The study of drug development targeting the stress response in the tumor microenvironment for the treatment of refractory cancer
| Project/Area Number |
24390029
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| 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 / 創薬化学 / 血管新生 / ERストレス / 血管新生阻害 / がん幹細胞 / 鉄代謝 / 血管新生阻害作用 |
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| 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.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders2015
Author(s)
Hattori Y, Mukaide T, Jiang L, Kotani T, Tsuda H, Mano Y, Sumigama S, Hirayama T, Nagasawa H, Kikkawa F and Toyokuni S.
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 56
Issue: 1
Pages: 57-63
DOI
NAID
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed
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[Presentation] Drug development targeting the adaptive responses of tumor cells to hypoxia and nutrition deprivation in tumor microenvironment2013
Author(s)
Narise, K., Okuda, K., Sakai, T., Hirayama, T., Nagasawa, H.,
Organizer
9th AFMC International Medicinal Chemistry Symosium
Place of Presentation
Taipei
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