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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 | Fang-Ying Lin | en |
dc.contributor.author | 林芳瑛 | zh_TW |
dc.date.accessioned | 2021-06-16T05:26:50Z | - |
dc.date.available | 2019-10-09 | |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-14 | |
dc.identifier.citation | 1 El-Serag, H. B. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142, 1264-1273 e1261, (2012).
2 El-Serag, H. B. & Rudolph, K. L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132, 2557-2576, (2007). 3 Seeger, C. & Mason, W. S. Hepatitis B virus biology. Microbiology and molecular biology reviews : MMBR 64, 51-68 (2000). 4 Freeman, A. J. et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 34, 809-816, (2001). 5 Ojo, O. S. et al. Hepatitis D virus antigen in HBsAg positive chronic liver disease in Nigeria. East African medical journal 75, 329-331 (1998). 6 Chen, C. H. 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. Journal of clinical gastroenterology 40, 745-752 (2006). 7 Oettle, A. G. The aetiology of primary carcinoma of the liver in Africa: a critical appraisal of previous ideas with an outline of the mycotoxin hypothesis. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 39, 817-825 (1965). 8 Montesano, R., Hainaut, P. & Wild, C. P. Hepatocellular carcinoma: from gene to public health. Journal of the National Cancer Institute 89, 1844-1851 (1997). 9 Hainaut, P. et al. Database of p53 gene somatic mutations in human tumors and cell lines: updated compilation and future prospects. Nucleic acids research 25, 151-157 (1997). 10 Bialecki, E. S. & Di Bisceglie, A. M. Diagnosis of hepatocellular carcinoma. HPB : the official journal of the International Hepato Pancreato Biliary Association 7, 26-34, (2005). 11 Dalla Palma, L., Pozzi-Mucelli, R. S., Bazzocchi, M., Pozzi-Mucelli, R. & Ferrara, P. [Comparative evaluation of echography, computerized tomography and magnetic resonance imaging in the diagnosis of hepatocellular carcinoma in cirrhotic patients]. La Radiologia medica 81, 8-15 (1991). 12 Gomaa, A. I., Khan, S. A., Leen, E. L., Waked, I. & Taylor-Robinson, S. D. Diagnosis of hepatocellular carcinoma. World journal of gastroenterology : WJG 15, 1301-1314 (2009). 13 Gupta, S., Bent, S. & Kohlwes, J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Annals of internal medicine 139, 46-50 (2003). 14 Fujiyama, S., Izuno, K., Gohshi, K., Shibata, J. & Sato, T. Clinical usefulness of des-gamma-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma. Digestive diseases and sciences 36, 1787-1792 (1991). 15 Sterling, R. K. et al. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. The American journal of gastroenterology 102, 2196-2205, (2007). 16 Cabibbo, G., Latteri, F., Antonucci, M. & Craxi, A. Multimodal approaches to the treatment of hepatocellular carcinoma. Nature clinical practice. Gastroenterology & hepatology 6, 159-169, (2009). 17 Farazi, P. A. & DePinho, R. A. Hepatocellular carcinoma pathogenesis: from genes to environment. Nature reviews. Cancer 6, 674-687, (2006). 18 Feitelson, M. A. et al. Genetic mechanisms of hepatocarcinogenesis. Oncogene 21, 2593-2604, (2002). 19 Block, T. M., Mehta, A. S., Fimmel, C. J. & Jordan, R. Molecular viral oncology of hepatocellular carcinoma. Oncogene 22, 5093-5107, (2003). 20 Xie, B., Wang, D. H. & Spechler, S. J. Sorafenib for treatment of hepatocellular carcinoma: a systematic review. Digestive diseases and sciences 57, 1122-1129, (2012). 21 Gauthier, A. & Ho, M. Role of sorafenib in the treatment of advanced hepatocellular carcinoma: An update. Hepatology research : the official journal of the Japan Society of Hepatology 43, 147-154, (2013). 