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22 Apr 2024 at 01:54
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Bibliography on: Mesothelioma and Asbestos


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RJR: Recommended Bibliography 22 Apr 2024 at 01:54 Created: 

Mesothelioma and Asbestos

Mesothelioma is a rare, but deadly form of cancer that is often (nearly always) associated with prior exposure to asbestos. The latency between exposure and disease onset is long, usually 20-50 years, making this a difficult cause-effect system to study.

Created with PubMed® Query: ( asbestos AND mesothelioma ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2024-04-20

Gómez Herrero H, B Álvarez Galván (2024)

Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.

Radiologia, 66 Suppl 1:S3-S9.

BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography.

MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis.

RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%.

CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.

RevDate: 2024-04-19

Ejegi-Memeh S, Sherborne V, Mayland C, et al (2024)

Mental health and wellbeing in mesothelioma: A qualitative study exploring what helps the wellbeing of those living with this illness and their informal carers.

European journal of oncology nursing : the official journal of European Oncology Nursing Society, 70:102572 pii:S1462-3889(24)00070-X [Epub ahead of print].

PURPOSE: Mesothelioma is an incurable, asbestos related cancer with a poor prognosis. Little is known about how patients and carers living with the condition manage their mental health and wellbeing needs. This paper reports findings on interventions being used by patients and informal carers living with mesothelioma and those which they find most helpful.

METHODS: In-depth interviews with patients (n = 10) and (informal) carers (n = 11) living with mesothelioma in the UK. We analysed our data inductively using a reflexive thematic analysis approach.

RESULTS: Participants described the importance of both smaller and larger actions and strategies which helped with their mental health. This included spending more time with family and friends and going on holidays. Professionals who participants said supported their mental health journey included not only specialist nurses and mental health professionals but also legal and Asbestos Support Group professionals. The latter demonstrates the unique needs and support required for this population. Exposure to asbestos as the cause of mesothelioma, has led to a social justice aspect of the experience of living with this cancer. Participants reported the importance of collective action to their mental health and wellbeing. The data indicate that patients and carers may have distinct mental health and wellbeing requirements and need to manage these in different ways at different times.

CONCLUSIONS: Findings have implications for nurses and other key professionals working in healthcare, community and legal settings supporting this client group, and for those living with mesothelioma who want to understand ways to enhance their own wellbeing.

RevDate: 2024-04-18

Liu RA, Wang BY, Chen X, et al (2024)

Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.

Genetic testing and molecular biomarkers [Epub ahead of print].

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

RevDate: 2024-04-17

Yang SR, Jayakumaran G, Benhamida J, et al (2024)

Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features.

Clinical cancer research : an official journal of the American Association for Cancer Research pii:743086 [Epub ahead of print].

PURPOSE: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined.

EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using the FACETS algorithm.

RESULTS: 210 patients were evaluable for LOH analysis using FACETS. In this cohort, GNH was detected in 10 cases (4.8%). Compared to non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, while SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, p=0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Out of three patients with GNH DPMs who received immune checkpoint blockade (ICB), two achieved a clinician assessed partial response.

CONCLUSIONS: GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary ICB response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.

RevDate: 2024-04-17

Mirra L, Beretta GL, Lisini D, et al (2024)

Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.

Current medicinal chemistry pii:CMC-EPUB-139795 [Epub ahead of print].

Pleural mesothelioma is a rare neoplastic disease with aggressive features. Patient survival is poor due to the lack of early symptoms and the absence of effective therapeutic strategies. The development of pleural mesothelioma is mainly associated with asbestos exposure and related chronic inflammation. From a molecular-based perspective, this disease is a heterogeneous tumor lacking actionable alterations. The median overall survival of patients affected by this tumor does not exceed 16 months from diagnosis. Molecular and biochemical approaches have shown that this disease is characterized by resistance to drug-induced apoptosis associated with the activation of cell survival pathways and expression of anti-apoptotic proteins. Thus, there is an urgent need to develop efficient and safe therapeutic strategies. Here, we review the pharmacological options available for the treatment of this disease with specific reference to the antitumor agents used in systemic therapies. In addition, novel pharmacological approaches, such as drug delivery tools, to improve pleural mesothelioma treatment are discussed.

RevDate: 2024-04-15

Gibson AEJ, Ahmed W, Longworth L, et al (2024)

Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.

The patient [Epub ahead of print].

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers.

METHODS: This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models.

RESULTS: Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving.

CONCLUSIONS: This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.

RevDate: 2024-04-15

Miller E, Beckett EM, Cheatham D, et al (2024)

A review of the mesotheliogenic potency of cleavage fragments found in talc.

Toxicology and industrial health [Epub ahead of print].

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

RevDate: 2024-04-09

Kadariya Y, Sementino E, Ruan M, et al (2024)

Low Exposures to Amphibole or Serpentine Asbestos in Germline Bap1-mutant Mice Induce Mesothelioma Characterized by an Immunosuppressive Tumor Microenvironment.

Cancer research communications, 4(4):1004-1015.

UNLABELLED: Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene-environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM.

SIGNIFICANCE: We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.

RevDate: 2024-04-07

Stevens ME, Paustenbach DJ, Lockhart NJ, et al (2024)

The presence of erionite in North American geologies and the estimated mesothelioma potency by region.

Inhalation toxicology [Epub ahead of print].

OBJECTIVE: Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers.

MATERIALS AND METHODS: Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined.

RESULTS AND DISCUSSION: The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5.

CONCLUSION: The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).

RevDate: 2024-03-29

Lanfranco A, Rakhshan S, Alberti D, et al (2024)

Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes.

European journal of medicinal chemistry, 270:116334 pii:S0223-5234(24)00214-9 [Epub ahead of print].

Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.

RevDate: 2024-03-27

Mei W, Zhang YP, SJ Yang (2024)

[Research progress on pathogenesis of malignant mesothelioma].

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases, 42(3):232-240.

The occurrence of malignant mesothelioma is related to exposure of asbestos. And many researchers have conducted in-depth analysis of the molecular changes of mesothelioma, showed that its molecular characteristics were chromosome changes, including chromosome rearrangement, gene mutation and gene deletion. Recent studies have strengthened our understanding of molecular characterization of mesothelioma, such as targeted mutations of tumor suppressor genes, differential gene expression, changes of miRNA and signal pathways. It is of great significance for the early diagnosis, clinical treatment and prognosis of malignant mesothelioma to explore the pathogenesis and development of malignant mesothelioma. This article reviews the research progress on the pathogenesis and carcinogenesis-related molecules of malignant mesothelioma.

RevDate: 2024-03-27

Wang ZZ, Zhang JJ, Song PP, et al (2024)

[Survival analysis of 37 cases of malignant mesothelioma].

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases, 42(3):191-195.

Objective: To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma. Methods: In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) (P<0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients (P>0.05) . Conclusion: The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.

RevDate: 2024-03-27

Mirabelli D, Somigliana AB, Azzolina D, et al (2024)

Lung fibre burden and risk of malignant mesothelioma in shipyard workers: a necropsy-based case-control study.

Annals of work exposures and health pii:7635545 [Epub ahead of print].

OBJECTIVES: In Italy, the highest pleural cancer mortality and incidence have been observed among Italian regions where the 2 largest Italian shipyards were (and are) located. The objective of this study was to assess the exposure-response relationship for mesothelioma among male workers employed in the Monfalcone, Italy, shipyard.

METHODS: We conducted a necropsy-based case-control study. Cases (N = 102) were mesothelioma decedents and controls were those with lung cancer (N = 84). Complete job histories were available; the lung fibre content was measured using a scanning electron microscope with X-ray fluorescence, after sample preparation according to the European Respiratory Society guidelines. Odds ratios and 95% confidence intervals of mesothelioma by fibre type and lung fibre burden, as a categorical or continuous variable, were assessed by unconditional logistic regression, adjusted for age and time since exposure cessation. Analyses for the amphibole and chrysotile lung fibre burden were mutually adjusted. We calculated a cumulative exposure index by applying a job-exposure matrix to the job histories of study cases and assessed its correlation with the lung fibre burden.

RESULTS: We found an odds ratio of 22.0 (confidence intervals 5.66-85.7) for the highest lung fibre burden category (mean 43.8 million total asbestos fibres per gram of dry tissue) compared with the reference (mean 0.48). Using log10-transformed lung fibre burden, we found that the odds ratio was 3.71 (confidence intervals 2.03-6.79) for a 10-fold lung fibre burden increase. Results for the amphibole lung fibre burden were similar. Odds ratios increased over chrysotile lung fibre burden categories (P-trend = 0.025), and the odds ratio for a 10-fold increase was 4.73 (confidence intervals 0.32-70.4).

CONCLUSIONS: The cumulative exposure index was correlated with total and amphibole lung fibre burden, but not with chrysotile lung fibre burden. Mesothelioma risk was proportional to total, amphibole, and chrysotile lung fibre burden in shipyard workers.

RevDate: 2024-03-27

Roggli VL, Pavlisko EN, Glass CH, et al (2024)

Response to the editor-Environmental Research this letter is a critique of the paper by Roggli et al. (1) regarding chronological trends of the fiber burden in mesothelioma cases.

RevDate: 2024-03-24

Sherborne V, Wood E, Mayland CR, et al (2024)

The mental health and well-being implications of a mesothelioma diagnosis: A mixed methods study.

European journal of oncology nursing : the official journal of European Oncology Nursing Society, 70:102545 pii:S1462-3889(24)00043-7 [Epub ahead of print].

PURPOSE: Mesothelioma is an incurable, asbestos-related cancer with a poor prognosis. There is scant evidence about the mental health and well-being impacts on patients and carers living with the illness. This study aimed to investigate mesothelioma's impact on mental health and well-being and the scale of mental health conditions in patients and informal carers.

METHODS: A mixed-methods design was used: a cross-sectional survey of mesothelioma patients and informal carers plus semi-structured interviews with patients and carers. The survey used validated scales collecting data on mental health aspects of mesothelioma: the EQ5D to assess health-related quality-of-life; the Hospital Anxiety and Depression scale; the PCL-5 to assess Posttraumatic Stress; and the Posttraumatic Growth Inventory. The datasets were integrated during analysis.

RESULTS: 96 useable survey responses were received. A clinical level of depression was reported by 29 participants (30.21%), of anxiety by 48 (50%), of posttraumatic distress disorder by 32 (33.33%), and of posttraumatic growth by 34 (35.42%). Carers had worse scores than patients. Three main themes were developed from interviews with 10 patients and 11 carers: 'Prognosis', 'Support from services', and 'Social connections and communication'.

CONCLUSIONS: Healthcare professionals delivering a mesothelioma diagnosis require regular training in communication skills plus updating in current treatment options, so they provide an appropriate mix of realism and hope. Better signposting to mental health support is needed for patients and carers. Our introduction of posttraumatic growth into the mesothelioma literature is novel. We recommend specialist nurses are trained to recognise, understand, and foster posttraumatic growth.

RevDate: 2024-03-23

Gill RR, Nowak AK, Giroux DJ, et al (2024)

The IASLC Mesothelioma Staging Project: Proposals for Revisions of the 'T' Descriptors in the Forthcoming 9[th] Edition of the TNM Classification for Pleural Mesothelioma.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer pii:S1556-0864(24)00086-8 [Epub ahead of print].

BACKGROUND: The primary tumor (T) component in the 8[th] edition of pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of pleural tumor has been shown to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming 9[th] edition of the PM staging system.

METHODS: The International Association for the Study of Lung Cancer (IASLC) prospectively collected data on PM patients. Sum of maximum pleural thickness (Psum) was recorded. Optimal combinations of Psum and 8[th] edition cT descriptors were assessed using recursive binary splitting algorithm, with bootstrap resampling to correct for the adaptive nature of the splitting algorithm and validated in the 8[th] edition data. Overall survival (OS) was calculated by the Kaplan-Meier method and differences in OS assessed by the log-rank test.

RESULTS: Of 7,338 patients submitted, 3,598 were eligible for cT analysis and 1,790 had Psum measurements. Recursive partitioning identified optimal cutpoints of Psum at 12 and 30 mm which, in combination with extent of invasion, yielded four prognostic groups for OS. Fmax >5mm indicated poor prognosis. cT4 category (based on invasion) showed similar performance to 8[th] edition. Three 8[th] edition descriptors were eliminated based on low predictive accuracy. Eighth edition pT descriptors remained valid in 9[th] edition analyses.

