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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 華國泰(Kuo-Tai Hua) | |
| dc.contributor.author | Ching-Hsuan Chan | en |
| dc.contributor.author | 詹靖瑄 | zh_TW |
| dc.date.accessioned | 2021-06-17T08:26:40Z | - |
| dc.date.available | 2019-08-27 | |
| dc.date.copyright | 2019-08-27 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-13 | |
| dc.identifier.citation | 1. Simoes, P.K., et al., Epidemiology of pancreatic adenocarcinoma. Chinese Clinical Oncology, 2017. 6(3).
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Wei, D., et al., Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene, 2003. 22(3): p. 319-29. 42. Wang, L., et al., Overexpression of G protein-coupled receptor GPR87 promotes pancreatic cancer aggressiveness and activates NF-kappaB signaling pathway. Mol Cancer, 2017. 16(1): p. 61. 43. Ren, B., et al., Tumor microenvironment participates in metastasis of pancreatic cancer. Mol Cancer, 2018. 17(1): p. 108. 44. Korc, M. and R.E. Friesel, The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets, 2009. 9(5): p. 639-51. 45. Markowitz, J. and W.E. Carson, 3rd, Review of S100A9 biology and its role in cancer. Biochim Biophys Acta, 2013. 1835(1): p. 100-9. 46. Cross, S.S., et al., Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers. 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Thewes, V., et al., The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERalpha-negative breast cancer. Oncogene, 2017. 36(29): p. 4124-4134. 54. Mayers, J.R. and M.G. Vander Heiden, Nature and Nurture: What Determines Tumor Metabolic Phenotypes? Cancer Res, 2017. 77(12): p. 3131-3134. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74258 | - |
| dc.description.abstract | 近年來胰臟癌的死亡率逐年攀升，在2018年世界衛生組織的統計報告指出胰臟癌目前在全球癌症罹患率中名列第十一名，胰臟癌有著高致死率，在罹癌初期沒有典型症狀，亦缺乏能早期預測的生物性指標。胰臟癌中最常見的類型是胰臟腺癌，此類型病患佔所有胰臟癌患者中的85%，在第一期癌症五年存活率約12%，癌症一旦轉移後，五年存活率便會低於5%，因此尋找能夠調控胰臟癌進程的分子十分重要。Adducin蛋白是細胞骨架的組成分子，而Alpha-adducin（ADD1）是adducin蛋白的次單位，因此ADD1在細胞骨架的生理功能上可能扮演重要角色，在過去的文獻中曾發現ADD1在不同癌症中，可能透過不同的機制扮演致癌基因或抑癌基因的角色。本研究試圖探討ADD1是否在胰臟癌的癌症轉移中扮演關鍵角色，研究初期利用臨床資料庫分析，我們發現在胰臟癌患者中ADD1表現量高的患者存活率較差，有作為預後的指標的潛力，進一步以動物實驗來探討ADD1在活體中扮演的角色，從實驗結果得知ADD1表現量高低會顯著影響癌症轉移至器官的嚴重程度，同時，我們從細胞實驗的結果發現ADD1表現量下降時，癌細胞的侵襲能力增加；此外，我們也發現ADD1並非透過focal adhesion來影響胰臟癌細胞侵襲性，且透過Microarray的分析，我們認為ADD1可能會調控branched chain amino acid transaminase 1(BCAT1)進而造成癌症轉移能力增加。綜合以上實驗結果，從臨床資料庫分析以及動物實驗的結果來看，ADD1似乎在活體上扮演著致癌基因的角色，但是在細胞功能上的機制仍需要再深入探討。 | zh_TW |
| dc.description.abstract | Pancreatic cancer is ranked 11th in the cancer incidence rate. Pancreatic cancer has high mortality and is hard to be diagnosed in the early stage. Pancreatic adenocarcinoma is the most common type of pancreatic cancer, attributing about 85% of cases. The 5-year survival rate of patients would be under 5 % when the cancer cells have already metastasized. Therefore, it is urgent to find the molecular which can regulate pancreatic cancer metastasis. Adducin is a family of cytoskeletal proteins and encoded by three genes (alpha, beta, gamma). ADD1 is an alpha subunit of adducin family. ADD1 has a crucial role in regulating the formation and function of cytoskeleton. In previous studies, some reports have shown that ADD1 could promote tumor cell growth. However, another study showed that ADD1 would reduce cell proliferation. The roles of ADD1 in tumorigenesis are still unclear. In my research, we tried to investigate the roles of α-adducin (ADD1) in pancreatic ductal adenocarcinoma (PDAC). We analyzed the clinical database and found that there was negative correlation between the expression level of ADD1 and the survival of PDAC patients. Moreover, knockdown of ADD1 decreased PDAC-derived cancer cell line metastasis in in vivo study. In contrast, overexpression of ADD1 could promote cancer cell metastasis. Meanwhile, knockdown of ADD1 in PDAC cell lines promoted cell migration and invasion abilities, whereas overexpression of ADD1 suppressed invasion abilities. Moreover, we found that ADD1 may not affect cell metastasis through focal adhesion pathway. The microarray data showed that BCAT1 may be probably regulated by ADD1 in PDAC. Overall, based on the clinical database analysis and animal experiment, our findings revealed that ADD1 might be an oncogene in PDAC. However, the mechanism needs to be investigated afterward. