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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡丰喬 | |
dc.contributor.author | Guan-Hung Kuo | en |
dc.contributor.author | 郭冠宏 | zh_TW |
dc.date.accessioned | 2021-06-15T11:27:19Z | - |
dc.date.available | 2017-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-18 | |
dc.identifier.citation | 1. 認識頭頸癌. Available from: http://cisc.twbbs.org/lib/project/books/book01.php.
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Dey, J.H., et al., Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis. Cancer Res, 2010. 70(10): p. 4151-62. 61. Faraone, D., et al., Heterodimerization of FGF-receptor 1 and PDGF-receptor-alpha: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells. Blood, 2006. 107(5): p. 1896-902. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49408 | - |
dc.description.abstract | Head and neck squamous cell carcinoma (HNSCC) causes significantly high morbidity and mortality in Taiwan, but effective treatments remain lacking. Therefore, our specific aim is to identify novel therapeutic targets against the progression of HNSCC. Fibroblast growth factor receptor 3 (FGFR3), a tyrosine kinase receptor, is critical for embryogenesis, wound healing and angiogenesis. Its aberrant expression causes developmental disorders and several cancers, including multiple myeloma, bladder cancer and prostate cancer. Recent reports suggested that differential expression of FGFR3 isoforms was linked to tumor progression in colorectal and pancreatic cancers. However, whether and how FGFR3 contributes to HNSCC progression is not known. To answer these questions, we examined the expression levels of FGFR3 isoforms in HNSCC from patients of different clinical stages. We found that in late stages of HNSCC, the expression levels of FGFR3 went up slightly. Among the isoforms, FGFR3IIIc isoform was slightly decreased, but FGFR3IIIb isoform did not change during tumor progression. These results were different from previous reports about FGFR3 in other cancers. We therefore perturbed FGFR3 activities in HNSCC cell lines to observe their effects on cell migration. Our results showed that FGFR3 knockdown increased cell migration, and that FGFR3IIIb overexpression reduced cell motility and decreased ERK & AKT signaling. However, FGFR3IIIc manipulation showed no effects on cell migration. These results imply that FGFR3IIIb suppresses HNSCC progression. In the meantime, our results also revealed that (1) effects of FGFR inhibitors on cell migration were regulated by other receptor signaling, such as epithelial growth factor receptor (EGFR), and (2) FGFR2 inhibition reduced cell motility. Though these in vitro data were not totally consistent with clinical data, our findings suggest that FGFR3 has complicated interactions with FGFR2 and other signal transduction molecules. Further investigation is needed to clarify these puzzles | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:27:19Z (GMT). No. of bitstreams: 1 ntu-105-R03443020-1.pdf: 5070078 bytes, checksum: 29cad5bf33117296a88cce05708a7a32 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii ABSTRACT iii 目錄 v 圖目錄 x 表目錄 xii 第一章 導論 1 1. 