Novel strategy of drug therapy for inflammatory bowel diseases based on the combination of drug transport and intestinal immunology.

• Project/Area Number: 23659077
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TERADA Tomohiro 滋賀医科大学, 医学部, 教授 (10324641)
• Co-Investigator(Kenkyū-buntansha): ANDOH Akira 滋賀医科大学, 大学院・医学系研究科, 教授 (90252395)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 薬学 / 薬剤反応性 / 薬理学 / 薬物トランスポータ / 炎症性腸疾患

Research Abstract

Expression of peptide transporter PEPT1 in the large intestine of inflammatory bowel disease (IBD) patients was specifically induced in the inflammatory region. Furthermore, this expression was suggested to be stimulated by intestine-specific transcription factor CDX2. Based on the literature and molecular design methods, eight kinds of amino acid derivatives of 5-aminosalicylic acid were synthesized, which can become the substrates for PEPT1. The interaction of PEPT1 with these amino acid derivatives of 5-aminosalicylic acid will be evaluated from the view points of in vitro and in vivo.

Research Products

• [Journal Article] Bile salt-stimulated phospholipid efflux mediated by ABCB4 localized in nonraft membranes (2013)
  • Author(s): Morita, S., Terada, T.
  • Journal Title: J. Lipid Res Volume: 54(5) Issue: 5 Pages: 1221-1230
  • DOI: 10.1194/jlr.m032425
  • Peer Reviewed
• [Journal Article] Neutralization of complement component C5 ameliorates the development of dextran sulfate sodium (DSS)-colitis in mice (2013)
  • Author(s): Aomatsu T, Imaeda H, Takahashi K, Fujimoto T, Kasumi E, Ban H, Bamba S, Yoden A, Tamai H, Fujiyama Y, Andoh A.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 52 Issue: 1 Pages: 72-75
  • DOI: 10.3164/jcbn.12-63
  • NAID: 130004879316
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer. (2013)
  • Author(s): Masahide Fukudo
  • Journal Title: Clin. Pharmacokinet. Volume: in press
  • Peer Reviewed
• [Journal Article] Pharmacokinetic interaction between sorafenib and prednisolone in a patient with hepatocellular carcinoma. (2013)
  • Author(s): Satoshi Noda
  • Journal Title: Cancer Chemother. Pharmacol. Volume: in press
  • Peer Reviewed
• [Journal Article] Renal tubular secretion of varenicline by multidrug and toxin extrusion (MATE) transporters. (2012)
  • Author(s): Kajiwara, M., Masuda, S., Watanabe, S., Terada, T., Katsura, T. and Inui, K.
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 27(6) Pages: 563-569
  • NAID: 130004933508
  • URL: https://www.jstage.jst.go.jp/article/dmpk/27/6/27_DMPK-11-RG-156/_pdf
  • Peer Reviewed
• [Journal Article] Specific and sensitive enzymatic measurement of sphingomyelin in cultured cells (2012)
  • Author(s): Morita, S., Terada, T.
  • Journal Title: Chem. Phys. Lipids Volume: 165(5) Issue: 5 Pages: 571-576
  • DOI: 10.1016/j.chemphyslip.2012.06.003
  • Peer Reviewed
• [Journal Article] Enzymatic measurement of phosphatidylserine in cultured cells. (2012)
  • Author(s): Morita, S., Terada, T.
  • Journal Title: J. Lipid Res Volume: 53(2) Issue: 2 Pages: 325-330
  • DOI: 10.1194/jlr.d021808
  • Peer Reviewed
• [Journal Article] Recent advances in structural biology of peptide transporters (2012)
  • Author(s): Terada, T. and Inui, K.
  • Journal Title: Curr. Top. Membr Volume: 70 Pages: 257-274
  • DOI: 10.1016/b978-0-12-394316-3.00008-9
  • Peer Reviewed
• [Journal Article] The severity of dextran sodium sulfate-induced colitis can differ between dextran sodium sulfate preparations of the same molecular weight range (2012)
  • Author(s): Bamba, S., Andoh, A., Ban, H., Imaeda, H., Aomatsu, T., Kobori, A., Mochizuki, Y., Shioya, M., Nishimura, T., Inatomi, O., Sasaki, M., Saitoh, Y., Tsujikawa, T., Araki, Y. and Fujiyama, Y.
  • Journal Title: Dig. Dis. Sci Volume: 57(2) Issue: 2 Pages: 327-334
  • DOI: 10.1007/s10620-011-1881-x
  • Peer Reviewed
• [Journal Article] Renal tubular secretion of varenicline by multidrug and toxin extrusion (MATE) transporters. (2012)
  • Author(s): Moto Kajiwara
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 27 Pages: 563-569
  • Peer Reviewed
• [Journal Article] Impact of genetic variation in breast cancer resistance protein (BCRP/ABCG2) on sunitinib pharmacokinetics. (2012)
  • Author(s): Tomoyuki Mizuno
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 27 Pages: 631-639
