| Project/Area Number |
17K09466
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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 |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
Yoshida Michihiro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (20636328)
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| Co-Investigator(Kenkyū-buntansha) |
内藤 格 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30527750)
志村 貴也 名古屋市立大学, 医薬学総合研究院(医学), 講師 (90405192)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | オートタキシン / 膵癌 / 分子標的治療 / 腹膜播種 / 腹膜播種モデル / オートタキシン阻害剤 / 動物実験 / 血中濃度測定 / オートタキシン阻害薬の膵癌増殖への影響 / 膵臓癌 / 新規分子標的 |
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| Outline of Final Research Achievements |
Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX-LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. Many findings obtained through this study demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC.
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| Academic Significance and Societal Importance of the Research Achievements |
最も予後不良な癌腫である膵癌に対し、今回の研究を通じてオートタキシンの新たなバイオマーカーおよび治療ターゲットとしての可能性を解明した。今回の研究期間中に抗癌剤耐性獲得に対する貢献も明らかとなっており、今後この分野でのさらなる研究の推進により、オートタキシン・LPAを中心に、臨床応用に直結するような新たな治療薬の誕生に期待したい。
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