| Project/Area Number |
19K17785
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | 血管肉腫 / ISO-HAS / パゾパニブ / VEGFR阻害薬 / 抗IL-17抗体 / 抗L-17抗体 / 抗VEGF抗体 / angiosarcoma / 分子標的薬 |
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| Outline of Research at the Start |
血管肉腫細胞株への抗VEGF阻害抗体単独投与および抗IL-17抗体併用投与で、腫瘍細胞増殖抑制を比較検討する。また当科で樹立した血管肉腫マウスモデルISOS-1（Masuzawa et al. J. Dermatol.Sci.16:91-98,1998）を用いて、がん微小環境が存在するin vivoにおいても腫瘍細胞増殖抑制効果が認められるかについて検討する。
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| Outline of Final Research Achievements |
Pazopanib is a second-line drug for angiosarcoma, but few studies have examined its therapeutic effect in vitro or in vivo. We established mouse models of human angiosarcoma and mouse angiosarcoma, both of which demonstrated suppression of tumor cell growth in the pazopanib-treated group compared to the negative control group. In addition, the cell viability by adding pazopanib using the human angiosarcoma cell line; ISO-HAS, and the human lymphangiosarcoma cell line; Mo-LAS decreased in a concentration-dependent manner, and a tumor growth inhibitory effect was observed.
Regarding the treatment resistance of pazopanib, which is a clinical problem, the involvement of IL-17 in the tumor microenvironment was examined. In the mouse angiosarcoma model, no tumor growth inhibitory effect was observed compared to the pazopanib monotherapy group and the pazopanib + anti-IL-17 antibody combination administration group.
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| Academic Significance and Societal Importance of the Research Achievements |
血管肉腫は悪性南部腫瘍としてパゾパニブが保険適用となったが、実際血管肉腫に対するパゾパニブの治療効果を証明する基礎研究はほとんどなく、その治療効果は不定であった。今回我々は、血管肉腫マウスモデルおよび、血管肉腫細胞株を用いて血管肉腫に対するパゾパニブの効果を証明し得た。実際の臨床課題としては、パゾパニブで得られる無増悪生存率は３ー４ヶ月程度で治療耐性となっていることが予想される。耐性の出現を抑制する併用治療の開発が今後の課題であると考える。
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