Chemopreventive effects of vitamin K cycle using human iPS cells

• Project/Area Number: 22590133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Nagoya City University (2012); Shinshu University (2010-2011)
• Principal Investigator: NAKAMURA Katsunori 名古屋市立大学, 大学院・薬学研究科, 准教授 (20361363)
• Co-Investigator(Kenkyū-buntansha): MATSUNAGA Tamihide 名古屋市立大学, 大学院・薬学研究科, 教授 (40209581) ; OHMORI Shigeru 信州大学, 医学部附属病院, 教授 (70169069)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ケモプリベンション / ビタミン K / iPS 細胞 / PIVKA-II / VKORC1 / ビタミンKサイクル / ヒトiPS細胞 / 発がん予防機構

Research Abstract

Final goal of this study was to find the way to improve the cancer chemotherapies and cancer chemo-preventions from the information of Vitamin K cycle-related genetic polymorphisms. The human iPS cells would be useful as an appropriate assay of a variety of drug metabolism study as well as the study of cancer chemo-preventions. The effect of Vitamin Kcycle-related genetic polymorphisms on warfarin maintenance dose was observed and this could havesome importance when warfarin prescribed during cancer chemotherapies.

Research Products

• [Journal Article] Differentiation of monkey embryonic stem cells to hepatocytes by feeder-free dispersion culture and expression analyses of cytochrome p450 enzymes responsible for drug metabolism. (2013)
  • Author(s): Maruyama J, Matsunaga T, Yamaori S, Sakamoto S, Kamada N, Nakamura K, Kikuchi S, Ohmori S.
  • Journal Title: Biol Pharm Bull Volume: 36(2) Pages: 292-298
  • NAID: 130002480763
  • Peer Reviewed
• [Journal Article] Differentiation of monkey embryonic stem cells to hepatocytes by feeder-free dispersion culture and expression analyses of cytochrome p450 enzymes responsible for drug metabolism. (2013)
  • Author(s): J Maruyama
  • Journal Title: Biol Pharm Bull Volume: 36 Pages: 292-298
  • Peer Reviewed
• [Journal Article] 心臓血管外科手術施行後のワルファリン初期投与計画におけるCYP2C9及び VKORC1の遺伝子多型情報の臨床上の意義 (2013)
  • Author(s): 川名純一
  • Journal Title: アプライド・セラピューティクス Volume: 4 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Treatment of a GIST patient with modifieddose of sunitinib by measurement of plasma drug concentrations. (2012)
  • Author(s): Hashita T, Katsuyama Y, Nakamura K, Momose Y, Komatsu D, Koide N, Miyagawa S, Nakamura T, Yamamoto K, Ohmori S.
  • Journal Title: Oncol Lett. Volume: 4(3) Pages: 501-504
  • Peer Reviewed
• [Journal Article] Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers. Drug Metab Pharmacokinet. (2012)
  • Author(s): Tsuchiya H, Matsunaga T, Aikawa K, Kamada N, Nakamura K, Ichikawa H, Sasaki K, Ohmori S.
  • Journal Title: Drug Metab Pharmacokinet. Volume: 27(6) Pages: 598-604
  • Peer Reviewed
• [Journal Article] Lower expression of HNF4α and PGC1α might impair rifampicin-mediated CYP3A4 induction under conditions where PXR is overexpressed in human fetal liver cells. (2012)
  • Author(s): Takezawa T, Matsunaga T, Aikawa K, Nakamura K, Ohmori S.
  • Journal Title: Drug Metab Pharmacokinet. Volume: 27(4) Pages: 430-438
  • NAID: 130004463268
  • Peer Reviewed
• [Journal Article] Effect of CYP2C19 gene variations on thalidomide treated patients in Japanese. (2012)
  • Author(s): Matsuzawa N, Nakamura K, Matsuda M, Ishida F, Ohmori S
  • Journal Title: Biol Pharm Bull Volume: 35(3) Pages: 317-320
  • Peer Reviewed
• [Journal Article] CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. (2012)
  • Author(s): Nakamura K, Obayashi K, Araki T, Aomori T, Fujita Y, Okada Y, Kurabayashi M, Hasegawa A, Ohmori S, Nakamura T, Yamamoto K.
