Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor : establishment and xenograft of a cell line to predict clinical efficacy

• Material Type: 博士論文
• Title: Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor : establishment and xenograft of a cell line to predict clinical efficacy
• Author/Editor: Kanemaru, Yu
• Publication Date: 2020-03-23
• Publication Date (W3CDTF): 2020-03-23
• Alternative Title: BRAF阻害剤とMEK阻害剤の併用療法が奏功した類上皮性膠芽腫の1例より樹立した患者由来細胞株を用いた治療効果の検討
• Degree Grantor: 新潟大学
• Date Granted: 2020-03-23
• Date Granted (W3CDTF): 2020-03-23
• Dissertation Number: 甲第4683号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲第4683号
• Text Language Code: eng
• Subject Heading: Epithelioid glioblastoma; BRAF V600E; Targeted therapy; Precision medicine
• Note (General): Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations – BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600Emutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.; Acta Neuropathologica Communications. 2019, 7, 119.; 新大院博(医)甲第917号; 元資料の権利情報 : 【○!C】 The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
• DOI: info:doi/10.1186/s40478-019-0774-7; https://doi.org/info:doi/10.1186/s40478-019-0774-7
• Persistent ID (NDL): info:ndljp/pid/11538613; https://dl.ndl.go.jp/pid/11538613
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-09-07T06:04:08+09:00
• Date Created (W3CDTF): 2020-08-31
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10191/00051806
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp