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en: A novel BRD4 degrader, ARV-825, attenuates lung fibrosis through senolysis and antifibrotic effect.

en: These results suggest that ARV825 may impact the progressive and irreversible course of fibrotic lung diseases.

ja: For senescent cells, ARV825 induced the expression of an apoptosis marker while reducing the expression of BRD4 and senescence markers. On the other hand, for early passage pre-senescent cells, ARV825 reduced the expression of collagen type 1 and α-smooth muscle actin. In an experimental mouse model of lung fibrosis, ARV825 attenuated lung fibrosis and improved lung function. Immunohistochemical staining revealed a significant decrease in the number of senescent alveolar type 2 cells in lung tissue due to ARV825 treatment.

en: Respiratory Investigation

ja: Respiratory Investigation


en: A polo-like kinase inhibitor identified by computational repositioning attenuates pulmonary fibrosis.

en: These findings suggest that targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis by inhibiting lung fibroblast proliferation without affecting lung epithelial cells. In addition, while in silico screening is useful, it is essential to fully determine the biological activities of candidates by wet-lab validation studies.

en: Respiratory Research

ja: Respiratory Research


en: Immune checkpoint inhibitor-related pneumonitis with atypical radiologic features in a patient with anti-aminoacyl-tRNA synthetase antibody.

en: A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies was admitted for dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow with cystic structures and peribronchovascular consolidation. Although we treated him with high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation of pneumonitis with progressive fibrosis and volume loss. A re-evaluation identified anti-aminoacyl-tRNA synthetase antibody in the serum collected before ICI administration. This case highlights the importance of re-evaluating pre-existing autoimmune disorders in patients who develop ICI-related pneumonitis with atypical radiologic features.

en: Respiratory Medicine Case Reports

ja: Respiratory Medicine Case Reports


en: The lymphocyte-specific protein tyrosine kinase-specific inhibitor A-770041 attenuates lung fibrosis via the suppression of TGF-β production in regulatory T-cells.

en: These results suggest that Lck inhibition attenuated lung fibrosis by suppressing TGF-β production in Tregs and support the role of Tregs in the pathogenesis of lung fibrosis.

en: PLoS ONE

ja: PLoS ONE


en: Type A thymoma: a rare cause of neoplastic cardiac tamponade with long-term survival.

en: This case indicates that neoplastic cardiac tamponade, even in elderly patients, should not necessarily be regarded as a terminal cancer and requires a systematic investigation for underlying causes.

en: BMC Pulmonary Medicine

ja: BMC Pulmonary Medicine


en: Lysophosphatidic acid, ceramide 1-phosphate and sphingosine 1-phosphate in peripheral blood of patients with idiophathic pulmonary fibrosis

en: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonias. Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are signaling lipids that evoke growth factor-like responses to many cells. Recent studies revealed the involvement of LPA and S1P in the pathology of IPF. In this study, we determined LPA, S1P and ceramide 1-phosphate (C1P) in peripheral blood plasma of IPF patients, and examined correlation to the vital capacity of lung (VC), an indicator of development of fibrosis. Blood plasma samples were taken from eleven patients with IPF and seven healthy volunteers. The lipids of the sample were extracted and subjected to liquid chromatography-tandem mass spectrometry for analysis. Results showed that there is a significant negative correlation between VC and plasma LPA levels, indicating that IPF patients with advanced fibrosis had higher concentration of LPA in their plasma. Average of S1P levels were significantly higher in IPF patients than those in healthy subjects. Although it is not statistically significant, a similar correlation trend that observed in LPA levels also found between VC and S1P levels. These results indicated that plasma LPA and S1P may be associated with deterioration of pulmonary function of IPF patients. J. Med. Invest. 69 : 196-203, August, 2022.

en: The Journal of Medical Investigation : JMI


en: A Case of Radiation-associated Angiosarcoma Presenting as Massive Pleural Effusion.

en: A 67-year-old man was admitted to our hospital for massive pleural effusion. He had a history of mandibular gingival carcinoma treated with radiation therapy (RT). Based on the cytology findings of pleural effusion and a thoracoscopic pleural biopsy, we finally diagnosed him with radiation-associated angiosarcoma. Retrospective cell-block immunocytochemistry with pleural effusion also showed potential utility for the diagnosis. This case highlights the importance of considering the possibility of radiation-associated secondary cancer in patients with pleural effusion who have a history of RT.

