Update of in vitro, in vivo and ex vivo fluoro‑edenite effects on malignant mesothelioma: A systematic review (Review)

Abstract

Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in in vitro , in vivo and ex vivo experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO • production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, in silico analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This in silico approach could represent an effort in the field of biomarker discovery for MM.

Asbestos in High-Risk Communities: Public Health Implications

“…Erionite is strongly carcinogenic in laboratory animals [ 32 , 70 , 71 ] and has been assessed by IARC as a Group1 human carcinogen [ 72 ]. Similarly, fluoro-edenite [ 73 ] another asbestiform amphibole is responsible for excess mesothelioma in Biancavilla, Italy [ 74 , 75 ]. Non-regulated carcinogenic asbestiform fibers such as erionite have wide natural distribution across the US West [ 76 ] and could readily be disturbed in a variety of ways.…”

Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study

“…Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the mesothelial layer of the pleura and traditionally related to the exposure to asbestos fibers [ 1 ]. Despite the strong association with occupational or residential exposure to asbestos fibers, other asbestos-like fibers, including erionite and fluoro-edenite (FE) fibers, have been demonstrated as alternative pathogenetic agents capable of promoting MPM [ 2 , 3 , 4 ]. In detail, epidemiological studies performed between 1988 and 1997 demonstrated high incidence and mortality rates of MPM in Biancavilla, a small town near Mt.…”

“…In detail, epidemiological studies performed between 1988 and 1997 demonstrated high incidence and mortality rates of MPM in Biancavilla, a small town near Mt. Etna in Sicily (Italy), linked to environmental and occupational exposure to FE fibers [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. These latter fibers were isolated in the lava rocks excavated from a local stone quarry and used for about 50 years for building purposes [ 4 , 5 , 6 ].…”

“…Etna in Sicily (Italy), linked to environmental and occupational exposure to FE fibers [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. These latter fibers were isolated in the lava rocks excavated from a local stone quarry and used for about 50 years for building purposes [ 4 , 5 , 6 ]. Subsequent studies demonstrated their morphological and size similarities with tremolite amphibolic asbestos fibers [ 4 , 5 , 6 ]; therefore, FE fibers have been declared carcinogenic by the International Agency for Research on Cancer (IARC; Lyon, France) [ 7 ].…”

“…These latter fibers were isolated in the lava rocks excavated from a local stone quarry and used for about 50 years for building purposes [ 4 , 5 , 6 ]. Subsequent studies demonstrated their morphological and size similarities with tremolite amphibolic asbestos fibers [ 4 , 5 , 6 ]; therefore, FE fibers have been declared carcinogenic by the International Agency for Research on Cancer (IARC; Lyon, France) [ 7 ]. MPM carries a poor outcome, given its low rates of response to treatments and it is often diagnosed at an advanced stage; therefore, the median survival is approximately 6 to 12 months [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”