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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 牙醫專業學院
  4. 臨床牙醫學研究所
Please use this identifier to cite or link to this item: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17784
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???org.dspace.app.webui.jsptag.ItemTag.dcfield???ValueLanguage
dc.contributor.advisor郭彥彬(Yen-Ping Kuo)
dc.contributor.authorYue-Ju Lien
dc.contributor.author李月如zh_TW
dc.date.accessioned2021-06-08T00:43:31Z-
dc.date.available2030-01-01-
dc.date.copyright2015-09-24
dc.date.issued2015
dc.date.submitted2015-08-12
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17784-
dc.description.abstract癌症是目前世界上非常棘手的問題,也是臨床上病人死亡的重要疾病之一。雖然它已被研究長達數十年,但是目前對它的致病機轉及治療方針瞭解並不完全。不同的癌症種類,例如:口腔癌及大腸直腸癌,甚至於不同亞型,像是大腸癌中的微星粒不穩定型(MSI)及穩定型(MSS)致病機轉及治療結果也不盡相同。在本研究中,我們透過微陣列分析出的幾個特殊基因,期望找出其在不同癌症中的調控機轉。運用高通量的分析方法偵測調控癌症轉移的可能下游影響分子,並使用即時聚合酶鏈鎖反應法分析病人檢體來確認這些基因的角色,包括:ataxia telangiectasia mutated interactor (ATMIN),同時進一步分析其與臨床預後的關係。藉由體外細胞株給予或去除基因來評估其功能,及原位注射或脾臟注射的小鼠動物模式來觀察淋巴轉移及肝臟轉移,研究結果發現ATMIN的高表現量與口腔癌及大腸癌中微星粒穩定型的臨床期別成正比且病人預後較差,但卻與微星粒不穩定亞型的臨床期別成反比而病人預後較佳。總結來說,基因的功能仰賴不同的癌症或亞型而有不同的影響力,相信此論文提供了未來癌症個人化醫療之重要的參考證據。zh_TW
dc.description.abstractCancer is the serious issue worldwide and responsible for many deaths. Even though it has been studied for several decades, it is still mysterious. The different cancer types, such as oral squama cancer cell (OSCC) and colorectal cancer cell (CRC), and even the same cancer with different subtypes, such as CRC microsatellite instable (MSI) and CRC microsatellite stable (MSS), come out with different ways. In this study, we aimed to explore the roles of several genes that were identified by microarray analysis and their regulatory mechanisms in different cancer types. The high throughput analysis was used to detect the downstream effectors of target gene-regulated metastasis. The cancers specimens were detected by Quantitative RT-PCR to confirm the roles of the genes, including ataxia telangiectasia mutated interactor (ATMIN), and were analyzed with these gene expression and clinical outcomes by Kaplan–Meier analyses. The functions of ectopic genes expression or silencing on cell behavior were evaluated in vitro. Lymph node metastasis and liver metastasis abilities were investigated by orthotropic and splenic injection in animal model. Interestingly, ATMIN mRNA expression was correlated with advanced stages in OSCC and CRC/MSS, but negatively correlated with CRC/MSI population. Moreover, in vivo animal experiments were confirmed the result as clinical samples. In conclusion, the gene functions were various depending on cancer types even subtypes, it provides the strong evidence for personalize medical treatment.en
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dc.description.tableofcontentsContent
論文口試委員會審定書 i
中文摘要 ii
Abstract iii
Content v
Chapter I Introduction 1
1.1 ataxia telangiectasia mutated interactor (ATMIN) 2
1.2 Cancer progression 3
1.2.1 Cancer generation 3
1.2.2 Oral squama cancer cell (OSCC) 4
1.2.3 Colorectal cancer cell (CRC) 6
Chapter II The roles of ATMIN in OSCC 10
2.1 Rational 11
2.2 Material and Method 12
2.3 Results 17
Chapter III The roles of ATMIN in CRC 20
3.1 Rational 21
3.2 Material and Method 22
3.3 Results 29
Chapter IV Discussion 38
Chapter V Conclusion 44
Chapter VI Reference 46
Chapter VII Tables, Figures and Figures legends 54
Chapter VIII Publication list 86
Chapter IX Appendix 88
dc.language.isoen
dc.title運動失調毛細血管擴張症突變相互作用因子在癌症進程中之角色zh_TW
dc.titleThe role of ataxia telangiectasia mutated interactor in cancer progressionen
dc.typeThesis
dc.date.schoolyear103-2
dc.description.degree博士
dc.contributor.coadvisor張正琪(Cheng-Chi Chang)
dc.contributor.oralexamcommittee楊慕華(Muh-Hwa Yang),李心予,林本仁
dc.subject.keyword運動失調毛細血管擴張突變相互作用因子,醛??,微星粒不穩定亞型,微星粒穩定亞型,口腔癌,大腸直腸癌,乙型連環蛋白,zh_TW
dc.subject.keywordATMIN,ALDOC,MSI,MSS,OSCC,CRC,beta-catenin,en
dc.relation.page99
dc.rights.note未授權
dc.date.accepted2015-08-12
dc.contributor.author-college牙醫專業學院zh_TW
dc.contributor.author-dept臨床牙醫學研究所zh_TW
dc.date.embargo-terms2030-01-01
Appears in Collections:臨床牙醫學研究所

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