Case Report Successful Erlotinib Treatment for a Patient with Gefitinib-Related Hepatotoxicity and Lung Adenocarcinoma Refractory to Intermittently Administered Gefitinib

A 73-year-old Japanese man was histologically diagnosed with lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor. The patient was treated with gefitinib for 6 weeks until he developed substantially elevated hepatic enzyme levels that resulted in the discontinuation of gefitinib. Gefitinib was reintroduced with an intermittent treatment schedule after the transaminase levels normalized, but the patient's enzyme levels rose again, and the cancer progressed. Gefitinib was eventually replaced with erlotinib. There was stable disease for 7 weeks without any signs of liver toxicity. Thus, erlotinib may be a beneficial and well-tolerated treatment option for patients with gefitinib-related hepatotoxicity

Immunogenicity of trivalent influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy

Lung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4–6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients

Pulmonary syphilis with a cicatricial variant of organizing pneumonia: a case report

Abstract Background Syphilis is a chronic disease that progresses in the primary, secondary, latent, and tertiary stages. Pulmonary manifestations of syphilis are rare, and their histological features have not been well-described. Case presentation A 78-year-old man was referred to our hospital because of a solitary nodular shadow in the right middle lung field on a chest radiograph. Five years prior, a rash appeared on both legs. He was tested for syphilis at a public health center, and the non-treponemal test result was negative. When he was approximately 35 years old, he had unspecified sexual intercourse. Chest computed tomography showed a 13-mm nodule with a cavity in S6 of the right lower lobe of the lung. Robot-assisted resection of the right lower lobe was performed because of suspected localized right lower lobe lung cancer. A cicatricial variant of organizing pneumonia (CiOP) was observed, and immunohistochemistry identified Treponema pallidum inside the macrophages in the nodule cavity. The rapid plasma regain (RPR) value was negative, and the Treponema pallidum hemagglutination assay was positive. The patient was diagnosed as having secondary syphilis with pulmonary involvement. Insidious progression of secondary syphilis may result in CiOP and a negative RPR test result. Conclusions We report the first case of pulmonary syphilis with a histological pattern of CiOP. It may be asymptomatic and difficult to diagnose because the RPR test may be negative for a long period of time. When either non-treponemal or treponemal test results are positive, the possibility of pulmonary syphilis should be considered along with appropriate medical treatment

Crucial Role of Extracellular Vesicles in Bronchial Asthma

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists

Phospholipase Cε plays a crucial role in neutrophilic inflammation accompanying acute lung injury through augmentation of CXC chemokine production from alveolar epithelial cells

Abstract Background We have shown that phospholipase Cε (PLCε), an effector of Ras and Rap1 small GTPases, plays pivotal roles in inflammation and inflammation-associated carcinogenesis by augmenting proinflammatory cytokine production from epithelial cells of various organs. The purpose of this study is to analyze its role in neutrophilic alveolar inflammation accompanying acute lung injury (ALI), focusing on that in alveolar epithelial cells (AECs), which are known to make a major contribution to the pathogenesis of ALI. Methods We examine the effect of the PLCε genotypes on the development of ALI induced by intratracheal administration of lipopolysaccharide (LPS) to PLCε wild-type (PLCε +/+ ) and knockout (PLCε ΔX/ΔX ) mice. Pathogenesis of ALI is analyzed by histological examination of lung inflammation and measurements of the levels of various cytokines, in particular neutrophil-attracting chemokines such as Cxcl5, by quantitative reverse transcription-polymerase chain reaction and immunostaining. Primary cultures of AECs, established from PLCε +/+ and PLCε ΔX/ΔX mice, are used to analyze the roles of PLCε, protein kinase D (PKD) and nuclear factor-κB (NF-κB) in augmentation of LPS-induced Cxcl5 expression. Results Compared to PLCε +/+ mice, PLCε ΔX/ΔX mice exhibit marked alleviation of lung inflammation as shown by great reduction in lung wet/dry weight ratios, accumulation of inflammatory cells in the alveolar space and thickening of alveolar walls as well as the number of neutrophils and the protein concentration in bronchoalveolar lavage fluid. Also, LPS-induced expression of the CXC family of chemokines, in particular Cxcl5, is substantially diminished in the total lung and AECs of PLCε ΔX/ΔX mice. Moreover, LPS-induced Cxcl5 expression in primary cultured AECs is markedly suppressed on the PLCε ΔX/ΔX background (p < 0.05 versus PLCε +/+ AECs), which is accompanied by the reduction in phosphorylation of inhibitor κB (IκB), PKD and nuclear translocation of NF-κB p65. Also, it is suppressed by the treatment with inhibitors of PKD and IκB kinase, suggesting the involvement of the PLCε-PKD-IκB-NF-κB pathway. Conclusions PLCε-mediated augmentation of the production of the CXC family of chemokines, in particular Cxcl5, in AECs plays a crucial role in neutrophilic alveolar inflammation accompanying ALI, suggesting that PLCε may be a potential molecular target for the treatment of acute respiratory distress syndrome