請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5980
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 周綠蘋(Lu-Ping Chow) | |
dc.contributor.author | Sheng-Wei Tseng | en |
dc.contributor.author | 曾聖為 | zh_TW |
dc.date.accessioned | 2021-05-16T16:19:01Z | - |
dc.date.available | 2018-09-24 | |
dc.date.available | 2021-05-16T16:19:01Z | - |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-13 | |
dc.identifier.citation | 1. El-Serag, H.B., Hepatocellular Carcinoma. The new england journal o f medicine, 2011. 365(12): p. 1118-1127.
2. Bartosch, B., Hepatitis B and C viruses and hepatocellular carcinoma. Viruses, 2010. 2(8): p. 1504-1509. 3. Department of Health, E.Y., R.O.C.(Taiwna), Cause of Death Statistics. 2012: Department of Health, Executive Yuan, R.O.C.(Taiwna). 4. Perz, J.F., et al., The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol, 2006. 45(4): p. 529-538. 5. Society, A.C., Cancer Facts and FIGS 2012. 2012, American Cancer Society. 6. Amarapurkar, D.N., et al., How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J Gastroenterol Hepatol, 2007. 22(6): p. 788-793. 7. Chen CH, et al., Prevalence and Risk Factors of Nonalcoholic Fatty Liver Disease in an Adult Population of Taiwan: Metabolic Significance of Nonalcoholic Fatty Liver Disease in Nonobese Adults. J Clin Gastroenterol, 2006. 40(8): p. 745-752. 8. Kohler, H.-H., et al., Hepatocellular Carcinoma in a Patient with Hereditary Hemochromatosis and Noncirrhotic Liver. A Case Report. Pathology - Research and Practice, 1999. 195(7): p. 509-513. 9. Dragani, T.A., Risk of HCC: Genetic heterogeneity and complex genetics. Journal of Hepatology, 2010. 52: p. 252-257. 10. Evert, M. and F. Dombrowski, Hepatocellular carcinoma in the non-cirrhotic liver. Pathologe, 2008. 29(1): p. 47-52. 11. Ohira, H., et al., Clinical features of hepatocellular carcinoma in patients with autoimmune hepatitis in Japan. J Gastroenterol, 2013. 48(1): p. 109-114. 12. Haruyo IWADATE, et al., Hepatocellular Carcinoma Associated with Wilson's Disease. Internal Medicine, 2004. 43(11): p. 1042-1045. 13. Alessandro Tagger, P.D., et al., Prevalence of GB Virus-C/Hepatitis G Virus Infection in Patients With Cryptogenic Chronic Liver Disease and in Patients With Primary Biliary Cirrhosis or Wilson's Disease. THE AMERICAN JOURNAL OF GASTROENTEROLOGY, 1999. 94(2): p. 484-488. 14. Organization, W.H., Hepatitis B. 2012, World Health Organization. 15. Gust, I.D., Epidemiology of hepatitis B infection in the Western Pacific and South East Asia. Gut, 1996: p. 18-23. 16. Lavanchy, D., Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. Journal of Viral Hepatitis, 2004. 11: p. 97-107. 17. Yun-Fan Liaw and C.-M. Chu, Hepatitis B virus infection. Lancet, 2009. 373: p. 582-592. 18. Samal, J., M. Kandpal, and P. Vivekanandan, Molecular mechanisms underlying occult hepatitis B virus infection. Clin Microbiol Rev, 2012. 25(1): p. 142-163. 19. Moradpour, D., F. Penin, and C.M. Rice, Replication of hepatitis C virus. Nat Rev Microbiol, 2007. 5(6): p. 453-463. 20. Alter, M.J., Epidemiology of hepatitis C virus infection. World J Gastroenterol, 2007. 13: p. 2436-2441. 21. Poynard, T., et al., Viral hepatitis C. The Lancet, 2003. 362(9401): p. 2095-2100. 22. Sun, C.A., Incidence and Cofactors of Hepatitis C Virus-related Hepatocellular Carcinoma: A Prospective Study of 12,008 Men in Taiwan. American Journal of Epidemiology, 2003. 157(8): p. 674-682. 23. Tanaka, Y., et al., Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology, 2006. 130(3): p. 703-714. 24. Rehermann, B. and M. Nascimbeni, Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol, 2005. 5(3): p. 215-229. 25. Freeman, A.J., et al., Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology, 2001. 34(4 Pt 1): p. 809-816. 26. Rogers, A.E. and P.M. Newberne, Nutrition and Aflatoxin Carcinogenesis. Nature, 1971. 