bims-mesote 2022-10-02 papers

Issue of 2022–10–02
five papers selected by
Laura Mannarino, Humanitas Research

Clin Oncol (R Coll Radiol). 2022 Sep 22. pii: S0936-6555(22)00374-0. [Epub ahead of print]

What's Current and What's New in Mesothelioma?

J L Leal, W Hoang, J Xue, B Dunne, T John, S Harden.

Malignant mesothelioma is a rare disease with limited treatment options. In malignant pleural mesothelioma (MPM), radical trimodality approaches, including surgery, radiotherapy and systemic chemo- and immunotherapy, have been delivered in some countries but remain controversial due to a lack of randomised evidence. Even in the unresectable scenario, surgery and radiotherapy play an important role in managing pleural effusions and pain, which may optimise wellbeing and maintain performance status. From the systemic treatment point of view, the recent incorporation of anti-angiogenics and, more importantly, immunotherapy has changed the standard of care in a space where chemotherapy with platinum and pemetrexed was the only therapeutic intervention with demonstrated benefits in overall survival. Histology is essential in determining an initial treatment plan as non-epithelioid MPMs may have a higher substantial survival improvement with dual immunotherapy compared with chemotherapy, whereas chemotherapy remains an option for epithelioid MPM; however, predictive biomarkers for systemic therapy are not entirely validated to guide the selection, as a subgroup of MPM patients might not benefit from immunotherapy. This overview approaches how the overall management of mesothelioma is evolving to incorporate the recent changes in the standards of care.

Keywords: Chemotherapy; immune checkpoint inhibitors; immunotherapy; malignant pleural mesothelioma; mesothelioma radiotherapy; mesothelioma surgery

DOI: https://doi.org/10.1016/j.clon.2022.08.029

Cancer Drug Resist. 2022 ;5(3): 814-828

Butein-instigated miR-186-5p-dependent modulation of TWIST1 affects resistance to cisplatin and bioenergetics of Malignant Pleural Mesothelioma cells.

Mario Cioce, Daniela Rutigliano, Annamaria Puglielli, Vito Michele Fazio.

Aim: Malignant pleural mesothelioma is a chemoresistant tumor, and biphasic and sarcomatoid histologies portend the worst prognosis for malignant pleural mesothelioma (MPM) patients. We obtained the microRNA expression profile of three biphasic-sarcomatoid MPM cell lines to identify commonly expressed microRNAs and evaluate the effect of butein, a chemo-sensitizing compound, on this microRNA subset. Methods: Nanostring-based microRNA profiling and analysis through the ROSALIND platform were employed to identify the commonly modulated microRNAs and their targets. MicroRNA-mimic transfection, Luciferase assay, and Western blotting were employed to show specific perturbation of TWIST1 levels by miR-186-5p. Sphere-forming assays, invasion assay, and metabolic profiling were used to assess the biological consequences of the butein-instigated miR-186-5p-mediated perturbation of TWIST1 levels. TGCA analysis was used to search for the correlation between TWIST1 and miR-186-5p levels in biphasic and epithelioid MPM specimens. Results: We identified a set of perturbed microRNAs, common to three biphasic/sarcomatoid MPM cell lines, after butein treatment. When focusing on miR-186-5p, we unraveled a butein-ignited and miR-186-5p-mediated modulation of TWIST1 levels which affected the 3D anchorage-independent growth, cisplatin resistance, invasion, and bioenergetics of the MPM cell lines tested. We showed that miR-186-5p and TWIST1 levels are anti-correlated in biphasic MPM specimens from TCGA. Conclusion: We unraveled a novel mechanism of action of butein, which attenuated the pro-tumorigenic features of MPM at least through a miR-186-5p-TWIST1 axis. We suggest that those activities converge into the chemo-sensitizing effect of this compound and may be of translational relevance.

Keywords: Mesothelioma; TWIST1; anchorage-independent growth; butein; cancer metabolism; chemoresistance; invasion; miR-186-5p; pithelial-to-mesenchymal transition (EMT)

DOI: https://doi.org/10.20517/cdr.2022.56

Medicine (Baltimore). 2022 Sep 30. 101(39): e30711

Factors affecting the life expectancy in malignant pleural mesothelioma: Our 10 years of studies and experience.

