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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 于明暉 | zh_TW |
dc.contributor.advisor | Ming-Whei Yu | en |
dc.contributor.author | 蔡旻儒 | zh_TW |
dc.contributor.author | Min-Ru Tsai | en |
dc.date.accessioned | 2021-07-10T22:11:10Z | - |
dc.date.available | 2024-02-28 | - |
dc.date.copyright | 2018-10-11 | - |
dc.date.issued | 2018 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | 第五章、 參考文獻
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A quantitative metabolomics profiling approach for the noninvasive assessment of liver histology in patients with chronic hepatitis C. Clin Transl Med 2016;5(1):33. 47. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science (New York, N.Y.) 2009;324(5930):1029-1033. 48. Gao R, Cheng J, Fan C, et al. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma. Sci Rep 2015;5:18175. 49. Levine RJ, Conn HO. Tyrosine metabolism in patients with liver disease. J Clin Invest 1967;46(12):2012-20. 50. Huang Q, Tan Y, Yin P, et al. Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics. Cancer Res 2013;73(16):4992-5002. 51. Yang Y, Li C, Nie X, et al. 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(1)H NMR-based serum metabolic profiling in compensated and decompensated cirrhosis. World Journal of Gastroenterology : WJG 2012;18(3):285-290. 58. Yu MW, Chen CJ. Hepatitis B and C viruses in the development of hepatocellular carcinoma. Crit Rev Oncol Hematol 1994;17(2):71-91. 59. Constantinou MA, Papakonstantinou E, Spraul M, et al. 1H NMR-based metabonomics for the diagnosis of inborn errors of metabolism in urine. Analytica Chimica Acta 2005;542(2):169-177. 60. R. GKP, M. SS, K. NJ, et al. Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data. NMR in Biomedicine 1990;3(4):166-172. 61. Lenz EM, Bright J, Knight R, et al. Cyclosporin A-induced changes in endogenous metabolites in rat urine: a metabonomic investigation using high field 1H NMR spectroscopy, HPLC-TOF/MS and chemometrics. Journal of Pharmaceutical and Biomedical Analysis 2004;35(3):599-608. 62. D. BJ, C. BJC, J. SP. NMR studies of body fluids. NMR in Biomedicine 1989;2(5‐6):246-256. 63. Nowick JS, Khakshoor O, Hashemzadeh M, et al. DSA: A New Internal Standard for NMR Studies in Aqueous Solution. Organic Letters 2003;5(19):3511-3513. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77604 | - |
dc.description.abstract | 背景與目的: B型肝炎病毒感染肝細胞並干擾代謝途徑,在過去的病例對照研究中,肝細胞癌患者與非肝細胞癌患者有明顯的代謝差異,然而,與B型肝炎病毒相關肝細胞癌自然病程及發病機制仍尚未清楚。本研究主旨在前瞻性地調查男性B型肝炎帶原者中肝細胞癌發展相關的代謝變化。
材料與方法: 首先,從已發表的病例世代研究中選擇108名肝細胞癌病例並配對108名對照個案探索重要代謝物,後續由另一個獨立巢式病例對照研究進行驗證(63名肝細胞癌病例和107名對照),上述所有參與者皆為B型肝炎表面抗原陽性且年齡大於30歲之男性。我們檢測了基線及長期追縱下的血漿代謝組學圖譜,鑑定出的差異代謝物也與12名Child-Pugh B級和24 Child-Pugh C級的臨床肝硬化患者進行比較。代謝體實驗使用一維度氫原子核磁共振質譜儀測定,而多變量分析則以PLS-DA進行,利用廣義線性混合模型和廣義估計方程式探討特定代謝物與肝細胞癌之間的縱向關係。 結果: 從長期趨勢可以發現,tyrosine、glutamine、glutamate於病例組與對照組有顯著差異,具體而言,tyrosine和glutamate在病例組有相對較高的濃度,並與病毒量有顯著正相關,而glutamine則在病例組有相對較低的濃度,與病毒量有顯著負相關。Tyrosine、glutamine在肝硬化族群中也發現相似的關係。 結論: 本研究發現胺基酸代謝小分子的改變與B型肝炎病毒相關肝細胞癌的發展有關,其中glutamine觀察到負相關,tyrosine和glutamate觀察到正相關。 | zh_TW |
dc.description.abstract | Background and Aims: Hepatitis B virus (HBV) infects hepatocytes that can interfere with some of metabolic pathways. Previous case-control studies have shown distinct metabolic profiles in patients with hepatocellular carcinoma (HCC) vs. those without. However, the natural history and pathogenesis of HBV-related HCC remained largely unknown. This study aimed to prospectively investigate metabolic changes in relation to the development of HCC among male HBV carriers.
