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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61254完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳進庭(Chin-tin Chen) | |
| dc.contributor.author | Ｍu-Ching Huang | en |
| dc.contributor.author | 黃睦晴 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:56:12Z | - |
| dc.date.available | 2015-08-20 | |
| dc.date.copyright | 2013-08-20 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-08 | |
| dc.identifier.citation | 1. Ackroyd, R., et al., The history of photodetection and photodynamic therapy.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61254 | - |
| dc.description.abstract | 五胺基酮戊酸光動力療法(ALA-mediated Photodynamic Therapy, ALA-PDT)，主要是利用外源投予5-aminolevulinic acid (ALA) 的方式，藉由細胞中血紅素生成路徑代謝成內生性的光感物質PpIX。由於其具有腫瘤選擇性的優點，本實驗室希望將ALA-PDT 發展成治療第一型神經纖維瘤(Neurofibromatosis type I, NF1)的療法。實驗室先前研究結果顯示利用ALA-PDT 搭配其他藥物處理NF1細胞株，對於細胞毒殺的效果產生協同效應，其中主要原因是在在這些藥物存在下細胞內由ALA 所代謝產生的光感物質PpIX 之累積增加，進而達到增強光動力治療的效果。CX1 造成PpIX 之累積量提升，可能的影響機制包括以下幾點: (1)增加細胞對於ALA 的吸收；(2)參與在原血紅素生成路徑中；(3)抑制PpIX或其前軀物排出細胞外。有研究指出PpIX 或其前軀物會透過ABCG2轉運幫浦排出至細胞外，而ABCG2 近年來被證實與腫瘤的多重抗藥性(multidrug resistance,MDR)有關，因此在本篇研究中我們首要探討的是這些藥物是否藉由影響ABCG2 而提升PpIX 之累積，藉由了解這些藥物是否為ABCG2 之調節者，未來或許能夠將這些藥物發展為治療抗藥性癌細胞的合併用藥。 | zh_TW |
| dc.description.abstract | ALA-mediated Photodynamic Therapy (ALA-PDT) is performed by exogenous administration of 5-aminolevulinic acid (ALA). Due to its tumor selective advantage, we intend to develop ALA-PDT for the treatment of Neurofibromatosis type I (NFI). Previously, we found that certain chemical compound can synergistically enhance ALA-PDT by elevating the level of PpIX in S462 cell. The mechanisms involved in enhancing PpIX accumulation might be: (1) enhances ALA uptake; (2) alters heme biosynthesis pathway; (3) inhibits PpIX or its precursor efflux from cell. It has been shown that PpIX and/or its precursors are the substrate of ABCG2. Given the role of ABCG2 that confers tumor multidrug resistance (MDR), the prime purpose of this study is to verify whether these compound is a modulator of ABCG2. