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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳漢忠 | |
dc.contributor.author | Wen-Wei Lin | en |
dc.contributor.author | 林文瑋 | zh_TW |
dc.date.accessioned | 2021-06-08T05:06:33Z | - |
dc.date.copyright | 2011-10-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-04 | |
dc.identifier.citation | Albelda SM, Oliver PD, Romer LH, Buck CA. (1990). EndoCAM: a novel endothelial cell–cell adhesion molecule. The Journal of Cell Biology 110, 1227–1237.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23632 | - |
dc.description.abstract | 現今針對頭頸部癌的治療方式,早期癌症是以放射線療法或外科手術切除為主,晚期癌症則是以放射線療法結合化療或手術的合併治療予以控制。然而癌細胞對藥物所產生的抗藥性,是導致治療失敗及病人死亡的主要原因。因此尋找有關癌細胞抗藥性的基因,是迫切需要解決的問題。過去研究顯示,腫瘤微環境的刺激會誘導癌細胞內一內質網伴隨蛋白GRP78的大量表現,其作用與癌細胞的抗藥性有關。除了抗藥性,GRP78也參與腫瘤的生長、移動能力及轉移等。目前對於GRP78在頭頸部癌細胞內所扮演的角色尚未完全醭清,因此我們希望了解GRP78在頭頸部癌之致病機轉中,所扮演的功能性角色為何。在本研究中,我們分析臨床檢體及細胞株後發現,GRP78的表現量與頭頸部癌的惡性程度呈現正相關性。接著利用人類反轉錄病毒載體攜帶短夾型RNA(shRNA)抑制GRP78在口腔癌細胞內的表現,發現其生長、移動、轉移能力及抗藥性均有明顯受到抑制的現象。我們進一步將穩定抑制GRP78的口腔癌細胞株異體移植至免疫缺陷型小鼠體內後,發現抑制GRP78的表現除了影響細胞生長外,也會透過影響HIF1α及VEGF 的表現抑制腫瘤血管的生成。此外,將穩定抑制GRP78 的口腔癌細胞株進行DNA 微陣列分析後發現,GRP78 的下降會影響到許多與癌症發展相關基因的表現。綜合以上結果,GRP78 在頭頸部癌中,不僅會影響細胞生長、移動、抗藥性及腫瘤血管生成的能力,也會影響許多基因的表現,可能使癌症更加惡化。因此GRP78 未來將有潛力成為新的治療標的分子。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:06:33Z (GMT). No. of bitstreams: 1 ntu-100-R98450004-1.pdf: 14951759 bytes, checksum: 81a2767126505f58e34f091af2e11de9 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 誌謝 .................................................................................................................................. i
中文摘要 .......................................................................................................................... ii Abstract .......................................................................................................................... iii Contents .......................................................................................................................... iv Content of figures and tables ........................................................................................ vi List of abbreviations ....................................................................................................... 1 Introduction .................................................................................................................... 4 1.1 Epidemiology of head and neck cancer .............................................................. 4 1.2 Treatments of head and neck cancer................................................................... 4 1.3 Drug resistance in head and neck cancer ............................................................ 5 1.4 Heat shock proteins (HSPs) and GRP78 protein ................................................ 6 1.5 Unfolded protein response (UPR) ...................................................................... 7 1.6 Roles of GRP78 in cancer progression ............................................................... 9 1.7 Roles of GRP78 in tumor angiogenesis ............................................................ 11 1.8 Roles of GRP78 in drug resistance ................................................................... 11 1.9 Mechanisms for GRP78 in promoting cancer progression and drug resistance 12 1.10 Application of nucleic acid-based agents and chemotherapeutic agents for cancer treatment ...................................................................................................... 13 Materials and Methods ................................................................................................ 16 2.1 Cell lines and culture condition ........................................................................ 16 2.2 Western blotting (WB) ..................................................................................... 16 2.3 Transduction with lentiviral vectors expressing shRNA .................................. 17 2.4 Colony-forming assays ..................................................................................... 18 2.5 Cell proliferation assay ..................................................................................... 18 2.6 Cell migration and Invasion ............................................................................. 18 2.7 Real-time quantitative PCR assays ................................................................... 19 2.8 Luciferase activity assay ................................................................................... 20 2.9 Immunofluorescence assay (IFA) ..................................................................... 20 2.10 Immunohistochemistry (IHC) ........................................................................ 21 2.11 Cytotoxcity assay ............................................................................................ 22 2.12 Cell cycle analysis .......................................................................................... 22 2.13 Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay ....................................................................................................................... 22 2.14 Xenograft tumors ............................................................................................ 23 2.15 cDNA microarray ........................................................................................... 23 2.16 Statistical analysis .......................................................................................... 24 Results ............................................................................................................................ 25 3.1 Elevated expression of GRP78 in various cancers ........................................... 25 3.2 GRP78 plays an important role in carcinogenesis of head and neck cancer .... 25 3.3 Knockdown of GRP78 inhibits cell growth and colony formation in vitro ..... 26 3.4 Knockdown of GRP78 suppresses cell migration and invasion in vitro .......... 26 3.5 Knockdown of GRP78 inhibits tumor growth in vivo ...................................... 27 3.6 Knockdown of GRP78 reduces tumor angiogenesis ........................................ 27 3.7 GRP78 regulates expression of multiple genes ................................................ 28 3.8 GRP78 regulates NF-κB transcriptional activity.............................................. 29 3.9 Up-regulation of GRP78 in tumor specimens after doxorubicin treatment...... 30 3.10 GRP78 confers drug resistance in SAS cells.................................................. 30 Discussion ...................................................................................................................... 32 References ..................................................................................................................... 53 | |
dc.language.iso | en | |
dc.title | 探討GRP78於頭頸部癌生成中扮演之功能性角色 | zh_TW |
dc.title | Study the Functional Roles of GRP78 in Tumorigenesis of Head and Neck Cancer | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林國儀,呂仁,高承福 | |
dc.subject.keyword | 頭頸部癌,口腔癌,GRP78,抗藥性,腫瘤血管生成, | zh_TW |
dc.subject.keyword | Head and neck cancer,GRP78,drug resistance,short hairpin RNA,hypoxia-inducible factor 1 alpha,vascular endothelial growth factor,angiogenesis, | en |
dc.relation.page | 60 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-07-05 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
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ntu-100-1.pdf 目前未授權公開取用 | 14.6 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。