頭頸部鱗狀上皮細胞癌 (Head and neck squamous cell carcinoma)是台灣重要的健康問題 1 1-1 頭頸癌概論及流行病學 1 1-2 臨床治療及其限制 2 2. 上皮-間質轉換(Epithelial to mesenchymal transition ,EMT)影響了頭頸癌的轉移 2 2-1 上皮-間質轉換是癌症轉移的重要階段 2 2-2 上皮-間質轉換與頭頸癌的進展有關 3 3. 纖維母細胞生長因子受器(Fibroblast growth factor receptors ,FGFRs)影響了EMT與癌症轉移 4 3-1 FGFRs是EMT的marker 4 3-2 FGFR的構造及訊息傳遞 4 3-3 FGFRs的表現與isoform和疾病的進展有關 6 3-4 FGFRs 在頭頸癌中有高度表現 7 4. 研究動機 7 第二章 材料與方法 9 1. 細胞培養 9 2. 細胞遷移實驗(Cell migration assay) 9 2-1 細胞前置處理 9 2-2 活細胞攝影 (Live cell imaging) 9 2-3 影像分析 10 3. 細胞蛋白質萃取(Protein extraction)與西方墨點法(Western blotting) 10 3-1 細胞蛋白質萃取 10 3-2 膠體製備及電泳 11 3-3 電泳及蛋白質轉漬 11 3-4 一級抗體與二級抗體免疫結合 11 3-5 ECL呈色及定量分析 13 3-6 Western blot buffer 成分配方 13 4. 核糖核酸萃取與反轉錄酶聚合酶鏈反應 (RNA extraction & Reverse transcription polymerase chain reaction, RT-PCR) 14 4-1 核糖核酸萃取 14 4-2 反轉錄反應 14 4-3 聚合酶鏈反應(Polymerase chain reaction, PCR) 15 4-4 膠體製備及電泳 16 4-5 即時聚合酶連鎖反應(Real-time polymerase chain reaction, Real-time PCR) 16 5. 慢病毒基因靜默技術 (Lentivirus shRNA knockdown) 17 5-1 病毒來源 17 5-2 慢病毒感染流程 17 6. 質體DNA過度表現(Plasmid DNA overexpression) 18 7. 流式細胞分選(Cell sorting) 18 第三章 結果 19 1. 頭頸癌臨床表徵與纖維母細胞生長因子受器第三型(FGFR3)表現的關係 19 1-1 臨床檢體收集 19 1-2 FGFR3的表現量與臨床分期、腫瘤大小的關係 19 2. 纖維母細胞生長因子受器(FGFRs)在頭頸癌細胞株的表現 22 2-1 蛋白質表現量分析 22 2-2 mRNA表現量分析 23 3. 以細胞遷移實驗來觀察FGFRs和癌細胞轉移的關係 23 4. FGFRs抑制劑AZD4547對細胞遷移的影響 25 4-1 AZD4547藥物對FGFRs的抑制能力 25 4-2 在full serum環境下給予藥物對細胞遷移的影響 25 4-3 不同纖維母細胞生長因子對細胞遷移之影響 26 4-4 在serum free環境下給予藥物對細胞遷移的影響 27 5. FGFR3表現量對細胞遷移能力之影響 30 5-1 FGFRs基因靜默(shRNA Knockdown)對細胞遷移之影響 30 5-2 過量表現(Overexpression)FGFR3對細胞遷移之影響 34 6. FGFR3過量表現對下游訊息傳遞的影響 38 第四章 討論 41 1. FGFR3IIIb減緩細胞移動,IIIc沒有顯著效果 41 2. 抑制FGFR2能減緩細胞移動 41 3. FGR3IIIb過量表現能使下游訊息傳遞減弱 42 4. FGFR3IIIb可能和FGFR2形成heterodimmer 42 5. FGFR3IIIc可能影響其他細胞功能 44 6. 未來方向 45 第五章 參考文獻 46 第六章 補充資料 50 1. FGF與FGFR的結合專一性 50 2. 程式碼(Scripts) 51 2-1 標定細胞核在每張影像中的位置(z_calcnuclei.m) 51 2-2 對細胞移動路徑進行追蹤(z_tracenuclei.m) 53 2-3 計算各個細胞移動時的參數(z_getcellparameters.m) 54 2-4 將細胞移動的影像製作成影片(z_plot_cell_traces.m) 57 2-5 利用shRNA病毒盤的配置來整理細胞移動的參數資料(calc_shRNA_speed.m) 59 2-6 檢查軟體在每張影像中所計算到的細胞數(checkallcellden.m by 軒兆) 61 | |
dc.language.iso | zh-TW | |
dc.title | 纖維母細胞生長因子受器第三型對頭頸部鱗狀上皮細胞癌細
胞遷移與癌症病程的影響 | zh_TW |
dc.title | Fibroblast growth factor receptor 3 affects cell migration and cancer progression in head and neck squamous cell carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 賈景山,張玉芳 | |
dc.subject.keyword | 頭頸癌,FGFR3,癌症轉移,細胞遷移,異構體轉換, | zh_TW |
dc.subject.keyword | Head and neck cancer,FGFR3,cancer metastasis,cell migration,isoform switch, | en |
dc.relation.page | 61 | |
dc.identifier.doi | 10.6342/NTU201603057 | |
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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