A promising ovarian cancer therapy in the application of a Band-Aid type peptide-based treatment
| Project/Area Number |
16K11148
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nara Medical University |
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Principal Investigator |
Yoshida Shozo 奈良県立医科大学, 医学部, 研究員 (40347555)
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| Co-Investigator(Kenkyū-buntansha) |
山田 有紀 奈良県立医科大学, 医学部, 助教 (20588537)
小林 浩 奈良県立医科大学, 医学部, 教授 (40178330)
栗田 典之 豊橋技術科学大学, 工学(系)研究科(研究院), 准教授 (40283501)
長安 実加 奈良県立医科大学, 医学部附属病院, 研究員 (80623496)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 卵巣がん / 低分子阻害薬 / 浸潤 / 転移 / 獲得耐性 / 卵巣癌 / 低分子医療薬 / uPA / 阻害剤 / 癌 |
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| Outline of Final Research Achievements |
Recent biochemical experiments have revealed that a variety of proteases play important roles in cancer invasion and metastasis. The receptor for the PA, uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. In the present study, we propose some peptides composed of these important residues and investigate the specific interactions and the binding affinity between uPAR and the peptides at an electronic level, using ab initio molecular simulations. With computational prediction algorithms and structure-based drug design, we identified KG6 that does not enter the pocket of its receptor. KG6 inhibited cancer cell invasion, without affecting cell viability, accompanied by the suppression of ERK-1 phosphorylation and then matrix metalloproteinase (MMP)-9 expression. KG6 did not show the acquired resistance for at least 3 months. These data were also confirmed by animal experiments.
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| Academic Significance and Societal Importance of the Research Achievements |
癌治療としての低分子医薬品としてチロシンキナーゼ、PARP、Rafキナーゼ、MEK、CDK、プロテアソームに対する阻害薬などが開発されている。本邦において使用できる新規分子標的薬は、初回効果を発揮してもほとんどの患者は薬剤耐性獲得により治療効果が減弱するという、低分子医薬品に共通の欠点がある。そこで、我々が得意とする分子シミュレーション法によりペプチドを設計・試作することが可能である。本提案は、獲得耐性を生じにくい低分子医薬品の開発であるが、この技術はキナーゼドメインの鍵穴ポケットにも応用可能であり、他の低分子医薬品へ応用・展開が可能となる。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.2016
Author(s)
Arakawa N, Kobayashi H, Yonemoto N, Masuishi Y, Ino Y, Shigetomi H, Furukawa N, Ohtake N, Miyagi Y, Hirahara F, Hirano H, Miyagi E.
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Journal Title
PLoS One.
Volume: 11
Issue: 10
Pages: e0165609-e0165609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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