ABSTRACT
BACKGROUND AND OBJECTIVE: Mesothelial cells and cardiomyocytes have shared embryonic mesodermal origin. Cardiomyocytes release BNP under stretch. We searched whether malignant mesothelioma cells also secrete BNP and if so, this has a meaningful impact. METHODS: Part I: Prospectively, patients with pleural lesions on CT having malignant mesothelioma effusions (MME, n = 13) were compared to patients with malignant effusions with pleural lesions (MEa, n = 14). Age-matched patients with ME without pleural lesions (MEb, n = 16) and non-malignant effusions (NME, n = 25) were analysed. Part II: Retrospectively, samples from patients with mesothelioma (n = 14), lung cancer (n = 8) or heart failure (n = 9) were used. BNP was measured in pleural fluid and blood/plasma. Part III: BNP was assessed in the culture supernatants of benign (MeT-5A) and malignant mesothelioma cell lines (M14K-epithelioid, MSTO-biphasic and ZL34-sarcomatoid) (n = 10 per cell line in three different biological replicates). RESULTS: In vitro, BNP concentration was significantly higher in the supernatant of all malignant cell lines than benign ones (P < 0.01), denoting BNP's production from the former. The pleural fluid to blood BNP ratio in MME was extremely high in Part I and Part II subjects (28.3 ± 12.1 and 25.9 ± 8.6, respectively) versus 1.1 ± 0.3 and 0.4 ± 0.1 in Part I ME and NME, respectively (P < 0.0001), and 0.8 ± 0.1 and 0.4 ± 0.1 in Part II ME and NME, respectively (P < 0.0001). BNP ratio ≥2.11 in Part I had 92% sensitivity and 94.5% specificity for MME (P < 0.0001). CONCLUSION: BNP is secreted from malignant mesothelial cells. In clinical practice, the pleural fluid to blood BNP ratio can help in the diagnosis of malignant mesothelioma.
Subject(s)
Mesothelioma, Malignant/diagnosis , Mesothelioma, Malignant/pathology , Natriuretic Peptide, Brain/metabolism , Aged , Cell Line, Tumor , Female , Humans , Male , Mesothelioma, Malignant/blood , Natriuretic Peptide, Brain/blood , Prospective Studies , Retrospective StudiesABSTRACT
The impact of temsirolimus was investigated in a murine model of malignant pleural effusion (MPE) created with intrapleural injection of Lewis Lung Cancer (LLC) cells. Temsirolimus (1 or 20 mg/kg) did not affect the pleural fluid volume or the number of pleural tumour foci. In addition, temsirolimus did not affect vascular endothelial growth factor expression by LLC cells in vitro. In conclusion, temsirolimus did not curtail experimental lung-adenocarcinoma-induced MPE.
Subject(s)
Adenocarcinoma/drug therapy , Lung Neoplasms/drug therapy , Neoplasms, Experimental , Pleural Effusion, Malignant/prevention & control , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Animals , Cell Line, Tumor , Immunosuppressive Agents/therapeutic use , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Pleural Effusion, Malignant/metabolism , Pleural Effusion, Malignant/pathologyABSTRACT
BACKGROUND AND OBJECTIVE: The role of pro-inflammatory interleukin-17A (IL-17A), in pleural diseases is unknown. We sought to investigate IL-17A expression and its clinical implications in patients with pleural effusion (PE) and IL-17A involvement in the pathobiology of pleural inflammation elicited by bacterial products. METHODS: Pleural and blood IL-17A content was examined in 84 patients with PE of different aetiologies, and the diagnostic value of pleural IL-17A was explored in 92 patients with neutrophil-predominant PE. IL-17A contribution in pleural inflammation was evaluated in mice injected intrapleurally with either IL-17A or bacterial products with or without IL-17A-neutralizing antibodies. RESULTS: IL-17A was upregulated in the pleural space of patients with parapneumonic PE. It was detected in a minority of patients with tuberculous PE and very uncommonly in patients with malignant or other pleural exudates. Pleural fluid (PF) IL-17A levels were correlated with markers of acute pleural inflammation, as well as vascular endothelial growth factor and IL-8 levels. Among patients with neutrophil-predominant PE, PF IL-17A was detected only in those with parapneumonic PE, although the sensitivity of the test was low (<50%). Intrapleural injection of IL-17A elicited a neutrophil-predominant inflammatory response in mice, and IL-17A neutralization partially blocked pleural neutrophilia induced by intrapleural administration of bacterial products. CONCLUSIONS: IL-17A is involved in pleural inflammation related to bacterial infection. Moreover, pleural IL-17A levels may be helpful in uncovering an infectious aetiology among patients with neutrophil-predominant PE.
