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Seminars in Thoracic and Cardiovascular... 2022
Topics: Heart Neoplasms; Humans; Mesothelioma; Mesothelioma, Malignant; Pericardium; Treatment Outcome
PubMed: 34469797
DOI: 10.1053/j.semtcvs.2021.08.017 -
Cancer Treatment and Research 2023There is no denying that many revolutions took place in the fight against cancer during the last decades. However, cancers have always managed to find new ways to... (Meta-Analysis)
Meta-Analysis
There is no denying that many revolutions took place in the fight against cancer during the last decades. However, cancers have always managed to find new ways to challenge humankinds. Variable genomic epidemiology, socio-economic differences and limitations of widespread screening are the major concerns in cancer diagnosis and early treatment. A multidisciplinary approach is essentially to manage a cancer patient efficiently. Thoracic malignancies including lung cancers and pleural mesothelioma are accountable for little more than 11.6% of the global cancer burden [4]. Mesothelioma is one of the rare cancers, but concern is the incidences are increasing globally. However, the good news is first-line chemotherapy with the combination of immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and mesothelioma has showed promising respond and improved overall survival (OS) in pivotal clinical trials [10]. ICIs are commonly referred as immunotherapy are antigens on the cancer cells, and inhibitors are the antibodies produce by the T cell defence system. By inhibiting immune checkpoints, the cancer cells become visible to be identified as abnormal cells and attack by the body's defence system [17]. The programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1) inhibitors are commonly used immune checkpoint blockers for anti-cancer treatment. PD-1/PD-L1 are proteins produced by immune cells and mimic by cancer cells that are implicated in inhibiting T cell response to regulate our immune system, which results tumour cells escaping the defence mechanism to achieve immune surveillance. Therefore, inhibiting immune checkpoints as well as monoclonal antibodies can lead to effective apoptosis of tumour cells [17]. Mesothelioma is an industrial disease caused by significant asbestos exposure. It is the cancer of the mesothelial tissue which presents in the lining of the mediastinum of pleura, pericardium and peritoneum, most commonly affected sites are pleura of the lung or chest wall lining [9] as route of asbestos exposure is inhalation. Calretinin is a calcium binding protein, typically over exposed in malignant mesotheliomas and the most useful marker even while initial changes take place [5]. On the other hand, Wilm's tumour 1 (WT-1) gene expression on the tumour cells can be related to prognosis as it can elicit immune response, thereby inhibit cell apoptosis. A systematic review and meta-analysis study conducted by Qi et al. has suggested that expression of WT-1 in a solid tumour is fatal however, it gives the tumour cell a feature of immune sensitivity which then acts positively towards the treatment with immunotherapy. Clinical significance of WT-1 oncogene in treatment is still hugely debatable and needs further attention [21]. Recently, Japan has reinstated Nivolumab in patients with chemo-refractory mesothelioma. According to NCCN guidelines, the salvage therapies include Pembrolizumab in PD-L1 positive patients and Nivolumab alone or with Ipilimumab in cancers irrespective of PD-L1 expression [9]. The checkpoint blockers have taken over the biomarker-based research and demonstrated impressive treatment options in immune sensitive and asbestos-related cancers. It can be expected that in near future the immune checkpoint inhibitors will be considered as approved first-line cancer treatment universally.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immunotherapy; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Nivolumab; Programmed Cell Death 1 Receptor; Receptors, Death Domain
PubMed: 37306905
DOI: 10.1007/978-3-031-27156-4_5 -
Proceedings of the National Academy of... Jan 2023is a powerful tumor suppressor gene characterized by haplo insufficiency. Individuals carrying germline mutations often develop mesothelioma, an aggressive malignancy...
