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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳漢忠(Han-Chung Wu) | |
dc.contributor.author | Min-Shan Chen | en |
dc.contributor.author | 陳民珊 | zh_TW |
dc.date.accessioned | 2021-06-08T04:23:03Z | - |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-06-29 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22636 | - |
dc.description.abstract | 乳癌是女性常見的癌症之一,在所有女性癌症中,乳癌死亡率高居第二名。由於目前的化療藥物大都缺少腫瘤專一性難以將藥物高劑量帶到腫瘤,導致化療效果不彰。因此,發展能夠標的原位或轉移腫瘤的標的配體 (ligand) 是迫切需要的目標,此標的配體可以藉由配體藥引之藥物傳輸系統 (ligand-mediated delivery system) 來提高化療藥物的專一性,除此之外,此配體還可以用於造影系統來診斷癌症的發生或術後的評估。在先前的研究中,我們利用噬菌體顯現法 (phage display) 已尋找出能與乳癌細胞株結合的新穎胜肽,利用流式細胞發現帶有此胜肽的噬菌體可以辨認大部分的乳癌細胞株。更進一步,藉由穿透式的顯微鏡觀察細胞的核內體 (endosome), 發現相較於對照組有2.4倍的微脂體累積在實驗組中。施打帶有冷光酵素表現的人類乳癌細胞於免疫不全老鼠,藉由冷光造影監測藥物處理後的癌細胞生長情形,可發現攜帶抗癌藥物的標的微脂體可增加癌細胞的死亡,進而抑制腫瘤生長。更甚者,造影的研究顯示,此標的胜肽結合螢光造影物質後可以專一性的辨認腫瘤,在2小時的時候,累積在腫瘤的訊號為對照組的21.8倍。 目前的研究指出,此腫瘤標的胜肽不但可以提高藥物的專一性來增進乳癌的治療效果,未來還能用於造影系統來診斷或追蹤乳癌的發生。 | zh_TW |
dc.description.abstract | Breast cancer is the most common form of cancer and the second leading cause of cancer-related mortality among women worldwide. The lack of tumor specificity in anticancer drugs leads to dose-limiting toxicity that compromise the effect of chemotherapy. In addition, the development of a novel ligand for targeting of primary and metastatic breast cancers is exigently needed. This targeting ligand would not only improve the specificity of chemotherapy through ligand-mediated delivery system, but can also be used as an imaging system to detect and predict cancer prognosis. In the present study, we discovered a novel peptide, selected from phage-displayed peptide libraries that bound to breast cancer cells. We observed that this targeting phage had higher binding activity to most breast cancer cell lines using flow cytometry. When the targeting peptide was coupled to liposomes carrying doxorubicin, the drug acumination in the endosome of cancer cells was 2.4-fold as compared to control peptide using transmission electron microscopy analysis. Moreover, in severe combined immunodeficiency (SCID) mice bearing luciferase-expressing breast cancer xenografts, the targeting liposomes carrying doxorubicin specifically bound to tumor masses. The ligand-mediated drugs enhance death of cancer cells in xenografts model by monitoring of luminescent imaging from tumor. Furthermore, in the imaging studies, targeting peptides were conjugated with fluorescent agents to monitor cancer localization in tumor-bearing mice. Quantification of the fluorescence showed that 21.8-fold higher fluorescent agents accumulated in tumor from targeting group than of non-targeting group. The current study indicates that tumor-specific peptide may be used to improve the systemic treatment of breast cancer by increasing specificity of anticancer drugs and imaging probes to breast cancer. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:23:03Z (GMT). No. of bitstreams: 1 ntu-99-R97450004-1.pdf: 1754736 bytes, checksum: b192709833710c161f97327cd8e9d6e7 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii Abstract iii Contents v Introduction 1 1.1 Epidemiology of breast cancer 1 1.2 Types of Breast Cancer 2 1.3 Treatment of breast cancer 3 1.4 Targeted therapy of breast cancer 4 1.5 Imaging and diagnosis of breast cancer 11 1.6 Quantum dot imaging for cancer detection 13 1.7 Anti-cancer nanotechnology for cancer delivery 14 1.8 Peptide-mediated targeting liposomes 15 1.9 Isolation of tumor-homing peptides by in vitro phage display 16 Materials and Methods 18 2.1 Cell lines and cultures 18 2.2 Peptide synthesis and labeling 18 2.3 Identification of peptides binding to cancer cells 19 2.4 Preparation of synthetic peptide-conjugated liposomal doxorubicin 19 2.5 Endocytosis of liposome conjugates SP90 by BT483 20 2.6 Flow cytometry analysis 20 2.7 MTT cell proliferation Assay 21 2.8 Animal model for the study of tumor localization of liposomal doxorubicin 21 2.9 Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) staining 22 2.10 Immunoflurorescence 22 2.11 Synthesis of SP90-conjugated Quantum Dots (QDs) 23 2.12 Quantification of the number of viable cells by bioluminescence assay 23 2.13 In vivo imaging of human breast cancer xenografts 24 2.14 Phage labeling and imaging 25 2.15 Statistical analyses 25 Result 26 3.1 Effect of doxorubicin on breast cancer cell growth and cell proliferation 26 3.2 Binding activity of PC90 with breast cancer cell lines 26 3.3 Internalization of SP90-mediated liposomes by BT483 cells 27 3.4 Imaging in vitro and in vivo using SP90-QD nanoprobes 28 3.5 Imaging in vivo using labeled phage 29 3.6 Therapeutic effect of SP90-mediated targeting liposomes on late cancer stage 30 3.7 Examination of tumor blood vessels and apoptotic cells in the study of SP90-mediated targeting liposomes 31 3.8 SP90-conjugated liposomes enhanced drug delivery into tumor 31 3.9 Image and character of BT483-GL cells in vitro 32 3.10 Enhanced therapeutic efficacy of targeting liposomes in BT483-GL tumor models 33 Discussion 34 Figures 40 References 53 | |
dc.language.iso | en | |
dc.title | 乳癌細胞專一性胜肽運用於乳癌之治療及造影 | zh_TW |
dc.title | Breast cancer cell-specific peptides for targeted drug delivery and imaging | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張正琪(Cheng-Chi Chang),呂仁(Jean Lu) | |
dc.subject.keyword | 乳癌,配體,配體藥引藥物傳輸系統,噬菌體顯現法,標的微脂體,腫瘤標的胜肽, | zh_TW |
dc.subject.keyword | breast cancer,ligand,ligand-mediated delivery system,phage display,targeting liposome,tumor-specific peptide, | en |
dc.relation.page | 67 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-06-29 | |
dc.contributor.author-college | 牙醫專業學院 | 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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