Materials and Methods: In the discovery phase, 108 HCC cases and 108 matched controls were selected from a published case-cohort study. The results were replicated in an independent nested case-control study of 63 HCC cases and 107 controls. All participants were hepatitis B surface antigen-positive men aged ≥30. We examined metabolomics profiles in plasma collected at baseline and follow-up. Differential metabolites identified were also compared with clinical cirrhotic patients, with 12 Child-Pugh class B and 24 Child-Pugh class C. Metabolic profiles were analyzed by 1H nuclear magnetic resonance spectroscopy follow by multivariate analysis, specifically partial least squares discriminant analysis. The longitudinal relationship between specific metabolites and HCC were explored using generalized linear mixed model (GLMM) and generalized estimating equation (GEE) model. Result: From longitudinal analysis, we found that tyrosine, glutamine, and glutamate were significantly different between cases and controls. Specifically, tyrosine and glutamate had a relatively high abundance in the HCC cases also had a significantly positive correlation with HBV viral load, whereas glutamine had a relatively low abundance in the HCC cases as well as having a significantly negative correlation with viral load. Similar associations with liver cirrhosis were also found for tyrosine and glutamine. Conclusion: The data showed that metabolic alteration in amino acids was associated with the development of HBV-related HCC, with negative association observed for glutamine and positive associations observed for tyrosine and glutamate. | en |
dc.description.provenance | Made available in DSpace on 2021-07-10T22:11:10Z (GMT). No. of bitstreams: 1 ntu-107-R05849002-1.pdf: 2172293 bytes, checksum: c2b0e6260aed87a03de1a52597bde0d5 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 目錄
口試委員審定書................................................................................................................i 致謝...................................................................................................................................ii 中文摘要..........................................................................................................................iii 英文摘要..........................................................................................................................iv 圖目錄................................................................................................................ ...........viii 表目錄..............................................................................................................................ix 第一章、研究背景.............................................................................................................1 B 型肝炎與肝細胞癌之進展............................................................................................1 慢性 B型肝炎自然史........................................................................................................1 病毒因子與肝臟疾病之關係...........................................................................................2 代謝體學...........................................................................................................................3 肝臟疾病的代謝體學研究...............................................................................................4 研究目的...........................................................................................................................6 第二章、材料與方法.......................................................................................................7 研究架構...........................................................................................................................7 研究樣本...........................................................................................................................7 血漿的 1H NMR 分析......................................................................................................9 圖譜前處理與代謝物辨認.............................................................................................10 統計分析.........................................................................................................................10 第三章、結果.................................................................................................................12 研究個案基線特性.........................................................................................................12 鑑別重要代謝小分子.....................................................................................................12 重要代謝小分子追蹤期間內變化趨勢.........................................................................13 代謝小分子濃度變化與病毒因子之關係.....................................................................13 基線代謝小分子與肝細胞癌危險性.............................................................................14 肝硬化病人之代謝分布.................................................................................................15 第四章、討論.................................................................................................................16 芳香族胺基酸代謝.........................................................................................................17 Glutamine 及Glutamate 代謝.........................................................................................18 Glucose-Alanine 循環.....................................................................................................18 胺基酸與檸檬酸循環.....................................................................................................19 第五章、參考文獻.........................................................................................................21 | - |
dc.language.iso | zh_TW | - |
dc.title | 早期代謝體變化與HBV帶原者發生肝細胞癌的關係:擴展研究 | zh_TW |
dc.title | Extended Study of Early Metabolomics in Hepatocellular Carcinoma Patients versus Controls among HBV Carriers | en |
dc.type | Thesis | - |
dc.date.schoolyear | 106-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.coadvisor | 林靖愉 | zh_TW |
dc.contributor.coadvisor | Ching-Yu Lin | en |
dc.contributor.oralexamcommittee | 李文宗;林志陵;薛玉梅;黃奕文 | zh_TW |
dc.contributor.oralexamcommittee | Wen-Chung Lee;Chih–Lin Lin;Yu-Mei Hsueh;Yi-Wen Huang | en |
dc.subject.keyword | B型肝炎病毒,代謝體學,肝細胞癌,肝硬化, | zh_TW |
dc.subject.keyword | hepatitis B virus,metabolomics,hepatocellular carcinoma,cirrhosis, | en |
dc.relation.page | 44 | - |
dc.identifier.doi | 10.6342/NTU201801977 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2018-07-26 | - |
dc.contributor.author-college | 公共衛生學院 | - |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | - |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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