229(5279): p. 62-63. 27. Farazi, P.A. and R.A. DePinho, Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 2006. 6(9): p. 674-687. 28. Craig J. McClain, et al., Monocyte activation in alcoholic liver disease. Alcohol, 2002. 27(1): p. 53-61. 29. David J. Kurz, et al., Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. Journal of Cell Science, 2004. 117(11): p. 2417-2416. 30. Mark A Feitelson, et al., Genetic mechanisms of hepatocarcinogenesis. Oncogene, 2002. 21(16): p. 2593-2604. 31. Block, T.M., et al., Molecular viral oncology of hepatocellular carcinoma. Oncogene, 2003. 22(33): p. 5093-5107. 32. Ryuya Shimoda, Makoto Nagashima, and M. Sakamoto, Increased Formation of Oxidative DNA Damage, 8- Hydroxydeoxyguanosine, in Human Livers with Chronic Hepatitis. Cancer Research, 1994. 54(12): p. 3171-3172. 33. Ahmad, W., et al., A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation. Virol J, 2011. 8(8): p. 1-16. 34. Lars Zender, et al., Cancer gene discovery in hepatocellular carcinoma. Journal of Hepatology, 2010. 52(6): p. 921-929. 35. Villanueva, A., et al., Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology, 2008. 135(6): p. 1972-83, 1983 e1-11. 36. Chiang, D.Y., et al., Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Research, 2008. 68(16): p. 6779-688. 37. Tanabe KK, et al., Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA, 2008. 299(1): p. 53-60. 38. Villanueva A, et al., Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis, 2007. 27(1): p. 55-76. 39. Philip PA, et al., Phase II study of erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol, 2005. 23(27): p. 6657–6663. 40. Thomas M, et al., Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma. Cancer, 2007. 110(5): p. 1059-1067. 41. M, P., Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer, 2008. 8(12): p. 915-928. 42. Sachdev D and Y. D, Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther, 2007. 6(1): p. 1-12. 43. De Souza AT, et al., M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nat Genet, 1995. 11(4): p. 447-449. 44. Tovar V, et al., IGF activation in a molecular subclass of hepatocellular carcinoma and pre-clinical efficacy of IGF-1R blockage. J Hepatol, 2010. 52(4): p. 550-559. 45. Takayama H, et al., Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc Natl Acad Sci U S A, 1997. 94(2): p. 701-706. 46. Lutterbach B, et al., Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Research, 2007. 67(5): p. 2081-2088. 47. Ueki T, et al., Expression of hepatocyte growth factor and its receptor c-met proto-oncogene in hepatocellular carcinoma. Hepatology, 1997. 25(4): p. 862-866. 48. Johnson GL and L. R, Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 2002. 298(5600): p. 1911-1912. 49. Nakanishi K, et al., Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma. Cancer, 2005. 103(2): p. 307-312. 50. G, T., mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther, 2009. 9(2): p. 247-261. 51. KS, Z., Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation. Nat Rev Genet, 2008. 9(5): p. 329-340. 52. Zaret K and G. M, Generation and Regeneration of Cells of the Liver and Pancreas. Science, 2008. 322(5907): p. 1490-1494. 53. Boyault S, et al., Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology, 2007. 45(1): p. 42-52. 54. Hoshida Y, et al., Gene expression in fixed tissues and outcome in hepatocellular carcinoma. The new engl and journa l o f medicine, 2008. 359(19): p. 1995-2004. 55. Naugler WE, et al., Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science, 2007. 6(317): p. 121-124. 56. Poon RT, et al., Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg, 2004. 91(10): p. 1354-1360. 57. Yoshiji H, et al., Synergistic effect of basic fibroblast growth factor and vascular endothelial growth factor in murine hepatocellular carcinoma. Hepatology, 2002. 