研究者詳細 - 阪本　考司

The Importance of Appropriate Diagnosis in the Practical Management of Chronic Obstructive Pulmonary Disease 国際誌

Hashimoto Naozumi, Wakahara Keiko, Sakamoto Koji

DIAGNOSTICS 11 巻 ( 4 ) 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Diagnostics

Chronic obstructive pulmonary disease (COPD) is projected to continue to contribute to an increase in the overall worldwide burden of disease until 2030. Therefore, an accurate assessment of the risk of airway obstruction in patients with COPD has become vitally important. Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the American Thoracic Society (ATS) and European Respiratory Society (ERS), and the Japanese Respiratory Society (JRS) provide the criteria by which to diagnose COPD, many studies suggest that it is in fact underdiagnosed. Its prevalence increases, while the impact of COPD-related systemic comorbidities is also increasingly recognized in clinical aspects of COPD. Although a recent report suggests that spirometry should not be used to screen for airflow limitation in individuals without respiratory symptoms, the early detection of COPD in patients with no, or few, symptoms is an opportunity to provide appropriate management based on COPD guidelines. Clinical advances have been made in pharmacotherapeutic approaches to COPD. This article provides a current understanding of the importance of an appropriate diagnosis in the real-world management of COPD.

DOI： 10.3390/diagnostics11040618

Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state 査読有り国際共著国際誌

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 9 巻 ( 3 ) 頁： e14727 2021年2月

Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation 査読有り国際誌

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

RESPIROLOGY 25 巻 ( 11 ) 頁： 1152 - 1159 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Respirology

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

Clinical burden of immune checkpoint inhibitor-induced pneumonitis 査読有り国際誌

Sakamoto Koji, Fukihara Jun, Morise Masahiro, Hashimoto Naozumi

RESPIRATORY INVESTIGATION 58 巻 ( 5 ) 頁： 305 - 319 2020年9月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Respiratory Investigation

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

肺線維症新規治療に関する基礎研究肺線維症の病態形成におけるメフリンの役割

中原義夫, 橋本直純, 阪本考司, 榎本篤

日本呼吸器学会誌 9 巻 ( 増刊 ) 頁： 139 - 139 2020年8月

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年7月

High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial Pneumonia: A retrospective observational study 査読有り国際誌

Omote N.

Nagoya Journal of Medical Science 82 巻 ( 2 ) 頁： 301 - 313 2020年5月

Reply to "Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With NoneSmall-Cell Lung Cancer Who Received Programmed Death-1 Inhibitors" 査読有り国際誌

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

CLINICAL LUNG CANCER 21 巻 ( 3 ) 頁： E205 - E205 2020年5月

Acute exacerbations of fibrotic interstitial lung diseases 査読有り国際誌

Suzuki Atsushi, Kondoh Yasuhiro, Brown Kevin K., Johkoh Takeshi, Kataoka Kensuke, Fukuoka Junya, Kimura Tomoki, Matsuda Toshiaki, Yokoyama Toshiki, Fukihara Jun, Ando Masahiko, Tanaka Tomonori, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

RESPIROLOGY 25 巻 ( 5 ) 頁： 525 - 534 2020年5月

Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer 査読有り国際誌

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

NAGOYA JOURNAL OF MEDICAL SCIENCE 81 巻 ( 3 ) 頁： 427 - 438 2019年8月

Repressive role of stabilized hypoxia inducible factor 1 alpha expression on transforming growth factor beta-induced extracellular matrix production in lung cancer cells 査読有り国際誌

Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Omote Norihito, Miyazaki Shinichi, Nakahara Yoshio, Imaizumi Kazuyoshi, Kawabe Tsutomu, Hasegawa Yoshinori

CANCER SCIENCE 110 巻 ( 6 ) 頁： 1959 - 1973 2019年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Science

Activation of transforming growth factor β (TGF-β) combined with persistent hypoxia often affects the tumor microenvironment. Disruption of cadherin/catenin complexes induced by these stimulations yields aberrant extracellular matrix (ECM) production, characteristics of epithelial-mesenchymal transition (EMT). Hypoxia-inducible factors (HIF), the hallmark of the response to hypoxia, play differential roles during development of diseases. Recent studies show that localization of cadherin/catenin complexes at the cell membrane might be tightly regulated by protein phosphatase activity. We aimed to investigate the role of stabilized HIF-1α expression by protein phosphatase activity on dissociation of the E-cadherin/β-catenin complex and aberrant ECM expression in lung cancer cells under stimulation by TGF-β. By using lung cancer cells treated with HIF-1α stabilizers or carrying doxycycline-dependent HIF-1α deletion or point mutants, we investigated the role of stabilized HIF-1α expression on TGF-β-induced EMT in lung cancer cells. Furthermore, the underlying mechanisms were determined by inhibition of protein phosphatase activity. Persistent stimulation by TGF-β and hypoxia induced EMT phenotypes in H358 cells in which stabilized HIF-1α expression was inhibited. Stabilized HIF-1α protein expression inhibited the TGF-β-stimulated appearance of EMT phenotypes across cell types and species, independent of de novo vascular endothelial growth factor A (VEGFA) expression. Inhibition of protein phosphatase 2A activity abrogated the HIF-1α-induced repression of the TGF-β-stimulated appearance of EMT phenotypes. This is the first study to show a direct role of stabilized HIF-1α expression on inhibition of TGF-β-induced EMT phenotypes in lung cancer cells, in part, through protein phosphatase activity.

DOI： 10.1111/cas.14027