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

Our plain-English summary of Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review (Review), by V. Filetti, E. Vitale, G. Broggi, et al (Biomedical Reports, 2020).

The study

• Authors: V. Filetti, E. Vitale, G. Broggi, M.P. Hagnäs, S. Candido, A. Spina, C. Lombardo
• Journal: Biomedical Reports
• Published: 2020;13(6):60
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright: © Filetti et al.

In plain English

This article is a systematic review, not a new experiment. The authors searched SCOPUS and Medline (PubMed) for English-language experimental studies on fluoro-edenite, an asbestos-like fiber from volcanic rock around Biancavilla, Sicily, Italy. They included 24 studies: cell experiments, rat experiments, and studies of tissue from Biancavilla-area sheep and from human malignant mesothelioma. In the reviewed cell studies, fibrous but not prismatic fluoro-edenite caused marked changes in lung epithelial cells. Fibrous fluoro-edenite also increased the release of the inflammatory signals IL-6 and IL-8. In one reviewed study, nitric oxide production rose after crocidolite but not after fluoro-edenite. Another found that one form of fluoro-edenite had a markedly strong effect on nitric oxide production in mouse macrophage cells. In the reviewed rat studies, prismatic fluoro-edenite did not cause mesothelioma. Among rats that died after fibrous fluoro-edenite injection, mesothelioma caused 82.5% of deaths after injection into the abdominal cavity and 14.3% after injection into the pleural cavity. Fiber sizes in sheep lymph nodes resembled those found in the lung of a Biancavilla housewife who died of mesothelioma. The authors concluded that computer-based study of microRNAs represents an effort toward finding mesothelioma biomarkers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review of published in vitro, in vivo and ex vivo experimental studies, carried out according to PICo criteria
• Who was studied: 24 published experimental studies found by searching SCOPUS and Medline (PubMed) from March 4 to August 4, 2020, English language only. Table I lists 11 in vitro studies (human and mouse cell lines: A549, MeT-5A, J774, JU77, human lung fibroblasts), 2 in vivo studies (Sprague-Dawley rats) and 11 ex vivo studies (lung and lymph-node tissue of sheep from the Biancavilla area, and human malignant mesothelioma tissue)
• Exposure: Fluoro-edenite from Biancavilla (Sicily, Italy), in prismatic and fibrous forms. Some reviewed studies compared it with crocidolite and tremolite. Rat studies used single intraperitoneal or intrapleural injection; sheep were exposed environmentally
• Main results:
  • In the reviewed rat studies, among deceased rats given fibrous fluoro-edenite, 82.5% of those treated by intraperitoneal injection and 14.3% of those treated by intrapleural injection died of mesothelioma
  • In the reviewed rat studies, prismatic fluoro-edenite did not cause mesothelioma
  • In reviewed studies of A549 lung epithelial cells, fibrous fluoro-edenite caused dramatic changes in the actin network
  • In reviewed studies of A549 lung epithelial cells, fibrous fluoro-edenite increased secretion of IL-6 and IL-8 over time
  • In one reviewed study (Cardile et al, ref. 64) of A549 cells, J774 cells and human lung fibroblasts, nitric oxide synthesis and iNOS expression increased after crocidolite but not after fluoro-edenite exposure
  • In another reviewed study (ref. 78), fluoro-edenite form 19 had a markedly strong effect on nitric oxide biosynthesis, and form 27 stimulated ROS generation, in J774 mouse macrophage cells, in contrast to MeT-5A cells
  • In a reviewed miRNA study, non-malignant MeT-5A mesothelial cells were more sensitive to fluoro-edenite fibers than JU77 mesothelioma cells
  • Fluoro-edenite fiber dimensions in lymph nodes of sheep from the Biancavilla area were similar to those found in the lung of a Biancavilla housewife who died of malignant mesothelioma
  • In a reviewed study of human fluoro-edenite-induced malignant mesothelioma tissue, AQP1 overexpression was associated with longer median overall survival
  • In their discussion, citing other literature, the authors noted that the poor sensitivity of mesothelin, the only FDA-approved mesothelioma biomarker, limits its value for diagnosis
• The authors' conclusion: The authors concluded that computer-based (in silico) study of miRNA expression represents an effort in the field of biomarker discovery for malignant mesothelioma

Topics

Medical terms in this study, explained in our Lexicon: fluoro-edenite, Mesothelioma, Systematic Review, Asbestiform, Biancavilla, Tremolite, Actinolite, Neoplasm.

Related studies

• Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study — G. Broggi, G. Angelico, et al. (2021)
• Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report — C. Lombardo, G. Maugeri, et al. (2024)
• Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells — V. Rapisarda, R. Salemi, et al. (2016)
• Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report — R. Caltabiano, C. Loreto, et al. (2018)
• Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes — Y. Grosse, D. Loomis, et al. (2014)
• Pleural mesothelioma cases in Biancavilla are related to a new fluoro-edenite fibrous amphibole — P. Comba, A. Gianfagna, et al. (2003)

Browse return to medical research.