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Nature Communications Mar 2022The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies...
The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Epithelium; Mesothelioma; Mice; Transcription Factors; Zebrafish; Zebrafish Proteins
PubMed: 35354817
DOI: 10.1038/s41467-022-29311-7 -
International Journal of Molecular... Mar 2020Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the... (Review)
Review
Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the pleural cavity, while the remaining cases initiate in the peritoneal cavity, in the pericardial cavity or on the tunica vaginalis. Usually, mesotheliomas grow in a diffuse pattern and tend to enclose and compress the organs in the various body cavities. Mesothelioma incidence is increasing worldwide and still today, the prognosis is very poor, with a reported median survival of approximately one year from presentation. Thus, the development of alternative and more effective therapies is currently an urgent requirement. The aim of this review article was to describe recent findings about the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas. The potential clinical implications of these findings are discussed.
Topics: Antineoplastic Agents; Curcumin; Humans; Mesothelioma, Malignant; Phytochemicals; Pleura; Pleural Neoplasms; Prognosis
PubMed: 32155978
DOI: 10.3390/ijms21051839 -
AME Case Reports 2023Malignant mesothelioma (MM) is a rare cancer with poor prognosis. It is less common that two serosal cavities are involved when the patient seeks medical attention...
BACKGROUND
Malignant mesothelioma (MM) is a rare cancer with poor prognosis. It is less common that two serosal cavities are involved when the patient seeks medical attention firstly. The current first-line chemotherapy for advanced MM is a combination with cisplatin and pemetrexed. However, nedaplatin, a second-generation platinum-based antitumor agent, has the similar therapeutic effects as cisplatin but lower toxicity and higher water solubility. To our knowledge, this is the first case of co-existing pericardial and pleural MM treated with nedaplatin and pemetrexed and responding well.
CASE DESCRIPTION
A 33-year-old woman, who had worked in a kiln for more than 10 years, suffered from dyspnea and chest tightness for 6 days. Chest computed tomography (CT) showed a massive pericardial effusion. She was diagnosed tuberculous pericarditis and received 6 months antituberculosis treatment (rifampicin, isoniazide, pyrazinamide, ethambutol). But it was ineffective and she was re hospitalized again due to massive pleural effusion and pericardial effusion. She was diagnosed with co-existing pericardial and pleural MM finally based on pleural biopsy and cytology of pericardial effusion. She was responding well excitedly to chemotherapy with nedaplatin and pemetrexed with high tolerance. Bone marrow toxicity or recurrent massive pericardial or pleural effusion were not observed during chemotherapy. However, she gave up chemotherapy and has survived for 22 months, from the onset symptoms.
CONCLUSIONS
In terms of clinical tolerance and less adverse reactions, we suggest that chemotherapy of nedaplatin with pemetrexed may be a more appropriate treatment in advanced MM. Further clinical trials are warrant.
PubMed: 37942039
DOI: 10.21037/acr-22-102 -
Annals of Translational Medicine Dec 2022Pericardial mesothelioma (PeM) is a rare disease with non-specific symptoms at the onset, because of its rarity, the relevant literature is limited to case reports and...
BACKGROUND
Pericardial mesothelioma (PeM) is a rare disease with non-specific symptoms at the onset, because of its rarity, the relevant literature is limited to case reports and small case series, with no cases exceeding 100 in more than 20 years. As the most common initial symptoms are chest tightness and shortness of breath, early diagnosis is difficult, and the beginning of treatment is easily delayed. We present a rare case of difficult-to-diagnose PeM in which the diagnosis was clarified by surgery and the patient achieved a long survival, providing clinicians with our experience in treating this disease at an early stage of diagnosis and early treatment.
CASE DESCRIPTION
A 65-year-old female patient attended Affiliated Hospital of Zunyi Medical University, complaining about chest tightness and shortness of breath after activity for the last 2 months, accompanied by edema of the lower limbs in last month. A well circumscribed anterior-mediastinal, partially cystic mass was observed on the chest computed tomography. The patient's heart was compressed by the mass, and the patient had cardiac tamponade symptoms. Cardiac ultrasound showed the enlargement of the right heart, a widened pulmonary artery, pulmonary hypertension, and severe tricuspid regurgitation. The nature of the mass could not be determined prior to the surgery. Anterior superior mediastinal tumour resection and partial pericardial resection and closed thoracic drainage in a median open chest were performed, and pathohistological analysis revealed localized pericardial, epithelioid mesothelioma. In a follow-up after 19 months patient was generally well and without specific discomfort.
CONCLUSIONS
Differential diagnosis of the anterior mediastinal mass is broad. In patients with a mediastinal tumour who have significant symptoms, are difficult to diagnose and can tolerate surgery, the thoracic surgeon can use surgery as early as possible to make a definitive diagnosis, save the patient's life, and/or improve the patient's quality of life, experienced pathologist is essential to make fast and correct diagnosis.