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:56:12Z (GMT). No. of bitstreams: 1 ntu-102-R00b22021-1.pdf: 6743681 bytes, checksum: 1b892ea56838973a1e18252574662ef1 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II 目錄 III 圖目錄 VII 第一章 緒論 1 1.1 光動力治療(Photodynamic Therapy, ALA-PDT) 1.1.1 發展起源 1 1.1.2 光動力治療的作用機制 1 1.1.3 五胺基酮戊酸(ALA) 1 1.1.3.1 原血紅素生成路徑(heme biosynthetic pathway) 2 1.1.3.2 臨床優勢 3 1.1.3.3 臨床上應用 3 1.1.3.4 缺點與改良 4 1.2 第一型神經纖維瘤NF1 5 1.2.1 病理機轉 5 1.2.2 臨床表徵 6 1.3 多重抗藥性 (Multi-drug resistance, MDR) 7 1.3.1 多重抗藥性機制 7 1.3.2 ABCG2 8 1.3.2.1 ABCG2 基本介紹 8 1.3.2.2 ABCG2 表現 8 1.3.2.3 ABCG2 對於癌細胞多重抗藥性之重要性 9 1.3.2.4 ABCG2 對於光動力之影響 10 1.4 研究動機與目的 10 IV 第二章 材料與方法 12 2.1 藥品與儀器 12 2.1.1 藥品 12 2.1.2 細胞培養耗材 14 2.1.3 儀器 14 2.2 細胞株 (Cell line) 15 2.3 細胞培養與繼代 15 2.4 細胞解凍與冷凍 16 2.5 細胞計數 17 2.6 表現ABCG2 於細胞中 17 2.6.1 建構ABCG2 基因質體 17 2.6.2 建立大量表現ABCG2 基因之細胞株 18 2.6.3 分析ABCG2 表現位置 18 2.7 mRNA 定量分析 18 2.7.1 RNA 萃取 (RNA extraction) 18 2.7.2 反轉錄 (Reverse Transcription, RT) 19 2.7.3 聚合酶鏈鎖反應 (Polymerase Chain Reaction, PCR) 19 2.7.4 洋菜膠體電泳分析 20 2.8 西方墨點法 (Western blot) 20 2.8.1 蛋白質萃取 (Protein extraction) 20 2.8.2 烷基硫酸鈉聚丙醯胺凝膠電泳 (SDS-PAGE) 21 2.8.3 化學冷光免疫分析(Chemiluminescence Immunoassay, CLIA) 21 2.9 藥物含量分析 22 2.9.1 光感物質累積試驗 22 2.9.2 Mitoxantrone 排出試驗 22 V 2.9.3 PpIX 排出試驗 23 2.9.4 ALA 累積量實驗 23 2.10 統計分析 24 第三章 結果 25 3.1 CX1 可有效提升多種光感物質於細胞中之累積量 25 3.1.1 CX1 可提升細胞中PpIX 之累積量 25 3.1.2 CX1 對於另外兩種藉由ABCG2 排出之光感物質的影響 25 3.2 CX1 對於ABCG2 之影響 25 3.2.1 C 端帶有GFP 之ABCG2 無法實行正常功能 26 3.2.1.1 大量表現ABCG2 之細胞，其藥物累積程度與正常細胞無差異 26 3.2.1.2 C 端帶有GFP 之ABCG2 沒有正確表現於細胞膜上 26 3.2.2 轉染N 端帶有GFP 之ABCG2 於HEK293 細胞中 27 3.2.3 CX1 對於ABCG2 的影響並不明顯 28 3.3 細胞密度是影響CX1 效果之重要因素 29 3.3.1 CX1 對於PpIX 累積量之提升程度於細胞密度高時較為顯著 29 3.3.2 CX1 類似物對於PpIX 累積量之影響同樣受細胞密度影響 29 3.4 細胞密度可能的影響因子 30 3.4.1 細胞密度對培養液pH 值之影響 30 3.4.2 細胞密度對細胞內鐵離子含量的影響 30 3.5 CX1 對於ALA 累積量之影響 31 第四章討論 32 4.1 CX1 對於ABCG2 之影響 32 4.1.1 S462 細胞中ABCG2 之表現 32 4.1.2 ABCG2/GFP 融合蛋白 33 4.2 細胞密度對CX1 之效果有顯著影響 35 VI 4.2.1 細胞密度對培養液pH 值之影響 35 4.2.2 細胞密度影響細胞內鐵離子含量 35 4.3 CX1 對於PpIX 累積量提升之機制探討 37 4.3.1 CX1 對ALA 吸收之影響－CX1 能夠使細胞內ALA 累積量略微增加 37 4.3.2 CX1 對原血紅素生成路徑之影響－CX1 可能扮演鐵離子螯和劑之角色 38 4.3.3 CX1 對PpIX 排出之影響－CX1 主要不是影響ABCG2 39 第五章結論 40 參考文獻 61 | |
| dc.language.iso | zh-TW | |
| dc.subject | ALA-PDT | zh_TW |
| dc.subject | MDR | zh_TW |
| dc.subject | ABCG2 | zh_TW |
| dc.title | CX1對於增進五胺基酮戊酸光動力治療之機制探討 | zh_TW |
| dc.title | The Action Mechanisms of Compound X1 in Enhancing
ALA Mediated Photodynamic Therapy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許瑞祥(Ruey-Shyang Hseu),黃慶璨(Ching-Tsan Huang),蔡翠敏(Tsui-min Tsai) | |
| dc.subject.keyword | ALA-PDT,ABCG2,MDR, | zh_TW |
| dc.relation.page | 71 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-09 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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