Updated on 2021/03/31

写真a

 
SAKAMOTO Koji
 
Organization
Nagoya University Hospital Respiratory Medicine Assistant professor of hospital
Title
Assistant professor of hospital
Contact information
メールアドレス

Degree 1

  1. 博士(医学) ( 2012.7   名古屋大学 ) 

Research Areas 1

  1. Life Science / Respiratory medicine

Current Research Project and SDGs 1

  1. 細胞外微粒子の呼吸器への影響

Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    - 2012.3

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    Country: Japan

  2. Nagoya University   Graduate School, Division of Medical Sciences

    - 2012.3

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    Country: Japan

Professional Memberships 8

  1. 日本呼吸器学会

  2. 日本アレルギー学会

  3. 日本感染症学会

  4. American Thoracic Society

  5. 日本内科学会

  6. 日本呼吸器学会

  7. 日本内科学会

  8. 日本アレルギー学会

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Awards 3

  1. International Session Award

    2017  

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    Award type:Award from international society, conference, symposium, etc.  Country:Japan

  2. The I.M. Rosenzweig Junior Investigator Award

    2016   Pulmonary Fibrosis Foundation  

    Koji Sakamoto

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:United States

  3. Scientific Abstract Award

    2014   American Thoracic Society  

    Koji Sakamoto

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

 

Papers 62

  1. Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of IPF. Reviewed International coauthorship International journal

    Koji Sakamoto, Taiki Furukawa, Yasuhiko Yamano, Kensuke Kataoka, Ryo Teramachi, Anjali Walia, Atsushi Suzuki, Masahide Inoue, Yoshio Nakahara, Changwan Ryu, Naozumi Hashimoto, Yasuhiro Kondoh

    The European respiratory journal   Vol. 57 ( 1 )   2021.1

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1183/13993003.01346-2020

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  2. Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors. Reviewed International journal

    Jun Fukihara, Koji Sakamoto, Junji Koyama, Takayasu Ito, Shingo Iwano, Masahiro Morise, Masahiro Ogawa, Yasuhiro Kondoh, Tomoki Kimura, Naozumi Hashimoto, Yoshinori Hasegawa

    Clinical lung cancer   Vol. 20 ( 6 ) page: 442 - +   2019.11

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    INTRODUCTION: Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated. PATIENTS AND METHODS: A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors. RESULTS: Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP. CONCLUSION: Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.

    DOI: 10.1016/j.cllc.2019.07.006

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  3. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state Reviewed International coauthorship International journal

    Omote Norihito, Sakamoto Koji, Li Qin, Schupp Jonas C., Adams Taylor, Ahangari Farida, Chioccioli Maurizio, DeIuliis Giuseppe, Hashimoto Naozumi, Hasegawa Yoshinori, Kaminski Naftali

    PHYSIOLOGICAL REPORTS   Vol. 9 ( 3 ) page: e14727   2021.2

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    DOI: 10.14814/phy2.14727

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  4. Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation. Reviewed International journal

    Shinichi Arizono, Taiki Furukawa, Hiroyuki Taniguchi, Koji Sakamoto, Tomoki Kimura, Kensuke Kataoka, Tomoya Ogawa, Fumiko Watanabe, Yasuhiro Kondoh

    Respirology (Carlton, Vic.)   Vol. 25 ( 11 ) page: 1152 - 1159   2020.11

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    BACKGROUND AND OBJECTIVE: The efficacy of supplemental oxygen during exercise remains unclear for patients with IPF, as there have been conflicting results from recent prospective studies with small sample sizes. METHODS: This prospective, single-blind, randomized, crossover trial evaluated the efficacy of supplemental oxygen compared with placebo air during exercise in consecutive patients with IPF without resting hypoxaemia at initial evaluation. Patients with <90% SpO2 in a 6MWT using room air were randomly assigned to a CWRET at 80% of peak work rate with oxygen or placebo air gas via nasal cannula at 4 L/min. The primary endpoint was the effect of supplemental oxygen on endurance time. RESULTS: We recruited 72 consecutive patients (median age: 66.5 years, % FVC: 84.6%, % DLCO : 61.4%). Supplemental oxygen significantly increased the endurance time (340-424 s; P < 0.001) and minimum SpO2 (88.0-94.0%; P < 0.001) compared with placebo air. Furthermore, supplemental oxygen significantly improved dyspnoea and leg fatigue. In a multivariate linear regression analysis, the endurance time on air was an independent explanatory variable of the improvement rate of endurance time (P = 0.02). CONCLUSION: In mild-moderate IPF with exercise-induced hypoxaemia even without resting hypoxaemia, supplemental oxygen during exercise improved the endurance time, desaturation and subjective symptoms. Patients with shorter endurance times with placebo air showed better improvement with supplemental oxygen.

    DOI: 10.1111/resp.13829

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  5. Clinical burden of immune checkpoint inhibitor-induced pneumonitis. Invited Reviewed International journal

    Koji Sakamoto, Jun Fukihara, Masahiro Morise, Naozumi Hashimoto

    Respiratory investigation   Vol. 58 ( 5 ) page: 305 - 319   2020.9

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    Immune checkpoint inhibitors (ICIs) have been a breakthrough in medical oncology. However, many patients experience a novel type of adverse drug reaction that has a unique clinical presentation, called immune-related adverse events (irAEs). A breakdown of self-tolerance and an exaggerated autoimmune reaction by the host are assumed to be the underlying mechanisms. Therefore, special attention to the optimal diagnosis and management is required. Among the various effects of irAE, pneumonitis has been recognized as an important manifestation because of its high morbidity and mortality. As the application of ICIs is expanding to a wider variety of tumor types, as well as its use with cytotoxic agents and radiation, clinicians are highly likely to encounter this complication. In this review, we will summarize the current understanding of the underlying mechanisms, incidence, risk factors, optimal diagnostic workup, and management of ICI-related pneumonitis (IRP). We will also review fundamental information on drug-induced lung toxicity in the oncology setting. In addition, research perspectives focused on better risk stratification and management to avoid serious complications in the future are presented.

    DOI: 10.1016/j.resinv.2020.05.008

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  6. Acute Exacerbation of Pleuroparenchymal Fibroelastosis Secondary to Allogenic Hematopoietic Stem Cell Transplantation.

    Murakami Y, Sakamoto K, Okumura Y, Suzuki A, Mii S, Sato M, Yokoi T, Hashimoto N, Hasegawa Y

    Internal medicine (Tokyo, Japan)     2020.7

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    DOI: 10.2169/internalmedicine.4995-20

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  7. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial Pneumonia: A retrospective observational study Reviewed International journal

    Omote N.

