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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張逸良(Yih-Leong Chang) | |
| dc.contributor.author | Ching-Yin Chen | en |
| dc.contributor.author | 陳敬尹 | zh_TW |
| dc.date.accessioned | 2021-06-15T14:02:26Z | - |
| dc.date.available | 2020-09-25 | |
| dc.date.copyright | 2015-09-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-20 | |
| dc.identifier.citation | 1 Parkin, M. et al. Tumors of Lung WHO classification (2014).
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Human molecular genetics 23, 1964-1974, doi:10.1093/hmg/ddt589 (2014). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52003 | - |
| dc.description.abstract | 肺臟多型性上皮癌為一種較稀少但較為惡化的腫瘤，經常發生全身性的轉移並且在臨床上發現有化療的抗藥性。腫瘤中的壞死是在肺臟多型性上皮癌一個常見的特色，許多報告中表示腫瘤中壞死的出現和較高度的異質性以及腫瘤細胞的演化相關，造成較差的預後。在本實驗中，將鄰近以及遠離腫瘤內壞死的細胞各別做顯微刮取並蒐集，將兩區域的細胞進行人類染色體套數分析；分析後發現一半的肺臟多型性上皮癌在鄰近腫瘤內壞死區域的細胞有較高程度的異質性較高比例的非整倍體，並以著絲點螢光原位雜交技術來佐證這樣的發現；在螢光原位雜交的實驗中，鄰近腫瘤內壞死區域的細胞含有較多數量的著絲點訊號。基於這樣的發現，我們檢視了控制細胞分裂有關的蛋白質 STAG2、AURKA、BUBR1 以及 MAD2。其中發現 STAG2蛋白在鄰近腫瘤內壞死區域有表現量降低的現象，STAG2蛋白是一個cohesin的蛋白組件，STAG2的缺少可能造成cohesin的功能異常並最終影響細胞分裂中染色體的分離最後形成非整倍體。
其餘的細胞分裂控制蛋白AURKA、BUBR1以及MAD2在鄰近以及遠離腫瘤內壞死區域的表現量變異不大，這樣的發現指向STAG2是一個獨立的調控染色體非整倍體的因子。更深入的腫瘤區域性分析將以電腦攝影分析來提供更詳細的區域性的資訊。 這實驗提供了肺臟多型性上皮癌概略性腫瘤壞死和較差的預後之間的影響因素，而更深入的影響機制還需更深入的研究。 | zh_TW |
| dc.description.abstract | Pulmonary pleomorphic carcinoma is an uncommon type of malignant tumor with frequent distant metastasis, and chemo-resistant on clinical course. Necrosis had been observed commonly which was reported to connect with poorer prognosis and contribute to intratumoral heterogeneity and subclonal evolution. In this study we microdissected tumor cells from peri-necrotic and away from necrotic region for copy number variation identification. Here we found that half of the pleomorphic carcinoma cases showed distinct population between regions. Further assay of chromosome instability was achieved by FISH; signals of centromeres were amplified at peri-necrotic region. Therefore, we screened mitosis regulators STAG2, Aurora kinase A (AURKA), BUBR1 and MAD2 by IHC. Here we found STAG2 protein is commonly attenuated at peri-necrotic region. STAG2 is a subunit of cohesion complex. Loss of STAG2 is contribute to cohesin function error in mitosis and alternatively causes chromosome instability.
Other mitotic regulators AURKA, BUBR1 and MAD2 showed little difference between the two populations, suggesting that STAG2 to be a unique effect to regulate aneuploidy. Further regional difference will be assay by computer photography for more detail. This study gives a brief idea of how necrosis participated in pulmonary pleomorphic carcinoma of poorer clinical prognosis, molecular mechanisms remain further study. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T14:02:26Z (GMT). No. of bitstreams: 1 ntu-104-R02444006-1.pdf: 61369036 bytes, checksum: efcaca305996e97299e909c0eb59895b (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 目錄
Abstract 1 摘要 2 前言 3 肺癌 3 肺臟多型性上皮癌 4 壞死 5 非整倍體 6 材料及方法 7 腫瘤檢體及型態分析 7 切片製備 7 Hematoxylin及eosin 染色 7 腫瘤組織顯微取樣及DNA純化 8 染色體套數變異度分析 8 免疫染色 9 免疫螢光原位雜交 (fluorescence in situ hybridization, FISH) 10 實驗結果 11 染色體異質性分析 11 Cohesin複合物的形成 13 染色質絲的形成及連接 14 有絲分裂檢查點調控因子的表現 15 端粒的延長 17 結論以及討論 19 Figure 1 23 Figure 2 25 Figure 3 26 Figure 4 28 Figure 5 31 Figure 6 35 Figure 7 39 Figure 8 41 Figure 9 43 Figure 10 44 表一: 免疫染色中抗體資訊 45 表二:FISH探針基本資訊 46 表三: 病患的臨床資料 47 Supplementary Figure 1: nCounter® Copy Number Variation Assay 49 參考資料 50 | |
| dc.language.iso | zh-TW | |
| dc.subject | 非整倍體 | zh_TW |
| dc.subject | 肺臟多型性上皮癌 | zh_TW |
| dc.subject | STAG2 | zh_TW |
| dc.subject | 腫瘤異質性 | zh_TW |
| dc.subject | intratumoral heterogeneity | en |
| dc.subject | STAG2 | en |
| dc.subject | pulmonary pleomorphic carcinoma | en |
| dc.subject | aneuploidy | en |
| dc.title | 肺臟多型性上皮癌中鄰近腫瘤壞死區域STAG2的缺失和非整倍體增加之關聯 | zh_TW |
| dc.title | Loss of STAG2 is associated with peri-necrotic increased aneuploidy in pulmonary pleomorphic carcinoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 施金元,蔡孟峰 | |
| dc.subject.keyword | 肺臟多型性上皮癌,STAG2,非整倍體,腫瘤異質性, | zh_TW |
| dc.subject.keyword | pulmonary pleomorphic carcinoma,STAG2,aneuploidy,intratumoral heterogeneity, | en |
| dc.relation.page | 54 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-20 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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