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Affiliation |
Faculty of Pharmaceutical Sciences Department of Pharmaceutical Sciences |
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Title |
Assistant Professor |
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Laboratory Address |
Josai University, bldg 21, room 423, Keyakidai 1-1, Sakado, Saitama, 350-0295, Japan |
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Laboratory Phone number |
+81-49-271-8107 |
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Laboratory Fax number |
049-271-8107 |
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Contact information |
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External Link |
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Seki Tomohiro
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Research Areas 【 display / non-display 】
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Life Science / Pharmaceutical analytical chemistry and physicochemistry
From School 【 display / non-display 】
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Josai University Faculty of Pharmaceutical Science Graduated
2006.04 - 2012.03
Country：Japan
From Graduate School 【 display / non-display 】
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Josai University Graduate School, Division of Pharmaceutical Sciences Doctor's Course Completed
2012.04 - 2016.03
Country：Japan
Employment Record in Research 【 display / non-display 】
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Josai University Faculty of Pharmaceutical Sciences Department of Pharmaceutical Sciences Assistant Professor
2019.04
External Career 【 display / non-display 】
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National Institutes of Health Ntional Cancer Institute, Center for Cancer Research, Radiation Biology Branch Researcher
2016.07 - 2018.01
Country：United States
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National Institutes of Health Ntional Cancer Institute, Center for Cancer Research, Radiation Biology Branch
2018.02 - 2019.03
Country：United States
Professional Memberships 【 display / non-display 】
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日本薬剤学会
2012.03
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日本薬学会
2011.03
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日本DDS学会
2011.03
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日本シクロデキストリン学会
2011.03 - 2016.03
Research Career 【 display / non-display 】
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高分子ナノシートを用いたin vitro薬物膜透過評価への適用と経皮薬物送達システムへの応用
(not selected)
Project Year： 2019.04 -
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CD44陽性がん標的指向性を有するプロドラッグ型グルタチオン応答薬物放出システム
Grant-in-Aid for Scientific Research
Project Year： 2019.04 -
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インスリン製剤のアミロイド化に関する基礎的研究
(not selected)
Project Year： 2019.04 -
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動的核偏極MRIを用いた非侵襲的in vivo腫瘍代謝イメージング
(not selected)
Project Year： 2016.07 -
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糖応答性インスリン放出システムに関する
(not selected)
Project Year： 2010.04 -
Papers 【 display / non-display 】
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Study on a Novel Transdermal Therapeutic System that Combines the Achievement of Supersaturation by pH-shift Method and User–Activated System Reviewed
Takahiro Suzuki, Tomohiro Seki, Toshinobu Seki
Journal of Pharmaceutical Innovation 2023
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Study of Polymer Nanofilms Using for High-Throughput Screening in the Development of Transdermal Therapeutic System Reviewed
70 ( 12 ) 868 - 875 2022.12
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PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study Reviewed
Tomohiro Sek, Yu Saida, Shun Kishimoto, Jisook Lee, Yasunori Otowa, Kazutoshi Yamamoto, Gadisetti VR Chandramouli, Nallathamby Devasahayam, James B. Mitchell, Murali C. Krishna, Jeffery R. Brende
Neoplasia 30 100793 2022.05
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier
Purpose
PEGylated human hyaluronidase (PEGPH20) enzymatically depletes hyaluronan, an important component of the extracellular matrix, increasing the delivery of therapeutic molecules. Combinations of chemotherapy and PEGPH20, however, have been unsuccessful in Phase III clinical trials. We hypothesize that by increasing tumor oxygenation by improving vascular patency and perfusion, PEGPH20 will also act as a radiosensitization agent.
Experimental Design
The effect of PEGPH20 on radiation treatment was analyzed with respect to tumor growth, survival time, p02, local blood volume, and the perfusion/permeability of blood vessels in a human pancreatic adenocarcinoma BxPC3 mouse model overexpressing hyaluronan synthase 3 (HAS3).
Results
Mice overexpressing HAS3 developed fast growing, radiation resistant tumors that became rapidly more hypoxic as time progressed. Treatment with PEGPH20 increased survival times when used in combination with radiation therapy, significantly more than either radiation therapy or PEGPH20 alone. In mice that overexpressed HAS3, EPR imaging showed an increase in local pO2 that could be linked to increases in perfusion/permeability and local blood volume immediately after PEGPH20 treatment. Hyperpolarized [1-13C] pyruvate suggested PEGPH20 caused a metabolic shift towards decreased glycolytic flux. These effects were confined to the mice overexpressing HAS3 - no effect of PEGPH20 on survival, radiation treatment, or pO2 was seen in wild type BxPC3 tumors.
