Development of hybrid therapy using iron chelators and regenerative therapy for advanced hepatocellular carcinoma with decompensated liver cirrhosis
| Project/Area Number |
20K08358
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Takami Taro 山口大学, 大学院医学系研究科, 教授 (60511251)
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| Co-Investigator(Kenkyū-buntansha) |
山本 直樹 山口大学, 教育・学生支援機構, 教授 (90448283)
松本 俊彦 山口大学, 大学院医学系研究科, 講師 (70634723)
藤澤 浩一 産業医科大学, 産業生態科学研究所, 教授 (00448284)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝硬変症 / 肝細胞癌 / 鉄キレート剤 / 間葉系幹細胞 / 骨髄間葉系幹細胞 / 骨髄細胞 |
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| Outline of Research at the Start |
非代償性肝硬変症を背景に持つ進行肝細胞癌に対して「抗癌作用としての鉄キレート肝動注治療」と「肝機能サポートとしての培養骨髄MSC肝動脈投与療法」のハイブリット療法は生命予後を改善させるという作業仮説を肝硬変合併肝癌モデルで検証する。
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| Outline of Final Research Achievements |
In rats fed with choline-deficient L-amino acid-defined diet, developing cirrhosis with liver tumors, iron chelator treatment tended to suppress the tumor development, but further investigation of the effects of MSCs including MSC passages was necessary. On the other hand, in the iron chelator-resistant cancer cell line, an increase in lactate production was caused by a metabolic shift to the glycolytic pathway, showing that the anti-tumor effect of iron chelator was enhanced when the lactate concentration in the cancer microenvironment was lower. Therefore, these results suggest that MSCs may have a novel effect of suppressing the glycolytic shift of hepatocellular carcinoma cells in liver cirrhosis.
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| Academic Significance and Societal Importance of the Research Achievements |
肝臓領域のアンメット・メディカルニーズのひとつは「分子標的薬投与ができない肝予備能不良例(Child-Pugh B)における切除不能進行肝細胞癌」である。今回、ラット肝発癌肝硬変モデルおよび細胞共培養系により鉄キレート剤の抗腫瘍メカニズムを検証することができ、新たなMSC抗腫瘍機序を想起することができ、今後のハイブリッド療法の開発につながる。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Double cancer of primary hepatic angiosarcoma and hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Hepatol Res. 2023 Feb 24.2023
Author(s)
Yamauchi Y, Saeki I, Yamasaki T, Egusa M, Nishiyama N, Fujioka T, Kawamoto D, Nishimura T, Tanabe N, Oono T, Matsumoto T, Ishikawa T, Marumoto Y, Matsukuma S, Shindo Y, Tokumitsu Y, Yoshimine S, Murakami J, Tanaka T, Kimura S, Hoshii Y, Hamano K, Nagano H, Takami T.
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Journal Title
Hepatol Res.
Volume: -
Issue: 7
Pages: 681-686
DOI
Related Report
Peer Reviewed
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[Journal Article] Diagnostic criteria for acute-on-chronic liver failure and related disease conditions in Japan2022
Author(s)
Mochida S, Nakayama N, Terai S, Yoshiji H, Shimizu M, Ido A, Inoue K, Genda T, Takikawa Y, Takami T, Kato N, Abe M, Abe R, Inui A, Ohira H, Kasahara M, Chayama K, Hasegawa K, Tanaka A.
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Journal Title
Hepatol Res.
Volume: 52(5)
Issue: 5
Pages: 417-421
DOI
Related Report
Peer Reviewed
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[Journal Article] Long-term efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A multicenter retrospective study2022
Author(s)
Kawaratani H, Kondo Y, Tatsumi R, Kawabe N, Tanabe N, Sakamaki A, Okumoto K, Uchida Y, Endo K, Kawaguchi T, Oikawa T, Ishizu Y, Hige S, Takami T, Terai S, Ueno Y, Mochida S, Takikawa Y, Torimura T, Matsuura T, Ishigami M, Koike K, Yoshiji H
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Journal Title
J Clin Med.
Volume: 11(6)
Issue: 6
Pages: 1571-1571
DOI
Related Report
Peer Reviewed / Open Access
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