The development of a novel mechanism therapeutic drug for rare intractable inflammatory diseases
Project/Area Number |
24249033
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied pharmacology
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Research Institution | Tohoku University |
Principal Investigator |
MIYATA Toshio 東北大学, 医学(系)研究科(研究院), 教授 (10222332)
|
Co-Investigator(Kenkyū-buntansha) |
DAN Takashi 東北大学, 医学系研究科, 准教授 (00512451)
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Co-Investigator(Renkei-kenkyūsha) |
ICHIMURA Atsuhiko 東北大学, 医学系研究科, 非常勤講師 (10609209)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2014: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2013: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2012: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
|
Keywords | 薬理学 / 生理活性 / 生体分子 |
Outline of Final Research Achievements |
The study was performed to specify an adaptation of PAI-1 inhibitors which were effective and safe against rare intractable inflammatory diseases. Finding bone marrow regeneration promoted by PAI-1 inhibitors in umbilical cord blood transplantation, led the doctor’s investigated phase 1 clinical trials. Non-clinical safety studies were carried out from the discovery of the efficacy in multiple sclerosis models. Furthermore, as a result of PAI-1 inhibition in ovarian carcinoma cell lines, cell proliferation was suppressed by increasing the apoptosis and the G2/M phase cells. Moreover, the evaluation of the effects of PAI-1 inhibitors in bleomycin-induced lung fibrosis models, it was found that the lung hydroxyproline content was reduced significantly.
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis.2015
Author(s)
Kobayashi N, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K, Manabe S, Hara S, Takashima Y, Dan T, Pastan I, Miyata T, Kurihara H, Matsusaka T, Reiser J, Nagata M.
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Journal Title
Am J Physiol Renal Physiol
Volume: 308・6
Issue: 6
Pages: F614-F626
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer.2015
Author(s)
Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T, Yaegashi N.
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Journal Title
Cancer Biol Ther.
Volume: 16
Pages: 253-260
Related Report
Peer Reviewed
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[Journal Article] PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice.2014
Author(s)
Eren M, Boe AE, Murphy SB, Place AT, Nagpal V, Morales-Nebreda L, Urich D, Quaggin SE, Budinger GR, Mutlu GM, Miyata T, Vaughan DE.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 13
Issue: 19
Pages: 7090-7095
DOI
Related Report
Peer Reviewed
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[Journal Article] A smoll molecule inhibitor to plasminogen activator inhibitor 1 inhibits macrophage migration.2013
Author(s)
Ichimura A, Matsumoto S, Suzuki S, Dan T, Yamaki S, Sato Y, Kiyomoto H, Ishii N, Okada K, Matsuo O, Hou FF, Vaughan DE, van Ypersele de Strihou S, Miyata T.
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 33
Issue: 5
Pages: 935-942
DOI
Related Report
Peer Reviewed
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[Journal Article] Kidney failure: aims for the next 10 years and barriers to success2013
Author(s)
Remuzzi G, Benigni A, Finkelstein FO, Grunfeld JP, Joly D, Katz I, Liu ZH, Miyata T, Perico N, Rodriguez-Iturbe B, Antiga L, Schaefer F, Schieppati A, Schrier RW, Tonelli M
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Journal Title
Lancet
Volume: 382
Issue: 9889
Pages: 353-362
DOI
Related Report
Peer Reviewed
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[Journal Article] Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice2012
Author(s)
Yoshihiko Tashiro, Chiemi Nishida, Kaori Sato-Kusubata, Makiko Ohki-Koizumi, Makoto Ishihara, Aki Sato, Ismael Gritli, Hiromitsu Komiyama, Yayoi Sato, Takashi Dan, Toshio Miyata, Ko Okumura, Yuichi Tomiki, Kazuhiro Sakamoto, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
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Journal Title
Blood
Volume: 119
Issue: 26
Pages: 6382-6393
DOI
Related Report
Peer Reviewed
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