 2 Finland Rodlike, durable Tremolite Ca 2 Mg 5 Si 8 O 22 (OH) 2 Exists in some deposits of Rodlike, durable Canadian chrysotile Actinolite Ca 2 (Mg, Fe) 5 Si 8 O 22 (OH) 2 Not mined * Only member of the serpentine family. Other types of asbestos are classified as amphiboles. problem (5). Although mesothelioma is a rare disease, with an annual incidence in the United States of 2000 to 3000 cases, a steady rise in cases has been reported (6). In Europe, the incidence of malignant pleural mesothelioma has risen for decades and is expected to peak between the years 2010 and 2020 (7). In Germany, a study conducted on 1605 patients in the mesothelioma register ( ), found that 70% had a history of exposure to asbestos (8). In the United Kingdom, asbestos reportedly accounts for some 600 cases of mesothelioma and 100 cases of bronchial carcinoma per year (9). The incidence of mesothelioma has been rapidly increasing and is expected to increase even more from the present total of 1300 to more than 3000 cases per year. Exposure to fibers is associated with most of these cases (10). The link between amphibole asbestos exposure and pleural mesothelioma is the result of the pioneering work of Wagner and colleagues (11), who found a relationship between the high incidence of the disease and people working at or living near crocidolite (blue) asbestos mines, with intermediate levels of disease near amosite mines, and no tumors in chrysotile miners. Lung burden studies (see Chapter 1) have also confirmed that the amphibole subgroup of asbestos (crocidolite, amosite) is the one more strongly associated with the development of both malignant mesothelioma and lung cancers (12). In a recent study on 1445 cases of mesothelioma in the United States, it was determined that commercial amphiboles were responsible for most of the mesothelioma cases observed (13). Chrysotile asbestos may produce mesothelioma in humans, but the number of cases is small and the required exposures large (12). Heavy exposures to chrysotile asbestos alone, or with negligible amphibole contamination, can cause malignant mesothelioma and other lung cancers in humans (14), but studies evaluating worker populations that are transient and may be exposed to different types of fibers over a lifetime are difficult to interpret. Some studies have implicated tremolite fibers as the likely etiologic factor in mesotheliomas associated with chrysotile exposure (15 17). However, others suggest that chrysotile does cause mesothelioma, although it may be far less potent than amphibole asbestos (18). Although the association between amphibole asbestos exposure and the development of malignant mesothelioma is well documented (19), available information suggests that other factors contribute to its etiol-

3 ogy. Some studies suggest that genetic factors may play an important role in the etiology of the disease (20,21). Also, compelling multiinstitutional studies suggest that SV40 tumor (T)-antigen (Tag) is present in a large percentage of human mesotheliomas. Approximately 60% of mesotheliomas in the United States are positive for SV40 Tag (22,23), and possible mechanisms are discussed in other chapters of this volume (see Chapter 3). Properties of Asbestos Associated with Carcinogenic Potential The carcinogenic potential of asbestos fibers has been linked to their geometry, size, and chemical composition. Because of the increased potential of long (>5 mm) fibers to cause mesothelioma and fibrosis after intrapleural or intraperitoneal administration to rodents (24), health concerns for long respirable fibers [World Health Organization (WHO) criteria: length >5 mm, diameter <3 mm] are considerable (25). In addition to size, the chemical composition of fibers plays an important role in determining the durability, biopersistence, and biodegradability of asbestos types. The greater durability of amphiboles compared to chrysotile appears to be one of the principal reasons for their greater carcinogenic potential. Amphibole fibers persist at sites of tumor development and may serve as stimuli for neoplastic growth of cells (26,27). Studies on the retention of asbestos fibers in lung tissues of asbestos workers show that concentrations of amphibole fibers increase with durations of exposure, whereas chrysotile concentration does not (28). Studies also indicate that the lung fiber content of amphiboles is less than that required for chrysotile in the induction of mesothelioma (29). The persistence of the amphibole fibers at the site of tumor formation is important to both tumor induction and promotion because the mean latency period between initial exposure to asbestos and the development of mesothelioma is around 30 to 40 years (19,30). Role of Reactive Oxygen and Nitrogen Species (ROS/RNS) in Asbestos Bioreactivity An important unresolved issue is whether asbestos fiber carcinogenicity is through direct effects of asbestos on mesothelial cells or through indirect mechanisms involving oxidative stress (31,32). A ramification of interaction of long (>5 mm) fibers with cells is frustrated phagocytosis and a prolonged oxidative burst (Fig. 2.1) (33). The increased durability and high iron content of the amphiboles crocidolite and amosite also may contribute to their higher carcinogenic potential through oxidants catalyzed by iron or surface reactions occurring on the fiber. Iron-rich durable fibers such as crocidolite, which contain as much as 36% iron by weight, also may have increased reactivity because of the oxidation state of iron, i.e., increases in ferrous iron, aiding in its chelation (34). The cytotoxicity of crocidolite fibers in M.E. Ramos-Nino et al 23

4 24 Chapter 2 Asbestos-Induced Mesothelioma Figure 2.1. Scanning electron microscopy showing phagocytosis of long asbestos fibers by alveolar macrophages. human lung carcinoma cells is directly linked to iron mobilization and is followed by increased ferritin synthesis, a perpetual feedback system for uptake of iron by cells (35,36). Studies on animal models and cell cultures have confirmed that asbestos fibers generate ROS and RNS (19,32,37), and these effects may be potentiated by the inflammation associated with fiber exposures (38). Asbestos also activates redox-sensitive transcription factors such as nuclear factor kappa B (NF-kB) (39) and activator protein-1 (AP-1) (40), which lead to increased cell survival, inflammation, and, paradoxically, the upregulation of antioxidant enzymes such as manganese superoxide dismutase (38). This enzyme is also overexpressed in asbestos-related mesotheliomas (41,42), rendering them highly resistant to oxidative stress in comparison to normal mesothelial cells. Moreover, its overexpression prevents cell injury by asbestos (43). In human pleural mesothelial cells in vitro, crocidolite asbestos causes oxidative stress and DNA single-strand breaks (44), but these are not exacerbated by pretreatment with inhibitors of antioxidant enzymes. Other studies have demonstrated overexpression of enzymes related to oxidative stress, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) (45,46), and endothelial nitric oxide synthase

5 (enos) in malignant mesotheliomas (47). Thioredoxin, a small redoxactive protein reduced by the selenoprotein thioredoxin reductase and reduced nicotinamide adenine dinucleotide phosphate (NADPH), is associated in other models of cancer with cell growth and differentiation and is also overexpressed in mesothelioma cells. This protein might be a factor governing the poor prognosis of mesotheliomas and their reduced responsiveness to conventional therapies (48). Overexpression of gamma-glutamylcysteine synthetase, a rate-limiting enzyme in glutathione-associated pathways, could also play an important role in the primary drug resistance of mesotheliomas (49). Catalytically active 5-lipooxygenase could also be involved in the regulation of proliferation and survival in mesotheliomas via a vascular endothelial growth factor (VEGF)-related circuit (50). M.E. Ramos-Nino et al 25 Cytogenetic Changes by Asbestos Fibers in Mesothelial Cells and Mesotheliomas Chromosomal changes and cytogenetic responses to asbestos have been observed in rodent and human mesothelial cells in culture (51 53). Although human mesothelial cells may be more sensitive to the cytotoxic effects of asbestos than bronchial epithelial cells or fibroblasts (52), it is unclear whether individual sensitivity to asbestos fibers is due to specific genetic traits. For example, the glutathione-s-transferase M1 (GSTM1) genotypes of patients with mesothelioma suggest that the lack of the GSTM1 gene does not render human mesothelial cells more sensitive to chromosomal damage by amosite asbestos fibers. However, GSTM1 null cells are more susceptible than GSTM1- positive cells to growth inhibitory effects of fibers (54). A complex profile of somatic genetic changes has been revealed in human malignant mesotheliomas. These changes implicate a multistep process of tumorigenesis. The occurrence of multiple, recurrent cytogenetic deletions suggests that loss or inactivation of tumor suppressor genes are critical to the development and progression of mesothelioma. Deletions of specific regions in the short (p) arms of chromosomes 1, 3, and 9 and long (q) arms of 6, 13, 15, and 22q are repeatedly observed, and loss of a copy of chromosome 22 is the single most consistent numerical change (55). Relatively little is known about the early changes in the genesis of mesothelioma. Of the known cytogenetic changes, the most frequent is loss of p16/cdkn2a-p14 ARF at 9p21(by homozygous deletion) (56), adversely affecting both Rb and p53 pathways, respectively. NF2 (merlin), a tumor suppressor located at 22q12 (by an inactivating mutation coupled with allelic loss) is also frequently altered in mesotheliomas (57 60). Other conventional proto-oncogenes and tumor suppressor genes have been investigated including N-ras (61), Ha- and Ki-ras (62), and the tumor suppressor gene p53, but no consistently frequent mutations have been found (61 63).