is a powerful tumor suppressor gene characterized by haplo insufficiency. Individuals carrying germline mutations often develop mesothelioma, an aggressive malignancy of the serosal layers covering the lungs, pericardium, and abdominal cavity. Intriguingly, mesotheliomas developing in carriers of germline mutations are less aggressive, and these patients have significantly improved survival. We investigated the apparent paradox of a tumor suppressor gene that, when mutated, causes less aggressive mesotheliomas. We discovered that mesothelioma biopsies with biallelic mutations showed loss of nuclear HIF-1α staining. We demonstrated that during hypoxia, binds, deubiquitylates, and stabilizes HIF-1α, the master regulator of the hypoxia response and tumor cell invasion. Moreover, primary cells from individuals carrying germline mutations and primary cells in which was silenced using siRNA had reduced HIF-1α protein levels in hypoxia. Computational modeling and co-immunoprecipitation experiments revealed that mutations of residues I675, F678, I679, and L691 -encompassing the C-terminal domain-nuclear localization signal- to A, abolished the interaction with HIF-1α. We found that binds to the N-terminal region of HIF-1α, where HIF-1α binds DNA and dimerizes with HIF-1β forming the heterodimeric transactivating complex HIF. Our data identify as a key positive regulator of HIF-1α in hypoxia. We propose that the significant reduction of HIF-1α activity in mesothelioma cells carrying biallelic mutations, accompanied by the significant reduction of HIF-1α activity in hypoxic tissues containing germline mutations, contributes to the reduced aggressiveness and improved survival of mesotheliomas developing in carriers of germline mutations.
Topics: Humans; Heterozygote; Hypoxia-Inducible Factor 1, alpha Subunit; Mesothelioma; Mesothelioma, Malignant; Mutation; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 36656861
DOI: 10.1073/pnas.2217840120 -
Journal of Thoracic Oncology : Official... Sep 2018Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium,... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected to increase worldwide in the next two decades. However, even with the use of multimodality treatment, MPM remains challenging to treat, with a 5-year survival rate of less than 5%. The International Association for the Study of Lung Cancer has gathered experts in different areas of mesothelioma research and management to summarize the most significant scientific advances and new frontiers related to mesothelioma therapeutics.
Topics: Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant
PubMed: 29966799
DOI: 10.1016/j.jtho.2018.06.011 -
Annals of Epidemiology May 2017Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the... (Review)
Review
PURPOSE
Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the pericardium and tunica vaginalis testis (TVT). This review provides a better understanding of the epidemiology of mesothelioma of these extrapleural sites.
METHODS
We conducted a systematic review of the epidemiologic and clinical literature on pericardial mesothelioma and mesothelioma of the TVT. We also analyzed U.S. Surveillance, Epidemiology, and End Results cancer registry data to describe incidence patterns of these malignancies.
RESULTS
An etiologic role of asbestos exposure has been hypothesized for pericardial and TVT mesotheliomas, but no analytical case-control epidemiologic studies exist to test this relationship. A substantial proportion of cases with these malignancies report no known asbestos exposure. In large occupational cohorts with heavy asbestos exposures, no cases of pericardial or TVT mesothelioma have been reported. Trends in the incidence of these malignancies do not match those of pleural mesothelioma, which correspond to historical trends of commercial asbestos use. A male preponderance of pericardial mesothelioma is not evident.
CONCLUSIONS
In the absence of analytic epidemiologic studies, the etiologic role of environmental risk factors for mesothelioma of the pericardium and TVT remains elusive.
Topics: Asbestos; Female; Heart Neoplasms; Humans; Male; Mesothelioma; Middle Aged; Occupational Diseases; Pericardium; Registries; Testicular Neoplasms; Testis; United States
PubMed: 28527639
DOI: 10.1016/j.annepidem.2017.04.001 -
BMC Cardiovascular Disorders Mar 2023Pericardial calcification is usually a marker of chronic diseases, and its occurrence in rapidly progressing malignant primary pericardial mesothelioma (PPM) is...