    Nagoya Journal of Medical Science   Vol. 82 ( 2 ) page: 301 - 313   2020.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nagoya Journal of Medical Science  

    DOI: 10.18999/nagjms.82.2.301

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  8. Reply to "Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death-1 Inhibitors". Reviewed International journal

    Jun Fukihara, Koji Sakamoto, Junji Koyama, Takayasu Ito, Shingo Iwano, Masahiro Morise, Masahiro Ogawa, Yasuhiro Kondoh, Tomoki Kimura, Naozumi Hashimoto, Yoshinori Hasegawa

    Clinical lung cancer   Vol. 21 ( 3 ) page: E205 - E205   2020.5

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    DOI: 10.1016/j.cllc.2019.11.013

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  9. Acute exacerbations of fibrotic interstitial lung diseases. Reviewed International journal

    Suzuki A, Kondoh Y, Brown KK, Johkoh T, Kataoka K, Fukuoka J, Kimura T, Matsuda T, Yokoyama T, Fukihara J, Ando M, Tanaka T, Hashimoto N, Sakamoto K, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 25 ( 5 ) page: 525 - 534   2020.5

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    DOI: 10.1111/resp.13682

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  10. <Editors' Choice> Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer. Reviewed International journal

    Yu Okada, Naozumi Hashimoto, Shingo Iwano, Koji Kawaguchi, Takayuki Fukui, Koji Sakamoto, Kenji Wakai, Kohei Yokoi, Yoshinori Hasegawa

    Nagoya journal of medical science   Vol. 81 ( 3 ) page: 427 - 438   2019.8

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    Although the lower limit of normal (LLN) of FEV1/FVC detects at-risk patients for postoperative outcomes among Japanese chronic obstructive pulmonary disease (COPD) patients with resected lung cancer, there was a lack of a Japanese reference equation to calculate the LLN of FEV1/FVC. Renewed Japanese spirometric reference variables might enable us to verify clinical impact of the LLN of FEV1/FVC among the Japanese population. To evaluate the clinical impact of the LLN of FEV1/FVC by using this renewed reference, data were retrospectively analyzed from 609 newly diagnosed lung cancer patients who had undergone thoracic surgery between 2006 and 2011. The combined assessment of the 0.70 fixed ratio and the LLN of the FEV1/FVC ratio classified the 609 subjects into the COPD (214 subjects), non-COPD (337 subjects), and in-between (58 subjects) groups, respectively. All of the relative odds ratios (ORs) of postoperative outcomes for the comparison between the in-between and non-COPD groups did not show significant confidence intervals (CIs). On the other hand, the adjusted ORs of postoperative outcomes for the COPD group versus the non-COPD group were 2.840 (95% CI: 1.824-4.421) for prolonged oxygen therapy (POT), 1.836 (95% CI: 1.166-2.890) for prolonged postoperative stays, and 1.637 (95% CI: 1.007-2.663) for combined complications. Adjusted comparisons of POT between the in-between and COPD groups also showed a significant relative OR of 2.984 (95% CI: 1.447-6.153). A standardized assessment of the LLN of FEV1/FVC by a renewed Japanese spirometric reference provides risk stratification for postoperative outcomes in the population.

    DOI: 10.18999/nagjms.81.3.427

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  11. Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells. Reviewed International journal

    Ando A, Hashimoto N, Sakamoto K, Omote N, Miyazaki S, Nakahara Y, Imaizumi K, Kawabe T, Hasegawa Y

    Cancer science   Vol. 110 ( 6 ) page: 1959 - 1973   2019.6

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    DOI: 10.1111/cas.14027

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  12. Performance of the COPD Assessment Test in patients with connective tissue disease-associated interstitial lung disease

    Suzuki Atsushi, Kondoh Yasuhiro, Swigris Jeffrey James, Matsuda Toshiaki, Kimura Tomoki, Kataoka Kensuke, Ando Masahiko, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    RESPIRATORY MEDICINE   Vol. 150   page: 15-20   2019.4

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    DOI: 10.1016/j.rmed.2019.01.017

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  13. Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus. Reviewed International journal

    Yamano Y, Taniguchi H, Kondoh Y, Ando M, Kataoka K, Furukawa T, Johkoh T, Fukuoka J, Sakamoto K, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 23 ( 11 ) page: 1041 - 1048   2018.11

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    DOI: 10.1111/resp.13365

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  14. Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis

    Teramachi Ryo, Kondoh Yasuhiro, Kataoka Kensuke, Taniguchi Hiroyuki, Matsuda Toshiaki, Kimura Tomoki, Yokoyama Toshiki, Yamano Yasuhiko, Furukawa Taiki, Sakamoto Koji, Hashimoto Naozumi, Hasegawa Yoshinori

    RESPIRATORY MEDICINE   Vol. 143   page: 147-152   2018.10

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    DOI: 10.1016/j.rmed.2018.09.011

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  15. Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease. Reviewed International journal

    Suzuki A, Kondoh Y, Swigris JJ, Ando M, Kimura T, Kataoka K, Yamano Y, Furukawa T, Numata M, Sakamoto K, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 23 ( 9 ) page: 851 - 859   2018.9

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    DOI: 10.1111/resp.13293

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  16. Prognostic evaluation by oxygenation with positive end-expiratory pressure in acute exacerbation of idiopathic pulmonary fibrosis: A retrospective cohort study.

    Suzuki A, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Sakamoto K, Hasegawa Y

    The clinical respiratory journal   Vol. 12 ( 3 ) page: 895 - 903   2018.3

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    DOI: 10.1111/crj.12602

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  17. Thin-section computed tomography-determined usual interstitial pneumonia pattern affects the decision-making process for resection in newly diagnosed lung cancer patients: a retrospective study Reviewed

    Hashimoto N, Ando A, Iwano S, Sakamoto K, Okachi S, Matsuzaki A, Okada Y, Wakai K, Yokoi K, Hasegawa Y

    BMC Pulm Med   Vol. 18 ( 1 ) page: 2   2018.1

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    DOI: 10.1186/s12890-017-0565-5

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  18. A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis

    Furukawa Taiki, Kondoh Yasuhiro, Taniguchi Hiroyuki, Yagi Mitsuaki, Matsuda Toshiaki, Kimura Tomoki, Kataoka Kensuke, Johkoh Takeshi, Ando Masahiko, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL   Vol. 51 ( 1 )   2018.1

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    DOI: 10.1183/13993003.01311-2017

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  19. Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma Reviewed International journal

    Koji Sakamoto, Satoru Ito, Naozumi Hashimoto, Yoshinori Hasegawa

    BMC CANCER   Vol. 17 ( 1 ) page: 526   2017.8

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    Background: Bleomycin-induced lung injury, a major complication of chemotherapy for germ cell tumors, occasionally fails to respond to the standard treatment with corticosteroids and develops into severe respiratory insufficiency. Little is known about salvage treatment for refractory cases.
    Case presentation: A 63-year-old man who had been diagnosed with stage I seminoma and undergone a high orchiectomy 1 year previously developed swelling of his left iliac lymph node and was diagnosed with a recurrence of the seminoma. He was administered a standard chemotherapy regimen of cisplatin, etoposide, and bleomycin. At the end of second cycle, he developed a dry cough and fever that was accompanied by newly-identified bilateral infiltrates on chest X-ray. Despite initiation of oral prednisolone, his exertional dyspnea and decline in pulmonary functions continued to be aggravated. High-dose pulse treatment with methylprednisolone was introduced and improved his symptoms and radiologic findings. However, the maintenance dose of oral prednisolone allowed reactivation of the disease with evidence of newly-developed bilateral lung opacities on high-resolution CT scans. Considering his glucose intolerance and cataracts as complications of corticosteroid treatment, administration of pirfenidone was initiated with the patient's consent. Pirfenidone at 1800 mg/day was well tolerated, and resolved his symptoms and abnormal opacities on a chest CT scan. Subsequently, the dose of prednisolone was gradually tapered without worsening of the disease. At the most recent follow-up, he was still in complete remission of seminoma with a successfully tapered combination dose of prednisolone and pirfenidone.
    Conclusions: Pirfenidone, a novel oral agent with anti-inflammatory and -fibrotic properties, should be considered as a salvage drug for refractory cases of bleomycin-induced lung injury.

