Cancers

Research

14 pages, 1942 KiB

Open AccessArticle

Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma—A Retrospective Multicenter Analysis

by Sarah Hintermair, Stephanie Iser, Alexander Varga, Melanie Biesinger, Tomas Bohanes, Ali Celik, Muhammet Sayan, Aykut Kankoç, Nalan Akyurek, Betul Öğüt, Elisabeth Stubenberger and Bahil Ghanim

Cancers 2024, 16(10), 1817; https://doi.org/10.3390/cancers16101817 - 10 May 2024

Viewed by 2148

Abstract

Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter [...] Read more.

Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5–55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7–14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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13 pages, 1189 KiB

Open AccessEditor’s ChoiceArticle

Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma

by Stephanie Iser, Sarah Hintermair, Alexander Varga, Ali Çelik, Muhammet Sayan, Aykut Kankoç, Nalan Akyürek, Betül Öğüt, Pietro Bertoglio, Enrico Capozzi, Piergiorgio Solli, Luigi Ventura, David Waller, Michael Weber, Elisabeth Stubenberger and Bahil Ghanim

Cancers 2024, 16(1), 93; https://doi.org/10.3390/cancers16010093 - 24 Dec 2023

Cited by 1 | Viewed by 2016

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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13 pages, 847 KiB

Open AccessArticle

Second Primary Cancers in a Population-Based Mesothelioma Registry

by Carolina Mensi, Simona Stella, Barbara Dallari, Sabrina Rugarli, Angela Cecilia Pesatori, Giovanni Luca Ceresoli and Dario Consonni

Cancers 2023, 15(6), 1746; https://doi.org/10.3390/cancers15061746 - 13 Mar 2023

Cited by 1 | Viewed by 1638

Abstract

Background: The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration. Methods: We evaluated the occurrence of SPCs within PM cases collected [...] Read more.

Background: The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration. Methods: We evaluated the occurrence of SPCs within PM cases collected from 2000 to 2018 by the Lombardy Mesothelioma Registry and their prognostic implications. Kaplan–Meier analysis was performed to estimate median survival times, together with univariate and multivariate Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of death. Results: The median overall survival (OS) of the entire study population (N = 6646) was 10.9 months (95% CI: 10.4–11.2); patient age and histotype were the strongest prognostic factors. No substantial survival difference was observed by the presence of an SPC (10.5 months in 1000 patients with an SPC vs. 10.9 months in 5646 patients in the non-SPC group, HR 1.03, p = 0.40). Shorter OS in the SPC group was only observed in 150 patients with the non-epithelioid subtype (median OS of 5.4 vs. 7.1 months, HR 1.21, p = 0.03). Conclusions: The diagnosis of an SPC did not influence the outcome of PM patients in the overall study population but was associated with shorter OS in non-epithelioid cases. Further studies are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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18 pages, 5727 KiB

Open AccessArticle

Water-Soluble Truncated Fatty Acid–Porphyrin Conjugates Provide Photo-Sensitizer Activity for Photodynamic Therapy in Malignant Mesothelioma

by Sam Bonsall, Simeon Hubbard, Uthaman Jithin, Joseph Anslow, Dylan Todd, Callum Rowding, Tom Filarowski, Greg Duly, Ryan Wilson, Jack Porter, Simon Turega and Sarah Haywood-Small

Cancers 2022, 14(21), 5446; https://doi.org/10.3390/cancers14215446 - 5 Nov 2022

Cited by 2 | Viewed by 2784

Abstract

Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated [...] Read more.

