Tokushima University / Educator and Researcher Directory --- Shinohara, Yusei

Personal Web Page

https://researchmap.jp/Yusei_Shinohara (researchmap)

Field of Study

○	Bioorganic Chemistry, Medicinal Chemistry, Drug Delivery Science

Subject of Study

○

Book / Paper

(See https://researchmap.jp/Yusei_Shinohara (researchmap) for Published Book / Papers / Presentations.)

Academic Paper (Judged Full Paper):

1.	Hiroki Shimada, Yusei Shinohara, Yoshihiro Uto and Hisatsugu Yamada : A Triple-Resonance NMR Strategy for the Selective Detection of NAD+ and NADH Derived from a 13C/15N-Nicotinamide Riboside Probe in the Liver Extracts of Mice, Sensors, 26, 9, 2026. (Summary) Alterations in the ratio of oxidized and reduced nicotinamide adenine dinucleotide (NAD⁺/NADH) reflect the intracellular redox state and have been implicated in a broad spectrum of pathological conditions, including neurogenetic disorders, heart failure, and liver diseases. In the present study, we demonstrate the selective detection of probe-derived NAD⁺ and NADH signals in mouse liver extracts by means of a triple-resonance nuclear magnetic resonance (NMR) spectroscopy technique. We prepared ¹³C/¹⁵N-enriched nicotinamide riboside (¹³C/¹⁵N-NR), which undergoes enzymatic conversion to NAD⁺ and NADH in the liver, and detected these labeled metabolites by ¹H-{¹³C-¹⁵N} triple-resonance NMR measurements. This study provides a methodological proof-of-concept for the selective detection of NAD-related signals derived from a stable-isotope labeled probe in mouse liver extracts. (Keyword) labeled nicotinamide riboside / NAD+/NADH / stable isotope-enriched molecular probe / triple-resonance NMR (Link to Publication Site) ● Publication site (DOI): 10.3390/s26092714 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 42122439 ● Summary page in Scopus @ Elsevier: 2-s2.0-105038433898 (DOI: 10.3390/s26092714, PubMed: 42122439, Elsevier: Scopus)
2.	Yuya Higashi, Momoka Goda, Saya Kobayashi, Yusei Shinohara, Aoi Komatsu, Masahide Tominaga, Hiroshi Harada, Fuyuhiko Tamanoi, Yoshihiro Uto and Kotaro Matsumoto : Iodine-Hoechst Enhances X-ray Sensitivity of Cancer Cells Under Normal and Low Oxygen Conditions, Anticancer Research, 46, 3, 1197-1211, 2026. (Summary) Iodine-Hoechst (IH) is a derivative of Hoechst dye that binds minor grooves of DNA. This chemical has been used for cell labeling studies such as nuclear staining; however, its use in radiation therapy has not been explored fully. We investigated enhancement of X-ray sensitivity of cancer cells by IH. Cell survival was examined over a range of X-ray doses, survival curves were generated, and the enhancement ratio (ER) was calculated. Double-strand DNA breaks were examined by a γH2AX assay. We then investigated whether the radiosensitivity-enhancing effect of IH occurs under low oxygen conditions. Additionally, reactive oxygen species (ROS) production was measured using dichlorodihydrofluorescein diacetate. As a first step to investigate the effect of IH on X-ray inhibition of tumor growth, we employed the chorioallantoic membrane (CAM) assay, a simple, versatile cancer model. IH enhanced X-ray sensitivity of cancer cells, with an ER of 1.29 based on 10% survival values. X-ray-induced DNA double-strand breaks were increased by IH. Upon exposing cells to low oxygen conditions, X-ray sensitivity decreased, consistent with the idea that X-ray sensitivity decreases under low oxygen. Even under this condition, IH enhancement persisted, revealing that the radiosensitivity-enhancing effect was not significantly affected by oxygen. This enhancement does not involve ROS, as X-ray-induced ROS production was unchanged by IH. In the CAM assay, transplantation of cancer cells led to tumor formation within the egg. Intravenous injection of IH resulted in the delivery of IH to the tumor. X-ray irradiation of the tumor inhibited tumor growth, and this was enhanced by IH. Our results reveal that IH enhances radiation sensitivity of cancer cells, and this effect is observed even under low oxygen conditions. (Keyword) CAM model / double-strand DNA breaks / Iodine-Hoechst / low oxygen conditions / radiation sensitivity enhancement (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.18023 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 41760278 ● Summary page in Scopus @ Elsevier: 2-s2.0-105031742343 (DOI: 10.21873/anticanres.18023, PubMed: 41760278, Elsevier: Scopus)
