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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19068完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳漢忠,江俊斌 | |
| dc.contributor.author | Meng-Jhe Chung | en |
| dc.contributor.author | 鍾孟哲 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:43:59Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-16 | |
| dc.identifier.citation | Arteaga C. Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol. 2003, 30, 3–14.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19068 | - |
| dc.description.abstract | 表皮生長因子受體 (EGFR)為erbB家族中的一員，在過去的文獻中發現其參與在數種癌症的發生與惡化。在30%上皮細胞癌中EGFR有突變、基因重複或是錯誤調節。因此研發專一性針對EGFR的標靶治療是具有前景的治療方式。本實驗室先前利用噬菌體顯示法 (phage display) 挑選出兩株能夠專一性結合表皮生長因子受體外域 (EGFR-Ex) 之人類單鍊免疫球蛋白變異區段 (scFv)。將標的表皮生長因子受體之人類單鍊免疫球蛋白變異區段與微脂體進行鍵結後，發現能提升微脂體與肝癌、肺癌以及頭頸部癌細胞株結合和內化。將此標的物與包裹藥物之微脂體進行鍵結後發現標的之微脂體與未標的之微脂體相比能更加有效毒殺癌細胞。接著以活體內腫瘤導向，發現能有效與腫瘤細胞結合。於治療異體移植頭頸部癌之免疫缺陷小鼠中，發現接上此標物物後能更加有效提升小鼠之存活。綜合上續之結果，發現標的表皮生長因子受體人類單鍊免疫球蛋白變異區段之微脂體藥物能更加有效提升藥物傳輸於治療頭頸部癌。 | zh_TW |
| dc.description.abstract | Epidermal growth factor receptor, a member of the ErbB family, has been reported to involve in pathogenesis and progression in a plethora of cancer types. Genetic aberration of EGFR such as activating mutation and amplification are implicated in about 30% of all epithelial cancers including head and neck squamous cell carcinoma (HNSCC). Therefore, it is rational and promising to develop a targeted regimen toward this receptor. Previous work of our laboratory acquired two novel scFvs that could specifically bind to EGFR extracellular domains (EGFR-Ex) through phage display technique. Conjugation of these two scFvs to liposome enhanced binding and internalization ability compared to non-targeting counterpart in cell lines of liver, lung and head and neck cancer cells. Furthermore, EGFR scFv-conjugated liposomal doxorubicin or vinorelbine could augment their cytotoxic effects on cancer cells. The specificity and binding ability of EGFR scFv were also verified through in vivo homing assay. In the FaDu-derived subcutaneous xenograft model, EGFR scFv-conjugated liposomal drugs reduced the tumor burden more efficiently and increased the survival rates than non-targeting liposomal drugs. Taken together, these results reveal the potential benefit of EGFR-specific scFv in respect of therapeutic enhancement of targeted drug delivery in the treatment of head and neck cancer. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:43:59Z (GMT). No. of bitstreams: 1 ntu-105-R03450011-1.pdf: 3944515 bytes, checksum: 28f9a84c8b3bcae25b298f483be68e02 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 中文摘要 3
Abstract 4 Contents 6 Content of figures and tables 8 List of abbreviations 9 Introduction 11 1.1 Epidemiology and pathogenesis of head and neck cancer 11 1.2 Detection and diagnosis of head and neck cancer 14 1.3 Treatment of head and neck cancer 14 1.4 Epidermal growth factor receptor (EGFR) 17 1.5 EGFR signaling pathway in cancer 18 1.6 Anti-EGFR targeted therapy 19 1.7 Resistance to anti-EGFR therapy 22 1.8 Nanoparticles drug delivery system 24 1.9 Targeted imaging system 25 1.10 Single chain variable fragment (scFv) 27 Material and Methods 30 2.1 Cell lines and culture condition 30 2.2 Protein extraction and Western blot analysis 30 2.3 Expression and purification of soluble scFv 31 2.4 Internalization assay of scFv 32 2.5 Preparation of EGFR scFv-conjugated liposomes containing SRB, doxorubicin or vinorelbine 33 2.6 Characterization of lipid nanoparticles 35 2.7 Internalization ability of liposome conjugates EGFR scFv 35 2.8 Cell viability assay 35 2.9 Enzyme-linked immunosorbent assay (ELISA) 36 2.10 In vivo homing experiments and tissue distribution of phages 37 2.11 Immunohistochemical staining of phage binding to tumor mass of xenograft 37 2.12 RNA extraction, quantitative reverse transcription polymerase chain reaction (qRT-PCR) 38 2.13 In vivo xenograft model for targeted therapeutic efficacy 39 2.14 Conjugation of scFv to quantum dots (QD) 39 2.15 Flow cytometric analysis 40 2.18 Statistical analysis 40 Results 42 3.1 Identification of endogenous EGFR expression in human cancer cell lines. 42 3.2 Expression and purification of anti-EGFR scFv. 42 3.3 Elevated binding and internalization ability of EGFR-s7 and EGFR-s10 scFv. 43 3.4 Enhancement of liposomal SRB binding and internalization ability by EGFR-s7 and EGFR-s10. 43 3.5 Production and characterization of EGFR-targeted scFv-conjugated liposomal drugs. 44 3.6 Enhancement of liposomal drug intracellular delivery and cytotoxicity in vitro by EGFR-s7 and EGFR-s10. 45 3.7 In vivo validation of tumor-homing ability of EGFR-targeted phage clones. 46 3.8 Therapeutic potential of combination therapy in HNSCC xenograft model. 47 3.9 In vitro validation of tumor-homing ability of EGFR-targeted phage clones. 47 Discussion 49 Table 53 References 70 | |
| dc.language.iso | en | |
| dc.subject | 藥物傳輸系統 | zh_TW |
| dc.subject | 單鍊免疫球蛋白變異區段 | zh_TW |
| dc.subject | 表皮生長因子受體 | zh_TW |
| dc.subject | 頭頸部癌 | zh_TW |
| dc.subject | EGFR | en |
| dc.subject | drug delivery systems | en |
| dc.subject | scFv | en |
| dc.subject | head and neck cancer | en |
| dc.title | 發展抗表皮生長因子受體人類單鍊抗體結合藥物傳輸系統於頭頸部鱗狀細胞癌之標靶治療 | zh_TW |
| dc.title | Development of Anti-EGFR scFv-mediated Drug Delivery Systems for Targeted Therapy of Head and Neck Squamous Cell Carcinoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王逸平,蕭培文,李文山 | |
| dc.subject.keyword | 頭頸部癌,表皮生長因子受體,單鍊免疫球蛋白變異區段,藥物傳輸系統, | zh_TW |
| dc.subject.keyword | head and neck cancer,EGFR,scFv,drug delivery systems, | en |
| dc.relation.page | 81 | |
| dc.identifier.doi | 10.6342/NTU201602146 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2016-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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