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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧哲明(Che-Ming Teng),潘秀玲(Shiow-Lin Pan) | |
| dc.contributor.author | Tzu-Han Lin | en |
| dc.contributor.author | 林子涵 | zh_TW |
| dc.date.accessioned | 2021-05-19T18:01:59Z | - |
| dc.date.available | 2025-06-30 | |
| dc.date.available | 2021-05-19T18:01:59Z | - |
| dc.date.copyright | 2015-09-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-07-01 | |
| dc.identifier.citation | 1.Alenghat T, Artis D (2014). Epigenomic regulation of host-microbiota interactions. Trends in immunology 35(11): 518-525.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7996 | - |
| dc.description.abstract | 血管新生 (angiogenesis) 是從已存在體內的血管分化再形成新血管網絡的一個生理過程，無論是在生物的生長發育、組織的分化、傷口修復以及腫瘤的增生與轉移等皆佔有重要調控的角色。組蛋白去乙醯酶抑制劑 (HDAC inhibitor) 為近年來新穎的抗癌小分子化合物，藉由調控histone以及 non-histone蛋白的去乙醯化程度，影響致癌基因 (oncogene) 以及抑癌基因 (tumor suppressor gene) 的表現，最終以達抑制癌症的療效。本篇論文的主題在探討MPT0E028對於血管新生促進因子 (endothelial growth factors；EGM-2) 引起血管新生的抑制作用與分子機轉。MPT0E028為一個異羥肟酸 (N-hydroxamic acid) 的衍生物，同時也是一個HDAC抑制劑，已有許多研究證實此化合物能抑制癌細胞的生長並減緩疾病進程，目前已進入臨床試驗第一期。首先，在本篇論文的功能性實驗中發現MPT0E028能夠抑制人類臍靜脈內皮細胞的增生、細胞的移行以及類血管管腔的形成。同時利用西方墨點法，顯示MPT0E028也會影響第二型血管內皮生長因子受器 (VEGFR2) 的下游訊號傳遞，包括抑制Erk1/2、Akt、p38 MAPK、Src以及FAK的磷酸化。在in vivo matrigel plug assay以及腫瘤異體移植中，也證實MPT0E028在體內具有明顯抑制血管生成以及減緩腫瘤生長的作用。因此總結以上實驗結果，MPT0E028在未來臨床發展上，值得進一步研發成可同時抗癌以及抗血管新生之HDAC抑制劑，且可能機制為藉由抑制VEGFR2訊息傳遞表現量，達到抑制血管新生的作用。 | zh_TW |
| dc.description.abstract | Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels and is also a normal and vital process in growth and development, wound healing, formation of granulation tissue as well as tumor proliferation and metastasis. It has been reported that histone deacetylase inhibitors (HDAC inhibitors) are a novel class of small molecular anticancer agents through modulating the acetylation/deacetylation of histones and/or non-histone proteins and therefore altering the expression of oncogenes or tumor suppressors.
MPT0E028, a novel derivative of N-hydroxamic acid, as well as a small molecular HDAC inhibitor, has been shown to reduce advanced solid tumor growth and has entered phase I clinical trial. In this study, under the induction of EGM-2, MPT0E028 showed an effect of inhibiting angiogenesis including cell proliferation, cell migration and tube formation. MPT0E028 also inhibited the VEGFR2 downstream signaling, including reducing Erk1/2, Akt, p38 MAPK, Src and FAK phosphorylation. And by matrigel plug assay, MPT0E028 also showed an in vivo inhibitory effect in blood vessel formation. Taken together these studies, we can make a brief summary that MPT0E028 plays an inhibitory role in angiogenesis and may be through inhibiting VEGFR2 downstream signaling. After further investigation of MPT0E028, the new HDACi may be a potential candidate of possessing both anti-cancer and anti-angiogenesis properties to inhibit tumor progression in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-19T18:01:59Z (GMT). No. of bitstreams: 1 ntu-104-R02443019-1.pdf: 5102774 bytes, checksum: cf564c41fa931294301b4632c48dd16d (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員審定書............................I
致謝....................................II 縮寫表..................................IV 中文摘要.................................1 英文摘要.................................2 第一章 研究動機與目的....................4 第二章 文獻回顧.........................5 第三章 實驗材料與方法 第一節 實驗材料........................48 第二節 實驗方法........................51 第四章 實驗結果........................62 第五章 討論............................69 第六章 結論與展望.......................78 參考文獻.................................98 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討HDAC抑制劑MPT0E028抑制腫瘤血管新生之體外及體內的作用機轉 | zh_TW |
| dc.title | A novel action mechanism for MPT0E028, a HDAC inhibitor, inhibits tumor angiogenesis in vitro and in vivo. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃德富(Tur-Fu Huang),顏茂雄(Mao-Hsiung Yen),楊春茂(Chuen-Mao Yang) | |
| dc.subject.keyword | HDAC抑制劑,抗血管新生, | zh_TW |
| dc.subject.keyword | HDAC inhibitor,anti-angiogenesis, | en |
| dc.relation.page | 109 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2015-07-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-06-30 | - |
| 顯示於系所單位： | 藥理學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf | 4.98 MB | Adobe PDF | 檢視/開啟 |
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