3.	Tsuyoshi Takara, Rei Takara, Aya Kobayashi, Hina Shirakata, Shinobu Ambai, Yusei Shinohara and Yoshihiro Uto : Serum-Derived Macrophage-Activating Factor ExhibitsAnti-Tumor Activity via M2-to-M1 Macrophage Reprogramming, International Journal of Translational Medicine, 4, 439-449, 2024. (Tokushima University Institutional Repository) ● Metadata: 2012829 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijtm4030029 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.3390/ijtm4030029 (Tokushima University Institutional Repository: 2012829, DOI: 10.3390/ijtm4030029)
4.	Yusei Shinohara, Yuki Komiya, Kashin morimoto, Yoshio Endo, Minoru Terashima, Takeshi Suzuki, Takahisa Takino, Itasu Ninomiya, Hisatsugu Yamada and Yoshihiro Uto : Development of UTX-143, a Selective Sodium-hydrogen Exchange Subtype 5 Inhibitor, using Amiloride as a Lead Compound, Bioorganic & Medicinal Chemistry, 99, 117603, 2024. (Summary) NHE5, an isoform of the Na/H exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143, which has NHE5-selective inhibitory activity, using a structure-activity relationship approach. UTX-143 showed selective cytotoxic effects on cancer cells and reduced the migratory and invasive abilities of cancer cells. These results suggest a new concept wherein drugs exhibit cancer-specific cytotoxic effects through selective inhibition of NHE5 and the possibility of UTX-143 as a lead NHE5-selective inhibitor. (Keyword) Amiloride / Sodium / Sodium-Hydrogen Exchangers / Membrane Proteins / Hydrogen / Hydrogen-Ion Concentration (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2024.117603 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38246115 ● Summary page in Scopus @ Elsevier: 2-s2.0-85183558460 (DOI: 10.1016/j.bmc.2024.117603, PubMed: 38246115, Elsevier: Scopus)
5.	Hirari Yamahana, Yusei Shinohara, Yoshio Endo, Tohru Obata, Hisatsugu Yamada and Yoshihiro Uto : Enhancing Effect of Novel Schiff Base Derivatives, UTX-134 and UTX-135, on 5-Aminolevulinic Acid-based Photodynamic Therapy, ALA-Porphyrin Science, 10, 1, 1-14, 2021. (Keyword) 5-aminolevulinic acid / protoporphyrin IX / photodynamic therapy / shiff-base
6.	Yusei Shinohara, Yoshio Endo, Chiaki Abe, Ikkyu Shiba, Masahiro Ishizuka, Tohru Tanaka, Yutaka Yonemura, Syunichiro Ogura, Masahide Tominaga, Hisatsugu Yamada and Yoshihiro Uto : Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy., Photodiagnosis and Photodynamic Therapy, 20, 182-188, 2017. (Summary) 5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various cancers. Recently, we found that treatment of cancer cells with the Schiff base derivative TX-816 along with ALA could significantly increase the efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to 3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX-816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT. Furthermore, DCSA could restore the sensitivity of cancer cells that acquired resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might be a useful compound for designing prodrug-type ALA-PDT enhancers. (Keyword) 5-Aminolevulinic acid / Photodynamic therapy / Protoporphyrin IX / Schiff base (Link to Publication Site) ● Publication site (DOI): 10.1016/j.pdpdt.2017.10.014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29056554 ● Summary page in Scopus @ Elsevier: 2-s2.0-85032287431 (DOI: 10.1016/j.pdpdt.2017.10.014, PubMed: 29056554, Elsevier: Scopus)

Proceeding of Domestic Conference:

