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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李心予 | zh_TW |
| dc.contributor.advisor | Hsinyu Lee | en |
| dc.contributor.author | 虞智凱 | zh_TW |
| dc.contributor.author | Zhi-Kai Yu | en |
| dc.date.accessioned | 2025-06-05T16:09:20Z | - |
| dc.date.available | 2025-06-06 | - |
| dc.date.copyright | 2025-06-05 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-05-29 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/97411 | - |
| dc.description.abstract | 神經母細胞瘤是嬰兒期最常見的顱外實體腫瘤，起源於胚胎發育期間神經脊細胞的異常增生，通常發生於與交感神經系統相關的區域。芳香烴接受器（Aryl hydrocarbon receptor, AHR）為一種配體活化的轉錄因子，已知能促進神經母細胞瘤細胞的分化。四氫皮質酮（Tetrahydrocorticosterone, THB）作為一種內源性糖皮質激素，近期被鑑定為可活化AHR的內源性配體，並能調控斑馬魚的神經生成與神經分化。此外，一種結構上與THB相似的合成化合物，稱為Compound Y，亦已被開發。基於上述發現，本研究假設Compound Y與THB可透過活化AHR，促進神經母細胞瘤細胞分化，進而抑制其增生。在本研究中，Compound Y與THB皆可有效抑制神經母細胞瘤細胞的增生，並提升神經分化標誌物，包括生長相關蛋白43（GAP43）與神經元特異性烯醇酶（NSE）的表現。此外，本研究亦建立一套以GAP43啟動子活性為基礎的螢光酶篩選平台，以加速分化促進劑的篩選流程。利用來自TH-MYCN轉基因小鼠的原代神經母細胞瘤細胞進行體外實驗，進一步確認Compound Y具有抑制細胞增生的作用。體內分析亦顯示，Compound Y能顯著延緩腫瘤進展並延長TH-MYCN小鼠的存活時間。綜合以上結果，Compound Y與THB具備透過AHR介導的分化機制治療神經母細胞瘤的潛力，為未來的治療策略提供重要依據。 | zh_TW |
| dc.description.abstract | Neuroblastoma is the most common extracranial solid tumor in infancy, originating from aberrant proliferation of neural crest cells during embryonic development and typically arising in regions associated with the sympathetic nervous system. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, has been shown to promote the differentiation of neuroblastoma cells. Tetrahydrocorticosterone (THB), a glucocorticoid, was recently identified as an endogenous AHR activator that regulates neurogenesis and neural differentiation in zebrafish. In addition, a synthetic compound structurally similar to THB, referred to as Compound Y, has been developed. Based on these findings, it was hypothesized that both Compound Y and THB promote neuroblastoma cell differentiation through AHR activation, thereby inhibiting cell proliferation. In this study, both Compound Y and THB were demonstrated to inhibit neuroblastoma cell proliferation while enhancing the expression of neural differentiation markers, including growth-associated protein 43 (GAP43) and neuron-specific enolase (NSE). To facilitate efficient identification of differentiation-inducing compounds, a luciferase-based screening platform targeting GAP43 promoter activity was established. Additionally, ex vivo experiments using primary neuroblastoma cells derived from TH-MYCN transgenic mice confirmed the growth-inhibitory effects of Compound Y. In vivo analysis further demonstrated that Compound Y significantly slowed tumor progression and prolonged survival in TH-MYCN mice. Collectively, these findings highlight the therapeutic potential of Compound Y and THB in neuroblastoma treatment by targeting AHR-mediated differentiation pathways. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-06-05T16:09:20Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-06-05T16:09:20Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 論文口試委員審定書 I
誌謝 II 中文摘要 III Abstract IV Table of Contents VI List of Figures VIII 1. Introduction 01 1-1 Neuroblastoma 01 1-2 Aryl hydrocarbon receptor 06 1-3 Tetrahydrocorticosterone 10 Rationale 12 2. Materials and methods 13 2-1 Cell culture 13 2-2 Chemical reagents 13 2-3 Cell viability assay 14 2-4 Western blot 14 2.5 Plasmid construction and luciferase assay 16 2-6 Bioinspired Nanodroplet Processing (BioNDP) platform 16 2-7 Primary tumor cells isolation 17 2-8 Animal maintenance 18 2-9 Statistical analysis 19 3. Results 21 3-1 Compound Y and THB inhibit neuroblastoma cell proliferation 21 3-2 Compound Y and THB induce neuronal differentiation in neuroblastoma cells 21 3-3 Compound Y and THB enhance GAP43 promoter activity in SK-N-SH cells 22 3-4 Compound Y inhibits proliferation of primary neuroblastoma cells 23 3-5 Compound Y attenuates neuroblastoma tumor growth in vivo 24 3-6 Compound Y prolongs survival in TH-MYCN mice 24 4. Discussion 26 5. References 29 6. Figures 40 | - |
| dc.language.iso | en | - |
| dc.subject | 芳香烴接受器 | zh_TW |
| dc.subject | TH-MYCN轉基因小鼠 | zh_TW |
| dc.subject | 神經母細胞瘤 | zh_TW |
| dc.subject | 神經分化 | zh_TW |
| dc.subject | 四氫皮質酮 | zh_TW |
| dc.subject | Neural differentiation | en |
| dc.subject | Neuroblastoma | en |
| dc.subject | TH-MYCN transgenic mice | en |
| dc.subject | Tetrahydrocorticosterone | en |
| dc.subject | Aryl hydrocarbon receptor | en |
| dc.title | 四氫皮質酮和其異構體對於神經母細胞瘤治療之研究 | zh_TW |
| dc.title | Investigating the Effect of Tetrahydrocorticosterone and Its Isomers on Neuroblastoma Treatment | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 許文明;廖永豐;吳沛翊 | zh_TW |
| dc.contributor.oralexamcommittee | Wen-Ming Hsu;Yung-Feng Liao;Pei-Yi Wu | en |
| dc.subject.keyword | 四氫皮質酮,芳香烴接受器,神經分化,神經母細胞瘤,TH-MYCN轉基因小鼠, | zh_TW |
| dc.subject.keyword | Tetrahydrocorticosterone,Aryl hydrocarbon receptor,Neural differentiation,Neuroblastoma,TH-MYCN transgenic mice, | en |
| dc.relation.page | 54 | - |
| dc.identifier.doi | 10.6342/NTU202501007 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-05-29 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生命科學系 | - |
| dc.date.embargo-lift | 2025-06-06 | - |
| 顯示於系所單位： | 生命科學系 | |
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