6 26 Chapter 2 Asbestos-Induced Mesothelioma Cell Signaling Pathways, Growth Factors, and Early Response Proto-Oncogenes The studies cited above suggest that cell proliferation by asbestos may play a more critical role in the promotion and progression of mesotheliomas. Carcinogenesis was classically thought to be a proliferationdriven process. However, it is now recognized that neoplastic growth is an imbalance between apoptosis and proliferation. In support of this concept, a dynamic balance between apoptosis and cell proliferation is observed in mesothelial cells exposed to crocidolite asbestos (64). Studies in vitro indicate that asbestos can induce apoptosis in mesothelial cells through formation of ROS (65,66) and mitochondrial pathways (31,67). Malignant mesothelioma (MM) routinely expresses the antiapoptotic protein Bcl-xl and the proapoptotic proteins Bax and Bak. Moreover, antisense oligonucleotides against Bcl-xl engender apoptosis in mesothelioma cell lines (68). Inhibitor of apoptosis protein-1 (IAP-1) promotes mesothelioma cell survival, whereas reduced IAP-1 results in increases in apoptotic pathways and reduced resistance to chemotherapeutic drugs (69). Cell signaling pathways induced by asbestos through receptors on the cell surface trigger early-response proto-oncogenes, activation of transcription factors such as AP-1, and AP-1 dependent gene expression (40,70). Studies in our group have found that the epidermal growth factor receptor (EGFR) is an important target of asbestos. This growth factor is required for proliferation of human mesothelial cells (71), and is produced in an autocrine fashion in mesotheliomas (72). Autophosphorylation of the EGFR occur in mesothelial cells after in vitro exposures to asbestos. Moreover, aggregation and phosphorylation of the EGFR by long fibers initiates cell signaling cascades linked to asbestos-induced injury and mitogenesis (73,74). Increased expression of EGFR in rat pleural mesothelial cells correlates with the carcinogenicity of mineral fibers (75). We have also shown that the EGFR is causally linked to activation of the mitogen-associated protein kinase (MAPK) cascade and increased expression of the proto-oncogenes c-fos and c-jun (73,76). Expression of both Fos and Jun family members (components of the transcription factor AP-1 complex) is required for transition through the G1 phase and entry into the S phase of the cell cycle (70). Moreover, overexpression of c-jun induces cell proliferation and transformation (77). Most recently, extracellular signal-regulated kinase (ERK-1/2) induced activation by asbestos has been linked to the induction of Fra-1, an important component of the AP-1 complex that is causally related to anchorage-independent growth in mesothelioma (41). Complementary DNA (cdna) microarray analyses have shown increased expression of c-myc, egfr, and fra-1 in rat mesotheliomas (78). Other growth factors and their receptors also are important in malignant mesothelioma including transforming growth factor-a (TGF-a),

7 which binds to the EGFR (79). Although normal mesothelial cells, asbestos-transformed mesothelioma cells, and spontaneously transformed mesothelial cells express functional EGFR (55), only cell lines derived from asbestos-induced mesotheliomas express and secrete TGF-a, which binds to the EGF receptor with high affinity. In addition, TGF-a acts as an autocrine growth factor for asbestos-induced mesotheliomas, and their growth is inhibited with use of a neutralizing TGF-a antibody (79). Insulin-like growth factor-ii, which functions as an autocrine growth factor in normal mesothelial and mesothelioma cells (71,80), and its corresponding receptor also are important in proliferation of mesothelioma cells (81). Platelet-derived growth factor (PDGF) (82) may also be an autocrine growth factor for human mesothelioma cells as both PDGF A- and B- chain messenger RNAs (mrnas) are expressed at higher levels in mesothelioma as opposed to normal mesothelial cell lines (83), and PDGF-like mitogenic activity is observed using mesothelioma cell line conditioned medium (84). Transforming growth factor (TGF)-b 1, responsible for regulatory functions in many pathologic processes including pleural fibrosis, increases pleural fluid formation in part by stimulating production of VEGF, a regulator of pleural inflammation and cell proliferation (85); VEGF is important in vascular permeability and pleural effusion formation as well as growth of mesothelioma cells (86,87). Increased levels of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), known growth factors for mesothelial cells, have been detected in pleural lavage fluids of patients (88). Although HGF is produced in general by mesenchymal cells, recent work by Cacciotti and colleagues (87) shows that the HGF receptor Met, a proto-oncogene product whose activation leads to cell growth and altered morphogenesis, is activated in SV40-positive human mesothelioma cells. Also, high expression levels of c-met have been detected in rat mesothelioma cells and are fra-1 dependent (89). M.E. Ramos-Nino et al 27 Effects of Asbestos on Extracellular Matrix Malignant mesotheliomas exhibit elevated amounts of hyaluronan, and hyaluronan synthesis enhances cell proliferation, anchorage independent growth and cell migration in a number of tumor types (90). The hyaluronan receptor gene cd44 is detected in high amounts by oligonucleotide microarray analysis of human and rat mesothelioma cell lines and may play a role in mesothelial cell motility and migration (89). Other extracellular components such as fibrin deposition via increased expression of tissue factor (TF) may play a role in pleural injury or neoplasia (91). In a study on 16 patients in whom matrix metalloproteinases (MMP)-1, -2, -3, -7, and -9 and tissue inhibitors -1 and -2 were evaluated, MMP-1 and -2 were related directly to invasion and spread of pleural malignant mesothelioma (92).

8 28 Chapter 2 Asbestos-Induced Mesothelioma Figure 2.2. Hypothetical schema of cell signaling in mesothelial cells by asbestos. Conclusion The reports cited in this chapter provide much insight into mechanisms of asbestos-induced mesotheliomas and the properties of amphibole asbestos fibers that initiate injury and compensatory mesothelial cell hyperplasia. The chemical composition of these fibers and their durability at sites of tumor development may induce chronic activation of cell signaling pathways and transcription factors linked to expression of a number of genes critical to tumor initiation, promotion, progression, and angiogenesis (Fig. 2.2). Many of these pathways have been reported after infection of human mesothelial cells with SV40 (72). Regardless of their etiology, since human mesotheliomas appear to have a number of autocrine growth factor pathways governing proliferation, a focus on common downstream signaling molecules is merited in prevention and therapy of mesotheliomas. References 1. Manning C, Vallyathan V, Mossman B. Diseases caused by asbestos: mechanisms of injury and disease development. Int Immunopharmacol Cancer Res 2002;2 3: Algranti E: Asbestos: current issues related to cancer and to uses in developing countries. Cad Saude Publica 1998;14(suppl 3): Pigg B. The uses of chrysotile. Ann Occup Hyg 1994;38: Guthrie GT, Mossman BT. Health effects of mineral dusts. In: Ribbe PH, ed. Reviews in Mineralogy. Washington, DC: Mineralogical Society of America, 1993;28:1 584.

