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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72939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 | Yi-Chien Wu | en |
| dc.contributor.author | 吳宜謙 | zh_TW |
| dc.date.accessioned | 2021-06-17T07:11:03Z | - |
| dc.date.available | 2024-07-24 | |
| dc.date.copyright | 2019-07-24 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-07-19 | |
| dc.identifier.citation | 1. 民國106年主要死因統計結果分析. 中華民國衛生福利部統計處.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72939 | - |
| dc.description.abstract | 癌症為造成人口死亡的重要原因，多年來一直高居世界人口的十大死因第二名，而隨著醫療發展的進步與新藥的開發，針對不同癌症，病患獲得更好的治療，癌症的預後結果也隨之改善。然而，在癌症治療過程中，癌細胞對治療產生抗性的而造成治癒效果不佳一直是治療上所需面對的問題。對於治療這些具有抗藥性的癌症，目前有效的方式之一為併用療法: 透過併用兩種或以上不同毒殺機制的藥物治療癌症。本篇研究即希望透過併用藥物以及微脂體劑型，製備出雙效微脂體作為一併用療法。本研究的第一部分，我們將化療藥物 Irinotecan (IRT) 以及光感物質 Chlorin e6 (Ce6) 同時包覆在微脂體中，希望藉由化療藥物與光動力治療的搭配毒殺表現ABCG2的抗性細胞。在此一部分，我們利用細胞實驗來驗證此一微脂體對細胞的毒性以及探討可能的毒殺機制。此外，我們利用添加同銅離子以及改良雙效微脂體的製備方法，針對此一微脂體的在血漿中的穩定性做進一步的優化。第二部分，我們希望利用化療藥物 IRT 搭配天然植物萃取物 Curcumin (CUR) 發展出另一種併用療法，用於治療因化學藥物誘發表現 COX-2 基因的癌細胞。這一部分的研究主要探討微脂體 IRT與 CUR兩種藥物併用下毒殺細胞的效果，並進一步探討兩種藥物併用下對細胞 COX-2 基因表現量之影響。 | zh_TW |
| dc.description.abstract | For many years, cancer has been the leading cause of death in the world. Although the medical advances have improved the prognosis and treatments, the rate of recurrence and death for several types of cancer remain disappointingly high, and this is often due to drug resistance of the cancer. One of the more effective ways to treat drug-resistant cancers is combinational therapy: using two or more medications that exert different cytotoxic mechanisms. In this study, we sought to develop a combination therapy based on liposomal irinotecan (IRT) in combination with chlorin e6 (Ce6) or curcumin (CUR). In the first part of our study, IRT and Ce6 were coloaded into PL-IRT-Ce6 liposomes. The liposome was developed to kill drug-resistant cancer cells that express the drug efflux transporter ABCG2. The cytotoxicity and the possible cytotoxic mechanism of PL-IRT-Ce6 were examined by in vitro studies. In addition, we improved the stability of PL-IRT-Ce6 by adding Cu2+ as the trapping agent of IRT as well as changing the liposome preparation method. In the second part of this study, we developed another combination therapy based on the use of liposomal IRT in combination with CUR, as CUR is thought to be able to downregulate IRT-induced expression of COX-2. In this latter part of the study, we focused on the cytotoxicity and the regulation of COX-2 expression when cells were treated with PL-IRT plus CUR. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T07:11:03Z (GMT). No. of bitstreams: 1 ntu-108-R06B22005-1.pdf: 3599793 bytes, checksum: e7a0d50fa4f6e2c4cb9ba23c40437792 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 摘要 1
