Asbestos Exposure Research Articles

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the ‘test, re-test’ principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).

HMGB1 released by mesothelial cells drives the development of asbestos-induced mesothelioma

Asbestos is the main cause of malignant mesothelioma. Previous studies have linked asbestos-induced mesothelioma to the release of HMGB1 from the nucleus to the cytoplasm, and from the cytoplasm to the extracellular space. In the cytoplasm, HMGB1 induces autophagy impairing asbestos-induced cell death. Extracellularly, HMGB1 stimulates the secretion of TNFα. Jointly, these two cytokines kick-start a chronic inflammatory process that over time promotes mesothelioma development. Whether the main source of extracellular HMGB1 were the mesothelial cells, the inflammatory cells, or both was unsolved. This information is critical to identify the targets and design preventive/therapeutic strategies to interfere with asbestos-induced mesothelioma. To address this issue, we developed the conditional mesothelial HMGB1-knockout (Hmgb1ΔpMeso) and the conditional myelomonocytic-lineage HMGB1-knockout (Hmgb1ΔMylc) mouse models. We establish here that HMGB1 is mainly produced and released by the mesothelial cells during the early phases of inflammation following asbestos exposure. The release of HMGB1 from mesothelial cells leads to atypical mesothelial hyperplasia, and in some animals, this evolves over the years into mesothelioma. We found that Hmgb1ΔpMeso, whose mesothelial cells cannot produce HMGB1, show a greatly reduced inflammatory response to asbestos, and their mesothelial cells express and secrete significantly reduced levels of TNFα. Moreover, the tissue microenvironment in areas of asbestos deposits displays an increased fraction of M1-polarized macrophages compared to M2 macrophages. Supporting the biological significance of these findings, Hmgb1ΔpMeso mice showed a delayed and reduced incidence of mesothelioma and an increased mesothelioma-specific survival. Altogether, our study provides a biological explanation for HMGB1 as a driver of asbestos-induced mesothelioma.

Deep Learning Neural Network-Guided Detection of Asbestos Bodies in Bronchoalveolar Lavage Samples

Introduction: Asbestos is a global occupational health hazard, and exposure to it by inhalation predisposes to interstitial as well as malignant pulmonary morbidity. Over time, asbestos fibers embedded in lung tissue can become coated with iron-rich proteins and mucopolysaccharides, after which they are called asbestos bodies (ABs) and can be detected in light microscopy (LM). Bronchoalveolar lavage, a cytological sample from the lower airways, is one of the methods for diagnosing lung asbestosis and related morbidity. Search for ABs in these samples is generally laborious and time-consuming. We describe a novel diagnostic method, which implements deep learning neural network technology for the detection of ABs in bronchoalveolar lavage samples (BALs). Methods: BALs with suspicion of asbestos exposure were scanned as whole slide images (WSIs) and uploaded to a cloud-based virtual microscopy platform with a neural network training interface. The images were used for training and testing a neural network model capable of recognizing ABs. To prioritize the model’s sensitivity, we allowed it to also make false-positive suggestions. To test the model, we compared its performance to standard LM diagnostic data as well as the ground truth (GT) number of ABs, which we established by a thorough manual search of the WSIs. Results: We were able to reach overall sensitivity of 93.4% (95% CI: 90.3–95.7%) in the detection of ABs in comparison to their GT number. Compared to standard LM diagnostic data, our model showed equal to or higher sensitivity in most cases. Conclusion: Our results indicate that deep learning neural network technology offers promising diagnostic tools for routine assessment of BALs. However, at this stage, a human expert is required to confirm the findings.

