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Development of a competitive enzyme-linked immunosorbent assay for therapeutic drug monitoring of afatinib

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Journal of Pharmaceutical Analysis 2019年第1期9卷 49-54页

作者： Rintaro Sogawa Tetsuya Saita Yuta Yamamoto Sakiko Kimura Yutaka Narisawa shinya Kimura Masashi Shin Department of Pharmacy Saga University Hospital Applied Life Science Department Faculty of Biotechnology and Life Science Sojo University Division of Hematology Respiratory Medicine and Oncology Department of Internal Medicine Faculty of Medicine Saga University

Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.

关键词： Afatinib Enzyme-linked immunosorbent assay Therapeutic drug monitoring Tyrosine-kinase inhibitor

Surgical removal of a large mobile left ventricular thrombus via left atriotomy

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World Journal of Clinical Cases 2014年第2期2卷 32-35页

作者： Daizo Tanaka shinya Unai James T Diehl Hitoshi Hirose Division of Cardiothoracic Surgery Department of Surgery Thomas Jefferson University

Left ventricular(LV) thrombus is a life-threatening complication of severe LV dysfunction. Ventriculotomy has been a commonly performed procedure for LV thrombus; however, it often further decrease LV function after surgery. We present an alternative approach to thrombectomy in order to minimize the postoperative LV dysfunction. A 37-year-old female with a postpartum cardiomyopathy found to have poor LV function and a large left ventricular apical thrombus(3 cm × 3 cm) attached to the apex by a narrow stalk. Given her severe LV dysfunction, the LV thrombus was approached via left atriotomy under cardiopulmonary bypass. The LV thrombus was easily extracted with gentle traction via the mitral valve. Postoperatively, the patient was discharged home without any embolization event or inotropic support. LV thrombectomy via left atriotomy through the mitral valve could be an alternative option for the patients with poor LV function with a mobile LV thrombus.

关键词： Left ventricular thrombus Atriotomy Cardiomyopathy Surgical thrombectomy Pedunculated thrombus

Facile Fabrication of AII-SWNT Field-Effect Transistors

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Nano Research 2011年第6期4卷 580-588页

作者： shinya Aikawa Rong Xiang Erik Einarsson Shohei Chiashi Junichiro Shiomi Eiichi Nishikawa Shigeo Maruyama Department of Mechanical Engineering The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo 113-8656 Japan Department of Electrical Engineering Tokyo University of Science 1-3 Kagurazaka Shinjuku-ku Tokyo 162-8601 Japan Global Center of Excellence for Mechanical Systems Innovation The University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo l 13-8656 Japan

Field-effect transistors （FETs） have been fabricated using as-grown single-walled carbon nanotubes （SWNTs） for the channel as well as both source and drain electrodes. The underlying Si substrate was employed as the back-gate electrode. Fabrication consisted of patterned catalyst deposition by surface modification followed by dip-coating and synthesis of SWNTs by alcohol chemical vapor deposition （CVD）. The electrodes and channel were grown simultaneously in one CVD process. The resulting FETs exhibited excellent performance, with an I ON/I OFF ratio of 10^6 and a maximum ON-state current （/ON） exceeding 13 uA. The large I ON is attributed to SWNT bundles connecting the SWNT channel with the SWNT electrodes. Bundling creates a large contact area, which results in a small contact resistance despite the presence of Schottky barriers at metallic-semiconducting interfaces. The approach described here demonstrates a significant step toward the realization of metal-free electronics.

关键词： Single-walled carbon nanotube field-effect transistor patterned synthesis self-assembled monolayer Schottky barrier interfacial dipole

New acoustic system for continuous measurement of river discharge and water temperature

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Water Science and Engineering 2010年第1期3卷 47-55页

作者： Kiyosi KAWANISI Arata KANEKO shinya NIGO Mohammad SOLTANIASL Mahmoud F. MAGHREBI Graduate School of Engineering Hiroshima University Ministry of Land InfrastructureTransport and Tourism(Kitaku) Civil Engineering Department Ferdowsi University of Mashhad

In many cases, river discharge is indirectly estimated from water level or streamflow velocity near the water surface. However, these methods have limited applicability. In this study, an innovative system, the fluvial acoustic tomography system （FATS）, was used for continuous discharge measurement. Transducers with a central frequency of 30 kHz were installed diagonally across the river. The system＇s significant functions include accurate measurement of the travel time of the transmission signal using a GPS clock and the attainment of a high signal-to-noise ratio as a result of modulation of the signal by the 10th order M-sequence. In addition, FATS is small and lightweight, and its power consumption is low. Operating in unsteady streamflow, FATS successfully measured the cross-sectional average velocity. The agreement between FATS and acoustic Doppler current profilers （ADCPs） on water discharge was satisfactory. Moreover, the temporal variation of the cross-sectional average temperature deduced from the sound speed of FATS was similar to that measured by a temperature sensor near the bank.

