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    Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/4240


    Title: 薑黃素及?唑類衍生物對抗人類神經膠質母細胞瘤之研究
    Study on Anti-tumor activities of Curcumin and Carbazole Derivatives in Human Glioblastoma
    Authors: 葉雅雯
    Ya-Wen,Yeh
    Contributors: 中山醫學大學;醫學院;醫學研究所;林志立
    Keywords: 多型性神經膠母細胞癌;薑黃素;替莫唑胺
    Glioblastoma Multiforme;Curcumin;temozolomide
    Date: 2011
    Issue Date: 2011-10-25T07:32:27Z (UTC)
    Abstract: 在惡性的腦部腫瘤中神經膠質母細胞瘤(Glioblastoma)是最常見的。根據統計在美國每年約有18000人被診斷出有惡性腦腫瘤,而其中多型性神經膠母細胞癌(Glioblastoma Multiforme;GBM)在成人中約佔50%至60%的病例。而關於神經膠質母細胞瘤世界衛生組織將之分為四個等級,而GBM是屬於是第四級其五年存活率則不到5 %。臨床上對於多型性神經膠母細胞癌治療方法是外科手術搭配放射療法及合併化學治療,但是因為惡性腫瘤容易再復發的特性,因此多型性神經膠母細胞癌預後其實是不樂觀的。
    對於抑制多型性神經膠母細胞癌的再復發,目前臨床有發展出一種新的化學療法,經由服用替莫唑胺 (Temozolomide) 之甲基化促進劑,可以延緩惡性腫瘤的復發及可以延長因外科手術或放射療法後延長病人的生命。替莫唑胺雖可以短時間內有很強的作用抑制多型性神經膠母細胞癌,長期使用仍有大多數病人對此藥產生抗藥性,對於延長生命還是有限,因此,研發新的治療方法,是目前臨床所需處理的問題。
    許多的文獻報告指出,天然的食材Curcumin被廣泛應用於各種疾病的治療與預防,尤其是在治療癌症上,因此,我們用以評估對於GBM的影響。結果發現Curcumin可以有效的抑制GBM型態改變。而在Curcumin合併GBM的臨床用藥TMZ處理上有加成的作用,並可以誘發自體吞噬細胞死亡。我們進一步的發現其自體吞噬細胞死亡的訊息傳遞路徑可能增加AMPK的活性,而使下游蛋白mTOR的活性減少,進而增加LC3-II蛋白的表現量增加。所以,透過Curcumin合併TMZ誘導自噬性細胞死亡,可能是一個可以有效對抗GBM的方式。

    The most common malignant brain tumor is Glioblastoma. There are 18000 people newly diagnosed as primary malignant brain tumor in United States, and 50-60% patients are Glioblastoma multiforme (GBM). Gliomas are divided into 4 grades. Glioblastoma Multiforme belongs to grade 4 and the 5 year survival rate is less than 5%. The current managements are surgical treatment, concurrent chemoradiation therapy, and stereotactic radiosurgery. Advances in treatment have been very poorly, significant improvement in survival has been lacking for many years and prognosis not very well. Despite total surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and nonadjacent areas of normal brain parenchyma.
    Even thought, long-term using of temozolomide can also lead to resistance of this drug and tumor recurrence. The mandatory work is to find out new ways to control tumor. We have an idea that if we can enhance the methylation of the promoter of MGMT gene. Tumor killing and tumor control will be effective and extended. Curcumin has been using on breast Ca and skin Ca control via activating apoptosis of tumor cells. We are also interested whether curcumin can enhance methylation or inhibit tumor growth.
    In our study, Curcumin combined with temozolomide can promote the killing effect on tumor cells and induce autophagy of tumor cells. Furthermore, we found the cascade of autophage is to increase the activity of AMPK and lead to downstream protein (mTOR) deactivated. Then the amount of LC3-II protein will increase.
    In conclusion, scientists are interested in autophagy for tumor killing and tumor control. Many reports point out that atuophagy and methylation of MGMT plays an important role in cancer treatment. Curcumin combined with TMZ can induce autophagy of tumor cells. It might be an effective way to against GBM.
    URI: https://ir.csmu.edu.tw:8080/ir/handle/310902500/4240
    Appears in Collections:[醫學研究所] 博碩士論文

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