Filiz Cimen, Yetkin Agackiran, Sevim Düzgün, Melike Aloglu, Aysegül Senturk, Sükran Atikcan.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. In our study, we aimed to investigate the specific clinical, laboratory, and radiological features of the tumor and the prognostic effect of SUVmax (maximum standardized uptake values) according to PET/CT (positron emission tomography). Demographic, therapeutic, clinical, and survival information of patients diagnosed with histologically-validated pleural mesothelioma in our hospital between January 2010 to December 2019 will be retrospectively scanned from the hospital records. A total of 116 patients, 61 men (52.6%), and 55 women (47.4%), were analyzed. Thirty five patients (30.2%) were over the age of 65. Percentage of patients over 65 years of age, neutrophil count, and PET SUV Max values, asbestos exposure and pleural thickening rate were significantly higher in the deceased patients' group than in the living patients' group (P = .042, P = .039, P = .002, P = .004, P = .037). T stage (tumor stage), N stage (lymph nodes stage), metastasis stage, and Grade distribution were significantly higher in the deceased patients' group than in the living patients' group (P < .000, P < .000, P = .003, P < .000). The rates of chemotherapy and surgical treatment, right lung location, and epithelioid pathology were significantly lower in the deceased patients' group compared to the living patients' group (P = .016, P = .030, P = .018, P = .008). The mean follow-up time was 13 months. Key determinants of survival in MPM include age, male gender, neutrophil increase, pleural thickening, high PET SUV max values, stage, histological type, asbestos exposure, and treatment regimen.

DOI: https://doi.org/10.1097/MD.0000000000030711

Pol J Pathol. 2022 Sep 29. pii: 47863. [Epub ahead of print]

Investigation of pd-l1 (cd274), pd-l2 (pdcd1lg2), and ctla-4 expressions in malignant pleural mesothelioma by immunohistochemistry and real-time polymerase chain reaction methods.

Fatma Sule Kutlar Dursun, Ulas Alabalik.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignant disease with a poor prognosis, which affects the surface mesothelium of the pleural cavity. Immune checkpoints are responsible for controlling the immune system to avoid autoimmunity and prevent tissue damage. In this study, we aimed to investigate the expression of cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) immuno-control receptors in MPM patients and the relationship of the expression with tumour types and prognostic parameters.
MATERIAL AND METHODS: In this study, we evaluated 50 MPM cases. Immunohistochemically CTLA-4, PD-L1, and PD-L2 were detected by using monoclonal anti-CTLA-4, anti-PD-L1, and anti-PD-L2. Real-time polymerase chain reaction (RT-PCR) analysis was performed with the primers CTLA-4, PD-L1, and PD-L2.
RESULTS: Statistically, no significant relation was determined between the PD-L1, PD-L2, and CTLA-4 expressions (immunohistochemical and RT-PCR methods) and the MPM histological type. Interestingly significant correlation was observed between the mean survival time and immunohistochemical PD-L2 expression; thus, long-term survival was observed in cases with PD-L2 expression.
CONCLUSIONS: Programmed death ligand 1, PD-L2, and CTLA-4 expression were observed in some MPM cases, suggesting that treatments targeting immune checkpoints may be effective. Because immunohistochemical expression of PD-L2 is associated with better prognosis, it may provide useful clues in the follow-up of patients.

Keywords: PD-L1 (CD274); PD-L2 (PDCD1LG2); immune checkpoints; malignant pleural mesothelioma; programmed cell death ligand 1; programmed cell death ligand 2; CTLA-4

DOI: https://doi.org/10.5114/pjp.2022.119752

Saf Health Work. 2022 Sep;13(3): 302-307

Analysis of Mortality from Asbestos-Related Diseases in Brazil Using Multiple Health Information Systems, 1996-2017.

Eduardo Algranti, Vilma S Santana, Felipe Campos, Leonardo Salvi, Cézar A Saito, Franciana Cavalcante, Heleno R Correa-Filho.

Background: In Brazil, asbestos was intensively used from the 1960s until its ban in 2017. Mesothelioma, asbestosis, and pleural plaques are typical asbestos-related diseases (ARD-T). To create an ARD-T national database, death records from 1996-2017 were retrieved from several health information systems (HIS).
Methods: All national HIS containing coded diagnoses (ICD-10) and death information were obtained. Linkage was performed to create a single database of ARD-T death records, either as underlying or contributory causes, in adults aged 30 years and older.
Results: A total of 3,057 ARD-T death records were found, 2,405 (76.4%) of which being malignant mesotheliomas (MM). Pleural MM (n = 1,006; 41.8%) and unspecified MM (n = 792; 32.9%) prevailed. Male to female MM ratio (M:F) was 1.4:1, and higher ratios were found for non-malignant ARD-T: 3.5:1 for asbestosis and 2.4:1 for pleural plaques. Male crude annual mesothelioma mortality (CMmm x1,000,000) was 0.98 in 1996 and 2.26 in 2017, a 131.1% increment, while for females it was 1.04 and 1.25, a 20.2% increase, correspondingly. The small number of deaths with asbestosis and pleural plaques records precluded conclusive interpretations.
Conclusions: Even with the linkage of several HIS, ARD-T in death records remained in low numbers. MM mortality in men was higher and showed a rapid increase and, along with non-malignant ARD-T, higher M:F ratios suggested a predominant pattern of work-related exposure. The monitoring of workplace and environmental asbestos exposure needs to be improved, as well as the workers surveillance, following the recent Brazilian ban.

Keywords: Asbestos; Asbestosis; Mesothelioma; Occupational exposure; Pleural plaques

DOI: https://doi.org/10.1016/j.shaw.2022.04.006