請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68042
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄭安理 | |
dc.contributor.author | Yu-Yun Shao | en |
dc.contributor.author | 邵幼雲 | zh_TW |
dc.date.accessioned | 2021-06-17T02:11:40Z | - |
dc.date.available | 2018-02-22 | |
dc.date.copyright | 2018-02-22 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-01-09 | |
dc.identifier.citation | 1. Parkin DM, Bray F, Ferlay J, et al: Global cancer statistics, 2002. CA Cancer J Clin 55:74-108, 2005
2. Ferlay J, Bray F, Pisani P, et al: GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide, Version 1.0., Lyon: IARC Press, 2001 3. Morgan TR, Mandayam S, Jamal MM: Alcohol and hepatocellular carcinoma. Gastroenterology 127:S87-96, 2004 4. el-Serag HB: Epidemiology of hepatocellular carcinoma. Clin Liver Dis 5:87-107, vi, 2001 5. Donato F, Tagger A, Chiesa R, et al: Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. Hepatology 26:579-84, 1997 6. Bosch FX, Ribes J, Diaz M, et al: Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:S5-S16, 2004 7. Kuper H, Tzonou A, Kaklamani E, et al: Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer 85:498-502, 2000 8. Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118:3030-44, 2006 9. Hellerbrand C, Hartmann A, Richter G, et al: Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors. Dig Dis 19:345-51, 2001 10. Kaczynski J, Hansson G, Hermodsson S, et al: Minor role of hepatitis B and C virus infection in the etiology of hepatocellular carcinoma in a low-endemic area. Scand J Gastroenterol 31:809-13, 1996 11. Rabe C, Pilz T, Klostermann C, et al: Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma. World J Gastroenterol 7:208-15, 2001 12. Schoniger-Hekele M, Muller C: Elevated serum levels of sFas in acute viral hepatitis. Eur J Gastroenterol Hepatol 13:1507-8, 2001 13. Hsu C, Cheng JC, Cheng AL: Recent advances in non-surgical treatment for advanced hepatocellular carcinoma. J Formos Med Assoc 103:483-95, 2004 14. Yeo W, Mok TS, Zee B, et al: A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst 97:1532-8, 2005 15. Cheng AL, Kang YK, Chen Z, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:25-34, 2009 16. Llovet JM, Ricci S, Mazzaferro V, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378-90, 2008 17. Bruix J, Qin S, Merle P, et al: Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 389:56-66, 2017 18. Laurent-Puig P, Legoix P, Bluteau O, et al: Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 120:1763-73, 2001 19. Okabe H, Ikai I, Matsuo K, et al: Comprehensive allelotype study of hepatocellular carcinoma: potential differences in pathways to hepatocellular carcinoma between hepatitis B virus-positive and -negative tumors. Hepatology 31:1073-9, 2000 20. Moinzadeh P, Breuhahn K, Stutzer H, et al: Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. Br J Cancer 92:935-41, 2005 21. Bluteau O, Beaudoin JC, Pasturaud P, et al: Specific association between alcohol intake, high grade of differentiation and 4q34-q35 deletions in hepatocellular carcinomas identified by high resolution allelotyping. Oncogene 21:1225-32, 2002 22. Marchio A, Pineau P, Meddeb M, et al: Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients. Oncogene 19:3733-8, 2000 23. Iizuka N, Oka M, Yamada-Okabe H, et al: Comparison of gene expression profiles between hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma by oligonucleotide microarray data on the basis of a supervised