22 Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000). 23 Llovet, J. M. & Bruix, J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48, 1312-1327, (2008). 24 Villanueva, A. et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 135, 1972-1983, 1983 e1971-1911, (2008). 25 Johnson, G. L. & Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912, (2002). 26 Ong, S. E. et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Molecular & cellular proteomics : MCP 1, 376-386 (2002). 27 Picotti, P., Aebersold, R. & Domon, B. The implications of proteolytic background for shotgun proteomics. Molecular & cellular proteomics : MCP 6, 1589-1598, (2007). 28 Lee, I. N. et al. Identification of complement C3a as a candidate biomarker in human chronic hepatitis C and HCV-related hepatocellular carcinoma using a proteomics approach. Proteomics 6, 2865-2873, (2006). 29 Lee, I. N. et al. Identification of human hepatocellular carcinoma-related biomarkers by two-dimensional difference gel electrophoresis and mass spectrometry. Journal of proteome research 4, 2062-2069, (2005). 30 Olofsson, M. H. et al. Cytokeratin-18 is a useful serum biomarker for early determination of response of breast carcinomas to chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 13, 3198-3206, (2007). 31 Ludwig, J. A. & Weinstein, J. N. Biomarkers in cancer staging, prognosis and treatment selection. Nature reviews. Cancer 5, 845-856, (2005). 32 Petersen, T. N., Brunak, S., von Heijne, G. & Nielsen, H. SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature methods 8, 785-786, (2011). 33 Nagele, E., Vollmer, M., Horth, P. & Vad, C. 2D-LC/MS techniques for the identification of proteins in highly complex mixtures. Expert review of proteomics 1, 37-46, (2004). 34 Horvath, K., Fairchild, J. & Guiochon, G. Optimization strategies for off-line two-dimensional liquid chromatography. Journal of chromatography. A 1216, 2511-2518, (2009). 35 Chen, C. Y. et al. Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics study of a thyroid hormone-regulated secretome in human hepatoma cells. Molecular & cellular proteomics : MCP 11, M111 011270, (2012). 36 Yao, L., Zhang, Y., Chen, K., Hu, X. & Xu, L. X. Discovery of IL-18 as a novel secreted protein contributing to doxorubicin resistance by comparative secretome analysis of MCF-7 and MCF-7/Dox. PloS one 6, e24684, (2011). 37 Karagiannis, G. S. et al. In-depth proteomic delineation of the colorectal cancer exoproteome: Mechanistic insight and identification of potential biomarkers. Journal of proteomics 103, 121-136, (2014). 38 Liu, L., Sakai, T., Sano, N. & Fukui, K. Nucling mediates apoptosis by inhibiting expression of galectin-3 through interference with nuclear factor kappaB signalling. The Biochemical journal 380, 31-41, (2004). 39 Dagher, S. F., Wang, J. L. & Patterson, R. J. Identification of galectin-3 as a factor in pre-mRNA splicing. Proceedings of the National Academy of Sciences of the United States of America 92, 1213-1217 (1995). 40 Shimura, T. et al. Galectin-3, a novel binding partner of beta-catenin. Cancer research 64, 6363-6367, (2004). 41 Inohara, H. & Raz, A. Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. Cancer research 55, 3267-3271 (1995). 42 Fukumori, T. et al. Galectin-3 regulates mitochondrial stability and antiapoptotic function in response to anticancer drug in prostate cancer. Cancer research 66, 3114-3119, (2006). 43 Matarrese, P. et al. Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties. International journal of cancer. Journal international du cancer 85, 545-554 (2000). 44 Nangia-Makker, P. et al. Galectin-3 induces endothelial cell morphogenesis and angiogenesis. The American journal of pathology 156, 899-909, (2000). 