9 5. Bocchetta RP, Powers A, Foddis R, Stekala E, Pass HI, Carbone M. SV40 and the pathogenesis of mesothelioma. Semin Cancer Biol 2001;11: Grondin S, Sugarbaker D. Malignant mesothelioma of the pleural space. Oncology 1999;13: Boutin C, Schlesser M, Frenay C, Astoul P. Malignant pleural mesothelioma. Eur Respir J 1998;12: Neumann V, Gunthe S, Mulle K, Fischer M. Malignant mesothelioma German mesothelioma register Int Arch Occup Environ Health 2001;74: Coggon D. Occupational cancer in the United Kingdom. Environ Health Perspect 1999;107(suppl 2): Statement on malignant mesothelioma in the United Kingdom. Thorax 2001;56: Wagner J, Sleggs C, Marchand P. Diffuse pleural mesotheliomas and asbestos exposure in the North Western Cape Province. Br J Ind Med 1960;17: Churg A. Chrysotile, tremolite, and malignant mesothelioma in man. Chest 1988;93: Roggli VL, Sharma A, Butnor KJ, Sporn T, Vollmer RT. Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases. Ultrastruct Pathol 2002;26: Yano E, Wang Z, Wang X, Wang M, Lan Y. Cancer mortality among workers exposed to amphibole-free chrysotile asbestos. Am J Epidemiol 2001;154: Churg A, Wiggs B. Fiber size and number in amphibole asbestos-induced mesothelioma. Am J Pathol 1984;115: Roggli V, Vollmer R, Butnor K, Sporn T. Tremolite and mesothelioma. Ann Occup Hyg 2002;46: MacDonald J, McDonald A. Chrysotile, tremolite, and mesothelioma. Science 1995;267(5199): Steenland K, Stayner L. Silica, asbestos, man-made mineral fibers, and cancer. Cancer Causes Control 1997;8: Mossman B, Bignon J, Corn M, Seaton A, Gee J. Asbestos: scientific developments and implications for public policy. Science 1990;247: Roushdy-Hammady I, Siegel J, Emri S, Testa J, Carbone M. Genetic susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey. Lancet 2001;357(9254): Huncharek M. Non-asbestos related diffuse malignant mesothelioma. Tumori 2002;88: Carbone M. Simian virus 40 and human tumors: it is time to study mechanisms. J Biol Chem 1999;76: Klein G, Powers A, Croce C. Association of SV40 with human tumors. Oncogene 2002;21: Health Effects Institute. Asbestos in Public and Commercial Buildings: A Literature Review and Synthesis of Current Knowlegdge. Cambridge, MA: Health Effects Institute Asbestos Research, Vu V, Lai D. Approaches to characterizing human health risks of exposure to fibers. Environ Health Perspect 1997;105(suppl 5): Woodworth C, Mossman B, Craighead J. Induction of squamous metaplasia in organ cultures of hamster trachea by naturally occurring and synthetic fibers. Cancer Res 1983;43: Jaurand M, Gaudichet A, Halpern S, Bignon J. In vitro biodegradation of chrysotile fibres by alveolar macrophages and mesothelial cells in culture: comparison with a ph effect. Br J Ind Med 1984;41: M.E. Ramos-Nino et al 29

10 30 Chapter 2 Asbestos-Induced Mesothelioma 28. Albin M, Pooley FD, Stromberg U, et al. Retention patterns of asbestos fibres in lung tissue among asbestos cement workers. Occup Environ Med 1994;51: Churg A, Wiggs B, Depaoli L, Kampe B, Stevens B. Lung asbestos content in chrysotile workers with mesothelioma. Am Rev Respir Dis 1984;130: Mossman B, Kamp D, Weitzman S. Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. Cancer Invest 1996;14: Shukla A, Jung M, Stern M, et al. Asbestos induces mitochondrial DNA damage and dysfunction linked to the development of apoptosis. Am J Physiol Lung Cell Mol Physiol 2003;285(5):L1018 L Kamp D, Graceffa P, Pryor W, Weitzman S. The role of free radicals in asbestos-induced diseases. Free Radic Biol Med 1992;12: Hansen K, Mossman B. Generation of superoxide (O 2- ) from alveolar macrophages exposed to asbestiform and nonfibrous particles. Cancer Res 1987;47: Gulumian M, Bhoolia D, Du Toit R, et al. Activation of UICC crocidolite: the effect of conversion of some ferric ions to ferrous ions. Environ Res 1993;60: Chao C, Lund L, Zinn K, Aust A. Iron mobilization from crocidolite asbestos by human lung carcinoma cells. Arch Biochem Biophys 1994;314: Fang R, Aust A. Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos. Arch Biochem Biophys 1997;340: Janssen Y, Van Houten B, Borm P, Mossman B. Cell and tissue responses to oxidative damage. Lab Invest 1993;69: Kinnula V. Oxidant and antioxidant mechanisms of lung disease caused by asbestos fibres. Eur Respir J 1999;14: Janssen Y, Barchowsky A, Treadwell M, Driscoll K, Mossman B. Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells. Proc Natl Acad Sci USA 1995;92: Ramos-Nino M, Haegens A, Shukla A, Mossman B. Role of mitogenactivated protein kinases (MAPK) in cell injury and proliferation by environmental particulates. Mol Cell Biochem 2002; : Ramos-Ninos M, Timblin C, Mossman B. Mesothelial cell transformation requires increased AP-1 binding activity and ERK-dependent Fra-1 expression. Cancer Res 2002;62(21): Kahlos K, Pitkanen S, Hassinen I, Linnainmaa K, Kinnula V. Generation of reactive oxygen species by human mesothelioma cells. Br J Cancer 1999; 80: Mossman B, Surinrut P, Brinton B, et al. Transfection of a manganesecontaining superoxide dismutase gene into hamster tracheal epithelial cells ameliorates asbestos-mediated cytotoxicity. Free Radic Biol Med 1996;21: Ollikainen T, Linnainmaa K, Kinnula V. DNA single strand breaks induced by asbestos fibers in human pleural mesothelial cells in vitro. Environ Mol Mutagen 1999;33: Marrogi A, Pass H, Khan M, Metheny-Barlow L, Harris C, Gerwin B. Human mesothelioma samples overexpress both cyclooxygenase-2 (COX- 2) and inducible nitric oxide synthase (NOS2): in vitro antiproliferative effects of a COX-2 inhibitor. Cancer Res 2000;60:

11 46. Edwards J, Faux S, Plummer S, et al. Cyclooxygenase-2 expression is a novel prognostic factor in malignant mesothelioma. Clin Cancer Res 2002; 8: Soini Y, Puhakka A, Kahlos K, et al. Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1. Histopathology 2001;39: Sun X, Dobra K, Bjornstedt M, Hjerpe A. Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells. Differentiation 2000;66: Jarvinen K, Soini Y, Kahlos K, Kinnula V. Overexpression of gamma-glutamylcysteine synthetase in human malignant mesothelioma. Hum Pathol 2002;33: Romano M, Catalano A, Nutini M, et al. 5-lipoxygenase regulates malignant mesothelial cell survival: involvement of vascular endothelial growth factor. FASEB J 2001;15: Jaurand M, Kheuang L, Magne L, Bignon J. Chromosomal changes induced by chrysotile fibres or benzo-3,4-pyrene in rat pleural mesothelial cells. Mutat Res 1986;169: Lechner JF, Tokiwa T, LaVeck M, et al. Asbestos-associated chromosomal changes in human mesothelial cells. Proc Natl Acad Sci USA 1985;82: Health Effects Institute. Asbestos in Public and Commercial Buildings: A Literature Review and Synthesis of Current Knowlegdge. Cambridge, MA: Health Effects Institute Asbestos Research, Pelin K, Hirvonen A, Taavitsainen M, Linnainmaa K. Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors. Mutat Res 1995;334: Murthy S, Testa J. Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma. J Cell Physiol 1999; 180: Hirao T, Bueno R, Chen C, Gordon G, Heilig E, Kelsey K. Alterations of the p16(ink4) locus in human malignant mesothelial tumors. Carcinogenesis 2002;23: Bianchi A, Mitsunaga S, Cheng J, et al. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci USA 1995;92: Sekido Y, Pass H, Bader S, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res 1995;55: Lee H, Chang T, Tebalt MR, Senderowicz A, Szabo E. Induction of differentiation accompanies inhibition of Cdk2 in a non-small cell lung cancer cell line. Int J Oncol 1999;15: Lechner J, Tesfaigzi J, Gerwin B. Oncogenes and tumor-suppressor genes in mesothelioma a synopsis. Environ Health Perspect 1997;105(suppl 5): Papp T, Schipper H, Pemsel H, et al. Mutational analysis of N-ras, p53, p16ink4a, p14arf and CDK4 genes in primary human malignant mesotheliomas. Int J Oncol 2001;18: Kitamura F, Araki S, Suzuki Y, Yokoyama K, Tanigawa T, Iwasaki R. Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma in relation to asbestos exposure: a study of 12 American patients. Ind Health 2002;40: M.E. Ramos-Nino et al 31

