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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79022完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳青周 | zh_TW |
| dc.contributor.author | 賴昱岑 | zh_TW |
| dc.contributor.author | Yu-Tsen Lai | en |
| dc.date.accessioned | 2021-07-11T15:37:23Z | - |
| dc.date.available | 2024-02-28 | - |
| dc.date.copyright | 2018-10-11 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Reference
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79022 | - |
| dc.description.abstract | 表皮生長因子酪胺酸激酶抑制劑(EGFR-TKI)作為activating mutation非小細胞肺癌病人之一線用藥，初期能有效抑制腫瘤生長，但抗藥性終究會產生而導致腫瘤復發。本研究發現，第一代(HCC827/IR)及第三代(H1975/AR)抗藥性細胞株皆表現EMT及癌幹細胞之特性，且伴隨組蛋白去乙醯酶6(HDAC6)高度表現。HDAC6選擇性抑制劑ACY1215可反轉EMT並減少細胞遷移。ACY1215也能透過停滯細胞週期於S或是G2/M時期，進而誘發細胞凋亡、抑制群落形成。ACY1215與EGFR-TKI之加成藥效能克服對第一代抗藥性細胞及第三代抗藥性細胞產生之繼發性抗藥性。另一方面，引用shRNA 減弱HDAC6之表現，可降低波形蛋白(Vimentin)及ALDH1A1之表現。由於HCC827/IR不具有T790M突變、H1975/AR不具有C797S突變，說明HDAC6可能是導致非小細胞肺癌抗藥性之罪魁禍首。 | zh_TW |
| dc.description.abstract | As the first-line treatment for NSCLC patients with EGFR activating mutations, EGFR-TKIs effectively inhibit tumor progression but acquired resistance invariably develops. In this study, we found that both gefitinib-resistant (HCC827/IR) and AZD9291-resistant (H1975/AR) cells expressed characteristics of EMT and CSC, along with HDAC6 overexpression. A selective HDAC6 inhibitor-ACY1215 not only reversed EMT but also reduced cell migration. Meanwhile, ACY1215 could trigger apoptosis through cell cycle arrest at S or G2/M phase and further inhibited colony formation. Synergistic interaction between ACY1215 and EGFR-TKIs overcame the acquired resistance in both HCC827/IR and H1975/AR. On the other hand, knockdown of HDAC6 down-regulated the protein level of Vimentin and ALDH1A1. Since HCC827/IR and H1975/AR did not harbor T790M and C797S respectively, these results demonstrated that HDAC6 might be the culprit to confer EGFR-independent resistance in NSCLC. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:37:23Z (GMT). No. of bitstreams: 1 ntu-107-R05443018-1.pdf: 5169762 bytes, checksum: 49e06c59f565cd74be687a743f0e04fb (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 論文口試委員審定書 i
致謝 ii 中文摘要 iii Abstract iv Abbreviation v Chapter 1. Introduction 1 1.1 Lung cancer 2 1.2 EGFR-targeted therapy in NSCLC 11 1.3 Histone Deacetylase inhibitor 16 1.4 Cancer stem cell (CSC) 23 1.5 Epithelial-mesenchymal transition (EMT) 29 Study motivation 33 Chapter 2. Materials and methods 34 Chapter 3. Results 44 Chapter 4. Discussion 64 Chapter 5. Conclusion 68 Reference 70 | - |
| dc.language.iso | en | - |
| dc.subject | 波形蛋白 | zh_TW |
| dc.subject | 組蛋白去乙醯?6 | zh_TW |
| dc.subject | 表皮生長因子酪胺酸激?抑制劑 | zh_TW |
| dc.subject | Vimentin | en |
| dc.subject | EGFR-TKI | en |
| dc.subject | HDAC6 | en |
| dc.title | HDAC6在非小細胞肺癌對EGFR-TKI抗藥性角色之研究 | zh_TW |
| dc.title | Role of HDAC6 in EGFR-TKI Resistant Non-Small Cell Lung Cancer | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 吳明賢;施金元 | zh_TW |
| dc.contributor.oralexamcommittee | ;; | en |
| dc.subject.keyword | 表皮生長因子酪胺酸激?抑制劑,組蛋白去乙醯?6,波形蛋白, | zh_TW |
| dc.subject.keyword | EGFR-TKI,HDAC6,Vimentin, | en |
| dc.relation.page | 75 | - |
| dc.identifier.doi | 10.6342/NTU201803249 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2018-08-15 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 藥理學研究所 | - |
| dc.date.embargo-lift | 2023-10-11 | - |
| 顯示於系所單位： | 藥理學科所 | |
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