Establishment of cellular models for investigating of cancer chronotherapy

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590645
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Saitama Medical University
• Principal Investigator: IKEDA Masaaki 埼玉医科大学, 医学部, 教授 (80232198)
• Co-Investigator(Kenkyū-buntansha): KUMAGAI Megumi 埼玉医科大学, 医学部, 助手
• Project Period (FY): 2011 – 2013
• Keywords: 概日リズム / 時計遺伝子 / 抗癌剤 / 時間治療 / 腫瘍細胞 / プロモーター / ルシフェラーゼ

Research Abstract

Chronotherapy for cancer has improved therapy for cancer. Dosing time of anticancer drugs is appeared to be influencing to effectiveness and toxicity of chemotherapy for cancer. But no precise mechanisms of cancer chronotherapy are elucidated, so far. To clarify the molecular basis of chronotheray for cancer, we have been trying to establish a cell model system for chronotherapy. Irinotecan is an agent for targeting topoisomerase I and inhibit its enzymatic activity. It is known that genes of irinotecan related factors, such as topoisomerase I, ABCB1 and UGTA1 are oscillated in circadian manner. We cloned promoter region of topoisomerase I, ABCB1 and UGTA1 and constructed reporters using multicolor luciferase system, established by Nakajima et al. The application of these reporters to this study will be helpful to understand the coordination of clock genes and irinotecan related factors in cancer cells and the reactions to the treatment of iriotecan.

Research Products

• [Journal Article] A Novel Splicing Variant of Peroxisome Proliferator-Activated Receptor-γ(Pparγ1sv) Cooperatively Regulates Adipocyte Differentiation with Pparγ2 (2013)
  • Author(s): Takenaka Y, Inoue I, Nakano T, Shinoda Y, Ikeda M, Awata T, SKatayama S
  • Journal Title: PloS ONE Volume: 8(6) Pages: e65583
  • Peer Reviewed
• [Journal Article] In vitro circadian period is associated with circadian/sleep preference (2013)
  • Author(s): Hida A, Kitamura S, Ohsawa Y, Enomoto M, Katayose Y, Motomura Y, Moriguchi Y, Nozaki K, Watanabe M, Aritake S, Higuchi S, Kato M, Kamei Y, Yamazaki S, Goto Y, Ikeda M, Mishima K
  • Journal Title: Scientific Reports Volume: 3 Pages: 2074
  • Peer Reviewed
• [Journal Article] Real-Time Analysis of the Circadian Oscillation of the Rev-ErbβPromoter (2013)
  • Author(s): Yang F, Inoue I, Kumagai M, Takahashi S, Nakajima Y, Ikeda M
  • Journal Title: J Atheroscler Thromb Volume: 20 Pages: 267-76
  • Peer Reviewed
• [Journal Article] A Dual-Color Luciferase Assay System Reveals Circadian Resetting of Cultured Fibroblasts by Co-Cultured Adrenal Glands (2012)
  • Author(s): Noguchi T, Ikeda M, Ohmiya Y, Nakajima Y
  • Journal Title: PLoS ONE Volume: 7(5) Pages: e37093
  • DOI: 10.1371/journal.pone.0037093
  • Peer Reviewed
• [Presentation] Role of HIF1αfactor on mammalian circadian system (2014)
  • Author(s): 池田正明, 熊谷恵, 上野宗久, 岡部尚志
  • Organizer: シンポジウム:環境適応と時計シグナル～環境・ストレスへの応答系としての概日システム.The 91st Meeting for the Physiological Society of Japan
  • Place of Presentation: Kagoshima
  • Year and Date: 20140316-18
• [Presentation] The impact of HIF1α/ARNT on the Per2 transcriptional activity in renal cancer cells (2013)
  • Author(s): Okabe T, Kumagai M, Ikeda M, Shirotake S, Kodaira K, Oyama M, Ueno M
  • Organizer: AUA Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20130504-08
• [Presentation] Understanding the circadian signalosome to establish a basis for cancer chronotherapy (2013)
  • Author(s): Ikeda M
  • Organizer: 2nd Swiss Chronobiology Meeting
  • Place of Presentation: Fribourg, Swiss
  • Year and Date: 2013-09-05
• [Presentation] Understanding the circadian signalosome to establish a basis for cancer chronotherapy. Symposium:"Circadian Signalosome;Capturing Chrono-biosignal, toward Chrono-Molecular Medicine" (2013)
  • Author(s): Ikeda, M
  • Organizer: The 90th Meeting for the Physiological Society of Japan
  • Place of Presentation: Funabori, Japan
  • Year and Date: 2013-03-29
• [Presentation] 腎癌細胞におけるHIF1α/ARNTによるPer2転写活性の促進 (2013)
  • Author(s): 岡部尚志, 熊谷恵, 城武卓, 古平喜一郎, 小山政史, 上野宗久, 池田正明
  • Organizer: 第22回泌尿器科分子・細胞研究会
  • Place of Presentation: 高知県
  • Year and Date: 2013-03-09
• [Presentation] 腫瘍の時間治療の分子基盤確立を目指して−トポイソメラーゼIの発現動態の解析を中心としてー (2012)
  • Author(s): 熊谷恵, 岡部尚志, 上野宗久, 池田正明
  • Organizer: 第14回応用薬理シンポジウム
  • Place of Presentation: 甲府市
  • Year and Date: 20120903-04
• [Presentation] 末梢時計機能は個人の概日/睡眠特性を反映する (2012)
  • Author(s): 肥田昌子, 北村真吾, 片寄泰子, 榎本みのり, 大澤要介, 渡邊真紀子, 野崎健太郎, 有竹清夏, 樋口重和, 加藤美恵, 守善也, 亀井雄一, 池田正明, 三島和夫
  • Organizer: 第35回日本神経科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2012-09-18
• [Presentation] HIF1α/ARNT may affect the Per2 transcriptional activity (2012)
  • Author(s): Okabe T, Kumagai M, Shirotake S, Kodaira K, Oyama M, Ueno M, Ikeda M
  • Organizer: 29th Japan-Korea Urological Congress
  • Place of Presentation: 鹿児島県
  • Year and Date: 2012-09-15
• [Presentation] 末梢リズムは個人の睡眠特性・生物時計特性を反映する (2012)
  • Author(s): 肥田昌子, 北村真吾, 大澤要介, 片寄泰子, 野崎健太郎, 榎本みのり, 有竹清夏, 樋口重和, 加藤美恵, 亀井雄一, 池田正明, 三島和夫
  • Organizer: 第19回日本時間生物学会
  • Place of Presentation: 札幌市
  • Year and Date: 2012-09-15
• [Presentation] Molecular mechanism underlying resetting of the circadian oscillation of Bmal1 (2012)
  • Author(s): Ikeda M
  • Organizer: 1st Swiss Chronobiology Meeting
  • Place of Presentation: Fribourg, Swiss
  • Year and Date: 2012-09-06
• [Presentation] Effects of USF1 on the circadian oscillation of clock genes (2011)
  • Author(s): Kumagai M, Piao C, Yang F, Chiba Y, Nakajima Y, Ikeda M
  • Organizer: XII Congress of the European Biological Rhythms Society
  • Place of Presentation: Oxford, England
  • Year and Date: 20110820-26
• [Remarks]
  • URL: http://www.saitama-med.ac.jp/uinfo/seiri2/Masaaki%20Ikeda2.html