Clinical trials evaluating intrapleural photodynamic therapy (PDT) are ongoing for mesothelioma. Several issues still hinder the development of PDT, such as those related to the inherent properties of photosensitizers. Herein, we report the synthesis, photophysical, and photobiological properties of three porphyrin-based photosensitizers conjugated to truncated fatty acids (C5SHU to C7SHU). Our photosensitizers exhibited excellent water solubility and high PDT efficiency in mesothelioma. As expected, absorption spectroscopy confirmed an increased aggregation as a consequence of extending the fatty acid chain length. In vitro PDT activity was studied using human mesothelioma cell lines (biphasic MSTO-211H cells and epithelioid NCI-H28 cells) alongside a non-malignant mesothelial cell line (MET-5A). The PDT effect of these photosensitizers was initially assessed using the colorimetric WST-8 cell viability assay and the mode of cell death was determined via flow cytometry of Annexin V-FITC/PI-stained cells. Photosensitizers appeared to selectively localize within the non-nuclear compartments of cells before exhibiting high phototoxicity. Both apoptosis and necrosis were induced at 24 and 48 h. As our pentanoic acid-derivatized porphyrin (C5SHU) induced the largest anti-tumor effect in this study, we put this forward as an anti-tumor drug candidate in PDT and photo-imaging diagnosis in mesothelioma. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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21 pages, 3184 KiB

Open AccessArticle

ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100

by Elia Ranzato, Gregorio Bonsignore and Simona Martinotti

Cancers 2022, 14(17), 4126; https://doi.org/10.3390/cancers14174126 - 26 Aug 2022

Cited by 5 | Viewed by 2184

Abstract

Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. [...] Read more.

Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. To explore the biology of malignant pleural mesothelioma (MPM), we previously observed that MPM cell lines show high expression of the GRP78 protein, which is a chaperone protein and the master regulator of the unfolded protein response (UPR) that resides in the endoplasmic reticulum (ER). Based on our previous studies showing the importance of GRP78 in MPM, we observed that BOLD-100, a specific modulator of GRP78 and the UPR, shows cytotoxicity against MPM cells. Our studies demonstrated that BOLD-100 increases ROS production and Ca²⁺ release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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18 pages, 814 KiB

Open AccessArticle

An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma

by Emily K. Colvin, Amanda L. Hudson, Lyndsey L. Anderson, Ramyashree Prasanna Kumar, Iain S. McGregor, Viive M. Howell and Jonathon C. Arnold

Cancers 2022, 14(15), 3813; https://doi.org/10.3390/cancers14153813 - 5 Aug 2022

Cited by 10 | Viewed by 8281

Abstract

Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in [...] Read more.

Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines. A panel of 13 phytocannabinoids inhibited growth of human (MSTO and H2452) and rat (II-45) mesothelioma cells in vitro, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent compounds. Treatment with CBD or CBG resulted in G0/G1 arrest, delayed entry into S phase and induced apoptosis. CBD and CBG also significantly reduced mesothelioma cell migration and invasion. These effects were supported by changes in the expression of genes associated with the cell cycle, proliferation, and cell movement following CBD or CBG treatment. Gene expression levels of CNR1, GPR55, and 5HT1A also increased with CBD or CBG treatment. However, treatment with CBD or CBG in a syngeneic orthotopic rat mesothelioma model was unable to increase survival. Our data show that cannabinoids have anti-cancer effects on mesothelioma cells in vitro and alternatives of drug delivery may be needed to enhance their effects in vivo. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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Graphical abstract

10 pages, 470 KiB

Open AccessArticle

External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma

by Eline Janssens, Eline Schillebeeckx, Kathleen Zwijsen, Jo Raskin, Joris Van Cleemput, Veerle F. Surmont, Kristiaan Nackaerts, Elly Marcq, Jan P. van Meerbeeck and Kevin Lamote

Cancers 2022, 14(13), 3182; https://doi.org/10.3390/cancers14133182 - 29 Jun 2022

Cited by 3 | Viewed by 2259

Abstract

During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, [...] Read more.