High prevalence of upper lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis in patients with round atelectasis

BackgroundUpper-lung field pulmonary fibrosis (upper-PF), radiologically consistent with pleuroparenchymal fibroelastosis (PPFE), was reported to develop in patients with a history of asbestos exposure and tuberculous pleurisy, indicating that chronic pleuritis is correlated with upper-PF development. Round atelectasis reportedly emerges after chronic pleuritis. This study aimed to clarify the association between round atelectasis and upper-PF. MethodsWe examined the radiological reports of all consecutive patients with round atelectasis between 2006 and 2018 and investigated the incidence of upper-PF development. ResultsAmong 85 patients with round atelectasis, 21 patients (24.7%) were confirmed to finally develop upper-PF lesions. Upper-PF was diagnosed after round atelectasis recognition in more than half of the patients (13/21, 61.9%), whereas upper-PF and round atelectasis were simultaneously detected in the remaining 8 patients. At the time of round atelectasis detection, almost all patients (19/21, 90.5%) had diffuse pleural thickening and round atelectasis was commonly observed in non-upper lobes of 19 patients (90.5%). Fourteen patients had round atelectasis in unilateral lung, and the remaining 7 patients had round atelectasis in bilateral lungs. Among all 14 patients with unilateral round atelectasis, upper-PF developed on the same (n = 11) or both sides (n = 3). Thus, upper-PF emerged on the same side where round atelectasis was present (14/14, 100%). The autopsy of one patient revealed a thickened parietal-visceral pleura suggestive of chronic pleuritis. Subpleural fibroelastosis was also observed. ConclusionsUpper-PF occasionally develops on the same side of round atelectasis. Upper-PF may develop as a sequela of chronic pleuritis.

Multiple institutions’ research findings using the National Mesothelioma Virtual Bank

Mesothelioma remains an under-researched cancer due to the lack of high-quality patient samples and clinical information, especially outcomes and asbestos exposure data. The National Mesothelioma Virtual Bank (NMVB) is a biobank in which mesothelioma annotated biospecimens can be made widely available to the research community. Here, we summarized the significant research findings from 20 publications that utilized the NMVB samples for novel biomarker and therapeutic discoveries. The results showed that the use of the NMVB resource was utilized for a number of basic science studies including, but not limited to, studies of biomarkers, abnormal gene expression, and potential therapeutic targets. Some selected findings from these studies include the identification of positive biomarkers such as miRNAs, autoantibodies, and HMGB1. Genes that have mutations or high/low levels of expression like BAP1 or BLM genes can play essential roles in mesothelioma. Algorithms like SPaRTAN and GES can help to understand cell activities. Treatments investigated include thiostrepton, interferon-β gene, and Brentuximab. Publications reviewed indicated a significant impact of the NMVB resource utilized in significant studies focusing on biomarker and therapeutic discoveries, which can act as a model for rare diseases, especially in oncology.

An overview on multimodal imaging for the diagnostic workup of pleural mesothelioma.

Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.

Occupational Asbestos Related Diseases in Indonesia: A Call for Urgent Action and Awareness

Despite many countries have either reduced or banned asbestos use, Indonesia has yet to ban the use of asbestos. Asbestos exposure poses significant health risks, particularly respiratory diseases such asbestos-related lung cancer, mesothelioma, and asbestosis known as an asbestos-related disease. According to the World Health Organization (WHO), asbestos is a major global health concern with millions of people exposed to its hazards and resulting in a significant number of deaths each year. We conducted a literature review study on the topic of asbestos-related diseases in Indonesia. Based on our findings, due to the large amount of asbestos being handled, it is expected that there should be hundreds to a thousand cases of asbestos-related disorders in Indonesia each year. Unfortunetely it is uncommon to find and diagnose cases of asbestos-related diseases in Indonesia. The lack of awareness, inadequate diagnosis, and underreporting of asbestos-related diseases contribute to the challenges faced in Indonesia. The study emphasizes the need for a comprehensive ban on asbestos, safer alternative materials, standardized medical surveillance for exposed workers, increased awareness and cooperation among stakeholders to eliminate asbestos-related diseases in Indonesia.

