Development of a novel therapy for cancer cachexia targeting the purine metabolism in the central nervous system

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15037
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: National Agriculture and Food Research Organization (2019); National Cancer Center Japan (2018)
• Principal Investigator: Uzu Miaki 国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門, 研究員 (20802896)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: がん悪液質 / プリンヌクレオチド代謝 / アストロサイト / 炎症 / コラーゲンビトリゲル膜

Outline of Final Research Achievements

<Research Achievement during the 1st year> Cancer cachexia model was prepared by subcutaneous injection of 85As2 cells (a gastric cancer cell line) into BALB/cAJcl-nu/nu nude mice. The model mice started to present cachexic symptoms such as a decrease of body weight and food intake 2 weeks after 85As2 inoculation. Therefore, the alteration in the central nervous system was investigated at that time point. It was revealed that the purine nucleotide metabolism and the expression of astrocytic marker was increased in the forebrain of the model mice.
<Research Achievement during the 2nd year> A blood-brain barrier model composed of astrocytes and brain microvascular endothelial cells was fabricated utilizing a collagen vitrigel membrane. The model showed high responsiveness to inflammatory stimuli, suggesting that this model is useful for the investigation of the role of astrocytes in the pathogenesis of cancer cachexia.

Free Research Field

薬理系薬学

Academic Significance and Societal Importance of the Research Achievements

本研究は、未だに有効な治療法の確立されていないがん悪液質において、中枢神経系のプリンヌクレオチド代謝やアストロサイトの活性制御が新規治療法となり得ることを明らかにした。また、本研究において新たに構築した血液脳関門モデルはがん悪液質の迅速なスクリーニングを可能とすることが期待される。以上より、本研究はがん緩和医療の発展に貢献し得ると考えられる。