In non-small-cell lung cancer, an exon 19 deletion and L858R point mutation in the epidermal growth factor receptor (EGFR) are predictors of a response to EGFR-tyrosine kinase inhibitors. However, it is uncertain whether other uncommon EGFR mutations associated with sensitivity inhibitors.A post-hoc analysis assess prognostic factors was performed use patients (exon deletion, L858R, G719X, L861Q) who were treated gefitinib NEJ002 study, which compared carboplatin-paclitaxel as first-line...

Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), antioxidant, inhibited adhesion molecule expression and cytokine production lung cells. When NAC is inhaled into alveolar space, it expected to directly interact with inflammatory cells elevate glutathione levels epithelial lining fluids. therefore examined whether inhibits fibrosis induced by bleomycin (BLM). Male ICR mice were given a...

Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil inhibitor, sivelestat, could alleviate fibrosis; however, antifibrotic mechanisms have not yet been clarified. We examined mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, this study. To elucidate we murine model bleomycin-induced early-stage After intratracheal instillation bleomycin, sivelestat was administered intraperitoneally once day for 7 or 14...

Numerous in vitro and vivo studies both animals patients with asthma have shown that interleukin (IL)-9 is an important inflammatory mediator asthma. To examine the effects of IL-9 antagonism on airway inflammation, ovalbumin-sensitized BALB/c mice were intravenously given anti-IL-9 antibody or isotype-matched control 30 minutes before challenge aerosolized ovalbumin. Airway response to methacholine was measured, samples bronchoalveolar lavage fluid (BALF) obtained 24 hours after last...

A small GTPase, Rho, plays key roles in cell adhesion, motility, and contraction after stimulation. Among Rho effectors isolated, the family of Rho-associated coiled-coil-forming protein kinases (ROCK) is implicated Rho-mediated adhesion smooth muscle contraction. The effect a specific inhibitor ROCK, Y-27632, was evaluated murine model acute lung injury induced by intravenous injection Escherichia coli endotoxin (lipopolysaccharide [LPS]). Lung edema measuring extravascular leakage...

Background: Type 2 helper T-cell cytokines including IL-13 play a central role in the pathogenesis of bronchial asthma (BA).During course our research, attention was drawn to dipeptidyl peptidase-4 (DPP4) as one molecules that were induced from epithelial cells (BECs) by stimulation.DPP4 could become new biomarker or therapeutic target.The aim this study investigate expression DPP4 asthmatic airway, and its pathophysiology asthma.Methods: BECs isolated patients with inhaled...

We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation endothelial cells on increase in permeability induced by H2O2. Bovine pulmonary microvascular (BPMVEC) were grown to confluence a microporous filter and 125I-albumin clearance rate across monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no direct effect transendothelial permeability. However, pretreatment enhanced susceptibility BPMVEC H2O2; that is, H2O2 (10 microM) alone effect,...

Transforming growth factor-alpha and epidermal factor (EGF), the ligands for EGF receptor (EGFR), stimulate fibroblast proliferation play an important role in pathogenesis of pulmonary fibrosis. Therefore, inhibition EGFR signal by tyrosine kinase inhibitor (EGFR-TKI) may prevent However, there is a possibility that blocking inhibit epithelial cell repair, thereby exaggerating lung fibrosis.To investigate effect EGFR-TK on fibrosis.We looked at effects EGFR-TKIs gefitinib (20, 90, 200 mg/kg)...

Cysteinyl leukotrienes (CysLTs) play an important role in eosinophilic airway inflammation. In addition to their direct chemotactic effects on eosinophils, indirect have been reported. Eotaxin is a potent eosinophil-specific factor produced mainly by fibroblasts. We investigated whether CysLTs augment inflammation via eotaxin production Leukotriene (LT)C(4) alone had no effect human fetal lung fibroblasts (HFL-1). However, LTC(4) stimulated IL-13-treated fibroblasts, thereby indirectly...

We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate involvement decreased anticancer immunity advanced lung cancer patients. analyzed population DC using flow cytometry. then determined BODIPY 650/665, a fluorophore with an affinity for lipids. Compared healthy controls, number treatment-naive patients was significantly reduced. In stage III + IV disease, numbers myeloid (mDCs) plasmacytoid were also Lipid evaluated based on...

Collagen type I is one of the major deposits in thickening reticular basement membrane asthma.In this study, we assessed turnover collagen asthma by measuring procollagen C-terminal peptide (PICP) and telopeptide (ICTP) induced sputum.PICP but not ICTP was found to be significantly higher subjects than normal volunteers (P < 0.05). In asthma, PICP inversely correlated with %FEV(1.0) (r = -0.539), its levels increased upon exacerbation 0.05), indicating that synthesis increases during...

Dendritic cells (DCs) are professional antigen-presenting that play a crucial role in the initiation and modulation of immune responses. Human circulating blood DCs divided into two major subsets: myeloid (mDCs); plasmacytoid (pDCs). Furthermore, mDCs subdivided Th1-promoting (mDC1s); Th2-promoting (mDC2s). Although CD1a, CD1c, CD141 generally used for classifying mDC subsets, their adequacy as specific marker remains unclear. We performed this study to compare mDC, pDC, mDC1, mDC2 subsets...

Forestry and field workers who work outdoors are at high risk for Hymenoptera stings may develop occupation-related allergies from being stung. However, clinical immunological surveys of in the occupational setting have rarely been reported. We surveyed natural history Japanese forestry (FWs) electrical facility (EFFWs), we assessed utility measuring specific (s)IgE Ab to Hymenptera venom.Questionnaires on hornet paper wasp were completed by 999 FWs, 354 EFFWs, 365 office as controls between...

Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood. Its expression increased IL-13-overexpressing mouse airways. However, its function human airways poorly understood.Distal proximal bronchial epithelial (BECs) were isolated from bronchoscopic brushings of disease control (D-CON), COPD, inhaled corticosteroid-treated asthma (ST-Asthma) corticosteroid-naïve (SN-Asthma) patients. ITLN-1 mRNA freshly BECs, primary cultured BECs with or without IL-13 inhibition...

To clarify the clinical features of organizing pneumonia (OP) associated with rheumatoid arthritis (RA) and to determine whether development OP is related RA activity.A cross-sectional study was conducted, in which medical records 499 consecutive patients who visited our hospital during one month were reviewed. diagnosed by pathological findings trans-bronchial biopsy or (typical computed tomography findings, no causative agents, good response glucocorticoids, lack antibiotics).Among...

To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in pathogenesis radiation pneumonitis and to determine whether measurement soluble ICAM-1 (sICAM-1) levels is useful for predicting onset pneumonitis, sICAM-1 were measured serum bronchoalveolar lavage (BAL) fluids from patients with lung malignancy who received radiotherapy. A total 30 irradiated a dose approximately 60 Gy. Blood samples taken before, midway after BAL was also performed before radiotherapy seven cases....

Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced mice by decreasing oxidative stress. Lung was induced female ICR intratracheal instillation 5 mg x kg(-1) BLM. Edaravone (300 kg(-1)) administered intraperitoneal administration 1 h before BLM challenge. significantly improved survival rate treated with from 25...

The cellular mechanisms involved in the development of silicosis have not been fully elucidated. This study aimed to examine influence silica-induced lung injury on autophagy. Suspensions crystalline silica particles were administered transnasally C57BL/6j mice. Immunohistochemical examination for Fas and p62 protein expression was performed using tissue specimens. Two-dimensional quantitative analysis deposits lungs situ sections by an in-air microparticle induced X-ray emission (in-air...