35(4): p. 834-842. 58. W., S., et al., Intrinsic tumour suppression. Nature, 2004. 432(7015): p. 307-315. 59. Aguilar F, et al., Geographic variation of p53 mutational profile in nonmalignant human liver. Science, 1994. 264(5163): p. 1317-1319. 60. Liebman HA, et al., Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. The new Engl and journal o f medicine, 1984. 310: p. 1427-1431. 61. Michael L. Volk∗, et al., Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: A comparison of AFP, DCP, and AFP-L3. Cancer Biomarkers, 2007. 3(2): p. 79-87. 62. Sterling, R.K., et al., Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. Am J Gastroenterol, 2007. 102(10): p. 2196-205. 63. Cabibbo, G., et al., Multimodal approaches to the treatment of hepatocellular carcinoma. Nat Clin Pract Gastroenterol Hepatol, 2009. 6(3): p. 159-169. 64. Xie, B., D.H. Wang, and S.J. Spechler, Sorafenib for treatment of hepatocellular carcinoma: a systematic review. Dig Dis Sci, 2012. 57(5): p. 1122-1129. 65. DS, G., The molecular perspective: the ras oncogene. Oncologist, 1999. 4(3): p. 263-264. 66. Stockl L, et al., Integrity of c-Raf-1/MEK signal transduction cascade is essential for hepatitis B virus gene expression. oncogene, 2003. 22(17): p. 2604-2610. 67. Giambartolomei S, et al., Sustained activation of the Raf/MEK/Erk pathway in response to EGF in stable cell lines expressing the Hepatitis C Virus (HCV) core protein. Oncogene, 2001. 20(20): p. 2606-2610. 68. Gollob JA, et al., Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol, 2006. 33(4): p. 392-406. 69. Wilhelm SM, 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 Research, 2004. 64(19): p. 7099-7109. 70. Gauthier, A. and M. Ho, Role of sorafenib in the treatment of advanced hepatocellular carcinoma: An update. Hepatol Res, 2013. 43(2): p. 147-154. 71. Chen KF, et al., Activation of phosphatidylinositol 3-kinase/Akt signaling pathway mediates acquired resistance to sorafenib in hepatocellular carcinoma cells. J Pharmacol Exp Ther, 2011. 337(1): p. 133-161. 72. Blivet-Van Eggelpoel MJ, et al., Epidermal growth factor receptor and HER-3 restrict cell response to sorafenib in hepatocellular carcinoma cells. J Hepatol, 2012. 57(1): p. 108-115. 73. van Malenstein H, et al., Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth. Cancer Lett, 2013. 329(1): p. 74-83. 74. Chen YL, et al., Sorafenib inhibits transforming growth factor β1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes. Hepatology, 2011. 53(5): p. 1708-1718. 75. Shimizu S, et al., Inhibition of autophagy potentiates the antitumor effect of the multikinase inhibitor sorafenib in hepatocellular carcinoma. Int J Cancer, 2012. 131(3): p. 548-557. 76. Rutz, S. and A. Scheffold, Towards in vivo application of RNA interference - new toys, old problems. Arthritis Res Ther, 2004. 6(2): p. 78-85. 77. Mullenders, J. and R. Bernards, Loss-of-function genetic screens as a tool to improve the diagnosis and treatment of cancer. Oncogene, 2009. 28(50): p. 4409-4420. 78. Rao, D.D., et al., siRNA vs. shRNA: similarities and differences. Adv Drug Deliv Rev, 2009. 61(9): p. 746-759. 79. Riccaboni, M., I. Bianchi, and P. Petrillo, Spleen tyrosine kinases: biology, therapeutic targets and drugs. Drug Discov Today, 2010. 15(13-14): p. 517-530. 80. Wei-Tien Tai, et al., Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma. Journal of Hepatology, 2011. 55(5): p. 1041-1048. 81. White, C.A. and L.A. Salamonsen, A guide to issues in microarray analysis: application to endometrial biology. Reproduction, 2005. 130(1): p. 1-13. 82. Mardis, E.R., Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet, 2008. 9: p. 387-402. 83. Git, A., et al., Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA, 2010. 16(5): p. 991-1006. 84. Noble, W.S., How does multiple testing correction work? Nat Biotechnol, 2009. 