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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 廖泰慶 | |
dc.contributor.author | Hsiao-Lung Cheng | en |
dc.contributor.author | 鄭筱瓏 | zh_TW |
dc.date.accessioned | 2021-05-13T08:38:54Z | - |
dc.date.available | 2019-06-23 | |
dc.date.available | 2021-05-13T08:38:54Z | - |
dc.date.copyright | 2016-06-23 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-06-04 | |
dc.identifier.citation | Abdel-Wahab, O., Klimek, V.M., Gaskell, A.A., Viale, A., Cheng, D., Kim, E., Rampal, R., Bluth, M., Harding, J.J., Callahan, M.K., Merghoub, T., Berger, M.F., Solit, D.B., Rosen, N., Levine, R.L., Chapman, P.B., 2014. Efficacy of intermittent combined RAF and MEK inhibition in a patient with concurrent BRAF- and NRAS-mutant malignancies. Cancer Discovery 4, 538-545.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/3939 | - |
dc.description.abstract | ⿊⾊素瘤是由⿊⾊素細胞或⿊⾊素母細胞異常增⽣所造成的。KIT 是⼀種受體型酪氨酸激酶 (Receptor tyrosine kinase),對⿊⾊素細胞之增殖、遷徙及存活扮演很重要的角⾊。NRAS 是⼀群小的三磷酸鳥苷酶 (GTPase),與許多細胞的增殖、遷徙及存活有關。我們先前的研究分別在⽝⿊⾊素瘤細胞和組織發現 KIT L578P (T1733C) 和 NRAS Q61K (C181A) 突變,這兩個基因突變都是⼈⿊⾊素瘤的病因,因此我們想探討這兩個突變與⽝⿊⾊素瘤的關係。首先我們從台⼤動
物醫院病理資料庫收集了源自於130 個動物的139 個⽝⿊⾊素瘤組織蠟塊,其中的91 個組織以組織免疫化學染⾊法評估蛋白質的表現,結果 KIT 蛋白質表現評估為強、中、弱及陰性的,分別有45% (41/91)、22% (20/91)、32% (29/91) 及1% (1/91),⽽ NRAS 蛋白質表現評估為強、中、弱及陰性的,分別有76%(69/91)、9% (8/91)、15% (14/91) 及0% (0/91)。另外有73 個檢體的 DNA,我們 以聚合酶連鎖反應搭配限制酶片段長度多形性 (Polymerase chain reactionrestricted fragment length polymorphism, PCR-RFLP) ⽅法進⾏基因型篩檢,結果顯示分別有16% (12/73) 及75% (55/73) 的腫瘤帶有 KIT L578P (T1733C) 及 NRAS Q61K (C181A) 突變,我們也首次在⽝⿊⾊素瘤組織發現 NRAS Q61E (C181G) 突變;但另⼀項技術-⾼解析度熱溶解曲線分析 (High-resolution melting curve analysis, HRM) 無法成功被應用於本研究之基因型篩檢。最後我們將上述的結果分別與腫瘤類型、位置及分級進⾏交叉分析,結果發現發⽣在嘴唇的⽝⿊⾊素瘤,其 NRAS 的表現會增加 (p<0.05);另外,有 KIT L578P 突變的非⼝腔型⿊⾊素瘤,其 KIT 蛋白質表現會增加 (p<0.05);其它的交叉分析就沒有關聯性。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-05-13T08:38:54Z (GMT). No. of bitstreams: 1 ntu-105-R02629014-1.pdf: 1686521 bytes, checksum: 7baa5ade41e3bcf4c414adb3567d7e6a (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 目錄
口試委員審定書 ....................................................................................... I 誌謝 ....................................................................................................... II 中文摘要 ................................................................................................ III 英文摘要 ................................................................................................ IV 目錄 ....................................................................................................... VI 圖目錄 .................................................................................................... IX 表目錄 ..................................................................................................... X 第一章 文獻探討 (Background and literature review)................................. 1 1.1 犬黑色素瘤........................................................................................... 1 1.1.2 犬黑色素瘤的治療.............................................................................. 3 1.1.3 犬黑色素瘤的病因.............................................................................. 3 1.2 KIT ..................................................................................................... 3 1.2.1 KIT 蛋白質基本構造以及功能.............................................................. 3 1.2.2 KIT 的突變........................................................................................ 5 1.2.3 探討 KIT 作為人類腫瘤治療的標靶...................................................... 6 1.3 NRAS.................................................................................................. 7 1.3.1 NRAS 蛋白質基本構造以及功能.......................................................... 7 1.3.2 NRAS 的突變 ................................................................................... 8 1.3.3 探討 NRAS 作為人黑色素瘤治療的標靶 .............................................. 9 1.4 高解析度熱溶解曲線分析 ...................................................................... 9 1.4.1 增幅圖形.......................................................................................... 10 1.4.2 熱溶解曲線...................................................................................... 11 1.4.3 標準化數據...................................................................................... 11 1.4.4 差異圖形......................................................................................... 11 1.4.5 影響的因子...................................................................................... 11 第二章 前言 (Introduction)...................................................................... 14 第三章 材料與方法 (Material and method) .............................................. 15 3.1 犬黑色素瘤病歷之收集........................................................................ 15 3.2 免疫組織化學染色.............................................................................. 15 3.3 基因型篩檢........................................................................................ 17 3.3.1 染色體去氧核糖核酸萃取.................................................................. 17 3.3.2 限制片段長度多形性聚合酶連鎖反應................................................. 18 3.3.3 質體之建立..................................................................................... 19 3.3.4 高解析度熱溶解曲線分析法 ............................................................. 22 3.4 統計分析........................................................................................... 22 第四章 結果 (Result) ............................................................................... 24 4.1 犬黑色素病歷之收集........................................................................... 24 4.2 蛋白質表現........................................................................................ 24 4.3 基因型篩檢........................................................................................ 25 4.4 建構 HRM 進行基因型篩檢................................................................. 25 4.5 統計分析........................................................................................... 26 第五章 討論 (Discussion)......................................................................... 27 5.1 犬黑色素病歷之收集............................................................................ 27 5.2 去黑色素條件之調整及蛋白質表現評估................................................. 27 5.3 基因型篩檢......................................................................................... 28 5.4 統計分析............................................................................................ 29 第六章 結論 (Conclusion) ........................................................................ 31 參考文獻 (Reference) .............................................................................. 32 | |
dc.language.iso | zh-TW | |
dc.title | 探討基因突變、蛋白質表現及腫瘤分級在犬黑色瘤之相關性 | zh_TW |
dc.title | The Correlation among Gene Mutations, Protein Expression and Tumor Stage in Canine Melanoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林辰栖,劉振軒,詹昆衛 | |
dc.subject.keyword | 犬黑色素瘤,KIT,NRAS,基因突變,免疫組織化學染色,PCR-RFLP, | zh_TW |
dc.subject.keyword | canine melanoma,KIT,NRAS,gene mutation,IHC,PCR-RFLP, | en |
dc.relation.page | 74 | |
dc.identifier.doi | 10.6342/NTU201600285 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2016-06-06 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
顯示於系所單位: | 獸醫學系 |
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