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T08:26:40Z (GMT). No. of bitstreams: 1 ntu-108-R06447008-1.pdf: 3765474 bytes, checksum: 65e5b834879cf4c9653b6c44c58c8cc1 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝……………………………................................……..….i
中文摘要..............................................................................ii ABSTRACT.........................................................................iii CONTENTS........................................................................iv LIST OF FIGURES..............................................................v LIST OF TABLES................................................................v Chapter 1 Introduction.........................................................1 1.1 Pancreatic ductal adenocarcinoma: Epidemiology, diagnosis and therapies......................................................1 1.2 Alpha-adducin (ADD1): structure, function, and related disorder…………….................................................3 1.3 Motivation and purpose…………………………………………………………6 Chapter 2 Materials and methods........................................7 Chapter 3 Results...............................................................13 3.1. ADD1 expression correlates with the survival of PDAC patients..............................................................................13 3.2. ADD1 would promote cancer cell metastasis in orthotopic animal model....................................................13 3.3. ADD1 has minor effect on cell proliferation................15 3.4. ADD1 inhibits cell migration and invasion in PDAC cell line.....................................................................................16 3.5. ADD1 could be involved in cancer stem cell generation..........................................................................16 3.6. Focal adhesion would not be involved in the mechanism regulated by ADD1 in cancer cell motility.......17 3.7. ADD1 may control cancer cell motility through unique regulation in nuclei............................................................18 3.8.BCAT1 was probably regulated by ADD1 in PDAC.....19 Chapter 4 Discussion.........................................................20 Tables and Figures............................................................26 Reference.........................................................................52 | |
| dc.language.iso | en | |
| dc.subject | 癌症轉移 | zh_TW |
| dc.subject | 胰臟癌 | zh_TW |
| dc.subject | 細胞骨架蛋白 | zh_TW |
| dc.subject | Pancreatic cancer | en |
| dc.subject | alpha-adducin (ADD1) | en |
| dc.subject | cancer metastasis | en |
| dc.title | 探討細胞骨架蛋白ADD1在胰臟癌轉移侵襲之角色 | zh_TW |
| dc.title | The Roles of Cytoskeleton Protein Alpha-Adducin (ADD1) in Pancreatic Cancer Invasion and Metastasis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 簡銘賢,翁孟仕 | |
| dc.subject.keyword | 胰臟癌,細胞骨架蛋白,癌症轉移, | zh_TW |
| dc.subject.keyword | Pancreatic cancer,alpha-adducin (ADD1),cancer metastasis, | en |
| dc.relation.page | 55 | |
| dc.identifier.doi | 10.6342/NTU201903161 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-08-13 | |
| 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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