Abstract 2 Chapter 1. Introduction 11 1.1 Cancer 11 1.2 Chemotherapy 12 1.3 Combination Therapy 13 1.4 Irinotecan 14 1.5 Photodynamic Therapy 15 1.5.1 The mechanism of PDT-induced cytotoxicity 16 1.5.2 Photosensitizers (PS) 17 1.5.3 Chlorin e6 (Ce6) 18 1.6 Curcumin (CUR) 19 1.7 Liposomes 20 1.7.1 Introduction to liposomes 20 1.7.2 Methods for preparing liposomes 21 1.7.3 Liposome applications in drug delivery 23 1.7.4 Liposomal irinotecan 24 1.8 Cyclooxygenases (COXs) 24 1.8.1 Cyclooxygenase-2 (COX-2) 25 1.8.2 Regulation of COX-2 expression 26 1.9 Rationale and Objectives 27 Chapter 2. Materials and Methods 29 2.1 Materials and Equipment 29 2.1.1 Materials 29 2.1.2 Equipment 31 2.2 Cell Lines 32 2.2.1 Cell culture medium 32 2.2.2 Cell subculture 32 2.2.3 Cryopreservation procedure and recovery of cryopreserved cells 33 2.3 Cell Counting 34 2.4 Liposome Preparation 34 2.4.1 PL-Ce6 34 2.4.2 PL-IRT 35 2.4.3 PL-IRT-Ce6 36 2.4.4 PL-IRT (Cu2+) 36 2.4.5 PL-IRT-Ce6 (Cu2+) 37 2.5 Characterization of Liposomes 38 2.6 Determination of Total Phosphorus in Liposome 38 2.7 Serum Stability Test 39 2.8 Ce6 Stability of PL-IRT-Ce6 (Cu2+) 40 2.9 The Cytotoxicity of PL-IRT-Ce6 40 2.10 Cellular uptake of PL-IRT-Ce6 42 2.11 Intracellular IRT Accumulation Post-PDT 42 2.12 Drug Treatment for ABCG2 Expression Analysis 43 2.13 The Anticancer Activity of PL-IRT+CUR 44 2.14 Drug Treatment for COX-2 Expression Analysis 45 2.15 mRNA Expression Analysis 45 2.15.1 RNA extraction 45 2.15.2 Reverse transcription, RT 46 2.15.3 Polymerase chain reaction, PCR 46 2.15.4 Gel electrophoresis 48 2.16 Statistical Analysis 48 Chapter 3. Results 49 3.1 The Dual-effect Liposome PL-IRT-Ce6 49 3.1.1 Preparation and characterization of PL-IRT-Ce6 49 3.1.2 Cytotoxicity of PL-IRT-Ce6 51 3.2 The Cytotoxic Mechanism of PL-IRT-Ce6 52 3.2.1 Pancreatic cancer cell drug resistance 52 3.2.2 Equal intracellular drug uptake in the absence of PDT 53 3.2.3 PL-IRT-Ce6 increases the level of intracellular IRT post-PDT 54 3.2.4 PL-IRT-Ce6 decreases the level of ABCG2 post-PDT 55 3.2.5 AsPC-1 cells are less sensitive to PL-IRT-Ce6 than MIA PaCa-2 cells 56 3.3 Optimization of PL-IRT-Ce6 56 3.3.1 Preparation and characterization of PL-IRT-Ce6 (Cu2+) 56 3.3.2 The stability of PL-IRT-Ce6 (Cu2+) is improved in 80% serum 58 3.4 The effect of PL-IRT on COX-2 mRNA Expression 59 3.4.1 CUR reduces IRT-mediated COX-2 upregulation 60 3.5 PL-IRT+CUR A375 cell cytotoxicity 61 Chapter 4. Discussion 61 4.1 Preparation of PL-IRT-Ce6 61 4.1.1 Stability of PL-IRT-Ce6 61 4.1.2 Optimization of PL-IRT-Ce6 by the addition of a trapping agent and use of a post-loading method 62 4.1.3 Characterization of PL-IRT-Ce6 (Cu2+) 65 4.2 The Cytotoxic Mechanism of PL-IRT-Ce6 66 4.3 The effect of PL-IRT in Combination with CUR on A375 cells 68 Chapter 5. Conclusion 69 References 90 | |
| dc.language.iso | en | |
| dc.title | 發展 Irinotecan 與 Chlorin e6 雙效微脂體藥物 | zh_TW |
| dc.title | Development of a Dual-effect Liposome Encapsulating
Irinotecan and Chlorin e6 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳?承(Hsuan-Chen Wu),廖泰慶,謝堅銘 | |
| dc.subject.keyword | 併用療法,光動力治療,Irinotecan,Chlorin e6,Curcumin,COX-2, | zh_TW |
| dc.subject.keyword | Combination therapy,Photodynamic therapy,Irinotecan,Chlorin e6,Curcumin,COX-2, | en |
| dc.relation.page | 98 | |
| dc.identifier.doi | 10.6342/NTU201901588 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-07-22 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-108-1.pdf 目前未授權公開取用 | 3.52 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。