Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy, thus early diagnosis of MPM is extremely critical. CT scans have limited accuracy in the differentiation between benign and malignant pleural disease. Several studies have reported that 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the assessment of thoracic malignancy such as lung cancer. Here, we investigated the clinical utility of PET in patients with MPM. The maximum SUV (SUVmax) of 18F-FDG was measured in 47 MPM patients and 29 non-MPM patients including those with pleural thickening. We demonstrated that patients with MPM had significantly higher SUVmax levels than a population with non-malignant pleural disease. The Kaplan-Meier method revealed significant differences in overall survival between groups with SUVmax levels lower and higher than the assumed cut-off. Our data suggest that SUVmax levels are useful as an aid for diagnosis and prognosis of MPM.

Background/Aims: Sphingosine regulates cellular differentiation, cell growth, and apoptosis. The present study aimed at understanding sphingosine-regulated mesothelioma cell proliferation. Methods: Human malignant mesothelioma cells such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells were cultured. The siRNA to silence the protein kinase C (PKC)-δ-targeted gene was constructed and transfected into cells. MTT assay, cell cycle analysis using a flow cytometry, and cell-free PKC-δ assay were carried out. Results: For all the cell types sphingosine inhibited cell growth in a concentration (1-100 µM)-dependent manner. The sphingosine effect was not prevented by rottlerin, an inhibitor of protein kinase C-δ (PKC-δ); conversely, rottlerin further enhanced the sphingosine effect or rottlerin suppressed mesothelioma cell growth without sphingosine. In the cell-free PKC assay, sphingosine attenuated PKC-δ activity. Knocking-down PKC-δ induced cell cycle arrest at the G0/G1 phase and inhibited cell growth. Conclusion: The results of the present study show that sphingosine suppressed mesothelioma cell proliferation by inhibiting PKC-δ, to induce cell cycle arrest at the G0/G1 phase.

Abstract. Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM exhibits a limited response to conventional chemotherapy and radiotherapy. This, early diagnosis of MPM is essential. Malignant tumor progression requires the destruction of the basement membrane, which is constructed from extracellular matrix (ECM) materials. Various types of human tumor cells are reported to produce ECM-degrading proteases that are important in tumor progression. Among this group of proteolytic enzymes, matrix metalloproteinases (MMPs) are thought to be important due to their wide degrading function. We investigated the pleural effusion MMP-3 levels of patients with MPM and compared them with those of a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The pleural effusion MMP-3 concentrations of 52 MPM patients and 67 non-MPM patients were measured. The results showed that the MPM patients had significantly higher pleural effusion MMP-3 levels than the population with non-malignant pleuritis. The overall survival of the MPM patients with lower pleural effusion MMP-3 levels was longer than that of patients with higher pleural effusion MMP-3 levels. Our data therefore suggest a clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma. IntroductionMalignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure (1-3). The lifetime risk of MPM is associated with a history of occupational and/or environmental asbestos exposure (4). Due to the long latency period (typically over 30 years) between the first asbestos exposure and the onset of the disease, MPM remains a universally fatal disease of increasing incidence worldwide (1,2,5), although asbestos usage has recently decreased in Western countries and Japan.Malignant tumor progression requires the destruction of the basement membrane (BM), which is constructed from extracellular matrix (ECM) materials. Various human tumor cells are reported to produce ECM-degrading proteases that are important in tumor progression (6). Among this group of proteolytic enzymes, matrix metalloproteinases (MMPs) are thought to be important due to their wide degrading function. MMPs are zinc-dependent endopeptidases, whose activities are targeted to all components of the ECM (7).MMP-3 is known to be involved in tumor cell invasion and metastasis (8). The increased expression of MMP-3 has been reported in several malignant tumors, including esophageal cancer (9), breast cancer (10) and glioma (11). Moreover, a correlation between a higher MMP-3 expression and disease progression has been reported in patients with gastric cancer (12), hepatocellular carcinoma (13) and bladder cancer (14). However, the clinical importance of MMP-3 in MPM patients has not been fully investigated, although MMP-3 expression has been reported in certain MPM cells (15,16). In this study, we evaluated the clinical role of the p...