PubMed: 36660732
DOI: 10.21037/atm-22-4719 -
Veterinary Sciences Aug 2021Idiopathic pericarditis (IP) and pericardial mesothelioma (PM) are causes of pericardial effusion in dogs. Pericardiectomy can be a definitive treatment in the case of...
Idiopathic pericarditis (IP) and pericardial mesothelioma (PM) are causes of pericardial effusion in dogs. Pericardiectomy can be a definitive treatment in the case of idiopathic pericardial effusion or a short-term intervention for mesothelioma. The aim of the present study was to investigate which histopathologic parameters are correlated with clinical outcomes in a cohort of dogs that underwent pericardiectomy. The histopathological findings of 22 IPs and 5 PMs were compared with clinical and survival data and the immunohistochemical characterization of immune cells (CD3, CD79α, Iba1). In IP, the mesothelium was lost in 20 cases, reactive in 9, atypical in 3, and mesothelial papillary hyperplasia (MPH) was observed in 4 cases. Numerous macrophages were found in both IPs and PMs especially at the superficial layer of the pericardium. T lymphocytes were observed in mild to moderate numbers and were more numerous than B lymphocytes in both IPs and PMs. MPH was correlated with the quantity of lymphoplasmacytic infiltrate in the superficial layer, inversely related to the thickness of the pericardium, and associated with a longer overall survival. Pericardial fibrosis was present in 19 out of 22 IPs and in all mesotheliomas and was correlated with increased time from initial presentation and pericardiectomy and lymphoplasmacytic infiltrate in the deep zone. Pericardial thickness was correlated with the amount of lymphoplasmacytic and macrophagic infiltrate in the deep zone. Mesothelioma was associated with an increased number of pericardiocentesis procedures before pericardiectomy and with the presence of macrophages in the superficial pericardial layer, edema, fibrin, and hemorrhage. Disease-free interval and overall survival were significantly shorter in patients with mesothelioma compared with IP.
PubMed: 34437484
DOI: 10.3390/vetsci8080162 -
Translational Lung Cancer Research Jun 2020Malignant mesothelioma (MM) is uncommon, but very aggressive tumor arising from the mesothelial cells of pleura, pericardium, peritoneum, and tunica vaginalis. Despite... (Review)
Review
Malignant mesothelioma (MM) is uncommon, but very aggressive tumor arising from the mesothelial cells of pleura, pericardium, peritoneum, and tunica vaginalis. Despite multimodality treatments 5-year survival is only 5% after the diagnosis. Histology and TNM staging system are still the best prognostic factors. Furthermore, histologic subtype of MM determines the clinical management of the patients. According to the 2015 WHO classification, MM is divided into diffuse, localized and well differentiated papillary mesothelioma. Major histologic subtypes of diffuse MM, namely epithelioid, biphasic and sarcomatoid, have different prognosis. However, in the last decade it has become evident that more detailed subclassification and histologic/cytological characterization of MM have prognostic and perhaps predictive implications. In this review, major histologic subtypes and cytological features of MM are presented and their relation with prognosis and predictive biomarkers is discussed.
PubMed: 32676358
DOI: 10.21037/tlcr.2020.03.38 -
Frontiers in Veterinary Science 2023Canine mesothelioma is a rare malignant tumor that mostly affects body cavities, such as the pericardial and pleural cavities. Chemotherapy plays a crucial role in the...
INTRODUCTION
Canine mesothelioma is a rare malignant tumor that mostly affects body cavities, such as the pericardial and pleural cavities. Chemotherapy plays a crucial role in the treatment of canine mesotheliomas. We aimed to compare the antitumor effects of single-agent and combination chemotherapeutic agents on patient-derived primary cultures of canine pericardial mesothelioma established in this study. We planned to generate xenograft models for future studies.
MATERIAL AND METHODS
Effusion samples were collected from three dogs with histologically diagnosed pericardial mesothelioma and used for primary culture. Cultured cells were characterized by immunostaining for pan-cytokeratin AE1/AE3, vimentin, Wilms' tumor suppressor gene 1 (WT1), and cytokeratin 5 (CK5). To assess the tumorigenic properties of cells in the effusion and generate a xenograft model, the cell suspension was injected into a severe combined immunodeficient (SCID) mouse either subcutaneously (SC) or intraperitoneally (IP). Lastly, chemosensitivity of established primary cultures against four drugs, doxorubicin, vinorelbine, carboplatin, and gemcitabine, by single-agent treatment as well as combination treatment of carboplatin at a fixed concentration, either 10 or 100 μM, and gemcitabine at different concentrations ranging from 0-1000 μM was assessed by cell viability assay.