12 32 Chapter 2 Asbestos-Induced Mesothelioma 63. Mayall F, Jacobson G, Wilkins R. Mutations of p53 gene and SV40 sequences in asbestos-associated and non-asbestos-associated mesotheliomas. J Clin Pathol 1999;52: Goldberg J, Zanella C, Janssen Y, et al. Novel cell imaging approaches show induction of apoptosis and proliferation in mesothelial cells by asbestos. Am J Respir Cell Mol Biol 1997;17: Broaddus V, Yang L, Scavo L, Ernst J, Boylan A. Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species. J Clin Invest 1996;98: BeruBe K, Quinlan T, Fung H, et al. Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos. Am J Respir Cell Mol Biol 1996; 15: Kamp D, Panduri V, Weitzman S, Chandel N. Asbestos-induced alveolar epithelial cell apoptosis: role of mitochondrial dysfunction caused by ironderived free radicals. Mol Cell Biochem 2002; : Smythe WR, Mohuiddin I, Ozveran M, Cao XX. Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product. J Thorac Cardiovasc Surg 2002;123: Gordon GJ, Appasani K, Parcells JP, et al. Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma. Carcinogenesis 2002;23: Reddy S, Mossman B. Role and regulation of activator protein-1 (AP-1) in toxicant-induced responses of the lung. Am J Physiol (Lung Cell Mol Physiol) 2002;283(6):L1161 L Laveck M, Somers A, Moore L, Gerwin B, Lechner J. Dissimilar peptide growth factors can induce normal human mesothelial cell multiplication. In Vitro Cell Dev Biol 1988;24: Mossman B, Gruenert D. SV40, growth factors, and mesothelioma another piece of the puzzle. Am J Respir Cell Mol Biol 2002;26: Zanella C, Posada J, Tritton T, Mossman B. Asbestos causes stimulation of the ERK-1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res 1996;56: Pache J, Janssen Y, Walsh E, et al. Increased epidermal growth factor-receptor (EGF-R) protein in a human mesothelial cell line in response to long asbestos fibers. Am J Pathol 1998;152: Faux S, Houghton C, Hubbard A, Patrick G. Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres. Carcinogenesis 2000;21: Heintz N, Janssen Y, Mossman B. Persistent induction of c-fos and c-jun expression by asbestos. Proc Natl Acad Sci USA 1993;90: Timblin C, Janssen Y, Mossman B. Transcriptional activation of the protooncogene c-jun by asbestos and H 2 O 2 is directly related to increased proliferation and transformation of tracheal epithelial cells. Cancer Res 1995;55: Sandhu H, Dehnen W, Roller M, Abel J, Unfried K. mrna expression patterns in different stages of asbestos-induced carcinogenesis in rats. Carcinogenesis 2000;21: Walker C, Everitt J, Ferriola P, Stewart W, Mangum J, Bermudez E. Autocrine growth stimulation by transforming growth factor a in asbestostransformed rat mesothelial cells. Cancer Res 1995;55: Tubo R, Rheinwald J. Normal human mesothelial cells and fibroblasts transfected with the EJras oncogene become EGF-independent, but are not malignantly transformed. Oncogene Res 1987;1:

13 81. Rutten AA, Bermudez E, Stewart W, Everitt JI, Walker CL. Expression of insulin-like growth factor II in spontaneously immortalized rat mesothelial and spontaneous mesothelioma cells: a potential autocrine role of insulin-like growth factor II. Cancer Res 1995;55: Metheny-Barlow LJ, Flynn B, van Gijssel HE, Marrogi A, Gerwin BI. Paradoxical effects of platelet-derived growth factor-a overexpression in malignant mesothelioma. Antiproliferative effects in vitro and tumorigenic stimulation in vivo. Am J Respir Cell Mol Biol 2001;24: Gerwin B. Cytokine signaling in mesothelial cells: receptor expression closes the autocrine loop. Am J Respir Cell Mol Biol 1996;14: Sekhon H, Wright J, Churg A. Effects of cigarette smoke and asbestos on airway, vascular and mesothelial cell proliferation. Int J Exp Pathol 1995; 76: Lee YC, Lane KB. The many faces of transforming growth factor-beta in pleural diseases. Curr Opin Pulmon Med 2001;7: Strizzi L, Catalano A, Vianale G, et al. Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol 2001;193: Cacciotti P, Strizzi L, Vianale G, et al. The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor. Am J Respir Cell Mol Biol 2002;26: Adamson IY, Bakowska J. KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos. Exp Lung Res 2001;27: Ramos-Nino ME, Scapoli L, Martinelli M, Land S, Mossman BT. Microarray analysis and RNA silencing link fra-1 to cd44 and c-met expression. Cancer Res 2003;63(13): Li Y, Heldin P. Hyaluronan production increases the malignant properties of mesothelioma cells. Br J Cancer 2001;85: Bajaj MS, Pendurthi U, Koenig K, Pueblitz S, Idell S. Tissue factor pathway inhibitor expression by human pleural mesothelial and mesothelioma cells. Eur Respir J 2000;15: Hirano H, Tsuji M, Kizaki T, et al. Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinase, collagens, and Ki67 antigen in pleural malignant mesothelioma: an immunohistochemical and electron microscopic study. Med Electron Microsc 2002;35: M.E. Ramos-Nino et al 33

BE.104 Spring Evaluating Environmental Causes of Mesothelioma J. L. Sherley

BE.104 Spring Evaluating Environmental Causes of Mesothelioma J. L. Sherley BE.104 Spring Evaluating Environmental Causes of Mesothelioma J. L. Sherley Outline: 1) Toxicological mechanisms and causation evaluations 2) An environetics case: Asbestos and Mesothelioma Toxicological

More information

Influence of Fiber Type, Size, and Number in Human Disease: Conclusions from Fiber Burden Analysis

Influence of Fiber Type, Size, and Number in Human Disease: Conclusions from Fiber Burden Analysis Influence of Fiber Type, Size, and Number in Human Disease: Conclusions from Fiber Burden Analysis Andrew Churg, MD Department of Pathology University of British Columbia Vancouver, BC, Canada Techniques,

More information

Mesothelioma among brake mechanics: an expanded analysis of a casecontrol

Mesothelioma among brake mechanics: an expanded analysis of a casecontrol 1 Risk Anal. 2004 Jun;24(3):547-52. Related Articles, Links Mesothelioma among brake mechanics: an expanded analysis of a casecontrol study. Hessel PA, Teta MJ, Goodman M, Lau E. Exponent, Wood Dale, IL

More information

Update of the scientific evidence on asbestos and cancer. Kurt Straif, MD MPH PhD. The IARC Monographs

Update of the scientific evidence on asbestos and cancer. Kurt Straif, MD MPH PhD. The IARC Monographs Update of the scientific evidence on asbestos and cancer Kurt Straif, MD MPH PhD International Agency for Research on Cancer Lyon, France World Health Organisation Asturias, 17 March 2011 The IARC Monographs

More information

Mesothelioma. Mesothelioma and Asbestos 11/21/2009

Mesothelioma. Mesothelioma and Asbestos 11/21/2009 Mesothelioma Michele Carbone, M.D.,PH.D. Director Cancer Research Center of Hawaii Professor and Chairman, Dept. of Pathology J.A. Burns Medical School University of Hawaii Honolulu, HI 96813 Mesotheliomas

More information

Producing Analytical Data, Microscopy and Analytical Procedures

Producing Analytical Data, Microscopy and Analytical Procedures 1 The Role of Fiber Analysis in Asbestos Induced Lung Disease: TEM vs. SEM. Is There Controversy Elizabeth N. Pavlisko, M.D., Department of Pathology, Duke University Medical Center I. Introduction to

More information

Cancer Risk Factors in Ontario. Dusts and Fibres

Cancer Risk Factors in Ontario. Dusts and Fibres Cancer Risk Factors in Ontario Dusts and Fibres dusts ANd fibres risk factor/exposure Cancer The context where high risks were reported Magnitude of risk* Strength of evidence a Asbestos Larynx Occupational

More information

OCCUPATIONAL LUNG CANCER

OCCUPATIONAL LUNG CANCER OCCUPATIONAL LUNG CANCER Anwar Jusuf, Agus Dwi Susanto Department of Pulmonology & Respiratory Medicine, Faculty of Medicine University Of Indonesia - Persahabatan Hospital-Jakarta INTRODUCTION Occupational

More information

Francine Lortie-Monette, MD, MSc, CSPQ, MBA Department of Epidemiology and Biostatistics University of Western Ontario 2003

Francine Lortie-Monette, MD, MSc, CSPQ, MBA Department of Epidemiology and Biostatistics University of Western Ontario 2003 ASBESTOS Francine Lortie-Monette, MD, MSc, CSPQ, MBA Department of Epidemiology and Biostatistics University of Western Ontario 2003 Asbestosis Asbestosis is a model for other dust diseases as well as

More information

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function:

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function: Cancer is a genetic disease: Inherited cancer Sporadic cancer What is Cancer? Cancer typically involves a change in gene expression/function: Qualitative change Quantitative change Any cancer causing genetic

More information

Asbestos Fibre Concentrations in the Lungs of Brake Workers: Another Look

Asbestos Fibre Concentrations in the Lungs of Brake Workers: Another Look Ann. Occup. Hyg., Vol. 52, No. 6, pp. 455 461, 2008 Ó The Author 2008. Published by Oxford University Press on behalf of the British Occupational Hygiene Society doi:10.1093/annhyg/men036 Asbestos Fibre

More information

June 20, 2002. 2002.06.20: Wagner Testimony on Workplace Exposure to Asbestos. This is an archive page. The links are no longer being updated.