en: Internal Medicine

ja: Internal Medicine


en: Lenvatinib-induced Interstitial Pneumonia in a Patient with Hepatocellular Carcinoma.

en: Lenvatinib is a multi-targeted tyrosine kinase inhibitor available for the treatment of unresectable hepatocellular carcinoma (HCC). We herein report an 84-year-old-man with interstitial pneumonia caused by lenvatinib. Four months after the start of lenvatinib administration for HCC, chest computed tomography revealed bilateral ground-glass opacity. However, he continued to take lenvatinib for four more months until he complained of dyspnea on exertion. This is a case of lenvatinib-induced interstitial pneumonia that progressed relatively slowly with a long asymptomatic period despite the appearance of pneumonia on image findings.


en: Development of improved method to identify and analyze lung fibrocytes with flow cytometry in a reporter mouse strain.

en: Our findings suggest that the improved method can be a useful for the detection of pure lung fibrocytes and allows us to further analyze the characteristics of viable fibrocytes.

ja: cells.

en: Immunity, Inflammation and Disease

ja: Immunity, Inflammation and Disease


en: Blockade of Pan-Fibroblast Growth Factor Receptors Mediates Bidirectional Effects in Lung Fibrosis.

en: H]thymidine incorporation assays. The expression of FGFR was analyzed using IB or flow cytometry. We also investigated the effect of BGJ398 on pulmonary fibrosis induced by bleomycin in mice. Both lung fibroblasts and AECs expressed FGFRs. BGJ398 significantly inhibited the proliferation and migration of lung fibroblasts stimulated with FGF2. BGJ398 also reduced the proliferation of AECs in response to FGF2. Although the administration of BGJ398 ameliorated pulmonary fibrosis in bleomycin-treated mice, it increased mortality resulting from alveolar injury and inhibition of AEC regeneration. These data suggest that the total inhibition of FGFR signaling can suppress lung fibrosis by inhibiting fibroblast activities, although alveolar injury is simultaneously caused.

en: American Journal of Respiratory Cell and Molecular Biology


en: エタンブトールによる脱髄性末梢神経障害により急速進行性の歩行障害を呈した結核性胸膜炎の1例

en: 日本結核・非結核性抗酸菌症学会

ja: 日本結核・非結核性抗酸菌症学会


en: Functional analysis of human fibrocytes derived from monocytes reveals their profibrotic phenotype through paracrine effects

en: Fibrocytes, which are bone marrow-derived collagen-producing cells, were reported to play a role in the pathogenesis of pulmonary fibrosis. However, their function in pulmonary fibrosis is unclear. We analyzed their function compared with that of monocytes and localization in fibrotic tissues in patients with idiopathic pulmonary fibrosis (IPF). We compared the gene expression profile of monocyte-derived fibrocytes with that of monocytes by microarray analysis. Proliferation and differentiation into myofibroblasts were examined by 3H-thymidine incorporation assay and Western blotting. We measured the level of growth factors in the culture supernatant of fibrocytes by ELISA. The localization of fibrocytes in lung tissues of patients with IPF was determined by immunofluorescence staining. Compared with monocytes, fibrocytes had higher expression of extracellular matrix- and growth factor-encoding genes, including PDGF-B, FGF-2 and VEGF-B. Although fibrocytes did not proliferate in response to PDGF, co-culture of fibrocytes stimulated the growth of lung fibroblasts through the production of PDGF-BB. In the lung of IPF patients, CD45+Collagen-I+FSP-1+ cells, which have a similar phenotype to fibrocytes, were detected and co-stained with anti-PDGF antibody. This study suggested that fibrocytes function in pulmonary fibrosis partly by producing PDGF in the lungs of IPF patients. J. Med. Invest. 67 : 102-112, February, 2020.

ja: The Journal of Medical Investigation : JMI


en: Distinct improvement of pulmonary function, ground-glass opacity, hypoxia and physical findings in an idiopathic pulmonary fibrosis patient after pirfenidone treatment : a case report with a review of the literature.

en: Background : Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation : A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion : Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients. J. Med. Invest. 67 : 358-361, August, 2020.


en: The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice.

en: These results suggest that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs.

