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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蕭寧馨 | |
| dc.contributor.author | Ying-Chen Huang | en |
| dc.contributor.author | 黃映晨 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:31:54Z | - |
| dc.date.available | 2023-08-23 | |
| dc.date.copyright | 2018-08-23 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-16 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78953 | - |
| dc.description.abstract | B型肝炎病毒X蛋白質 (HBx) 是由B型肝炎病毒所編碼出來的一種多功能性蛋白質，與肝癌的形成有關。異位類淋巴結構 (ELSs) 是由B細胞和T 細胞所組成的淋巴集結體，常見於慢性發炎的部位。先前的研究指出肝細胞中的ELSs對於肝癌病患有較差的預後，再者，ELSs的形成與淋巴毒素 (LT)-β所驅動之非典型NF-κB訊息傳遞途徑的活化有關。為了瞭解HBx在晚期肝癌中形成ELSs所扮演的角色，我們將HBx基因分別利用轉染和感染的方式植入肝癌細胞株中，並以即時定量聚合酶連鎖反應和西方墨點法去鑑定LT家族與非典型NF-κB相關訊息的表達。研究結果顯示，在表現HBx的HA22T/VGH肝癌細胞株中，會增加LTα和LTβ的表現，並且透過活化非經典型NF-κB訊息傳遞路徑，促進下游效應因子─趨化因子CXCL12、CXCL13和CCL21的表達，吸引B細胞與T 細胞過來聚集。由我們的研究結果可知HBx亦具有調控ELSs形成的功能，此機制的明朗化將提供一種新型的免疫治療策略，治療由HBV誘導所形成之肝癌。 | zh_TW |
| dc.description.abstract | Hepatitis B virus X protein (HBx) is a multifunctional protein encoded by the hepatitis B virus that involved in hepatocarcinogenesis. Ectopic lymphoid-like structures (ELSs) are lymphoid aggregates mainly composed of B cells and T cells, frequently developed at sites of chronic inflammation. Hepatic ELSs indicates poor prognosis for hepatocellular carcinoma (HCC), which are associated with activation of the lymphotoxin (LT)-β-driven non-canonical NF-κB signaling pathway. To understand the role of HBx in ELSs formation in advanced HCC, we used HBx-transfected and HBx-infected HCC cell lines to identify the expression of LT family and non-canonical NF-κB signals by real-time PCR and western bloting. The data showed that HBx expression in HA22T/VGH cells up-regulated LTα, LTβ and their downstream effectors, the chemokines CXCL12, CXCL13 and CCL21 which are necessary for recruitment of B cells and T cells, through stimulating the non-canonical NF-κB signaling pathway. Our findings revealed that HBx also functioned as a regulator in ELSs formation, providing a possibility to develop a novel immunotherapeutic strategy for treating HBV-induced HCC. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:31:54Z (GMT). No. of bitstreams: 1 ntu-107-R05b22018-1.pdf: 3121855 bytes, checksum: be016dc7c5a33df5833e3db22a1b6293 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 謝誌 i