learning method. Cancer Res 62:3939-44, 2002 24. Iizuka N, Oka M, Yamada-Okabe H, et al: Molecular signature in three types of hepatocellular carcinoma with different viral origin by oligonucleotide microarray. Int J Oncol 24:565-74, 2004 25. Lee CF, Ling ZQ, Zhao T, et al: Distinct expression patterns in hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma. World J Gastroenterol 14:6072-7, 2008 26. Ura S, Honda M, Yamashita T, et al: Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology 49:1098-112, 2009 27. Messerini L, Novelli L, Comin CE: Microvessel density and clinicopathological characteristics in hepatitis C virus and hepatitis B virus related hepatocellular carcinoma. J Clin Pathol 57:867-71, 2004 28. Nasimuzzaman M, Waris G, Mikolon D, et al: Hepatitis C virus stabilizes hypoxia-inducible factor 1alpha and stimulates the synthesis of vascular endothelial growth factor. J Virol 81:10249-57, 2007 29. Gong G, Waris G, Tanveer R, et al: Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci U S A 98:9599-604, 2001 30. Hassan M, Selimovic D, Ghozlan H, et al: Hepatitis C virus core protein triggers hepatic angiogenesis by a mechanism including multiple pathways. Hepatology 49:1469-82, 2009 31. Kanda T, Steele R, Ray R, et al: Hepatitis C virus core protein augments androgen receptor-mediated signaling. J Virol 82:11066-72, 2008 32. Li Y, Chen J, Wu C, et al: Hepatitis B virus/hepatitis C virus upregulate angiopoietin-2 expression through mitogen-activated protein kinase pathway. Hepatol Res 40:1022-33, 2010 33. Mazzocca A, Sciammetta SC, Carloni V, et al: Binding of hepatitis C virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J Biol Chem 280:11329-39, 2005 34. Nunez O, Fernandez-Martinez A, Majano PL, et al: Increased intrahepatic cyclooxygenase 2, matrix metalloproteinase 2, and matrix metalloproteinase 9 expression is associated with progressive liver disease in chronic hepatitis C virus infection: role of viral core and NS5A proteins. Gut 53:1665-72, 2004 35. Jahan S, Khaliq S, Ijaz B, et al: Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis. Virol J 8:155, 2011 36. Shin JY, Hur W, Wang JS, et al: HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1. Exp Mol Med 37:138-45, 2005 37. Nie D, Shan X, Nie L, et al: Hepatitis C virus core protein interacts with Snail and histone deacetylases to promote the metastasis of hepatocellular carcinoma. Oncogene 35:3626-35, 2016 38. Quan H, Zhou F, Nie D, et al: Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition. Oncogene 33:2826-35, 2014 39. Wilhelm SM, Carter C, Tang L, et al: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099-109, 2004 40. Borenstein M, Hedges LV, Higgins JPT, et al: Introduction to Meta-analysis. Chichester (UK), John Wiley & Sons, 2008 41. Cheng AL, Guan Z, Chen Z, et al: Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer 48:1452-65, 2012 42. Bruix J, Raoul JL, Sherman M, et al: Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 57:821-9, 2012 43. Cheng AL, Kang Y, K., Lin DY, et al: Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial. J Clin Oncol 31:4067-4075, 2013 44. Johnson PJ, Qin S, Park JW, et al: Brivanib Versus Sorafenib As First-Line Therapy in Patients With Unresectable, Advanced Hepatocellular Carcinoma: Results From the Randomized Phase III BRISK-FL Study. J Clin Oncol 31:3517-24, 2013 45. Shao YY, Lin ZZ, Hsu CH, et al: Impact of Viral Etiology on the Outcomes of Patients with Advanced Hepatocellular