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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 彭福佐 | |
dc.contributor.author | Ke-Fan Pan | en |
dc.contributor.author | 潘可梵 | zh_TW |
dc.date.accessioned | 2021-06-16T05:24:29Z | - |
dc.date.available | 2019-10-09 | |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-14 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56347 | - |
dc.description.abstract | 攝護腺癌(Prostate cancer)為男性常見的癌症之一,根據行政院衛生署統計資料,攝護腺癌死亡率為癌症死亡率第七位。攝護腺癌的生長和分化受到雄性荷爾蒙調控,在癌症進展中,患者通常在治療過程中服用荷爾蒙拮抗藥物,而使攝護腺癌由荷爾蒙依賴型轉變為非荷爾蒙依賴型,進而造成癌症的惡化。本實驗室以荷爾蒙拮抗藥物bicalutamide (Casodex R )建立具有抗藥性之攝護腺癌細胞株,模擬臨床上攝護腺癌患者在接受荷爾蒙治療法失敗的情況。隨後以微陣列技術分析具有抗藥性細胞株與其對照組細胞株之間基因表現量之差異,發現Slit1 基因可能參與調控攝護腺癌之發展與惡化。進一步利用組織微陣列晶片觀察Slit1 蛋白的表現量在不同階段的攝護腺癌中是否有所不同,結果發現Slit1 主要表現於轉移型之攝護腺癌患者。
Slit 蛋白家族為分泌型蛋白,與其受體Roundabout (Robo)受體相接後,主要調控神經發育過程中軸突引導(axon guildance)以及神經遷移(neuronal migration)作用。研究指出與發育過程相關之蛋白往往在癌症發展中扮演重要的角色,Slit2 蛋白已被報導在不同腫瘤中皆有表現,但其表現量與癌症進展及存活率並無一致性。此外,過去文獻指出Slit2 蛋白具有促進血管新生之作用,誘導血管內皮細胞形成管狀構造並增加其遷移能力,使癌細胞透過新生血管獲得足夠養分以利生長。Slit3 也被發現透過誘導內皮細胞增生、遷移以及血管構造之形成來促進血管新生現象產生。然而尚未有文獻探討Slit1 蛋白在血管新生所扮演之角色為何,因此本研究利用in vitro 以及in vivo 方式探討Slit1 是否會造成血管新生現象。首先,利用quantitative Real-time PCR 分析人類臍靜脈內皮細胞中Slit 家族以及其受體Robo 家族基因表現情形,結果發現人類臍靜脈內皮細胞並不表現Slit1,而受體基因表現量最高為Robo4,Robo1 則次之,並利用免疫螢光染色法證實Robo1以及Robo4 表現情形。接著以酵素免疫吸附試驗(ELISA)觀察Slit1 以及Robo1、Robo4 結合情形,結果顯示Slit1 蛋白與Robo1 受體結合效力較Robo4 高出許多,推測Slit1 蛋白會與Robo1 受體結合進入細胞中。以Slit1 蛋白以及條件培養液處理人類臍靜脈內皮細胞後,觀察細胞增生(cell proliferation)、管狀構造形成(tube formation)以及傷口癒合檢測(wound healing)。結果顯示Slit1 蛋白僅有顯著性增加管狀構造之形成且具有一劑量效應關係,然對HUVEC 細胞之生長與細胞爬行能力並無顯著性差異。將Robo4 胜肽(peptide)與Slit1 蛋白預先混合後再給予HUVEC 細胞,其管狀構造形成現象也隨之消失,證實Slit 蛋白具有促進血管新生之功能。而在in vivo 部分,利用雞胚絨毛尿囊膜試驗觀察Slit1 是否會造成血管新生之現象,結果也發現Slit1 確實會誘導血管新生現象產生。未來將進一步針對管狀構造形成探討Slit1 造成血管新生之機制。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:24:29Z (GMT). No. of bitstreams: 1 ntu-103-R01447001-1.pdf: 1474020 bytes, checksum: 149a09b208c8720248d2f8939cbf21d9 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審定書
謝誌 縮寫表 (Abbreviations) ................................................................................ IV 圖表目錄 (Figures and Tables) ...................................................................... V 中文摘要.......................................................................................... VI 英文摘要....................................................................................... VIII 第一章 緒論 (Introduction) 1.1 攝護腺癌之背景介紹............................................................................... 1 1.2 攝護腺癌與血管新生之關連性............................................................... 2 1.3 血管內皮細胞與血管新生....................................................................... 3 1.4 攝護腺癌與Slit 之關係 ........................................................................... 5 1.5 Slit 之背景介紹 ........................................................................... 5 1.6 Slit 蛋白與癌症的相關性 ......................................................................... 6 1.7 Slit 蛋白與血管新生之相關性 ................................................................. 8 1.8 Slit 蛋白之受體Robo 與血管新生的關連性 .......................................... 