中文摘要 iii Abstract iv 第一章 緒論 1 1.1 B型肝炎病毒 (Hepatitis B Virus, HBV) 的感染與肝癌的發生 1 1.2 B型肝炎病毒X蛋白扮演重要的調控角色 3 1.3 HBV X蛋白質在細胞核與細胞質中參與的訊息調控 5 1.4 HBV X蛋白質與淋巴毒素 (Lymphotoxin, LT) 的關係 6 1.5 經典型與非經典型NF-κB訊息傳遞路徑的比較 8 1.6異位類淋巴結構 (Ectopic lymphoid-like structures, ELSs) 的組成與功能 10 1.7 異位類淋巴結構形成的機制 11 1.7.1異位類淋巴結構形成的初始階段 11 1.7.2 淋巴細胞的聚集 12 1.7.3 異位類淋巴結構的維持 13 1.8 異位類淋巴結構與肝癌的關係 14 第二章 研究動機、方向與設計 15 2.1 研究動機 15 2.2 實驗探討之方向與設計 16 2.3 本篇研究所設計的Scheme: 17 第三章 實驗材料與方法 18 3.1 實驗材料 18 3.1.1 藥品 18 3.1.2 試劑 19 3.1.3 抗體 20 3.1.4 引子序列 20 3.1.5 儀器 21 3.1.6 細胞株 22 3.1.7 質體圖譜 23 3.2 實驗方法 24 3.2.1 細胞培養(Cell culture) 24 3.2.2 轉形作用 (Transformation) 26 3.2.3 小量萃取質體DNA (Mini Plasmid DNA Extraction) 27 3.2.4 中量萃取質體DNA (Midi Plasmid DNA Extraction) 28 3.2.5 細胞轉染 (Transfection) 30 3.2.6 細胞感染 (Infection) 30 3.2.7 RNA萃取 (RNA extraction) 31 3.2.8 將mRNA轉成cDNA 32 3.2.9 即時聚合酶鏈鎖反應 (Real-time PCR) 33 3.2.10 蛋白質萃取 (Protein extraction) 33 3.2.11 西方墨點法 (Western Blot) 35 3.2.12 培養液濃縮 37 3.2.13 酵素連結免疫吸附分析法 (Enzyme-linked immunosorbent assay, ELISA) 38 3.2.14 T細胞遷移 (T cell transwell migration) 38 3.2.15 癌症基因體圖譜 (The Cancer Genome Atlas, TCGA) 之分析 39 3.2.16 統計 39 第四章 實驗結果 40 4.1 建立能夠持續而穩定表達HBV X蛋白質的HA22T/VGH肝癌細胞株 40 4.2 HBV X蛋白質在HA22T/VGH肝癌細胞中會促進淋巴毒素家族的表現 46 4.3在持續穩定表現HBV X蛋白質的HA22T/VGH肝癌細胞中會活化非經典型NF-κB訊息調控路徑 51 4.4在持續而穩定表現HBV X蛋白質的HA22T/VGH肝癌細胞中會增加細胞黏附分子的表現量 56 4.5在持續而穩定表現HBV X蛋白質的HA22T/VGH肝癌細胞中會增加趨化因子的表現 60 4.6在持續而穩定表現HBV X蛋白質的HA22T/VGH肝癌細胞會分泌趨化因子吸引免疫細胞的聚集 63 第五章 討論 66 第六章 結論與未來展望 68 第七章 參考文獻 69 | |
| dc.language.iso | zh-TW | |
| dc.subject | 異位類淋巴結構 | zh_TW |
| dc.subject | B 型肝炎病毒 | zh_TW |
| dc.subject | HBV X 蛋白質 | zh_TW |
| dc.subject | 淋巴毒素 | zh_TW |
| dc.subject | 非經典型NF-κB 訊息傳遞路徑 | zh_TW |
| dc.subject | HBV X protein | en |
| dc.subject | Ectopic lymphoid-like structure | en |
| dc.subject | Lymphotoxin | en |
| dc.subject | HBV | en |
| dc.subject | Noncanonical NF-B signaling pathway | en |
| dc.title | B 型肝炎病毒 X 蛋白質之探討：藉由調節淋巴毒素 α 和 β 的表現以促進肝癌細胞中異位類淋巴結構的生成 | zh_TW |
| dc.title | Analysis of the Hepatitis B Virus X Protein: Promotion of ectopic lymphoid-like structures formation by up-regulating lymphotoxin α and β expression in human hepatoma cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 何佳安 | |
| dc.contributor.oralexamcommittee | 徐士蘭,吳立真,蘇純立,謝淑貞 | |
| dc.subject.keyword | B 型肝炎病毒,HBV X 蛋白質,淋巴毒素,非經典型NF-κB 訊息傳遞路徑,異位類淋巴結構, | zh_TW |
| dc.subject.keyword | HBV,HBV X protein,Lymphotoxin,Noncanonical NF-B signaling pathway,Ectopic lymphoid-like structure, | en |
| dc.relation.page | 77 | |
| dc.identifier.doi | 10.6342/NTU201803694 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-16 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| dc.date.embargo-lift | 2023-08-23 | - |
| 顯示於系所單位： | 生化科技學系 | |
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