  • Journal Title: J Clin Pharm Ther Volume: 37(4) Pages: 481-485
  • Peer Reviewed
• [Journal Article] CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects (2012)
  • Author(s): Katsunori Nakamura
  • Journal Title: J Clin Pharm Ther Volume: (in press) Issue: 4 Pages: 481-485
  • DOI: 10.1111/j.1365-2710.2011.01317.x
  • Peer Reviewed
• [Journal Article] Treatment of a GIST patient with modified dose of sunitinib by measurement of plasma drug concentrations. (2012)
  • Author(s): T Hashita
  • Journal Title: Oncol Lett Volume: 4 Pages: 501-504
  • Peer Reviewed
• [Journal Article] Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers. (2012)
  • Author(s): H Tsuchiya
  • Journal Title: Drug Metab Pharmacokinet Volume: 27 Pages: 598-604
  • Peer Reviewed
• [Journal Article] Clinical screening assay for EGFR exon 19 mutations using PNA-clamp smart amplification process version 2 in lung adenocarcinoma. (2011)
  • Author(s): Araki T, Shimizu K, Nakamura T, Baba M, Kawai Y, Nakamura K, Mitani Y, Obayashi K, Aomori T, Fujita Y, Miyamae Y, Kakegawa S, Kaira K, Lezhava A, Hayashizaki Y, Takeyoshi I, Yamamoto K.
  • Journal Title: Oncol Rep Volume: 26(5) Pages: 1213-1219
  • Peer Reviewed
• [Journal Article] Determination of landiolol in human plasma by high-performance liquid chromatography with fluorescence detection. (2011)
  • Author(s): Aomori T, Matsumoto N, Nakamura K, Fujita Y, Sekizuka M, Araki T, Nakamura T, Yamamoto K.
  • Journal Title: Journal of Liquid Chromatography & Related Technologies. Volume: 34(19) Pages: 2411-2419
  • Peer Reviewed
• [Journal Article] Comparison of the inhibitory profiles of itraconazole and cimetidine in cytochrome P450 3A4 genetic variants. (2011)
  • Author(s): Akiyoshi T, Saito T, Murase S, Miyazaki M, Murayama N, Yamazaki H, Guengerich FP, Nakamura K, Yamamoto K, Ohtani H.
  • Journal Title: Drug Metab Dispos Volume: 39(4) Pages: 724-728
  • Peer Reviewed
• [Journal Article] Influence of CYP2C9 and VKORC1 polymorphisms on time to determine the warfarin maintenance dose (2011)
  • Author(s): Aomori T, Obayashi K, Fujita Y, Araki T, Nakamura K, Nakamura T, Kurabayashi M, Yamamoto K.
  • Journal Title: PHARMAZIE. Volume: 66 Pages: 222-225
  • Peer Reviewed
• [Journal Article] Influence of CYP2C9 and VKORC1 polymorphisms on time to determine the warfarin maintenance dose (2011)
  • Author(s): Aomori T, Obayashi K, Fujita Y, Araki T, Nakamura K, Nakamura T, Kurabayashi M, Yamamoto K
  • Journal Title: PHARMAZIE Volume: 66 Pages: 1-4
  • Peer Reviewed
• [Journal Article] Comparison of the inhibitory profiles of itraconazole and cimetidine in cytochrome P450 3A4 genetic variants (2011)
  • Author(s): Akiyoshi T, Saito T, Murase S, Miyazaki M, Murayama N, Yamazaki H, Guengerich FP, Nakamura K, Yamamoto K, Ohtani H
  • Journal Title: Drug Metab Dispos Volume: 39 Pages: 724-728
  • Peer Reviewed
• [Journal Article] Clinical screening assay for EGFR exon 19 mutations using PNA-clamp smart amplification process version 2 in lung adenocarcinoma (2011)
  • Author(s): Takuya Araki, Kimihiro Shimizu, Tomonori Nakamura, Masaru Baba, Yuki Kawai, Katsunori Nakamura, Yasumasa Mitani, Kyoko Obayashi, Tohru Aomori, Yukiyoshi Fujita, Yohei Miyamae, Seiichi Kakegawa, Kyoichi Kaira, Alexander Lezhava, Yoshihide Hayashizaki, Izumi Takeyoshi, Koujirou Yamamoto
  • Journal Title: Oncol Rep Volume: 26 Pages: 1213-1219
  • DOI: 10.3892/or.2011.1391
  • Peer Reviewed
