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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭明良 | |
| dc.contributor.author | Ching-Yao Yang | en |
| dc.contributor.author | 楊卿堯 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:16:57Z | - |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-18 | |
| dc.identifier.citation | 1. Okuda K, Kojiro M, Okuda H. Neoplasms of the liver. In: Schiff L, Schiff R, eds. Diseases of the liver. Philadelphia: Lippincott; 1993:1236-1296.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22399 | - |
| dc.description.abstract | 肝細胞癌是世界上最常見的癌症之一，高復發率是肝癌的致死主因之一，血管侵犯是高復發主要原因及預後差的主要危險因子， 因此， 若能找出有血管侵犯的肝癌和沒有血管侵犯的肝癌的差異表現之基因， 進而了解使肝癌變的較有侵犯性的機轉，甚至發現治療的方向， 將會很有意義。所以，這個研究計畫的目的是利用抑制性雜合扣除法及微陣列實驗， 來發現並選殖出有血管侵犯的肝癌和沒有血管侵犯的肝癌的差異表現之基因，並進一步的探索這些基因和肝癌在臨床表現的相關性, 並利用肝癌細胞株實驗來闡明其角色及機轉。
我們的實驗成功的找出二十個和肝癌腫瘤有無血管侵犯具有差異表現的基因，其中之一是LECT2 基因。臨床病理的研究顯示，LECT2 基因或蛋白表現較低的肝癌，統計後發現腫瘤的stage 較advanced，grade 較差，早期復發率高，預後較差。進一步的研究結果發現: LECT2 表現越低的肝癌細胞株，其爬行能力，侵犯性，以及穿越內皮細胞的能力越強; 動物實驗包括雞胚絨毛膜穿越血管實驗以及小鼠肝癌細胞株原位注射轉移實驗，含低LECT2 基因的肝癌細胞株，侵犯性及轉移率變強; 反之則變弱。分子機轉及訊息傳遞的研究則發現: LECT2 蛋白是全新發現的c-Met 的new ligand，透過和c-Met 的細胞膜外之domain 結合，抑制c-Met 磷酸化及其下游之訊息傳遞功能進而抑制肝癌的血管侵犯和轉移。 總結來說，我們是世界上第一個團隊發現LECT2 是c-Met 的new ligand，而且是重要的肝癌腫瘤抑制因子，極有潛力開發為生物標記及治療的應用。 | zh_TW |
| dc.description.abstract | One of the major problem in hepatocellular carcinoma (HCC) treatment is high recurrent rate. Vascular invasion of HCC is the major factor of recurrence. Through suppression subtraction hybridization and microarray, we identified leukocyte cell-derived chemotoxin 2 is a significantly down-regulated gene in vascular-invasive HCC as compared with non-vascular invasive HCC. Clinicopathologic research from 73 patients revealed low expressing level of LECT2 gene or protein in HCC correlated with vascular invasion, advanced stage, early recurrence, and poor prognosis. In vitro experiments revealed LECT2 gene expression status inversely correlated with abilities of migration, invasion, and transendothelial cell migration of HCC cell lines. LECT2 protein can inhibit these motility functions of HCC cells as well. In vivo experiments including chorioallantoic membrane intravasation assay, and orthotopic liver injection animal models revealed LECT2 can inhibit HCC cells vascular invasion and migration.
By dissection of the mechanism and tools of protein-protein interactions, we found LECT2 protein is a novel, new ligand of c-Met by directly binding to its extracellular domain, and attenuate phosphorylation of c-Met, and its down-stream signaling pathway. In conclusion, we are the first team to identify LECT2 is an important HCC tumor suppressor, a new, novel ligand of c-Met, and a promising biomarker and therapeutic target. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:16:57Z (GMT). No. of bitstreams: 1 ntu-100-D91447002-1.pdf: 21330737 bytes, checksum: 220cdf8f74d2773a491dbfb0627848a4 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 口試委員審定書......……………………………………………………………… i
誌謝………………………………………………………………………….……. ii Abbreviations………………………………………………………………….….. iv 中文摘要……………………………………………………………………..…… v 英文摘要....……………………………………………………………………..… vi Introduction ………………………………………………………………….……. 1 Materials and Methods ……………………………………………………………. 6 Results ………………………………………………………………….…………. 26 Discussion ………………………………………………………………….……... 45 Tables …..……………………………………………………………….………… 49 Figures and figure legends ...……………………………………………………… 51 References……………………………………………………………….………… 85 | |
| dc.language.iso | en | |
| dc.subject | LECT2 | zh_TW |
| dc.subject | 肝細胞癌 | zh_TW |
| dc.subject | 抑制性雜合扣除法 | zh_TW |
| dc.subject | 微陣列 | zh_TW |
| dc.subject | 血管侵犯 | zh_TW |
| dc.subject | 轉移 | zh_TW |
| dc.subject | hepatocellular carcinoma | en |
| dc.subject | metastasis | en |
| dc.subject | vascular invasion | en |
| dc.subject | Met | en |
| dc.subject | c-Met | en |
| dc.subject | leukocyte cell-derived chemotoxin 2 | en |
| dc.subject | HCC | en |
| dc.subject | LECT2 | en |
| dc.title | LECT2 蛋白透過抑制 c-Met 磷酸化及其功能
進而抑制肝癌的血管侵犯和轉移 | zh_TW |
| dc.title | Leukocyte Cell-Derived Chemotoxin 2 Inhibit Vascular Invasion and Metastasis of HCC by Attenuating Phosphorylation of c-Met | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 林明燦,洪文俊,李伯皇,陳炯年 | |
| dc.subject.keyword | 肝細胞癌,抑制性雜合扣除法,微陣列,血管侵犯,轉移,LECT2, | zh_TW |
| dc.subject.keyword | hepatocellular carcinoma,HCC,leukocyte cell-derived chemotoxin 2,LECT2,c-Met,Met,vascular invasion,metastasis, | en |
| dc.relation.page | 91 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2011-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
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