Basic research aimed at establishing effective chemotherapy for malignant meningioma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16550
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yamagata University
• Principal Investigator: SANOMACHI TOMOMI 山形大学, 医学部, 客員研究員 (20812465)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 悪性髄膜腫 / dCK / hENT1 / ゲムシタビン

Outline of Final Research Achievements

Malignant meningioma is an aggressive tumor with poor prognosis even after treatment with standard therapies of surgical resection and radiation therapy. Since there is no effective systemic therapy, the development of novel drugs for the treatment is needed. We have reported that gemcitabine, an anti-metabolite, is highly effective in malignant meningioma cells; however, its mechanism remains unknown. In this study, I demonstrated that the expression of hENT1 and dCK that help activate gemcitabine intracellularly was positively correlated to malignancy (WHO grades) and gemcitabine sensitivity in meningioma cell lines and that their expression was higher in high-grade meningioma tissues. In malignant meningioma cells, suppression of the expression and function of hENT1 and dCK decreased sensitivity to gemcitabine, suggesting that these molecules play an important role in gemcitabine sensitivity of high-grade meningioma cells.

Free Research Field

悪性髄膜腫

Academic Significance and Societal Importance of the Research Achievements

本研究では悪性髄膜腫のゲムシタビン高感受性の機序を解明するためにdCKとhENT1に着目し検討を行った。結果、dCKとhENT1がゲムシタビンの感受性に寄与していることが明らかとなり、ゲムシタビンの臨床応用を支持するとともに、それら分子が将来的に抗悪性腫瘍薬への反応性の予測因子として臨床応用可能となる可能性が考えられた。