1.	Yusei Shinohara, Saya Kobayashi, Hisatsugu Yamada, 東佑弥, 松本光太郎, 玉野井冬彦 and Yoshihiro Uto : 5-Iodo-2'-deoxyuridineのヨウ素由来オージェ効果を介した放射線増感作用, 第26回菅原・大西記念癌治療増感シンポジウム, Feb. 2026. (Keyword) 5-Iodo-2-deoxyuridine / オージェ電子 / 放射線増感剤
2.	Yusei Shinohara, 安部千秋 and Yoshihiro Uto : チロシンキナーゼ阻害剤を導入した新規シッフ塩基による5-アミノレブリン酸を用いるがん光線力学的療法の効果増強効果, 第29回日本バイオ治療法学会, Dec. 2025.
3.	KOBAYASHI Saya, Yusei Shinohara, Hisatsugu Yamada, 東佑弥, 松本光太郎, 玉野井冬彦 and Yoshihiro Uto : 5-Iodo-2'-deoxyuridineのヨウ素由来オージェ効果を介した放射線増感作用の評価, 2025年日本化学会中国四国支部大会香川大会, Nov. 2025.
4.	TAGUCHI Hikari, AKAMINE Wakana, Yusei Shinohara, Yoshihiro Uto and Hisatsugu Yamada : 多重共鳴拡散NMRを利用した生体的合成ポリマーの粒子径解析, 2025年日本化学会中国四国支部大会香川大会, Nov. 2025.
5.	TOHJOH Nanako, Yusei Shinohara, 今井宏彦, 近藤輝幸, Yoshihiro Uto and Hisatsugu Yamada : 11B MRI のためのメタクリレートポリマープローブの合成と機能評価, 2025年日本化学会中国四国支部大会香川大会, Nov. 2025.
6.	Yoshihiro Uto, Yusei Shinohara, 遠藤良夫 and 滝野隆久 : Development of selective inhibitors of Na+/H+ exchanger 5 (NHE5) related in cancer metastasis, 第84回日本癌学会学術総会, Sep. 2025.
7.	Yoshihiro Uto, Yusei Shinohara, 小林彩, 藤井理, NODA Shota, Mariko Niki, Yoshiaki Kubo and 稲垣正 : リポソーム化ビタミンCとnanoPDS化ビタミンCの皮膚浸透性および皮膚細胞に対する機能性の比較評価, 第25回抗加齢医学会総会, Jun. 2025.
8.	Yusei Shinohara, MORIMOTO Kashin, 小宮悠生, 二宮致, 遠藤良夫, 滝野隆久, Hisatsugu Yamada and Yoshihiro Uto : In silico 創薬によるNa+/H+交換輸送体5(NHE5)に対する選択的阻害剤の創製, 日本薬学会第145年会, Mar. 2025.
9.	YOSHINO Sohma, 藤井理, 田坂徹, Mariko Niki, Yoshihiro Uto and Yusei Shinohara : アトピー性⽪膚炎様モデルマウスに対する瞬芽ブドウ種⼦成分の改善効果, 第12回日本化学会中国四国支部大会岡山大会, Nov. 2024.
10.	TAKAHASHI Kohsuke, Yusei Shinohara, Yoshihiro Uto and Hisatsugu Yamada : 磁気共鳴イメージングのためのホスホセリンポリマープローブの合成と機能評価, 第12回日本化学会中国四国支部大会岡山大会, Nov. 2024.
11.	OHYAMA Tomoaki, TAGUCHI Hikari, Yusei Shinohara, Yoshihiro Uto and Hisatsugu Yamada : 多重共鳴拡散NMR法によるスルホベタインポリマーの⽣体内粒⼦径解析, 第12回日本化学会中国四国支部大会岡山大会, Nov. 2024.
12.	遠藤良夫, Yoshihiro Uto, Yusei Shinohara, 安部千秋, 小幡徹, 米村豊 and 小倉俊一郎 : Enhancing effect of novel Schiff base derivative combined with tyrosine kinase inhibitor on ALA-PDT, 第83回日本癌学会学術総会, Sep. 2024.
13.	Yusei Shinohara, 藤井理, 田坂徹, YOSHINO Sohma, NODA Shota, 小林彩, 中山清美, 佐藤宏晶 and Yoshihiro Uto : リポソーム化糖混合物による間質性肺炎の炎症抑制効果, 第76回日本生物工学会大会, Sep. 2024.
14.	Morimoto Kashin, KOMIYA Yuki, Yusei Shinohara, 二宮致, 遠藤良夫, 滝野隆久 and Yoshihiro Uto : アミロライドの構造活性相関による新規Na+/H+交換輸送隊5選択的阻害剤の創成, 第40回メディシナルケミストリーシンポジウム, Nov. 2023.
