Malignant pleural mesothelioma caused by environmental exposure to asbestos or erionite in rural Turkey: CT findings in 84 patients.

Şahin, Ahmet; Çöplü, Lütfi; Selçuk, Ziya; Eryilmaz, Muzaffer; Emri, Salïh; Akhan, Okhan; Barış, Y. İzzettin

doi:10.2214/ajr.161.3.8394641

Cited by 54 publications

(29 citation statements)

References 20 publications

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“…Kawashima and Libshitz (7) also described this volume loss of the involved hemithorax as a CT feature of MPM, which occurred in 42% of their cohort. Sahin et al (6) reported volume contraction in 73%, and Hierholzer et al (16) used the term shrinking lung for this phenomenon. However, it also is observed in patients with systemic sclerosis, rounded atelectasis, systemic lupus erythematosus, and primary Sjögren syndrome (7), as well as in patients with chronic empyema and hemothorax.…”

Section: Discussionmentioning

confidence: 99%

“…Computed tomography (CT) has been used widely as the primary imaging modality for evaluation of MPM (2)(3)(4)(5)(6). Although there are no pathognomonic features, circumferential pleural thickening with or without pleural effusion, nodular pleural thickening, involvement of the interlobar fissures, mediastinal pleural involvement, contraction of the pleura, and mediastinal lymph node invasion (6,7) are considered strongly suggestive of malignant pleural disease (MPD).…”

Section: Advances In Knowledgementioning

confidence: 99%

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Malignant Pleural Mesothelioma: Visual Assessment by Using Pleural Pointillism at Diffusion-weighted MR Imaging

Coolen¹,

Keyzer²,

Nafteux³

et al. 2015

Radiology

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Section: Discussionmentioning

confidence: 99%

Section: Advances In Knowledgementioning

confidence: 99%

Malignant Pleural Mesothelioma: Visual Assessment by Using Pleural Pointillism at Diffusion-weighted MR Imaging

Coolen¹,

Keyzer²,

Nafteux³

et al. 2015

Radiology

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show abstract

“…The International Agency for Research on Cancer classified erionite as a group 1 known human carcinogen and concluded that erionite is the cause of the MM epidemic in Cappadocia (8). Since then, research has shown that erionite exposures result in pleural and interstitial fibrotic changes, similar to those observed with asbestos exposures (9,10). Moreover, in vitro studies demonstrated that erionite exposure, but not asbestos exposure, is sufficient to cause malignant transformation of human mesothelial cells in tissue culture (11).…”

mentioning

confidence: 85%

Erionite exposure in North Dakota and Turkish villages with mesothelioma

Carbone

Barış

Bertino

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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164

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Exposure to erionite, an asbestos-like mineral, causes unprecedented rates of malignant mesothelioma (MM) mortality in some Turkish villages. Erionite deposits are present in at least 12 US states. We investigated whether increased urban development has led to erionite exposure in the United States and after preliminary exploration, focused our studies on Dunn County, North Dakota (ND). In Dunn County, ND, we discovered that over the past three decades, more than 300 miles of roads were surfaced with erionite-containing gravel. To determine potential health implications, we compared erionite from the Turkish villages to that from ND. Our study evaluated airborne point exposure concentrations, examined the physical and chemical properties of erionite, and examined the hallmarks of mesothelial cell transformation in vitro and in vivo. Airborne erionite concentrations measured in ND along roadsides, indoors, and inside vehicles, including school buses, equaled or exceeded concentrations in Boyali, where 6.25% of all deaths are caused by MM. With the exception of outdoor samples along roadsides, ND concentrations were lower than those measured in Turkish villages with MM mortality ranging from 20 to 50%. The physical and chemical properties of erionite from Turkey and ND are very similar and they showed identical biological activities. Considering the known 30-to 60-y latency for MM development, there is reason for concern for increased risk in ND in the future. Our findings indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted. asbestosis | cancer | carcinogenesis | environmental carcinogenesis | mineral fiber carcinogenesis

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“…An estimated 3000 cases per year are diagnosed in the United States, and most patients die within 1 year, with fewer than 5% of all patients cured even when intensive combined modality therapeutic strategies are employed. Mesothelioma has been linked to asbestos exposure (Craighead, 1987), and epidemiologic studies also show that mesothelioma risk increases after inhalation of the airborne mineral dust, erionite (Selcuk et al , 1992; Sahin et al , 1993). Mesothelioma histologic subtypes include epithelioid, spindled, or mixed (epithelioid and spindled; Craighead, 1987), of which the spindled subtype has the worst prognosis.…”

mentioning

confidence: 99%

Multipoint targeting of the PI3K/mTOR pathway in mesothelioma

Zhou

Liu

et al. 2014

Br J Cancer

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Background:Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis.Methods:Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations.Results:We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation.Conclusions:These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for therapeutic intervention.

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Malignant pleural mesothelioma caused by environmental exposure to asbestos or erionite in rural Turkey: CT findings in 84 patients.

Cited by 54 publications

References 20 publications

Malignant Pleural Mesothelioma: Visual Assessment by Using Pleural Pointillism at Diffusion-weighted MR Imaging

Malignant Pleural Mesothelioma: Visual Assessment by Using Pleural Pointillism at Diffusion-weighted MR Imaging

Erionite exposure in North Dakota and Turkish villages with mesothelioma

Multipoint targeting of the PI3K/mTOR pathway in mesothelioma

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