Malignant pleural mesothelioma (MPM) is an aggressive cancer. MPM cells express aquaporin-1 (AQP1) that in other cancers has been shown to participate in the tumor metastasis processes. However, in MPM patients AQP1 overexpression is an independent prognostic factor favoring survival. In this study we aimed at evaluating the role of AQP1 in cell adhesion, migration, and tumor sphere formation in nonmalignant mesothelial cells (MeT-5A) and in epithelioid (M14K) and sarcomatoid (ZL34) MPM cell lines. We used fibronectin (FN) or homologous cell-derived extracellular martrix (ECM) substratum to investigate the role of AQP1 in these experimental phenotypes, inhibiting AQP1 by 10(-5) M mercury chloride (MC). Deposited ECM during cell culture exhibited significant concentration differences among cell types. ZL34 cell adhesion was significantly higher than MeT-5A or M14K cells on FN and ECM. MeT-5A and M14K cell adhesion on FN was sensitive to AQP1 inhibition, whereas AQP1 inhibition on ECM was limited to M14K cells. Wound healing in ZL34 cells was significantly higher than MeT-5A and M14K cells on FN and ECM. AQP1 inhibition significantly lowered cell migration in ZL34 cells on FN and ECM. Sphere formation was not dependent on FN or ECM in the media. AQP1 inhibition in FN media reduced sphere formation in M14K cells, whereas, in ECM, all three cell types were sensitive to AQP1 inhibition.
BackgroundChronic obstructive pulmonary disease (COPD) remains a significant cause of morbidity and mortality, with high rates of underdiagnosis. There are no studies about following up COPD patients in primary health care. The aim of the current study was to estimate two-year mortality for COPD patients in primary care and assess the parameters associated with mortality.MethodsA total of 263 patients with a new COPD diagnosis were followed up for two years. Follow-up included phone contacts every six months for assessment of vital status, and re-examination visits every year after the initial diagnosis. Visits included performance on spirometry, assessment of smoking status, evaluation of adherence with treatment, and assessment of the number of exacerbations during the previous year.ResultsOne hundred and eighteen patients with COPD completed the study. The overall mortality was 27.9%. Most patients had quit smoking two years after the initial diagnosis, whereas the percentage of patients showing high adherence with treatment was 68%. Parameters associated with two-year mortality were age and coronary heart disease comorbidity.ConclusionThe mortality of patients with COPD in primary care remains significantly high, whereas adherence with treatment remains significant low. Age, smoking status, and a history of depression are major determinants of mortality in primary health care.
BackgroundMatrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been found elevated in exudative pleural effusions. In endothelial cells these MMPs increase paracellular permeability via the disruption of tight junction (TJ) proteins occludin and claudin. In the present study it was investigated if MMP2 and MMP9 alter permeability properties of the pleura tissue by degradation of TJ proteins in pleural mesothelium.ResultsIn the present study the transmesothelial resistance (RTM) of sheep pleura tissue was recorded in Ussing chambers after the addition of MMP2 or MMP9. Both enzymes reduced RTM of the pleura, implying an increase in pleural permeability. The localization and expression of TJ proteins, occludin and claudin-1, were assessed after incubation with MMPs by indirect immunofluorescence and western blot analysis. Our results revealed that incubation with MMPs did not alter neither proteins localization at cell periphery nor their expression.ConclusionsMMP2 and MMP9 increase the permeability of sheep pleura and this finding suggests a role for MMPs in pleural fluid formation. Tight junction proteins remain intact after incubation with MMPs, contrary to previous studies which have shown TJ degradation by MMPs. Probably MMP2 and MMP9 augment pleural permeability via other mechanisms.
Aims:The aim of this study was to evaluate the physicochemical properties of the pleural mesothelial barrier and of the biological markers that facilitate or eliminate the passage of molecules through the pleura.Methods and Material:Pleural fluid samples from sixty-five patients with heart failure were analyzed. The biological markers studied were lactate dehydrogenase (LDH), adenosine deaminase (ADA), interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), carcinoembryonic antigen (CEA), copper/zinc superoxide dismutase (CuZnSOD), matrix metalloproteinase-2 (MMP-2), -3 (MMP-3), -7(MMP-7), -8 (MMP-8) and -9 (MMP-9). Based on the pleural fluid/serum ratio, these molecules were divided into three groups: a) the LDH-like group with a pleural fluid/serum ratio between 0,4 and 0,8 (LDH, CEA, CuZnSOD, ADA, CRP, MMP-8), b) molecules with a pleural fluid/serum ratio less than 0,4 (MMP-7 and MMP-9) and c) molecules with a pleural fluid/serum ratio equal or above 1 (TNF-α, IL-6, MMP-2 and MMP-3).Results:No correlation between the molecular radius and the pleural fluid to serum ratio of the above biological markers was found.Conclusions:The molecular size is not a major determinant for the passage of molecules through the mesothelial barrier. Several other factors may influence the transport of the above molecules to pleural cavity, such as their charge and shape.
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