Objective (range, 5-47 months) 5%) had ILD-preceding myositis, and 4 (50%) had simultaneous onset. Chest high-resolution computed tomography frequently showed lung-base predominant ground glass opacities (GGO) with volume loss. The results of surgical lung biopsies indicated that 4 patients had nonspecific interstitial pneumonia (NSIP) and/or organizing pneumonia (OP) patterns. All but 1 received corticosteroid therapy, and 6 patients were also given cyclosporin. The mean duration of follow-up was 22 months

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Lung cancer is clearly the primary cause of cancer-related deaths worldwide. Recent molecular-targeted strategy has contributed to improvement of the curative effect of adenocarcinoma of the lung. However, such current treatment has not been developed for squamous cell carcinoma (SCC) of the disease. The new genome-wide RNA analysis of lung-SCC may provide new avenues for research and the development of the disease. Our recent microRNA (miRNA) expression signatures of lung-SCC revealed that clustered miRNAs miR-1/133a were significantly reduced in cancer tissues. Here, we found that restoration of both mature miR-1 and miR-133a significantly inhibited cancer cell proliferation, migration and invasion. Coronin-1C (CORO1C) was a common target gene of the miR-1/133a cluster, as shown by the genome-wide gene expression analysis and the luciferase reporter assay. Silencing of CORO1C gene expression inhibited cancer cell proliferation, migration and invasion. Furthermore, CORO1C-regulated molecular pathways were categorized by using si-CORO1C transfectants. Further analysis of novel cancer signaling pathways modulated by the tumor-suppressive cluster miR-1/133a will provide insights into the molecular mechanisms of lung-SCC oncogenesis and metastasis.

Neutropenia is a common laboratory finding in systemic lupus erythematosus (SLE). However, the molecular mechanism of SLE neutropenia has not been fully explained. In this study, we examined whether TNF-related apoptosisinducing ligand (TRAIL) is involved in the pathogenesis of SLE neutropenia using samples from SLE patients. Serum TRAIL levels in SLE patients with neutropenia were significantly higher than those of SLE patients without neutropenia and healthy volunteers. Serum TRAIL levels showed a significant negative correlation with neutrophil counts in SLE patients. The expression of TRAIL receptor 3 was significantly lower in SLE patients with neutropenia than in patients without neutropenia or in healthy volunteers. Treatment with glucocorticoids negated the decrease of TRAIL receptor 3 expression on neutrophils of SLE patients. TRAIL may accelerate neutrophil apoptosis of neutrophils from SLE patients, and autologous T cells of SLE patients, which express TRAIL on surface, may kill autologous neutrophils. IntroductionNeutropenia in systemic lupus erythematosus (SLE) was first described more than 70 years ago 1 and is found in about 50%-60% of patients with SLE. 2 Clinically, increased susceptibility to infections is a major cause of morbidity and mortality in patients with SLE. 3,4 In this regard, not only treatment with adrenal glucocorticoids and/or immunosuppressive drugs but also decreased numbers of polymorphonuclear neutrophils (PMNs) is obviously responsible for the increased incidence of infections. [5][6][7][8][9] However, the detailed molecular mechanism of neutropenia in SLE has not been fully elucidated.Traditionally, PMNs have been considered to be the first line cell component of the body defense mechanism against bacterial pathogens and were regarded as terminally differentiated cells incapable of protein synthesis and committed to death within 72 hours. [10][11][12] Recently, it was indicated that neutrophils were not only capable of receiving signals from different proinflammatory cytokines and chemokines, but also could synthesize many important proinflammatory cytokines and chemokines to modulate immune responses, such as interferon-gamma (IFN-␥), tumor necrosis factor alpha (TNF-␣), and interleukin-8 (IL-8). 13,14 And these proinflammatory mediators, relevant to the inflamed site in vivo, also act to modulate the constitutive death of neutrophils. 15,16 Regarding neutrophil apoptosis, Fas 17 and TNF-␣ 18 were reported to be able to shorten neutrophil lifespan at early time points. Recently, it was reported that TNF-related apoptosis-inducing ligand (TRAIL) could accelerate neutrophil apoptosis. 19 Also, TRAIL was reported to be involved in the monocyte apoptosis induced by T cells in SLE. 20 However, the role of TRAIL in neutropenia of SLE is still unclear.In this study, we have investigated the TRAIL receptors on neutrophils and TRAIL-induced neutrophil apoptosis using samples from SLE patients. A difference in the expression pattern of TRAIL receptors between SLE patients and healt...

Malignant pleural effusion (PE) is one of the poor prognostic factors in non-small cell lung cancer (NSCLC), and the detailed mechanism of the malignant PE formation is not fully elucidated. Recently, CXCR4, a receptor for chemokine stromal-derived factor-1alpha (SDF-1alpha) that can induce chemotaxis of cells, was reported to be expressed on NSCLC. In this study, we hypothesized that the SDF-1alpha/CXCR4 axis may be involved in the dissemination of malignant cells into pleural space, and investigated its expression, function, and signaling pathway using NSCLC cell lines and clinical samples from 43 patients with NSCLC with malignant PE. We found functional expression of CXCR4 on NSCLC cell lines, and also found that SDF-1alpha could induce migration via phosphatidylinositol 3 (PI-3) kinase- and p44/42 mitogen-activated protein kinase-dependent manner. The SDF-1alpha levels in malignant PE were significantly higher than those in transudate PE and showed a significant positive correlation with PE volumes. The sensitivity and specificity for prediction of recurrence of malignant PE was 61.5% and 83.3%, respectively (cutoff SDF-1alpha = 2,500 ng/ml), and better than those using pH of PE. Cancer cells in malignant PE expressed CXCR4, and mesothelial cells of the pleura stained positive for SDF-1alpha. The SDF-1alpha/CXCR4 axis is involved in the dissemination of NSCLC cells into pleural space.