CONCLUSION: Given reproducible prognostication by Psum, size criteria will be incorporated into cT1-T3 categories in the 9th edition. Current cT4 category and all pT descriptors will be maintained, with reclassification of fissural invasion as pT2.

RevDate: 2024-03-22

Singh S, Roy Pradhan S, Yadav A, et al (2023)

Banning asbestos in talcum powder: Time for action in India.

Dialogues in health, 3:100158 pii:S2772-6533(23)00062-X.

Long-term use of asbestos-contaminated talcum power has been reported to be the main causative agent for carcinogenesis in many research studies. In recent developments Johnson & Johnson has lost multimillion-dollar lawsuits for being associated with the development of mesothelioma and ovarian cancer by its talc-based baby powder. In May 2020, the company announced, the end of the sale of its baby powder in the USA and Canada and in August 2022, announced the global discontinuation by 2023. However, in India vast proportions of people are using talc-based baby powder and the products are readily available in the market. The purpose of this communication is to create awareness and draw attention of authorities for effective regulation, including prohibition of sale and retraction of the contaminated talc-based products from the Indian market at the earliest.

RevDate: 2024-03-21

Singh A, Bansal C, Singla D, et al (2024)

Peritoneal Malignant Mesothelioma Metastasizing to Lymph Node in Young Male-a Case Report.

Indian journal of surgical oncology, 15(1):145-148.

Peritoneal malignant mesothelioma is an uncommon neoplasm with a poor prognosis. We hereby report a case of a 20-year-old male, first diagnosed on biopsy with axillary lymph node metastasis. He presented with abdominal pain and axillary lymphadenopathy, with no history of asbestos exposure. CECT showed peritoneal thickening and ascites. Ascitic fluid cytology showed reactive morphology. The diagnosis of metastatic deposits of malignant mesothelioma was made on histopathology and confirmed by immunohistochemistry. Tumor cells were immune-reactive for CK 5/6, calretinin, D2-40, and WT1 and negative for TTF1, CK 20, and CD 3. This case report has two important highlights-(i) unusual presentation with axillary lymph node metastasis leading to diagnostic dilemma in a young male with no asbestos exposure history and (ii) confirmatory diagnostic role of IHC in Peritoneal malignant mesothelioma.

RevDate: 2024-03-20

Tuncel T, Ak G, Güneş HV, et al (2024)

Complex Genomic Rearrangement Patterns in Malignant Pleural Mesothelioma due to Environmental Asbestos Exposure.

Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, 43(2):13-27.

Malignant pleural mesothelioma (MPM) is a rare type of cancer, and its main risk factor is exposure to asbestos. Accordingly, our knowledge of the genomic structure of an MPM tumor is limited when compared to other cancers. In this study, we aimed to characterize complex genomic rearrangement patterns and variations to better understand the genomics of MPM tumors. We comparatively scanned 3 MPM tumor genomes by Whole-Genome Sequencing and High-Resolution SNP array. We also used various computational algorithms to detect both CNAs and complex chromosomal rearrangements. Genomic data obtained from each bioinformatics tool are interpreted comparatively to better understand CNAs and cancer-related Nucleotide variations in MPM tumors. In patients 1 and 2, we found pathogenic nucleotide variants of BAP1, RB1, and TP53. These two MPM genomes exhibited a highly rearranged chromosomal rearrangement pattern resembling Chromomanagesis particularly in the form of Chromoanasynthesis. In patient 3, we found nucleotide variants of important cancer-related genes, including TGFBR1, KMT2C, and PALLD, to have lower chromosomal rearrangement complexity compared with patients 1 and 2. We also detected several actionable nucleotide variants including XRCC1, ERCC2. We also discovered the SKA3-DDX10 fusion in two MPM genomes, which is a novel finding for MPM. We found that MPM genomes are very complex, suggesting that this highly rearranged pattern is strongly related to driver mutational status like BAP1, TP53 and RB1.

RevDate: 2024-03-19

Rota M, Viscardi A, Maghin F, et al (2024)

Mesothelioma among seamen: a systematic review and meta-analysis.

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) pii:00008469-990000000-00131 [Epub ahead of print].

OBJECTIVES: Navy personnel and seafarers live and work 24 h per day in the shipboard environment and they are exposed to asbestos fibers released into the confined spaces aboard ships. We conducted a systematic review and meta-analysis to quantify the mesothelioma risk of seamen working aboard ships, either commercial or naval vessels, as compared to that of the general population.

METHODS: We carried out a literature search in MEDLINE through PubMed and EMBASE, from inception to 31 December 2021, of all studies on seamen working aboard ships, either commercial or naval vessels, characterized by exposure to asbestos and providing mesothelioma risk estimates. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. The pooled standardized mortality ratio (SMR) was computed across eligible studies. The study protocol was registered on PROSPERO and reporting followed the preferred reporting items for systematic reviews and meta-analyses guidelines.

RESULTS: A total of 10 studies published from 1990 to 2020 were considered eligible and included in the systematic review and meta-analysis. All the included studies were of good quality, with a median score of seven out of nine. Overall, there were 235 mesothelioma cases/deaths in the included studies versus 115.6 expected, with a pooled SMR of 2.11 (95% confidence intervals, 1.70-2.62), in the absence of a significant between-study heterogeneity (I2 = 39%, P = 0.11).

CONCLUSION: A more than double excess risk for mesothelioma among seamen working aboard ships emerged from our meta-analysis.

RevDate: 2024-03-19

Dodson RF, Moline J, Salinas CD, et al (2024)

Elongated particulate burden in an individual who died of mesothelioma and had an occupational history as a talc "mucker".

Inhalation toxicology [Epub ahead of print].

INTRODUCTION: Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual's work history including working as a "mucker" at a specific "industrial" talc mine.

METHODS: Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed.

DISCUSSIONS/CONCLUSIONS: The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a "non-commercial" type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.

RevDate: 2024-03-19

Miao X, Yao T, Dong C, et al (2024)

Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990-2019 and prediction to 2035: worsening or improving?.

BMC public health, 24(1):832.

Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990-2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of - 1.05(95%CI: -1.2, -0.89) and -1.53(95%CI: -1.71, -1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.

RevDate: 2024-03-19
CmpDate: 2024-03-19

Barnes H, RF Hoy (2024)

Changing trends in mesothelioma: Important lessons for an occupational disease registry.

Respirology (Carlton, Vic.), 29(4):269-270.

RevDate: 2024-03-15

Frank AL (2024)

To the Editor-environmental research this letter is a critique of the paper by Roggli et al. (regarding chronological trends of the fiber burden in mesothelioma cases.

RevDate: 2024-03-14

Chellini E (2024)

[Is the epidemiological surveillance of malignant mesothelioma implemented in Italy still valid and necessary?].

Epidemiologia e prevenzione, 48(1):78-84.

The register of malignant mesotheliomas can still play an informative role in the context of both remediation activities and the health surveillance of former asbestos-exposed persons, and become an epidemiological surveillance system on the harmful effects of exposure to asbestos. It must, however, maintain and improve the level of quality achieved, resolve the problems that have emerged in the interaction between the local level (where cases and their exposure histories are identified, registered, assessed, and medical insurance procedures activated) and the central insurance body that also manages the national register, and become an active participant in research, including clinical research. All this is important to meet the social and welfare justice needs of individual cases.

RevDate: 2024-03-11

Costantino C, Ledda C, Riccò M, et al (2024)

Decade-long insights: tracking asbestos-related health impacts among formerly exposed workers in Palermo, Italy.

Annali di igiene : medicina preventiva e di comunita [Epub ahead of print].

BACKGROUND: Asbestos is a foremost occupational carcinogen globally. Despite the prohibition under Law 257/1992, Italy persists as one of the European nations most burdened by asbestos-related diseases (ARDs). This research assessed ARD cases in asbestosexposed workers from the Province of Palermo, Italy, spanning 2010-2021.

METHODS: Data acquisition utilized the epidemiological dataset from the 'Service of Prevention and Safety on Work Environment' under the Prevention Department of Palermo's Local Health Authority (LHA).

RESULTS: Between 2010 and 2021, we identified 245 ARD instances, comprising 163 Asbestosis/Pleural plaques, 41 Lung Cancers, 38 Mesotheliomas, and 3 unspecified cases. Multivariate analysis indicated a notable decline in temporal exposure for mesothelioma (HR=0.933; 95% CI=0.902-0.965) and lung cancer (HR=0.93; 95% CI=0.90-0.978) relative to pleural plaques/asbestosis. Tobacco use displayed a pronounced correlation with lung cancer (smoker HR=64.520 95% CI=13,075-318.390; former smoker HR=20.917 95% CI=4,913-89.048). A significant link was observed between mesothelioma and pleural plaques/asbestosis in those employed in shipbuilding and repair (HR=0.371 95% CI=0.155-0.892).

CONCLUSIONS: ARDs persist in clinical observations, even following the 1992 cessation of asbestos-related activities, emphasizing an enduring public health challenge. Enhancing prevention strategies is paramount, focusing on amplifying anamnestic and occupational data collection, thereby facilitating superior early diagnosis strategies for these maladies in the occupationally exposed cohort.

RevDate: 2024-03-11

Liu J, Lu Y, Liu Y, et al (2024)

A gene signature linked to fibroblast differentiation for prognostic prediction of mesothelioma.

Cell & bioscience, 14(1):33.

BACKGROUND: Malignant mesothelioma is a type of infrequent tumor that is substantially related to asbestos exposure and has a terrible prognosis. We tried to produce a fibroblast differentiation-related gene set for creating a novel classification and prognostic prediction model of MESO.

METHOD: Three databases, including NCBI-GEO, TCGA, and MET-500, separately provide single-cell RNA sequencing data, bulk RNA sequencing profiles of MESO, and RNA sequencing information on bone metastatic tumors. Dimensionality reduction and clustering analysis were leveraged to acquire fibroblast subtypes in the MESO microenvironment. The fibroblast differentiation-related genes (FDGs), which were associated with survival and subsequently utilized to generate the MESO categorization and prognostic prediction model, were selected in combination with pseudotime analysis and survival information from the TCGA database. Then, regulatory network was constructed for each MESO subtype, and candidate inhibitors were predicted. Clinical specimens were collected for further validation.

RESULT: A total of six fibroblast subtypes, three differentiation states, and 39 FDGs were identified. Based on the expression level of FDGs, three MESO subtypes were distinguished in the fibroblast differentiation-based classification (FDBC). In the multivariate prognostic prediction model, the risk score that was dependent on the expression level of several important FDGs, was verified to be an independently effective prognostic factor and worked well in internal cohorts. Finally, we predicted 24 potential drugs for the treatment of MESO. Moreover, immunohistochemical staining and statistical analysis provided further validation.

CONCLUSION: Fibroblast differentiation-related genes (FDGs), especially those in low-differentiation states, might participate in the proliferation and invasion of MESO. Hopefully, the raised clinical subtyping of MESO would provide references for clinical practitioners.

RevDate: 2024-03-09

Rigon M, Mutti L, M Campanella (2024)

Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer.

Molecular oncology [Epub ahead of print].

Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast-paced progression. To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.

RevDate: 2024-03-06

Haakensen VD, Öjlert ÅK, Thunold S, et al (2024)

UV1 telomerase vaccine with ipilimumab and nivolumab as second line treatment for pleural mesothelioma - A phase II randomised trial.

European journal of cancer (Oxford, England : 1990), 202:113973 pii:S0959-8049(24)00129-1 [Epub ahead of print].

PURPOSE: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM).

METHODS: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR. It was estimated that 69 PFS events were needed to detect a hazard ratio (HR) of 0.60 with 80% power and a one-sided alpha level of 0.10.

RESULTS: 118 patients were randomised. The median PFS determined by blinded independent central review (BICR) was 4.2 months (95%CI 2.9-9.8) in arm A and 4.7 months (95%CI 3.9-7.0) in arm B (HR 1.01, 80%CI 0.75-1.36 P = 0.979), after a median follow-up of 12.5 months (95%CI 9.7-15.6). The investigator-determined median PFS was 4.3 months (95%CI 3.0-6.8) in arm A and 2.9 months (95%CI 2.4-5.5) in arm B (HR 0.60, 80%CI 0.45-0.81 P = 0.025). Confirmed objective response rate (ORR) by BICR was 31% in arm A and 16% in arm B (odds ratio 2.44 80%CI 1.35-4.49 P = 0.056). After a median follow-up time of 17.3 months (95%CI 15.8-22.9), the OS was 15.4 months (95%CI 11.1-22.6) in arm A and 11.1 months (95%CI 8.8-18.1) in arm B, (HR 0.73, 80%CI 0.53-1.0, P = 0.197).

