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    Title: 開發基底細胞癌之斑馬魚品系用以篩選新型釕金屬錯合物之抗腫瘤前導藥物
    Other Titles: Using Basal Cell Carcinoma Transgenic Zebrafish Lines as Whole Organism Plateforms for Screening Novel Ruthenium-Derived Leading-Drugs
    Authors: 陳曜鴻
    Contributors: 淡江大學生命科學研究所
    Keywords: 基底細胞癌;角質蛋白;斑馬魚;穩定遺傳;藥物篩選;釕金屬錯合物;basal cell carcinoma;keratin;zebrafish;germ-line transmission;drugscreening;ruthenium-derived compounds
    Date: 2008
    Issue Date: 2010-04-15 15:37:22 (UTC+8)
    Abstract: 抗癌藥物的篩選如果有適當又便宜的疾病動物模式可使用,可降低成本, 大大提升效率。斑馬魚在基因轉殖以及穩定遺傳方面的技術已經成熟,儼然成為 研究癌症發生學不可或缺的利器。所以擬研提今年這個研究計畫,也就是應用基 因轉殖配合穩定遺傳的技術,在表皮細胞過度表現shh 與gli2 等致癌蛋白並且與 紅螢光蛋白(RFP)報導基因融合,期望得到穩定遺傳、會發紅螢光而且分別會罹 患先天性基底細胞癌與自發性基底細胞癌轉殖品系。最後利用這些轉殖品係來篩 選本校化學系所合成的小分子化學物資料庫(尤其是新型釕金屬錯合物),希望篩 選出抗皮膚癌之新型前導藥物藥。這些研究項目十分繁重,故擬分三年來完成下 列目標。 第一年計畫內容涵蓋:(1)構築shh 與gli 等致癌蛋白並且與紅螢光蛋白(RFP) 報導基因融合的表現質體;(2)顯微注射法將上述質體植入斑馬魚體內;(3)穩定 遺傳品系的獲得;(4)切片技術與組織染色;(5)轉殖品系的量產。 第二年計畫內容涵蓋:(1) 轉殖品系的量產;(2) 切片技術與組織染色;(3) 抗 體免疫螢光染色實驗的建立;(4) Microarray 的分析;(5) 先天性基底細胞癌與自 發性基底細胞癌的細胞癌化分子機制探討。 第三年計畫內容涵蓋:(1) 轉殖品系的量產;(2) 釕金屬錯合物的篩選;(3) 藥物處理後的動態螢光觀察;(4)抗體免疫螢光染色實驗的建立;(5)切片技術與 組織染色;(6)其他抗癌前導藥物的篩選。 Screening of the anti-tumor drugs is very laborious and expensive. The efficiencies will be greatly improved and the cost will be reduced if there is a suitable animal model ready to use. The transgenic and germ-line transmission techniques are mature enough to make it possible that using zebrafish as an animal model to study human cancer and diseases. We will create two zebrafish lines which are overexpression shh and gli oncoproteins on their skin and are ready for mimicking autosomal dominantly basal cell carcinoma syndrome and sporadic basal cell carcinoma, respectively, to screen anti-skin tumor leading-drugs in vivo in this 3-year project. Our proposal will be including: The first year: (1). Construction of the shh and gli fusing with RFP, and are driven by zebrafish keratin 18 promoter; (2). Microinjection these plasmids which are listed above into the zebrafish embryos; (3). Creating two germlines for mimicking autosomal dominantly basal cell carcinoma syndrome and sporadic basal cell carcinoma; (4). Using cryosection and immunohistochemical staining to further confirm the germlines; (5). Amplification of the cancer fish lines; The second year: (1). Amplification of the cancer fish lines; (2). Using cryosection and immunohistochemical staining to further confirm the germlines; (3). Using antibodies staining to study the endogenous oncoprotein levels; (4). Microarray analysis; (5). Discovery the molecular mechanisms of autosomal dominantly basal cell carcinoma syndrome and sporadic basal cell carcinoma. The third year: (1). Amplification of the cancer fish lines; (2). Screening for the novel ruthenium-derived compounds; (3). Phenotypic observations of the embryos after treated with ruthenium-derived compounds; (4). Using antibodies staining to study the endogenous oncoprotein levels; (5). Using cryosection and immunohistochemical staining to further investigating the germlines; (6) Screening for the other small chemical library to find novel anti-cancer leading drugs.
    Appears in Collections:[生命科學研究所] 研究報告

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