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In silico screening and characterization of modulators of the unfolded protein response (UPR)

Research Project

Project/Area Number 20790217
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionJapanese Foundation For Cancer Research

Principal Investigator

SAITO Sakae  Japanese Foundation For Cancer Research, 癌化学療法センター, 研究員 (20335491)

Research Collaborator TOMIDA Akihiro  (財)癌研究会, 癌化学療法センター, 部長 (40251483)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords創薬 / 癌 / 分子標的薬 / 小胞体ストレス / マイクロアレイ / 抗がん剤
Research Abstract

The unfolded protein response (UPR) is a homeostatic response in mammalian cells that allows cells to adapt to environmental changes and physiological stresses. The UPR has been recently associated with several human diseases, and UPR activation results in tumor malignancies and anti-tumor drug resistance in poorly vascularized solid tumors. Thus, disrupting the UPR is a promising target for cancer treatments. In the present study, we identified novel UPR-modulatory compounds by in silico screening using gene expression profiles. We demonstrated that these compounds inhibited UPR activation and caused selective and massive killing of cancer cells during glucose deprivation stress.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (13 results)

All 2010 2009 2008

All Journal Article (7 results) (of which Peer Reviewed: 4 results) Presentation (5 results) Book (1 results)

  • [Journal Article] Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions2010

    • Author(s)
      Naomi Haga, Sakae Saito, Yoshinori Tsukumo, Junko Sakurai, Aki Furuno, Takashi Tsuruo, Akohiro Tomida
    • Journal Title

      Cancer Science Vol.101,No.5

      Pages: 1125-1132

    • NAID

      10026591912

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel endoplasmic reticulum export signal: proline at the +2-position from the signal peptide cleavage site2009

    • Author(s)
      Yoshinori Tsukumo, Satomi Tsukahara, Sakae Saito, Takashi Tsuruo, Akihiro Tomida
    • Journal Title

      J Biol Chem. Vol.284,No.40

      Pages: 27500-27510

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation2009

    • Author(s)
      Sakae Saito, Aki Furuno, Junko Sakurai, Asami Sakamoto, Hae-Ryong Park, Kazuo Shin-ya, Takashi Tsuruo, Akihiro Tomida
    • Journal Title

      Cancer Research Vol.69,No.10

      Pages: 4225-4234

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] がんにおける小胞体ストレス-UPRを標的とした抗がん剤の開発2009

    • Author(s)
      齋藤さかえ, 冨田章弘
    • Journal Title

      最新医学 64巻

      Pages: 242-250

    • Related Report
      2009 Final Research Report
  • [Journal Article] 小胞体ストレス応答を標的とした癌治療2009

    • Author(s)
      齋藤さかえ, 冨田章弘
    • Journal Title

      実験医学 27巻,2号

      Pages: 298-304

    • Related Report
      2009 Final Research Report
  • [Journal Article] Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.2009

    • Author(s)
      Sakae Saito, et. Al.
    • Journal Title

      Cancer Research 69

      Pages: 4225-4234

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 小胞体ストレスとがん治療2008

    • Author(s)
      齋藤さかえ, 冨田章弘
    • Journal Title

      Cancer Frontier 10巻

      Pages: 26-31

    • NAID

      40016270403

    • Related Report
      2009 Final Research Report
  • [Presentation] Gene expression -based analysis identifies the unfolded protein response as a target for selective cancer cell killing2010

    • Author(s)
      Sakae Saito, et, al.
    • Organizer
      8th AACR-JCA Joint Conference
    • Place of Presentation
      Hilton Waikoloa Village (Hawaii, U.S. )
    • Year and Date
      2010-02-08
    • Related Report
      2009 Final Research Report
  • [Presentation] Gene expression-based analysis identifies the unfolded protein response as a target for selective cancer cell killing2010

    • Author(s)
      齋藤さかえ, 他
    • Organizer
      8th AACR-JCA Joint Conference
    • Place of Presentation
      Hilton Waikoloa Village(Hawaii, USA)
    • Year and Date
      2010-02-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] 遺伝子発現プロファイルを利用した小胞体ストレス応答制御薬剤の探索2009

    • Author(s)
      齋藤さかえ, 他
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] インシリコスクリーニングによる小胞体ストレス応答制御薬剤の探索2009

    • Author(s)
      齋藤さかえ, 他
    • Organizer
      第13回日本がん分子標的治療学会学術集会
    • Place of Presentation
      ホテルクレメント徳島(徳島県)
    • Year and Date
      2009-06-26
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] インシリコスクリーニングによる小胞体ストレス応答制御薬剤の探索2009

    • Author(s)
      齋藤 さかえ、他
    • Organizer
      第13回日本がん分子標的治療学会学術集会
    • Place of Presentation
      ホテルクレメント徳島
    • Year and Date
      2009-06-26
    • Related Report
      2008 Annual Research Report
  • [Book] マイクロアレイを用いた遺伝子発現解析2009

    • Author(s)
      齋藤さかえ, 冨田章弘
    • Publisher
      金芳堂
    • Related Report
      2009 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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