CONCLUSION: The primary endpoint was not met. Predefined analyses of response rates are in favour of adding the vaccine.

RevDate: 2024-03-01

Amakusa Y, Suzuki T, Hikosaka Y, et al (2024)

Successful treatment of simultaneous malignant pleural mesothelioma and pulmonary adenocarcinoma: A case report.

Oncology letters, 27(4):155 pii:OL-27-4-14288.

The present report described the case of a 74-year-old male patient with asbestos exposure whose chest computed tomography revealed a right lower lobe nodule and right pleural effusion. Pleural biopsy led to the diagnosis of epithelial malignant pleural mesothelioma (cT2N0M0, stage IB). Combination therapy with cisplatin + pemetrexed led to the complete remission of malignant pleural mesothelioma; however, the right lower lobe nodule grew in size over time. The patient was subsequently diagnosed with lung adenocarcinoma (cT1aN0M0, stage IA1) by computed tomography-guided biopsy performed 18 months after chemotherapy initiation and achieved remission of lung adenocarcinoma with stereotactic radiotherapy. The patient was alive without recurrence at the 12-month follow-up. The present case illustrated that multiple active regimens are currently available for malignant pleural mesothelioma and lung cancer that can aid in the treatment of complex cases.

RevDate: 2024-02-29

Shimizu D, Ishibashi M, Yamada T, et al (2024)

POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma.

Cancer genomics & proteomics, 21(2):158-165.

BACKGROUND/AIM: The prognosis of patients with malignant pleural mesothelioma (MPM) remains poor due to lack of effective therapeutic targets. DNA damage caused by long-time exposure to asbestos fibers has been associated with the development of MPM, with mutations at genes encoding DNA damage repair (DDR)-related molecules frequently expressed in patients with MPM. The present study was designed to identify novel therapeutic targets in MPM using large public databases, such as The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression project (GTEx) focused on DDR pathways.

MATERIALS AND METHODS: The correlations between mRNA expression levels of DDR-related genes and overall survival (OS) were analyzed in mesothelioma patients in TCGA mesothelioma (TCGA-MESO) datasets. The anti-tumor effects of small interfering RNAs (siRNA) against DDR-related genes associated with OS were subsequently tested in MPM cell lines.

RESULTS: High levels of mRNA encoding DNA polymerase delta 1, catalytic subunit (POLD1) were significantly associated with reduced OS in patients with MPM (p<0.001, Log-rank test). In addition, siRNA targeting POLD1 (siPOLD1) caused cell cycle arrest at the G1/S checkpoint and induced apoptosis involving accumulation of DNA damage in MPM cell lines.

CONCLUSION: POLD1 plays essential roles in overcoming DNA damage and cell cycle progression at the G1/S checkpoint in MPM cells. These findings suggest that POLD1 may be a novel therapeutic target in MPM.

RevDate: 2024-02-29
CmpDate: 2024-02-29

Järvholm B, A Burdorf (2024)

Asbestos and disease - a public health success story?.

Scandinavian journal of work, environment & health, 50(2):53-60.

OBJECTIVE: This paper discusses the failure and success of society to decrease the adverse health effects of asbestos exposure on workers' health in relation to scientific knowledge.

METHODS: The findings are based on a narrative literature review.

RESULTS: Early warnings of the adverse health effects of workplace exposure to asbestos were published already in the 1930s. Serious health effects, such as malignancies and fibrosis due to occupational asbestos exposure, were highlighted in major medical journals and textbooks in late 1960s. New technologies could detect also asbestos fibers in the lung of non-occupational exposed persons in the 1970s. The first bans for using asbestos came in the early 1970s, and more general bans by authorities came in the 1980s and continue until today.

CONCLUSIONS: The rather late recognition of adverse effects of asbestos exposure in the general population and measures to decrease the exposure through more general bans came rather late. However, the very strong measures such as general bans in many countries have been a success. A Swedish study showed that the general ban and other measures have decreased the risk of malignancies due to occupational exposure. The effect of the bans on adverse effects in the general population has yet to be studied. Analysis of fibers in the lungs of persons born after the bans could be an efficient method.

RevDate: 2024-02-27

Elkahwagy DM, Kiriacos CJ, Sobeih ME, et al (2024)

The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients.

Scientific reports, 14(1):4823.

Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30-40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.

RevDate: 2024-02-27

Kalla C, Ott G, Finotello F, et al (2024)

The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition.

Translational oncology, 43:101857 pii:S1936-5233(23)00243-7 [Epub ahead of print].

Targeting aberrantly expressed kinases in malignant pleural mesothelioma (MPM) is a promising therapeutic strategy. We here investigated the effect of the novel and highly selective Phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib (IOA-244) on MPM cells and on the immune cells in MPM microenvironment. To this aim, we analyzed the expression of PI3K-δ by immunohistochemistry in specimens from primary MPM, cell viability and death in three different MPM cell lines treated with roginolisib alone and in combination with ipatasertib (AKT inhibitor) and sapanisertib (mTOR inhibitor). In a co-culture model of patient-derived MPM cells, autologous peripheral blood mononuclear cells and fibroblasts, the tumor cell viability and changes in immune cell composition were investigated after treatment of roginolisib with nivolumab and cisplatin. PI3K-δ was detected in 66/89 (74%) MPM tumors and was associated with reduced overall survival (12 vs. 25 months, P=0.0452). Roginolisib induced apoptosis in MPM cells and enhanced the anti-tumor efficacy of AKT and mTOR kinase inhibitors by suppressing PI3K-δ/AKT/mTOR and ERK1/2 signaling. Furthermore, the combination of roginolisib with chemotherapy and immunotherapy re-balanced the immune cell composition, increasing effector T-cells and reducing immune suppressive cells. Overall, roginolisib induces apoptosis in MPM cells and increases the antitumor immune cell effector function when combined with nivolumab and cisplatin. These results provide first insights on the potential of roginolisib as a therapeutic agent in patients with MPM and its potential in combination with established immunotherapy regimen.

RevDate: 2024-02-27

Congedo MT, West EC, Evangelista J, et al (2024)

The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review.

Journal of thoracic disease, 16(1):671-687.

BACKGROUND AND OBJECTIVE: Malignant pleural mesothelioma (MPM) is a very aggressive primary tumor of the pleura whose main risk factor is exposure to asbestos. However, only a minority of exposed people develops MPM and the incidence of MPM cases without an apparent association with asbestos exposure has been increasing in recent years, suggesting that genetic predisposing factors may play a crucial role. In addition, several studies reported familial cases of MPM, suggesting that heredity may be an important and underestimated feature in MPM development. Several candidate genes have been associated with a predisposition to MPM and most of them play a role in DNA repair mechanisms: overall, approximately 20% of MPM cases may be related to genetic predisposition. A particular category of patients with high susceptibility to MPM is represented by carriers of pathogenic variants in the BAP1 gene. Germline variants in BAP1 predispose to the development of MPM following an autosomal dominant pattern of inheritance in the familial cases. MPMs in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. In the present narrative review, we presented a comprehensive overview of genetic susceptibility in the development of MPM.

METHODS: The narrative review is based on a selective literature carried out in PubMed in 2023. Inclusion criteria were original articles in English language, and clinical trials (randomized, prospective, or retrospective).

KEY CONTENT AND FINDINGS: We summarized the somatic and germline variants and the differences in terms of clinicopathological features and prognosis between gene-related MPM (GR-MPM) and asbestos-related MPM (AR-MPM). We also discussed the indications for screening, genetic testing, and surveillance of patients with BAP1 germline variants.

CONCLUSIONS: In this narrative review, we have emphasized that the BAP1 gene's harmful germline variations are inherited in an autosomal dominant manner in familial cases. MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.

RevDate: 2024-02-26

Nazar T, Gopalakrishnabhaktan A, Tashrifwala FAA, et al (2024)

Testicular mesothelioma disguised as hydrocele: a case report.

Journal of medical case reports, 18(1):114.

BACKGROUND: Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis.

CASE PRESENTATION: We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up.

CONCLUSION: Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.

RevDate: 2024-02-26

Qasim A, Allu SVV, Schmidt P, et al (2024)

Comprehensive Review of Mesothelioma Cases: From Diagnosis to Therapeutic Strategies.

Cureus, 16(1):e52859.

Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.

RevDate: 2024-02-24

Mukhopadhyay D, Cocco P, Orrù S, et al (2024)

The role of MicroRNAs as early biomarkers of asbestos-related lung cancer: A systematic review and meta-analysis.

Pulmonology pii:S2531-0437(24)00015-1 [Epub ahead of print].

BACKGROUND: Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM.

AIM: To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis.

METHODS: MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale.

RESULTS: From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132-3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197‑3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574-5p; no miRNA was found associated to LC prognosis.

CONCLUSION: Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.

RevDate: 2024-02-24

Oliveto S, Ritter P, Deroma G, et al (2024)

The Impact of 3D Nichoids and Matrix Stiffness on Primary Malignant Mesothelioma Cells.

Genes, 15(2): pii:genes15020199.

Malignant mesothelioma is a type of cancer that affects the mesothelium. It is an aggressive and deadly form of cancer that is often caused by exposure to asbestos. At the molecular level, it is characterized by a low number of genetic mutations and high heterogeneity among patients. In this work, we analyzed the plasticity of gene expression of primary mesothelial cancer cells by comparing their properties on 2D versus 3D surfaces. First, we derived from primary human samples four independent primary cancer cells. Then, we used Nichoids, which are micro-engineered 3D substrates, as three-dimensional structures. Nichoids limit the dimension of adhering cells during expansion by counteracting cell migration between adjacent units of a substrate with their microarchitecture. Tumor cells grow effectively on Nichoids, where they show enhanced proliferation. We performed RNAseq analyses on all the samples and compared the gene expression pattern of Nichoid-grown tumor cells to that of cells grown in a 2D culture. The PCA analysis showed that 3D samples were more transcriptionally similar compared to the 2D ones. The 3D Nichoids induced a transcriptional remodeling that affected mainly genes involved in extracellular matrix assembly. Among these genes responsible for collagen formation, COL1A1 and COL5A1 exhibited elevated expression, suggesting changes in matrix stiffness. Overall, our data show that primary mesothelioma cells can be effectively expanded in Nichoids and that 3D growth affects the cells' tensegrity or the mechanical stability of their structure.

RevDate: 2024-02-24

Okado S, Kato T, Hanamatsu Y, et al (2024)

CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.

International journal of molecular sciences, 25(4): pii:ijms25042270.

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

RevDate: 2024-02-22

Bairos Menezes M, Pedroso de Lima R, Dunões I, et al (2024)

A Complete Response to Pembrolizumab in Malignant Peritoneal Mesothelioma: A Case Report.

Cureus, 16(1):e52716.

Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the peritoneum with a poor prognosis and nonspecific clinical course. We discuss a case of MPeM in a 59-year-old male who presented with abdominal pain and distension, without any known previous asbestos exposure. The diagnosis was made after a second biopsy finally confirmed epithelioid MPeM in an advanced stage with pleural effusion. The patient underwent six cycles of chemotherapy with cisplatin and pemetrexed, experienced disease progression, and was then started on pembrolizumab as a second-line treatment. The patient achieved a complete response after two years of treatment with pembrolizumab and has been disease-free for almost four years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Despite the lack of evidence to support the treatment with immunotherapy for MPeM, our case report encourages its use, highlighting its ability to enable a complete response with pembrolizumab with an excellent quality of life.

RevDate: 2024-02-20

Mervic A, Goricar K, Blagus T, et al (2024)

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases.

Radiology and oncology, 58(1):87-98.

BACKGROUND: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).

SUBJECTS AND METHODS: We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.

RESULTS: Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).

CONCLUSIONS: Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.

RevDate: 2024-02-20

Tian T, Xie H, M Huang (2024)

Epithelial Malignant Pleural Mesothelioma Mimics Lymphoma on 18F-FDG PET/MRI: A Case Report.

Clinical nuclear medicine pii:00003072-990000000-00947 [Epub ahead of print].

Malignant pleural mesothelioma is a rare tumor with a poor prognosis. We describe a case of 55-year-old man without asbestos exposure history presenting with extensive lymph nodes with high 18F-FDG uptake in PET/MRI but atypical pleural manifestations thereby being misdiagnosed for lymphoma. Pathological examination concludes for an epithelioid mesothelioma-associated lymph node metastasis. This case emphasizes that with the extensive lymph node abnormalities shown in PET imaging, in addition to the general consideration of lymphoma, it is still necessary to be vigilant about the possibility of mesothelioma and emphasizes the necessity of pathological examination.

