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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賴明陽(Ming-Yang Lai) | |
| dc.contributor.author | Wen-Cheng Su | en |
| dc.contributor.author | 蘇文正 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:23:38Z | - |
| dc.date.available | 2015-03-12 | |
| dc.date.copyright | 2010-03-12 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-09-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45499 | - |
| dc.description.abstract | Ribavirin在臨床上已經運用於治療許多病毒感染的疾病，且有不錯的效果。而在C型肝炎病毒的治療上，與干擾素-α合併治療的效果能使C型肝炎病人的治療效果大幅改善。Ribavirin先前雖然有報告指出其可以有抗血管新生(anti-angiogenesis)及抑制IMPDH活性的能力，然而其干擾素-α抗病毒的作用機轉迄今未明。在此報告中發現，ribavirin經由誘導mTOR及p53的活性，並進而增加干擾素-α所調控抗病毒基因的產生。活化p53之表現，主要在於經由活化mTOR而影響p53的活性。Ribavirin經由活化mTOR進而影響p53的活性，可以有效的被rapamycin 及knockdown mTOR 所抑制。Ribavirin活化p53的結果，可以經由抑制mdm2及HAUSP的相互作用，得以使得活化p53蛋白質穩定的能力延長，並減少mdm2蛋白質穩定的能力。Ribavirin經由活化p53而使得干擾素-α訊息傳遞的重要組成成份IRF9 mRNA及蛋白質的增加。此結果使得在ribavirin與干擾素-α合併處理下的干擾素-α所調控抗病毒基因的mRNA及蛋白質均大幅度的增加。此結果使得mTOR及p53的活性在ribavirin與干擾素-α合併處理下，對於干擾素-α所調控的訊息傳遞上扮演很重要的角色。而這也可能是ribavirin與干擾素-α合併治療C型肝炎病人，進而達到改善C型肝炎病人的治療效果的成因之一。 | zh_TW |
| dc.description.abstract | Cellular mechanisms involving the enhancement of interferon (IFN) signaling by ribavirin remain poorly understood. Here, we identified a novel role of ribavirin in the communication between p53 and the mammalian target of rapamycin (mTOR) signaling. Ribavirin activates p53 by stimulating mTOR and promoting the interaction between mTOR and p53. In addition, ribavirin stabilizes p53 protein by ablation of the interaction between herpesvirus-associated ubiquitin-specific protease (HAUSP) and mdm2. Activated p53 stimulates the transcription of IFN regulatory factor 9 and subsequently enhances IFN signaling. Furthermore, ribavirin-induced activation of mTOR and p53 enhances IFN-dependent signaling for the IFN-α/ribavirin combined treatment. We conclude that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:23:38Z (GMT). No. of bitstreams: 1 ntu-98-D90448001-1.pdf: 33792714 bytes, checksum: 795a753c32f11cb25326d739eeed8caf (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 論文口試委員審定書………………………………………………………………… 1
序言或謝辭…………………………………………………………………………… 2 目錄 ………………………………………………………………………………….. 3 中文摘要……………………………………………………………………………… 4 Abstract………………………………………………………………………………... 5 Introduction……………………………………………………………………………. 6 Materials and methods……………………………………………………………….. 9 Results……………………………………………………………………………….. 13 Discussion…………………………………………………………………………… 20 Acknowledgements………………………………………………………………….. 25 References…………………………………………………………………………….. 26 Table 1…..……….……………………………………………………………………. 35 Figures ..………....………………………………………………………………… 36~ 69 | |
| dc.language.iso | en | |
| dc.subject | mTOR | zh_TW |
| dc.subject | 干擾素-α | zh_TW |
| dc.subject | ribavirin | zh_TW |
| dc.subject | p53 | zh_TW |
| dc.subject | ribavirin | en |
| dc.subject | mTOR | en |
| dc.subject | p53 | en |
| dc.subject | IFN-α | en |
| dc.title | Ribavirin經由活化mTOR及p53活性加強干擾素α的訊息 | zh_TW |
| dc.title | Ribavirin Enhances Interferon Signaling via Stimulation of mTOR and p53 Activities | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 黃麗華(Lih-Hwa Hwang),李芳仁(Fang-Jen Lee),劉俊人(Chun-Jen Liu),葉秀慧(Shiou-Hwei Yeh) | |
| dc.subject.keyword | 干擾素-α,ribavirin,mTOR,p53, | zh_TW |
| dc.subject.keyword | ribavirin,mTOR,p53,IFN-α, | en |
| dc.relation.page | 69 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-09-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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