• [Journal Article] Usefulness of peptide nucleic acid (PNA)-clamp smart amplification process version 2 (SmartAmp2) for clinical diagnosis of KRAS codon 1 2 mutations in lung adenocarcinoma: comparison of PNA-clamp Smart Amp2 and PCR-related methods. (2010)
  • Author(s): Araki T, Shimizu K, Nakamura K, Nakamura T, Mitani Y, O bayashi K, Fujita Y, Kakegawa S, Miyamae Y, Kaira K, Ishid ao T, Lezhava A, Hayashizaki Y, Takeyoshi I, Yamamoto K
  • Journal Title: J. Mol. Diagn. Volume: 12(1) Pages: 118-124
  • Peer Reviewed
• [Journal Article] Pharmacokinetic individualization of high-dose methotrexate chemothe rapy for the treatment of localized osteosarcoma. (2010)
  • Author(s): Fujita Y, Nakamura T, Aomori T, Nishiba H, Shinozaki T, Ya nagawa T, Takagishi K, Watan abe H, Okada Y, Nakamura K, Horiuchi R. Yamamoto K
  • Journal Title: J. Chemother. Volume: 22(3) Pages: 186-190
  • Peer Reviewed
• [Journal Article] ES細胞の肝細胞への分化と薬物動態試験への応用. (2010)
  • Author(s): 松永民秀,大森栄
  • Journal Title: 医学のあゆみ Volume: 232(2) Pages: 447-457
• [Presentation] ヒト人工多能性幹細胞から分化させた肝細胞様細胞による薬物代謝酵素の酵素誘導評価 (2012)
  • Author(s): 中村克徳、近藤祐樹、杉山留理、相川香織、松永民秀、大森栄
  • Organizer: 日本薬学会第132年回
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 糖原病 Ib 型患者肝非実質由来 iPS 細胞の樹立と肝臓、好中球への分化誘導及び機能評価. (2012)
  • Author(s): 佐藤大介, 前田徹, 伊藤哲哉, 松村治穂, 中村克徳, 絵野沢伸, 齋藤伸治, 松永民秀.
  • Organizer: 日本人類遺伝学会 第57回大会
  • Place of Presentation: 東京
• [Presentation] Small Molecule Compounds Enhance Differentiation to Hepatocytes from induced Pluripotent Stem Cells. (2012)
  • Author(s): Yuki Kondo, Takahiro Iwao, Sachimi Yoshihashi, Kayo Mimori, Ruri Sugiyama, Takamitsu Sasaki, Kiyoshi Nagata, Kouichi Kurose, Takuro Niwa, Satoshi Yamaori, Shigeru Ohmori, Katsunori Nakamura, Tamihide Matsunaga
  • Organizer: 第27回日本薬物動態学会年会
  • Place of Presentation: 船堀
• [Presentation] Generation of Human Induced Pluripotent Stem Cell Derived Enterocytes with Peptide Transport Function. (2012)
  • Author(s): Takahiro Iwao, Kiyoshi Nagata, Katsunori Nakamura, Tamihide Matsunaga.
  • Organizer: 第27回日本薬物動態学会年会
  • Place of Presentation: 東京
• [Presentation] 妊婦に対するお薬相談 妊娠と薬情報センター拠点病院に参加して (2012)
  • Author(s): 竹田晶子, 村田稔弥, 鳥羽美恵, 丸山順也, 中村克徳, 百瀬泰行, 金井誠, 大森栄.
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌市
• [Presentation] ヒト人工多能性幹細胞から分化させた肝細胞による薬物代謝酵素の酵素誘導評価 (2012)
  • Author(s): 中村克徳, 近藤祐樹, 杉山留理, 相川香織, 松永民秀, 大森 栄
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌市
• [Presentation] CYP3A4 各種変異型分子種の代謝活性に対する MBI 阻害剤の阻害強度の比較. (2012)
  • Author(s): 伊藤 真理恵, 秋好 健志, 村瀬 沙織, 宮崎 光江, 中村 克徳, 中村 智徳, Guengerich F. Peter, 山本 康次郎, 大谷壽一.
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌市
• [Presentation] Small Molecule Compounds Enhance Differentiation to Hepatocytes from induced Pluripotent Stem Cells. (2012)
  • Author(s): Yuki Kondo
  • Organizer: 第27回日本薬物動態学会年会
  • Place of Presentation: タワーホール船堀
• [Presentation] Generation of Human Induced Pluripotent Stem Cell Derived Enterocytes with Peptide Transport Function. (2012)
  • Author(s): Takahiro Iwao
  • Organizer: 第27回日本薬物動態学会年会
  • Place of Presentation: タワーホール船堀
• [Presentation] 遺伝薬理学を用いた個別化医療の推進に関する研究. (2011)
  • Author(s): 中村克徳, 大森栄
  • Organizer: 2011年度中部乳酸菌研究会
  • Place of Presentation: 新潟市
• [Presentation] 正常ヒト胎児肝細胞の CYP3A 発現に及ぼす擬似低酸素誘導化合物デフェロキサミンの影響 (2011)
  • Author(s): 青沼安希子,鈴木英二,中村克徳,松永民秀,大森栄
  • Organizer: 日本薬学会第131 年会
  • Place of Presentation: 静岡市
• [Presentation] 大型類人猿の肝薬物代謝酵素の特性について (2011)
  • Author(s): 星山望,中村克徳,松永民秀,大森栄
  • Organizer: 日本薬学会第131 年会
  • Place of Presentation: 静岡市
• [Presentation] 正常ヒト胎児肝細胞の CYP3A 発現に対する擬似低酸素誘導化合物の効果. (2010)
  • Author(s): 青沼安希子,鈴木英二,中村克徳,松永民秀,大森栄.