en: Experimental Lung Research

ja: Experimental Lung Research


en: Clinical features of interstitial pneumonia associated with systemic lupus erythematosus.

en: In SLE cases, IP primarily occurred in male and elderly patients. In addition to the NSIP pattern, the UIP pattern was evident on HRCT scans of IP-related SLE. The survival of SLE patients was unrelated to IP.

en: Respiratory Investigation


en: Development, validation, and comparison of gene analysis methods for detecting mutation from non-small cell lung cancer patients-derived circulating free DNA.

en: Oncotarget

ja: Oncotarget


en: The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice.

en: The signaling pathways of growth factors, including platelet-derived growth factor, can be considered specific targets for overcoming the poor prognosis of idiopathic pulmonary fibrosis. Nintedanib, the recently approved multiple kinase inhibitor, has shown promising antifibrotic effects in patients with idiopathic pulmonary fibrosis; however, its efficacy is still limited, and in some cases, treatment discontinuation is necessary owing to toxicities such as gastrointestinal disorders. Therefore, more effective agents with less toxicity are still needed. TAS-115 is a novel multiple tyrosine kinase inhibitor that preferably targets platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor, and c-FMS in addition to other molecules. In this study, we evaluated the antifibrotic effect of TAS-115 on pulmonary fibrosis in vitro and in vivo. TAS-115 inhibited the phosphorylation of PDGFR on human lung fibroblast cell line MRC-5 cells and suppressed their platelet-derived growth factor-induced proliferation and migration. Furthermore, TAS-115 inhibited the phosphorylation of c-FMS, a receptor of macrophage colony-stimulating factor, in murine bone marrow-derived macrophages and decreased the production of CCL2, another key molecule for inducing pulmonary fibrosis, under the stimulation of macrophage colony-stimulating factor. Importantly, the inhibitory effects of TAS-115 on both PDGFR and c-FMS were 3- to 10-fold higher than those of nintedanib. In a mouse model of bleomycin-induced pulmonary fibrosis, TAS-115 significantly inhibited the development of pulmonary fibrosis and the collagen deposition in bleomycin-treated lungs. These data suggest that strong inhibition of PDGFR and c-FMS by TAS-115 may be a promising strategy for overcoming the intractable pathogenesis of pulmonary fibrosis.

ja: American Journal of Respiratory Cell and Molecular Biology


en: 肺アスペルギローマ術後肺瘻に対してPushampSlide法とロープウェイ法を応用したEWS による気管支充填術が有用であった1例

en: Shikoku Acta Medica

ja: 四国医学雑誌


en: Disseminated tuberculosis after pregnancy progressed to paradoxical response to the treatment: report of two cases.

en: Physicians should recognize PR in tuberculosis patients with postpartum and then evaluate treatment efficacy.

ja: We present two sequential cases (Patient 1: 26-year-old; Patient 2: 29-year-old) of postpartum tuberculosis with pulmonary and extrapulmonary lesions (Patient 1: peritonitis; Patient 2: psoas abscess secondary to spondylitis). Both cases progressed to PR (worsening of pre-existing lung infiltrations (Patients 1, 2) and new contralateral effusion (Patient 2)) in a relatively short time after initiation of treatment (Patient 1: 1 week; Patient 2: 3 weeks), suggesting that immune modulations during pregnancy and delivery may contribute to the pathogenesis of both disseminated tuberculosis and its PR. The pulmonary lesions and effusion of both cases gradually improved without change of chemotherapy regimen.

en: BMC Infectious Diseases

ja: BMC Infectious Diseases


en: 喘息管理におけるクイックチェックの有用性

ja: 喘息管理におけるクイックチェックの有用性

en: Journal of Kochi Medical Association

ja: 高知県医師会医学雑誌


en: Primary Gingival Tuberculosis Diagnosed Based on Genetic Identification.

en: A case of primary gingival tuberculosis in a 71-year-old Japanese woman is herein presented. A serous saliva culture was positive for tuberculosis, and we recognized that the origin of the tuberculosis infection was the gingiva based on the genetic identification in gingival biopsy tissue. The definitive diagnosis was facilitated by the genetic identification, a useful modern tool for diagnosing infectious diseases. The location and clinical presentation of this lesion were unusual, which underlines the importance of considering tuberculosis in the differential diagnosis of oral lesions that affect the gingiva.

en: Internal Medicine