| Project/Area Number |
16K10582
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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 |
Digestive surgery
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| Research Institution | Yokohama City University (2017-2018)
Teikyo University (2016) |
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Principal Investigator |
Tanaka Kuniya 横浜市立大学, 医学研究科, 客員教授 (10295503)
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| Co-Investigator(Kenkyū-buntansha) |
松尾 憲一 帝京大学, 医学部, 講師 (10363839)
廣島 幸彦 横浜市立大学, 附属病院, 助教 (60718021)
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肝再生 / 肝切除 / 転移性肝癌 / ALPPS / 門脈塞栓 / ALPPS手術 / 肝再生シグナル |
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| Outline of Final Research Achievements |
A BALB/c mouse model (male, 8e10 weeks old) of liver metastasis labeled by red fluorescent protein was established. Changes in future liver remnant (FLR) volumes, tumor growth activity, and levels of cytokines and growth factors in liver tissues during the treatment period were compared among the models involving ALPPS, portal vein ligation (PVL), or sham operation.
Results: The ratio of the FLR volume to body weight at 24 h after the procedure was greater for ALPPS than for PVL and sham operation. No differences in tumor progression in the FLR were observed at any time point after the procedures. Within the deportalized liver (DL), although tumor progression was observed during a later period after ALPPS (9 days postoperative) and PVL (12 days postoperative), no acceleration of tumor growth after ALPPS was observed in an early period similar to PVL.
Conclusion: ALPPS induces a rapid increase in FLR volume and avoids remnant tumor progression during the early postoperative period.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らはALPPSの臨床データや臨床サンプルの組織像を詳細に検討し、ALPPS術後に急速に増大した残存予定肝細胞の未成熟性が術後肝不全の原因である可能性を指摘した。本研究により、ALPPS術後の固有の肝再生シグナル伝達経路はJak/STAT3が主経路であり、PDK1以下の経路をActivateすることにより、残存予定肝の機能的肝再生を促進できる可能性が示唆された。今後これらの知見を基盤としてさらなる検討を重ねることにより、ALPPSのMortalityを改善することが可能となり、大腸癌肝転移全体の治療成績の改善が見込まれる。
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