    DOI: 10.1186/s12885-017-3521-0

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  20. Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice Reviewed International journal

    Christine K. Wong, Candice A. Smith, Koji Sakamoto, Naftali Kaminski, Jonathan L. Koff, Daniel R. Goldstein

    JOURNAL OF IMMUNOLOGY   Vol. 199 ( 3 ) page: 1060 - 1068   2017.8

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    Influenza viral infections often lead to increased mortality in older people. However, the mechanisms by which aging impacts immunity to influenza lung infection remain unclear. We employed a murine model of influenza infection to identify these mechanisms. With aging, we found reduced numbers of alveolar macrophages, cells essential for lung homeostasis. We also determined that these macrophages are critical for influenza-induced mortality with aging. Furthermore, aging vastly alters the transcriptional profile and specifically downregulates cell cycling pathways in alveolar macrophages. Aging impairs the ability of alveolar macrophages to limit lung damage during influenza infection. Moreover, aging decreases alveolar macrophage phagocytosis of apoptotic neutrophils, downregulates the scavenging receptor CD204, and induces retention of neutrophils during influenza infection. Thus, aging induces defective phagocytosis by alveolar macrophages and increases lung damage. These findings indicate that therapies that enhance the function of alveolar macrophages may improve outcomes in older people infected with respiratory viruses.

    DOI: 10.4049/jimmunol.1700397

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  21. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model Reviewed International journal

    Luai Huleihel, Jacobo Sellares, Nayra Cardenes, Diana Alvarez, Rosa Faner, Koji Sakamoto, Guoying Yu, Maria G. Kapetanaki, Naftali Kaminski, Mauricio Rojas

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   Vol. 313 ( 1 ) page: L92 - L103   2017.7

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    Although different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing fibrosis, this protective effect is not observed with late administration of these cells, when fibrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antifibrotic) or miR-154 (profibrotic) could alter lung fibrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modified B-MSCs were intravenously administered to mice at day 7 after bleomycin instillation, and the mice were euthanized at day 14. Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no significant differences were observed in Ashcroft score and OH-proline. However, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modified mesenchymal stem cells as a potential future research in lung fibrosis.

    DOI: 10.1152/ajplung.00323.2016

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  22. Progression of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis with mild to moderate restriction Reviewed International journal

    Ryo Teramachi, Hiroyuki Taniguchi, Yasuhiro Kondoh, Masahiko Ando, Tomoki Kimura, Kensuke Kataoka, Atsushi Suzuki, Taiki Furukawa, Koji Sakamoto, Yoshinori Hasegawa

    RESPIROLOGY   Vol. 22 ( 5 ) page: 986 - 990   2017.7

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    Background and objectiveElevation of mean pulmonary arterial pressure (MPAP) is associated with poor prognosis in patients with idiopathic pulmonary fibrosis (IPF), yet the progression of MPAP in patients with IPF has not been sufficiently elucidated. We evaluated serial changes in MPAP and its determinants in patients with IPF with mild to moderate restriction.
    MethodsWe retrospectively reviewed patients with IPF who underwent initial evaluations including right heart catheterization (RHC) in our institute from May 2007 to December 2013 with follow-up RHC at least 1year later. Patients with forced vital capacity (FVC)&lt;50% predicted or those with pulmonary artery wedge pressure&gt;15mm Hg were excluded.
    ResultsA total of 95 patients were included. Median follow-up time of second RHC was 1.8years. MPAP increased significantly at follow-up (from 16.8 to 20.2mm Hg; P&lt;0.001), and annual change in MPAP (MPAP) was 1.8mm Hg/year. In multiple regression analysis, the lowest oxygen saturation (SpO(2) ) at 6-min walk test (6MWT) was an independent predictor of MPAP. When adjusted for age, sex, baseline MPAP and FVC % predicted, MPAP was a significant predictor of mortality (hazard ratio: 1.21; P=0.001).
    ConclusionMPAP was significantly associated with desaturation in the 6MWT, and with increased mortality in patients with IPF with mild to moderate restriction.
    We reviewed patients with idiopathic pulmonary fibrosis with mild to moderate restriction and showed that mean pulmonary arterial pressure (MPAP) was progressive. The lowest oxygen saturation (SpO(2) ) in the 6-min walk test at baseline was an independent predictor of annual change in MPAP.

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  23. COPD Assessment Test for measurement of health status in patients with idiopathic pulmonary fibrosis: A cross-sectional study. Reviewed

    Matsuda T, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Sakamoto K, Suzuki A, Furukawa T, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 22 ( 4 ) page: 721-727   2017.5

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    DOI: 10.1111/resp.12936

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  24. Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug-induced lung injury Reviewed International journal

    Atsushi Suzuki, Hiroyuki Taniguchi, Yasuhiro Kondoh, Masahiko Ando, Naohiro Watanabe, Tomoki Kimura, Kensuke Kataoka, Toshiki Yokoyama, Koji Sakamoto, Yoshinori Hasegawa

    RESPIROLOGY   Vol. 22 ( 4 ) page: 744 - 749   2017.5

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    Background and objectiveDrug-induced lung injury (DLI) can result from a vast number of agents, and sometimes presents findings similar to those of acute respiratory distress syndrome (ARDS). Previous studies have reported that circulating levels of soluble thrombomodulin (TM) reflect endothelial injuries, which play key roles in the development of ARDS. We hypothesized that endothelial injuries are an important aspect of pathogenesis in severe DLI. The primary aim of this study was to examine the associations between soluble TM and disease severity in DLI patients.
    MethodsOf the 2580 patients who underwent a bronchoalveolar lavage (BAL) procedure at Tosei General Hospital between May 2007 and February 2015, we retrospectively analysed the data of 68 DLI patients. Soluble TM in plasma and BAL fluid (BALF), and other biomarkers were included in our analysis.
    ResultsAt the time of diagnosis, 39 patients (57%) had respiratory failure (partial pressure of oxygen/inspiratory oxygen fraction ratio, PaO2 /FiO(2) ratio&lt;300). There was a significant negative linear correlation between the PaO2 /FiO(2) ratio and soluble TM in BALF (r=-0.448, P&lt;0.001). In a stepwise multiple regression analysis, soluble TM in BALF and surfactant protein D (SP-D) were the only independent determinants of the PaO2 /FiO(2) ratio. Additionally, in a multivariate logistic regression model, soluble TM in BALF (adjusted OR (aOR): 7.48, 95% CI: 1.60-34.98) and SP-D (aOR: 5.31, 95% CI: 1.40-20.15) was an independent predictor of respiratory failure (PaO2 /FiO(2) ratio&lt;300).
    ConclusionSoluble TM in BALF is an independent predictor of severe DLI. These findings underscore the importance of pulmonary endothelial injuries in the pathogenesis of severe DLI.
    Soluble thrombomodulin in bronchoalveolar lavage is an independent predictor of severe drug-induced lung injury (DLI). Pulmonary endothelial injuries are an important aspect of pathogenesis in severe DLI.