45 Park, M. T. et al. Suppression of extracellular signal-related kinase and activation of p38 MAPK are two critical events leading to caspase-8- and mitochondria-mediated cell death in phytosphingosine-treated human cancer cells. The Journal of biological chemistry 278, 50624-50634, (2003). 46 Zarubin, T. & Han, J. Activation and signaling of the p38 MAP kinase pathway. Cell research 15, 11-18, (2005). 47 Hendrickx, N. et al. Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. The Journal of biological chemistry 278, 52231-52239, (2003). 48 Olson, J. M. & Hallahan, A. R. p38 MAP kinase: a convergence point in cancer therapy. Trends in molecular medicine 10, 125-129, (2004). 49 Okuno, S., Saito, A., Hayashi, T. & Chan, P. H. The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis through interaction with Bim after transient focal cerebral ischemia. The Journal of neuroscience : the official journal of the Society for Neuroscience 24, 7879-7887, (2004). 50 Saxena, N. K. et al. Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer research 67, 2497-2507, (2007). 51 Dumic, J., Lauc, G. & Flogel, M. Expression of galectin-3 in cells exposed to stress-roles of jun and NF-kappaB. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 10, 149-158, (2000). 52 Kim, K., Mayer, E. P. & Nachtigal, M. Galectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins. Biochimica et biophysica acta 1641, 13-23 (2003). 53 Zeng, Y., Danielson, K. G., Albert, T. J., Shapiro, I. M. & Risbud, M. V. HIF-1 alpha is a regulator of galectin-3 expression in the intervertebral disc. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 22, 1851-1861, (2007). 54 Zhang, H. Y. et al. RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors. Endocrine 35, 101-111, (2009). 55 Raimond, J., Rouleux, F., Monsigny, M. & Legrand, A. The second intron of the human galectin-3 gene has a strong promoter activity down-regulated by p53. FEBS letters 363, 165-169 (1995). 56 Yoshitake, K. et al. Importin-alpha1 as a novel prognostic target for hepatocellular carcinoma. Annals of surgical oncology 18, 2093-2103, (2011). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56400 | - |
dc.description.abstract | 肝癌是全球發生率及死亡率極高的癌症之一,在台灣肝癌的發生率也有逐年增加的趨勢。目前臨床方面則是藉由肝癌的分期來選擇治療的方式,然而現行並沒有一個良好、快速且經濟的非侵入性診斷方法,能檢測肝癌的疾病進展與及時提供臨床早期判斷治療療效。因此,本研究由較易取得的血液檢體中,尋找適當的生物標記,來及時追蹤疾病進展與預後狀況之評估,產生極大的興趣。
近幾年,藉由蛋白質體學方法尋找有潛力之生物標記研究的興起,本研究利用細胞培養中標記穩定同位素胺基酸 (Stable Isotope Labeling of Amino acids in Culture, SILAC) 之差異蛋白質體學方法與離線二維液相層析質譜法 (Off-line 2D LC MS/MS),分析在肝癌細胞 (HuH-7) 中加入肝癌的唯一標靶藥物蕾莎瓦 (Sorafenib) 模擬達到治療效果後肝癌的分子機轉,鑑定到蛋白質中有427個蛋白質因為蕾莎瓦的處理而表現量下降。經由訊息傳遞資料庫 (Ingenuity Pathway Analysis, IPA) 分析肝癌細胞內分子與訊息傳遞的變化,發現表現量下降的蛋白質皆與抑制癌細胞的增生和促進癌細胞的死亡有關,再經過分泌性蛋白質軟體TMHMM、SignalP和 SecretomeP分析後,共預測有131個表現量下降的蛋白質具有分泌性,並從中篩選31 kDa凝集素為一個有潛力的生物標記。藉由西方點墨法驗證,肝癌細胞中與細胞外31 kDa凝集素確實會在蕾莎瓦的處理下表現量受到抑制。因此再深入探討肝癌細胞中訊息傳遞路徑與31 kDa凝集素表現量的關係,得知MAPK路徑中的ERK與p-38路徑的活化與31 kDa凝集素生成量有關。最後運用酵素連結免疫吸附法 (Enzyme-link Immunosorbent Assay, ELISA) 驗證肝癌病人血清中31 kDa凝集素的表現量比健康人高,而經過肝動脈化學栓塞療法 (Liver Transarterial Chemoembolization, TACE) 與標靶藥物蕾莎瓦治療後的病人血清中,31 kDa凝集素表現量與治療前有差異,表示31 kDa凝集素可能是肝癌中疾病進展或療效與藥效有關的生物標記,能有助於臨床判斷、治療選擇和抗癌藥物的開發。 | zh_TW |
dc.description.abstract | Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers. In Taiwan, it ranks on top three deadly cancers for many years. In clinic, the Barcelona-Clinic Liver Cancer (BCLC) staging classification links the stage of the disease to a specific treatment strategy. However, there has no fast and economic efficiently method for diagnosis the progression and prognosis of the liver cancer. Serum biomarkers secreted by a tumor can be used to evaluate cancer progression and to reflect the early effects of cancer therapeutics.