关键词： streamflow fluvial acoustic tomography cross-sectional average velocity unsteadyflow water temperature

Recent traction methods for endoscopic submucosal dissection

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World Journal of Gastroenterology 2016年第26期22卷 5917-5926页

作者： Kunihiro Tsuji Naohiro Yoshida Hiroyoshi Nakanishi Kenichi Takemura shinya Yamada Hisashi Doyama Department of Gastroenterology Ishikawa Prefectural Central Hospital

Endoscopic mucosal resection(EMR) is problematic with regard to en bloc and curable resection *** in endoscopic techniques have enabled novel endoscopic approaches such as endoscopic submucosal dissection(ESD), which has overcome some EMR problems, and has become the standard treatment for gastrointestinal tumors. However, ESD is technically difficult. Procedure time is longer and complications such as intraoperative perforation and bleeding occur more frequently than in EMR. Recently various traction methods have been introduced to facilitate ESD procedures, such as clip with line, external forceps, clip and snare, internal traction, double scope, and magnetic anchor. Each method must be used appropriately according to the anatomical characteristics. In this review we discuss recently proposed traction methods for ESD based on the characteristics of various anatomical sites.

关键词： Endoscopic submucosal dissection Traction Pharyngeal cancer Esophageal cancer Gastric cancer Colorectal cancer

Radiofrequency ablation in a porcine liver model:Effects of transcatheter arterial embolization with iodized oil on ablation time,maximum output,and coagulation diameter as well as angiographic characteristics

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World Journal of Gastroenterology 2007年第20期13卷 2841-2845页

作者： Motoki Nakai Morio Sato shinya Sahara Nobuyuki Kawai Hirohiko Tanihata Masashi Kimura Masaki Terada Department of Radiology Hidaka General Hospi-tal116-2 SonoGobo ShiWakayama 644-8655Japan Department of Radiol-ogy Wakayama Medical University 811-1KimiideraWakayama ShiWakayama 641-8510Japan

AIM:To evaluate the effects of combined radiofrequen-cy ablation and transcatheter arterial embolization with iodized oil on ablation time,maximum output,coagula-tion diameter,and portal angiography in a porcine liver model. METHODS: Radiofrequency ablation (RFA) was applied to in vivo livers of 10 normal pigs using a 17-gauge 3.0 cm expandable LeVeen RF needle electrode with or with-out transcatheter arterial embolization (TAE) with iodized oil (n = 5). In each animal,2 areas in the liver were ab-lated. Direct portography was performed before and af-ter RFA. Ablation was initiated at an output of 30 W,and continued with an increase of 10 W per minute until roll-off occurred. Ablation time and maximum output until roll-off,and coagulated tissue diameter were compared between the 2 groups. Angiographic changes on portog-raphy before and after ablation were also reviewed. RESULTS: For groups with and without TAE with iodized oil,the ablation times until roll-off were 320.6 ± 30.9 seconds and 445.1 ± 35.9 seconds,respectively,maxi-mum outputs were 69.0 ± 7.38 W and 87.0 ± 4.83 W and maximal diameters of coagulation were 41.7 ± 3.85 mm and 33.2 ± 2.28 mm. Significant reductions of abla-tion time and maximum output,and significantly larger coagulation diameter were obtained with RFA following TAE with iodized oil compared to RFA alone. Portography after RFA following TAE with iodized oil revealed more occlusion of the larger portal branches than with RFA alone. CONCLUSION: RFA following TAE with iodized oil can increase the volume of coagulation necrosis with lower output and shorter ablation time than RFA alone in nor-mal pig liver tissue.