Carcinoma Enrolled in Prospective Clinical Trials for Systemic Therapy. American Society of Clinical Oncology Gastrointestinal Cancers Symposium:Abstract 163, 2010 46. Chen CH, Huang GT, Yang PM, et al: Hepatitis B- and C-related hepatocellular carcinomas yield different clinical features and prognosis. Eur J Cancer 42:2524-9, 2006 47. Shao YY, Hsu CH, Cheng AL: Predictive Biomarkers of Antiangiogenic Therapy for Advanced Hepatocellular Carcinoma: Where Are We? Liver Cancer 2:93-107, 2013 48. Peixoto RD, Renouf DJ, Gill S, et al: Relationship of ethnicity and overall survival in patients treated with sorafenib for advanced hepatocellular carcinoma. J Gastrointest Oncol 5:259-64, 2014 49. Lin TH, Shao YY, Chan SY, et al: High Serum Transforming Growth Factor-beta1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib. Clin Cancer Res 21:3678-84, 2015 50. Hsieh CL, Chen BF, Wang CC, et al: Improved gene expression by a modified bicistronic retroviral vector. Biochem Biophys Res Commun 214:910-7, 1995 51. Im YK, La Selva R, Gandin V, et al: The ShcA adaptor activates AKT signaling to potentiate breast tumor angiogenesis by stimulating VEGF mRNA translation in a 4E-BP-dependent manner. Oncogene 34:1729-35, 2015 52. Summy JM, Trevino JG, Baker CH, et al: c-Src regulates constitutive and EGF-mediated VEGF expression in pancreatic tumor cells through activation of phosphatidyl inositol-3 kinase and p38 MAPK. Pancreas 31:263-74, 2005 53. Berra E, Pages G, Pouyssegur J: MAP kinases and hypoxia in the control of VEGF expression. Cancer Metastasis Rev 19:139-45, 2000 54. Luangdilok S, Box C, Harrington K, et al: MAPK and PI3K signalling differentially regulate angiogenic and lymphangiogenic cytokine secretion in squamous cell carcinoma of the head and neck. Eur J Cancer 47:520-9, 2011 55. Hayashi J, Aoki H, Kajino K, et al: Hepatitis C virus core protein activates the MAPK/ERK cascade synergistically with tumor promoter TPA, but not with epidermal growth factor or transforming growth factor alpha. Hepatology 32:958-61, 2000 56. Nakamura H, Aoki H, Hino O, et al: HCV core protein promotes heparin binding EGF-like growth factor expression and activates Akt. Hepatol Res 41:455-62, 2011 57. Tsutsumi T, Suzuki T, Moriya K, et al: Alteration of Intrahepatic Cytokine Expression and AP-1 Activation in Transgenic Mice Expressing Hepatitis C Virus Core Protein. Virology 304:415-424, 2002 58. Tzeng HE, Tsai CH, Chang ZL, et al: Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. Biochem Pharmacol 85:531-40, 2013 59. Dong W, Li Y, Gao M, et al: IKKalpha contributes to UVB-induced VEGF expression by regulating AP-1 transactivation. Nucleic Acids Res 40:2940-55, 2012 60. Meng Soo H, Garzino-Demo A, Hong W, et al: Expression of a Full-Length Hepatitis C Virus cDNA Up-Regulates the Expression of CC Chemokines MCP-1 and RANTES. Virology 303:253-277, 2002 61. Shrivastava A, Manna SK, Ray R, et al: Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors. J Virol 72:9722-8, 1998 62. El-Khoueiry AB, Sangro B, Yau T, et al: Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 389:2492-2502, 2017 63. Descamps V, Helle F, Louandre C, et al: The kinase-inhibitor sorafenib inhibits multiple steps of the Hepatitis C Virus infectious cycle in vitro. Antiviral Res 118:93-102, 2015 64. Himmelsbach K, Sauter D, Baumert TF, et al: New aspects of an anti-tumour drug: sorafenib efficiently inhibits HCV replication. Gut 58:1644-53, 2009 65. Kao JH, Chen PJ, Lai