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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 張逸良(Yih-Leong Chang) | |
dc.contributor.author | Kai-Hsiang Chuang | en |
dc.contributor.author | 莊凱翔 | zh_TW |
dc.date.accessioned | 2021-06-16T17:24:59Z | - |
dc.date.available | 2012-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-16 | |
dc.identifier.citation | 1 Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69-90
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Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res 2008; 14:4877-4882 56 Sakuma Y, Matsukuma S, Yoshihara M, et al. Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations. Am J Clin Pathol 2007; 128:100-108 57 Sequist LV, Bell DW, Lynch TJ, et al. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 2007; 25:587-595 58 Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7:169-181 59 Wheeler DL, Dunn EF, Harari PM. Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat Rev Clin Oncol 2010; 7:493-507 60 Eley GD, Reiter JL, Pandita A, et al. A chromosomal region 7p11.2 transcript map: its development and application to the study of EGFR amplicons in glioblastoma. Neuro Oncol 2002; 4:86-94 61 Park S, James CD. ECop (EGFR-coamplified and overexpressed protein), a novel protein, regulates NF-kappaB transcriptional activity and associated apoptotic response in an IkappaBalpha-dependent manner. Oncogene 2005; 24:2495-2502 62 Baras A, Yu Y, Filtz M, et al. Combined genomic and gene expression microarray profiling identifies ECOP as an upregulated gene in squamous cell carcinomas independent of DNA amplification. Oncogene 2009; 28:2919-2924 63 Baras A, Moskaluk CA. Intracellular localization of GASP/ECOP/VOPP1. J Mol Histol 2010; 41:153-164 64 Baras AS, Solomon A, Davidson R, et al. Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury. Lab Invest 2011; 91:1170-1180 65 Kendall J, Liu Q, Bakleh A, et al. 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Am J Respir Crit Care Med 2009; 179:123-133 71 Lin JC, Yang SC, Hong TM, et al. Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-kappaB pathways. J Med Chem 2009; 52:1903-1911 72 Slebos RJ, Livanos E, Yim HW, et al. Chromosomal abnormalities in bronchial epithelium from smokers, nonsmokers, and lung cancer patients. Cancer Genet Cytogenet 2005; 159:137-142 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63975 | - |
dc.description.abstract | 肺癌是致死率相當高的一種癌症。由於近幾年研究人員發現EGFR的突變可能和肺癌的形成有關,尤其是在亞州地區,是以有一系列針對EGFR相關的研究不斷的被加以報導;其中科學家發現當位於第七號染色體上的EGFR基因拷貝數目擴增時,常伴隨著有VOPP1(vesicular, overexpressed in cancer, prosurvival protein 1)基因的共同擴增現象產生。儘管目前已知VOPP1是一個具有促進細胞存活(pro-survival)能力的基因,但其在癌化過程中所扮演的角色與其和EGFR訊號因子間的關聯性仍不十分清楚。在本篇論文中,我們首先利用實驗室所建立的兩組細胞株模組CL1-5 / CL1-0(具有不同癌侵襲能力)以及PC9 / PC9 IR(對於標靶藥物Iressa不同反應性),建立VOPP1 overexpression 與knock down的穩定表現細胞;進一步,利用這些細胞進行一系列的功能性檢測,藉以瞭解VOPP1對於細胞移動能力、細胞凋亡,細胞增生及其對標把藥物治療之反應之影響。實驗結果顯示,當細胞大量表現VOPP1蛋白質時,可能藉由調控鈣黏著素E的表現進而抑制細胞的移動能力。不僅如此,我們的結果也發現,抑制VOPP1可以使對於標靶藥物Irresa具有抗藥性之PC9IR細胞株回復對Iressa的敏感度;同時我們也發現大量表現VOPP1時,對癌細胞生長速率並不會有太大的變化,但抑制VOPP1的表現量則會使得癌細胞生長速率減緩。綜合以上的研究結果,我們可以了解VOPP1在抑制癌轉移及標靶藥物抗藥性的治療上均扮演著極為重要的角色;未來若能針對其相關作用機轉作進一步的研究將有助於肺癌病患的治療。 | zh_TW |