재건축 안전진단 제도 개선 방안 연구

Reconstruction contributes to improving the quality of life of residents by creating an aging, unstable and poor residential environment into a safe and pleasant residential environment, and is also an important means of realizing basic constitutional rights such as people's right to pursue happiness, property rights, and housing freedom. However, the reconstruction project is causing a lot of confusion to the housing market and the people as related laws and systems repeatedly regulate and ease due to the ups and downs of the housing market and regime change.
 Accordingly, this study attempted to investigate and analyze legislative system improvement efforts raised by the National Assembly on the “Safety Diagnosis Standards for Housing Reconstruction” announced by the government and derive reasonable system improvement measures through Delphi, experts related to safety diagnosis. Based on this process, I would like to propose a plan to improve the current housing reconstruction safety diagnosis system.
 First, the authority to determine safety diagnosis, including the composition and ratio of each item of the safety diagnosis evaluation criteria, should be delegated to the head of the metropolitan government. Critics say that the Ministry of Land, Infrastructure and Transport does not reflect the characteristics of the region and hinders the smooth promotion of reconstruction projects by setting safety diagnosis standards uniformly and uniformly in different situations. Therefore, it is necessary to delegate the authority to decide on safety diagnosis standards to the heads of metropolitan local governments.
 Second, Article 2, Subparagraph 3 (b) of the current Urban Improvement Act defines “significant functional defects among buildings that have not secured seismic performance” as old-age defective buildings. However, whether or not seismic design is reflected in the structural safety evaluation item is omitted. Structural safety assessment items should include whether seismic design is reflected.
 Third, although geological conditions and ground conditions have a very significant impact on the structural safety of buildings, geological conditions and ground conditions are omitted from the structural stability evaluation items. The omission of these important evaluation factors is a factor that degrades the validity and reliability of the safety diagnosis evaluation results.
 Fourth, the use of asbestos building materials should be reflected in the safety diagnosis evaluation items. When inhaled into the human body, asbestos, a first-class carcinogen designated by the World Health Organization, causes fatal diseases such as asbestos lung disease, lung cancer, and malignant mesothelioma. Therefore, in Korea, the Asbestos Safety Management Act has been enacted to thoroughly manage asbestos exposure contained in buildings so that it does not damage public health.
 Fifth, it is necessary for local governments to support certain costs incurred by conducting safety diagnosis for housing reconstruction. However, some say that local governments should not invest in projects to rebuild private property, but the reconstruction project improves the residential environment of owners, such as local land, while creating public benefits such as roads, parks, community facilities, and public rental housing. It is currently supported by some local governments.

FOXM1 Promotes Mesothelioma Cell Migration and Invasion via Activation of SMAD Signaling.

Forkhead box M1 (FOXM1) is a transcription factor closely associated with various human malignancies and is considered an attractive target for cancer therapy. Mesothelioma is a malignancy primarily due to asbestos exposure and certain genetic factors, requiring a better understanding of tumorigenesis for improved treatment. Asbestos-exposed human mesothelial cells have been reported to up-regulate FOXM1 expression in a dose-dependent manner. FOXM1 expression was evaluated in mesothelioma tissues and cell lines. FOXM1 small interfering RNA was transfected into mesothelioma cell lines to analyze its biological functions and regulatory mechanisms. FOXM1 was over-expressed in mesothelioma tissues and cell lines. Knock-down of FOXM1 in mesothelioma cell lines inhibited cell proliferation, migration, and invasion. These results suggest that up-regulation of FOXM1 expression promotes mesothelioma tumorigenesis and progression. We previously reported that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes the proliferation, migration, and invasion of mesothelioma cell lines. In this study, IGF2BP3 knock-down suppressed FOXM1 expression in mesothelioma cell lines. Our results suggest that IGF2BP3, an upstream regulator, contributes to increased FOXM1 expression. Furthermore, IGF2BP3 and FOXM1 knock-down suppressed SMAD signaling by inhibiting SMAD2/3 phosphorylation in mesothelioma cell lines. IGF2BP3/FOXM1 promotes mesothelioma cell migration and invasion via SMAD signaling, highlighting IGF2BP3/FOXM1 as a potential target for mesothelioma treatment.

