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2014 Fiscal Year Final Research Report

The study of drug development targeting the stress response in the tumor microenvironment for the treatment of refractory cancer

Research Project

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Project/Area Number 24390029
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionGifu Pharmaceutical University

Principal Investigator

HIDEKO Nagasawa  岐阜薬科大学, 薬学部, 教授 (90207994)

Co-Investigator(Kenkyū-buntansha) OKUDA Kensike  岐阜薬科大学, 薬学部, 准教授 (00311796)
HIRAYAMA Tasuku  岐阜薬科大学, 薬学部, 助教 (10600207)
MORISHIGE Kenichiro  岐阜大学, 医学研究科, 教授 (90283788)
Project Period (FY) 2012-04-01 – 2015-03-31
Keywordsがん微小環境 / 低栄養 / 低酸素 / 二価鉄 / 酸化ストレス / 小胞体ストレス / 合成致死
Outline of Final Research Achievements

1) A study of structure-activity relationship of biguanides was conducted to explore selective antitumor agents blocking adaptive stress responses in the tumor microenvironment. We succeeded in synthesis of new derivatives which represented an improvement over a lead compound, phenformin in selective cytotoxicity under glucose deprivation, suppression HIF-1- and UPR-related protein expression, and angiogenesis inhibition. We also performed molecular modification to explore a probe molecule for target identification of the compound. 2) A novel iron(II)-specific fluorescent probe was developed to visualize the oxidative stress in tumor microenvironment. We found that iron(II) increased in tumor hypoxia by a fluorescence imaging study. 3) To explore antitumor substances targeting cancer metabolic reprogramming, we studied effects of extracts and fractions from Scutellaria barbata on the energy metabolism of cancer cells.

Free Research Field

創薬化学

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Published: 2016-06-03  

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