    DOI: 10.1111/resp.12965

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  25. Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis Reviewed International journal

    Argyris Tzouvelekis, Jose D. Herazo-Maya, Martin Slade, Jen-Hwa Chu, Giuseppe Deiuliis, Changwan Ryu, Qin Li, Koji Sakamoto, Gabriel Ibarra, Hongyi Pan, Mridu Gulati, Danielle Antin-Ozerkis, Erica L. Herzog, Naftali Kaminski

    RESPIROLOGY   Vol. 22 ( 3 ) page: 486 - 493   2017.4

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    Background and objective: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and variable clinical course. Although matrix metalloproteinase-7 (MMP-7) is emerging as an important IPF biomarker, reproducibility across studies is unclear. We aimed to determine whether a previously reported prognostic threshold for MMP-7 was predictive of mortality in an independent cohort of IPF patients.
    Methods: MMP-7 concentrations obtained from heparinized plasma samples were determined by ELISA in 97 patients with IPF and 41 healthy controls. The association of the previously published heparin plasma MMP-7 threshold of 12.1 ng/mL with all-cause mortality or transplant-free survival (TFS) was determined, either as an independent biomarker or as part of the modified personal clinical and molecular mortality index (m-PCMI).
    Results: MMP-7 plasma concentrations were significantly higher in IPF patients compared to healthy controls (14.40 +/- 6.55 ng/mL vs 6.03 +/- 2.51 ng/mL, P &lt; 0.001). The plasma MMP-7 threshold of 12.1 ng/mL was significantly associated with both all-cause mortality and TFS (unadjusted Cox proportional hazard ratio (HR) = 25.85 and 15.49, 95% CI: 10.91-61.23 and 5.41-44.34, respectively, P &lt; 0.001). MMP-7 concentrations, split by 12.1 ng/mL, were significantly (P &lt; 0.05) predictive of mortality and TFS after adjusting for age, gender, smoking and baseline pulmonary function parameters, in a multivariate Cox proportional hazards model. MMP-7 concentrations were negatively correlated with diffusing lung capacity of carbon monoxide (DLCO) (r = -0.21, P = 0.02), and positively with a mortality risk scoring system (GAP) that combines age, gender, forced vital capacity (FVC) and DLCO (r = 0.32, P = 0.001).
    Conclusion: This study confirms that MMP-7 concentrations could be used to accurately predict outcomes across cohorts and centres, when similar collection protocols are applied.

    DOI: 10.1111/resp.12920

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  26. SH2 Domain-Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis Reviewed International coauthorship International journal

    Argyrios Tzouvelekis, Guoying Yu, Christian L. Lino Cardenas, Jose D. Herazo-Maya, Rong Wang, Tony Woolard, Yi Zhang, Koji Sakamotol, Hojin Lee, Jae-Sung Yi, Giuseppe Deluliis, Nikolaos Xylourgidis, Farida Ahangari, Patty J. Lee, Vassilis Aidinis, Erica L. Herzog, Robert Homer, Anton M. Bennett, Naftali Kaminski

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195 ( 4 ) page: 500 - 514   2017.2

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    Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and no cure. The potential role of the ubiquitously expressed SH2 domain-containing tyrosine phosphatase-2 (SHP2) as a therapeutic target has not been studied in IPF.
    Objectives: To determine the expression, mechanistic role, and potential therapeutic usefulness of SHP2 in pulmonary fibrosis.
    Methods: The effects of SHP2 overexpression and inhibition on fibroblast response to profibrotic stimuli were analyzed in vitro in primary human and mouse lung fibroblasts. In vivo therapeutic effects were assessed in the bleomycin model of lung fibrosis by SHP2-lentiviral administration and transgenic mice carrying a constitutively active SHP2 mutation.
    Measurements and Main Results: SHP2 was down-regulated in lungs and lung fibroblasts obtained from patients with IPF. Immunolocalization studies revealed that SHP2 was absent within fibroblastic foci. Loss of SHP2 expression or activity was sufficient to induce fibroblast-to-myofibroblast differentiation in primary human lung fibroblasts. Overexpression of constitutively active SHP2 reduced the responsiveness offibroblasts to profibrotic stimuli, including significant reductions in cell survival and myofibroblast differentiation. SHP2 effects were mediated through deactivation of fibrosis-relevant tyrosine kinase and serine/threonine kinase signaling pathways. Mice carrying the Noonan syndrome-associated gain-of-function SHP2 mutation (SHP2(D61G/+)) were resistant to bleomycin-induced pulmonary fibrosis. Restoration of SHP2 levels in vivo through lentiviral delivery blunted bleomycin-induced pulmonary fibrosis.
    Conclusions: Our data suggest that SHP2 is an important regulator of fibroblast differentiation, and its loss as observed in IPF facilitates profibrotic phenotypic changes. Augmentation of SHP2 activity or expression should be investigated as a novel therapeutic strategy for IPF.

    DOI: 10.1164/rccm.201602-0329OC

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  27. Hemosiderin-laden macrophages are an independent factor correlated with pulmonary vascular resistance in idiopathic pulmonary fibrosis: a case control study Reviewed International journal

    Jun Fukihara, Hiroyuki Taniguchi, Masahiko Ando, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Taiki Furukawa, Takeshi Johkoh, Junya Fukuoka, Koji Sakamoto, Yoshinori Hasegawa

    BMC PULMONARY MEDICINE   Vol. 17 ( 1 ) page: 30   2017.2

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    Background: Increases in hemosiderin-laden macrophages (HLM) are reported to be observed in idiopathic pulmonary fibrosis (IPF). According to a recent study, significant correlation between hemosiderin deposition in the lung tissue of IPF and pulmonary hypertension evaluated by echocardiography has been suspected. In this study, we aimed to evaluate whether HLM in bronchoalveolar lavage fluid (BALF) is a factor correlated with pulmonary hemodynamic parameters evaluated by right heart catheterization in patients with IPF.
    Methods: Initial data from 103 consecutive patients with IPF who underwent surgical lung biopsy between November 2007 and March 2014 were retrospectively analyzed. The "HLM score" of BALF was established by dividing the number of Perls' Prussian blue stain positive macrophages by the total number of macrophages counted.
    Results: BALF showed an elevated HLM score (38.2%). Right heart catheterization revealed mean pulmonary arterial pressure (mPAP) of 16.3 mmHg and pulmonary vascular resistance (PVR) of 1.55 Wood units. HLM score was positively correlated with mPAP (rho = 0.204; rho = 0.038) and PVR (rho = 0.349, rho &lt; 0.001). In multivariate analysis, 6-min walk distance (standardized partial regression coefficient [beta], -0.391; p &lt; 0.001), minimum oxygen saturation during 6-min walk distance (beta, -0.294; rho = 0.001) and HLM score (beta, 0.265; rho = 0.002) were independently correlated with PVR.
    Conclusions: HLM score in BALF is an independent factor correlated with PVR in patients with IPF.

