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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林中梧(Chung-Wu Lin) | |
dc.contributor.author | Ting-Yun Liu | en |
dc.contributor.author | 劉亭勻 | zh_TW |
dc.date.accessioned | 2021-06-08T04:29:58Z | - |
dc.date.copyright | 2010-03-12 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-01-13 | |
dc.identifier.citation | Reference
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22833 | - |
dc.description.abstract | 中文摘要
大約有30~50%的霍金氏淋巴癌感染EB病毒,但對於感染EB病毒在臨床上對疾病的發展結果之影響仍未釐清。EB病毒轉錄的小片段RNAs (EBERs)出現在所有被EB病毒感染的疾病當中,但關於它們的功能仍未知。 將EBER1轉染至兩株霍金氏淋巴癌細胞株,KM-H2和L428,並以微陣列方式分析被EBER1誘導之基因改變。我們在霍金氏淋巴癌細胞株中發現EBER1會抑制p21cip1/waf1的表現;另外,p21cip1/waf1的正調控因子,如p53,EGR1,和STAT1也會受到抑制。在霍金氏淋巴癌細胞株中,p21cip1/waf1的表現會受到EBER1抑制,並對histone deacetylase inhibitors 和 proteasome inhibitors這兩種已知會誘導p21cip1/waf1 表現的藥物所引發的細胞凋亡具有抵抗性是具有相關性。根據分析臨床上的檢體,發現感染EB病毒的霍金氏淋巴癌其p21cip1/waf1和活化之caspase 3的表現較弱。臨床數據分析顯示,感染EB病毒的霍金氏淋巴癌之抑制p21cip1/waf1的表現,會有一個較差的兩年存活率(EB病毒感染霍金氏淋巴癌有45%存活率,相對應於未感染EB病毒霍金氏淋巴癌有77%存活率,p = 0.002)。 雖然EBER1抑制p21cip1/waf1表現的機制仍未釐清,但EBER1會抑制p21cip1/waf1的轉錄並且經由抑制p53,EGR1,和STAT1而對細胞凋亡具有抵抗性。EBER1具有抵抗細胞凋亡的能力,對於避免Reed-Sternberg cells對藥物產生的細胞凋亡以及感染EB病毒之霍金氏淋巴癌的臨床表現可能是很重要的。 | zh_TW |
dc.description.abstract | Abstract
About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (EBERs) are present in all EBV-infected cells, but their functions are still unknown. EBER1 was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for EBER1-induced changes. We found that EBER1 suppressed p21cip1/waf1 transcription in HL cell lines. In addition, positive regulators of p21cip1/waf1 transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of p21cip1/waf1 in the EBER1 | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T04:29:58Z (GMT). No. of bitstreams: 1 ntu-99-D92444002-1.pdf: 1730409 bytes, checksum: e2dd07e001071063c2fb7a8544ec1c6d (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | Contents
口試委員會審定書…………………………………………………………………. i 誌謝………………………………………………………………………….….….…..ii 中文摘要………………………………………………………………………….…. iii Abstract …………………………………………………….………………………..iv Contents ………………………………………………………………………….......v Chapter 1: Introduction ……………………………………………………..…....1 1.1 Epstein-Barr virus in tumorigenesis ……………………………….1 1.2 The lifecycle of EBV ………………………………………………...1 1.3 Properties of EBERs ………………………………………………...2 1.4 EBV in Hodgkin lymphoma ……………………………………….. 3 1.5 Significance………………………………………………………….. 3 1.6 Perspective…………………………………………………………... 4 1.7 Conclusion…………………………………………………………... 5 Chapter 2: EBV-positive HL is associated with suppression of p21cip1/waf1 and a worse prognosis ……………………………… 6 2.1 Introduction ……………………………………………………. 6 2.2 Materials and Methods …………………………………….... 8 2.2.1 Hodgkin lymphoma cell lines: KMH2 & L428 ………………..… 8 2.2.2 Construction of plasmids and selection of stable clones ………….8 2.2.3 Northern blotting …………………………………..………….…...9 2.2.4 Real-time RT-PCR for EBER1………………………………….....9 2.2.5 Microarray ………………………………………………………..10 2.2.6 RT-PCR for p21cip1/waf1 splicing variants ………………………...11 2.2.7 Real time RT-PCR for p21cip1/waf1……………………………......12 2.2.8 Western blotting………………………………………………….12 2.2.9 Cell cycle analysis ……………………………………………….12 2.2.10 Apoptosis assay ………………………………………………...13 2.2.11 Cell growth curve ………………………………………………13 2.2.12 ELISA ………………………………………………….……….13 2.2.13 Tissue sample …………………………………………………..14 2.2.14 Immunohistochemistry………………………………………….14 2.2.15 Statistical analysis ……………………………………………...14 2.3 Results……………………………………………………………15 2.3.1 EBER1 suppressed transcription of p21cip1/waf1…………………..15 2.3.2 Transcription factors of p21cip1/waf1, such as EGR1 & STAT1, were also decreased by EBER1………………………………………..15 2.3.3 EBER1 suppressed variant 1 of p21cip1/waf1 transcription ………..16 2.3.4 EBER1 suppressed the expressions of p21cip1/waf1, EGR1, STAT1, & p53 ………………………………………………………………16 2.3.5 EBER1-induced p21cip1/waf1 suppression was associated with decreased cyclin D2, but did not change the cell cycle distributions ……………………………………………………..17 2.3.6 EBER1 conferred resistance to apoptosis induced by TSA & MG115 ………………………………………………………….17 2.3.7 EBV+ Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis ………………………………18 2.3.8 An anti-apoptotic model for EBER1-induced p21cip1/waf1 suppression………………………………………………………19 2.4 Discussion ……………………………………………………….20 Chapter 3: Loss of CD7, independent of Galectin-3 expression, implies a worse prognosis in Adult T-cell leukemia/lymphoma ….24 3.1 Introduction ……………………………………………………24 3.2 Materials and Methods ………………………………….…. 26 3.2.1 Patients & tissue samples …………………………………….…. 26 3.2.2 Immunohistochemistry ………………………………………...... 26 3.2.3 Statistical analysis…………………………………………………26 3.3 Results…………………………………………………………... 27 3.3.1 Gal-3 expression was variable among ATLLs, but Gal-3+ stromal cells could always be identified ……………………….…………27 3.3.2 CD7 expression could be identified in a subset of ATLLs……….27 3.3.3 The CD7- group belonged to the acute subtype with a worse prognosis ………………………………………………………....27 3.3.4 Taiwanese and Japanese ATLLs had similar clinicopathological manifestations …………………………………………………….27 3.3.5 Cytogenetic changes frequently involved 9q …………………......28 3.4 Discussion……………………………………….…………….....29 Tables……………………………………………………………………………………....31 Figures…………………………………………………………………………..37 References…………………………………………………………………………...46 | |
dc.language.iso | en | |
dc.title | EB病毒感染霍金氏淋巴癌會抑制p21cip1/waf1的表現並導致較差的預後 | zh_TW |
dc.title | EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 陳美如,周綠蘋,蔡孟勳,吳漢忠 | |
dc.subject.keyword | 霍金氏淋巴癌,預後, | zh_TW |
dc.subject.keyword | Hodgkin lymphoma,EBV,EBER1,p21cip1/waf1,prognosis, | en |
dc.relation.page | 61 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2010-01-13 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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