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研究生:莊智程
研究生(外文):Chuang chi chen
論文名稱:探討Gelsolin的調降及其生理意義於人類子宮頸上皮細胞癌
論文名稱(外文):Down-regulation of gelsolin expression and its clinicopathological significance in human cervical carcinoma
指導教授:林光輝林光輝引用關係
學位類別:碩士
校院名稱:長庚大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:44
中文關鍵詞:子宮頸癌生物標記二維電泳
外文關鍵詞:cervical cancerbiomarker2-dimensional polyacrylamide gel electrophoresis
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子宮頸癌 (cervical cancer) 位居女性癌症排名的第二位,但至目前為止對於子宮頸癌發生的分子機制所知有限,從過去文獻來看,在子宮頸癌發現的生物標記 (biomarker) 為數不少,但並非每一個都適合做為子宮頸癌診斷 (diagnosis) 與預後 (prognostic) 的基準,所以本實驗利用蛋白質體二維電泳(2-dimensional polyacrylamide gel electrophoresis, 2D-PAGE) 方法,比較正常和子宮頸癌組織中表現有顯著差異的蛋白,gelsolin就是其中一例。而gelsolin在細胞中的角色就是經由調節肌動蛋白單體 (actin monomer, G-actin) 的聚合作用 (polymerization) 和肌動蛋白纖維體 (actin filament, F-actin) 的去聚合作用 (depolymerization) 來維持細胞的形態 (morphology) 和能動力 (motility)。從西方墨點法得知,在45個cases中有明顯調降的佔33對(73.3%),而整體調降的倍率為2.03倍。從西方墨點法中也得知,gelsolin調降較多時 (>2.03倍) 病人在治療後容易復發而且病患的tumor size也較大。免疫組織染色的統計結果顯示gelsolin的表現量和子宮頸癌的臨床分期及腫瘤細胞分化程度無關。另一方面,比較10個正常人血清和10個患有子宮頸癌病人的血清,gelsolin的表現量在病人的血清中下降了1.4倍。結論:由二維電泳可以有效率的找出新的蛋白分子如geloslin,做為臨床上的應用。
Cancer of the uterine cervix is the second most common cause of death from gynecologic cancer worldwide. To study the differential expression of proteins in normal and cancerous cervical tissues, and identify new molecular markers for diagnosis and prognosis, as well as develop new therapeutic targets of the disease which two-dimensional electrophoresis (2DE). The differential expression of proteins was confirmed using Western blot, and immunohistochemical analysis. The clinical correlations and prognostic significance of those aberrantly expressed proteins were evaluated to determine the novel cervical cancer biomarkers. The data indicate the expression of cytoplasmic gelsolin was significantly down-regulated in 73% of cervical patients (n=45) and was selected for further study. The gelsolin expression in cervical tumor tissues was decreased by 2.03-fold (range, 0.74–7.46-fold) compared with noncancerous regions. Significant decrease in gelsolin might related to disease recurrence after treatment and massive tumor size in cervical cancer patients by western blot analysis. Decreased gelsolin expression was not associated with clinical stage by immunohistochemistry staining analysis. In conclusion, differential expression analysis of proteomes may be useful for the development of new molecular markers for diagnosis and prognosis of cervical carcinoma, such as cytoplasmic gelsolin.
指導教授推薦書…………………………………………………
口試委員會審定書………………………………………………
授權書…………………………………………………………… iii
誌謝……………………………………………………………… iv
中文摘要………………………………………………………… v
英文摘要………………………………………………………… vi
目錄 …………………………………………………………… vii
背景及文獻資料回顧…………………………………………… 1
子宮頸癌簡介 ……………………………………………… 1
子宮頸癌的生物標記 ……………………………………… 2
Gelsolin在細胞內的角色 …………………………………… 3
Gelsolin與細胞凋亡 ………………………………………… 3
Gelsolin在癌細胞內的表現量 ……………………………… 4
Gelsolin與細胞的增生 ……………………………………… 4
Gelsolin與轉移和侵入的矛盾關係 ………………………… 5
論文研究目的 …………………………………………………… 6
研究方法 ………………………………………………………… 7
臨床檢體和前處理 ………………………………………… 7
二維電泳 …………………………………………………… 7
第一維 ………………………………………………… 7
1. Rehydration loading 法 ………………………… 7
2. Cup loading 法 ………………………………… 7
第二維 ………………………………………………… 8
銀染和掃描 ……………………………………………… 9
膠內切割和MALDI-TOF質譜分析 ………………………… 9
西方墨點法 …………………………………………………… 11
MMP zymography ……………………………………………… 12
免疫組織化學染色 …………………………………………… 13
實驗結果
二維電泳的結果……………………………………………… 14
區分plasma gelsolin和cytoplasmic gelsolin…………………… 14
以西方墨點法偵測正常組織和子宮頸癌組織cytoplasmic gelsolin的表現量……………………………………………………… 15
以西方墨點法偵側正常人血清和患有子宮頸癌病人血清內plasma gelsolin的表現量……………………………………… 16
MMP zymography結果………………………………………… 17
以免疫組織化學染色偵測子宮頸癌組織中cytoplasmic gelsolin的表現量………………………………………………………… 17
討論 ………………………………………………………………… 19
常用的子宮頸癌血清腫瘤標記探討 ………………………… 20
二維電泳實驗結果的探討…………………………………… 20
Gelsolin在子宮頸癌組織調降的探討………………………. 21
Gelsolin調降機制的探討…………………………………… 21
參考文獻…………………………………………………………… 23
附錄………………………………………………………………… 26
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國家衛生研究院 (NHRI) 癌症研究組,«子宮頸癌篩檢及治療共識»,(再版),台北,臺灣癌症臨床研究合作組織,民國八十九年。
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