2015-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/660492摘要：泌尿上皮癌(urothelial carcinoma)的發生率為每十萬人中11.6，是台灣地區第十大常見的惡性腫瘤。台灣與巴爾幹半島地區同為全世界上泌尿道(腎盂及輸尿管)泌尿上皮癌發生率最高的地區，且數倍於歐美等西方國家。台灣大學公衛系王榮德教授發現於西元1997年至西元2003年七年間，有39%的國人服用了含馬兜鈴酸的中藥材。這樣的結果說明台灣人長期處於馬兜鈴酸的環境中。我們的研究也發現了超過六成的上泌尿道泌尿上皮癌病人的腎實質中含有馬兜鈴酸的印記，有超過三成以上的病人有馬兜鈴酸直接致癌的標記，特色性突變。然而，馬兜鈴酸引起的上泌尿道泌尿上皮癌，相較於其他上泌尿道泌尿上皮癌，不但腫瘤較惡性，也容易在對側上泌尿道復發。若能早期診斷這些復發腫瘤，將有機會保留住病人僅剩的一側腎臟，以避免須接受透析治療。此外，對於過去有馬兜鈴酸暴露史的人們，早期診斷的工具也許能讓他們免於須接受單側腎臟摘除之手術。因此，本研究祉在發展血液與尿液中之生物指標，協助醫師們早期診斷泌尿上皮癌。首先，我們將收集上泌尿道泌尿上皮癌病人，於接受腎臟與輸尿管摘除手術前之血液與尿液檢體，分析有無特定之腫瘤標記(此已有鼓舞性的結果)，如DNA特定片段等。此後，我們將分析這些腫瘤標記，於手術後何時會消失。最後，會分析這些腫瘤標記在病人未來復發時的表現狀況。藉此來評估目前有潛力的腫瘤標記可否作為早期診斷泌尿上皮癌的工具。<br> Abstract: Urothelial carcinoma is the 10th leading malignancy in Taiwan, and the incidence is about 11.6/100,000 person-year. Both Taiwan and Balkan areas had the highest incidence of the upper urinary tract urothelial carcinoma (UTUC) around the world. In Taiwan, Professor JD Wang et al. discovered that 39% of Taiwanese people had taken aristolochia-containing Chinese herbal regimens during the period from 1997 to 2003, suggesting that a large part of Taiwanese populations had been exposed to aristolochiic acid before 2003. We also discovered aristolactam-DNA adduct could be detected in the renal cortex of more than 60% of our UTUC patients, and the carcinogenic effect of aristolochic acid was observed in more than 30% of patients by measuring the signature TP53 mutations in tumors. Unfortunately, aristolochic acid-induced UTUC tumors were more malignant and had a higher risk of contralateral upper urinary tract recurrence comparing with UTUC tumors caused by other carcinogens. If we can diagnose these recurrent tumors early, the UTUC patients will have chance to preserving the kidney they only have, and avoid the life-long dialysis. In addition, the early diagnostic tool can be applied for screening urothelial tumors in the population who had exposed to aristolochia or possible aristolochia containing herbs. The removal of diseased kidney or ureter might be avoided in some patients by early diagnosis of UTUC. The purpose of this study is to develop biomarkers, which can help physician detect urothelial carcinoma early, in urine and blood. Firstly, we will enroll UTUC patients who will receive nephroureterectomies and collect the fresh tissues from tumor, cortex, urothelium, urine and plasma. The efficacy of the biomarkers, such as free and circulating DNA fragments, would be analyzed. Secondly, we will use these useful biomarkers in the routine examinations during the period of followup, and decide the exact efficacy of recurrence prediction in our UTUC patients.泌尿上皮癌尿液游離基因循環基因馬兜鈴酸膀胱復發上泌尿道復發urothelial carcinomafree DNA in urinecirculating DNAaristolochic acidbladder recurrenceupper urinary tract recurrence