    DOI: 10.1186/s12890-017-0376-8

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  28. The St. George's Respiratory Questionnaire as a prognostic factor in IPF Reviewed International journal

    Taiki Furukawa, Hiroyuki Taniguchi, Masahiko Ando, Yasuhiro Kondoh, Kensuke Kataoka, Osamu Nishiyama, Takeshi Johkoh, Junya Fukuoka, Koji Sakamoto, Yoshinori Hasegawa

    RESPIRATORY RESEARCH   Vol. 18 ( 1 ) page: 18   2017.1

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    Background: It is unclear whether health related quality of life (HRQL) may have a predictive value for mortality in idiopathic pulmonary fibrosis (IPF). We investigated the relationship between HRQL assessed using the St. George's Respiratory Questionnaire (SGRQ) and survival time in patients with IPF, and tried to determine a clinical meaningful cut off value to predict poorer survival rates.
    Methods: We retrospectively analyzed consecutive patients with IPF who underwent an initial evaluation from May 2007 to December 2012. The diagnosis of IPF was made according to the 2011 international consensus guidelines. We used Cox proportional hazard models to identify independent predictors for mortality rate in patients with IPF.
    Results: We examined 182 eligible cases, average age was 66 years old, and 86% were male. Mean levels of percent predicted FVC, DLco, six-minute-walk test distance, and the SGRQ total score were around 80%, 58%, 580 m, and 34 points. On multivariate analysis, the SGRQ total score (hazard ratio [HR], 1.012; 95% confidence interval [CI] 1.001-1.023; P = .029) and percent predicted FVC (HR, 0.957; 95% CI 0.944-0.971, P &lt; .001) were independent predictors for mortality rate. Moreover, a score higher than 30 points in the SGRQ total score showed higher mortality rate (HR, 2.047; 95% CI, 1.329-3.153; P = .001).
    Conclusions: The SGRQ total score was one of independent prognostic factors in patients with IPF. Total scores higher than 30 points were associated with higher mortality rates.

    DOI: 10.1186/s12931-017-0503-3

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  29. Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia. Reviewed

    Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Arizono S, Nishimura K, Sakamoto K, Ito S, Ando M, Hasegawa Y

    Respirology (Carlton, Vic.)   Vol. 22 ( 1 ) page: 120-125   2017.1

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    DOI: 10.1111/resp.12863

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  30. Exogenous induction of unphosphorylated PTEN reduces TGFβ-induced extracellular matrix expressions in lung fibroblasts. Reviewed

      Vol. 25 ( 1 ) page: 86-97   2017.1

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    DOI: 10.1111/wrr.12506

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  31. Depression Is Significantly Associated with the Health Status in Patients with Idiopathic Pulmonary Fibrosis. Reviewed

    Matsuda T, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Nishimura K, Nishiyama O, Sakamoto K, Hasegawa Y

    Internal medicine (Tokyo, Japan)   Vol. 56 ( 13 ) page: 1637-1644   2017

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    DOI: 10.2169/internalmedicine.56.7019

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  32. Impact of mild to moderate COPD on feasibility and prognosis in non-small cell lung cancer patients who received chemotherapy

    Omote Norihito, Hashimoto Naozumi, Morise Masahiro, Sakamoto Koji, Miyazaki Shinichi, Ando Akira, Nakahara Yoshio, Hasegawa Yoshinori

    INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE   Vol. 12   page: 3541 - 3547   2017

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    DOI: 10.2147/COPD.S149456

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  33. PULMONARY REHABILITATION IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: COMPARISON WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Arizono Shinichi, Taniguchi Hiroyuki, Sakamoto Koji, Kondoh Yasuhiro, Kimura Tomoki, Kataoka Kensuke, Ogawa Tomoya, Watanabe Fumiko, Tabira Kazuyuki, Kozu Ryo

    SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES   Vol. 34 ( 4 ) page: 283-289   2017

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  34. Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease. Reviewed International journal

    Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Watanabe F, Tabira K, Kozu R

    Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG   Vol. 34 ( 4 ) page: 283 - 289   2017

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    DOI: 10.36141/svdld.v34i4.5549

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  35. Impact of Thin-Section Computed Tomography-Determined Combined Pulmonary Fibrosis and Emphysema on Outcomes Among Patients With Resected Lung Cancer. Reviewed

    Hashimoto N, Iwano S, Kawaguchi K, Fukui T, Fukumoto K, Nakamura S, Mori S, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    The Annals of thoracic surgery   Vol. 102 ( 2 ) page: 440-7   2016.8

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    DOI: 10.1016/j.athoracsur.2016.03.014

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  36. Mean pulmonary arterial pressure as a prognostic indicator in connective tissue disease associated with interstitial lung disease: a retrospective cohort study. Reviewed

    Takahashi K, Taniguchi H, Ando M, Sakamoto K, Kondoh Y, Watanabe N, Kimura T, Kataoka K, Suzuki A, Ito S, Hasegawa Y

    BMC pulmonary medicine   Vol. 16 ( 1 ) page: 55   2016.4

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    DOI: 10.1186/s12890-016-0207-3

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  37. Biomarkers in the Evaluation and Management of Idiopathic Pulmonary Fibrosis. Reviewed

    Tzouvelekis A, Herazo-Maya J, Sakamoto K, Bouros D

    Current topics in medicinal chemistry   Vol. 16 ( 14 ) page: 1587-98   2016

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  38. Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers. Reviewed

    Kohnoh T, Hashimoto N, Ando A, Sakamoto K, Miyazaki S, Aoyama D, Kusunose M, Kimura M, Omote N, Imaizumi K, Kawabe T, Hasegawa Y

    Cancer cell international   Vol. 16   page: 33   2016

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    DOI: 10.1186/s12935-016-0308-3

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  39. Lung-Dominant Connective Tissue Disease: Clinical, Radiologic, and Histologic Features. Reviewed

    Omote N, Taniguchi H, Kondoh Y, Watanabe N, Sakamoto K, Kimura T, Kataoka K, Johkoh T, Fujimoto K, Fukuoka J, Otani K, Nishiyama O, Hasegawa Y

    Chest   Vol. 148 ( 6 ) page: 1438-1446   2015.12

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    DOI: 10.1378/chest.14-3174

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  40. Direct regulation of transforming growth factor β-induced epithelial-mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells. Reviewed

      Vol. 106 ( 12 ) page: 1693-704   2015.12

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    DOI: 10.1111/cas.12831

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  41. Recombinant Human Thrombomodulin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Reviewed

    Kataoka K, Taniguchi H, Kondoh Y, Nishiyama O, Kimura T, Matsuda T, Yokoyama T, Sakamoto K, Ando M

    Chest   Vol. 148 ( 2 ) page: 436-443   2015.8

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    DOI: 10.1378/chest.14-2746

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  42. Risk stratification by the lower limit of normal of FEV1/FVC for postoperative outcomes in patients with COPD undergoing thoracic surgery. Reviewed

    Osuka S, Hashimoto N, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    Respiratory investigation   Vol. 53 ( 3 ) page: 117-23   2015.5

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    DOI: 10.1016/j.resinv.2015.01.005

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  43. Broader criteria of undifferentiated connective tissue disease in idiopathic interstitial pneumonias. Reviewed

    Kondoh Y, Johkoh T, Fukuoka J, Arakawa H, Tanaka T, Watanabe N, Sakamoto K, Kataoka K, Kimura T, Taniguchi H

    Respiratory medicine   Vol. 109 ( 3 ) page: 389-96   2015.3

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    DOI: 10.1016/j.rmed.2015.01.009

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  44. Endurance time is the most responsive exercise measurement in idiopathic pulmonary fibrosis. Reviewed

    Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Watanabe F, Nishiyama O, Nishimura K, Kozu R, Tabira K

    Respiratory care   Vol. 59 ( 7 ) page: 1108-15   2014.7

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    DOI: 10.4187/respcare.02674

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  45. Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. Reviewed

    Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K, Yousef H, LeJeune M, Coon TA, Redinger CJ, Chensny L, Manor E, Schatten G, Kaminski N

    American journal of physiology. Lung cellular and molecular physiology   Vol. 306 ( 6 ) page: L534-42   2014.3

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    DOI: 10.1152/ajplung.00149.2013

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  46. Crizotinib-induced acute interstitial lung disease in a patient with EML4-ALK positive non-small cell lung cancer and chronic interstitial pneumonia. Reviewed