June 20, 2002. 2002.06.20: Wagner Testimony on Workplace Exposure to Asbestos. This is an archive page. The links are no longer being updated. Page 1 of 6 skip navigational links This is an archive page. The links are no longer being updated. Statement by Gregory R. Wagner, M.D. Director, Division of Respiratory Disease Studies National Institute

More information

Scientific Update on Safe Use of Asbestos. Robert P. Nolan, PhD International Environmental Research Foundation New York, New York www.ierfinc.

Scientific Update on Safe Use of Asbestos. Robert P. Nolan, PhD International Environmental Research Foundation New York, New York www.ierfinc. Scientific Update on Safe Use of Asbestos Robert P. Nolan, PhD International Environmental Research Foundation New York, New York www.ierfinc.org When We Talk about Asbestos What Do We Mean? Anthophyllite

More information

Uses and Abuses of Pathology in Asbestos-exposed Populations

Uses and Abuses of Pathology in Asbestos-exposed Populations Uses and Abuses of Pathology in Asbestos-exposed Populations Jerrold L. Abraham, MD Department of Pathology State University of New York Upstate Medical University Syracuse, NY, 13210 USA The term: Asbestosis,

More information

D.M. Bernstein * WHO review Page 1 of 8

D.M. Bernstein * WHO review Page 1 of 8 A review of the WHO s document on the adverse health effects of exposure to asbestos and WHO's recommendations on the prevention of asbestos-related diseases D.M. Bernstein * The WHO s Programme on Occupational

More information

Department of BioScience Technology Chung Yuan Christian University 2015/08/13

Department of BioScience Technology Chung Yuan Christian University 2015/08/13 Department of BioScience Technology Chung Yuan Christian University 2015/08/13 Cancer Cells Cancer, the 1st leading cause of death, is an example of a disease that arises from abnormalities in cell function

More information

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies. Biochemistry Journal. August 1, 2007 405, pp.

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies. Biochemistry Journal. August 1, 2007 405, pp. Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies 1 Biochemistry Journal August 1, 2007 405, pp. 559 568 Joseph Friedman, Sarah Kraus, Yirmi Hauptman, Yoni Schiff

More information

Lung cancer and asbestos

Lung cancer and asbestos Lung cancer and asbestos Bureau Veritas Training Bill Sanderson For the benefit of business and people To begin with.. There are known knowns, that is there are things we know that we know. There are known

More information

ASBESTOS. Know what it is and how you can protect yourself. environmental affairs Department: Environmental Affairs REPUBLIC OF SOUTH AFRICA

ASBESTOS. Know what it is and how you can protect yourself. environmental affairs Department: Environmental Affairs REPUBLIC OF SOUTH AFRICA ASBESTOS Know what it is and how you can protect yourself environmental affairs Department: Environmental Affairs REPUBLIC OF SOUTH AFRICA 1 What is asbestos? The term asbestos designates a group of naturally

More information

Health Effects of Asbestos Exposure

Health Effects of Asbestos Exposure Health Effects of Asbestos Exposure Jill Dyken, PhD, PE John Wheeler, PhD, DABT Agency for Toxic Substances and Disease Registry Asbestos Science Seminar Folsom, California August 18-19, 2004 Agency for

More information

Asbestos, Asbestosis, and Lung Cancer

Asbestos, Asbestosis, and Lung Cancer Asbestos, Asbestosis, and Lung Cancer David Weill, M.D. Stanford University Medical Center Stanford, CA David Weill, M.D., is a professor of medicine in the Division of Pulmonary and Critical Care Medicine

More information

The Management of Asbestos at the University of Manitoba

The Management of Asbestos at the University of Manitoba The Management of Asbestos at the University of Manitoba WHAT IS ASBESTOS? Asbestos is a name given to a group of minerals which occur naturally as masses of long silky fibres. Asbestos is known for its

More information

- Compensation issues

- Compensation issues Charité- Universitätsmedizin Berlin Institut für Arbeitsmedizin Prof. Dr. med. X. Baur Prevention, recognition and compensation of asbestosinduced diseases (AD) - Which diseases are asbestos-related? -

More information

Pharmacology of the Respiratory Tract: COPD and Steroids

Pharmacology of the Respiratory Tract: COPD and Steroids Pharmacology of the Respiratory Tract: COPD and Steroids Dr. Tillie-Louise Hackett Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Associate Head, Centre of Heart

More information

Epidemiology of Malignant Mesothelioma An Outline

Epidemiology of Malignant Mesothelioma An Outline Commentary Ann. Occup. Hyg., Vol. 54, No. 8, pp. 851 857, 2010 Ó The Author 2010. Published by Oxford University Press on behalf of the British Occupational Hygiene Society doi:10.1093/annhyg/meq076 Epidemiology

More information

Current Usage and Health Significance of the Modern Use of Chrysotile Products: Review of Recently Published Evidence

Current Usage and Health Significance of the Modern Use of Chrysotile Products: Review of Recently Published Evidence Current Usage and Health Significance of the Modern Use of Chrysotile Products: Review of Recently Published Evidence John Hoskins Health & Safety Consultant, Haslemere, Surrey, UK ASBESTOS SERPENTINE

More information

Non Small Cell Lung Cancer: Scientific Discoveries and the Pursuit of Progress

Non Small Cell Lung Cancer: Scientific Discoveries and the Pursuit of Progress Non Small Cell Lung Cancer: Scientific Discoveries and the Pursuit of Progress Lung Cancer Accounts for 14% of All New Cancer Diagnoses in the United States 1 Lung cancer is the second most common malignancy

More information

Oxidant and antioxidant mechanisms of lung disease caused by asbestos fibres

Oxidant and antioxidant mechanisms of lung disease caused by asbestos fibres Eur Respir J 1999; 14: 706±716 Printed in UK ± all rights reserved Copyright #ERS Journals Ltd 1999 European Respiratory Journal ISSN 0903-1936 REVIEW Oxidant and antioxidant mechanisms of lung disease

More information

Call for an International Ban on Asbestos

Call for an International Ban on Asbestos Call for an International Ban on Asbestos To eliminate the burden of disease and death that is caused worldwide by exposure to asbestos, The Collegium Ramazzini calls for an immediate ban on all mining

More information

ERZSÉBET TÓTH (Eötvös L. University, Budapest): ASBESTOS-RELATED DISEASES AND REGULATIONS

ERZSÉBET TÓTH (Eötvös L. University, Budapest): ASBESTOS-RELATED DISEASES AND REGULATIONS ERZSÉBET TÓTH (Eötvös L. University, Budapest): ASBESTOS-RELATED DISEASES AND REGULATIONS Outline 1. History and legal definition (mineralogy + morphology) 2. The useful properties of asbestos, its success

More information

HANDLING LUNG CANCER CLAIMS

HANDLING LUNG CANCER CLAIMS HANDLING LUNG CANCER CLAIMS JENNIFER S. KILPATRICK SWANSON, MARTIN & BELL, LLP 330 North Wabash Avenue Suite 3300 Chicago, Illinois 60611-3604 (312) 321-3517 (312) 321-0990 jkilpatrick@smbtrials.com 1

More information

Asbestos. General information

Asbestos. General information Asbestos General information Key Points Fire Non flammable and non combustible under normal conditions Chemically inert under normal conditions. Resistant to most solvents, acids and alkalis In the event

More information

Asbestos and Mesothelioma in Ontario

Asbestos and Mesothelioma in Ontario Asbestos and Mesothelioma in Ontario May 29, 2010 CARWH Conference: Worker Health in a Changing world of work Loraine Marrett, PhD Outline Part I: Asbestos & its uses Part II: Asbestos & cancer Part III:

