Background/Aim: Amrubicin (AMR) has shown promising activity for lung cancer. However, little is known about the mechanism underlying resistance to this agent. The aim of this study was to elucidate the mechanism underlying resistance to AMR. Materials and Methods: We first developed amrubicinol (AMR-OH)-resistant cell lines (H520/R and DMS53/R) by exposing lung cancer cell lines (H520 and DMS53) to increasing concentrations of AMR-OH and performed functional analysis by using these cell lines. Results: Transcriptome analyses showed that amphiregulin (AREG) was the most highly up-regulated gene in both AMR-OH-resistant cell lines compared to parent cells. Conditioned medium from DMS53/R cells reduced the sensitivity to AMR-OH in DMS53 cells. In contrast, DMS53/R cells transfected with siRNA directed against AREG recovered their sensitivity to AMR-OH. An additional administration of cetuximab with amrubicinol also restored the sensitivity to AMR-OH. Conclusion: Amphiregulin plays an important role in resistance to AMR-OH.
Objective The objective of this study was to evaluate the concerns and anxieties of hospitalized coronavirus disease (COVID-19) patients. Methods A questionnaire was distributed to patients on discharge. The responses were analyzed once they were returned by mail. Results Responses were received from 27 of 39 patients (average age, 50 ± 17 years). Among the participants, 16 were male (59.3%), 19 were symptomatic (70.4%), and two required a ventilator (7.4%). Anxiety about symptom exacerbation was reported by 36.0% of participants. Quarantine-associated stress was experienced by 60.0% of participants, and 72.0% of participants supported the change in federal policy that allows asymptomatic patients and patients with mild conditions to isolate themselves at a hotel or their home. Following discharge, 44.0% of participants experienced anxieties regarding their lives after discharge, and 56.0% were anxious regarding discrimination and rumors. During hospitalization, 68.0% of participants re-evaluated their attitude toward health, 44.0% regretted the preventative measures they took before contracting COVID-19, and 44.0% felt guilty for becoming infected. Conclusions Participants experienced various kinds of stress related to hospitalization for COVID-19. There was a trend of people being more concerned about their relationships than their own health. Therefore, as asymptomatic participants and participants with mild symptoms also experienced psychological stresses, it is also necessary to consider the psychological and social effects of the disease.
Abstract Background Lettuce‐associated respiratory allergy has never been reported before. The aim of this study was to clarify the clinical condition of lettuce‐associated respiratory allergy and to identify the lettuce antigen which induces allergic symptoms. Methods We distributed questionnaires to 1168 lettuce farmers and performed medical examinations in those who exhibited respiratory symptoms related to occupational exposure to lettuce. We analysed specific IgE‐binding proteins in the sera of patients through immunoblotting analysis and determined molecular characterization of the IgE‐binding bands using liquid chromatography‐mass spectrometry. Results A total of 932 farmers (80%) responded to the questionnaire. Of those, 7% exhibited lettuce‐associated respiratory symptoms, during harvesting and packaging. Thirteen patients were diagnosed with allergy to lettuce and agreed to undergo further examinations. The percentage of activated basophils in these patients was significantly higher compared with that reported in negative controls ( P < .05). Lettuce‐specific IgE (ImmunoCAP ® ) and skin prick testing was positive in 46% and 62% of patients, respectively. Notably, occupational lettuce‐allergic asthma was detected in one patient through specific bronchial provocation testing. The IgE‐binding bands recognized in the sera of >50% of patients were identified as epidermis‐specific secreted glycoprotein EP1‐like (51 kDa). Conclusion The present analysis identified a novel lettuce allergen. This allergen may have clinically useful applications, such as specific IgE testing and allergen‐specific immunotherapy.
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.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 (PLCεΔX/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 PLCεΔX/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.Compared to PLCε+/+ mice, PLCεΔX/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 PLCεΔX/ΔX mice. Moreover, LPS-induced Cxcl5 expression in primary cultured AECs is markedly suppressed on the PLCεΔX/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.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.
Abstract Objective This study aims to examine changes in patients’ perspectives and outlooks regarding the disease and their health after hospitalization for COVID-19 and investigate their discrimination and harassment experiences. This prospective observational study surveyed discharged patients who had been admitted to Hyogo Prefectural Tamba Medical Center in Japan for COVID-19. Patient characteristics, changes in outlook and behaviors after discharge, and incidents of discrimination and harassment were examined. The study was conducted in two waves: March–June 2020 and July–September 2020. Results Responses were obtained from 27 patients aged 50 ± 17 years, including 16 men (59.3%). We found most patients feared infection before hospitalization (88.5%) and had taken some preventive measures (96.3%), however after discharge, all (100%) practiced social distancing and infection prevention. Twenty patients (80%) considered changing their lifestyles, and 19 (79.2%) decided to use sick leave when they felt ill; these trends were more prominent during the second wave. Six patients (23.1%) reported experiencing discrimination or harassment after discharge. While most patients with COVID-19 had a strong fear of infection before hospitalization, their views about health and health behaviors changed after hospitalization.
Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has improved the diagnostic accuracy of transbronchial biopsy (TBB) for malignant peripheral pulmonary nodules (PPNs). Many underscore the importance of tumor localization but reproducible results on other aspects that affect yield are few. We aimed to analyze the diagnostic performance of TBB with EBUS-GS and to know what group of patients can benefit most.The database of patients with malignant PPNs (≤30 mm) who underwent EBUS-GS TBB at the National Cancer Center Hospital, Tokyo, Japan from April 2012 to March 2013 was retrospectively reviewed and analysed based on lesion and procedural characteristics.Most PPNs (N=212) were adenocarcinoma, measuring 20 mm [mean, standard deviation (SD) 5.45]. Overall diagnostic accuracy was 67.5% (143 of 212 cases). Factors that significantly affected and predicted diagnostic success were EBUS probe within (P=0.001) and parenchymal location that was not adjacent to the costal visceral pleura (P=0.001). When combined, these variables achieved an 87% (59 of 68 lesions) diagnostic yield. CT scan characteristic, lesion size, lobe location, and GS size were non-contributory.EBUS-GS TBB is an acceptable diagnostic method for small peripheral lung cancer. It can be maximized for PPNs that are away from the pleura and when the EBUS probe can be placed within the lesion.
Therapy for lung cancer has recently evolved to include molecular targeted therapy and adequate amounts of lung cancer tissue are needed to identify particular phenotypes. For this purpose, quite a number of investigations on diagnostic bronchoscopy have been undertaken. Corollary to the increasing number of transbronchial biopsies for peripheral pulmonary nodules is the increased chances of radiation exposure during fluoroscopy. Our aim was to determine the dose and risk factors of radiation exposure to medical staff.Endobronchial ultrasonography with a guide sheath under X-ray fluoroscopy was performed on 132 cases of peripheral pulmonary lesions. The radiation exposure dose to medical staff (operator physicians, assistant physicians, nurses and radiological technologists) was measured.The median time of fluoroscopy was 7.6 min (range 1.5-23.9). The median radiation exposure dose to operator physicians was 12 μSv/exam (range 1-99), while that of the other medical staff was lower. In a multivariate analysis, body mass index and the location of the radial ultrasound probe had significantly higher odds ratios.The risk factors for an increased radiation exposure dose were patients' BMI and the location of the radial ultrasound probe. But even then, the radiation exposure dose to medical staff during endobronchial ultrasonography with a guide sheath was very low, especially for nurses and radiological technologists in whom the exposure dose was negligible.