RevDate: 2024-02-13

Tilsed CM, Morales MLO, Zemek RM, et al (2024)

Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.

BMC cancer, 24(1):203.

BACKGROUND: Chemotherapy 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.

METHODS: We 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.

RESULTS: The 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.

CONCLUSIONS: Despite 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.

RevDate: 2024-02-10

Mizuhashi K, Okamoto K, Nabeshima K, et al (2024)

Detailed clinical course of a patient with rapidly progressing sarcomatoid pleural mesothelioma without p16 deletion with systemic haematogenous metastasis to soft tissues.

BMJ case reports, 17(2): pii:17/2/e257618.

Sarcomatoid mesothelioma is difficult to differentiate from other mesotheliomas. Here, we describe the case of a man in his early 80s with sarcomatoid mesothelioma and a history of asbestos exposure. He initially presented with right-sided chest pain and was examined. Right-sided pleural effusion was detected; therefore, he was hospitalised. Based on the observed pleural effusion and biopsy result, the presence of a malignant tumour was excluded; hence, he was diagnosed with benign asbestos pleurisy. He subsequently developed left-sided pleural effusion, masses and lung nodules, and died 9.5 months after the initial examination. A definitive diagnosis of sarcomatoid mesothelioma with rapid systemic progression was established after detailed investigations using autopsy specimens. This rare case of mesothelioma-without p16 deletion (detected using fluorescence in situ hybridisation)-presented differently from the usual sarcomatoid mesothelioma.

RevDate: 2024-02-10

Xiong X, Zhang S, Liao X, et al (2024)

An umbrella review of the evidence associating occupational carcinogens and cancer risk at 19 anatomical sites.

Environmental pollution (Barking, Essex : 1987) pii:S0269-7491(24)00245-8 [Epub ahead of print].

Occupational exposure to carcinogens of increasing cancer risk have been extensively suggested. A robust assessment of these evidence is needed to guide public policy and health care. We aimed to classify the strength of evidence for associations of 13 occupational carcinogens (OCs) and risk of cancers. We searched PubMed and Web of Science up to November 2022 to identify potentially relevant studies. We graded the evidence into convincing, highly suggestive, suggestive, weak, or not significant according to a standardized classification based on: random-effects p value, number of cancer cases, 95% confidence interval of largest study, heterogeneity between studies, 95% prediction interval, small study effect, excess significance bias and sensitivity analyses with credibility ceilings. The quality of meta-analysis was evaluated by AMSTAR 2. Forty-eight articles yielded 79 meta-analyses were included in current umbrella review. Evidence of associations were convincing (class I) or highly suggeastive (class II) for asbestos exposure and increasing risk of lung cancer among smokers (RR = 8.79, 95%CI: 5.81-13.25 for cohort studies and OR = 8.68, 95%CI: 5.68-13.24 for case-control studies), asbestos exposure and increasing risk of mesothelioma (RR = 4.61, 95%CI: 2.57-8.26), and formaldehyde exposure and increasing risk of sinonasal cancer (RR = 1.68, 95%CI: 1.38-2.05). Fifteen associations were supported by suggestive evidence (class III). In summary, the current umbrella review found strong associations between: asbestos exposure and increasing risk of lung cancer among smokers; asbestos exposure and increasing risk of mesothelioma; and formaldehyde exposure and higher risk of sinonasal cancer. Other associations might be genuine, but substantial uncertainty remains.

RevDate: 2024-02-06

Subahi EA, Fadul A, Mohamed A, et al (2024)

Biphasic Peritoneal Mesothelioma Is a Rare Tumor and a Diagnostic Challenge: A Case Report.

Cureus, 16(1):e51725.

Malignant peritoneal mesothelioma (MPM) is a rare subtype of mesothelioma. There are three main histological subtypes of mesothelioma: epithelioid, sarcomatoid, and biphasic (mixed). Risk factors include asbestos exposure, previous radiation, and some germline mutations. Treatment includes surgical resection of amenable tumors or cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We present a 34-year-old male who presented with weight loss, night sweats, and pleuritic chest pain and was found to have ascites with peritoneal nodularity on abdominal imaging. He had a history of tuberculosis contact, but no history of asbestos exposure. After a long challenging and interesting diagnostic process, he was subsequently diagnosed with biphasic MPM. The diagnostic challenge stems from not only the rarity of the tumor but also from the absence of risk factors, the unavailability of some special laboratory investigations, in addition to the potentially misleading effect of tuberculosis exposure history, a top differential diagnosis in the case. This is a case report of a really challenging and totally unexpected diagnosis of biphasic peritoneal mesothelioma in a patient with tuberculosis exposure, constitutional symptoms, but no history of asbestos exposure. It highlights the diagnostic process as well as the importance of early diagnosis to improve the overall survival of such malignancies.

RevDate: 2024-02-01

Fitzgerald SM (2024)

Resolving asbestos and ultrafine particulate definitions with carcinogenicity.

Lung cancer (Amsterdam, Netherlands), 189:107478 pii:S0169-5002(24)00011-4 [Epub ahead of print].

As asbestos fibers and other fine particles have been studied extensively to correlate physical and chemical properties with their potential for negative human health impact on inhalation, there remains no concise definitions for the individual particle types nor collective considerations of combined variabilities. Extensive studies relating negative health to asbestos morphology, chemistry, surface effects, and biodurability form general qualitative bins of what is more likely causative or less, but do not provide enough information to quantitatively dismiss particles with parameters outside any given range. Further, natural mineral species and accessory mineralization makes standardization of universally applicable reference materials nearly unobtainable. With modern advent of engineered nanoparticles, we are adding even more unknowns to the universe of the microscopic size fraction and its potential for human disease, and our paradigm is challenged.

RevDate: 2024-02-01

Alratrout H, Boumarah DN, Alghusnah ES, et al (2023)

Synchronous Malignant Peritoneal Mesothelioma and Sigmoid Adenocarcinoma: a Challenging Clinical Entity.

Medical archives (Sarajevo, Bosnia and Herzegovina), 77(5):400-404.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) represents a rare clinical entity. The synchronous existence of MPM with other malignancies as colonic adenocarcinoma have been rarely reported. Its diagnosis and management are challenging given its complexity and rarity.

OBJECTIVE: Herein, we report a case of epithelioid subtype of MPM occurring synchronously with sigmoid colonic adenocarcinoma, along with review of the literature.

CASE PRESENTATION: An elderly female patient was referred as case of rectosigmoid mass. She reported history of abdominal pain, per-rectal bleeding, anorexia, and significant weight loss. Her computed-tomography scan of the abdomen revealed a fistulizing sigmoid mass and multiple enlarged lymphnodes with omental nodulation. The colonoscopy revealed a large fungating mass and the endoscopic biopsies were reported as colonic adenocarcinoma. The patient was scheduled laparoscopic low anterior resection. However, the diagnostic laparoscopy revealed several nodules disseminated all over the peritoneum, suggestive of peritoneal mesothelioma. Therefore, the decision was changed to create transverse colostomy after examination obtaining multiple biopsies from the omental and peritoneal nodules. The histopathological revealed MPM and the final diagnosis was sigmoid adenocarcinoma with synchronous MPM. The patient was started on palliative chemotherapy (capecitabine) without active management of MPM because of her general condition. She was followed up with a good clinical course.

CONCLUSION: MPM is an overlooked entity with vague clinical presentation. Synchronous MPM with colorectal cancer is rare with only few published case reports. Its diagnosis is challenging, and its management should be tailored according to the patient. This case is the first reported case in Saudi Arabia and the Middle East.

RevDate: 2024-01-31

Reamon-Buettner SM, Rittinghausen S, Klauke A, et al (2024)

Malignant peritoneal mesotheliomas of rats induced by multiwalled carbon nanotubes and amosite asbestos: transcriptome and epigenetic profiles.

Particle and fibre toxicology, 21(1):3.

BACKGROUND: Malignant mesothelioma is an aggressive cancer that often originates in the pleural and peritoneal mesothelium. Exposure to asbestos is a frequent cause. However, studies in rodents have shown that certain multiwalled carbon nanotubes (MWCNTs) can also induce malignant mesothelioma. The exact mechanisms are still unclear. To gain further insights into molecular pathways leading to carcinogenesis, we analyzed tumors in Wistar rats induced by intraperitoneal application of MWCNTs and amosite asbestos. Using transcriptomic and epigenetic approaches, we compared the tumors by inducer (MWCNTs or amosite asbestos) or by tumor type (sarcomatoid, epithelioid, or biphasic).

RESULTS: Genome-wide transcriptome datasets, whether grouped by inducer or tumor type, showed a high number of significant differentially expressed genes (DEGs) relative to control peritoneal tissues. Bioinformatic evaluations using Ingenuity Pathway Analysis (IPA) revealed that while the transcriptome datasets shared commonalities, they also showed differences in DEGs, regulated canonical pathways, and affected molecular functions. In all datasets, among highly- scoring predicted canonical pathways were Phagosome Formation, IL8 Signaling, Integrin Signaling, RAC Signaling, and TREM1 Signaling. Top-scoring activated molecular functions included cell movement, invasion of cells, migration of cells, cell transformation, and metastasis. Notably, we found many genes associated with malignant mesothelioma in humans, which showed similar expression changes in the rat tumor transcriptome datasets. Furthermore, RT-qPCR revealed downregulation of Hrasls, Nr4a1, Fgfr4, and Ret or upregulation of Rnd3 and Gadd45b in all or most of the 36 tumors analyzed. Bisulfite sequencing of Hrasls, Nr4a1, Fgfr4, and Ret revealed heterogeneity in DNA methylation of promoter regions. However, higher methylation percentages were observed in some tumors compared to control tissues. Lastly, global 5mC DNA, m6A RNA and 5mC RNA methylation levels were also higher in tumors than in control tissues.

CONCLUSIONS: Our findings may help better understand how exposure to MWCNTs can lead to carcinogenesis. This information is valuable for risk assessment and in the development of safe-by-design strategies.

RevDate: 2024-01-31

Tagarakis G, Tsolaki F, I Tagarakis (2024)

Commentary: The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.

Frontiers in public health, 12:1336545.

RevDate: 2024-01-31

Fazzo L, Grande E, Zona A, et al (2023)

Mortality rates from asbestos-related diseases in Italy during the first year of the COVID-19 pandemic.

Frontiers in public health, 11:1243261.

BACKGROUND AND AIM: Patients with interstitial lung diseases, including asbestosis, showed high susceptibility to the SARS-CoV-2 virus and a high risk of severe COVID-19 symptoms. Italy, highly impacted by asbestos-related diseases, in 2020 was among the European countries with the highest number of COVID-19 cases. The mortality related to malignant mesotheliomas and asbestosis in 2020 and its relationship with COVID-19 in Italy are investigated.

METHODS: All death certificates involving malignant mesotheliomas or asbestosis in 2010-2020 and those involving COVID-19 in 2020 were retrieved from the National Registry of Causes of Death. Annual mortality rates and rate ratios (RRs) of 2020 and 2010-2014 compared to 2015-2019 were calculated. The association between malignant pleural mesothelioma (MPM) and asbestosis with COVID-19 in deceased adults ≥80 years old was evaluated through a logistic regression analysis (odds ratios: ORs), using MPM and asbestosis deaths COVID-19-free as the reference group. The hospitalization for asbestosis in 2010-2020, based on National Hospital Discharge Database, was analyzed.

RESULTS: In 2020, 746,343 people died; out of them, 1,348 involved MPM and 286 involved asbestosis. Compared to the period 2015-2019, the mortality involving the two diseases decreased in age groups below 80 years; meanwhile, an increasing trend was observed in subjects aged 80 years and older, with a relative mortality risks of 1.10 for MPM and 1.17 for asbestosis. In subjects aged ≥80 years, deaths with COVID-19 were less likely to have MPM in both genders (men: OR = 0.22; women: OR = 0.44), while no departure was observed for asbestosis. A decrease in hospitalization in 2020 with respect to those in 2010-2019 in all age groups, both considering asbestosis as the primary or secondary diagnosis, was observed.

CONCLUSIONS: The increasing mortality involving asbestosis and, even if of slight entity, MPM, observed in people aged over 80 years during the 1[st] year of the COVID-19 pandemic, aligned in part with the previous temporal trend, could be due to several factors. Although no positive association with COVID-19 mortality was observed, the decrease in hospitalizations for asbestosis among individuals aged over 80 years, coupled with the increase in deaths, highlights the importance of enhancing home-based assistance during the pandemic periods for vulnerable patients with asbestos-related conditions.