  • Peer Reviewed
• [Journal Article] Pharmacokinetic/pharmacodynamic analysis of a hemodialyzed patient treated with 25 mg of sunitinib (2012)
  • Author(s): Noda, S., Terada, T.
  • Journal Title: Case Rep. Oncol Volume: 5 Issue: 3 Pages: 627-632
  • DOI: 10.1159/000345694
  • Peer Reviewed
• [Journal Article] Effects of phosphatidylethanolamineN-methyltransferase on phospholipid composition, microvillus formation and bile salt resistance in LLC-PK1 cells (2011)
  • Author(s): Morita, S., Terada, T.
  • Journal Title: FEBS J Volume: 278(24) Issue: 24 Pages: 4768-4781
  • DOI: 10.1111/j.1742-4658.2011.08377.x
  • Peer Reviewed
• [Journal Article] Human NPC1L1 expression is positively regulated by PPARα (2011)
  • Author(s): Iwayanagi, Y., Takada, T., Tomura, F., Yamanashi, Y., Terada, T.
  • Journal Title: Pharm. Res Volume: 28(2) Issue: 2 Pages: 405-412
  • DOI: 10.1007/s11095-010-0294-4
  • Peer Reviewed
• [Journal Article] Interleukin-33 suppresses Notch ligand expression and prevents goblet cell depletion in dextran sulfate sodium-induced colitis (2011)
  • Author(s): Imaeda, H., Andoh, A., Aomatsu, T., Uchiyama, K., Bamba, S., Tsujikawa, T., Naito, Y. and Fujiyama, Y.
  • Journal Title: Int. J. Mol. Med. Volume: 28(4) Pages: 573-578
  • DOI: 10.3892/ijmm.2011.718
  • Peer Reviewed
• [Journal Article] Human NPC1L1 expression is positively regulated by PPARα. (2011)
  • Author(s): Iwayanagi Y et al.
  • Journal Title: Pharm. Res. Volume: 28 Pages: 405-412
  • Peer Reviewed
• [Journal Article] Plasma and pleural fluid pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small-cell lung cancer with pleural effusion. (2011)
  • Author(s): Masago K et al.
  • Journal Title: Clin. Lung Cancer Volume: 12 Pages: 307-312
  • Peer Reviewed
• [Journal Article] Effects of phosphatidylethanolamine N-methyltransferase on phospholipid composition, microvillus formation and bile salt resistance in LLC-PK1 cells. (2011)
  • Author(s): Morita S et al.
  • Journal Title: FEBS J. Volume: 278 Pages: 4768-4781
  • Peer Reviewed
• [Presentation] Healthcare Professionalを目指して (2013)
  • Author(s): 寺田智祐
  • Organizer: 第34回秋田県臨床薬学研究会
  • Place of Presentation: 秋田市にぎわい交流館（秋田市）
  • Invited
• [Presentation] PK/PD approaches for optimal molecular targeted cancer therapy (2012)
  • Author(s): Terada, T., Mizuno, T., Fukudo, M., Inui, K. and Katsura, T.
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: 東京
• [Presentation] 薬物動態研究の臨床応用 (2012)
  • Author(s): 寺田智祐
  • Organizer: 第32回日本眼薬理学会
  • Place of Presentation: 滋賀
• [Presentation] ファーマコゲノミクス検査に基づく個別化 (2012)
  • Author(s): 寺田智祐
  • Organizer: 医療薬学フォーラム2012
  • Place of Presentation: 福岡
• [Presentation] ファーマコゲノミクス検査に基づく個別化 (2012)
  • Author(s): 寺田智祐
  • Organizer: 医療薬学フォーラム2012
  • Place of Presentation: 福岡国際会議場（福岡市）
  • Invited
• [Presentation] 薬物動態研究の臨床応用 (2012)
  • Author(s): 寺田智祐
  • Organizer: 第32回日本眼薬理学会
  • Place of Presentation: 淡海プラザ（大津市）
  • Invited
• [Presentation] CKDシールを活用した医薬連携 (2012)
  • Author(s): 寺田智祐、宇津 貴
  • Organizer: 第22回日本医療薬学会
  • Place of Presentation: 朱鷺メッセ（新潟市）
  • Invited
• [Presentation] PK/PD approaches for optimal molecular targeted cancer therapy (2012)
  • Author(s): Terada, T., Mizuno, T., Fukuto, M., Inui, K. and Katsura, T.
  • Organizer: 日本薬物動態学会第27回年会
  • Place of Presentation: 江戸川区民ホール（東京都）
  • Invited
• [Presentation] がん領域におけるチーム医療と薬剤師の役割 (2011)
  • Author(s): 寺田智祐、森井博朗
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: 浜松
• [Presentation] PK/PD and optimal usage of anticancer drugs: Viewpoints from the pharmacists (2011)
  • Author(s): Terada, T.
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島
• [Presentation] がんを専門とする薬剤師のキャリアパス-臨床薬学研究者の立場から- (2011)
  • Author(s): 寺田智祐
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Role of pharmacists in the frontline of pharmacotherapy (2011)
  • Author(s): Terada, T.
  • Organizer: 第21回日本医療薬学会
  • Place of Presentation: 神戸
• [Presentation] 新規経口マルチキナーゼ阻害剤の体内動態とpharmacogenomics (2011)
  • Author(s): 寺田智祐
  • Organizer: 第9回日本臨床腫瘍学会学術集会
  • Place of Presentation: 横浜
• [Presentation] 小腸におけるペプチド吸収とトランスポータ (2011)
  • Author(s): 寺田智祐
  • Organizer: 第49回小腸研究会(招待講演)
  • Place of Presentation: 都市センターホテル
• [Book] ペプチドトランスポーターの発現・機能ならびに消化管における薬物輸送の制御. 難吸収性薬物の吸収性改善と新規投与製剤の開発, 山本 昌監修 (2012)
  • Author(s): 寺田智祐
  • Publisher: シーエムシー出版