JSI-124 inhibits cell proliferation and tumor growth by inducing autophagy and apoptosis in murine malignant mesothelioma.

Malignant pleural mesothelioma (MPM), mainly caused by asbestos exposure, has a poor prognosis and lacks effective treatment compared with other cancer types. The intracellular transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed and hyperactivated in most human cancers. In this study, the role of STAT3 in murine MPM was examined. Inhibition of the Janus kinase 2 (JAK2)/STAT3 pathway with the selective inhibitor JSI-124 has an antitumor effect in murine MPM. Specifically, we demonstrated that JSI-124 inhibits murine MPM cell growth and induces apoptotic and autophagic cell death. Exposure of RN5 and AB12 cells to JSI-124 resulted in apoptosis via the Bcl-2 family of proteins. JSI-124 triggered autophagosome formation, accumulation, and conversion of LC3I to LC3II. Autophagy inhibitors, Chloroquine (CQ) and Bafilomycin A1 (Baf-A1), inhibited autophagy and sensitized RN5 and AB12 cells to JSI-124-induced apoptosis. Our data indicate that JSI-124 is a promising therapeutic agent for MPM treatment.

Epidemiology of Asbestosis between 2010-2014 and 2015-2019 Periods in Colombia: Descriptive Study.

Asbestosis is a prevalent worldwide problem, but scarce data sourced from developing countries are available. We describe the sociodemographic characteristics and patterns in the occurrence of care provided for asbestosis in Colombia during the periods 2010-2014 and 2015-2019 to establish the behavior, trends, and variables associated with concentrations among people attended by asbestosis. A retrospective descriptive study was carried out with data from the Integrated Social Protection Information System (SISPRO) for two 5-year periods. People attended by asbestosis (ICD-10: J61) were identified; the frequency of patient visits, sociodemographic characteristics, case distribution patterns, and trends in both five-year periods were described, as was the crude frequency (cFr, 95% CI) of asbestosis (1,000,000 people/year) in both five-year periods (cFr ratio, 95% CI). During the period 2010-2019, 765 people attended by asbestosis were identified; there were 308 people attended by asbestosis between 2010-2014 (cFr: 2.20, 1.96-2.47), and ther were 457 people attended by asbestos between 2015-2019 (cFr: 3.14, 2.92-3.50). In both periods, the estimated cFr in men was nine times the estimated cFr in women. The cFr increased in the 2015-2019 period (cFr_ratio: 1.23, 1.06-1.43). Compared with the 2010-2014 period, the cFr of asbestosis increased in women (cFr_ratio: 1.44, 1.03-2.01), in the Andean (cFr_ratio: 1.61, 1.35-1.95) and Caribbean regions (cFr_ratio: 1. 66, 1.21-2.30), in the urban area (cFr_ratio: 1.24, 1.05-1.48), and in the age groups 45-59 years (cFr_ratio: 1.34, 1.001-1.79) and ≥60 years (cFr_ratio: 1.43, 1.13-1.83). During two five-year periods, the cFr of asbestosis was higher in men; between the first and second five-year periods, it increased significantly, especially in urbanized geographic areas and in populations aged ≥45 years. The estimates possibly reflect the effect of disease latency or the expected impact of public health policies to monitor asbestos exposure and complications.

Does previous asbestos exposure increase the risk of a post coronary artery bypass graft (CABG) pleural effusion – a routine data study?