Conclusions
PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation. The response of the treatment may potentially be monitored by non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment. -
Structure-guided design enables development of a hyperpolarized molecular probe for the detection of aminopeptidase N activity in vivo Reviewed
Yutaro Saito, Hiroyuki Yatabe, Iori Tamura, Yohei Kondo, Ryo Ishida, Tomohiro Seki, Keita Hiraga, Akihiro Eguchi, Yoichi Takakusagi, Keisuke Saito, Nobu Oshima, Hiroshi Ishikita, Kazutoshi Yamamoto, Murali C. Krishna, Shinsuke Sando
Science Advances 8 ( 13 ) 2022.03
Language：English Publishing type：Research paper (scientific journal)
Dynamic nuclear polarization (DNP) is a cutting-edge technique that markedly enhances the detection sensitivity of molecules using nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This methodology enables real-time imaging of dynamic metabolic status in vivo using MRI. To expand the targetable metabolic reactions, there is a demand for developing exogenous, i.e., artificially designed, DNP-NMR molecular probes; however, complying with the requirements of practical DNP-NMR molecular probes is challenging because of the lack of established design guidelines. Here, we report Ala-[1-13C]Gly-d2-NMe2 as a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity. We developed this probe rationally through precise structural investigation, calculation, biochemical assessment, and advanced molecular design to achieve rapid and detectable responses to enzyme activity in vivo. With the fabricated probe, we successfully detected enzymatic activity in vivo. This report presents a comprehensive approach for the development of artificially derived, practical DNP-NMR molecular probes through structure-guided molecular design.
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Structure-based relaxation analysis reveals C-terminal [1-13C]glycine-d2 in peptides has long spin-lattice relaxation time that is applicable to in vivo hyperpolarized magnetic resonance studies International coauthorship
Yohei Kondo, Yutaro Saito, Tomohiro Seki, Yoichi Takakusagi, Jumpei Morimoto, Hiroshi Nonaka, Koichiro Miyanishi, Wataru Mizukami, Makoto Negoro, Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Masayuki Matsuo, Natarajan Raju, Rolf Swenson, Murali C. Krishna, Kazutoshi Yamamoto, and Shinsuke Sando
ChemRxiv (American Chemical Society (ACS) 2022.01
Presentations 【 display / non-display 】
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ヒアルロン酸をナノキャリアとするグルタチオン応答ノシル化ドキソルビシンの活性化評価
幸村 友菜、関 智宏、関 俊暢
第２７回創剤フォーラム若手研究会
Event date： 2022.09
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A newly designed hyperpolarized molecular probe enables the in vivo detection of aminopeptidase N activity from the tumor regions in animals
Hiroyuki Yatabe, Yutaro Saito, Iori Tamura, Yohei Kondo, Ryo Ishida, Tomohiro Seki, Keita Hiraga, Akihiro Eguchi, Yoichi Takakusagi, Keisuke Saito, Nobu Oshima, Hiroshi Ishikita, Kazutoshi Yamamoto, Murali C. Krishna, Shinsuke Sando
WMIC2022
Event date： 2022.09
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ノシル化ドキソルビシンのグルタチオン応答活性化とDNAとの相互作用の評価
関 智宏、幸村 友菜、関 俊暢
第２１回シンポジウム、第２０回夏期セミナー
Event date： 2022.08
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Multimodal molecular imaging assessment of tumor microenvironment. Hyaluronan depletion induces tumor reoxygenation and radiosensitization
Shun C Kishimoto, Tomohiro Seki, Yu Saida, Yasunori Otowa, Kota Yamashita, Kazutoshi Yamamoto, Nallathamby Devasahayam, Jeffrey R Brender, Murali C Krishna
ISMRM 31th meeting & exhibition 2022
Event date： 2022.05
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グルタチオン応答開裂性ノシル化ドキソルビシンの活性化とDNAとの相互作用の評価
幸村 友菜、関 智宏、関 俊暢
日本薬学会第142年会
Event date： 2022.03
Awards 【 display / non-display 】
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JSPS Fellowship for Japanese Biomedical and Behavioral Researchers Fellowship at NIH Award
2018.08 Japan Society for the Promotion of Science (JSPS)
Tomohiro Seki
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
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Excellent Poster Presentation Award GOLD Prize
2014.11 第20回創剤フォーラム若手研究会 (日本薬剤学会)
関 智宏
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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ポスター賞
2014.09 第31回シクロデキストリンシンポジウム (日本シクロデキストリン学会)
関 智宏
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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若手研究奨励賞
2014.07 物理系薬学部会 (フィジカルファーマフォーラム2014)
関 智宏
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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Most Impressive Debater賞
2014.05 日本薬剤学会第29年会
関 智宏
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
Scientific Research Funds Acquisition Results 【 display / non-display 】
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CD44がん標的能とエンドソーム脱出能を持つグルタチオン応答プロドラッグ型DDS
Grant number：23K14660 2023.04 - 2026.03
科学研究費補助金 若手研究
Authorship：Principal investigator
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CD44陽性がん標的指向性を有するプロドラッグ型グルタチオン応答薬物放出システム
Grant number：20K16421 2020.04 - 2023.03
科学研究費補助金 若手研究
Authorship：Principal investigator
Committee Memberships 【 display / non-display 】
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日本薬剤学会 第30回日本薬剤学会学生主催シンポジウムSNPEE2015 委員
2015.05 - 2016.05
Committee type：Academic society
Social Activities 【 display / non-display 】
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叡明高校 模擬授業 「からだの中での薬の運命」
Role(s)： Lecturer
2021.12
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埼玉県立岩槻高校 模擬授業 「からだの中での薬の運命」
Role(s)： Lecturer
埼玉県立岩槻高校 2020.11
Audience： High school students