More information

Publikationsliste Claudia Götz

Publikationsliste Claudia Götz Publikationsliste Claudia Götz 1. Reinhard,B., Götz, C., and Faillard, H.: Synthesis of N-Acetyl-9-Oacetylneuraminic acid α-p-aminophenylthioketoside and its application as ligand in the affinity chromatography

More information

New Insights into Merkel Cell Carcinoma

New Insights into Merkel Cell Carcinoma New Insights into Merkel Cell Carcinoma Bruce R. Smoller, MD Professor and Chair, Department of Pathology Professor, Department of Dermatology University of Arkansas for Medical Sciences Merkel cell carcinoma

More information

Recent Review Papers on Simian-Virus (SV-40), Asbestos and Mesothelioma. Bibliography

Recent Review Papers on Simian-Virus (SV-40), Asbestos and Mesothelioma. Bibliography Evans AS, Mueller NE (1990) Viruses and cancer causal associations. Ann Epidemiol 1(1): 71-92. Carbone M, Rizzo P & Pass HI (1995) Association of Simian Virus 40 with Rodent and Human Mesotheliomas. DNA

More information

Naturally Occurring Asbestos (NOA) General Overview

Naturally Occurring Asbestos (NOA) General Overview Naturally Occurring Asbestos (NOA) General Overview Lee R. Shull PhD Health, Ecology and Risk Practice MWH Global Sacramento, CA CASH NOA Workshop January 24, 2006 Presentation Outline Brief background

More information

Malignant Mesothelioma State of the Art

Malignant Mesothelioma State of the Art Malignant Mesothelioma State of the Art Paul Baas The Netherlands Cancer Institute August 12, 2011, Carlsbad, CA Summary Diagnosis; epithelial type subdivided Pleiomorphic vs other Staging: IASLC-IMIG

More information

Pathologist s Discussion of Plaintiffs Latest Theories

Pathologist s Discussion of Plaintiffs Latest Theories Pathologist s Discussion of Plaintiffs Latest Theories Mary Beth Beasley, MD Mt. Sinai Medical Center Annenberg Building 15th Floor Room 50 1468 Madison Avenue New York, NY 10029 (212) 241-5307 mbbeasleymd@yahoo.com

More information

Asbestos and Mesothelioma in Thailand

Asbestos and Mesothelioma in Thailand MD, DScMed, FRCP, FRACP, hon. FACP Emeritus Professor and Fellow of the Academy of Science, the Royal Institute of Thailand Abstract Chrysotile, a serpentile asbestos, has been used in a number of Thai

More information

ASBESTOS DISEASES. Dr Alastair Robertson

ASBESTOS DISEASES. Dr Alastair Robertson ASBESTOS DISEASES Dr Alastair Robertson Occupational Health Department University Hospital Birmingham Birmingham B29 6JF 01216278285 Alastair.robertson@uhb.nhs.uk Occupational Lung Disease Unit Birmingham

More information

Toxicity of Amphibole Asbestos

Toxicity of Amphibole Asbestos Toxicity of Amphibole Asbestos Disclaimer: The material presented in these slides has been reviewed by the U.S. EPA and approved for presentation. Approval does not signify that the contents necessarily

More information

Malignant Mesothelioma: an Update

Malignant Mesothelioma: an Update Malignant Mesothelioma: an Update Nico van Zandwijk Asbestos Diseases Research Institute Bernie Banton Centre University of Sydney Australia Physicians Week RACP 19-5-2009 Health Risks of Asbestos Fibers

More information

Asbestos and Mesothelioma a briefing document for the Metropolitan Police

Asbestos and Mesothelioma a briefing document for the Metropolitan Police Asbestos and Mesothelioma a briefing document for the Metropolitan Police Prepared by Professor John Cherrie, Heriot Watt University, Edinburgh, UK. Introduction The purpose of this document is to provide

More information

Asbestos: health effects and risk. Peter Franklin Senior Scientific Officer, EHD Senior Research Fellow, UWA

Asbestos: health effects and risk. Peter Franklin Senior Scientific Officer, EHD Senior Research Fellow, UWA Asbestos: health effects and risk Peter Franklin Senior Scientific Officer, EHD Senior Research Fellow, UWA What is asbestos Naturally occurring mineral that has crystallised to form long thin fibres and

More information

Asbestos related health risks

Asbestos related health risks Asbestos related health risks Pascal DUMORTIER *,** & Paul DE VUYST** *a-ulab ** Chest Department Hopital ERASME Asbestos related health risks Asbestos : some facts Asbestos related diseases Detection

More information

Molecular mechanisms of carcinogenesis. Nik Hodges School of Biosciences

Molecular mechanisms of carcinogenesis. Nik Hodges School of Biosciences Molecular mechanisms of carcinogenesis Nik Hodges School of Biosciences N.Hodges@bham.ac.uk Aims What is cancer at the cellular level? How do chemical and physical agents cause cancer? How do we test for

More information

Mesothelioma Trends as Predictors of the Asbestos- Related Lung Cancer Burden

Mesothelioma Trends as Predictors of the Asbestos- Related Lung Cancer Burden Mesothelioma Trends as Predictors of the Asbestos- Related Lung Cancer Burden Valerie McCormack UICC World Cancer Congress Montreal August 2012 Outline Background Estimating the lung cancer mortality burden

More information

Determination of Asbestos Exposure by Pathology and Clinical History

Determination of Asbestos Exposure by Pathology and Clinical History 16 Determination of Asbestos Exposure by Pathology and Clinical History Allen R. Gibbs The determination of whether an abnormal asbestos exposure took place is important in mesothelioma cases because of

More information

Asbestos Diseases. What Is Asbestos?

Asbestos Diseases. What Is Asbestos? 1 Asbestos Diseases What Is Asbestos? Asbestos is a term applied to a group of minerals formed into rock and mined in a similar way to coal. In this form, asbestos is made up of strong, fine and flexible

More information

COPD, INFLAMMATION, AND LUNG CANCER. Jerome S Brody, M.D., Professor of Medicine and. Avrum Spira, M.D., Assistant Professor of Medicine

COPD, INFLAMMATION, AND LUNG CANCER. Jerome S Brody, M.D., Professor of Medicine and. Avrum Spira, M.D., Assistant Professor of Medicine COPD, INFLAMMATION, AND LUNG CANCER Jerome S Brody, M.D., Professor of Medicine and Avrum Spira, M.D., Assistant Professor of Medicine Pulmonary Center and Department of Medicine Boston University School

More information

ASBESTOS FIBRES IN THE LUNGS OF CHRYSOTILE MINERS AND MILLERS A PRELIMINARY REPORT

ASBESTOS FIBRES IN THE LUNGS OF CHRYSOTILE MINERS AND MILLERS A PRELIMINARY REPORT Ann. occup. llyy.. Vol.. Mos. I 4. pp. 4-4. 98. Primed in Great Bnlain. Inhaled Panicles V 0003 4878/8,004-OSO3.00/O Pergamon Press Lid. (' 98 British Occupational Hygiene Society. ASBESTOS FIBRES IN THE

More information

VIRUSES AND CANCER. Michael Lea

VIRUSES AND CANCER. Michael Lea VIRUSES AND CANCER 2012 Michael Lea VIRAL ONCOLOGY - LECTURE OUTLINE 1. Historical Review 2. Viruses Associated with Cancer 3. RNA Tumor Viruses 4. DNA Tumor Viruses HISTORICAL REVIEW Historical Review

More information

Asbestos. a mineral habit characterized by long, thin, strong, flexible fibers equivalent to hairs or whiskers. How long?

Asbestos. a mineral habit characterized by long, thin, strong, flexible fibers equivalent to hairs or whiskers. How long? Asbestos The term asbestiform describes a mineral habit characterized by long, thin, strong, flexible fibers equivalent to hairs or whiskers How long? Definition varies Modern Uses of Asbestos Asbestos

More information

Asbestos and Related Durable Fibers: Too Ubiquitous, Too Persistent, Too Complex to Put Health Risks to Rest?