    Watanabe N, Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Kataoka K, Sakamoto K

    Acta oncologica (Stockholm, Sweden)   Vol. 53 ( 1 ) page: 158-60   2014.1

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    DOI: 10.3109/0284186X.2013.802838

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  47. Efficacy of combined therapy with cyclosporin and low-dose prednisolone in interstitial pneumonia associated with connective tissue disease. Reviewed

    Watanabe N, Sakamoto K, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Ono K, Fukuoka J, Nishiyama O, Hasegawa Y

    Respiration; international review of thoracic diseases   Vol. 87 ( 6 ) page: 469-77   2014

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    DOI: 10.1159/000358098

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  48. Significance of pulmonary arterial pressure as a prognostic indicator in lung-dominant connective tissue disease. Reviewed

    Suzuki A, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Sakamoto K, Nishiyama O, Hasegawa Y

    PloS one   Vol. 9 ( 9 ) page: e108339   2014

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    DOI: 10.1371/journal.pone.0108339

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  49. Endobronchial ultrasound transbronchial needle aspiration in older people. Reviewed

    Okachi S, Imai N, Imaizumi K, Hase T, Shindo Y, Sakamoto K, Aso H, Wakahara K, Hashimoto I, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y

    Geriatrics & gerontology international   Vol. 13 ( 4 ) page: 986-92   2013.10

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    DOI: 10.1111/ggi.12043

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  50. Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. Reviewed

    Watanabe F, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Arizono S, Nishiyama O, Hasegawa Y

    Respiratory medicine   Vol. 107 ( 4 ) page: 622-8   2013.4

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    DOI: 10.1016/j.rmed.2012.12.013

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  51. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Reviewed

    Kimura M, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Aso H, Sakamoto K, Hasegawa Y

    Respiration; international review of thoracic diseases   Vol. 85 ( 6 ) page: 456-63   2013

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    DOI: 10.1159/000345221

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  52. Involvement of TGFβ-induced phosphorylation of the PTEN C-terminus on TGFβ-induced acquisition of malignant phenotypes in lung cancer cells. Reviewed

      Vol. 8 ( 11 ) page: e81133   2013

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    DOI: 10.1371/journal.pone.0081133

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  53. Predictors of the need to initiate noninvasive ventilation in stable outpatients with acute exacerbation of chronic obstructive pulmonary disease. Reviewed

    Taga S, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Aso H, Sakamoto K, Hasegawa Y

    Internal medicine (Tokyo, Japan)   Vol. 52 ( 16 ) page: 1781-6   2013

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  54. Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury. Reviewed

    Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y

    Am J Physiol Lung Cell Mol Physiol.   Vol. 303 ( 1 ) page: L43-53   2012.7

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  55. Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells.

    Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y.

    Mol Carcinog   Vol. 51   page: 400-410   2012

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  56. Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures.

    Sakamoto K, Taniguchi H, Kondoh Y, Wakai K, Kimura T, Kataoka K, Hashimoto N, Nishiyama O, Hasegawa Y.

    Respir Med   Vol. 106 ( 3 ) page: 436-42   2012

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  57. Risk factors of acute exacerbation of idiopathic pulmonary fibrosis. Reviewed

    Kondoh Y, Taniguchi H, Katsuta T, Kataoka K, Kimura T, Nishiyama O, Sakamoto K, Johkoh T, Nishimura M, Ono K, Kitaichi M.

    Sarcoidosis Vasc Diffuse Lung Dis   Vol. 27   page: 103-110   2010

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  58. Serum KL-6 in fibrotic NSIP: Correlations with physiologic and radiologic parameters.

    Sakamoto K, Taniguchi H, Kondoh Y, Johkoh T, Sumikawa H, Kimura T, Nishiyama O, Kato K, Kataoka K, Ono K, Kitaichi M, Hasegawa Y.

    Respir Med   Vol. 104   page: 127-133   2009

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  59. Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease.

    Sakamoto K, Taniguchi H, Kondoh Y, Ono K, Hasegawa Y, Kitaichi M.

    Eur Respir Rev   Vol. 18   page: 129-132.   2009

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  60. 原発性肺クリプトコッカス症の臨床的検討 Reviewed

    阪本 考司, 麻生 裕紀, 横山 俊樹, 加藤 景介, 西山 理, 木村 智樹, 近藤 康博, 谷口 博之

    感染症学雑誌   Vol. 4   page: 403-407   2007.7

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  61. びまん性肺疾患に対する外科的肺生検の検討 合併症、診断効率と早期死亡について

    阪本 考司, 横山 俊樹, 麻生 裕紀, 岩木 舞, 野間 聖, 加藤 景介, 西山 理, 木村 智樹, 近藤 康博, 谷口 博之

    日本呼吸器学会雑誌   Vol. 44 ( 10 ) page: 675-680   2006.10

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  62. 化学療法を施行したIV期非小細胞肺癌におけるQuality of Life

    西山 理, 谷口 博之, 近藤 康博, 木村 智樹, 加藤 景介, 野間 聖, 岩木 舞, 麻生 裕紀, 阪本 考司, 清水 淳市

    日本呼吸器学会雑誌   Vol. 44 ( 5 ) page: 368-373   2006.5

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▼display all

MISC 12

  1. The Role of Meflin Expression in Fibroblasts During Development of Pulmonary Fibrosis

    Hashimoto N., Nakahara Y., Sakamoto K., Enomoto A., Yokoi T., Suzuki A., Inoue M., Wakahara K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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  2. Single-Cell RNAseq of Aging Mouse Lungs Reveals Global and Cell-Specific Inflammatory Aberrations

    Cosme C. Jr., McDonough J. E., Adams T., Schupp J. C., Omote N., Ahangari F., Deluliis G., Sakamoto K., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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  3. Silica Nanoparticle Induced Lung Injury in Mice: Dissecting Relative Contribution of Its Size and Surface Modification

    Inoue M., Sakamoto K., Suzuki A., Nakahara Y., Hashimoto N., Hasegawa Y., Sawada M.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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  4. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S716 - S716   2019.10

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  5. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL   Vol. 54   2019.9

  6. Recurrent Acute Exacerbations of Fibrotic Interstitial Lung Diseases

    Suzuki A., Kondoh Y., Brown K. K., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Ando M., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 199   2019

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  7. TINCR, a Long Intergenic Noncoding RNA Decreased in IPF, Is a Novel Regulator of Airway Epithelial Cell Differentiation

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Xylourgidis N., DeIuliis G., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 199   2019

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  8. Risk Factor Evaluation of Programmed Death 1 Inhibitor Related Pneumonitis in Patients with Non-Small Cell Lung Cancer

    Fukihara J., Sakamoto K., Iwano S., Morise M., Hashimoto N., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 197   2018

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  9. Risk Stratification For Airflow Obstruction-Related Outcomes Based On A Renewed Japanese Spirometric Reference By Using The Lambda-Mu-Sigma Method

    Hashimoto N., Okada Y., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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  10. Unphosphorylated Pten Inhibits Tgf beta-Induced Aberrant Cell Motility In Epithelial Cells Via Differential Phosphatase Activities

    Hashimoto N., Sakamoto K., Miyazaki S., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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  11. The Impact Of CT-Detected Usual Interstitial Pneumonia Pattern As The Decision-Making Factor For Treatment Of Lung Cancer

