In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.

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SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.

We evaluated the diagnostic and prognostic efficacy of human epididymis protein 4 (HE4) for lung cancer patients by using our novel enzyme-linked immunosorbent assay (ELISA) system. We measured serum HE4 levels of cancer patients including 49 lung cancer and 18 ovarian cancer patients. Furthermore, we evaluated the relationship between serum HE4 levels and overall survival after chemotherapy of 24 lung cancer patients. Serum HE4 levels were significantly higher for non-small, small cell lung cancer and ovarian cancer patients than for healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated for differentiation of lung cancer patients and healthy controls. AUC for serum HE4 was 0.988 for differentiating lung cancer patients from healthy controls, with a cutoff value of 6.56 ng/ml (sensitivity = 89.8%, specificity = 100%). Serum HE4 levels were elevated in 36/40 (90.0%) non-small cell lung cancer patients, 8/9 (88.9%) small cell lung cancer patients and 8/18 (44.4%) ovarian cancer patients. High levels of serum HE4 (>15 ng/ml) after chemotherapy were significantly correlated with worse overall survival after the treatment. These findings suggest that serum HE4 is a potential diagnostic and prognostic marker for lung cancer patients.

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Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum. Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN. In this study, we applied the 11-25 mAb to in vivo imaging to detect MSLN-expressing tumors. In in vitro and ex vivo immunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells. We showed the accumulation of Alexa Fluor 750-labeled 11-25 mAb in MSLN-expressing tumor xenografts in athymic nude mice. Then, 11-25 mAb was labeled with 64Cu via a chelating agent DOTA and was used in both in vitro cell binding assay and in vivo positron emission tomography (PET) imaging in the tumor-bearing mice. We confirmed that 64Cu-labeled 11-25 mAb highly accumulated in MSLN-expressing tumors as compared to MSLN-negative ones. The 64Cu-labeled 11-25 mAb is potentially useful as a PET probe capable of being used for wide range of tumors, rather than 18F-FDG that occasionally provides nonspecific accumulation into the inflammatory lesions.

The seismonastic movement of Mimosa pudica is triggered by a sudden loss of turgor pressure. In the present study, we compared the cell cytoskeleton by immunofluorescence analysis before and after movement, and the effects of actin- and microtubule-targeted drugs were examined by injecting them into the cut pulvinus. We found that fragmentation of actin filaments and microtubules occurs during bending, although the actin cytoskeleton, but not the microtubules, was involved in regulation of the movement. Transmission electron microscopy revealed that actin cables became loose after the bending. We injected phosphatase inhibitors into the severed pulvinus to examine the effects of such inhibitors on the actin cytoskeleton. We found that changes in actin isoforms, fragmentation of actin filaments and the bending movement were all inhibited after injection of a tyrosine phosphatase inhibitor. We thus propose that the phosphorylation status of actin at tyrosine residues affects the dynamic reorganization of actin filaments and causes seismonastic movement.