RevDate: 2024-01-22

Kang MS, Chae WR, Lee YJ, et al (2023)

Occupational and Environmental Asbestos Exposure and Survival of Patients with Asbestos-Related Cancer: A Follow-Up Study on Patients with Malignant Mesothelioma and Asbestos-Related Lung Cancer in Korea.

Toxics, 12(1): pii:toxics12010020.

Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group.

RevDate: 2024-01-22

Visonà SD, Capella S, Borrelli P, et al (2023)

Asbestos burden in lungs of non-occupationally exposed women from Broni (Pavia, Italy): a postmortem SEM-EDS study.

Journal of thoracic disease, 15(12):6555-6569.

BACKGROUND: In Italy the incidence of malignant mesothelioma (MM) among women is remarkably high, due to the several contexts in which women had been exposed to asbestos. However, very few studies in literature focus on the inorganic lung content in women. The aim of this retrospective, observational study is to investigate the asbestos lung burden, in terms of concentration, dimensions and type of asbestos, in 42 women who died from MM and had been non-occupationally exposed to asbestos during the activity of the asbestos-cement plant located in Broni (Pavia, Northern Italy) where mainly chrysotile, crocidolite and amosite were used.

METHODS: Lung samples taken during forensic autopsies have been digested using sodium hypochlorite and filtered through a cellulose-ester membrane. The filter was examined using a scanning electron microscope and the chemical composition of the fibers was analyzed using an electron dispersive spectroscopy. The number of detected inorganic fibers, asbestos fibers and asbestos bodies (ABs) were normalized to 1 gram of dry tissue.

RESULTS: In six samples no asbestos has been detected. Overall, the most represented kind of asbestos was amosite, followed by crocidolite, tremolite/actinolite asbestos and chrysotile. The concentration of all inorganic fibers was significantly higher in women with environmental and household exposures compared with those with only environmental exposure (P=0.025), as well as the concentration of asbestos fibers (P=0.019) and ABs (P=0.049). We found a significant correlation between the concentration of asbestos fibers and the duration of exposure (rho =0.413, P=0.008), as well as with the latency of MM (rho =0.427, P=0.005). The distance of the residential address from the factory and the time spent daily in contact with asbestos did not influence the lung asbestos burden.

CONCLUSIONS: These results suggest the relevance of the lung clearance of asbestos, regarding mainly chrysotile. As a consequence, although scanning electron microscopy -energy dispersive X-ray spectroscopy (SEM-EDS) is considered the most reliable tool for assessing previous exposure to asbestos, its results should be interpreted with caution, especially in a legal context. In addition, our data confirm the relevance of environmental and household exposure in determining asbestos concentration in lungs and highlight the importance of household exposure.

RevDate: 2024-01-22

Schüz J, Kovalevskiy E, Olsson A, et al (2024)

Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).

Journal of the National Cancer Institute pii:7577290 [Epub ahead of print].

BACKGROUND: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.

METHODS: This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.

RESULTS: A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.

CONCLUSION: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

RevDate: 2024-01-19

Behers BM, Guske CW, Behers BJ, et al (2024)

Malignant Epithelioid Mesothelioma of the Tunica Vaginalis Testis Presenting as Hydrocele in a Kidney Transplant Recipient.

Case reports in urology, 2024:9227764.

Mesotheliomas of the tunica vaginalis testis are rare malignant tumors that can present as a scrotal mass or hydrocele. These tumors are typically aggressive with high rates of recurrence and metastasis. Suspected risk factors for malignant mesothelioma include asbestos exposure, chronic inflammation, trauma, and persistent hydrocele. We report the case of a malignant epithelioid mesothelioma of the tunica vaginalis testis that presented as a finding at hydrocelectomy and was ultimately treated with radical inguinal orchiectomy. This patient was on chronic immunosuppression therapy with tacrolimus and mycophenolate mofetil secondary to a kidney transplant but had none of the common risk factors for mesothelioma formation. To our knowledge, this is the first case describing a possible connection between chronic immunosuppression and mesothelioma of the tunica vaginalis. However, future studies are needed to investigate this association and discern whether this could have played a role in our patient or if his mesothelioma formation was coincidental.

RevDate: 2024-01-11

Iser S, Hintermair S, Varga A, et al (2023)

Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.

Cancers, 16(1): pii:cancers16010093.

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.

RevDate: 2024-01-09

Carney JM, Sporn TA, Roggli VL, et al (2024)

The diagnosis of asbestosis in the 21[st] century: a clinicopathological correlation of 102 cases.

Ultrastructural pathology [Epub ahead of print].

Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21[st] century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.

RevDate: 2024-01-08

Hung YP, LR Chirieac (2024)

Molecular and Immunohistochemical Testing in Mesothelioma and Other Mesothelial Lesions.

Archives of pathology & laboratory medicine pii:498212 [Epub ahead of print].

CONTEXT.—: Molecular testing has increasingly been utilized in the evaluation of mesothelioma. Diffuse mesothelioma comprises multiple distinct genetic subgroups. While most diffuse mesotheliomas lack oncogenic kinase mutations and instead harbor alterations involving tumor suppressors and chromatin regulators, a minor subset of tumors is characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion.

OBJECTIVE.—: To provide updates on the salient molecular features of diffuse mesothelioma, mesothelioma in situ, and other mesothelial lesions: well-differentiated papillary mesothelial tumor, adenomatoid tumor, peritoneal inclusion cyst, and others. We consider the diagnostic, prognostic, and predictive utility of molecular testing in mesothelial lesions.

DATA SOURCES.—: We performed a literature review of recently described genetic features, molecular approaches, and immunohistochemical tools, including BAP1, MTAP, and merlin in mesothelioma and other mesothelial lesions.

CONCLUSIONS.—: Our evolving understanding of the molecular diversity of diffuse mesothelioma and other mesothelial lesions has led to considerable changes in pathology diagnostic practice, including the application of immunohistochemical markers such as BAP1, MTAP, and merlin (NF2), which are surrogates of mutation status. In young patients and/or those without significant asbestos exposure, unusual mesothelioma genetics such as germline mutations, ALK rearrangement, and ATF1 rearrangement should be considered.

RevDate: 2024-01-05

Carney JM, Roggli VL, Glass CH, et al (2023)

The over diagnosis of diffuse mesothelioma: An analysis of 311 cases with recommendations for the avoidance of pitfalls.

Annals of diagnostic pathology pii:S1092-9134(23)00146-6 [Epub ahead of print].

BACKGROUND: The diagnosis of mesothelioma may be challenging. We investigated a large database of cases in order to determine the frequency with which a diagnosis of mesothelioma was made incorrectly and the most frequent causes of error.

DESIGN: A database including more than 4000 consultation cases of histologically confirmed mesothelioma was examined to identify cases in which mesothelioma was diagnosed by at least one pathologist when the available information pointed towards a different diagnosis.

RESULTS: There were 311 cases misdiagnosed as mesothelioma. The most common category was metastatic carcinoma to the pleura or peritoneum (129 cases: 73 lung carcinomas, 15 renal cell carcinomas). The next most common category was primary lung cancer (111 cases: 55 sarcomatoid carcinoma, 56 pseudomesotheliomatous carcinoma). The third most common category was primary malignancies arising from or near the serosal membranes (33 cases). The fourth most common category was fibrous pleurisy (38 cases). The most common errors were failure to consider important radiographic information regarding the gross distribution of tumor, lack of awareness or consideration of another malignancy, overreliance on certain immunohistochemical results, and failure to perform certain diagnostic histochemical, immunohistochemical, or ultrastructural studies.

CONCLUSIONS: There are a number of diagnostic pitfalls that can lead to the over diagnosis of mesothelioma. Careful attention to clinical and radiographic information as well as performance of appropriate ancillary tests can help to prevent such misdiagnoses. Detailed examples will be presented to assist in the avoidance of these pitfalls with emphasis on the most commonly observed errors.

RevDate: 2024-01-04

van der Linde LIS, Hantzsch-Kuhn B, Ellebrecht D, et al (2024)

[Interdisciplinary diagnostics and therapy of malignant mesothelioma].

Pneumologie (Stuttgart, Germany) [Epub ahead of print].

The asbestos-related malignant mesothelioma (MM) is one of the common occupational cancers in Germany with approximately 1000 new cases per year. Provided that the appropriate diagnostic criteria are fulfilled, MM can be diagnosed with high specificity from both histological and cytological specimens. However, many MM are detected cyto-/histologically only at advanced stages. Clinical/radiological aspects complement each other and enable interdisciplinary assessment of tumor stage and individualized decisions on the best possible therapeutic options. Diagnostically, video-assisted thoracoscopy (VATS) has the highest priority. Therapy planning is based on the MM subtype, tumor spread and stage, and the patient's clinical condition. MM has generally a very unfavorable prognosis. Accordingly, the standard therapy aims at a macroscopic radical tumor resection in terms of cytoreduction within the framework of a suitable multimodal therapy concept (chemotherapy, radiotherapy, psychooncology). The aim of palliative measures should be primarily symptom control. Overall, interdisciplinary diagnosis and therapy of MM is crucial for the best possible care of MM patients.

RevDate: 2024-01-03

Shaker N, Blankenship H, Shaker N, et al (2024)

Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.

International journal of surgical pathology [Epub ahead of print].

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.

RevDate: 2023-12-28

Brims F, Kumarasamy C, Menon L, et al (2023)

The Western Australian Mesothelioma Registry: Analysis of 60 years of cases.

Respirology (Carlton, Vic.) [Epub ahead of print].

BACKGROUND AND OBJECTIVE: Australia introduced a partial ban on asbestos consumption in 1984. There is continuing concern about exposure to asbestos in the built environment and non-occupational exposures. The aim of this study was to describe epidemiological trends of mesothelioma in Western Australia (WA) over the 60 years since the first case was recorded.

METHODS: Every case of mesothelioma notified to the WA Cancer Registry is reviewed by an expert panel. Data include demographic and clinical variables including principal mode of asbestos exposure and age at first exposure. Trends over time for survival, latency and pathological subtype of mesothelioma where analysed. Incidence rates for cases exposed during home renovation where calculated.

RESULTS: Two thousand seven hundred ninety-six cases of mesothelioma were identified with males comprising the majority (n = 2368, 84.7%). The median (IQR) age at diagnosis was 70 (62-78) years, and median latency of 47 (38-55) years. Pleural mesothelioma was recorded in 2620 (93.7%) cases with the epithelioid subtype most prevalent (n = 1730, 61.9%). Overall, median survival was 298 (128-585) days and latency 46 (37-54) years, both effectively doubling over the study period. Non-occupational exposures were proportionally higher in females (52.6%), compared with males (9.5%). Home renovation was the primary exposure in 227 (8.1%) cases, with number of cases and incidence rate ratio peaking in 2005/09 but subsequently decreasing.

CONCLUSION: The annual number of cases of mesothelioma in WA may have hit a plateau. The majority of females have non-occupational exposures and incidence rates from home renovation exposure may have peaked, suggesting the ban on asbestos has been effective.

RevDate: 2023-12-23

Weber DG, Casjens S, Wichert K, et al (2023)

Tasks and Experiences of the Prospective, Longitudinal, Multicenter MoMar (Molecular Markers) Study for the Early Detection of Mesothelioma in Individuals Formerly Exposed to Asbestos Using Liquid Biopsies.

Cancers, 15(24): pii:cancers15245896.

Mesothelioma is an aggressive cancer, strongly associated with prior exposure to asbestos. Commonly, tumors are detected at late stages of the disease. Detection at early stages might be meaningful, because therapies might be more effective when the tumor burden is relatively low and the tumor has not spread to distant sites. Circulating biomarkers in blood might be a promising tool to improve the early detection of mesothelioma, but for screening in asymptomatic subjects, candidate biomarkers need to be validated in appropriate studies. This study was conducted to assess the performance of biomarkers in liquid biopsies to detect mesothelioma at early stages. Over a period of 10 years, 2769 volunteers formerly exposed to asbestos were annually examined and liquid biopsies were collected. A follow-up was completed 17 months after the last blood collection. The article provides a detailed overview of our lessons learned and experiences of conducting a prospective, longitudinal, multicenter study. The existing cohort of individuals at risk is highly suitable for the validation of blood-based biomarkers for the early detection of mesothelioma as well as lung cancer.

RevDate: 2023-12-23

Bertin B, Zugman M, G Schvartsman (2023)

The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions.

Cancers, 15(24): pii:cancers15245808.

The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.