27(12): p. 1135-1137. 85. Wang Hua-Yi and Z. Zhao-Xiang, Functions of Spleen Tyrosine Kinase (Syk) Gene and Its Correlation to Neoplasms. Chinese Journal of Cancer, 2007. 26(5): p. 555-560. 86. Coopman PJ, et al., The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature, 2000. 406(6797): p. 742-747. 87. Hoeller C, et al., The non-receptor-associated tyrosine kinase Syk is a regulator of metastatic behavior in human melanoma cells. J Invest Dermatol, 2005. 124(6): p. 1293-1299. 88. Masuda ES and S. J, Syk inhibitors as treatment for allergic rhinitis. Pulm Pharmacol Ther, 2008. 21(3): p. 461-467. 89. Leseux L, et al., Syk-dependent mTOR activation in follicular lymphoma cells. Blood, 2006. 108(13): p. 4156-4162. 90. Gururajan M, et al., Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth. J Immunol, 2007. 178(1): p. 111-121. 91. Yanagi, S., et al., Syk expression and novel function in a wide variety of tissues. Biochem Biophys Res Commun, 2001. 288(3): p. 495-8. 92. Riccaboni, M., et al., Spleen tyrosine kinases: biology, therapeutic targets and drugs. Drug Discovery Today, 2010. 15(13): p. 517-530. 93. Riehl, A., et al., The receptor RAGE: Bridging inflammation and cancer. Cell Commun Signal, 2009. 7(12): p. 12-18. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5980 | - |
dc.description.abstract | 肝癌在人類社會中已成為盛行率及死亡率高的癌症之一,在國內亦是危害國人健康的頭號殺手。然而,由於我們對於造成肝癌的因子,包含相關基因、蛋白質分子、細胞狀況甚至環境的機轉及交互作用仍缺乏全面性的了解,導致其治療困難且預後不佳。而目前經FDA核准的唯一一個肝癌標靶治療藥物是蕾莎(sorafenib),為一個多種激酶(kinase)的抑制劑,可抑制肝癌細胞生長並促進細胞死亡;然而,其療效仍然有限,因此探討其可能影響的未知分子標的已成為肝癌治療上重要的研究課題之一。
近年來,利用核醣核酸干擾技術探討基因間的交互作用,以及鑑定對藥物具感受性的基因已被廣泛應用,在此基礎上,我們希望能建立在異種移植動物模式(xenograft model)中進行核醣核酸干擾篩選的平台。因此,初步我們挑選了96種激酶(kinase),並以小髮夾RNA(shRNA)庫抑制其基因表現,比較在小鼠中經藥物處理前後的腫瘤其shRNA對於基因抑制的變化情形。 經次世代定序(nexe-generation sequencing)與統計分析後,發現3個基因的shRNA讀值在經藥物處理前後有顯著改變,而其中脾酪胺酸激酶(Syk)於先前的研究被指出在某些癌症中是具潛力的藥物標靶,因此我們挑選了Syk進行後續實驗。 我們首先利用shRNA與抑制劑分別抑制HuH-7細胞中的Syk表現並以西方墨點法確認抑制效果。之後利用細胞生存試驗比較正常細胞與Syk受抑制的細胞,發現Syk被抑制後細胞對sorafenib的感受性增加,50%抑制濃度(IC50)由6.7μM下降至4.0μM。另外我們也發現,和正常的HuH-7細胞相比,單純抑制Syk並不會對細胞生長造成影響,但若同時加入sorafenib,則會使細胞生長受明顯抑制,雖然其中的詳細機制及Syk在肝癌中可能扮演的角色、功能仍須進一步探討,但期望此平台能應用於更大規模的篩選及其他疾病的研究中。 | zh_TW |
dc.description.abstract | Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in humans. Despite its significance, there are only limited numbers of effective therapeutic options, partially because our understanding of the genetic, molecular, cellular and environmental mechanisms that drive disease pathogenesis is far from comprehensive. So far, the only one molecular targeted therapy drug for HCC is
sorafenib, which is a multi-kinase inhibitor. However, the mechanism underlying the therapeutic effect of sorafenib remains unclear, and several “off-targets” were recently discovered. Thus, to identify targets that sensitize to sorafenib may provide important information on HCC treatment. Recently, genome-wide target gene knocked down by the pooled RNAi Consortium (TRC) shRNA library has been widely used, and it can be combined with drug treatment to become a platform for identifying potential drugs with synergistic effect. Based on this technology, we want to identify the sorafenib-sensitizing targets in HCC by in vivo RNAi screening. In our study, we transfected the pooled shRNA packaged by lentivirus into a HCC cell line, HuH-7 and injected these resulting cells subcutaneously into nude mice to knock down 96 kinases. After tumors grew, the nude mice were then divided into two groups, control and sorafenib treatment. After analyzing the genomic DNA of tumors by next-generation sequencing, three genes were found that their shRNA ratios were dramatically different between treatment and control groups. Although the functional roles of these genes among the list in resistance to sorafenib are still undetermined, Syk has been reported as a potent modulator of epithelial cell