RESULTS
Primary cultures were successfully generated and characterized by dual positivity for AE1/AE3 and vimentin and positive staining for WT-1 and CK5, confirming the mesothelial origin of the cells. In the xenograft models, SC mouse developed a subcutaneous mass, whereas IP mouse developed multiple intraperitoneal nodules. The masses were histopathologically consistent with mesotheliomas. The chemosensitivity assay revealed that carboplatin had the highest anti-tumor effects among the four tested single-agent treatments. Furthermore, carboplatin at 100 μM combined with gemcitabine at clinically relevant doses demonstrated the augmented anti-tumor effects compared to single-agent treatment.
DISCUSSION AND CONCLUSION
Primary cultures and xenograft models generated in this study could be useful tools for and studies of canine mesothelioma. Carboplatin is a highly effective chemotherapeutic agent against canine mesothelioma when used as a sole agent and in combination with gemcitabine.
PubMed: 38026668
DOI: 10.3389/fvets.2023.1267359 -
Veterinary Medicine and Science Mar 2023The characteristics of non-electrocardiography- and electrocardiography-gated multidetector computed tomography have not been extensively studied in veterinary clinics...
OBJECTIVES
The characteristics of non-electrocardiography- and electrocardiography-gated multidetector computed tomography have not been extensively studied in veterinary clinics but it can be useful for cardiac imaging. This study aimed to ascertain the differences between non-electrocardiography and electrocardiography gating methods and to establish their clinical utility based on patient history.
METHODS
Six client-owned dogs (two with patent ductus arteriosus, two with heart base tumour, one with pericardial mesothelioma, and one with normal health) were included in this study. All the dogs were examined using a non-electrocardiography-gated scan, followed by a retrospective electrocardiography-gated scan. Images were reviewed to determine the optimal scan timing and R-R interval in non-electrocardiography- and electrocardiography-gated images, respectively, for detailed coronary artery imaging, diagnostic quality of the best coronary artery visualisation in non-electrocardiography- and electrocardiography-gated images through visual assessment of the main coronary artery branches, and branching patterns of the left coronary artery. Further, we compared the size and margin demarcation of the heart or pericardial lesions in non-electrocardiography- and electrocardiography-gated images obtained from patients with heart or pericardial tumours.
RESULTS
The optimal scan timing and R-R interval were the second-scan timing and end-diastole (70%-90%), respectively. Second-scan non-electrocardiography-gated images allowed coronary artery evaluation, indicating high-grade quality in visual assessment, except for the septal branch. Electrocardiography-gated images, but not non-ECG-gated images, clearly revealed pericardial nodules in two dogs.
CLINICAL SIGNIFICANCE
Our findings suggest the respective clinical utilities of non-electrocardiography- or electrocardiography-gated imaging using high-slice cardiac computed tomography based on patient history.
Topics: Dogs; Animals; Retrospective Studies; Electrocardiography; Heart; Hospitals, Animal; Tomography
PubMed: 36318187
DOI: 10.1002/vms3.985 -
Pediatric and Developmental Pathology :... 2021Malignant mesothelioma is a neoplasm of serosal surfaces, most commonly affecting the pleura. The peritoneum, pericardium, and tunica vaginalis are less frequently...
Malignant mesothelioma is a neoplasm of serosal surfaces, most commonly affecting the pleura. The peritoneum, pericardium, and tunica vaginalis are less frequently involved. Malignant mesothelioma with fusion in young adults was recently reported in the literature. Here, we present two pediatric cases of translocation-associated malignant mesothelioma in the peritoneum and pericardium respectively. Both cases lacked a known exposure history. Microscopy in both cases showed predominantly epithelioid morphology with ample eosinophilic cytoplasm, and immunohistochemistry was positive for pan-keratin, calretinin, and WT1. Both cases showed gene rearrangement by RNA sequencing, which was instrumental in confirming the diagnosis of malignant mesothelioma and to exclude more common pediatric sarcomas, especially in the context of limited sampling.
Topics: Adolescent; Child; Gene Fusion; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Mesothelioma; Mesothelioma, Malignant; Oncogene Proteins, Fusion; RNA-Binding Protein EWS; Young Adult
PubMed: 34121509
DOI: 10.1177/10935266211021222 -
Cancers Nov 2022Malignant Mesothelioma (MM) is an aggressive neoplasm of the pleural mesothelium, less frequently peritoneal and exceptionally of the vaginal tunic of the testicle and...
Malignant Mesothelioma (MM) is an aggressive neoplasm of the pleural mesothelium, less frequently peritoneal and exceptionally of the vaginal tunic of the testicle and pericardium [...].
PubMed: 36428633
DOI: 10.3390/cancers14225540