Asbestos and Related Durable Fibers: Too Ubiquitous, Too Persistent, Too Complex to Put Health Risks to Rest? Asbestos and Related Durable Fibers: Too Ubiquitous, Too Persistent, Too Complex to Put Health Risks to Rest? Philip M. Cook Mid-Continent Ecology Division National Health and Environmental Effects Research

More information

A disease of populations of cells that live, divide, invade and spread without regard to normal limits

A disease of populations of cells that live, divide, invade and spread without regard to normal limits 1 Targeted Cancer Therapies Mark McKeage Medical Oncology Specialist Professor in Clinical Pharmacology 2 Cancer Definition- A disease of populations of cells that live, divide, invade and spread without

More information

Changing Trends in Mesothelioma Incidence. Hans Weill, M.D. Professor of Medicine Emeritus Tulane University Medical Center

Changing Trends in Mesothelioma Incidence. Hans Weill, M.D. Professor of Medicine Emeritus Tulane University Medical Center Changing Trends in Mesothelioma Incidence Hans Weill, M.D. Professor of Medicine Emeritus Tulane University Medical Center International Conference on Chrysotile Montreal, May 23, 2006 Global Mesothelioma

More information

Workers around the world who encounter hazardous substances are aware of the measures needed

Workers around the world who encounter hazardous substances are aware of the measures needed Introduction Workers around the world who encounter hazardous substances are aware of the measures needed to protect themselves from acute exposures to these chemicals. However, workers are often less

More information

Sir William Osler: Listen to the patient; the patient tells you everything.

Sir William Osler: Listen to the patient; the patient tells you everything. Sir William Osler: Listen to the patient; the patient tells you everything. Jean-Martin Charcot: The patient is a liar. Epidemiology of Mesothelioma Jeffrey H. Mandel, MD, MPH Division of Environmental

More information

بسم هللا الرحمن الرحيم

بسم هللا الرحمن الرحيم بسم هللا الرحمن الرحيم Updates in Mesothelioma By Samieh Amer, MD Professor of Cardiothoracic Surgery Faculty of Medicine, Cairo University History Wagner and his colleagues (1960) 33 cases of mesothelioma

More information

How Cancer Begins???????? Chithra Manikandan Nov 2009

How Cancer Begins???????? Chithra Manikandan Nov 2009 Cancer Cancer is one of the most common diseases in the developed world: 1 in 4 deaths are due to cancer 1 in 17 deaths are due to lung cancer Lung cancer is the most common cancer in men Breast cancer

More information

What has changed to justify the US Senate s bill to ban asbestos now?

What has changed to justify the US Senate s bill to ban asbestos now? Comments of Professor Richard Wilson Department of Physics & Center for Risk Analysis Harvard University Cambridge, Massachusetts On the Proposed Asbestos Ban Senate Employment and Workplace Safety Subcommittee

More information

MULTIPLE MYELOMA. Dr Malkit S Riyat. MBChB, FRCPath(UK) Consultant Haematologist

MULTIPLE MYELOMA. Dr Malkit S Riyat. MBChB, FRCPath(UK) Consultant Haematologist MULTIPLE MYELOMA Dr Malkit S Riyat MBChB, FRCPath(UK) Consultant Haematologist Multiple myeloma is an incurable malignancy that arises from postgerminal centre, somatically hypermutated B cells.

More information

Asbestos Trends Worldwide, with Richard Lemen

Asbestos Trends Worldwide, with Richard Lemen Asbestos Trends Worldwide, with Richard Lemen Ashley Ahearn Views and opinions expressed in these podcasts are those of the interview subjects and do not necessarily reflect the views, opinions, or policies

More information

Future Oncology: Technology, Products, Market and Service Opportunities

Future Oncology: Technology, Products, Market and Service Opportunities Brochure More information from http://www.researchandmarkets.com/reports/296370/ Future Oncology: Technology, Products, Market and Service Opportunities Description: Future Oncology is an analytical newsletter

More information

P L E U R A L M E S O T H E L I O M A

P L E U R A L M E S O T H E L I O M A For media outside the US, UK and Canada only P L E U R A L M E S O T H E L I O M A 1. Overview 2. What is pleural mesothelioma? 3. How common is pleural mesothelioma? 4. What are the risk factors for pleural

More information

Incidence of Malignant Pleural Mesothelioma due to Environmental Asbestos Fiber Exposure in the Southeast of Turkey

Incidence of Malignant Pleural Mesothelioma due to Environmental Asbestos Fiber Exposure in the Southeast of Turkey Clinical Investigations Respiration 2000;67:610 614 Received: November 26, 1999 Accepted after revision: June 27, 2000 Incidence of Malignant Pleural Mesothelioma due to Environmental Asbestos Fiber Exposure

More information

The Physiology of Hyperbaric Oxygen Therapy. Free Radicals and Reactive Oxygen Species. I. Introduction Definition, Source, function and Purpose

The Physiology of Hyperbaric Oxygen Therapy. Free Radicals and Reactive Oxygen Species. I. Introduction Definition, Source, function and Purpose The Physiology of Hyperbaric Oxygen Therapy Free Radicals and Reactive Oxygen Species I. Introduction Definition, Source, function and Purpose A. Definition of free radicals and reactive oxygen species

More information

CARCINOGENICITY TESTING OF ASBESTOS FIBRES - A PRELIMINARY STUDY

CARCINOGENICITY TESTING OF ASBESTOS FIBRES - A PRELIMINARY STUDY CARCINOGENICITY TESTING OF ASBESTOS FIBRES - A PRELIMINARY STUDY Extensive data is available on lung cancer and pleural mesothelioma caused by asbestos in man and animals. The object of the present work

More information

ASBESTOS AWARENESS. Environmental Health And Safety. www.uoguelph.ca/ehs MAINTENANCE CONTRACTORS

ASBESTOS AWARENESS. Environmental Health And Safety. www.uoguelph.ca/ehs MAINTENANCE CONTRACTORS ASBESTOS AWARENESS MAINTENANCE CONTRACTORS Environmental Health And Safety www.uoguelph.ca/ehs March 2007 ASBESTOS AWARENESS AT THE UNIVERSITY OF GUELPH What is Asbestos? The term asbestos refers to a

More information

IWU PHYSICAL PLANT SAFETY PROGRAM. Toxic and Hazardous Substances, Title 29 Code of Federal Regulations (CFR) Part 1910.1001, Subpart Z Asbestos

IWU PHYSICAL PLANT SAFETY PROGRAM. Toxic and Hazardous Substances, Title 29 Code of Federal Regulations (CFR) Part 1910.1001, Subpart Z Asbestos STANDARDS Toxic and Hazardous Substances, Title 29 Code of Federal Regulations (CFR) Part 1910.1001, Subpart Z Asbestos 1. INTRODUCTION IWU has a responsibility to provide a safe environment for students,

More information

Asbestos Presence in a Factory that Produced Asbestos-Containing Products

Asbestos Presence in a Factory that Produced Asbestos-Containing Products Asbestos Presence in a Factory that Produced Asbestos-Containing Products Hana Fajkovi Department of Geology, Faculty of Science, University of Zagreb, Horvatovac 95, 10000 Zagreb, Croatia, e-mail: (hanaf@geol.pmf.hr)

More information

NHS Barking and Dagenham Briefing on disease linked to Asbestos in Barking & Dagenham

NHS Barking and Dagenham Briefing on disease linked to Asbestos in Barking & Dagenham APPENDIX 1 NHS Barking and Dagenham Briefing on disease linked to Asbestos in Barking & Dagenham 1. Background 1.1. Asbestos Asbestos is a general name given to several naturally occurring fibrous minerals

More information

Molecular and genetic changes in asbestos-related lung cancer

Molecular and genetic changes in asbestos-related lung cancer Available online at www.sciencedirect.com Cancer Letters 265 (2008) 1 15 Mini-review Molecular and genetic changes in asbestos-related lung cancer Penny Nymark a, *, Harriet Wikman b, Tuija Hienonen-Kempas

More information

Occupational respiratory diseases due to Asbestos. Dirk Dahmann, IGF, Bochum

Occupational respiratory diseases due to Asbestos. Dirk Dahmann, IGF, Bochum Occupational respiratory diseases due to Asbestos Dirk Dahmann, IGF, Bochum Contents Introduction Diseases Further Effects Preventive Strategies Conclusion Asbestos minerals Woitowitz, 2003 Imports (+

More information

Neoplasms. Review of Normal Cells. Bio 375 Pathophysiology

Neoplasms. Review of Normal Cells. Bio 375 Pathophysiology Neoplasms Bio 375 Pathophysiology Review of Normal Cells During its life span, each cell follows the basic cell cycle of growth and reproduction called mitosis The timing of each event varies with the

