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研究生:賴文國
研究生(外文):Lai, Wen-Kuo
論文名稱:探討腦膜瘤類幹細胞的放射抗性和帝拔癲:放射治療效應與機轉
論文名稱(外文):To investigate radioresistant meningioma stem-like cells and Valproic acid: rediotherapeutic effects and mechanisms
指導教授:闕小輝馬辛一
指導教授(外文):Chueh, SheauHueiMa, HsinI
口試委員:李進成馬辛一闕小輝
口試委員(外文):Lee, Chin-ChengMa, Hsin-IChueh, Sheau-Huei
口試日期:2011-03-31
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:38
中文關鍵詞:腦膜瘤類幹細胞帝拔癲
外文關鍵詞:meningioma stem-like cellsValproic acid
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腦膜瘤最難治療是因為它常有復發的情形發生。這次的研究中,我們利用藥物VPA針對腦膜瘤具有抗放射線的特性而導致腦膜瘤復發的情形去做研究分析,進而改善腦膜瘤放射治療的方法。先前我們實驗室已經從人類腦膜瘤中建立純化出腦膜瘤類癌幹細胞,此細胞株具有幹細胞蛋白的表現而且會在幹細胞培養液裡形成球團形狀的能力。此外,我們也發現腦膜瘤類癌幹細胞較腦膜瘤貼盤細胞具有放射抗性;當我們在腦膜瘤類癌幹細胞裡加入藥物VPA時,會使細胞週期G2/M停止並使得sub G1期減少,更進一步發現到,當腦膜瘤類癌幹細胞裡的磷酸化cdc2蛋白和細胞凋亡蛋白上升時,會使得腦膜瘤類癌幹細胞降低其放射抗性,另外,我們也有發現腦膜瘤類癌幹細胞裡的磷酸化H2AX蛋白量也有上升的趨勢並伴隨著DNA斷裂的情形。最後,我們發現藥物VPA和放射線同時處理的腦膜瘤類癌幹細胞,注射在裸鼠基底核部位,腫瘤形成能力與對照組相比較有下降的情形。根據以上結果,推斷藥物VPA在未來可以提供腦膜瘤放射抗性的特性去做治療和抑制,更進一步降低腦膜瘤復發的情形。
The main problem in the recurrence of meningioma is their radioresistant behaviour. In this study, we investigated the effect of valproic acid (VPA) on meningioma to improve the radiotherapy. We previously have isolated and characterized the brain tumor stem-like cells from human meningiomas. We found that meningioma stem-like cells possessed the stem cell markers and have ability to take sphere shapes in stem cell culture condition. In addition, Meningioma sphere cells (MgSCs) are more resistant to radiation treatment than daughter meningioma adhesion cells (MgACs). However, treatment of MgSCs with VPA alone induced cell cycle G2/M arrest and decreased subG1. Moreover, we show that the reduction of radioresistance in MgSCs was mediated through the rise in phosphorylated-CDC2, apoptotic proteins. We also show that DNA damage by phosphorylated-H2AX on Western blot. Furthermore, we test the effect of valproic acid on tumor growth in vivo following orthotopic inoculation into the brains of nude mice. The corresponding hematoxyline and eosin staining found significant suppression of tumor growth in valproic acid-treated group. These results suggest that valproic acid may serve as a potential medication in radiation resistant meningiomas.
正文目錄……………………………………………Ⅰ
圖文目錄……………………………………………Ⅱ
縮寫表………………………………………………Ⅲ
中文摘要……………………………………………Ⅳ
英文摘要……………………………………………Ⅴ
緒論…………………………………………………1
實驗材料與方法……………………………………4
實驗結果……………………………………………12
實驗討論……………………………………………17
實驗結論……………………………………………21
參考文獻……………………………………………35

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