关键词： Liver Radiofrequency ablation Transcatheter arterial embolization Iodized oil Angiography Hepatocellular carcinoma

Laparoscopic hemicolectomy in a patient with situs inversustotalis

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World Journal of Gastroenterology 2007年第37期13卷 5035-5037页

作者： Yushi Fujiwara Yosuke Fukunaga Masayuki Higashino shinya Tanimura Masashi Takemura Yoshinori Tanaka Harushi Osugi Department of Gastroenterological Surgery Osaka City General Hospital 2-13-22 Miyakojima-Hondoori Miyakojima-ku Osaka 534-0021 Japan Department of Gastroenterological Surgery Osaka City University Graduate School of Medicine 1-4-3 Asahi-machi Abeno-ku Osaka 545-8585 Japan

As among persons with normal anatomy, occasional patients with situs inversus develop malignant tumors. Recently, several laparoscopic operations have been reported in patients with situs inversus. We describe laparoscopic hemicolectomy with radical lymphadenectomy in such a patient. Careful consideration of the mirror-image anatomy permitted safe operation using techniques not otherwise differing from those in ordinary cases. Thus, curative laparoscopic surgery for colon cancer in the presence of situs inversus is feasible and safe.

关键词： Situs inversus Colon cancer Laparoscopicsurgery Hemicolectomy Radical lymphadenectomy

Quantitative index calculated by ^(99m)Tc-GSA scintigraphy

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Chinese Journal of Cancer Research 2014年第6期26卷 641-643页

作者： Morikatsu Yoshida shinya Shiraishi Noriko Tsuda Fumi Sakamoto Seiji Tomiguchi Yasuyuki Yamashita Department of Diagnostic Radiology Graduate School of Life Sciences Kumamoto University Department of Diagnostic Medical Imaging School of Health Faculty of Life Sciences Kumamoto University

99mTc-galactosyl human serum albumin（GSA） scintigraphy is useful to evaluate hepatic function and hepatic functional reserve. A reliable SPECT and CT integrated system is now commercially available. Using this system, we can obtain 99mTc-GSA SPECT/CT fused imaging with a small registration error. Therefore, the 99mTc-GSA scintigraphy techniques prove more useful in clinical practice than have been previously reported. In the latest Annals of Surgical Oncology on Oct 2014, the uptake index（UI） values calculated from 99mTc-GSA scintigraphy are reported to be useful for predicting the functional reserve of the future remnant liver. In this paper, we describe the usefulness of 99mTc-GSA scintigraphy as well as some cautions that are necessary as regards using the system.

关键词： 99mTc-GSA scintigraphy SPECT/CT uptake index(UI)

Visible Light-Induced Photocatalysis on Carbon Nitride Deposited Titanium Dioxide： Hydrogen Production from Sacrificial Aqueous Solutions

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Chinese Journal of Chemistry 2017年第2期35卷 165-172页

作者： shinya Higashimoto Kohji Hikita Masashi Azuma Mari Yamamoto Masanari Takahashi Yoshihisa sakata Masaya Matsuoka Hisayoshi Kobayashi Department of Applied Chemistry College of Engineering Osaka Institute of Technology 5-16-10miya Asahi-ku Osaka 535-8585 Japan Osaka Municipal Technical Research Institute 1-6-50 Morinomiya Joto-ku Osaka 536-8553 Japan Graduate School of Science andEngineering Yamaguchi University 2-16-1 Tokiwadai Ube 755-8611 Japan Department of Applied Chemistry Graduate School of Engineering Osaka Prefecture University 1-1 Gakuen-cho Naka-ku Sakai Osaka 599-8531 Japan Department of Chemistry and Materials Technology Kyoto Institute of Technology Matsugasaki Sakyo-ku Kyoto 606-8585 Japan

Carbon and nitrogen species-involved TiO2 （CN-TiO2） were systematically synthesized by thermal condensa- tion of cyanuric acid on the TiO2 surface. And the photocatalytic reactions for H2 production from sacrificial aque- ous solutions were performed on several CN-TiO2 photocatalyst under visible-light irradiation. The photocatalytic activity of the CN-TiO2 was influenced by total amounts of carbon and nitrogen species, and the preferable activity was ten times higher than that of pristine carbon nitride. Here, the states of the CN-TiO2 photocatalyst were charac- terized by XPS, FT-IR and UV-Vis spectroscopy as well as DFT calculations. The photo-electrochemical measure- ments confirmed that the enhancement of H2 production is associated with effective charge separation under photo- excitation of highly dispersed carbon nitride on the TiO2 surface.

关键词： carbon nitride TiO2 visible light photo-electrochemistry DFT calculation sacrificial H2 production