RevDate: 2023-12-23

Cedres S, Valdivia A, Iranzo P, et al (2023)

Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy.

Cancers, 15(24): pii:cancers15245787.

Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20-40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.

RevDate: 2023-12-23

Cerbone L, Orecchia S, Bertino P, et al (2023)

Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.

Cancers, 15(24): pii:cancers15245716.

Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have been performed on mesothelioma arising at different sites. These studies highlight a genomic landscape mainly characterized by a high prevalence (>20%) of genomic aberrations leading to functional losses in oncosuppressor genes such as BAP1, CDKN2A, NF2, SETD2 and TP53. Nevertheless, to date, evidence of the effect of targeting these alterations with specific drugs is lacking. Conversely, 1-2% of mesothelioma might harbor activating mutations in oncogenes with specifically approved drugs. The goal of this review is to summarize NGS applications in mesothelioma and to provide insights into target therapy of mesothelioma guided by NGS.

RevDate: 2023-12-22

Ledda C, Loreto C, Lombardo C, et al (2023)

Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers.

Translational oncology, 40:101872 pii:S1936-5233(23)00258-9 [Epub ahead of print].

Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.

RevDate: 2023-12-21

Beckett EM, Abelmann A, Roberts B, et al (2023)

An updated evaluation of reported no-observed adverse effect levels for chrysotile, amosite, and crocidolite asbestos for lung cancer and mesothelioma.

Critical reviews in toxicology, 53(10):611-657.

This analysis updates two previous analyses that evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. We reviewed recently published studies, as well as updated information from previous studies. Based on the 16 studies considered for chrysotile (<10% amphibole), we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma; it should be noted that smoking or previous or concurrent occupational exposure to amphiboles (if it existed) was not controlled for. NOAEL values ranged from 2.3-<11.5 f/cc-years to 1600-3200 f/cc-years for lung cancer and from 100-<400 f/cc-years to 800-1599 f/cc-years for mesothelioma. The range of best-estimate NOAELs was estimated to be 97-175 f/cc-years for lung cancer and 250-379 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased risk at any exposure level, while all but one of the six studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Only eight cases of peritoneal mesothelioma were reported in all studies on predominantly chrysotile-exposed cohorts combined. This analysis also proposed best-estimate amosite and crocidolite NOAELs for mesothelioma derived by the application of relative potency estimates to the best-estimate chrysotile NOAELs for mesothelioma and validated by epidemiology studies with exposure-response information. The best-estimate amosite and crocidolite NOAELs for mesothelioma were 2-5 f/cc-years and 0.6-1 f/cc-years, respectively. The rate of peritoneal mesothelioma in amosite- and crocidolite-exposed cohorts was between approximately 70- to 100-fold and several-hundred-fold higher than in chrysotile-exposed cohorts, respectively. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile, amosite, and crocidolite exposures.

RevDate: 2023-12-21

Shenouda M, Gudmundsson E, Li F, et al (2023)

Convolutional Neural Networks for Segmentation of Malignant Pleural Mesothelioma: Analysis of Probability Map Thresholds (CALGB 30901, Alliance).


Malignant pleural mesothelioma (MPM) is the most common form of malignant mesothelioma, with exposure to asbestos being the primary cause of the disease. To assess response to treatment, tumor measurements are acquired and evaluated based on a patient's longitudinal computed tomography (CT) scans. Tumor volume, however, is the more accurate metric for assessing tumor burden and response. Automated segmentation methods using deep learning can be employed to acquire volume, which otherwise is a tedious task performed manually. The deep learning-based tumor volume and contours can then be compared with a standard reference to assess the robustness of the automated segmentations. The purpose of this study was to evaluate the impact of probability map threshold on MPM tumor delineations generated using a convolutional neural network (CNN). Eighty-eight CT scans from 21 MPM patients were segmented by a VGG16/U-Net CNN. A radiologist modified the contours generated at a 0.5 probability threshold. Percent difference of tumor volume and overlap using the Dice Similarity Coefficient (DSC) were compared between the standard reference provided by the radiologist and CNN outputs for thresholds ranging from 0.001 to 0.9. CNN annotations consistently yielded smaller tumor volumes than radiologist contours. Reducing the probability threshold from 0.5 to 0.1 decreased the absolute percent volume difference, on average, from 43.96% to 24.18%. Median and mean DSC ranged from 0.58 to 0.60, with a peak at a threshold of 0.5; no distinct threshold was found for percent volume difference. The CNN exhibited deficiencies with specific disease presentations, such as severe pleural effusion or disease in the pleural fissure. No single output threshold in the CNN probability maps was optimal for both tumor volume and DSC. This study emphasized the importance of considering both figures of merit when evaluating deep learning-based tumor segmentations across probability thresholds. This work underscores the need to simultaneously assess tumor volume and spatial overlap when evaluating CNN performance. While automated segmentations may yield comparable tumor volumes to that of the reference standard, the spatial region delineated by the CNN at a specific threshold is equally important.

RevDate: 2023-12-13

Liu B, Niu L, FF Lee (2023)

Utilizing residential histories to assess environmental exposure and socioeconomic status over the life course among mesothelioma patients.

Journal of thoracic disease, 15(11):6126-6139.

BACKGROUND: Exposure misclassification based solely on the address at cancer diagnosis has been widely recognized though not commonly assessed.

METHODS: We linked 1,015 mesothelioma cases diagnosed during 2011-2015 from the New York State Cancer Registry to inpatient claims and LexisNexis administrative data and constructed residential histories. Percentile ranking of exposure to ambient air toxics and socioeconomic status (SES) were based on the National Air Toxic Assessment and United States Census data, respectively. To facilitate comparisons over time, relative exposures (REs) were calculated by dividing the percentile ranking at individual census tract by the state-level average and subtracting one. We used generalized linear regression models to compare the RE in the past with that at cancer diagnosis, adjusting for patient-level characteristics.

RESULTS: Approximately 43.7% of patients had residential information available for up to 30 years, and 96.0% up to 5 years. The median number of unique places lived was 4 [interquartile range (IQR), 2-6]. The time-weighted-average RE from all addresses available had a median of -0.11 (IQR, -0.50 to 0.30) for air toxics and -0.28 (IQR, -0.65 to 0.25) for SES. RE associated with air toxics (but not SES) was significantly higher for earlier addresses than addresses at cancer diagnosis for the 5-year [annual increase =1.24%; 95% confidence interval (CI): 0.71-1.77%; n=974] and 30-year (annual increase =0.36%; 95% CI: 0.25-0.48%; n=444) look-back windows, respectively.

CONCLUSIONS: Environmental exposure to non-asbestos air toxics among mesothelioma patients may be underestimated if based solely on the address at diagnosis. With geospatial data becoming more readily available, incorporating cancer patients' residential history would lead to reduced exposure misclassification and accurate health risk estimates.

RevDate: 2023-12-13

Tibaduiza Torres AL, Betancur Romero JE, Silva Aparicio A, et al (2023)

[Malignant mesothelioma in Colombia: burden of disease, overview, and subnational sociodemographic index, 2015-2020Mesotelioma maligno na Colômbia: carga de morbidade, visão geral e índice sociodemográfico subnacional, entre 2015 e 2020].

Revista panamericana de salud publica = Pan American journal of public health, 47:e95 pii:RPSP.2023.95.

OBJECTIVE: Establish the disease burden of malignant mesothelioma (MM) in Colombia between 2015 and 2020, and its association with the subnational sociodemographic development index (SDI) and with asbestos sites.

METHODS: Mixed ecological study of the Colombian population diagnosed with MM (according to ICD-10) from 2015 to 2020. The global burden of disease (GBD) was estimated using the methodology proposed by Murray and Lopez, based on prevalence and mortality data obtained from official sources. The subnational (departmental level) SDI was estimated as a measure of socioeconomic development. Linear regressions were established with the GBD, SDI, and documented asbestos sites.

RESULTS: The estimated GBD of MM in Colombia during 2015-2020 was 51.71 disability-adjusted life years (DALYs) per 1 000 000 inhabitants (15 375.79 total DALYs), with predominance in people over 50 years of age (91.1%) and males (66.4%).Bogotá and Valle del Cauca were the departments with the highest number of adjusted DALYs. Bogotá had the highest SDI and Guainía and Cesar had the lowest. There was evidence of an association between DALYs and SDI, explaining 22.8% of DALYs.

CONCLUSION: Malignant mesothelioma is the cause of a large number of DALYs, predominantly in the departments with greater socioeconomic development and with companies that used to use asbestos. However, possible underdiagnosis of MM limits analysis of the information.

RevDate: 2023-12-10

Turati F, Rossi M, Spinazzè A, et al (2023)

Occupational asbestos exposure and ovarian cancer: updated systematic review.

Occupational medicine (Oxford, England) pii:7468554 [Epub ahead of print].

BACKGROUND: The association between asbestos exposure and ovarian cancer has been questioned given the possible misdiagnosis of peritoneal mesothelioma as ovarian cancer.

AIMS: To update a systematic review on ovarian cancer risk in women occupationally exposed to asbestos, exploring the association with the time since first exposure and the duration of exposure.

METHODS: We searched PubMed from 2008 onwards, screened previous systematic reviews, combined standardized mortality ratios (SMR) using random effect models and quantified heterogeneity using the I2 statistic. To assess tumour misclassification, we compared the distribution of observed excess ovarian cancers (OEOC) to that expected (EEOC) from the distribution of peritoneal cancers in strata of latency and exposure duration.

RESULTS: Eighteen publications (20 populations), including a pooled analysis of 21 cohorts, were included. The pooled SMR was 1.79 (95% confidence interval 1.38-2.31), with moderate heterogeneity between studies (I2 = 42%), based on 144 ovarian cancer deaths/cases. The risk was increased for women with indirect indicators of higher exposure, longer duration and latency, and lower for chrysotile than for crocidolite exposure. The effect of duration and latency could not be completely disentangled, since no multivariate analysis was available for time-related variables. The dissimilarity index between OEOC and EEOC for the time since first exposure was small suggesting a similar pattern of risk.

CONCLUSIONS: While some misclassification between ovarian and peritoneal cancers cannot be excluded, the observed excess risk of ovarian cancer should be added to the overall disease burden of asbestos.

RevDate: 2023-12-09

Visonà SD, Bertoglio B, Capella S, et al (2023)


Carcinogenesis pii:7464959 [Epub ahead of print].

The causal attribution of asbestos related diseases to past asbestos exposures is of crucial importance in clinical and legal contexts. Often this evaluation is made based on the history of exposure, but this method presents important limitations. To assess past asbestos exposure, pleural plaques (PP), lung fibrosis and histological evidence of ferruginous bodies (FB) can be used in combination with anamnestic data. However, such markers have never been associated with a threshold value of inhaled asbestos. With this study we attempted to shed light on the dose-response relationship of PP, lung fibrosis and FBs, investigating if their prevalence in exposed individuals who died from malignant mesothelioma (MM) is related to the concentration of asbestos in lungs assessed using scanning electron microscopy equipped with energy dispersive spectroscopy. Moreover, we estimated the values of asbestos concentration in lungs associated with PP, lung fibrosis and FB. Lung fibrosis showed a significant positive relationship with asbestos lung content, whereas PP and FB did not. We identified, for the first time, critical lung concentrations of asbestos related to the presence of PP, lung fibrosis and FB at histology (respectively, 19 800, 26 400 and 27 400 fibers per gram of dry weight), that were all well-below the background levels of asbestos identified in our laboratory. Such data suggest that PP, lung fibrosis and FB at histology should be used with caution in the causal attribution of MM to past asbestos exposures, while evaluation of amphibole lung content using analytical electron microscopy should be preferred.

RevDate: 2023-12-08

Yang D, Zhou Y, K Lv (2023)

Analysis of Ki67 Protein Expression and Clinicopathological Features in Patients with Peritoneal Mesothelioma.

Alternative therapies in health and medicine pii:AT9817 [Epub ahead of print].

BACKGROUND: At present, there are many treatments for peritoneal mesothelioma, but the treatment of peritoneal mesothelioma is still facing great challenges. Distant metastasis is the main cause of poor prognosis and death of patients with peritoneal mesothelioma. Ki67 is a cell proliferation marker. In recent years, it has been found to be used as a molecular marker for the diagnosis, treatment and prognosis of different tumor cells. Ki67 has been shown to play a crucial role in the occurrence and development of a variety of cancers. However, the clinical significance and biological function of Ki67 in peritoneal mesothelioma remain poorly understood.