9 1.9 研究動機................................................................................... 11 第二章 實驗材料與方法 (Materials and Methods) 2.1 實驗材料................................................................................... 12 2.2.1 人類臍靜脈內皮細胞 (Human Umbilical Vein Endothelial Cells, HUVECs)之 分離與培養...................................................................................... 17 2.2.2 免疫組織染色 (Immunohistochemical staining) ............................................. 17 2.2.3 免疫螢光染色 (Immunoflourecence) ................................................. 18 2.2.4 定量即時聚合酶連鎖反應 (Quantitative Real Time Polymerase Chain Reaction, qRT-PCR) ....................................................................... 19 2.2.5 酵素免疫吸附試驗 (Enzyme-linked immunosorbent assay, ELISA).............. 19 2.2.6 慢病毒製備與感染 (Lentivirus production and infection) .............................. 20 2.2.7 西方墨點法 (Western blot analysis) ................................................... 21 2.2.8 細胞增生試驗 (Cell proliferation assay) ............................................ 22 2.2.9 傷口癒合檢測 (Wound healing assay) ............................................... 23 2.2.10 管狀構造形成試驗 (Tube formation assay) .................................... 23 2.2.11 雞胚絨毛尿囊膜試驗 (Chick Chorioallantoic Membrane assay) .................. 24 2.2.12 統計分析(Statistic analysis) .............................................................. 24 第三章 實驗結果 (Results) 3.1 Slit1 蛋白表現量在攝護腺癌進展過程中的變化 ............................................... 26 3.2 內皮細胞之細胞特異性標誌CD31 以及CD105 存在於人類臍靜脈內皮細胞的 細胞膜表面...................................................................................... 26 3.3 Slit 家族以及其受體Robo 家族於人類臍靜脈內皮細胞基因的表現量 .......... 27 3.4 Slit1 之受體Robo1 以及Robo4 表現於人類臍靜脈內皮細胞之細胞膜表面 .. 27 3.5 Slit1 與其受體Robo1、Robo4 結合效力的比較 .................................. 28 3.6 含Slit1 之pWPI 載體感染293T 細胞 .................................................. 29 3.7 Slit1 對人類臍靜脈內皮細胞增生的影響 ............................................. 29 3.8 Slit1 蛋白影響人類臍靜脈內皮細胞遷移的能力 ............................................... 30 3.9 Slit1 蛋白誘導人類臍靜脈內皮細胞管狀構造形成的作用 ............................... 31 3.10 Slit1 蛋白於體內試驗中誘導血管新生作用 ....................................... 33 第四章 討論 (Discussion) 4.1 Slit1 蛋白造成血管新生現象 ................................................................. 35 4.2 Slit1 蛋白以及其受體Robo 於神經發育過程之角色與癌症之相關性 ............ 36 4.3 神經軸突導向分子與癌症進展過程之相關性..................................... 39 4.4 促血管新生因子所造成血管新生現象之探討..................................... 40 4.4 Slit1 於轉移型攝護腺癌表現量之探討 ................................................. 41 第五章 總結 (Conclusion) ......................................................................... 43 參考文獻 (References) ............................................................................... 44 圖表集 (Figures and Tables) ....................................................................... 50 | |
dc.language.iso | zh-TW | |
dc.title | 探討Slit1 蛋白在轉移型攝護腺癌進展過程中血管新生所扮演的角色 | zh_TW |
dc.title | Study on the Role of Slit1 Protein Associated with Angiogenesis of Prostate Cancer Metastasis | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 劉興華,華國泰,李明學,林泰元 | |
dc.subject.keyword | Slit1,血管新生,人類臍靜脈內皮細胞,管狀構型, | zh_TW |
dc.subject.keyword | Slit1,angiogenesis,Human Umbilical Vein Endothelial Cells (HUVECs),tube formation, | en |
dc.relation.page | 63 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 毒理學研究所 | zh_TW |
顯示於系所單位: | 毒理學研究所 |
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