dc.description.abstract | Lung cancer is the leading cause of cancer-related mortality in the world. Recently, scientists find that EGFR mutation may correlate with lung cancer occurrence especially in Asia. For this reason, more and more references about EGFR and its signaling regulation have been reported. One of them is the finding about co-amplification of EGFR and VOPP1(vesicular, overexpressed in cancer, prosurvival protein 1)on chromosome 7. Until now, we only understand that VOPP1 can promote cell survival but the detail mechanism of VOPP1 in cancer progression and its cross-talk associated with EGFR signaling are still unclear. In this study, we first established VOPP1 overexpression and knock down stable cells in CL1-5/ CL1-0 and PC9/ PC9IR cell models. Then, we used these cell lines to explore the functional role of VOPP1 in cancer cell migration, apoptosis, cell proliferation and sensitivity of target therapy. Our results showed that VOPP1 could inhibit cell migration through up regulate the expression of E-cadherin. Not only this effect, we also observed that knock down the expression of VOPP1 in PC9IR cells can increase the sensitivity of Irresa. In cell proliferation, we also found that overexpression VOPP1 could not affect cell proliferation rate in all our experimental cells, but knock down the expression of VOPP1 in CL1-5 and PC9IR cells may attenuate cell proliferation in both cells. Collectively, we understand that VOPP1 play an important role in suppression of cancer metastasis and resistance of target therapy. It should be helpful for lung cancer treatment to clarify the detail mechanism of how VOPP1 involved in cell migration and drug resistance in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:24:59Z (GMT). No. of bitstreams: 1 ntu-101-R99444005-1.pdf: 1271340 bytes, checksum: c1a0d38078d4249854d62bb5bd80caf8 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 中文摘要 2
Abstract 3 目錄 4 第一章 前言 8 1 肺癌 8 1.1 癌轉移 8 1.2 上皮生長因子接受器 11 2 VOPP1 14 2.1 VOPP1於細胞內位置 15 2.2 VOPP1透過NF-κB促進細胞存活 16 2.3 VOPP1與EGFR關係 16 3 實驗目標: 18 第二章 材料方法 19 1 細胞培養 19 2 VOPP1 表現質體的建構 19 3 VOPP1 相關病毒製備及穩定表現細胞的建立 20 4 核醣核酸萃取 20 5 逆轉錄酶鏈式反應 21 6 即時定量逆轉錄酶鏈式反應 21 7 西方免疫轉漬法 22 8 傷口癒合試驗 22 9 細胞侵襲能力試驗 23 10 單細胞定位追蹤 23 11 抗體 24 12 細胞增生試驗 24 13 細胞存活度試驗 24 第三章 結果 26 1 大量表現VOPP1於高癌侵襲能力的細胞株CL1-5降低細胞爬行能力(migration ability) 26 2 利用單細胞追蹤試驗來檢測VOPP1對於細胞爬行能力的影響 27 3 大量表現VOPP1於細胞株CL1-5誘使鈣黏著素E (E-cadherin)表現量上升 27 4 在肺腺癌細胞株CL141中大量表現VOPP1使得細胞爬行能力下降以及E-cadherin表現量上升 29 5 抑制內生性VOPP1表現量於細胞株CL1-0 降低E-cadherin表現量,並引起細胞型態改變 30 6 大量表現VOPP1似乎對於CL1-5的癌侵襲能力不造成影響 31 7 VOPP1對於細胞生長速率的影響 31 8 VOPP1在EGFR活化突變的細胞株中表現量較多 32 9 抑制內生性VOPP1表現量提升細胞株PC9 IR對標靶藥物Iressa的反應 33 10 大量表現VOPP1於Iressa敏感細胞株PC9似乎沒有顯著增加藥物耐受性 34 第四章 討論 35 第五章 圖表及列表 38 Figure 1. 在具有癌高侵襲能力的肺癌細胞株CL1-5 中大量表現VOPP1可以降低細胞爬行能力 39 Figure 2. 利用單細胞追蹤試驗來分析細胞爬行能力 41 Figure 3. 在高癌侵襲能力的肺癌細胞株CL1-5 中大量表現VOPP1誘使 E-cadherin mRNA表現量上升 42 Figure 4. 在高癌侵襲能力的肺癌細胞株CL1-5 中大量表現VOPP1誘使E-cadherin 蛋白表現量上升 43 Figure 5. 在具有癌高侵襲能力的肺癌細胞株CL141 中大量表現VOPP1細胞爬行能力下降,提高E-cadherin表現量 45 Figure 6. 抑制內生性VOPP1的細胞株CL1-0 使得E-cadherin表現量下降,細胞型態傾向上皮-間質轉化 46 Figure 7. 大量表現 VOPP1肺癌細胞株CL1-5 中似乎對於癌侵襲能力沒有顯著影響 48 Figure 8. VOPP1對於細胞增生造成的影響 49 Figure 9. 肺癌細胞株內生性VOPP1訊息核醣核酸表現量 50 Figure 10. 肺癌細胞株內生性VOPP1蛋白表現量 51 Figure 11. 在對標靶藥物Iressa有抗性的細胞株PC9 IR中抑制內生性 VOPP1可提高細胞對於藥物的反應 52 Figure 12. 在對標靶藥物敏感的細胞株PC9中大量表現VOPP1似乎不會增加細胞對藥物的抗性 53 Table 1. 細胞株整理 54 Table 2 . VOPP1 表現質體的建構使用核酸引子 55 Table 3 . 逆轉錄酶鏈式反應使用引子 56 第六章 參考文獻 57 | |
dc.language.iso | zh-TW | |
dc.title | VOPP1在肺腺癌中透過提高E-cadherin表現量進而抑制細胞移動能力 | zh_TW |
dc.title | VOPP1 Inhibits Cell Migration Through Up-regulatory E-cadherin in Lung Adenocarcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 楊泮池(Pan-Chyr Yang) | |
dc.contributor.oralexamcommittee | 陳惠文(Huei-Wen Chen) | |
dc.subject.keyword | 肺癌,癌轉移,Iressa,EGFR,VOPP1, | zh_TW |
dc.subject.keyword | lung cancer,metastasis,Iressa,EGFR,VOPP1, | en |
dc.relation.page | 67 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-16 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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