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2018 Fiscal Year Final Research Report

The correlation between introducing necroptosis on malignant mesothelioma and chemoresistance

Research Project

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Project/Area Number 17K16040
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionChiba University

Principal Investigator

ISHIWATA TSUKASA  千葉大学, 医学部附属病院, 医員 (50791480)

Project Period (FY) 2017-04-01 – 2019-03-31
Keywords悪性胸膜中皮腫 / ネクロプトーシス
Outline of Final Research Achievements

We assessed the efficacy of introducing necroptotic cell death on malignant mesothelioma cells. The method of combination with TNF-α, IAP inhibitor and pan-caspase inhibitor showed the highest efficacy in introducing necroptosis. We confirmed the necroptosis by inhibition of cell death using necrostatin-1, increase the amount of phosphorylate proteins of RIPK1, RIPK3 and MLKL, and morphological change observed by the electron microscope. In cisplatin-resistant malignant mesothelioma cells, the cell deaths through necroptosis were observed more compared to in wild type or pemetrexed-resistant type. The expression level of MDR1, MRP1 and MRP2 that are related to cisplatin resistance did not show a correlation to the efficacy of necroptosis.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

悪性胸膜中皮腫はアスベスト曝露と密接に関連し,壁側胸膜の中皮細胞から発生する極めて予後不良の腫瘍である.今後わが国で増加すると予想されている悪性腫瘍のひとつである.しかしながら,悪性胸膜中皮腫に対する有効な治療法の確立は遅れており,新しい治療法が待たれている.悪性胸膜中皮腫に対するネクロプトーシス誘導の報告は少ない.今回我々が誘導に成功した方法を用い,ネクロプトーシス誘導を悪性胸膜中皮腫の治療として発展させるための基本的アプローチ方法として今後応用できる可能性がある.

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Published: 2020-03-30  

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