臺灣博碩士論文加值系統

關於口腔癌的形成有許多理論，目前為止臨床上都無法有效的觀察到由口腔癌前病變轉變為癌的過程。部分的癌症會出現相關癌前病變，然而如此的癌前病變位於臟器內，無明顯症狀或型態，因此大多數無法進行臨床觀察，然而口腔內之癌前病變，種類多且發生率高，檢測與觀察最為容易，是最可以被用於研究癌變過程的目標。台灣地區口腔癌發生率居高不下，此點被認為是研究如何控制口腔癌的重要方向，本研究論文即以口腔癌前病變為研究對象，探討口腔癌前病變轉變成癌的可能機轉並開發早期診斷工具。
研究首先為開發非侵入性偵測口腔癌前病變組織型態之裝置。以上皮細胞內輔酶FAD, NADH所產生之自體螢光反應為實驗方法，偵測不同型態與組織退變程度的口腔癌前病變，藉病變區與對照區的螢光發射強度差異來分析。此外亦進行癌前病變上念珠菌落的培養，了解念珠菌在相同個體，患側與對照側黏膜表面菌落的分布。這些方法的優點均為非侵入性偵測，並可以使用於大規模篩檢。
口腔癌前病變需要能方便長期觀察的工具，對於癌前病變的癌變更需要完整的理論假設，讓實驗長期驗證此假設的真實性，因此是極為困難的工作，本研究可提供此研究部分基礎，期待日後可早日得知口腔癌前病變癌變的全貌，實現控制口腔癌的長期目標。

On the malignant transformation of oral cancer, there are several theories, however to clinically effective observe their transformation process is hard. Some cancer had premalignant change before frankly malignant behavior emerges. Oral premalignant lesions prevalence is high, therefore easy in detection and observation. Such characters make them be a good candidate in studying cancer transformation process. These series researches focus on the oral precancerous lesions, try to study the mechanism of oral premalignant lesions into malignancy. Furthermore early detection modality for control the damage from oral cancer was also developed.
The first section of the study is to develop a non-invasive oral premalignant lesions detection kit. The autofluorescence reaction from the coenzymes FAD and NADH of epithelial cell were used to be the detecting autofluorescence material. The goal is to study the fluorescence parameter correspond to the different clinical feature and histologic grade of oral premalignant lesions. The fluorescence intensity between the lesions and the control area was interpreted. In addition, the candidiasis colony of the premalignant lesions were also carried out to understand the distribution of rosette in the same individual, ipsilateral and control side colonies. The advantage of this method is that non-invasive detection can be used for large screening program.
The oral premalignant lesions detecting kits that can be a long term follow up tools. For the observation carcinogenesis of premalignant lesions available instrument is required. One more complete set of theoretical hypothesis is needed, which makes it extremely difficult for the experiment to verify their authenticity. We try to provide some basis research and look forward to know the overall picture of premalignant lesions transformation process in the future, ultimately to achieve the goal, controlling oral cancer damage.

目 錄
致 謝.......4
縮寫表.......5
目 錄.......6
圖目錄.......8
表目錄.......10
中文摘要.......10
英文摘要.......12
第一章 緒論.......13
第一節：研究動機與重要性.......13
第二節 研究目的.......14
第三節 文獻查證.......16
一、口腔癌前病變介紹與分類.......16
二、口腔癌前病變的偵測與診斷.......17
三、口腔癌前病變惡性轉變機率.......18
四、自體螢光反應基本原理.......20
五、念珠菌與口腔癌前病變.......22
六、口腔癌前病變之評等與分類.......24
七、以口腔癌病人模型，探討口腔癌前病變之癌變與對口腔癌治療之衝擊.......25
第四節 研究假設.......27
第二章 研究方法與材料.......28
第一節 自體螢光反應偵測口腔癌前病變.......28
一、手持式自體螢光偵測器.......28
二、FAD及NADH模組.......28
三、FAD 與NADH 前期檢測標準試劑.......29
第二節 念珠菌與口腔癌前病變.......30
第三節 口腔癌前病變評等系統.......33
第四節 以口腔癌病人模型，探討口腔癌前病變之癌變與對口腔癌治療之衝擊。.......35
第三章 結果.......37
第一節 口腔癌前病變自體螢光反應.......37
第二節 白色念珠菌與口腔癌前病變.......39
第三節 口腔癌前病變評等系統.......44
第四節 利用口腔癌病人模型，探討口腔癌前病變之癌變與對口腔癌治療之衝擊.......45
一、檳榔咀嚼習慣率分析.......45
二、口腔與口咽可辨識癌前病變和二次原發性口腔癌相關性.......45
三、VOPL和SPOC之間相關性分析.......46
第四章 討論.......47
第一節 自體螢光反應偵測口腔癌前病變.......47
第二節 念珠菌與口腔癌前病變.......51
第三節 癌前病變評等系統.......52
第五章 結論與展望.......56
參考文獻.......58
圖表.......66
圖 目 錄
附圖1 FAD與NADH的能量吸收與螢光發射光譜.......66
圖1 (a)HITACHI Spectrometer F-7000 (b)口腔癌檢體置於容器中 --67
圖2 (a)手持式裝置 (b)探頭段 (c)延伸段 (d)電路段 (e)手持段 --67
圖3 光源、接收器和光學濾光片搭配的探測頭--68
圖4 NADH模組使用光電二極體搭配光學濾光片接收光譜頻帶--68
圖5 FAD模組使用光電二極體搭配光學濾光片接收光譜頻帶--69
圖6 SIGMA-ALDRICH N4505藥品與螢光反應波段--69
圖7 SIGMA-ALDRICH F6625藥品與螢光反應波段--70
圖8 (a)均質性白斑 (b)非均質性白斑--70
圖9 紅白斑--71
圖10 紅斑症--71
圖11 (a,b,c)多發性單一型態 (d,e)多發性多型態--72
圖12 口腔黏膜下纖維化--73
圖13 口腔念珠菌型態--74
圖14 口腔念珠菌菌落數量多寡區分--75

表 目 錄
表一 口腔癌前病變評等系統表--76
表二 手持式自體螢光偵測器測試藥品螢光量結果--77
表三 OPMD病例其口內自體螢光FAD減損，NADH增加及 Redox ratio--78
表四 病患及病變因素與口腔念珠菌菌落數量圖表--82
表五 測試樣本群組嚼食檳榔與無嚼食檳榔者口腔癌前病變評分等級表 --85
表六 不同評分項目間相連性分析--86
表七 嚼食檳榔習慣者之個人與腫瘤相關資料分析--87
表八 有嚼食檳榔習慣者VOPL and SPOC之臨床及病理特徵分析--89
表九 SPOC＋病例之邏輯回歸分析顯示原始和校正比值和95％信賴區間 --91
表十 對VOPL和SPOC之間的關聯進行分層邏輯回歸分析--92
表十一 按VOPL病灶的形態學等級進行危險值評估--93

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