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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 華國泰 | |
| dc.contributor.author | Ji-Qing Chen | en |
| dc.contributor.author | 陳季青 | zh_TW |
| dc.date.accessioned | 2021-06-08T00:46:00Z | - |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-07-31 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17911 | - |
| dc.description.abstract | 肝細胞所分泌的第二型白血球趨化因子 (Leukocyte Cell-Derived Chemotoxin 2; LECT2)為多功能的cytokine。目前已知LECT2為肝癌 (Hepatocellular carcinoma; HCC)的抑癌因子。而於我們先前的研究中發現LECT2可以抑制肝癌細胞上之肝細胞生長因子受體 (MET)的磷酸化，進而影響肝癌細胞的轉移及血管侵犯。此外，我們也發現血液中LECT2濃度和肝癌病人預後有高度相關性。雖然LECT2為分泌性蛋白，但目前未有證據顯示LECT2除了對肝癌細胞有影響外，是否對其他種類的癌細胞也會產生影響。在過去的文獻中指出，卵巢癌在腹腔膜上的adhesion能力跟MET磷酸化有密切關係。因此，我們想要了解LECT2是否會影響對HCC之外腫瘤細胞的惡性進程。本次實驗中我們先以卵巢癌做為實驗材料。首先，將老鼠卵巢癌細胞株ID8以腹腔注射方式打入wild type和LECT2 基因剔除鼠後，發現LECT2基因剔除鼠所形成的腹水體積及腹膜上的腫瘤數目都有明顯增加的現象。另一方面，在in vitro實驗中，也發現卵巢癌細胞株在有LECT2的處理下，migration、invasion和adhesion能力都有下降的趨勢，而這些現象皆跟MET磷酸化受到抑制所相關。而我們也發現LECT2可能會藉由調控integrin α5及β1來抑制卵巢癌細胞的adhesion能力。因此我們推論小鼠在缺乏LECT2之後會促使MET磷酸化增加，進而強化卵巢癌細胞對腹腔的侵犯及轉移能力；造成卵巢癌的惡性進程。綜合以上觀察，LECT2除了對HCC有影響之外，對於其他種類的腫瘤發展也有一定的影響力。因此，對於LECT2在抑癌機制上的探討或許可提供新穎的治療方式及具有發展抗癌藥物的潛力。 | zh_TW |
| dc.description.abstract | The multi-function cytokine, leukocyte cell-derived chemotoxin 2 (LECT2), is secreted by hepatocytes, has been known as a tumor suppressor in hepatocellular carcinoma (HCC). In our previous study, we have demonstrated that LECT2 could inhibit the phosphorylation of hepatocyte growth factor (HGF) receptor as known as MET in HCC cell lines, thus resulted in reduction of migration, invasion of HCC. Moreover, we have also found that the serum level of secreted LECT2 was highly correlated with patients’ prognosis. Although LECT2 is a secreted protein, there is no evidence indicate that LECT2 can involve in the progression of other cancer types. It had been reported adhesion of ovarian cancer cells to peritoneal membrane were highly related to the phosphorylation of MET. Herein, we investigate whether LECT2 can inhibit tumor growth and progression in ovarian cancer. First, the mouse ovarian cancer cell line ID8 was inoculated in wild type or LECT2 knockout mice. The in vivo data shown that the ascites volumes and tumor numbers in LECT2 knockout mice were significantly higher than WT mice. Moreover, we observed the migration, invasion, and cell adhesion abilities of ovarian cancer were all inhibited by LECT2 recombinant protein in vitro, and these phenomenon were correlated with decreasing of MET phosphorylation. We also found integrin α5 and β1 may involve in LECT2-mediated regulation of cell adhesion. We inferred that the increase of peritoneal metastasis of ovarian cancer in LECT2 deficiency mice were, at least in part, through increasing MET phosphorylation. In conclusion, our results demonstrated that LECT2 may involve in the progression of ovarian cancer. Further evaluation of the mechanism of LECT2 on cancer suppression may provide the novel therapeutic methods on anti-cancer drug development. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T00:46:00Z (GMT). No. of bitstreams: 1 ntu-104-R02447009-1.pdf: 3287741 bytes, checksum: c0d1d211fbef525c27f0b4820ace5f26 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員審定書--------------------------------------------Ⅰ
誌謝----------------------------------------------------Ⅱ Abbreviations------------------------------------------Ⅲ 中文摘要------------------------------------------------Ⅳ Abstract -----------------------------------------------Ⅴ Introduction -------------------------------------------1 1. Leukocyte cell-derived chemotaxin 2 (LECT2) 2. Ovarian cancer 3. Hepatocyte growth factor (HGF) and its receptor (HGFR/MET) in ovarian cancer 4. Motivation and purpose Materials and Methods-----------------------------------8 Results------------------------------------------------15 1 Ovarian cancer progression in vivo 2 Suppression of invasion, migration, adhesion ability through inhibition of MET phosphorylation 3 Inhibition ability of LECT2 on adhesion 4 LECT2 expression level in response to progression of ovarian cancer Discussion---------------------------------------------24 Figures and figure legends ----------------------------30 References --------------------------------------------46 | |
| dc.language.iso | en | |
| dc.title | 探討第二型白血球趨化因子在卵巢癌惡性進程之角色 | zh_TW |
| dc.title | Evaluation of the Roles of Leukocyte Cell-derived Chemotoxin 2 in Ovarian Cancer Progression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 簡銘賢,魏凌鴻 | |
| dc.subject.keyword | 第二型白血球趨化因子,卵巢癌惡性進程, | zh_TW |
| dc.subject.keyword | LECT2,ovarian cancer, | en |
| dc.relation.page | 51 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| Appears in Collections: | 毒理學研究所 | |
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