growth and may be a potent molecular target in cancers. We then used shRNA and its specific inhibitor, BAY 61-3606, to knock down Syk activity in HuH-7 cells. By cell viability assay, the HuH-7 cells are more sensitive to sorafenib, and the IC50 of sorafenib drops from 6.7μM to 4.0μM as Syk is inactivated. Furthermore, the growth rate of Syk silenced HuH-7 cells was also much slower than that of HuH-7 control cells, which suggested that Syk may have a synergistic effect with sorafenib on cell growth or survival and may be a potential target in HCC treatment. Although the regulation mechanisms and functions of Syk still need to be further elucidated, the screening platform in this study can provide us some potential targets on disease treatment. | en |
dc.description.provenance | Made available in DSpace on 2021-05-16T16:19:01Z (GMT). No. of bitstreams: 1 ntu-102-R00442008-1.pdf: 1862544 bytes, checksum: 3bd65041d4bc8b3fb24061effc87afd1 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員會審定書........................................i
謝誌.................................................ii 中文摘要.............................................iii 英文摘要..............................................iv 縮寫.................................................vi 第一章 導論.........................................1 1.1 肝癌 (liver cancer).............................1 1.2 肝癌形成過程中的重要分子機轉.........................5 1.3 肝癌的治療與蕾莎瓦 (sorafenib).....................9 1.4 核醣核酸干擾篩選技術 (RNA interference screening)..17 1.5 研究動機與目的....................................20 1.6 研究策略.........................................21 第二章 實驗材料......................................23 2.1 生物材料.........................................23 2.2 儀器及設備.......................................23 2.3 酵素及抗體.......................................24 2.4 藥品與試劑組.....................................25 2.5 軟體............................................26 第三章 實驗方法......................................27 3.1 肝癌細胞株的培養...................................27 3.2 小髮夾RNA(shRNA)抑制目標基因.......................27 3.3 抗生素篩選........................................30 3.4 基因組DNA(genomic DNA)萃取........................30 3.5 異種移植(xenograft)動物模式........................32 3.6 聚合酶鏈鎖反應、產物濃縮及膠體純化回收..................34 3.7 次世代定序 (Next-generation sequencing, NGS)及結果 分析............................................38 3.8 蛋白質分析法.....................................39 3.9 細胞生存能力試驗 (MTT Assay)......................42 第四章 結果.........................................44 4.1 利用異種移植(xenograft)動物模式進行核醣核酸干擾篩選....44 4.2 以次世代定序(Next-generation sequencing)及統計方法分析核醣 核酸干擾篩選之結果.................................44 4.3 以西方墨點法初步驗證動物實驗篩選......................45 4.4 以小髮夾RNA(shRNA)抑制皮酪胺酸激酶(Syk)之基因表現......45 4.5 以細胞生存能力試驗(MTT assay)驗證結合sorafenib與抑制Syk 基因對肝癌細胞株之影響..............................46 第五章 討論.........................................48 5.1 研究策略之探討....................................48 5.2 脾酪胺酸激酶 (Spleen tyrosine kinase, Syk)之功能...52 5.3 其他具有潛力之標的.................................55 5.4 結論與未來展望....................................56 第六章 參考文獻......................................58 圖表.................................................64 | |
dc.language.iso | zh-TW | |
dc.title | 利用核醣核酸干擾篩選技術探討肝癌模式中對Sorafenib具感受性之基因 | zh_TW |
dc.title | Identification of sorafenib-sensitizing genes in hepatocellular carcinoma by RNAi screening | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 俞松良(Sung-Liang Yu),顏伯勳(Bo-Shiun Yan) | |
dc.subject.keyword | 肝細胞癌,核醣核酸干擾篩選技術,蕾莎瓦,脾酪胺酸激酶, | zh_TW |
dc.subject.keyword | Hepatocellular carcinoma,RNA interference screening,sorafenib,Syk, | en |
dc.relation.page | 85 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2013-08-13 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-102-1.pdf | 1.82 MB | Adobe PDF | 檢視/開啟 |
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。