Recently, the proteome-based approaches have been widely applied in searching potential cancer biomarkers. According to the proteomic analysis, we can find out a tumor biomarker whose function may involve in the disease progression and prognosis. Moreover, the biomarker also can be a potential therapeutic indicator. Until now, Sorafenib is the only drug of molecular targeted therapy for HCC. We applied the quantitative proteomics method (Stable Isotope Labeling of Amino acids in Culture, SILAC) to analyze the differences of protein expression levels between HuH-7 and Sorafenib-treated HuH-7 cells. We further used the off-line 2D LC MS/MS approach to identify the above proteins. The Ingenuity Pathway Analysis (IPA) was performed to analyze the difference function between HuH-7 and Sorafenib-treated HuH-7 cells. According to the our results, 2611 quantified proteins were identified from the SILAC experiments, and 427 proteins expression level were decreased after Sorafenib treatment. We found that most proteins were related to the survival and proliferation of cancer cells. By using TMHMM, SignalP and SecretomeP softwares, a total of 131 proteins were classified as the secreted proteins, and the non-classical secreted protein. We found 31 kDa-lectin may correlate to cancer proliferation and survival. Furthermore, we used the Western blotting to validate the candidates and find the 31 kDa-lectin regulated by the MAPK signaling pathway. ELISA analysis further showed that 31 kDa-lectin expression levels were up-regulated in HCC patients, and the expression levels of 31 kDa-lectin were reduced in HCC patients’ serum after TACE and Sorafenib treatment. According to the above results, we conclude that 31 kDa-lectin is a potential biomarker of disease progression and therapy efficacy, and it is expected to become valuable in routine clinical care and anticancer drug development. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:26:50Z (GMT). No. of bitstreams: 1 ntu-103-R01442015-1.pdf: 2636164 bytes, checksum: 330b4effaa99dcb581e20d881bd77bde (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審定書 i
謝誌 ii 中文摘要 iii Abstract iv 縮寫 vi 目錄 viii 圖目錄 xi 表目錄 xii 第一章 導論 1 第一節 肝癌 1 1.1 肝癌之流行病學 1 1.2 肝癌的危險因子 2 1.3 肝癌的診斷 3 1.4 肝癌的分期 5 1.5 肝癌癌化過程與病理組織特徵 5 第二節 臨床治療 7 2.1 手術切除 7 2.2 肝臟移植 7 2.3 局部消融術 7 2.4 肝動脈化學栓塞療法 7 2.5 分子標靶治療 7 第三節 蕾莎瓦 (Sorafenib) 8 第四節 肝癌形成過程中的重要分子機轉 9 第五節 蛋白質體學 10 5.1 蛋白質體學定義 10 5.2 定量蛋白質體學 10 5.3 蛋白質體學在癌症生物標記研究上的應用 10 第六節 生物標記 11 6.1 生物標記的定義 11 6.2 腫瘤生物標記 11 第七節 研究動機 12 第二章 實驗材料 13 第一節 肝癌細胞株 13 第二節 血清樣本 13 第三節 抗體 13 第四節 藥品 14 第五節 試劑組 15 第六節 重要儀器 15 第七節 酵素 16 第八節 軟體及資料庫 16 第三章 實驗方法 17 1.1 細胞的培養 (Cell culture) 17 1.2 細胞的計數與細胞的存活率 (Cell counting and cell viability) 17 第二節 蛋白質分析法 17 2.1 蛋白質濃度測定 (BCA protein assay) 17 2.2 十二烷基磺酸鈉-聚丙醯胺凝膠電泳法 (SDS-PAGE) 18 2.3 電泳膠體的染色 (Protein staining) 20 2.4 西方點墨法 (Western blot) 22 第三節 Sorafenib影響HuH-7細胞蛋白質表現差異之鑑定 24 3.1 細胞培養中標記穩定同位素胺基酸 (Stable Isotope Labeling of Amino acids in Culture, SILAC) 24 3.2 膠體內水解 (In-gel digestion) 24 3.3 溶液中水解 (In-solution digestion) 25 3.4 高效能液相層析法 (High Performance Liquid Chromatography) 26 3.5 液相層析偶合串聯式質譜儀分析 (NanoLC-MS/MS analysis) 27 3.6 生物資訊 (Bioimformation) 28 第四節 肝癌細胞分泌體的收集 29 第五節 訊息傳遞的研究 29 5.1 細胞加藥處理 (Drug treatment) 29 5.2 裂解細胞 (Cell lysis) 29 5.3 細胞裂解液的配置 (Preparation of RIPA cell lysis buffer) 30 第六節 血清中蛋白質濃度測定 30 6.1 酵素連結免疫吸附法 (Enzyme-link immunosorbent assay,ELISA) 30 6.2 Diluent buffer的配置 (Preparation of diliuent buffer) 30 第四章 實驗結果 31 第一節 分析鑑定以藥物Sorafenib處理HuH-7細胞之蛋白質表現差異 31 1. 