BACKGROUND
Pericardial calcification is usually a marker of chronic diseases, and its occurrence in rapidly progressing malignant primary pericardial mesothelioma (PPM) is extremely rare. Therefore, this atypical imaging appearance contributes to more frequent misdiagnosis of PPM. However, no systematic summary currently exists of the imaging characteristics of malignant pericardial calcification in PPM. In our report, its clinical characteristics are discussed in detail, to provide a reference to reduce the misdiagnosis rates of PPM.
CASE PRESENTATION
A 50-year-old female patient was admitted to our hospital, presenting primarily with features suggestive of cardiac insufficiency. Chest computed tomography revealed significant pericardial thickening and localized calcification, suspicious of constrictive pericarditis. A chest examination performed through a midline incision showed a chronically inflamed and easily-ruptured pericardium that was closely adherent to the myocardium. Post-operative pathological examination confirmed a diagnosis of primary pericardial mesothelioma. Six weeks postoperatively, the patient experienced symptom recurrence and abandoned chemotherapy and radiation therapy. Nine months postoperatively, the patient died of heart failure.
CONCLUSION
We report this case to highlight the rare finding of pericardial calcification in patients with primary pericardial mesothelioma. This case illustrated that confirmation of pericardial calcification cannot completely rule out rapidly developing PPM. Therefore, understanding the different radiological features of PPM can help to reduce its rate of early misdiagnosis.
Topics: Female; Humans; Middle Aged; Mesothelioma; Diagnosis, Differential; Pericardium; Pericarditis, Constrictive; Mesothelioma, Malignant; Heart Neoplasms; Heart Failure; Thymus Neoplasms
PubMed: 36890475
DOI: 10.1186/s12872-023-03142-w -
Frontiers in Oncology 2022Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium... (Review)
Review
Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.
PubMed: 35223506
DOI: 10.3389/fonc.2022.823839 -
Klinicka Onkologie : Casopis Ceske a... 2019Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea... (Review)
Review
Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.
Topics: Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Mesothelioma; Peritoneal Neoplasms
PubMed: 31610664
DOI: 10.14735/amko2019333 -
European Heart Journal Feb 2024
Topics: Humans; Mesothelioma; Pericardium; Heart Neoplasms
PubMed: 38085299
DOI: 10.1093/eurheartj/ehad763 -
Modern Pathology : An Official Journal... Sep 2023Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be...
Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases. Two patients were female and 1 was male, aged between 66 and 75 years. Two patients each had prior asbestos exposure and were smokers. Histologic subtypes were epithelioid in 2 cases and biphasic in 1 case. Immunohistochemical staining identified expression of cytokeratin AE1/AE3 and calretinin in all cases, D2-40 in 2 cases, and WT1 in 1 case. Staining for tumor suppressors revealed loss of p16, MTAP, and Merlin (NF2) expression in 2 cases and loss of BAP1 and p53 in 1 case. Abnormal cytoplasmic BAP1 expression was observed in an additional case. Protein expression abnormalities correlated with NGS results, which showed concurrent complete genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, and NF2 in 2 mesotheliomas and of BAP1 and TP53 in 1 mesothelioma each, respectively. In addition, 1 patient harbored a pathogenic BRCA1 germline mutation, which resulted in biallelic inactivation in the mesothelioma. All mesotheliomas were mismatch repair proficient and showed several chromosomal gains and losses. All patients died from disease. Our study demonstrates that pericardial mesotheliomas share common morphologic, immunohistochemical, and molecular genetic features with pleural mesothelioma, including recurrent genomic inactivation of canonical tumor suppressors. Our study adds new insights into the genetic landscape of primary pericardial mesothelioma and highlights BRCA1 loss as a potential contributing factor in a subset of cases, thereby contributing to refined precision diagnostics for this rare cancer.
Topics: Humans; Male; Female; Aged; Lung Neoplasms; Neoplasm Recurrence, Local; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Heart Neoplasms; Thymus Neoplasms; Ubiquitin Thiolesterase; Biomarkers, Tumor
PubMed: 37295554
DOI: 10.1016/j.modpat.2023.100237