Asbestos Diseases Research Institute

Background: Asbestos remains a significant global public health issue, with approximately 255,000 deaths attributed to exposure each year, primarily through occupational contact. Mesothelioma rates continue to rise, particularly in areas with a history of industrial exposure. Despite this burden, many countries lack reliable surveillance systems. Colombia has clusters like the one observed in Sibaté, highlighting the urgency of establishing structured, evidence-based surveillance systems. Objective: The aim is to synthesize international experiences to guide the design and implementation of surveillance strategies in Colombia and other low- and middle-income countries facing similar challenges. Methods: Following the JBI methodology for scoping reviews, comprehensive searches were conducted in Medline (PubMed), Embase, the Cochrane Library (OVID), and Google Scholar. Only English-language articles were included, and no time restrictions were applied. Results: Fourteen studies from 11 countries were included, with the majority coming from Italy, followed by Colombia and Brazil. Three main themes emerged: (1) numerous cohort studies reported increased risks of mesothelioma and lung cancer among asbestos-exposed workers, supporting the need for long-term follow-up; (2) structured surveillance systems-such as Italy's ReNaM and Brazil's Datamianto-demonstrated effective models combining data integration, regular medical evaluations, and policy enforcement; (3) considerable variability in surveillance design, target populations, and reporting standards, especially between high-income and resource-limited settings, highlighting the lack of global standardization. Conclusions: Structured, context-specific surveillance programs are essential to identify and manage the health burden of asbestos exposure. International models offer practical frameworks that could be adapted to Colombia's needs. Investing in such systems would strengthen public health responses, improve early detection of asbestos-related diseases (ARDs), and support environmental and occupational justice in affected communities. The included studies do not mention monitoring according to the degree of exposure.

BackgroundRice bran is the outer layer of rice grains (Oryza sativa). Due to its rich bioactive components, it has long been used in cosmetics. However, the mechanism by which it delays skin aging remains unclear.MethodsIn this study, volatile polar solvents combined with microbial fermentation were utilized to enhance the yield and bioavailability of functional components in rice bran extract (RBE). The crude RBE was fermented with Aspergillus oryzae for 14 days to promote enzymatic decomposition into smaller and more bioavailable molecules. The components in the fermented RBE were qualitatively analyzed by UPLC-QTOF-MS/MS. The expression of collagen in two-dimensional and three-dimensional cell cultures was evaluated by qPCR technology. The expressions of collagen and elastin and the changes in water content and elastic modulus in the skin of mice were evaluated by histopathology, immunofluorescence staining, and transepidermal water loss (TEWL).ResultsThrough UPLC-QTOF-MS/MS analysis, eight key compounds, including azelaic acid, ferulic acid, γ-tocotrienols, and squalene, were identified in RBE, mainly lipids and polyphenols. The treatment of RBE significantly upregulated the expression of type I collagen in MSF cells and the expression of type III collagen in MSF 3D cell spheres (by approximately 12 times). The results of tissue staining showed that the content of collagen in the skin after RBE treatment increased by 10% compared with the control group. The results of immunofluorescence staining confirmed that RBE could increase the content of elastin in the skin. The TEWL results showed that the skin moisture content and elastic coefficient of mice treated with RBE increased by more than 10% compared with those of the untreated group.ConclusionBoth in vitro and in vivo studies have shown that RBE can significantly improve the synthesis of collagen and elastin in the skin, reduce water loss in mouse skin, increase collagen deposition in the skin, and ultimately improve skin elasticity and overall quality. This green, solvent-efficient, and fermentation-enhanced approach offers a sustainable strategy for utilizing rice bran as a high-value cosmetic ingredient with strong potential for skincare applications.

Although the association between certain occupational exposures and the development of autoimmune rheumatic disease was first described over a century ago, this association has only become more widely recognized in the past 10 years because of the use of high-silica-content engineered stone in construction and home renovation. There is now a substantial and growing body of evidence that occupational dust and chemical exposure, be it through mining, stonemasonry, building or other trades, increases the risk of various systemic autoimmune rheumatic diseases (SARDs) including rheumatoid arthritis and systemic sclerosis. Although the pathogenic mechanisms of silica-induced autoimmunity are not fully elucidated, it is thought that alveolar macrophage ingestion of silica and the ensuing phagosomal damage is an initiating event that ultimately leads to production of autoantibodies and immune-mediated tissue injury. The purportedly causal association between occupational exposure to chemicals, such as organic solvents, and an increased risk of SARDs is less frequently recognized compared with silica dust, and its immunopathogenesis is less well understood. An appreciation of the importance of occupational dust and chemical exposures in the development of SARDs has implications for workplace health and safety regulations and offers a unique opportunity to better understand autoimmune disease pathogenesis and implement preventative strategies.

BackgroundChemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects. Therefore, there is a need for alternative immunomodulatory drugs that enhance chemotherapy.MethodsWe used gene expression data from cyclophosphamide (CY) responders and non-responders to identify existing clinically approved drugs that could phenocopy a chemosensitive tumor microenvironment (TME), and tested combination treatments in multiple murine cancer models.ResultsThe vitamin A derivative tretinoin was the top predicted upstream regulator of response to CY. Tretinoin pre-treatment induced an inflammatory, interferon-associated TME, with increased infiltration of CD8 + T cells, sensitizing the tumor to subsequent chemotherapy. However, while combination treatment significantly improved survival and cure rate in a CD4+ and CD8+ T cell dependent manner in AB1-HA murine mesothelioma, this effect was model-selective, and could not be replicated using other cell lines.ConclusionsDespite the promising data in one model, the inability to validate the efficacy of combination treatment in multiple cancer models deprioritizes tretinoin/cyclophosphamide combination therapy for clinical translation.

Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.

Abstract Single cell RNA sequencing is an ubiquitous method for studying changes in cellular states within and across conditions. Differential expression (DE) analysis may miss subtle differences, especially where transcriptional variability is not unique to a specific condition, but shared across multiple conditions or phenotypes. Here, we present CDR-g (Concatenate-Decompose-Rotate genomics), a fast and scalable strategy based on spectral factorisation of gene coexpression matrices. CDR-g detects subtle changes in gene coexpression across a continuum of biological states in multi-condition single cell data. CDR-g collates these changes and builds a detailed profile of differential cell states. Applying CDR-g, we show that it identifies biological pathways not detected using conventional DE analysis and delineates novel, condition-specific subpopulations in single-cell datasets.

The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients. Here, we map the transcriptional profiles of 144 responding and non-responding tumours within two mouse models at four time points during ICB. We find that responding tumours display on/fast-off kinetics of type-I-interferon (IFN) signaling. Phenocopying of this kinetics using time-dependent sequential dosing of recombinant IFNs and neutralizing antibodies markedly improves ICB efficacy, but only when IFNβ is targeted, not IFNα. We identify Ly6C+/CD11b+ inflammatory monocytes as the primary source of IFNβ and find that active type-I-IFN signaling in tumour-infiltrating inflammatory monocytes is associated with T cell expansion in patients treated with ICB. Together, our results suggest that on/fast-off modulation of IFNβ signaling is critical to the therapeutic response to ICB, which can be exploited to drive clinical outcomes towards response.

Abstract Particles longer than 5 μm and with a length/diameter ratio >3 are defined as fibers. Asbestos or other fibers are still identified in residential environments due to the emission from asbestos‐used building materials. The respiratory system is the primary route of asbestos exposure; under a longer residence time, asbestos‐related adverse health effects are inevitable. Currently, asbestos fibers have been replaced with man‐made vitreous fibers (MMVFs); however, studies have revealed some similar biological effects of MMVFs with asbestos. Therefore, MMVFs‐induced diseases need to be determined by analyzing their deposition characteristics and foci in human respiratory tracts. In this study, we used computational fluid dynamics method to investigate fibers' airflow and deposition patterns in two realistic human respiratory models. Two drag models were used to predict the deposition of uniform 1 μm (asbestos) and 3.66 μm (carbon fiber‐CF) diameter, 15–300 μm long fibers. Two drag models provided comparable results with the experimental data. Comparatively, asbestos deposition was independent of fiber length, while CF deposition increased proportionally to fiber length. The highest level of local deposition was detected in the anterior nasal cavity. The results obtained from this study can extend current knowledge of human vitreous fiber exposure‐related lung diseases.

TPS8586 Background: Standard first line treatment for unresectable malignant pleural mesothelioma (MPM) is platinum-based chemotherapy with pemetrexed. Two recent, single-arm, phase 2 trials (DREAM1 and PrE05052) combining the PD-L1 inhibitor durvalumab and standard first line cisplatin and pemetrexed (CP) exceeded pre-specified criteria for proceeding to phase 3. DREAM3R aims to determine the effectiveness of adding durvalumab to first line CP chemotherapy in advanced MPM. Methods: Treatment-naïve patients with advanced MPM will be randomised (2:1) to EITHER durvalumab 1500 mg every 3 weeks plus doublet chemotherapy (cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) every 3 weeks for 4-6 cycles, followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target sample size is 480 patients (320 durvalumab, 160 control) recruited over 27 months, with follow up for an additional 24 months. This provides over 85% power if the true hazard ratio for overall survival is 0.70, with 2-sided alpha of 0.05, assuming a median survival of 15 months in the control group. Key inclusion criteria: MPM of any histological subtype; measurable disease as per RECIST 1.1 modified for mesothelioma (mRECIST 1.1) without prior radiotherapy to these sites; ECOG PS 0-1; and, adequate hematologic, renal, and liver function tests. Key exclusion criteria: prior systemic anticancer treatment for MPM; diagnosis based only on cytology or fine needle aspiration biopsy; contraindication to immunotherapy; and conditions requiring immunosuppressives or corticosteroids. Stratification: Age (18-70 years vs. > 70), sex, histology (epithelioid vs. non-epithelioid), and region (USA vs. ANZ). The primary endpoint is overall survival. Secondary endpoints include progression-free survival; objective tumour response (by mRECIST 1.1 and iRECIST); adverse events; health-related quality of life; and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DREAM and PrE0505 studies, PD-L1 expression, tumour mutation burden, nuanced genomic characteristics, and HLA subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma. Clinical trial information: NCT04334759. and ACTRN 12620001199909.