    Ando A., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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  12. Single Cell Rna-Sequencing Reveals Distinct Effects Of Inhibition Of Fendrr, A Long Non-Coding Rna Implicated In Fibroblast To Myofibroblast Differentiation

    Adams T., Sakamoto K., Ahangari F., Munivar A., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 195   2017

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Presentations 27

  1. Assessment of Circulating Mitochondrial DNA as a Liquid Biomarker in Acute Exacerbation of Idiopathic Pulmonary Fibrosis International conference

    Sakamoto K., Furukawa T., Yamano Y., Teramachi R., Kataoka K., Hashimoto N., Kondoh Y., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2019

    Language:English   Presentation type:Poster presentation  

  2. Possible UIP Pattern with Traction Bronchiectasis on HRCT: Prognostic Impact in IIP International conference

    Fukihara J., Kondoh Y., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Furukawa T., Johkoh T., Fukuoka J., Sakamoto K., Hashimoto N., Hasegawa Y., Brown K. K.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2018

    Language:English   Presentation type:Poster presentation  

  3. Lung Epithelium Overexpressed Noncoding Rna (leon): A Potential Regulator Of Epithelial Gene Expression In Idiopathic Pulmonary Fibrosis International conference

    Guardela B. Juan, Herazo-Maya J. D., Sakamoto K., Li Q., Deluliis G., Yan X., Prasse A., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2017

    Language:English   Presentation type:Poster presentation  

  4. Performance Of The Saint George's Respiratory Questionnaire (sgrq) In Patients With Connective Tissue Disease-Associated Interstitial Lung Disease (ctd-Ild) International conference

    Suzuki A., Taniguchi H., Kondoh Y., Swigris J. J., Yamano Y., Furukawa T., Numata-Nakamura M., Sakamoto K., Ando M., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

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    Event date: 2017

    Language:English   Presentation type:Poster presentation  

  5. Transduction of PTEN with mutated its C-terminal phosphorylation sites inhibits TGFb- induced phe notype alterations through epithelial-mesenchymal transition International conference

    K. Sakamoto, N. Hashimoto, D. Aoyama, M. Kusunose, M. Kimura, T. Kohnoh, K. Imaizumi, Y. Hasegawa.

    American Thoracic Society 2012 International Conference 

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    Event date: 2012

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  6. Acute Exacerbation of IPF Following Bronchoalveolar Lavage Procedures International conference

    K. Sakamoto, H. Taniguchi, Y. Kondoh, K. Wakai, T. Kimura, K. Kataoka, N. Hashimoto, O. Nishiyama, Y. Hasegawa.

    Chest 2011 Annual Congress 

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    Event date: 2011

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  7. Modulated Expression Of Surfactant Protein D In Acute Lung Injury Might Be Associated With Epithelial-Mesenchymal Transition In Epithelial Cells International conference

    K. Sakamoto, N. Hashimoto, K. Imaizumi, H. Taniguchi, Y. Kondoh, T. Kohnoh, D. Aoyama, T. Ogawa, Y. Hasegawa.

    American Thoracic Society 2011 International Conference 

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    Event date: 2011

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  8. Modulated expression of surfactant protein D in acute lung injury might be associated with epithelial-mesenchymal transition in epithelial cells. International conference

    K. Sakamoto, N. Hashimoto, Y. Hasegawa.

    FASEB Summer Research Conferences 2010 

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    Event date: 2010

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  9. EMT-Related Gene, Twist, for Phenotype Change in Lung Cancer Cells International conference

    K. Sakamoto, N. Hashimoto, K. Imaizumi, H. Nakashima, T. Kohnoh, D. Aoyama, T. Ogawa, Y. Hasegawa.

    American Thoracic Society 2010 International Conference 

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    Event date: 2010

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  10. Increased Circulating Mitochondrial DNA Content Predicts Fatal Complication and Worse Prognosis in Idiopathic Pulmonary Fibrosis International conference

    Sakamoto K., Furukawa T., Yamano Y., Teramachi R., Suzuki A., Nakahara Y., Inoue M., Kataoka K., Hashimoto N., Kondoh Y., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  11. The Role of Meflin Expression in Fibroblasts During Development of Pulmonary Fibrosis International conference

    Hashimoto N., Nakahara Y., Sakamoto K., Enomoto A., Yokoi T., Suzuki A., Inoue M., Wakahara K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  12. Single-Cell RNAseq of Aging Mouse Lungs Reveals Global and Cell-Specific Inflammatory Aberrations International coauthorship International conference

    Cosme C. Jr., McDonough J. E., Adams T., Schupp J. C., Omote N., Ahangari F., Deluliis G., Sakamoto K., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  13. Silica Nanoparticle Induced Lung Injury in Mice: Dissecting Relative Contribution of Its Size and Surface Modification International coauthorship International conference

    Inoue M., Sakamoto K., Suzuki A., Nakahara Y., Hashimoto N., Hasegawa Y., Sawada M.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  14. Pirfenidone Delays the Prescription of Concomitant Drugs in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Japanese Phase III Clinical Trial International conference

    Suzuki A., Sakaguchi H., Ebina M., Azuma A., Ogura T., Taguchi Y., Suga M., Takahashi H., Sugiyama Y., Kudoh S., Nukiwa T., Miyazawa S., Sakamoto K., Kondoh Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  15. Long Non-Coding RNA TINCR Is a Novel Regulator of Human Bronchial Epithelial Cell Differentiation International coauthorship International conference

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020 

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  16. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC International conference

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY  2019.10 

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  17. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury International conference

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2019.9.28 

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  18. Assessment of Circulating Mitochondrial DNA as a Liquid Biomarker in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

    Sakamoto K, Furukawa T, Yamano Y, Teramachi R, Kataoka K, Hashimoto N, Kondoh Y, Hasegawa Y

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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  19. TINCR, a Long Intergenic Noncoding RNA Decreased in IPF, Is a Novel Regulator of Airway Epithelial Cell Differentiation International coauthorship International conference

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Xylourgidis N., DeIuliis G., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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  20. Recurrent Acute Exacerbations of Fibrotic Interstitial Lung Diseases International conference

    Suzuki A., Kondoh Y., Brown K. K., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Ando M., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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  21. Loss of lncRNA FENDRR Induces Senescence in Adult Mouse Lungs International coauthorship International conference

    Xylourgidis N., Sakamoto K., Schupp J. C., Adams T., DeIuliis G., Omote N., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019 

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  22. The hypoxia-inducible factor 1a protein stabilizers inhibit transforming growth factor beta-induced extracellular matrix proteins in epithelial cells and fibroblasts International conference

    Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2018.9.15 

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  23. Possible UIP Pattern with Traction Bronchiectasis on HRCT: Prognostic Impact in IIP International coauthorship International conference

    Fukihara J, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Furukawa T, Johkoh T, Fukuoka J, Sakamoto K, Hashimoto N, Hasegawa Y, Brown K. K

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2018 

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  24. Exogenous induction of unphosphorylated PTEN reduces TGF beta-induced extracellular matrix expressions in lung fibroblasts International conference

    Motohiro Kimura, Naozumi Hashimoto, Masaaki Kusunose, Daisuke Aoyama, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Norihiro Omote, Kazuyoshi Imaizumi, Tsutomu Kawabe, Yoshinori Hasegawa

