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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: Identification of fibrocyte cluster in tumors reveals the role in antitumor immunity by PD-L1 blockade.

en: fibrocytes do not. Tumor-infiltrating fibrocytes acquire myofibroblast-like phenotypes through transforming growth factor β (TGF-β)/small mothers against decapentaplegic (SMAD) signaling. Thus, TGF-βR/SMAD inhibitor enhances the antitumor effects of dual VEGF and PD-L1 blockade by regulating fibrocyte differentiation. Fibrocytes are highlighted as regulators of the response to programmed death 1 (PD-1)/PD-L1 blockade.

ja: fibrocytes is enhanced by anti-PD-L1 antibody. Peritumoral implantation of fibrocytes enhances the antitumor effect of PD-L1 blockade in vivo; CD86

en: Cell Reports

ja: Cell 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: 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: Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker.

en: Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity.

en: Cancer Science

ja: Cancer Science


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: Internal Medicine

ja: Internal Medicine


en: Usefulness of imunohistochemical detection of Propionibacterium acnes in granulomas for differentiating sarcoidosis from other garanulomatous diseases; comparison between manual and automated immunohistochemical detection methods.

en: Microorganisms

ja: Microorganisms


en: Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes.

en: T cells when the activity is further enhanced by PD-L1/PD-1 blockade.

en: The Journal of Immunology

ja: The Journal of Immunology


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: Lysophosphatidic Acid Regulates the Differentiation of Th2 Cells and Its Antagonist Suppresses Allergic Airway Inflammation.

en: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma.

en: International Archives of Allergy and Immunology


en: Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells.

en: T cells in tumors, the number of Foxp3

ja: The combination of anti-PD-1 antibody with CDDP + PEM may be a promising therapy for MPM via inhibiting the accumulation of MDSCs and vessels in tumors.

en: Lung Cancer

ja: Lung Cancer


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 Journal of Medical Investigation : JMI