BackgroundDevelopment of pleural effusion (PE) following CABG is common. Post-CABG PE are divided into early- (within 30 days of surgery) and delayed-onset (30 days–1 year) which are likely due to distinct pathological processes. Some experts suggest asbestos exposure may confer an independent risk for late-onset post-CABG PE, however no large studies have explored this potential association.Research questionTo explore possible association between asbestos exposure and post-CABG PE using routine data.MethodsAll patients who underwent CABG 01/04/2013–31/03/2018 were identified from the Hospital Episode Statistics (HES) Database. This England-wide population was evaluated for evidence of asbestos exposure, pleural plaques or asbestosis and a diagnosis of PE or PE-related procedure from 30 days to 1 year post-CABG. Patients with evidence of PE three months prior to CABG were excluded, as were patients with a new mesothelioma diagnosis.Results68,150 patients were identified, of whom 1,003 (1%) were asbestos exposed and 2,377 (3%) developed late-onset PE. After adjusting for demographic data, Index of Multiple Deprivation and Charlson Co-morbidity Index, asbestos exposed patients had increased odds of PE diagnosis or related procedure such as thoracentesis or drainage (OR 1.35, 95% CI 1.03–1.76, p = 0.04). In those with evidence of PE requiring procedure alone, the adjusted OR was 1.66 (95% CI 1.14–2.40, p = 0.01). Additional subgroup analysis of the 518 patients coded for pleural plaques and asbestosis alone revealed an adjusted OR of post-CABG PE requiring a procedure of 2.16 (95% CI 1.38–3.37, p = 0.002).InterpretationThis large-scale study demonstrates prior asbestos exposure is associated with modestly increased risk of post-CABG PE development. The risk association appears higher in patients with assigned clinical codes indicative of radiological evidence of asbestos exposure (pleural plaques or asbestosis). This association may fit with a possible inflammatory co-pathogenesis, with asbestos exposure ‘priming’ the pleura resulting in greater propensity for PE evolution following the physiological insult of CABG surgery. Further work, including prospective studies and clinicopathological correlation are suggested to explore this further.

Change trends and related risk factors of disease burden on mesothelioma in Jiangsu Province from 1990 to 2019

Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.

Oxidative Stress and DNA Damages Induced by Occupational Exposure to Asbestos: A Systematic Review.

Asbestos is one of the most important environmental and occupational carcinogens. Nevertheless, the mechanisms by which asbestos fiber exposure causes chronic diseases are not fully understood. We performed the first systematic review on the epidemiological evidence to examine the association between occupational exposure to asbestos and oxidative stress and DNA damage. In this systematic review study, the PubMed and Scopus databases were searched for English-language publications. Eleven cross-sectional studies were included in the systematic review. A literature search was conducted by the main keywords including "Asbestos", "crocidolite", "chrysotile", "amphibole", "amosite", "Oxidative Stress", "DNA Damage", and "DNA injury". To evaluate the quality of studies, the "Newcastle-Ottawa Quality Assessment Scale" (NOS) was used. Overall, 1235 articles were achieved by searching in databases. Finally, by considering the inclusion, and exclusion criteria, 11 articles were conducted for this study. These studies were published between 1986 and 2020. Oxidative stress and DNA damage can occur in exposure to asbestos. Among various biomarkers, 8-OHdG is the best. The analysis of 8-oxodG in asbestos workers can help identify subjects with a higher level of genotoxic damage. This systematic review suggests that oxidative stress and DNA damage are two main outputs of asbestos exposure. Therefore, oxidative stress and DNA damage biomarkers can be used for identifying subjects at higher risk of cancer. These findings support policy initiatives aimed at detecting and eliminating asbestos fiber exposure and preventing potential health hazards in occupational settings.

Global, regional, and national burden of asbestosis from 1990 to 2019 and the implications for prevention and control

BackgroundAsbestosis is a common pneumoconiosis caused by long-term asbestos exposure. Analysis of the burden of asbestosis would help in creating informed public health strategies. MethodsData on asbestosis were analyzed using the Global Burden of Disease study 2019. The estimated annual percentage change (EAPC) was calculated to demonstrate temporal trends in the age-standardized rate (ASR) of asbestosis from 1990 to 2019. ResultsGlobally, 36,339 incident cases of asbestosis, led to 3572 deaths and 71,225 disability adjusted life years (DALYs) in 2019. During 1990–2019, the overall ASRs of incidence and DALYs declined by an annual average of 0.29 % and 0.27 %, with the respective EAPCs being −0.29 (95 % confidence interval [CI]: −0.43, −0.14) and −0.27 (95%CI: −0.53, −0.01). The ASRs of mortality increased with EAPC of 0.65 (95%CI: 0.34, 0.96). Trends in incidence and prevalence rose in females, but declined in males. The asbestosis burden was heterogeneous across regions and countries. The heaviest burden of asbestosis was observed in the United States, India, and China. Trends in ASRs of asbestosis varied across countries/territories. Pronounced increasing trends in incidence and prevalence occurred in Georgia, Iran, and Croatia. ConclusionsDecreasing incident trend of asbestosis was observed globally over the past three decades. However, the ongoing asbestosis burden highlighted that asbestosis remained a challenge to public health, and cost-effective measures were required to reduce the asbestosis burden.

