Analysis on the expression of protein regulating pharmacokinetics via oxidative stress-response lncRNA

• Project/Area Number: 17K08411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Mie University
• Principal Investigator: IKEMURA Kenji 三重大学, 医学部附属病院, 薬剤師 (70513935)
• Co-Investigator(Kenkyū-buntansha): 奥田 真弘 三重大学, 医学部附属病院, 教授 (70252426)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Long-noncoding RNA / 酸化ストレス / 薬物トランスポータ / P-糖蛋白質 / Long non-coding RNA / microRNA / microRNA-sponge / P-糖タンパク質 / 薬物代謝酵素 / lncRNA / 薬物動態

Outline of Final Research Achievements

Long-noncoding RNA (lncRNA) should regulate the expression of drug-metabolizing enzymes and drug transporters, which affect the efficacy and adverse effect of drugs. In the present study, we demonstrated that the expression level of P-glycoprotein (P-gp/MDR1) was increased in human colon carcinoma cell line Caco-2 cell by the exposure of oxidative stress. In addition, the present findings suggested that CRNDE (Colorectal neoplasia differentially expressed), which is a type of lncRNA, regulated the expression of MDR1.

Academic Significance and Societal Importance of the Research Achievements

lncRNAは、年齢・性別・疾患により発現量が変動することから、これまで未解決であった薬の薬効や副作用発現の個人差の解明に寄与する可能性が高く、今後の更なる研究の発展が期待される。また、P-糖蛋白質はがん細胞における抗がん薬耐性化に密接に関わる分子であることから、P-糖蛋白質の新たな発現調節機構の解明により、抗がん薬の耐性化の克服や抗がん薬の安全かつ有効な薬物治療の実現にも貢献可能である。