    WOUND REPAIR AND REGENERATION  2017  WILEY

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    Transforming growth factor beta (TGF beta) plays an important role in regulating aberrant extracellular matrix (ECM) production from alveolar/epithelial cells (AECs) and fibroblasts in pulmonary fibrosis. Although the tumor suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) can negatively control many TGF beta-activated signaling pathways via the phosphatase activity, hyperactivation of the TGF beta-related signaling pathways is often observed in fibrosis. Loss of PTEN expression might cause TGF beta-induced ECM production. In addition, TGF beta was recently shown to induce loss of PTEN enzymatic activity by phosphorylating the PTEN C-terminus. Therefore, we hypothesized that exogenous transfer of unphosphorylated PTEN (PTEN4A) might lead to reduce TGF beta-induced ECM expression in not only epithelial cells but also fibroblasts. Adenovirus-based exogenous PTEN4A induction successfully reduced TGF beta-induced fibronectin expression and retained beta-catenin at the cell membrane in human epithelial cells. Exogenous unphosphorylated PTEN also attenuated TGF beta-induced ECM production and inhibited TGF beta-induced b-catenin translocation in a human fibroblast cell line and in mouse primary isolated lung fibroblasts. Conversely, TGF beta-induced a-smooth muscle actin expression did not seem to be inhibited in these fibroblasts. Our data suggest that exogenous administration of unphosphorylated PTEN might be a promising strategy to restore TGF beta-induced loss of PTEN activity and reduce aberrant TGF beta-induced ECM production from epithelial cells and fibroblasts in lung fibrosis as compared with wild-type PTEN induction.

    Scopus

    PubMed

  25. Performance Of The Saint George's Respiratory Questionnaire (sgrq) In Patients With Connective Tissue Disease-Associated Interstitial Lung Disease (ctd-Ild) International conference

    Suzuki A, Taniguchi H, Kondoh Y, Swigris J. J, Yamano Y, Furukawa T, Numata-Nakamura M, Sakamoto K, Ando M, Hasegawa Y

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017 

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  26. Lung Epithelium Overexpressed Noncoding Rna (leon): A Potential Regulator Of Epithelial Gene Expression In Idiopathic Pulmonary Fibrosis International conference

    Guardela B. Juan, Herazo-Maya J. D, Sakamoto K, Li Q, Deluliis G, Yan X, Prasse A, Kaminski N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017 

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  27. Exogenous Induction Of Unphosphorylated Tumor Suppressor Phosphatase And Tensin Homolog Deleted On Chromosome 10 Modulates Transforming Growth Factor beta-Induced Extracellular Matrix Expression In Lung Fibroblasts International conference

    Omote N., Hashimoto N., Kimura M., Miyazaki S., Ando A., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017 

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KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. Immune-pathological diagnostic artificial intelligence development research for pulmonary fibrosis using fibrotic foci-specific enhanced micro-CT

    Grant number:20K21599  2020.7 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Challenging Research (Exploratory)  Grant-in-Aid for Challenging Research (Exploratory)

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  2. 呼吸器疾患患者に対するリハビリテーション方策(振動刺激療法)の新規開拓

    Grant number:20K10709  2020.4 - 2024.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    井上 貴行

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    Authorship:Coinvestigator(s)  Grant type:Competitive

    従来のリハビリテーション(リハ)の主要な方策は運動療法であるが、呼吸器疾患患者には軽労作でも重度の低酸素症状を来す患者や循環動態の不安定な患者など積極的な運動療法が行えない症例が数多く存在するため、運動療法の代替手段の開発が必要となっている。一方、振動刺激(VS)には筋萎縮の抑制や筋力の増大などの効果があることが報告されており、運動療法の代替手段となり得ることが実証されつつある。そこで本研究は、呼吸器疾患患者に対してVSを用いたリハを行うことで、筋萎縮や筋力、体力、日常生活動作、生活の質の低下を予防および抑制、さらには改善する効果が得られるかを網羅的に無作為化比較対照試験により検証する。

  3. 老化関連長鎖ノンコーディングRNAの制御による肺線維症難治性の克服

    Grant number:18K15948  2018.4 - 2021.3

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    阪本 考司

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    加齢関連難治肺疾患である肺線維症において、線維化誘導性の細胞老化に陥った線維芽細胞が難治性の病態形成に寄与するとの仮説から、新規の細胞運命決定である長鎖ノンコーディングRNA(lncRNA)に注目し、同病態の線維芽細胞の細胞老化を制御するlncRNA群を同定することで疾患の新たな治療介入標的や疾患のバイオマーカーにすることを目指している。R1年度は以下の研究を進めた。
    老化線維芽細胞関連lncRNAの同定:昨年度に同定したIPF関連lncRNAの一つであるXは細胞老化やTGFβ刺激により発現調節を受けていることが分かった。このため、老化線維芽細胞にウイルスベクターを用いてRNA遺伝子の形質導入、またsiRNAを用いて発現抑制をすることにより線維芽細胞の細胞老化と炎症性サイトカインの発現を制御できるかを検討した。
    また、組織微小環境がlncRNAの制御にかかわるため、肺線維症の形成に関与する微小環境因子、とくに組織低酸素に着目し線維芽細胞の細胞老化への影響を検討した。組織低酸素は老化線維芽細胞の表現型をリプログラミングすることが認められたため、R1年度は、その分子機序を同定すべく、低酸素の下流シグナル分子の阻害薬とアゴニストを使用して検討した。HIFの薬物的誘導により通常酸素下でも老化細胞のリプログラミングを観察することができた。
    ブレオマイシン肺線維症モデルにおける老化細胞可視化はARF-DTRマウスに対してブレオマイシンによる肺線維症の誘導を行ったところ、線維化の形成と老化細胞リポーターシグナルの増強を認めたが、DTRを利用した老化細胞の除去では肺線維化の改善は見られなかった。同様の事象は、別のモデルマウスを利用した検討でも米国の共同研究者たちも認めており、仮説の変更が必要と考えた。
    また細胞老化により病態形成を媒介するミトコンドリアDNAの肺線維症へ寄与を解析した。
    上述の様に当初の仮説、老化細胞の除去により肺線維症の形成を抑止することを証明するためのマウスモデルにおいて、DTを用いたp19陽性細胞の除去の治療効果が見られなかった。このため、作業仮説の修正が必要となった。細胞老化が炎症を誘導する機序に注目して新たなマウスモデルで検討する方策である。
    バイオマーカーの検索のために収集中の臨床検体は、今後のコロナウイルスの蔓延による受診抑制などで遅れる見込みがある。
    老化関連lncRNAの細胞老化制御と肺線維症治療効果の検討は、今後マウスモデルでinvivoで検討を進めていく予定である。
    細胞老化のリプログラムを促す細胞低酸素以下の分子機序の同定を進め、新たな創薬標的を探索する。
    新たな細胞老化のメディエーターであるミトコンドリアDNAの治療やバイオマーカーとしての可能性を検討する検討を本研究で予定したマウスモデルを利用して推進したい。

 

Teaching Experience (On-campus) 5

  1. 生涯健康と医学「大気環境と呼吸器疾患」

    2020

  2. 臓器別臨床講義 呼吸器

    2020

  3. 臓器別臨床講義 呼吸器

    2019

  4. 臓器別臨床講義 呼吸器

    2018

  5. 臓器別臨床講義 呼吸器

    2017

 

Social Contribution 1

  1. 特発性間質性肺炎~最新の治療と日常生活の注意点について~

    Role(s):Lecturer

    名古屋市瑞穗保健センター  難病講演会  2018.7