PURPOSE: To clarify the expression of Ki67 in peritoneal mesothelioma (PC), and to explore the relationship between the expression level of Ki67 and the clinicopathological parameters and prognosis of patients with PC, and to explore the potential of Ki67 as a therapeutic target and prognostic biomarker for PC.

METHODS: TIMER database was used to compare the expression levels of Ki67 mRNA and protein in mesothelioma tissues and adjacent tissues. The relationship between the expression level of Ki67 in mesothelioma and clinicopathological characteristics, and the relationship between the expression level of Ki67 and the level of immune infiltration in mesothelioma were analyzed. The prognostic value of Ki67 in mesothelioma patients was predicted, and the overall survival curve was drawn according to the follow-up data. LinkedOmics database and GSEA were used to perform co-expression analysis and enrichment analysis of Ki67, respectively.

RESULTS: Bioinformatics analysis showed that Ki67 was highly expressed in peritoneal mesothelioma (P < .01). Immunohistochemistry showed that the positive rate of Ki67 in peritoneal mesothelioma was high, and the number of Ki67 positive cases was 62.0% (31/50 cases). Univariate analysis showed that TNM stage (P = .007), asbestos (P < .001), chemotherapy (P < .001), and Ki67 expression level (P = .029) were associated with prognosis. Multivariate analysis showed that Ki67 expression level (P = .039) and TNM stage (P = .029) were independent risk factors for the prognosis of peritoneal mesothelioma. Peritoneal mesothelioma patients with high Ki67 expression have poor OS. In addition, Ki67 is also associated with the immune infiltration of mesothelioma.

CONCLUSION: Ki67 is highly expressed in peritoneal mesothelioma. Ki67 protein plays an important role in the development of peritoneal mesothelioma and is one of the important factors to evaluate the prognosis of patients with peritoneal mesothelioma.

RevDate: 2023-12-08

Martella S, Aiello MM, Bertaglia V, et al (2023)

Malignant Pleural Mesothelioma: Staging and Radiological Response Criteria in Patients Treated with Immune Checkpoint Inhibitors.

Targeted oncology [Epub ahead of print].

Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.

RevDate: 2023-12-06

Wang D, Wang YH, SC Chu (2023)

Case Report: Early diagnosis and bevacizumab-based chemotherapy for primary pericardial mesothelioma: a case with occupational asbestos exposure history.

Frontiers in cardiovascular medicine, 10:1257373.

BACKGROUND: Primary pericardial mesothelioma (PPM) is an exceedingly rare malignant cancer and has a poor prognosis, which has been partly attributed to its frequently delayed diagnosis due to its nonspecific syndromes, its similar presentation to benign pericardial diseases, and its non-definitive etiology. In many PPM cases, the time from presentation to definite diagnosis may last for several months or even over one year. Unlike pleural mesothelioma, the relationship between PPM and asbestos exposure remains unsettled. To date, there is no consensus on the treatment of PPM.

CASE REPORT: The patient is a 57-year-old male who had nonspecific syndromes and inconclusive image findings. The occupational long-term asbestos exposure history of this patient raised our concerns regarding potential malignancy when confronted with unexplained pericardial effusion accompanied by cardiac tamponade. The heightened suspicion prompted us to perform pericardiocentesis and biopsy on the third day after admission to our department. An early diagnosis of PPM was established by the pathological and immunohistochemical evaluation of the biopsy specimen two weeks after admission. Positron emission tomography-computed tomography revealed that the lesion was localized at the anterior part of the mediastinum without distant metastasis. This patient refused to receive cardiac surgery. He subsequently underwent six cycles of chemotherapy (cisplatin plus pemetrexed) in combination with bevacizumab (a humanized anti-VEGF antibody) as the first-line treatment, resulting in complete relief of symptoms and satisfactory outcomes with no complications. Four months after the first course, the patient initiated a second course of chemotherapy with a similar regimen, but he opted to discontinue the medical treatment after the initiation of the second course. The patient was transferred to the hospice care unit and unfortunately expired one year after the initial presentation.

CONCLUSION: We present a case of an early multidisciplinary clinical approach to diagnose and manage PPM with consideration of occupational asbestos exposure history and clinical symptoms. Bevacizumab-based chemotherapy remains an option for the treatment of PPM.

RevDate: 2023-12-04

Klebe S, Judge M, Brcic L, et al (2023)

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

Histopathology [Epub ahead of print].

AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers.

METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading.

CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).

RevDate: 2023-12-02

Visonà SD, Bertoglio B, Favaron C, et al (2023)

A postmortem case control study of asbestos burden in lungs of malignant mesothelioma cases.

Journal of translational medicine, 21(1):875.

BACKGROUND: Asbestos lung content is regarded as the most reliable tool for causal attribution of malignant mesothelioma (MM) to previous asbestos exposures. However, there is a lack of studies on asbestos burden in lungs of MM patients in comparison with healthy individuals. This study aims to provide such a comparison, investigating, as well, differences in asbestos lung burden with sex and time trends.

METHODS: Asbestos lung content has been assessed on formalin-fixed lung fragments using scanning electron microscopy coupled with energy dispersion spectroscopy (SEM-EDS) on individuals deceased from MM (cases) and healthy subjects without any lung disease who died from violent causes (controls) between 2005 and 2023.

RESULTS: Asbestos and asbestos bodies (ABs) were found, respectively, in 73.7% and 43.2% of cases and in 28 and 22% of controls; in MM cases the most represented asbestos types were crocidolite and amosite, whereas in controls it was tremolite-actinolite asbestos. The concentration of both asbestos fibers and ABs was statistically significantly higher in MM cases compared to controls. The mean asbestos fibers width was also significantly higher in cases than controls. Males and females with MM showed similar asbestos and ABs concentrations, but females had higher concentrations of chrysotile, and significantly lower fibers width compared to males. Time trends show that MM lung asbestos concentrations decreased starting in 2011.

DISCUSSION: The results suggest a correlation between asbestos burden in lungs and MM risk. The different concentration of chrysotile, as well as the different width of asbestos fibers in MM males and females might reflect a sex difference in response of the lung microenvironment to inhaled asbestos. Finally, this study provides the first pathological evidence of the effect of the ban of asbestos use, demonstrating a significant decrease of asbestos lung content after 2011.

RevDate: 2023-12-01

Zupanc C, Franko A, Strbac D, et al (2023)

The association of genetic factors with serum calretinin levels in asbestos-related diseases.

Radiology and oncology, 57(4):473-486.

BACKGROUND: Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility.

SUBJECTS AND METHODS: The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis.

RESULTS: Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes.

CONCLUSIONS: The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.

RevDate: 2023-11-30

McNamee N, Harvey C, Gray L, et al (2023)

Brief Report: Real-world toxicity and survival of combination immunotherapy in pleural mesothelioma - RIOMeso.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer pii:S1556-0864(23)02370-5 [Epub ahead of print].

BACKGROUND: Australia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-yr overall survival (OS) of 10%. First line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate743 (CM743) trial, with supportive data from the later line single arm MAPS2 trial. RIOMeso examines survival and toxicity of this regimen in real-world practice.

METHODS: Demographic and clinicopathological data of Australian patients treated with ipilimumab and nivolumab in first and subsequent line settings for pleural mesothelioma was collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log rank test. Toxicity was investigator-assessed using CTCAE v5.0.

RESULTS: 119 patients were identified from 11 centres. The median age was 72, 83% were male, 92% were ECOG ≤1, 50% were past or current smokers and 78% had known asbestos exposure. 50% were epithelioid, 19% sarcomatoid, 14% biphasic and 17% unavailable. Ipilimumab and nivolumab was used first line in 75% of patients. Median OS (mOS) was 14.5 months (95%CI 13.0-NA) for the entire cohort. For patients treated first line, mOS was 14.5 months (95%CI 12.5-NA) and in second or later line patients was 15.4 months (95%CI 11.2-NA). There was no statistically significant difference in mOS for epithelioid histology compared to non-epithelioid (19.1 months [95%CI 15.4-NA] vs 13.0 months [95%CI 9.7-NA] respectively, P=0.064). 24% of patients had a CTCAE grade ≥ 3 adverse event, including 3 treatment-related deaths. Colitis was the most frequent adverse event.

CONCLUSION: Combination immunotherapy in real-world practice has poorer survival outcomes and appears more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.

RevDate: 2023-11-30

Geyer SJ (2023)

A cluster of mesotheliomas reported in a case series does not implicate chrysotile asbestos-containing friction products as the cause of mesotheliomas.

RevDate: 2023-11-29

Miller A (2023)

Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.

American journal of industrial medicine [Epub ahead of print].

Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.

RevDate: 2023-11-29

Yoshida M, Jimbo N, Tsukamoto R, et al (2023)

Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma.

Diagnostic pathology, 18(1):126.

BACKGROUND: Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts.

CASE PRESENTATION: This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma.

CONCLUSION: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.

RevDate: 2023-11-28

Nash A, J Creaney (2023)

Genomic Landscape of Pleural Mesothelioma and Therapeutic Aftermaths.

Current oncology reports [Epub ahead of print].

PURPOSE OF REVIEW: In this article, we provide a comprehensive analysis of recent progress in the genetic characterisation of pleural mesothelioma, and the translation of these findings to clinical practice.

RECENT FINDINGS: Advancements in sequencing technology have allowed the identification of driver mutations and improved our understanding of how these mutations may shape the mesothelioma tumour microenvironment. However, the identification of frequently mutated regions including CDKN2A, BAP1 and NF2 have, to date, not yet yielded targeted therapy options that outperform standard chemo- and immunotherapies. Similarly, the association between mutational profile and the immune microenvironment or immunotherapy response is not well characterised. Further research into the link between tumour mutational profile and response to therapy is critical for identifying targetable vulnerabilities and stratifying patients for therapy.

RevDate: 2023-11-25

Sorino C, Mondoni M, Marchetti G, et al (2023)

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers.

Journal of clinical medicine, 12(22): pii:jcm12227006.

Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

RevDate: 2023-11-24

Nel AE, Pavlisko EN, VL Roggli (2023)

The Interplay between the Immune System, Tumor Suppressor Genes, and Immune Senescence in Mesothelioma Development and Response to Immunotherapy.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer pii:S1556-0864(23)02373-0 [Epub ahead of print].

Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable around 2500 cases annually. This trend is not unique to the US but is also a global phenomenon, associated with increased aging of populations worldwide. While geo-economic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency following asbestos exposure. However, the long latency period, often cited as a reason for mesothelioma's elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered tumor suppressor gene (TSG) function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, healthcare professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma.

RevDate: 2023-11-23

Somigliana AB, Barbieri PG, Cavallo A, et al (2023)

Lung asbestos fiber burden analysis: effects of the counting rules for legal medicine evaluations.

Inhalation toxicology [Epub ahead of print].

OBJECTIVES: The work shows the effect of counting rules, such as analysis magnification and asbestos fiber dimension to be count (with length ≥5 µm or also asbestos fibers with length <5 µm) in the lung asbestos fiber burden analysis for legal medicine evaluations.

METHODS: On the same lung tissue samples, two different analyses were carried out to count any asbestos fibers with length ≥1 µm and with length ≥5 µm. Results of the amphibole burden of the two analyses were compared by linear regression analysis on log10-transformed values.

RESULTS: The analysis should be carried out at an appropriate magnification and on samples prepared in such a way as they allow the counting of very fine fibers. If the analysis is limited to the asbestos fibers with length ≥5 µm, there is a high risk of not detecting possible residual chrysotile fiber burden and thinner crocidolite asbestos fibers.

CONCLUSIONS: On average we estimated that 1 amphibole fiber with length ≥5 µm corresponds to ∼8 amphibole fibers with length ≥1 µm in the lung. The values of the Helsinki criteria should be updated taking this into account.

RevDate: 2023-11-17

Salman A, Abdel Mageed SS, Fathi D, et al (2023)

Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma.

Pathology, research and practice, 252:154947 pii:S0344-0338(23)00648-9 [Epub ahead of print].

Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/β-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.

RevDate: 2023-11-17

John A, O'Sullivan H, S Popat (2023)

Updates in Management of Malignant Pleural Mesothelioma.

Current treatment options in oncology [Epub ahead of print].