Research Products

• [Journal Article] Maternal administration of tadalafil improves fetal ventricular systolic function in a Hey2 knockout mouse model of fetal heart failure. (2020)
  • Author(s): Miyoshi T, Hisamitsu T, Ishibashi-Ueda H, Ikemura K, Ikeda T, Miyazato M, Kangawa K, Watanabe Y, Nakagawa O, Hosoda H.
  • Journal Title: International Journal of Cardiology Volume: 302 Pages: 110-116
  • DOI: 10.1016/j.ijcard.2019.12.013
  • Peer Reviewed / Open Access
• [Journal Article] Oxidative DNA damage and apoptosis induced by aclarubicin, an anthracycline: role of hydrogen peroxide and copper. (2019)
  • Author(s): Mizutani H, Hayashi Y, Hashimoto M, Imai M, Ichimaru Y, Kitamura Y, Ikemura K, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
  • Journal Title: Anticancer Res Volume: 39 Issue: 7 Pages: 3443-3451
  • DOI: 10.21873/anticanres.13490
  • Peer Reviewed / Open Access
• [Journal Article] Maternal Blood Concentration of Tadalafil and Uterine Blood Flow in Pregnancy. (2019)
  • Author(s): Tanaka H, Maki S, Magawa S, Nii M, Tanaka K, Ikemura K, Toriyabe K, Ikeda T.
  • Journal Title: Medicina (Kaunas) Volume: 55（10） Issue: 10 Pages: 708-708
  • DOI: 10.3390/medicina55100708
  • Peer Reviewed / Open Access
• [Journal Article] Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein (2019)
  • Author(s): Ikemura Kenji、Hiramatsu Shun-ichi、Shinogi Yuri、Nakatani Yusuke、Tawara Isao、Iwamoto Takuya、Katayama Naoyuki、Okuda Masahiro
  • Journal Title: Scientific Reports Volume: 9 Issue: 1
  • DOI: 10.1038/s41598-019-56900-2
  • Peer Reviewed / Open Access
• [Journal Article] Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions. (2019)
  • Author(s): Tachibana Ryota, Umekawa Takashi, Yoshikawa Kento, Owa Takao, Magawa Shoichi, Furuhashi Fumi, Tsuji Makoto, Maki Shintaro, Shimada Kyoko, Kaneda K. Michiko, Nii Masafumi, Tanaka Hiroaki, Tanaka Kayo, Kamimoto Yuki, Kondo Eiji, Kato Ineko, Ikemura Kenji, Okuda Masahiro, et al.
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 234-234
  • DOI: 10.1038/s41598-018-36084-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk factors for the development of hypermagnesemia in patients prescribed magnesium oxide: a retrospective cohort study (2019)
  • Author(s): Wakai Eri, Ikemura Kenji, Sugimoto Hiroko, Iwamoto Takuya, Okuda Mamashiro
  • Journal Title: Journal of Pharmaceutical Health Care and Sciences Volume: 5 Issue: 1
  • DOI: 10.1186/s40780-019-0133-7
  • Peer Reviewed / Open Access
• [Journal Article] Oxidative DNA damage induced by pirarubicin, an anthracycline anticancer agent, in the presence of copper(II). (2018)
  • Author(s): Mizutani H, Nishimoto A, Hotta S, Ikemura K, Imai M, Miyazawa D, Ohta K, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S
  • Journal Title: Anticancer Research Volume: 38 Issue: 5 Pages: 2643-2648
  • DOI: 10.21873/anticanres.12506
  • Peer Reviewed / Open Access
• [Journal Article] Stereoselective Inhibition of Renal Basolateral Human Organic Anion Transporter 3 by Lansoprazole Enantiomers (2018)
  • Author(s): Hamada Yugo、Ikemura Kenji、Iwamoto Takuya、Okuda Masahiro
  • Journal Title: Pharmacology Volume: 101 Issue: 3-4 Pages: 176-183
  • DOI: 10.1159/000485920
  • Peer Reviewed
• [Journal Article] Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy (2017)
  • Author(s): Ikemura Kenji、Hiramatsu Shunichi、Okuda Masahiro
  • Journal Title: Frontiers in Pharmacology Volume: 8
  • DOI: 10.3389/fphar.2017.00911
  • Peer Reviewed / Open Access
• [Journal Article] Two cases of life-threatening arrhythmia induced by risperidone: evaluation of risperidone and 9-hydroxy-risperidone concentrations. (2017)
  • Author(s): Ito A, Enokiya T, Kawamoto E, Iwashita Y, Takeda T, Ikemura K, Okuda M, Imai H.
  • Journal Title: Acute Medicine & Surgery Volume: 印刷中 Issue: 3 Pages: 341-343
  • DOI: 10.1002/ams2.277
  • Peer Reviewed / Open Access
• [Journal Article] Tadalafil Improves L-NG-Nitroarginine Methyl Ester-Induced Preeclampsia With Fetal Growth Restriction-Like Symptoms in Pregnant Mice (2017)
  • Author(s): Yoshikawa Kento、Umekawa Takashi、Maki Shintaro、Kubo Michiko、Nii Masafumi、Tanaka Kayo、Tanaka Hiroaki、Osato Kazuhiro、Kamimoto Yuki、Kondo Eiji、Ikemura Kenji、Okuda Masahiro、Katayama Kan、Miyoshi Takekazu、Hosoda Hiroshi、Ma Ning、Yoshida Toshimichi、Ikeda Tomoaki
  • Journal Title: American Journal of Hypertension Volume: 31 Issue: 1 Pages: 89-96
  • DOI: 10.1093/ajh/hpx130