  • Organizer: 第20回日本病院薬剤師会東海ブロック学術大会・平成22年度 日本薬学東海支部例会
  • Place of Presentation: 静岡市
  • Year and Date: 2010-11-28
• [Presentation] サルES細胞の肝細胞への分化と薬物動態研究 (2010)
  • Author(s): 丸山順也,坂本栄,松永民秀,中村克徳,菊池伸次,大森栄
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮市
  • Year and Date: 2010-10-09
• [Presentation] ヒトES由来肝細胞のCYPIA誘導剤検出系としての評価 (2010)
  • Author(s): 土屋広行,松永民秀,中村克徳,市川比奈子,佐々木克典,大森栄
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮市
  • Year and Date: 2010-10-09
• [Presentation] 遺伝子多型を考慮したサリドマイド適正使用の試み. シンポジウム 20 病院薬剤師による薬物治療個別化への遺伝子情報の活用 (2010)
  • Author(s): 中村克徳,松澤直樹,大森 栄
  • Organizer: 第20回日本医療薬学会年会,シンポジスト
  • Place of Presentation: 千葉市
• [Presentation] 腎細胞癌患者におけるスニチニブ血中濃度と副作用の相関性. (2010)
  • Author(s): 坡下真大,勝山義彦,松澤直樹,井上博夫,栗崎功己,田辺智明,中村克徳,百瀬泰行,西沢 理,大森栄.
  • Organizer: 第20回日本医療薬学会年会
  • Place of Presentation: 千葉市
• [Presentation] ビタミン K 代謝の個人差と血栓塞栓症発症リスク因子の解析. (2010)
  • Author(s): 中村克徳, 大森栄
  • Organizer: 2010年度中部乳酸菌研究会
  • Place of Presentation: 松本市
• [Presentation] サル ES 細胞の肝細胞への分化と薬物動態研究 (DIFFERENTIATION OF MONKEY EMBRYONIC STEM CELLS TO HEPATOCYTES AND PHARMACOKINETIC STUDIES). (2010)
  • Author(s): 丸山順也, 坂本栄, 松永民秀, 中村克徳, 菊池伸次, 大森栄
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮市
• [Presentation] ヒト ES 由来肝細胞の CYP1A 誘導剤検出系としての評価(EVALUATION OF HUMAN EMBRYONIC STEM CELLS- DERIVEDHEPATOCYTES TO DETECTION SYSTEM OF CYPIA INDUCER). (2010)
  • Author(s): 土屋広行, 松永民秀, 中村克徳, 市川比奈子, 佐々木克典, 大森栄
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮市
• [Presentation] CYP2C19 遺伝子多型によるサリドマイド体内動態変化に関する研究. (2010)
  • Author(s): 松澤直樹,中村克徳,百瀬泰行,松永民秀,松田正之,大森 栄
  • Organizer: 第37回日本トキシコロジー学会学術年会
  • Place of Presentation: 宜野湾市
• [Presentation] HPLC-UV 検出器を用いた Sunitinib および活性代謝物N-desethylsunitinib 血中濃度測定法の確立と臨床応用. (2010)
  • Author(s): 勝山善彦,坡下真大,松澤直樹,中村克徳,西澤 理,大森 栄.
  • Organizer: 第27回日本 TDM 学会学術大会
  • Place of Presentation: 札幌市
• [Book] 薬物代謝学医療薬学・医薬品開発の基礎として第3版2.薬物の代謝反応 (2010)
  • Author(s): 大森栄(分担執筆)
  • Total Pages: 26
  • Publisher: 東京化学同人
• [Remarks]
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/department/master/i-pharm/results.html
• [Remarks]
  • URL: http://www.shinshu-u.ac.jp/graduate/medicine/master/m-science/yakuzai.html
• [Remarks]
  • URL: http://www.shinshu-u.ac.jp/graduate/medicine/doctoral/m-science/rinsyo.html