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated thoracic malignancy that is usually incurable. As demonstrated in the landmark MARS2 trial, surgical resection does not improve survival outcomes and its role in managing MPM is limited. Whilst platinum-pemetrexed chemotherapy in combination with bevacizumab was the standard first-line approach for unresectable disease, landmark phase 3 trials have now established the role of immune checkpoint inhibitors (CPIs) in the upfront management of unresectable disease: either nivolumab-ipilimumab or carboplatin-pemetrexed-pembrolizumab. Patient selection for optimal strategy remains an ongoing question. For relapsed disease novel genomic-based therapies targeting a range of aberrations including losses of the tumour suppressor genes BAP1, CDKN2A and NF2, are being evaluated. Nonetheless, the future of MPM therapeutics holds promise. Here we overview current treatment strategies in the management of MPM.

RevDate: 2023-11-15
CmpDate: 2023-11-15

Takefuji Y (2024)

An urgent call to action: The absolute necessity to ban asbestos production and sales.

The Science of the total environment, 906:167557.

The issue with asbestos highlights the shortcomings in the global management of health policies for dangerous substances. The perils of asbestos dust were identified about a century ago. A significant number of individuals succumb to asbestos-related diseases worldwide annually. A considerable portion of occupational cancer fatalities are believed to be due to asbestos. A large population across the globe is exposed to asbestos in their workplaces. To address issues like asbestos, it is crucial for policymakers to prioritize public interest, and third parties should actively participate in scrutinizing the actions of these policymakers.

RevDate: 2023-11-14

Gun RT, GM Kendall (2023)

Asbestos-related cancer in naval personnel: findings from participants in the British nuclear tests 1952-1967.

Scientific reports, 13(1):18842.

Asbestos-containing materials (ACM) were present in British and Australian naval vessels throughout the twentieth century. The aim of this study was to identify and quantify the incidence of cancer in naval personnel from onboard asbestos exposure. Subjects were four cohorts of subjects who had served in the armed forces of the United Kingdom and Australia in the 1950s and 1960s. All cohorts had previously been studied, three of them in relation to radiation exposures from British nuclear testing. Comparisons of SIRs between services were made to identify cancers attributable to asbestos exposure. Excess mesotheliomas were found in naval personnel in all cohorts. In all but one cohort the lung cancer incidence was highest in navy personnel. Comparison of other smoking-related conditions indicated that the excess in navy personnel was not smoking-related. The relatively high SIRs for mesothelioma and the occurrence of deaths from asbestosis were indicative of high levels of asbestos exposure, with an expectation of cases of asbestos-related lung cancer. The findings are consistent with the occurrence of significant excesses of mesotheliomas. In addition, notwithstanding some inconsistencies in the results between the cohorts, we estimated that approximately 27% of lung cancers in Australian seamen and 12% in British seamen were related to onboard asbestos exposure.

RevDate: 2023-11-09

Grignani P, Visonà SD, Fronda MV, et al (2023)

The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples.

Frontiers in public health, 11:1236558.

Asbestos-related diseases still represent a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a poor-prognosis cancer, arising from the serosal lining of the pleura, pericardium and peritoneum, triggered by asbestos exposure. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, considered to be both protective and harmful. Two sample sets of individuals were taken into consideration, both residing in Broni or neighboring cities (Northwestern Italy) where an asbestos cement factory was active between 1932 and 1993. The present study aims to compare the frequency of six SNPs involved in iron trafficking, previously found to be related to protection/predisposition to MM after asbestos exposure, between 48 male subjects with documented asbestos exposure who died of MM and 48 male subjects who were exposed to asbestos but did not develop MM or other neoplastic respiratory diseases (Non-Mesothelioma Asbestos Exposed - NMAE). The same analysis was performed on 76 healthy male controls. The allelic and genotypic frequencies of a sub-group of 107 healthy Italian individuals contained in the 1000 genomes database were considered for comparison. PCR-multiplex amplification followed by SNaPshot mini-sequencing reaction was used. The findings presented in this study show that the allelic and genotypic frequencies for six SNP markers involved in iron metabolism/homeostasis and the modulation of tumor microenvironment are not significantly different between the two sample sets of MM and NMAE. Therefore, the SNPs here considered do not seem to be useful markers for individual susceptibility to mesothelioma. This finding is not in agreement with previous literature.

RevDate: 2023-11-03

Esteban Porcar A, García Gómez M, Santana Yllobre L, et al (2023)

[Reconocimiento del mesotelioma de pleura como enfermedad profesional en la Comunidad Valenciana de 2012 a 2018.].

Revista espanola de salud publica, 97: pii:e202309074.

OBJECTIVE: Pleural mesothelioma is a neoplasm almost exclusively attributed to occupational exposure to asbestos and is legally considered an occupational disease. Nevertheless, only a few cases achieve that official recognition. The objective of this work was to describe and analyse this issue, and to identify the major obstacles to its recognition.

METHODS: A descriptive and retrospective epidemiological study of data was carried out, including figures and some characteristics, of all patients with pleural mesothelioma registered in the official health and labor registries of the Valencian Community from 2012 to 2018, using frequencies, proportions, and incidence rates.

RESULTS: There were large differences between the two sets of data collected in the different registries, especially regarding the number of cases. During the seven years of data examined, 590 pleural mesotheliomas were diagnosed in the Valencian public health system. Of these, the number of cases that were related to occupational exposure was at least 437. Despite the legal duty of doctors to report such cases, only 31 were reported as suspected occupational disease (7.09%), of which only 13 were ultimately officially recognized as such. It was estimated that the annual economic overcost to the public system of unrecognised patients with this occupational disease by was 2,2270,520 euros.

CONCLUSIONS: Only a small proportion of occupational mesotheliomas are officially recognized as such. This has important health care and economic repercussions for the individuals involved as well as for the public health system.

RevDate: 2023-11-02

Aydogdu G, S Özekinci (2023)

Contribution of BAP1 loss and p16 (CDKN2A) deletion analysis to the definitive diagnosis of mesothelioma in effusion cytology.

European review for medical and pharmacological sciences, 27(20):10001-10007.

OBJECTIVE: The cytological diagnosis of mesothelioma is a controversial issue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of BRCA1-associated protein (1) (BAP1) loss and p16 (CDKN2A) homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids.

MATERIALS AND METHODS: Between 2019-2022, 21 pleural and peritoneal fluid samples diagnosed with atypical mesothelial proliferation in our institution were included in the study. The slides of the cases that underwent BAP1 immunohistochemistry (IHC) were retrieved from the archive and re-examined. Homozygous deletion (HD) of p16 (CDKN2A) was investigated by the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples. At least 100 atypical mesothelial cells were counted in each case, and the HD threshold value was >10%.

RESULTS: The mean age of the cases was 63.47 years (34-90 years), female/male ratio was 3/1. Of the pleural mesothelioma cases, 16 were epithelioid, 2 were biphasic, and 1 were sarcomatoid. Two cases were diagnosed with peritoneal well-differentiated papillary mesothelioma (WDPM). BAP1 loss was observed in 11 (69%) of 16 cases. HD deletion of p16 (CDKN2A) was seen in 11 (58%) patients with FISH. The HD threshold value was 10-20% in 6 of the cases, 30-50% in 3 cases, and above 90% in 2 cases. While HD deletion was observed in p16 (CDKN2A) in all biphasic and sarcomatoid cases (n=3), no deletion was observed in peritoneal WDPM (n=2). Positivity was observed with at least one method in 12 (86%) of 14 pleural mesotheliomas who underwent both BAP1 IHC and p16 (CDKN2A) FISH. Due to technical reasons, the FISH signal could not be obtained in two cell blocks, so no results could be obtained.

CONCLUSIONS: Asbestos exposure in areas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cytological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Although the FISH method applied to cell blocks has cytology-specific limitations and difficulties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis.

RevDate: 2023-10-30

Qualiotto AN, Baldavira CM, Balancin M, et al (2023)

Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma.

Frontiers in immunology, 14:1268927.

BACKGROUND: The combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.

METHODS: The discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin & eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.

RESULTS: Most patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15-10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09-6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58-9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.

CONCLUSION: Tumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.

RevDate: 2023-10-30

Yu M, Yang D, Chen C, et al (2023)

Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure.

Journal of environmental science and health. Part C, Toxicology and carcinogenesis [Epub ahead of print].

Crocidolite is a carcinogen contributing to the pathogenesis of malignant mesothelioma. This study aimed to characterize the possible telomere-related events mediating the malignant transformation of mesothelial cells with and without SETD2 under crocidolite exposure. The crocidolite concentration resulting in 90% viable SETD2 knockout Met-5A (Met-5A[SETD2-KO]) and Met-5A were estimated to be 0.71 μg/cm[2] and 1.8 μg/cm[2], respectively, during 72 h of exposure, which was further employed in chronical crocidolite exposure during a 72 h exposure interval per time up to 1 month. Chronical crocidolite-exposed Met-5A[SETD2-KO] (chronical Cro-Met-5A[SETD2-KO]) had higher colony formation and increased telomerase reverse transcriptase (TERT) protein levels than chronical crocidolite-exposed Met-5A (chronical Cro-Met-5A) and Met-5A[SETD2-KO]. Chronical Cro-Met-5A[SETD2-KO] had longer telomere length (TL) than chronical Cro-Met-5A, although there were no changes in TL for either chronical Cro-Met-5A or chronical Cro-Met-5A[SETD2-KO] compared with their corresponding cells without crocidolite exposure. BIBR 1532, an inhibitor targeting TERT, partially reduced colony formation and TL for chronical Cro-Met-5A[SETD2-KO], while BIBR 1532 reduced TL but had no effect on colony formation for chronical Cro-Met-5A. Therefore, SETD2 deficient mesothelial cells are susceptible to malignant transformation during chronical crocidolite exposure, and TERT-dependent TL modification likely partially drives SETD2 loss-mediated early onset of mesothelial malignant transformation.

RevDate: 2023-10-29

May IJ, Nowak AK, Francis RJ, et al (2023)

The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.

Journal of medical imaging and radiation oncology [Epub ahead of print].

INTRODUCTION: Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters.

METHODS: Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle.

RESULTS: Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P = 0.028, HR = 1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis.

CONCLUSION: This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.

RevDate: 2023-10-28

Leinardi R, Petriglieri JR, Pochet A, et al (2023)

Distinct Pro-Inflammatory Mechanisms Elicited by Short and Long Amosite Asbestos Fibers in Macrophages.

International journal of molecular sciences, 24(20): pii:ijms242015145.

While exposure to long amphibolic asbestos fibers (L > 10 µm) results in the development of severe diseases including inflammation, fibrosis, and mesothelioma, the pathogenic activity associated with short fibers (L < 5 µm) is less clear. By exposing murine macrophages to short (SFA) or long (LFA) fibers of amosite asbestos different in size and surface chemistry, we observed that SFA internalization resulted in pyroptotic-related immunogenic cell death (ICD) characterized by the release of the pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation and gasdermin D (GSDMD)-pore formation. In contrast, macrophage responses to non-internalizable LFA were associated with tumor necrosis factor alpha (TNF-α) release, caspase-3 and -7 activation, and apoptosis. SFA effects exclusively resulted from Toll-like receptor 4 (TLR4), a pattern-recognition receptor (PRR) recognized for its ability to sense particles, while the response to LFA was elicited by a multifactorial ignition system involving the macrophage receptor with collagenous structure (SR-A6 or MARCO), reactive oxygen species (ROS) cascade, and TLR4. Our findings indicate that asbestos fiber size and surface features play major roles in modulating ICD and inflammatory pathways. They also suggest that SFA are biologically reactive in vitro and, therefore, their inflammatory and toxic effects in vivo should not be underestimated.

RevDate: 2023-10-27

Lee FW, Chen YH, Tran ND, et al (2023)

Association between Asbestos Exposure and the Incidence of Kidney Cancer: a Weight-of-Evidence Evaluation and Meta-analysis.

Current environmental health reports [Epub ahead of print].

PURPOSE OF REVIEW: Occupational asbestos exposure has been extensively linked to various cancers, with ongoing debates regarding its association with kidney cancer. This study aims to investigate the correlation between occupational asbestos exposure and kidney cancer incidence. Additionally, potential influencing factors are analyzed to enhance the comprehension of the relationship between asbestos exposure and kidney cancer.

RECENT FINDING: While asbestos has established strong associations with malignant mesothelioma and lung cancer, its connection to other malignancies such as gastric, colorectal, and kidney cancers remains under scrutiny. The current study presents mixed opinions on the relationship between asbestos exposure and kidney cancer. Our analysis revealed a potential association between asbestos exposure and the incidence of kidney cancer. Notably, among different types of asbestos, exposure to amphibole appeared to be particularly linked to a higher incident risk of kidney cancer.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

963 Red Tail Lane
Bellingham, WA 98226


E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

long standard version

RJR Picks from Around the Web (updated 11 MAY 2018 )