  • Peer Reviewed
• [Journal Article] Effect of lipid emulsion infusion on paliperidone pharmacokinetics in the acute overdose rat model: A potential emergency treatment for paliperidone intoxication (2017)
  • Author(s): Enokiya Tomoyuki、Zhang Erquan、Ikemura Kenji、Muraki Yuichi、Iwashita Yoshiaki、Iwamoto Takuya、Imai Hiroshi、Maruyama Kazuo、Okuda Masahiro
  • Journal Title: European Journal of Pharmaceutical Sciences Volume: 109 Pages: 217-222
  • DOI: 10.1016/j.ejps.2017.08.010
  • Peer Reviewed
• [Journal Article] Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study. (2017)
  • Author(s): Ikemura K, Oshima K, Enokiya T, Okamoto A, Oda H, Mizuno T, Ishinaga H, Muraki Y, Iwamoto T, Takeuchi K, Katayama N, Okuda M
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 印刷中 Issue: 5 Pages: 943-949
  • DOI: 10.1007/s00280-017-3296-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Impact of the number of repeated inhalations and patient characteristics on the residual amount of inhaled laninamivir octanoate hydrate dry powder in pediatric patients with influenza (2017)
  • Author(s): Murasaka Toshiki、Ikemura Kenji、Enokiya Tomoyuki、Muraki Yuichi、Ikemura Mayumi、Terada Koji、Iwamoto Takuya、Okuda Masahiro
  • Journal Title: Journal of Pharmaceutical Health Care and Sciences Volume: 3 Issue: 1
  • DOI: 10.1186/s40780-017-0094-7
  • Peer Reviewed / Open Access
• [Journal Article] Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through Generation of Hydrogen Peroxide. (2017)
  • Author(s): Mizutani H, Hotta S, Nishimoto A, Ikemura K, Miyazawa D, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S.
  • Journal Title: Anticancer Res. Volume: 37 Issue: 11 Pages: 6063-6069
  • DOI: 10.21873/anticanres.12054
  • Peer Reviewed / Open Access
• [Presentation] 入院時持参薬における処方複雑性が服薬管理及び糖尿病の治療効果に及ぼす影響 (2020)
  • Author(s): 若井恵里、池村健治、加藤千佳、岩本卓也、奥田真弘
  • Organizer: 日本薬学会第140年会
• [Presentation] 入院時持参薬に内服降圧薬を含む患者の血圧管理に及ぼす薬剤数及び処方内容の複雑性の影響 (2019)
  • Author(s): 加藤千佳、若井恵里、池村健治、岩本卓也、奥田真弘
  • Organizer: 医療薬学フォーラム2019
• [Presentation] 入院時持参薬における薬剤数及び処方複雑性が高血圧の治療効果に及ぼす影響 (2019)
  • Author(s): 若井恵里、池村健治、加藤千佳、岩本卓也、奥田真弘
  • Organizer: 第29回日本医療薬学会年会
• [Presentation] LC-MS/MS用抗てんかん薬一斉分析キットを用いた分析法の開発と評価 (2019)
  • Author(s): 池村真弓、石橋美紀、池村健治、岩本卓也, 奥田真弘
  • Organizer: 第29回日本医療薬学会年会
• [Presentation] 有害事象自発報告システム（FAERS）を用いたメトトレキサートの肝障害発現にフェブキソスタット併用が与える影響に関する解析 (2019)
  • Author(s): 中谷祐介、平松駿一、池村健治、岩本卓也、奥田真弘
  • Organizer: 日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2019
• [Presentation] 大量メトトレキサート療法時の肝障害発現に対するフェブキソスタット併用の影響 (2019)
  • Author(s): 平松駿一、池村健治、篠木優里、俵功、岩本卓也、片山直之、奥田真弘
  • Organizer: 日本薬学会第139年会
• [Presentation] Proton pump inhibitors as promising concomitant agents ameliorating cisplatin-induced nephrotoxicity (2018)
  • Author(s): Kenji Ikemura, Shunichi Hiramatsu, Yutaka Fujisawa, Takuya Iwamoto, Masahiro Okuda
  • Organizer: 78th FIP World Congress of Pharmacy and Pharmaceutical Sciences
  • Int'l Joint Research
• [Presentation] Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by reducing renal cisplatin accumulation in rats (2018)
  • Author(s): Shunichi Hiramatsu, Kenji Ikemura, Yutaka Fujisawa, Takuya Iwamoto, Masahiro Okuda
  • Organizer: 2018 International Meeting on 22nd MDO and 33rd JSSX
  • Int'l Joint Research
• [Presentation] ランソプラゾールは腎におけるヒト有機カチオントランスポータ2によるシスプラチンの輸送を阻害する (2017)
  • Author(s): 平松駿一、池村健治、藤澤豊、岩本卓也、奥田真弘
  • Organizer: 日本薬物動態学会第32回年会
• [Presentation] Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity: an epidemiological and in vivo rat evidence. (2017)
  • Author(s): Hiramatsu S, Ikemura K, Fujisawa Y, Iwamoto T, Okuda M
  • Organizer: 第11回次世代を担う若手医療薬科学シンポジウム
• [Presentation] Effect of lipid emulsion infusion on paliperidone pharmacokinetics in the acute overdose rat model: A potential emergency treatment for paliperidone intoxication. (2017)
  • Author(s): Enokiya T, Zhang E, Ikemura K, Muraki Y, Iwashita Y, Iwamoto T, Imai H, Maruyama K, Okuda M
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology 2017
  • Int'l Joint Research
• [Presentation] Impact of Lansoprazole Coadministration on Pemetrexed-induced Hematotoxicity: Stereoselective Inhibition of Human Organic Anion Transporter 3 by Lansoprazole Enantiomers. (2017)
  • Author(s): Okuda M, Ikemura K, Hamada Y, Kaya C, Enokiya T, Muraki Y, Nakahara H, Fujimoto H, Kobayashi T, Iwamoto T
  • Organizer: FIP PSWC 2017 6th Pharmaceutical Sciences World Congress
  • Int'l Joint Research