Iron links endogenous and exogenous nanoparticles

Current progress in biology and medical science is based on the observation at the level of nanometers via electron microscopy and computation. Of note, the size of most cells in higher species exists in a limited range from 5 to 50 μm. Recently, it was demonstrated that endogenous extracellular nanoparticles play a role in communication among various cellular types in a variety of contexts. Among them, exosomes in serum have been established as biomarkers for human diseases by analyzing the cargo molecules. No life on the earth can survive without iron. However, excess iron can be a risk for carcinogenesis in rodents and humans. Nano-sized molecules may cause unexpected bioeffects, including carcinogenesis, which is a process to establish cellular iron addiction with ferroptosis-resistance. Asbestos and carbon nanotubes are the typical examples, leading to carcinogenesis by the alteration of iron metabolism. Recently, we found that CD63, one of the representative markers of exosomes, is under the regulation of iron-responsive element/iron-regulatory protein system. This is a safe strategy to share excess iron in the form of holo-ferritin between iron-sufficient and -deficient cells. On the other hand, damaged cells may secrete holo-ferritin-loaded exosomes as in the case of macrophages in ferroptosis after asbestos exposure. These holo-ferritin-loaded exosomes can cause mutagenic DNA damage in the recipient mesothelial cells. Thus, there is an iron link between exogenous and endogenous nanoparticles, which requires further investigation for better understanding and the future applications.

Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations.

Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR). Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria. In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was -16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62-5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55-4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001). Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.

Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma.

Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells' transformation. Chronic inflammation supported by "frustrated" macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells' features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor-host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.

APE-1/Ref-1 Inhibition Blocks Malignant Pleural Mesothelioma Cell Proliferation and Migration: Crosstalk between Oxidative Stress and Epithelial Mesenchymal Transition (EMT) in Driving Carcinogenesis and Metastasis.

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and epithelial mesenchymal transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos-related primary oxidative damage is counteracted in the lungs by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet been fully understood. Moreover, asbestos exposure has been associated with induced EMT events, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells; as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Taken as a whole, these results show, for the first time, crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, thus improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

Australia’s Ongoing Challenge of Legacy Asbestos in the Built Environment: A Review of Contemporary Asbestos Exposure Risks

Asbestos remains ubiquitous in the Australian built environment. Of the 13 million tonnes of asbestos products installed in earlier decades, an estimated 50% remain in situ today. Because of the extensive past use of asbestos, and the increasing age of these products, the potential for exposure to asbestos fibres in both indoor and outdoor environments remains high, even while the actual asbestos exposure levels are mostly very low. Sources of these exposures include disturbance of in situ asbestos-containing materials (ACMs), for example during renovations or following disaster events such as fires, cyclones and floods. Our understanding of the risk of asbestos-related disease arising from long-term low-level or background exposure, however, is poor. We provide the most up-to-date review of asbestos exposure risks currently affecting different groups of the Australian population and the settings in which this can manifest. From this, a need for low-level asbestos monitoring has emerged, and further research is required to address whether current exposure monitoring approaches are adequate. In addition, we make the case for proactive asbestos removal to reduce the risk of ongoing asbestos contamination and exposure due to deteriorating, disturbed or damaged ACMs, while improving long-term building sustainability, as well as the sustainability of limited resources.