MY, et al: Genotypes of hepatitis C virus in Taiwan and the progression of liver disease. J Clin Gastroenterol 21:233-7, 1995 66. Liu CH, Kao JH: Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa. Int J Nanomedicine 9:2051-67, 2014 67. Jackson R, Psarelli EE, Berhane S, et al: Impact of Viral Status on Survival in Patients Receiving Sorafenib for Advanced Hepatocellular Cancer: A Meta-Analysis of Randomized Phase III Trials. J Clin Oncol 35:622-628, 2017 68. Bruix J, Cheng AL, Meinhardt G, et al: Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies. J Hepatol 67:999-1008, 2017 69. Cheng A-L, Finn RS, Qin S, et al: Phase III trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC). Journal of Clinical Oncology 35:4001-4001, 2017 70. Ipsen announces that phase 3 CELESTIAL trial of cabozantinib meets primary endpoint of overall survival in patients with advanced hepatocellular carcinoma, 2017 71. Shao YY, Shau WY, Chan SY, et al: Treatment efficacy differences of sorafenib for advanced hepatocellular carcinoma: a meta-analysis of randomized clinical trials. Oncology 88:345-52, 2015 72. Matsuzaki K, Murata M, Yoshida K, et al: Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology 46:48-57, 2007 73. Lambert MP, Paliwal A, Vaissiere T, et al: Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake. J Hepatol 54: 705-715, 2011 74. Su PF, Lee TC, Lin PJ, et al: Differential DNA methylation associated with hepatitis B virus infection in hepatocellular carcinoma. Int J Cancer 121:1257-64, 2007 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68042 | - |
dc.description.abstract | 肝細胞癌是一種相當特殊的癌症,因為大多數病人都有明確的病因。常見的病因包括B型肝炎、C型肝炎以及酒精性肝病變。不同的病因會導致不同的癌變機轉,所造成的癌症其分子標記也會有所不同。之前研究發現B型肝炎與C型肝炎在基因突變與基因表現等都不太一樣。
Sorafenib是晚期肝癌的標準第一線治療。在兩個第三期臨床試驗中,sorafenib被證實能延長病人的存活時間。在其中一個研究的子分析中,sorafenib似乎對於C型肝炎的肝癌病人有比較好的效果。因此,我試著探討肝炎病因對於肝細胞癌細胞的影響,不論是在臨床治療成效上或是癌細胞的生物特性上。 我使用PubMed及Cochrane資料庫來搜尋於2013年11月30日前已發表的第三期臨床試驗結果,且這些臨床試驗必須比較sorafenib與其他治療做為晚期肝細胞癌第一線治療的成效。我從已發表的文章中截取資料並為每一次分組病人計算統合風險比率。最後,我納入四個第三期臨床試驗於研究中,總共分析了3057位病的結果。C型肝炎的病人中,整體存活時間的統合風險比率是0.65(95%信賴區間為0.53-0.80),傾向使用sorafenib較佳,而無C型肝炎的病人中,整體存活時間的統合風險比率是0.87(95%信賴區間:0.79-0.96),雖亦傾向使用sorafenib較佳,但兩個統合風險比率的差別達到統計上顯著(p = 0.013)。相對的,類似的分析在其他子分組,例如不同地理區域、不同個人生活表現分數、不同腫瘤侵犯,都沒有統計上的顯著差別。此研究顯示sorafenib做為晚期肝細胞癌第一線治療,對於C型肝炎病人帶來的好處比無C型肝炎的病人來得大。 接著,我使用兩株過度表現C型肝炎核心蛋白的HuH7肝癌細胞株細胞(HuH7-core-high及HuH7-core-low,分別表現較高量或較低量的C型肝炎核心蛋白)進行研究。管柱形成實驗及基質膠栓實驗用來比較細胞促進血管生成的能力。在兩種不同的實驗中,HuH7-core-high及HuH7-core-low細胞都比控制組具有更強的血管新生活性,而HuH7-core-high的血管新生活性又比HuH7-core-low來得更明顯。這些表現C型肝炎核心蛋白的細胞株表現了比較多的血管內皮生長因子(VEGF),不論是在RNA或蛋白質上。若使用抗體抑制血管內皮生長因子,則HuH7-core-high細胞促進血管新生的能力會顯著下降。血管內皮生長因子的基因前方有AP-1的結合處,而HuH7-core-high細胞也的確比未表現核心蛋白的HuH7細胞有較高的AP-1活性及更多在核內表現的磷酸化c-jun。使用藥物或是基因表現抑制來降低HuH7-core-high細胞AP-1活性後,細胞的血管內皮生長因子表現下降且促進血管新生能力降低。在131位肝癌病人的檢體中,我們也發現C型肝炎病人的肝癌組織比B型肝炎病人的肝癌組織有較高的血管內皮生長因子表現。此研究發現C型肝炎核心蛋白藉由AP-1造成的血管內皮生長因子表現增強而擁有較高的促進血管新生能力。 總而言之,C型肝炎對於肝細胞癌細胞有重大的影響。臨床上,sorafenib做為晚期肝癌第一線治療,對C型肝炎病人能提供較大的幫助。而C型肝炎核心蛋白,更可藉著調控AP-1的活性,增強肝癌細胞血管內皮生長因子的表現,繼而使之有較強的促進血管新生能力。 | zh_TW |
dc.description.abstract | Hepatocellular carcinoma (HCC) is a unique type of cancer with known etiologies. Common etiologies include chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) and alcoholic liver disease. Different etiologies lead to distinctive carcinogenesis, so the molecular signatures of HCC from various etiologies may be diverse. Prior studies found that HBV-related HCC and HCV-related HCC differ in gene mutation, gene expression, etc.