During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM. The external validation cohort was prospectively recruited, consisting of 47 MPM patients and 76 asbestos-exposed (AEx) controls. The predictive performance of the previously developed model was assessed by determining the degree of agreement between the predicted and actual outcome of the participants (patient/control). Additionally, to optimise the performance, the model was updated by refitting it to the validation cohort. External validation revealed a poor performance of the original model as the accuracy was estimated at only 41%, indicating poor generalisability. However, subsequent updating of the model improved the differentiation between MPM patients and AEx controls significantly (73% accuracy, 92% sensitivity, and 92% negative predictive value), substantiating the validity of the original predictors. This updated model will be more generalisable to the target population and exhibits key characteristics of a potential screening test for MPM, which could significantly impact MPM management. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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17 pages, 1653 KiB

Open AccessArticle

Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients

by Arnulf Holzknecht, Oliver Illini, Maximilian J. Hochmair, Dagmar Krenbek, Ulrike Setinek, Florian Huemer, Erwin Bitterlich, Christoph Kaindl, Vladyslav Getman, Ahmet Akan, Michael Weber, Gunther Leobacher, Arschang Valipour, Michael R. Mueller and Stefan B. Watzka

Cancers 2022, 14(9), 2245; https://doi.org/10.3390/cancers14092245 - 30 Apr 2022

Cited by 2 | Viewed by 2995

Abstract

Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients’ survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of [...] Read more.

Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients’ survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4–20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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12 pages, 1123 KiB

Open AccessArticle

Effect of Asbestos Consumption on Malignant Pleural Mesothelioma in Italy: Forecasts of Mortality up to 2040

by Enrico Oddone, Jordy Bollon, Consuelo Rubina Nava, Dario Consonni, Alessandro Marinaccio, Corrado Magnani, Antonio Gasparrini and Francesco Barone-Adesi

Cancers 2021, 13(13), 3338; https://doi.org/10.3390/cancers13133338 - 3 Jul 2021

Cited by 14 | Viewed by 3734

Abstract

Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future [...] Read more.

Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future MPM cases in Italy until 2040, based on past asbestos consumption figures. Analyses were conducted using data on male MPM deaths (1970–2014) and annual asbestos consumption using data on domestic production, importation, and exportation. According to our model, the peak of MPM deaths is expected to occur in 2021 (1122 expected cases), with a subsequent decrease in mortality (344 MPM deaths in 2039). The exposure–response curve shows that relative risk (RR) of MPM increased almost linearly for lower levels of exposure but flattened at higher levels. The lag-specific RR grew until 30 years since exposure and decreased thereafter, suggesting that the most relevant contributions to the risk come from exposures which occurred 20–40 years before death. Our results show that the Italian MPM epidemic is approaching its peak and underline that the association between temporal trends of MPM and time since exposure to asbestos is not monotonic, suggesting a lesser role of remote exposures in the development of MPM than previously assumed. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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14 pages, 16907 KiB

Open AccessArticle

CSF1/CSF1R Axis Blockade Limits Mesothelioma and Enhances Efficiency of Anti-PDL1 Immunotherapy

by Sophia Fotiou Magkouta, Photene Christou Vaitsi, Apostolos Georgiou Pappas, Marianthi Iliopoulou, Chrysavgi Nikolaou Kosti, Katherina Psarra and Ioannis Theodorou Kalomenidis

Cancers 2021, 13(11), 2546; https://doi.org/10.3390/cancers13112546 - 22 May 2021

Cited by 31 | Viewed by 3968

Abstract

Colony-Stimulating Factor 1 (CSF1)/Colony-Stimulating Factor Receptor 1 (CSF1R) signaling orchestrates tumor-associated macrophage (TAM) recruitment and polarization towards a pro-tumor M2 phenotype, the dominant phenotype of TAMs infiltrating mesothelioma tumors. We hypothesized that CSF1/CSF1R inhibition would halt mesothelioma growth by targeting immunosuppressive M2 macrophages [...] Read more.

