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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡丰喬 | |
| dc.contributor.author | Ting-Xuan Lu | en |
| dc.contributor.author | 呂庭瑄 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:27:46Z | - |
| dc.date.available | 2016-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-17 | |
| dc.identifier.citation | Angelucci, A., and Bologna, M. (2007). Targeting vascular cell migration as a strategy for blocking angiogenesis: the central role of focal adhesion protein tyrosine kinase family. Curr Pharm Des 13, 2129-2145.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49418 | - |
| dc.description.abstract | 頭頸部鱗狀細胞癌(Head and neck squamous cell carcinoma, HNSCC)為發展進程迅速且目前無有效治療方法之癌症。故需找尋有效且新穎的治療方法。近期研究指出，鈣離子的訊息傳遞對細胞適當遷移以及極化極重要。不當的鈣離子訊息亦傳遞影響許多癌症生成，如乳癌、子宮頸癌以及大腸癌。因此，我們欲檢視頭頸癌生成時，鈣離子訊息傳遞是否受異常調控。
在55位頭頸癌病患檢體，我們發現store-operated calcium entry (SOCE)主要感受者以及作用者STIM1與ORAI1的mRNA表現量在臨床分期較嚴重的病患會下降。且STIM1/ORAI1 mRNA表現量與腫瘤大小呈負相關。因此我們假設SOCE會抑制頭頸癌的生成。 為了證明此假設，我們利用小分子藥物、RNA干擾以及過度表現方式，在三株頭頸癌細胞株，SAS、HSC-3以及CAL27中，調控SOCE的活性。結果顯示，利用藥理學方式抑制SOCE會增加HSC-3的速度；STIM1 knockdown會增加 HSC-3速度；以及在SAS過度表現STIM1後，細胞速度降低。因此STIM1可能具有抑制HNSCC細胞遷移的角色。為了研究在機轉上STIM1如何抑制癌細胞遷移，我們正在檢視與鈣離子相關且與細胞遷移相關的蛋白，如Pyk2、MLC、FAK以及paxillin。這些結果將會解釋在頭頸癌中SOCE對於細胞遷移以及癌症生成的影響。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:27:46Z (GMT). No. of bitstreams: 1 ntu-105-R02443028-1.pdf: 3924803 bytes, checksum: a68b58970c0e104d37243eeeca9f3fa7 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 目錄
縮寫表 3 中文摘要 4 Abstract 5 第一章、緒論 8 1. 頭頸部鱗狀細胞癌(Head and neck squamous cell carcinoma, HNSCC) 8 1-1 頭頸癌為重要的健康問題 8 1-2 侵犯及轉移(Invasion and metastasis)是頭頸癌重要與致死原因 9 1-3 轉移型頭頸癌治療缺乏有效的治療 9 2. 研究鈣離子以更了解頭頸癌 12 2-1鈣離子為影響癌細胞轉移之關鍵 12 2-2 鈣離子細胞遷移機轉 14 2-3 與細胞遷移相關的鈣離子訊息釋放 15 2-4 細胞遷移時鈣離子的恆定性維護 16 2-5 細胞遷移時鈣離子存量的維持Store-operated Ca2+ (SOC) Influx 18 2-6 . Stromal interaction molecule 1 (STIM1)影響許多癌症進程 21 研究動機：釐清STIM1在頭頸癌中的角色 23 第二章、材料與方法 26 第三章、結果 31 3-1 STIM1表現於頭頸癌細胞及SOCE抑制劑BTP2增加HSC-3細胞遷移速率 31 3-1-1 STIM1在細胞基本表現量及細胞遷移實驗方法 31 3-1-2 SOCE抑制劑對細胞遷移影響 32 3-2 利用Knockdown方式降低STIM1表現量 35 3-2-1 STIM1 短暫knockdown對於細胞遷移影響 35 3-2-2 利用knockdown STIM1之stable line觀察STIM1下降對細胞遷移影響 41 3-3過度表現YFP-STIM1對細胞遷移影響 47 3-3-1利用質體過度表現YFP-STIM1 47 3-3-2病毒感染使SAS過度表現YFP-STIM1 50 3-3-3 SAS給予不同MOI量病毒過度表現STIM1對速度影響 52 3-3-4 SAS中表現不同表現程度YFP/YFP-STIM1對細胞遷移影響 54 3-3-5 SAS表現不同程度YFP/YFP-STIM1 starvation後對細胞遷移影響 57 3-4 STIM1 表現下降影響細胞遷移機制 59 3-4-1 HSC-3 STIM1 knockdown增加細胞移動速度 59 3-4-2 CAL27 STIM1 knockdown 63 3-4-3 Serum starvation 條件下SAS過度表現YFP-STIM1對Pyk2影響 65 3-4-5 一般培養環境下SAS過度表現YFP-STIM1後Pyk2磷酸化表現 66 3-4-6 SAS過度表現YFP-STIM1後對MLC磷酸化影響 68 第四章、結論與討論 72 4-1 結論 72 4-1-1細胞遷移 72 4-1-2 鈣離子下游Pyk2與MLC磷酸化變化 73 4-2討論 74 4-2-1 臨床檢體中STIM1在不同TNM stage與腫瘤之mRNA表現量 74 4-2-2細胞基本STIM1含量與細胞遷移 75 4-3機轉：鈣離子下游Pyk2以及MLC磷酸化變化 83 4-4 展望 85 附錄 86 Reference 99 | |
| dc.language.iso | zh-TW | |
| dc.subject | ORAI1 | zh_TW |
| dc.subject | store-operated Ca2+ entry (SOCE) | zh_TW |
| dc.subject | 頭頸癌 | zh_TW |
| dc.subject | 細胞遷移 | zh_TW |
| dc.subject | STIM1 | zh_TW |
| dc.subject | store-operated Ca2+ entry (SOCE) | en |
| dc.subject | STIM1 | en |
| dc.subject | ORAI1 | en |
| dc.subject | head and neck cancer | en |
| dc.subject | cell migration | en |
| dc.title | STIM1對頭頸部鱗狀細胞癌遷移之機轉探討 | zh_TW |
| dc.title | STIM1 in head and neck squamous cell carcinoma: focusing on its role in cancer cell migration | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 陳青周 | |
| dc.contributor.oralexamcommittee | 張玉芳,張偉嶠 | |
| dc.subject.keyword | 頭頸癌,STIM1,ORAI1,store-operated Ca2+ entry (SOCE),細胞遷移, | zh_TW |
| dc.subject.keyword | head and neck cancer,STIM1,ORAI1,store-operated Ca2+ entry (SOCE),cell migration, | en |
| dc.relation.page | 106 | |
| dc.identifier.doi | 10.6342/NTU201602988 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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