臺灣博碩士論文加值系統

Ｂ、Ｃ型肝炎病毒感染造成急、慢性肝炎，慢性肝炎中，Ｂ型肝炎病毒感染有很高比例會導致肝硬化和肝癌，Ｃ型肝炎病毒感染有很高比例會發展為肝癌。肝細胞被破壞，重生(regeneration)時，染色體會發生變異，可能是肝癌發生的機轉之一。
肝癌的形成，可能是一個多步驟過程(multi-step process)，包括與訊息傳遞有關的基因或調控基因表現有關的基因的不正常變化。此包括細胞激素、生長因子及其受體，各種激醣，Ｇ蛋白及轉錄因子。
轉錄因子E4BP4和NREBP會抑制Ｂ型肝炎病毒的表現，C/EBP家族蛋白會增加Ｂ型肝炎病毒的表現。其蛋白表現很可能在肝癌組織和正常組織中不同。因此，在本論文中以轉錄因子E4BP4，NREBP 及C/EBPs (C/EBP α、C/EBP β、C/EBP δ)之抗體，以免疫組織化學及免疫螢光的方法，偵測在正常肝細胞和肝癌組織及其鄰近非腫瘤組織細胞之表現。
血清檢查Ｂ型肝炎表面抗原（HBsAg）陽性的病例中，五種轉錄因子在組織切片中表現陽性的百分率高於HBsAg陰性的病例。在HBsAg陽性的病例中，在腫瘤組織的陽性率為80-90%，而腫瘤旁邊正常組織的陽性率約為60%。血清檢查HBsAg陰性的病例中，在腫瘤組織的陽性率為65-88%，而腫瘤旁邊非腫瘤組織的陽性率約為35-53%。但E4BP4在腫瘤組織和鄰近的非腫瘤組織的陽性率皆較低。
五種轉錄因子的免疫染色皆表現在細胞核。一般而言，無論血清檢查HBsAg是陽性或陰性的病例，腫瘤組織的陽性百分率皆高於鄰近的非腫瘤組織和正常組織；在表現的強度上，腫瘤組織的表現高於其鄰近的非腫瘤組織，或腫瘤組織與鄰近的非腫瘤組織具有相同的表現。

Infection of hepatitis B virus (HBV) is a major public health problem worldwide and, particularly, in Taiwan. About 15 to 20% of patients infected with HBV develope chronic hepatitis. Chronic hepatitis carries significant mortality and morbidity as it can cause cirrhosis and hepatocellular carcinoma (HCC). Infection of hepatitis C virus (HCV) also cause acute and chronic hepatitis. About 20% of chronic carrier develope HCC. The chromosomal abnormality resulted from the hepatocyte regeneration may be one of the mechanism for the developement of HCC.
The developement of HCC is most probably a multi-step process. This includes the abnormal change of genes involved in the signal transduction and transcriptional regulation.
Transcription factor E4BP4 and NREBP inhibit the expression of HBV genes, while C/EBP family proteins stimulate its expression.
In this thesis, the expression of, E4BP4, NREBP and C/EBPs (C/EBP/α, C/EBP/β, C/EBP/δ) in HCC and its adjacent tissues were analyzed by immunohistochemistry and immunofluorescence.
Generally, the expression of these five transcription factors was in the nucleus. Positive rate of these five transcription factors in tumor tissues was higher than that of its adjacent non-tumorous parts. The positive rate of these five transcription factors in cases with positive serum HBsAg was higher than the cases with negative HBsAg.
In General, in cases with either positive or negative HBsAg, the level of expression of these five transcription factors in tumor tissues was stronger than those in the adjacent non-tumorous parts.

中文摘要 I
英文摘要 III
壹、緒論 1
第壹部份：Ｂ型肝炎病毒 1
一、Ｂ型肝炎病毒之宿主特異性 1
二、Ｂ型肝炎病毒之結構 2
三、Ｂ型肝炎病毒之複製過程 3
四、Ｂ型肝炎病毒的基因群構造及訊息RNA 4
五、Ｂ型肝炎病毒之轉錄調控 5
六、轉錄因子 10
(一) C/EBPs 10
(二) E4BP4 14
(三) NREBP 17
第貳部份：病毒性肝炎之血清學 19
一、Ａ型肝炎病毒 19
二、Ｂ型肝炎病毒 19
三、Ｃ型肝炎病毒 20
四、Ｄ型肝炎病毒 20
五、Ｅ型肝炎病毒 21
六、肝炎病毒的合併感染 21
第參部份：肝細胞癌之病理學 22
一、病理致病機制 22
二、肝細胞癌之病理學診斷 24
貳、材料與方法 27
參、結果 45
肆、討論 51
伍、參考文獻 54
陸、圖表 72

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