研究者詳細 - 川部　勤

Exogenous induction of unphosphorylated PTEN reduces TGF β-induced extracellular matrix expressions in lung fibroblasts 査読有り

Modulation of immunological activity on macrophages induced by diazinon 査読有り

OGASAWARA Nanako, MATSUSHIMA Miyoko, KAWAMURA Nami, ATSUMI Kazuko, YAMAGUCHI Takehiro, OCHI Haruka, KUSATSUGU Yuto, OYABU Sayaka, HASHIMOTO Naozumi, HASEGAWA Yoshinori, UEYAMA Jun, KAWABE Tsutomu

Toxicology 379 巻頁： 22-30 2017年

Respiration and heartbeat signal detection from airflow at airway in rat by catheter flow sensor with tmeparature compensation function 査読有り

HASEGAWA Yoshihiro, KAWAOKA Hidenori, YAMADA Takayuki, MATSUSHIMA Miyoko, KAWABE Tsutomu, SHIKIDA Mitsuhiro

Journal of Micromechanics and Microengineering 27 巻 2017年

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 25 巻 ( 1 ) 頁： 86 - 97 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

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.

DOI： 10.1111/wrr.12506

MEMS技術の医用応用査読有り

式田光宏, 長谷川義大, 川部勤, 松島充代子

表面技術 68 巻 ( 7 ) 頁： 367 - 372 2017年

Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers 査読有り

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

CANCER CELL INTERNATIONAL 16 巻 ( 1 ) 頁： 33 2016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：BIOMED CENTRAL LTD

Background: Persistent hypoxia stimulation, one of the most critical microenvironmental factors, accelerates the acquisition of epithelial-mesenchymal transition (EMT) phenotypes in lung cancer cells. Loss of phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression might accelerate the development of lung cancer in vivo. Recent studies suggest that tumor microenvironmental factors might modulate the PTEN activity though a decrease in total PTEN expression and an increase in phosphorylation of the PTEN C-terminus (p-PTEN), resulting in the acquisition of the EMT phenotypes. Nevertheless, it is not known whether persistent hypoxia can modulate PTEN phosphatase activity or whether hypoxia-induced EMT phenotypes are negatively regulated by the PTEN phosphatase activity. We aimed to investigate hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers.
Methods: Western blotting was performed in five lung cancer cell lines to evaluate total PTEN expression levels and the PTEN activation. In a xenograft model of lung cancer cells with endogenous PTEN expression, the PTEN expression was evaluated by immunohistochemistry. To examine the effect of hypoxia on phenotypic alterations in lung cancer cells in vitro, the cells were cultured under hypoxia. The effect of unphosphorylated PTEN (PTEN4A) induction on hypoxia-induced EMT phenotypes was evaluated, by using a Dox-dependent gene expression system.
Results: Lung cancer cells involving the EMT phenotypes showed a decrease in total PTEN expression and an increase in p-PTEN. In a xenograft model, loss of PTEN expression was observed in the tumor lesions showing tissue hypoxia. Persistent hypoxia yielded an approximately eight-fold increase in the p-PTEN/PTEN ratio in vitro. PTEN4A did not affect stabilization of hypoxia-inducible factor 1 alpha. PTEN4A blunted hypoxia-induced EMT via inhibition of beta-catenin translocation into the cytoplasm and nucleus.
Conclusion: Our study strengthens the therapeutic possibility that compensatory induction of unphosphorylated PTEN may inhibit the acquisition of EMT phenotypes in lung cancer cells under persistent hypoxia.

DOI： 10.1186/s12935-016-0308-3

Predictors of surgery-induced muscle proteolysis in patients undergoing cardiac surgery 査読有り

IIDA Yuki, YAMAZAKI Takenori, ARIMA Hajime, KAWABE Tsutomu, YAMADA Sumio

J Cardiol. 68 巻頁： 536 2016年

Direct regulation of TGF β-induced EMT by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells. 査読有り

KUSUNOSE Masaaki, HASHIMOTO Naozumi, KIMURA Motohiro, OGATA Ryo, AOYAMA Daisuke, SAKAMOTO Koji, MIYAZAKI Shinichi, ANDO Akira, OMOTE Norihiro, IMAIZUMI Kazuyoshi, KAWABE Tsutomu, HASEGAWA Yoshinori

Cancer Sci. 106 巻 ( 12 ) 頁： 1693 - 1704 2015年12月

Ppm level methane detection using micro-thermoelectric gas sensors with Pd/Al2O3 combustion catalyst films 査読有り

Nagai Daisuke, Nishibori Maiko, Itoh Toshio, Kawabe Tsutomu, Sato Kazuo, Shin Woosuck

SENSORS AND ACTUATORS B-CHEMICAL 206 巻頁： 488 - 494 2015年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Sensors and Actuators, B: Chemical

The CH4 combustion performance of a micro-thermoelectric gas sensor (TGS) with Pd-Al2O3 catalysts prepared using two different methods, impregnation and colloid mixing, has been investigated. Three crystal phases of Al2O3, α, θ, and γ, were used for the catalyst support; the Pd/θ-Al2O3 catalyst showed the best combustion performance. The Pd/θ-Al2O3 catalyst exhibited the best dispersion of Pd nanoparticles as analyzed by both a pulse adsorption technique and transmission electron microscopy. The effect of the catalyst thickness on the H2 and CH4 detection performance of the TGS using this Pd/θ-Al2O3 catalyst prepared using a colloid mixing method was investigated. It was found that the response voltage, ΔV, of the TGS to CH4 increased with increasing film thickness, but the ΔV to H2 decreased. The TGS with the Pd/θ-Al2O3 catalyst whose thickness was 35 μm could detect as low as 1 ppm of CH4 in air by the thermoelectric conversion of the combustor heat to an electrical voltage.

