臺灣博碩士論文加值系統

人類表皮型的癌症，像是胃癌、肺癌、大腸癌、胰腺癌、乳癌、頭頸癌等，占所有癌症死亡率的 50％ 以上，而導致這種類型癌症的特徵在於表皮生長因子受體 (EGFR) 的過度表現和其訊號途徑的活化。當表皮生長因子 (EGF) 與 EGFR 結合後，下游一系列的訊號就會被活化，使得癌細胞增殖、存活和轉移。癌症標靶藥物如EGFR抗體和酪氨酸激酶 (tyrosine kinase) 抑制劑的作用機轉即是針對 EGF 與其受體之間專一性的結合。
在本研究中，我們利用微脂體包覆化療藥物艾黴素 (LipoDox, LD)，試圖想要開發以 EGFR 為靶向的微脂體藥物，而其他幾個研究單位也探討了這種方法的研發。但是到目前為止並無顯著成果。為了開發 EGFR 靶向之標靶藥物，我們已經成功地純化出一個融合蛋白質並將其標記到微脂體包覆化療藥物艾黴素，未來，我們將繼續探討以此微脂體藥物來治療 EGFR 過度表現類型的癌症，我們計劃進行動物研究，以進一步證明 EGFR 標靶治療在臨床前研究的潛力。

Human epithelial cancers, such as gastric, lung, colorectal, pancreatic, breast, head and neck etc., are responsible for more than 50% of all cancer-related deaths. These cancers are characterized by significant expression of epidermal growth factor receptor (EGFR) and activation of its signaling pathway. Upon binding to EGF, EGFR results in activation of pathways important for proliferation, survival and metastasis of cancer cells. EGF-EGFR pathway is a well-characterized anticancer drug target of antibodies against EGFR and tyrosine kinase inhibitors.
In this thesis project, we tried to develop an EGFR targeting liposomal drug by liposomal doxorubicin (LipoDox, LD). This approach had been explored by several other research groups. However, success in this field is still limited. To develop an EGFR targeting therapy, we had successfully purified a protein X and labeled it to LD. We will continue exploring the incorporation of this EGFR targeting protein X with a liposomal drug for treatment of EGFR-expressing cancers. We also plan to conduct the animal study to further demonstrate the potential of this EGFR-targeting treatment in a preclinical setting.

誌謝……………………………………………………………..…..…...i
中文摘要………………………………………………………..............ii
Abstract……………………………………………………...…..…....iii
目錄……………………………………………………………….....…iv
圖目錄……………………………………………………………..…..v
表目錄………………………………………………………………...vi
第一章 緒論……………………………………………………….........1
第二章 研究材料與方法……………………………………………...12
第一節 研究材料……………………………………………….....12
第二節 研究方法………………………………………………….16
第三章 研究結果……………………………………………………...28
第四章 討論……………………………………………………………34
第五章 結論……………………………………………………………37
參考文獻………………………………………………………………..38
圖表…………………………………………………………………………………………….........50

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