15.	遠藤良夫, Yoshihiro Uto, Yusei Shinohara, 安部千秋, 小幡徹, 米村豊 and 小倉俊一郎 : Development of a novel TKI derivative for enhancing anticancer potential of 5-ALA-based photodynamic therapy, 第82回日本癌学会学術総会, Sep. 2023.
16.	Yusei Shinohara, 藤井理, Sohma Yoshino, 中山清美 and Yoshihiro Uto : シアル酸を含む糖混合物の老化線維芽細胞に対する抗老化活性の評価, 日本薬学会第143年会, Mar. 2023.
17.	Yuki Komiya, Kashin Morimoto, Yusei Shinohara, 二宮致, 遠藤良夫, 滝野隆久 and Yoshihiro Uto : アミロライド誘導体の構造活性相関による新規Na+/H+交換輸送体5 (NHE5) 選択的阻害剤UTX-143の創製, 2022年日本化学会中四国支部大会, Nov. 2022.
18.	Yusei Shinohara, Itasu Ninomiya, Yoshio Endo, Takahisa Takino and Yoshihiro Uto : Development of a Novel Amiloride Derivative as a Na+/H+ exchanger 5 selective inhibitor, 第79回日本癌学会学術総会, Oct. 2020.
19.	Yusei Shinohara, 遠藤良夫, 安部千秋, 小幡徹, 小倉俊一郎, 米村豊 and Yoshihiro Uto : 5-ALAを用いた光線力学療法における新規シッフ塩基併用による増強作用, 日本農芸化学会2020年度中四国支部大会, Sep. 2020.
20.	Yukari Kunieda, Yusei Shinohara, Yuya Tanaka, Hirari Yamahana, Yuri Fujiwara, Hisatsugu Yamada and Yoshihiro Uto : 放射線増感ユニットであるアセチルグルコースを修飾したEGFR阻害剤Erlotinib誘導体の創製, 第22回癌治療増感シンポジウム, Feb. 2020.
21.	Yusei Shinohara, 遠藤良夫, 安部千秋, 小幡徹, 小倉俊一郎, 米村豊 and Yoshihiro Uto : 5-アミノレブリン酸を用いたがん光線力学療法における新規シッフ塩基の併用による増強作用, 第22回癌治療増感シンポジウム, Feb. 2020.
22.	Yukari Kunieda, Yusei Shinohara, Yuya Tanaka, Hirari Yamahana, Yuri Fujiwara, Hisatsugu Yamada and Yoshihiro Uto : アセチルグルコースを修飾した放射線増感作用を有する抗腫瘍剤の創薬研究, 日本化学会中国四国支部大会徳島大会, Oct. 2019.
23.	遠藤良夫, Yoshihiro Uto, Yusei Shinohara, 安部千秋, 小幡徹, 小倉俊一郎 and 米村豊 : アミノレブリン酸を用いるがん光線力学的療法に対する新規シッフ塩基誘導体の感受性増強作用, 日本薬学会第139年会, Mar. 2019.
24.	Hirari Yamahana, Yusei Shinohara, Ayaka Hanyu, Yuya Tanaka, Hisatsugu Yamada and Yoshihiro Uto : Development of a Novel Acetyl Glucose-modified Gefitinib Derivative for Improvement of Radiosensitizing Effect, 日本化学会第99会年会, Mar. 2019.
25.	Yusei Shinohara and Yoshihiro Uto : Development of acetylglucose-modified gefitinib derivatives as a novel radiosensitizer, 第77回日本癌学会学術総会, Sep. 2018.
26.	遠藤良夫, Yoshihiro Uto, Ikkyu Shiba, Yusei Shinohara, 安部千秋, 小幡徹, 小倉俊一郎 and 米村豊 : アミノレブリン酸を用いるがん光線力学的療法に対するシッフ塩基誘導体の感受性増強作用, 日本薬学会第138年会, Mar. 2018.
27.	Yusei Shinohara, Ikkyu Shiba, Hisatsugu Yamada, 遠藤良夫, 石塚昌宏 and Yoshihiro Uto : 5-アミノレブリン酸を用いた光線力学治療ALA-PDTに対する増感剤TX-816の創製, 日本化学会第98春季年会, Mar. 2018.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

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Assistant Professor : Shinohara, Yusei

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)