DOI： 10.1016/j.snb.2014.09.059

Design and development of a suitable adsorbent to capture theophylline for non-invasive therapeutic drug monitoring with exhaled breath 査読有り

A. Yamamoto, S. Hioki, C. Tanada, T. Miwa, Y. Inoue, R. Yamamoto, M. Matsushima, T. Kawabe

ANALYTICAL METHODS 7 巻 ( 2 ) 頁： 423 - 427 2015年

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

The possibility of using exhaled breath as a substitute for blood/plasma in areas of therapeutic drug monitoring was investigated. Theophylline was used as a model chemical of non-volatile drugs and the adsorbents suitable for drug capture from exhaled breath were studied. Two macro-porous adsorbents with different monomer compositions were prepared by suspension copolymerization. The capture properties of the synthesized adsorbents and two conventional gas adsorbents packed in a cartridge were evaluated by both aerosol generation and rat expiration. The efficiency of drug capture did not improve by decreasing the pore size and by increasing the specific surface area. A hydrophilic region was found to be necessary for holding the aerosol particles on the adsorbent surface, but a hydrophobic region is also necessary for the adsorption of theophylline. The materials were applied to the intravenous bolus experiment of rats. The amount of theophylline collected from exhaled breath was in the range of 0-0.02 ng min(-1), and it varied similarly to the concentration in blood, which was in the range of 0-37 mu g mL(-1).

DOI： 10.1039/c4ay02243b

The suppressive effect of quercetin on Toll-like receptor 7-mediated activation in alveolar macrophages. 査読有り

YASUI Masahiro, MATSUSHIMA Miyoko, OMURA Aya, MORI Kanae, OGASAWARA Nanako, KODERA Yuka, SHIGA Marika, ITO Komei, KOJIMA Seiji, KAWABE Tsutomu

Pharmacology 96 巻 ( 5-6 ) 頁： 201-209 2015年

Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury. 査読有り

TAKASHIMA Koji, MATSUSHIMA Miyoko, HASHIMOTO Katsunori, NOSE Haruka, SATO Mitsuo, HASHIMOTO Naozumi, HASEGAWA Yoshinori, KAWABE Tsutomu.

Respir Res. 15 巻 ( 1 ) 頁： 150 2014年11月

Catheter flow sensor with temperature compensation for tracheal intubation tube system 査読有り

Mitsuhiro Shikida, Kazuhiro Yoshikawa, Takuya Matsuyama, Yudai Yamazaki, Miyoko Matsushima, Tsutomu Kawabe

SENSORS AND ACTUATORS A-PHYSICAL 215 巻頁： 155 - 160 2014年8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：ELSEVIER SCIENCE SA

A micro-electro-mechanical systems catheter flow sensor was integrated into the tracheal intubation tube system to prevent the insertion of the tube into the esophagus. A temperature sensing mechanism was integrated into the catheter flow sensor to compensate for the temperature change in air during flow-rate measurement, and the sensor was placed on the inside the slip joint by using an adapter produced using a molding process. The relationship between the sensor output and flow rate was evaluated, and closely matched sensor outputs for both the forward and backward flows were obtained. The tracheal tube in the modified system was inserted into the air passage of a rabbit, and the air flow passing through the tube was directly measured using the integrated catheter flow sensor in real time. By adding the temperature compensation mechanism, the volumes of the expired- and inspired-air almost matched. We believe that a doctor will easily be able to evaluate whether the tube is inserted into the bronchi or the esophagus when using the modified system. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.sna.2013.08.004

呼吸器内科医を対象とした喘息治療ステップダウンの実態調査

2. 武田直也、伊藤　理、指尾豊和、平松哲夫、木村智樹、大林浩幸、馬場研二、若原恵子、若山尚士、今泉和良、川部　勤、長谷川好規

アレルギー・免疫 21 巻 ( 4 ) 頁： 106-114 2014年3月

Postoperative muscle proteolysis affects systemic muscle weakness in patients undergoing cardiac surgery 査読有り

Iida Y, Yamazaki T, Kawabe T, Usui A, Yamada S

Int J Cardiol 172 巻 ( 3 ) 頁： 595-597 2014年1月

呼気吸気計測を目的とした自己温度補償型カテーテル流量センサの開発査読有り

松山拓矢, 山﨑雄大, 松島充代子, 川部勤, 式田光宏

電気学会論文誌E（センサ・マイクロマシン部門誌） 134 巻 ( 6 ) 頁： 126-131 - 131 2014年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：IEEJ Transactions on Sensors and Micromachines

We introduced groove structures in between the flow- and temperature-sensors to avoid the heat flow to the temperature sensor from the heater used as the flow sensing. The grooves were produced by oxygen plasma etching, and thermal isolation effect by those was confirmed by an infrared thermography. The relationships between the flow rate and the flow sensor output with and without temperature compensation were evaluated. We finally confirmed that the variations of the flow sensor output by the change of the fluid temperature were successfully compensated by the temperature sensor.

DOI： 10.1541/ieejsmas.134.126