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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳美玲 | |
| dc.contributor.author | Yu-Ting Hsiao | en |
| dc.contributor.author | 蕭育婷 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:25:04Z | - |
| dc.date.available | 2013-08-08 | |
| dc.date.copyright | 2008-08-08 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37345 | - |
| dc.description.abstract | 胰臟癌在臺灣是十大癌症死因之一。胰臟癌患者的平均存活時間只有四至六個月,並且整體的五年存活率小於百分之五。百分之八十五的胰臟癌在診斷確立時,已有遠處轉移或局部侵襲至臨近器官,此時只有少於百分之十能夠接受根除性手術治療,因此尋找更有效的藥物治療而且能改善存活率對於胰臟癌病人似乎是必要且急需的。GAPDH這個基因長久以來都被視為細胞內一種穩定表現的基因(Housekeeping gene)。到近幾年來,許多報導都指出在不同的腫瘤細胞快速生長過程中GAPDH mRNA往往有比較高表現量,甚至有研究認為GAPDH對於癌症的抗藥性扮演重要的地位。因此本篇論文則希望能夠藉由抑制GAPDH活性來達到對人類胰臟癌有更好的療效。碘乙酸 ( Iodoacetic acid,IAA ) 可以作為GAPDH的抑制劑。因為IAA會在蛋白質的Cysteine的Thiol group作Carboxymethylation而使酵素失去功能。本實驗將IAA作用於人類胰臟癌細胞株(MIA PaCa-2 and Panc-1),發現IAA和細胞凋亡的相關機制有關。從我們的結果顯示當IAA作用於人類胰臟癌細胞時,在Annexin V、Cytochrome C release、Caspase活化、及Hoechst染色觀察到細胞凋亡特徵。在ATP含量測量以及PI染色等實驗發現這樣死亡方式可能牽涉到Secondary necrosis之機制。為了更進一步了解IAA如何造成細胞凋亡原因,我們先在外加抗氧化劑NAC及還原劑DTT等實驗中看到NAC及DTT都可降低IAA所造成的細胞傷害。接著在Monochlorobimane ( MCB )螢光染色發現IAA引起細胞內GSH含量減少,加上許多文獻指出GSH減少與細胞內ROS產生是有關聯性的,因此在活細胞雷射掃描共軛焦顯微鏡以MitoSox染劑觀察細胞質中([O2•-]i)的變化,結果顯示IAA會誘發細胞內自由基([O2.-]i)含量上升。根據這些實驗結果我們推測IAA處理可能會引發細胞內ROS上升,細胞內氧化還原機制不平衡,同時細胞內的ATP來源受到阻礙,以致細胞內能量下降進而產生細胞凋亡及Secondary necrosis現象。 | zh_TW |
| dc.description.abstract | Pancreatic cancer is one of the tenth leading causes of death in Taiwan. The average survival duration for the patients with pancreatic cancer is about 4–6 months, and the overall 5-year survival rate is less than 5%. There are more than 85% of pancreatic cancers metastasized or extended locally at the time of diagnosis. Finally, there were less than 10% of the pancreatic cancer patients able to undergo curative resection. An effective treatment or novel agent for this devastating disease is urgently needed. Recent studies indicate that the cellular function of GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) could be involved in not only part of glycolysis, but also in novel signal pathways, especially in cancer cell survival of drug resistence. Moreover, there is static result show that the mRNA and protein expression of GAPDH in pancreatic adenocarcinoma is significant higher than in normal pancreas tissue. It would be of interest to study possible role of GAPDH in pancreatic cancer cells. There is ample evidence shows that iodoacetic acid (IAA) acts as an inhibitor of GAPDH because of its carboxymethylating ability on cysteine, an activate site of GAPDH. Human pancreatic cell lines (MIA PaCa-2 and Panc-1) were used, and we have found that IAA suppressed cancer cells viability and caused apoptotic cell death. These apoptotic signatures include phosphatidylserine exposure, cytochrome C release, activated caspases, and nuclear condensation. Nonetheless, we also consider that IAA-induced apoptosis would involve secondary necrotic cell death, according to our results of ATP decrease and propidium iodide (+) staining. Furthermore, we found that N-acetyl-L cysteine (NAC) and dithiothreitol (DTT) could attenuate the IAA-induced cellular damage. Results of glutathione (GSH) decline and accumulation of superoxide anion indicate that IAA could lead to imbalanced reduction-oxidation state of the cell, and then cause cell death. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:25:04Z (GMT). No. of bitstreams: 1 ntu-97-R95441001-1.pdf: 1649442 bytes, checksum: 6dffb2e6116c4fdc5a026716daa8961d (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 圖表次…………………………………………………Ⅲ
中文摘要………………………………………………Ⅴ 英文摘要………………………………………………Ⅶ 緒論……………………………………………………1 材料與方法……………………………………………14 結果……………………………………………………24 討論……………………………………………………33 結論與展望……………………………………………40 圖表……………………………………………………41 附錄……………………………………………………62 參考文獻………………………………………………65 | |
| dc.language.iso | zh-TW | |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 碘乙酸 | zh_TW |
| dc.subject | 人類胰臟癌細胞 | zh_TW |
| dc.subject | apoptosis | en |
| dc.subject | Iodoacetic acid | en |
| dc.subject | Human pancreatic cancer | en |
| dc.title | 碘乙酸( Iodoacetic acid )於人類胰臟癌細胞造成細胞凋亡機制之探討 | zh_TW |
| dc.title | The Mechanism of Iodoacetic Acid Induced Apoptosis in Human Pancreatic Caner Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 胡孟君,俞松良 | |
| dc.subject.keyword | 人類胰臟癌細胞,碘乙酸,細胞凋亡, | zh_TW |
| dc.subject.keyword | Human pancreatic cancer,Iodoacetic acid,apoptosis, | en |
| dc.relation.page | 80 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-21 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| 顯示於系所單位: | 生理學科所 | |
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