Basic research aimed at developing new drug therapies for malignant meningioma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17949
• 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, 医員 (20812465)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ゲムシタビン / 電離放射線 / 細胞老化 / 活性酸素種 / 放射線増感剤

Outline of Final Research Achievements

Development of a new treatment method for malignant meningioma, which has a poor prognosis, is desired. Previously, we reported that gemcitabine (Gem) was capable of long-term control of high-grade meningiomas in mouse models. Furthermore, we focused on dCK and hENT1 which are molecules involved in Gem sensitivity, and clarified the mechanism of Gem hypersensitivity in malignant meningiomas. Malignant meningioma is a disease that requires postoperative adjuvant radiation therapy, but the tumor suppressive effect of Gem in combination with ionizing radiation (IR) has not been investigated. Therefore, we investigated these interactions. By inducing aging, Gem sensitized malignant meningioma cells to IR, enhanced intracellular reactive oxygen species production by IR, and suppressed cell proliferation. In conclusion, the possibility of Gem as a radiosensitizer candidate for malignant meningioma was suggested.

Free Research Field

悪性髄膜腫

Academic Significance and Societal Importance of the Research Achievements

予後不良な疾患である悪性髄膜腫の新規候補薬剤としてゲムシタビン（Gem）高感受性の機序を解明するために分子dCKとhENT1に着目し、dCKとhENT1がGemの感受性を経て髄膜腫患者におけるより強い腫瘍細胞増殖活性並びにより短い予後に寄与していることが明らかとなった。悪性髄膜腫へのGemの有用性を支持すると共にそれら分子が将来的に抗悪性腫瘍薬への反応性予測因子となる可能性が考えられた。また悪性髄膜腫の術後補助放射線療法に着目し未検討であったGemとIRの併用効果を調べた。結果としてGemはIRの効果を高める放射線増感剤となりうることも示唆され、更にGemの臨床応用性を高める結果が示唆された。