2019 Fiscal Year Final Research Report
The search for therapeutic targets of chemotherapy-induced delayed nausea
Project/Area Number |
17K08951
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Applied pharmacology
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Research Institution | Osaka University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 抗悪性腫瘍薬 / 悪心 / 嘔吐 / ヒスタミン / オレキシン / 食欲不振 / マウス / パイカ行動 |
Outline of Final Research Achievements |
Cancer chemotherapy often induces anorexia, nausea and vomiting. Antiemetic agents are effective in inhibiting vomiting, but patients still experience nausea and anorexia. We previously reported that chemotherapeutic agent-induced nausea and anorexia are associated with an increase of inflammatory cytokines. Other studies demonstrated that antagonism of the histamine H4 receptor is known to have inhibition of production of Tumor necrosis factor (TNF)-α and that the central administration of TNF-α impairs the orexinergic system that excites the histaminergic system. In a series of experiments, we found that activation of the orexinergic and histaminergic pathway is involved in the therapeutic effect of an H4 receptor antagonist against cisplatin-induced nausea and anorexia. We considered that ligands with H4 receptor antagonistic activity together with histamine H3 receptor inverse agonistic activity can serve as treatments for chemotherapeutic agent-induced nausea and anorexia.
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Free Research Field |
薬理学
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Academic Significance and Societal Importance of the Research Achievements |
抗悪性腫瘍薬でがん治療を受ける患者にとって、日常生活に影響する程の悪心・嘔吐・食欲不振などの不快感を経験した患者は次の治療クールでも再び発症するものなら、がん治療そのものを拒否するまで考えるようになるなど、治療継続率を左右するアドヒアランスに非常に影響する問題となる。今回得られた研究成果により、抗悪性腫瘍薬による遅発性悪心など不快感は「末梢での炎症反応」と「睡眠リズム障害に随伴する病態」によるものと判明するに至った。これにより、ヒスタミン受容体リガンドやオレキシン受容体リガンドががん治療にともなう有害作用の治療薬として新しい臨床応用の可能性の端緒を開くものになった。
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