2023 Fiscal Year Final Research Report
Examination of the effect of neurokinin 1 receptor splicing variant expression on cancer-related thrombosis
| Project/Area Number |
21K08932
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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 55050:Anesthesiology-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
東 俊晴 国立研究開発法人国立国際医療研究センター, その他部局等, 医師 (60284197)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 単球 / 組織因子 / アポトーシス / 凝固活性小胞 |
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| Outline of Final Research Achievements |
The molecular mechanisms of tissue factor release from human monocytic cells were analyzed. We confirmed that activation of the thrombin receptor PAR1 contributes to tissue factor release. Inhibitors for neurokinin-1 receptor (NK1R) suppressed tissue factor release from human monocytic cells; however, these inhibitors did not act as competitive inhibitors for PAR1, implicating that NK1R is involved in tissue factor release through an autocrine/paracrine mechanism. It was confirmed that not the full-length NK1R expressed in activated cells, but the short form NK1R expressed in resting (non-activated) human monocytic cells, is involved in this process. Aprepitant, a clinically available NK1R inhibitor, was able to suppress tissue factor release from human monocytic cells, suggesting its potential therapeutic effect in conditions related to thrombosis enhancement by leukocytes.
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| Free Research Field |
麻酔学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、臨床使用が可能なNK1R阻害薬であるアプレピタントはヒト単球系細胞の組織因子放出を抑制可能であったため，白血球による血栓強化が関連する病態への治療効果が期待できると考えられた．がん患者数は増加する一方，医療の進歩によりがん患者の生存率は向上している．がん患者の死因のうち，がんの進展に次いで多いのが血栓塞栓症と言われており，治療が順調に進んでいたとしても，血栓塞栓症の併発による活動度の低下は予後に大きく影響する．薬剤による予防戦略の提案を行うことで，がん患者の予後改善に大きな貢献ができると期待される．
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