Colony-Stimulating Factor 1 (CSF1)/Colony-Stimulating Factor Receptor 1 (CSF1R) signaling orchestrates tumor-associated macrophage (TAM) recruitment and polarization towards a pro-tumor M2 phenotype, the dominant phenotype of TAMs infiltrating mesothelioma tumors. We hypothesized that CSF1/CSF1R inhibition would halt mesothelioma growth by targeting immunosuppressive M2 macrophages and unleashing efficient T cell responses. We also hypothesized that CSF1/CSF1R blockade would enhance the efficacy of a PDL1 inhibitor which directly activates CD8+ cells. We tested a clinically relevant CSF1R inhibitor (BLZ945) in mesothelioma treatment using syngeneic murine models. We evaluated the role of CSF1/CSF1R axis blockade in tumor-infiltrating immune subsets. We examined the effect of combined anti-CSF1R and anti-PDL1 treatment in mesothelioma progression. CSF1R inhibition impedes mesothelioma progression, abrogates infiltration of TAMs, facilitates an M1 anti-tumor phenotype and activates tumor dendritic and CD8+ T cells. CSF1R inhibition triggers a compensatory PD-1/PDL1 upregulation in tumor and immune cells. Combined CSF1R inhibitor with an anti-PDL1 agent was more effective in retarding mesothelioma growth compared to each monotherapy. In experimental mesotheliomas, CSF1R inhibition abrogates tumor progression by limiting suppressive myeloid populations and enhancing CD8+ cell activation and acts synergistically with anti-PDL1. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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21 pages, 3064 KiB

Open AccessArticle

Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature

by Luigi Vimercati, Domenica Cavone, Maria Celeste Delfino, Biagio Bruni, Luigi De Maria, Antonio Caputi, Stefania Sponselli, Roberta Rossi, Leonardo Resta, Francesco Fortarezza, Federica Pezzuto and Gabriella Serio

Cancers 2021, 13(9), 2278; https://doi.org/10.3390/cancers13092278 - 10 May 2021

Cited by 7 | Viewed by 6607

Abstract

Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either [...] Read more.

Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma “misclassification”, “misdiagnosis”, “diagnostic challenge” or “diagnostic pitfall” and on unsolved questions about its histogenesis and possible risk factors. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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20 pages, 7559 KiB

Open AccessArticle

Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells

by Maureen Keller, Katarina Reis, Anders Hjerpe, Katalin Dobra and Pontus Aspenström

Cancers 2021, 13(4), 685; https://doi.org/10.3390/cancers13040685 - 8 Feb 2021

Cited by 4 | Viewed by 2633

Abstract

Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, [...] Read more.

Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, which is dependent on dysregulated communication between the mesothelium and the microenvironment. This communication is dependent on the dynamic organization of the cytoskeleton. We have analyzed the organization and function of key cytoskeletal components in MM cell lines of increasing malignancies measured as migratory and invasive properties, and we show that highly malignant and invasive MM cells have an organization of the actin filament and vimentin systems that is distinct from the less malignant MM cell lines. In addition, the Hippo tumor suppressor pathway was inactivated in the invasive MM cells, which was seen as increased YAP nuclear localization. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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Review

Jump to: Research, Other

11 pages, 833 KiB

Open AccessReview

Malignant Pleural Mesothelioma: Current Understanding of the Immune Microenvironment and Treatments of a Rare Disease

by John Tedesco, Mark Jaradeh and Wickii T. Vigneswaran

Cancers 2022, 14(18), 4415; https://doi.org/10.3390/cancers14184415 - 11 Sep 2022

Cited by 4 | Viewed by 3512

Abstract

Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease [...] Read more.

Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease process with overall survival of roughly 6–12 months after the time of diagnosis. It is divided into three subtypes: epithelioid, mixed type, and sarcomatoid type, with the epithelioid subtype having the best overall survival. Often, the treatment is multimodality with surgery, chemotherapy, and radiation. The survival benefit is improved but remains marginal. New treatment options involving targeted immune therapies appear to offer some promise. The tumor microenvironment is the ecosystem within the tumor that interacts and influences the host immune system. Understanding this complex interaction and how the host immune system is involved in the progression of the disease process is important to define and guide potential treatment options for this devastating and rare disease. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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15 pages, 937 KiB

Open AccessReview

Epidemiology and Clinical Aspects of Malignant Pleural Mesothelioma

by Fraser Brims

Cancers 2021, 13(16), 4194; https://doi.org/10.3390/cancers13164194 - 20 Aug 2021

Cited by 35 | Viewed by 5800

Abstract

Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last [...] Read more.

Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last century and predominant occupational exposures mean that mesothelioma is mostly seen in males. Modern imaging techniques and advances in immunohistochemical staining have contributed to an improved diagnosis of mesothelioma. There have also been recent advances in immune checkpoint inhibition, however, mesothelioma remains very challenging to manage, especially considering its limited response to conventional systemic anticancer therapy and that no cure exists. Palliative interventions and support remain paramount with a median survival of 9–12 months after diagnosis. The epidemiology and diagnosis of mesothelioma has been debated over previous decades, due to a number of factors, such as the long latent period following asbestos exposure and disease occurrence, the different potencies of the various forms of asbestos used commercially, the occurrence of mesothelioma in the peritoneal cavity and its heterogeneous pathological and cytological appearances. This review will describe the contemporary knowledge on the epidemiology of mesothelioma and provide an overview of the best clinical practice including diagnostic approaches and management. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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21 pages, 655 KiB

Open AccessReview

Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

by Dannel Yeo, Laura Castelletti, Nico van Zandwijk and John E. J. Rasko

Cancers 2021, 13(16), 3932; https://doi.org/10.3390/cancers13163932 - 4 Aug 2021

Cited by 21 | Viewed by 4615

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many [...] Read more.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many other solid cancers overexpress MSLN, and this is associated with worse survival rates. However, this association has not been found in MPM, and the exact biological role of MSLN in MPM requires further exploration. Here, we discuss the current research on the diagnostic and prognostic value of MSLN in MPM patients. Furthermore, MSLN has become an attractive immunotherapy target in MPM, where better treatment strategies are urgently needed. Several MSLN-targeted monoclonal antibodies, antibody–drug conjugates, immunotoxins, cancer vaccines, and cellular therapies have been tested in the clinical setting. The biological rationale underpinning MSLN-targeted immunotherapies and their potential to improve MPM patient outcomes are reviewed. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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Other

Jump to: Research, Review

11 pages, 1232 KiB

Open AccessSystematic Review

Hyperthermic Intrathoracic Chemoperfusion for Malignant Pleural Mesothelioma: Systematic Review and Meta-Analysis

by Tommi Järvinen, Juuso Paajanen, Ilkka Ilonen and Jari Räsänen

Cancers 2021, 13(14), 3637; https://doi.org/10.3390/cancers13143637 - 20 Jul 2021

Cited by 13 | Viewed by 4794

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Hyperthermic intrathoracic chemoperfusion (HITHOC) is commonly used with surgery in limited disease. However, data on its effect on survival are limited. In this systematic review and meta-analysis, [...] Read more.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Hyperthermic intrathoracic chemoperfusion (HITHOC) is commonly used with surgery in limited disease. However, data on its effect on survival are limited. In this systematic review and meta-analysis, we analyzed a total of 11 observational articles. HITHOC was compared to control arm that did not receive HITHOC in three studies including 762 patients. The pooled analysis of these studies revealed an SMD of 0.24, with 95% CI of 0.06–0.41 favoring the HITHOC group, reaching statistical significance. The survival effect of HITHOC in epithelioid MPM vs. non-epithelioid MPM was analyzed in four studies. Pooled analysis showed an SMD of 0.79 (95% CI = 0.48–1.10) favoring epithelioid MPM. Based on available data, there seems to be a benefit with HITHOC in regards to overall survival in the treatment of all mesothelioma patients. Multicenter randomized controlled trials are needed to validate and standardize this treatment approach. Full article

(This article belongs to the Special Issue Recent Research on Mesothelioma)

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