| Project/Area Number |
16H05287
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤澤 浩一 山口大学, 大学院医学系研究科, 助教 (00448284)
高見 太郎 山口大学, 大学院医学系研究科, 講師 (60511251)
佐伯 一成 山口大学, 医学部附属病院, 助教 (60634756)
山本 直樹 山口大学, 大学教育機構, 准教授 (90448283)
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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 |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | 肝細胞癌 / 膵癌 / 鉄キレート剤 / deferasirox / deferoxamine / 癌 |
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| Outline of Final Research Achievements |
We have demonstrated the efficacy of deferoxamine (DFO) in hepatocellular carcinoma (HCC). Recently, deferasirox (DFX), a new oral iron chelator, has been developed. We evaluated the effects of DFX against HCC and pancreatic cancer which belong to refractory digestive system cancers. DFX inhibited the proliferation of hepatoma or pancreatic cell lines in a dose-dependent manner. In vivo, DFX treatment significantly suppressed the development of liver or pancreatic tumors. The combination therapy using DFX and gemcitabine against pancreatic cancer has significant anticancer effects though the suppression of ribonucleotide reductase. As the efficacy of DFX for advanced HCC patients in the pilot clinical study could not demonstrated, we considered an arterial infusion of DFO as a clinical application in advanced HCC patients. In addition, we found the mechanism for DFO resistance, which has the possibility of a novel treatment strategy for DFO.
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| Academic Significance and Societal Importance of the Research Achievements |
肝癌・膵癌ともに、他の消化器癌に比べ、難治かつ予後不良である。また日本は超高齢化社会を迎えており、両者とも高齢かつ進行癌で発見される患者が多い現状がある。進行癌の標準治療は化学療法である。肝癌の分子標的治療薬は高齢者にも導入可能だが、肝機能不良例には適応がない。一方、膵癌の化学療法は副作用が強く、高齢者には厳しい。本研究は、経口鉄キレート剤DFXにて抗腫瘍効果を検証した。鉄キレート剤は、抗癌剤でない故、高齢者にも優しい治療である。肝癌ではDFOの新たな治療戦略を、膵癌では抗癌剤併用DFX治療を提言でき、独創性もあり、意義のある研究と考える。
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