Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to conventional chemotherapy and radiotherapy. Therefore, diagnosing MPM early is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. MPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM. METHODS: HMGB1 production from MPM cell lines was measured using ELISA. Serum HMGB1 levels were also examined in 61 MPM patients and 45 individuals with benign asbestos-related diseases. RESULTS: HMGB1 concentrations of 2 out of 4 MPM cell lines were higher than that of normal mesothelial cell line, Met-5A. We demonstrated that patients with MPM had significantly higher serum levels of HMGB1 than the population who had been exposed to asbestos but had not developed MPM. The difference in overall survival between groups with serum HMGB1 levels that were lower and higher than assumed cut-off values was significant. CONCLUSIONS: Our data suggest that serum HMGB1 concentration is a useful prognostic factor for MPM.

Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intraperitoneal chemotherapy. Therefore, early diagnosis of DMPM is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. DMPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells, similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM. STUDY: The serum concentrations of HMGB1 were measured in 13 DMPM patients and 45 individuals with benign asbestos-related diseases. RESULT: We demonstrated that the patients with DMPM had significantly higher serum levels of HMGB1 compared with the population who had been exposed to asbestos but did not develop DMPM. CONCLUSION: Our data suggest that serum HMGB1 concentration is a useful serum marker for DMPM.

Isolated metastases of hepatocellular carcinoma in the left atrium, unresponsive to treatment with sorafenib.

Isolated metastases in the left atrium that are discontinuous with an intrahepatic hepatocellular carcinoma (HCC) are extremely rare. This is the case report of a 46-year-old male patient with pulmonary metastases from HCC, who presented with a tumor in the left lung, extending to the left atrium through the left pulmonary vein. Two weeks after the initiation of treatment with sorafenib, the tumor metastasized to the left parietal cerebral lobe, with an intracranial hemorrhage. Although the patient underwent gamma knife radiosurgery for the metastatic brain tumor, his condition gradually deteriorated and he succumbed to multiple organ failure 4 months later. Given the severe complications that have been reported in patients with this type of metastasis, immediate multidisciplinary treatment, including surgical resection, should be considered.

Naftopidil induces apoptosis in malignant mesothelioma cell lines independently of α1-adrenoceptor blocking.

BACKGROUND: Naftopidil, an α1-adrenoceptor blocker, has been clinically used for the treatment of benign prostate hyperplasia and hypertension. Emerging evidence has shown that naftopidil exhibits an antitumor effect on a variety of cancer types including prostate cancer. The aim of the present study was to investigate naftopidil-induced apoptosis in human malignant mesothelioma cells and to shed light on the underlying mechanism. MATERIALS AND METHODS: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, western blotting, and enzymatic assay of caspase-3, -8, and -9 activities were carried out on human malignant mesothelioma cell lines NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells. To knock-down α1D-adrenoceptor, siRNA to silence human α1D-adrenoceptor-targeted gene was constructed and transfected into cells. RESULTS: Naftopidil induced apoptosis in all the investigated malignant mesothelioma cells, and a similar effect was obtained with prazosin, another α1-adrenoceptor blocker. α1-Adrenoceptor is linked to Gq/11 protein involving activation of protein kinase C (PKC). Naftopidil-induced reduction in cell viability was inhibited by GF109203X, while prazosin-induced in cell viability was less affected. Knocking-down α1D-adrenoceptor promoted malignant mesothelioma cell proliferation. Both naftopidil and prazosin activated caspase-3 and -8 in all the investigated malignant mesothelioma cells. CONCLUSION: Naftopidil, as well as prazosin, has the potential to induce apoptosis in malignant mesothelioma cells by activating caspase-8 and the effector caspase-3, regardless of α1-adrenoceptor blocking.