For advanced HCC, sorafenib is the current standard first-line treatment because it was demonstrated to provide survival benefits in 2 phase III clinical trials. In the subgroup analysis of 1 of the 2 studies, sorafenib seemed to provide more benefits for patients with HCV-related HCC than for other patients. Therefore, I planned this study to explore the impact of hepatitis etiology on HCC, regarding the treatment efficacy and biological behaviors. PubMed and Cochrane library were searched for phase III clinical trials published before November 30, 2013 that compared sorafenib with other treatments as the first-line therapy for advanced HCC. I retrieved data from the published articles and then calculated synthesized hazard ratios (HRs) for patients of different subgroups. Four phase III clinical trials comparing sorafenib with other treatments, which enrolled 3057 patients, were included in the study. The synthesized HR of HCV (+) patients was 0.65 (95% confidence interval [CI], 0.53-0.80, favoring sorafenib), which was significantly lower than that of HCV (-) patients (0.87, 95% CI 0.79-0.96, p = 0.013). By contrast, the HRs between other subgroups, including geographic regions, performance status, and different tumor involvement, were not significantly different. With this study, I demonstrated that sorafenib provided more survival benefits to HCV (+) patients than to HCV (-) patients as the first-line therapy for advanced HCC. I used two HCC cell lines that overexpressed HCV core protein, HuH7-core-high and HuH7-core-low, with high and low core protein expression, respectively, for further experiments. I used tube formation and Matrigel plug assays to assess the proangiogenic activity. In both assays, HuH7-core-high and HuH7-core-low cells dose-dependently induced stronger angiogenesis than control cells. HuH7 cells with HCV core protein expression showed increased mRNA and protein expression of vascular endothelial growth factor (VEGF). VEGF inhibition by bevacizumab reduced the proangiogenic activity of HuH7-core-high cells. The promotor region of VEGF contains the binding site of activator protein-1 (AP-1). Compared with controls, HuH7-core-high cells had an increased AP-1 activity and nuclear localization of phospho-c-jun. AP-1 inhibition using either RNA knockdown or AP-1 inhibitors reduced the VEGF mRNA expression and the proangiogenic activity of HuH7-core-high cells. Among 131 tissue samples from HCC patients, HCV-related HCC revealed stronger VEGF expression than did hepatitis B virus-related HCC. With this study, I demonstrated that increased VEGF expression through AP-1 activation is a crucial mechanism underlying the proangiogenic activity of the HCV core protein in HCC cells. Above all, hepatitis C virus has pivotal impact on HCC cells. In clinical practice, sorafenib as first-line therapy for advanced HCC benefits HCV-positive patients more. Moreover, HCV core protein augments proangiogenic activity of HCC cells through AP-1 induced VEGF expression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T02:11:40Z (GMT). No. of bitstreams: 1 ntu-107-D00453003-1.pdf: 5602877 bytes, checksum: f3254ac0b8147d2e6908e688f5f635ea (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 口試委員會審定書…………………………………………………………………… i
序言…………………………………………………………………… ii 中文摘要…………………………………………………………...… iii 英文摘要…………………………………………………………….…. v 第一章 研究背景…………………………………………………… 1 第二章 C型肝炎與sorafenib治療效果的關聯性…………………. 5 2.1 引言…………………………………………………………… 5 2.2 方法…………………………………………………………… 5 2.3 結果…………………………………………………………… 7 2.4 討論…………………………………………………………… 9 第三章 C型肝炎核心蛋白對肝細胞癌細胞的影響………………. 11 3.1 引言………………………………………………………… 11 3.2 方法………………………………………………………… 11 3.3 結果………………………………………………………… 17 3.4 討論………………………………………………………… 21 第四章 結論及未來展望…………………………………………… 25 第五章 圖…………………………………………..………………… 27 第六章 表…………………………………………..………………… 40 參考文獻…………………...…………………………………….…… 46 附錄(發表論文正本)…….……………………………………….…… 55 | |
dc.language.iso | en | |
dc.title | C型肝炎病毒對肝細胞癌的影響 | zh_TW |
dc.title | Impact of Hepatitis C Virus Etiology on Hepatocellular Carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 趙毅,吳肇卿,劉俊人,徐志宏 | |
dc.subject.keyword | 血管新生,核心蛋白,C型肝炎,肝細胞癌,統合分析,索拉非尼, | zh_TW |
dc.subject.keyword | angiogenesis,core protein,hepatitis C virus,hepatocellular carcinoma,metaanalysis,sorafenib, | en |
dc.relation.page | 74 | |
dc.identifier.doi | 10.6342/NTU201704418 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-01-09 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 腫瘤醫學研究所 | zh_TW |
顯示於系所單位: | 腫瘤醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-107-1.pdf 目前未授權公開取用 | 5.47 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。