More information

State of the Art. Mechanisms in the Pathogenesis of Asbestosis and Silicosis. BROOKE T. MOSSMAN and ANDREW CHURG CONTENTS

State of the Art. Mechanisms in the Pathogenesis of Asbestosis and Silicosis. BROOKE T. MOSSMAN and ANDREW CHURG CONTENTS State of the Art Mechanisms in the Pathogenesis of Asbestosis and Silicosis BROOKE T. MOSSMAN and ANDREW CHURG Departments of Pathology, University of Vermont College of Medicine, Burlington, Vermont;

More information

MUTATION, DNA REPAIR AND CANCER

MUTATION, DNA REPAIR AND CANCER MUTATION, DNA REPAIR AND CANCER 1 Mutation A heritable change in the genetic material Essential to the continuity of life Source of variation for natural selection New mutations are more likely to be harmful

More information

Lesson 3 Reading Material: Oncogenes and Tumor Suppressor Genes

Lesson 3 Reading Material: Oncogenes and Tumor Suppressor Genes Lesson 3 Reading Material: Oncogenes and Tumor Suppressor Genes Becoming a cancer cell isn t easy One of the fundamental molecular characteristics of cancer is that it does not develop all at once, but

More information

Quantification of Non-Fibrous and Fibrous Particulates in Human Lungs: Twenty Year Update on Pneumoconiosis Database

Quantification of Non-Fibrous and Fibrous Particulates in Human Lungs: Twenty Year Update on Pneumoconiosis Database Ann. occup. Hyg., Vol. 46, Supplement 1, pp. 397 401, 2002 2002 British Occupational Hygiene Society Published by Oxford University Press DOI: 10.1093/annhyg/mef694 Quantification of Non-Fibrous and Fibrous

More information

1 page Overview. CONCURRENT 1D, 1E, 1F Biology & Pathogenesis Multi-Modality Immunology 1

1 page Overview. CONCURRENT 1D, 1E, 1F Biology & Pathogenesis Multi-Modality Immunology 1 1 page Overview 21 Oct Tuesday 1500 on REGISTRATION 1800 Welcome Reception & Cocktails at the Cape Town International Conference Centre (CTICC) 22 Oct Wednesday 0730 REGISTRATION 0830 OPENING 0900 PLENARY

More information

All About Asbestos. Read this booklet to learn more about:

All About Asbestos. Read this booklet to learn more about: All About Asbestos Read this booklet to learn more about: identifying asbestos-containing material in you home the health risks of asbestos what you can do about asbestos. What Is Asbestos? Asbestos is

More information

Male. Female. Death rates from lung cancer in USA

Male. Female. Death rates from lung cancer in USA Male Female Death rates from lung cancer in USA Smoking represents an interesting combination of an entrenched industry and a clearly drug-induced cancer Tobacco Use in the US, 1900-2000 5000 100 Per Capita

More information

Criteria for Attributing Lung Cancer to Asbestos Exposure

Criteria for Attributing Lung Cancer to Asbestos Exposure Criteria for Attributing Lung Cancer to Asbestos Exposure Philip T. Cagle, MD The article by Mollo and coworkers 1 examines the criteria for attribution of lung cancers to asbestos exposure, suggesting

More information

Pathogenesis and Diagnosis of Mesothelioma

Pathogenesis and Diagnosis of Mesothelioma Pathogenesis and Diagnosis of Mesothelioma Michele Carbone, M.D., Ph.D. University of Hawaii Cancer Center 701 Ilalo Street Honolulu, HI (808) 586-3013 mcarbone@cc.hawaii.edu Michele Carbone, M.D., Ph.D.,

More information

Asbestos Awareness Training

Asbestos Awareness Training Asbestos Awareness Training Topics Uses and forms of asbestos; Common locations of asbestos containing building materials (ACBM); Health effects from exposure; Recognition of ACM damage and deterioration;

More information

Science-Based Facts Relevant Health Issues 2015. For environmental occupational health safe and responsible use

Science-Based Facts Relevant Health Issues 2015. For environmental occupational health safe and responsible use Science-Based Facts Relevant Health Issues 2015 For environmental occupational health safe and responsible use SCIENCE-BASED FACTS AND RELEVANT HEALTH ISSUES 2015 ON THE DIFFERENT ASBESTOS FIBER TYPES:

More information

Table 2.4. Summary of design and findings from mesothelioma case-control studies

Table 2.4. Summary of design and findings from mesothelioma case-control studies categories Agudo et al. (2000) Barcelona and Cadiz, Spain 32 cases (77% males) of histologically con rmed malignant pleural mesothelioma identified from hospital in the region between //993 and 2/3/996.

More information

Asbestos Awareness at the University of Toronto

Asbestos Awareness at the University of Toronto Asbestos Awareness at the University of Toronto What is Asbestos? Asbestos is a general term given to a group of naturally occurring mineral silicates that are made up of long thin fibres. These fibrous

More information

HEALTH CARE FOR EXPOSURE TO ASBESTOS. 2010 The SafetyNet Centre for Occupational Health and Safety Research Memorial University www.safetynet.mun.

HEALTH CARE FOR EXPOSURE TO ASBESTOS. 2010 The SafetyNet Centre for Occupational Health and Safety Research Memorial University www.safetynet.mun. HEALTH CARE FOR PATIENTS WITH EXPOSURE TO ASBESTOS 2010 The SafetyNet Centre for Occupational Health and Safety Research Memorial University www.safetynet.mun.ca HEALTH CARE FOR PATIENTS WITH EXPOSURE

More information

PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES APOPTOSIS IS A NEWER TARGET FOR LUNGS CANCER

PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES APOPTOSIS IS A NEWER TARGET FOR LUNGS CANCER PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES APOPTOSIS IS A NEWER TARGET FOR LUNGS CANCER 1 Trivedi Upama N*., 2 Trivedi Naitik D., 3 Patel Madhubhai M., 4 Patel Jayvadan

More information

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.

More information

Mesothelioma. 1. Introduction. 1.1 General Information and Aetiology

Mesothelioma. 1. Introduction. 1.1 General Information and Aetiology Mesothelioma 1. Introduction 1.1 General Information and Aetiology Mesotheliomas are tumours that arise from the mesothelial cells of the pleura, peritoneum, pericardium or tunica vaginalis [1]. Most are

More information

Asbestos Burden Predicts Survival in Pleural Mesothelioma

Asbestos Burden Predicts Survival in Pleural Mesothelioma Asbestos Burden Predicts Survival in Pleural Mesothelioma The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Citation Published

More information

Diseases. Inflammations Non-inflammatory pleural effusions Pneumothorax Tumours

Diseases. Inflammations Non-inflammatory pleural effusions Pneumothorax Tumours Pleura Visceral pleura covers lungs and extends into fissures Parietal pleura limits mediastinum and covers dome of diaphragm and inner aspect of chest wall. Two layers between them (pleural cavity) contains

More information

Asbestos Related Diseases

Asbestos Related Diseases Asbestos Related Diseases Asbestosis Mesothelioma Lung Cancer Pleural Disease Asbestosis and Mesothelioma (LUNG CANCER) Support Group 1800 017 758 www.amsg.com.au ii Helping you and your family through

More information

Plaintiffs Experts Latest Pathological Theories

Plaintiffs Experts Latest Pathological Theories Plaintiffs Experts Latest Pathological Theories Kurt B. Gerstner Campbell Campbell Edwards & Conroy, P.C. One Constitution Center Boston, MA 02129 (617) 241-3086 kgerstner@campbell-trial-lawyers.com Kurt

More information

The Trend in Airborne Asbestos Concentrations at Plants Manufacturing Asbestos-Containing Products in Japan

The Trend in Airborne Asbestos Concentrations at Plants Manufacturing Asbestos-Containing Products in Japan Industrial Health 2001, 39, 127 131 Original Article The Trend in Airborne Asbestos Concentrations at Plants Manufacturing Asbestos-Containing Products in Japan Koji YOSHIZUMI 1 *, Hajime HORI 2, Toshihiko

More information

REPORT PERSPECTIVES IN LUNG CANCER 2010 AMSTERDAM

REPORT PERSPECTIVES IN LUNG CANCER 2010 AMSTERDAM REPORT PERSPECTIVES IN LUNG CANCER 2010 AMSTERDAM Valerie Van Damme, Isabelle Wauters, Johan Vansteenkiste Univ. Hospital Leuven and Leuven Lung Cancer Group Introduction Perspectives in Lung Cancer (PILC)

More information