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  1. NTU Theses and Dissertations Repository
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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46785
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor江俊斌,郭彥彬
dc.contributor.authorYi-Ching Liuen
dc.contributor.author柳依青zh_TW
dc.date.accessioned2021-06-15T05:41:29Z-
dc.date.available2012-10-05
dc.date.copyright2011-10-05
dc.date.issued2011
dc.date.submitted2011-08-04
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46785-
dc.description.abstract背景
Gα12為G蛋白家族中屬於Gα12/13次家族的一類,在人體正常的生理機能如血壓調控、肌肉收縮及胚胎發育過程中細胞正常的遷移,在神經系統的發育扮演重要角色。Gα12已知可能促進腫瘤生長(proliferation)及轉移(metastasis),在人體癌症如乳癌、攝護腺癌及鼻咽癌等的表現量都有提高的情形。本研究欲探討口腔癌中Gα12蛋白於病理組織中的表現量及與臨床各參數和存活時間的關係。
材料與方法
本研究利用免疫組織化學染色方法,探討Gα12於100例口腔鱗狀細胞癌(OSCC)、45例口腔上皮變異(OED)及36例正常口腔黏膜(NOM)中的表現,並以陽性染色指標Labeling index紀錄其染色程度。利用卡方檢定(Chi-square test)、Kaplan-Meier 存活率方法及Cox proportional hazard regression model來分析Gα12的表現與口腔鱗狀細胞癌患者臨床病理參數及存活率之相關性,並試圖尋找影響存活時間的獨立預後因子。
結果
在正常口腔黏膜Gα12的平均陽性標記指數為6.78% (最低),口腔上皮變異組的平均陽性標記指數為21.78%,口腔癌組的平均陽性標記指數為 51.27% (最高),可以看出從正常口腔黏膜、上皮變異至口腔癌,這個癌化的過程,Gα12的表現增加的情形,且達統計意義(P < 0.001)。Gα12的表現和患者的腫瘤大小與侵犯深度(T status)、淋巴結轉移與否(N status)、癌症臨床分期(Stage)有統計上相關。
各項臨床參數在Cox proportional hazard regression model分析中,以單變項分析後發現,腫瘤大小與侵犯深度、淋巴結轉移與否、腫瘤臨床分期及Gα12的陽性染色指標(LI)都與存活率有關;且以上四者經多變項分析均為影響存活時間的獨立因子(independent factor)(p<0.05);Gα12陽性染色指標若>50%,影響病人存活的危險率(hazard ration)高達5.289倍(p=0.045)。同樣地以Cox proportional hazard regression model分析組織病理中五項風險因子,由單變項分析中發現,原發腫瘤侵犯血管淋巴系統(lymphovascular invasion)、具有兩顆以上之轉移淋巴結(metastatic lymph nodes≧2)兩項與存活率有關,再經多變項分析後,發現此二者也是影響病患存活率的獨立因子。
若以Kaplan-Meier plots來觀察臨床及組織病理各項參數、Gα12的陽性染色指標與病人總存活時間(overall survival),經Log-Rank Test分析後,腫瘤大小與侵犯深度、淋巴結轉移與否、腫瘤臨床分期、原發腫瘤是否侵犯血管淋巴系統及是否具有兩顆以上之轉移淋巴結均影響病人的存活時間,且達統計上之意義(p<0.05)。而本研究探討的Gα12的陽性染色指標(LI)若>50%,則明顯降低了口腔癌病人的存活率(p=0.0009)。
結論
在本研究中,Gα12的陽性染色指標在口腔癌病理標本中的表現較高且具統計上意義,且與口腔細胞癌患者在臨床參數、組織病理的風險因子及存活時間有關。在口腔癌患者而言,Gα12的表現量指向較短的存活時間;而Gα12在切片組織中的表現程度,或許可以做為口腔癌的預後指標(prognostic marker)。
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dc.description.tableofcontents中文摘要V
英文摘要VII
第一章 序論及文獻回顧 9
1.1.口腔鱗狀細胞癌概論 9
1.1.1口腔鱗狀細胞癌簡介 9
1.1.2口腔鱗狀細胞癌之流行病學 10
1.1.2.1口腔鱗狀細胞癌之全球流行病學 10
1.1.2.2.口腔鱗狀細胞癌之台灣地區流行病學及疾病特色11
1.1.3口腔鱗狀細胞癌之危險因子及基因變異 11
1.1.4口腔鱗狀細胞癌之臨床分期 16
1.1.5現行對口腔鱗狀細胞之治療及預後 16
1.1.6口腔癌前病變 16
1.2 Gα12蛋白概論 17
1.2.1.1 G蛋白家族(G protein family) 17
1.2.1.2 G蛋白於細胞內之訊息傳遞(signaling tranduction)機制 19
1.2.2 Gα12在胚胎發育過程之角色19
1.2.3 Gα12之生理作用與其他疾病的關係 21
1.3 Gα12與癌症之關係 22
1.3.1 Gα12於細胞株(cell lines)及動物實驗(animal models)之研究 23
1.3.2 Gα12於人類癌症之發現 25
第二章 材料與方法 28
2.1實驗樣本 28
2.2標本之固定與包埋 28
2.3免疫組織化學染色(immunohistochemistry stain) 28
2.3.1反應原理28
2.3.2初級抗體的選擇 29
2.3.3 抗原抗體結合之偵測系統 29
2.3.4實驗步驟 30
2.4免疫組織化學染色之觀察與記錄 32
2.4.1觀察 32
2.4.2染色程度之定量 32
2.4.3臨床變數之紀錄 32
2.4.4統計分析 33
第三章 結果 35
3.1 Gα12於口腔鱗狀細胞癌(OSCC)、口腔上皮變異(DOE)及正常口腔上皮(NOM)之表現 35
3.2 Gα12免疫組織化學染色結果與患者臨床及組織病理各項參數之關係36
3.3 Gα12免疫組織化學染色與臨床、組織病理參數之單變量、多變量分析 40
3.4Gα12表現與存活時間分析 41
第四章 討論 42
第五章 結論 42
第六章 附表與附圖 47
參考文獻 62
dc.language.isozh-TW
dc.subject口腔上皮變異zh_TW
dc.subjectGα12蛋白zh_TW
dc.subject口腔鱗狀細胞癌zh_TW
dc.subjectoral epithelial dysplasiaen
dc.subjectGα12en
dc.subjectoral squamous cell carcinomaen
dc.titleGα12蛋白於口腔鱗狀細胞癌中之表現zh_TW
dc.titleExpression of Gα12 in oral squamous cell carcinomaen
dc.typeThesis
dc.date.schoolyear98-2
dc.description.degree碩士
dc.contributor.oralexamcommittee張龍昌
dc.subject.keywordGα12蛋白,口腔鱗狀細胞癌,口腔上皮變異,zh_TW
dc.subject.keywordGα12,oral squamous cell carcinoma,oral epithelial dysplasia,en
dc.relation.page72
dc.rights.note有償授權
dc.date.accepted2011-08-05
dc.contributor.author-college牙醫專業學院zh_TW
dc.contributor.author-dept臨床牙醫學研究所zh_TW
顯示於系所單位:臨床牙醫學研究所

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