Successful Treatment of Concomitant Pleural Mucosa-Associated Lymphoid Tissue Lymphoma and Monoclonal Gammopathy of Undetermined Significance with Lenalidomide, Rituximab, and Dexamethasone.

Concomitant plasma cell and B cell neoplasms in a single patient have been infrequently reported. It is known that the prognosis of these patients is worse than that of patients with single-disease onset. Generally, the chemotherapy specific for each disease is provided sequentially. It has been suggested that the specific chemotherapy for lymphoma could lead to the occurrence of refractory multiple myeloma (MM). We present a case with the concomitant occurrence of mucosa-associated lymphoid tissue (MALT) lymphoma and monoclonal gammopathy of undetermined significance (MGUS). MGUS does not usually require aggressive treatment. However, the potential adverse effects of MGUS on the treatment course of the B cell lymphoma were concerning. Therefore, we explored a new therapeutic approach that is simultaneously effective against both diseases. Combination therapy of lenalidomide (LEN) and rituximab (RIT) gained indication for follicular lymphoma and MALT lymphoma recently. LEN is also a key drug in MM treatment. Both diseases in our patient were effectively treated with the combination of LEN, RIT, and dexamethasone. With this combination therapy, we expect a prognostic improvement in concomitant MM and B cell lymphoma cases.

A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric modulator of FFAR1.

Selective free fatty acid receptor 1 (FFAR1)/GPR40 agonist fasiglifam (TAK-875), an antidiabetic drug under phase 3 development, potentiates insulin secretion in a glucose-dependent manner by activating FFAR1 expressed in pancreatic ß cells. Although fasiglifam significantly improved glycemic control in type 2 diabetes patients with a minimum risk of hypoglycemia in a phase 2 study, the precise mechanisms of its potent pharmacological effects are not fully understood. Here we demonstrate that fasiglifam acts as an ago-allosteric modulator with a partial agonistic activity for FFAR1. In both Ca(2+) influx and insulin secretion assays using cell lines and mouse islets, fasiglifam showed positive cooperativity with the FFAR1 ligand γ-linolenic acid (γ-LA). Augmentation of glucose-induced insulin secretion by fasiglifam, γ-LA, or their combination was completely abolished in pancreatic islets of FFAR1-knockout mice. In diabetic rats, the insulinotropic effect of fasiglifam was suppressed by pharmacological reduction of plasma free fatty acid (FFA) levels using a lipolysis inhibitor, suggesting that fasiglifam potentiates insulin release in conjunction with plasma FFAs in vivo. Point mutations of FFAR1 differentially affected Ca(2+) influx activities of fasiglifam and γ-LA, further indicating that these agonists may bind to distinct binding sites. Our results strongly suggest that fasiglifam is an ago-allosteric modulator of FFAR1 that exerts its effects by acting cooperatively with endogenous plasma FFAs in human patients as well as diabetic animals. These findings contribute to our understanding of fasiglifam as an attractive antidiabetic drug with a novel mechanism of action.

[Steroid responsive anti-Hu-associated paraneoplastic encephalitis with bilateral frontal lobe lesions].

A 46-year-old woman was admitted to our hospital because of behavioral changes. Her mentality was fluctuating vigorously and neurological examination revealed disorientation and word finding difficulty. MRI demonstrated bilateral frontal and right temporal lesions. Cerebrospinal fluid examination showed predominantly lymphocytic pleocytosis. Brain biopsy disclosed inflammation but not neoplasm. Repeated steroid therapy gave her a recovery in neurological manifestations and MRI findings. As we got a positive result of anti-Hu antibody after her complete recovery, we did screening for tumors and found small cell lung cancer. She got a chemotherapy and remains free of relapse of any symptoms. There have been few reports in that anti-Hu associated paraneolastic syndrome showed steroid responsive frontal lesions. We suggest that anti-Hu associated paraneoplastic encephalitis should be considered for steroid responsive encephalitis with brain lesions other than limbic system, because early detection of paraneoplastic encephalitis and timely antitumor treatment are important for patient's prognosis.

Is serum thioredoxin-1 a useful clinical marker for malignant pleural mesothelioma?

Malignant pleural mesothelioma (MPM), an asbestos-related aggressive malignant tumor of mesothelial origin, shows limited response to therapy and overall survival remains very poor. Reactive oxygen species play an important role in asbestos toxicity. Here, we found that the patients with MPM had significantly higher serum levels of thioredoxin-1 (TRX) than control population. The patients with advanced-stage MPM showed higher levels of TRX than those with early-stage MPM. The difference in overall survival between the groups with lower and higher serum TRX levels was significant. Our data suggest that serum TRX concentration could be a useful clinical marker for MPM.

Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma.

BACKGROUND: 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 so early diagnosis of MPM is very important. Vascular endothelial growth factor (VEGF), a potent mitogen for the vascular endothelium, is also known to be an autocrine growth factor for MPM. Here, we investigated the pleural effusion VEGF levels in patients with MPM and compared them to those of a population with a non-malignant pleuritis or lung cancer involving malignant pleural effusion. METHODS: The pleural effusion VEGF concentrations were measured in 46 MPM patients and 45 individuals with non-MPM individuals (25 individuals with non-malignant pleural effusions, and 20 individuals with lung cancer involving malignant pleural effusion). RESULTS: We demonstrated that patients with MPM had significantly higher pleural effusion VEGF levels than a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion, and the patients with advanced stage MPM showed higher levels of VEGF than the early stage MPM patients. The difference in overall survival between the groups with pleural effusion VEGF levels lower and higher than the assumed cut-off of 2000pg/ml was significant. CONCLUSIONS: Our data suggest that the pleural effusion VEGF concentration could be useful as an aid for the diagnosis of MPM and as a prognostic factor.