1 細胞培養中標記穩定同位素胺基酸之內在標準蛋白質校正 31 1.2 高效能液相層析之分離 31 1.3 Mascot軟體之蛋白鑑定分析 31 1.4 生物資訊分析蛋白質之疾病、功能與生理發展 31 1.5 生物資訊分析蛋白質之促進與抑制細胞的功能 32 1.6 生物資訊分析蛋白質之網路與癌細胞關係 32 第二節 HuH-7細胞之分泌性蛋白質分析 32 2.1 Sorafenib藥物處理HuH-7細胞之分泌性蛋白質表現差異 32 2.2 驗證HuH-7細胞加入Sorafenib之蛋白質表現差異 33 2.3 HuH-7細胞之分泌性蛋白質收集 33 第三節 Galectin-3之調控路徑 34 3.1 MAPK路徑與galectin-3之表現量關係 34 3.2 ERK路徑與galectin-3之表現量關係 34 3.3 p-38路徑與galectin-3之表現量關係 34 3.4 JNK路徑與galectin-3之表現量 35 第四節 臨床檢體之驗證 35 4.1 健康人與肝癌病人血液中galectin-3之含量 35 4.2 肝癌病人經肝動脈化學栓塞療法 (Liver Transarterial Chemoembolization, TACE) 治療後血液中galectin-3之含量 36 4.3 肝癌病人經Sorafenib治療後血液中galectin-3之含量 36 第五節 結論 37 第五章 討論 38 第一節 蛋白質體學的應用 38 第二節 生物資訊的應用 39 第三節 半乳糖凝集素之種類、功能與調控 40 第四節 複合型生物標記 41 第五節 生物標記與個人化醫療 42 第六章 參考文獻 44 圖 49 表 66 圖目錄 Figure 1. Schematic outline of the complete SILAC experiment to quantify differential proteins expression in HuH-7 cell during Sorafenib treatment. 50 Figure 2. Comparing the proteins expression of HuH-7 and Sorafenib-treated HuH-7 cell lysates. 51 Figure 3. HPLC separation of combined peptides. 52 Figure 4. Function and disease of down-regulated protein in Sorafenib-treated HuH-7 cell. 53 Figure 5. Secretome analysis of down-regulated proteins in Sorafenib-treated HuH-7 cell by TMHMM, SignalP, and SecretomeP. 54 Figure 6. Western blot analysis of galectin-3 expression levels in HuH-7 and Sorafenib-treated HuH-7 cell. 55 Figure 7. Conditioned media harvested from HuH-7 cells. 56 Figure 8. Western blot analysis of galectin-3 secretion levels in HuH-7 and Sorafenib-treated HuH-7 cell. 57 Figure 9. Effects of Sorafenib on galectin-3 expression in HuH-7 cell. 58 Figure 10. Effects of the inhibitor U0126 on galectin-3 expression in HuH-7 cell. 59 Figure 11. Effects of the inhibitor SB203580 on galectin-3 expression in HuH-7 cell. 60 Figure 12. Effects of the inhibitor SP600125 on galectin-3 expression in HuH-7 cell. 61 Figure 13. The possible mechanism of signaling pathway regulate galection-3 expression. 62 Figure 14. Distribution of the serum levels of galectin-3 in healthy donors, intermediate and advance hepatocellular carcinoma patients measured by ELISA. 63 Figure 15. Comparison of the serum Galectin-3 levels between pre- and post-TACE treatment in the intermediate stage of HCC patients. 64 Figure 16. Comparison of the serum Galectin-3 levels between pre- and post-Sorafenib treatment in the advanced stage of HCC patients. 65 表目錄 Table 1. Diseases and disorders of down-regulated proteins in Sorafenib-treated HuH-7 cell by IPA. 67 Table 2. Molecular and cellular functions of down-regulated proteins in Sorafenib-treated HuH-7 cell by IPA. 68 Table 3. Physiological system development and function of down-regulated proteins in Sorafenib-treated HuH-7 cell by IPA. 69 Table 4. Proteins function analysis of down-regulated proteins in Sorafenib-treated HuH-7 cell by IPA. 70 Table 5. Down-regulated and classified secreted proteins in Sorafenib-treated HuH-7 cell. 71 | |
dc.language.iso | zh-TW | |
dc.title | 以蛋白質體學方法鑑定與人類肝細胞癌相關之生物標記 | zh_TW |
dc.title | Identification of Human Hepatocellular Carcinoma-related Biomarker by Proteomic Approaches | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林亮音(Liang-Yin Lin),黃楓婷(Fong-Ting Huang) | |
dc.subject.keyword | 肝細胞癌,生物標記,凝集素,蛋白質體學,分泌性蛋白質, | zh_TW |
dc.subject.keyword | Hepatocellular carcinoma,biomarker,lectin,proteomics,secreted protein, | en |
dc.relation.page | 71 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-14 | |
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 |
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