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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡懷楨 | |
dc.contributor.author | Mei-Yan Su | en |
dc.contributor.author | 蘇玫燕 | zh_TW |
dc.date.accessioned | 2021-06-08T01:22:48Z | - |
dc.date.copyright | 2014-09-04 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-05 | |
dc.identifier.citation | 黃昱凱 (2007)。抗心律不整藥物Amiodarone影響斑馬魚胎胚心臟瓣膜的發育。臺灣大學分子與細胞生物學研究所碩士論文。
陳大淵 (2008)。抗心律不整藥物Amiodarone藉由抑制表皮間質轉換而干擾斑馬魚胚胎心臟瓣膜發育。臺灣大學分子與細胞生物學研究所碩士論文。 羅道明 (2010)。抗心律不整藥物Amiodarone抑制斑馬魚胎胚心臟瓣膜發育之分子機制。臺灣大學分子與細胞生物學研究所碩士論文。 羅浩展 (2012)。抗心律不整藥物Amiodarone抑制斑馬魚胎胚心臟瓣膜發育之受器與其調控機制。臺灣大學分子與細胞生物學研究所碩士論文。 Alessi, D.R., Andjelkovic, M., Caudwell, B., Cron, P., Morrice, N., Cohen, P., Hemmings, B.A. (1996). Mechanism of activation of protein kinase B by insulin and IGF-1. The EMBO Journal, 15:6541-6551. Ang, LC., Zhang, Y., Cao, L., Yang, B.L., Young, B., Kiani, C., Lee, V., Allan, K., and Yang, B.B. (1999). Versican enhances locomotion of astrocytoma cells and reduces cell adhesion through its G1 domain. Journal of Neuropathology and Experimental Neurology, 58:597–605. Arslan, F., Bosserhoff, A.K., Nickl-Jockschat, T., Doerfelt, A., Bogdahn, U., and Hau, P. (2007). The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-beta2. British Journal of Cancer, 96:1560–1568. Aspberg, A., Miura, R., Bourdoulous, S., Shimonaka, M., Heinegard, D., Schachner, M., Ruoslahti, E., and Yamaguchi, Y. (1997). The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety. Proceedings of the National Academy of Sciences of the United States of America, 94:10116-10121. Bargout, R., Jankov, A., Dincer, E., Wang, R., Komodromos, T., Ibarra-Sunga, O., Filippatos, G., and Uhal, B.D. (2000). Amiodarone induces apoptosis of human and rat alveolar epithelial cells in vitro. American Journal of Physiology - Lung Cellular and Molecular Physiology, 278:1039-1044. Baritussio, A., Marzini, S., Agostini, M., Alberti, A., Cimenti, C., Bruttomesso, D., Manzato, E., Quaglino, D., and Pettenazzo, A. (2001). Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of lysosomal enzymes. American Journal of Physiology - Lung Cellular and Molecular Physiology, 281:1189-1199. Basaria, S., and Cooper, D.S. (2005). Amiodarone and the thyroid. The American Journal of Medicine, 118:706-714. Bhowmick, N.A., Neilson, E.G., and Moses, H.L. (2004). Stromal fibroblasts in cancer initiation and progression. Nature, 432:332-337. Bolós, V., Peinado, H., Pérez-Moreno, M.A., Fraga, M.F., Esteller, M., and Cano, A. (2003). The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. Journal of Cell Science, 116:499-511. Boreddy, S.R., and Srivastava, S.K. (2013). Deguelin suppresses pancreatic tumor growth and metastasis by inhibiting epithelial-to-mesenchymal transition in an orthotopic model. Oncogene, 32:3980-3991. Boulton, T.G., Nye, S.H., Robbins, D.J., Ip, N.Y., Radziejewska, E., Morgenbesser, S.D., DePinho, R.A., Panayotatos, N., Cobb, M.H., and Yancopoulos, G.D. (1991). ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell, 65:663-675. Cano, A., Pérez-Moreno, M.A., Rodrigo, I., Locascio, A., Blanco, M.J., del Barrio, M.G., Portillo, F., and Nieto, M.A. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2:76-83. Charlier, R., Deltour, G., Tondeur, R., and Binon, F. (1962). Studies in the benzofuran series. VII. Preliminary pharmacological study of 2-butyl-3-(3,5-diiodo-4-beta-N-diethylaminoethoxybenzoyl)-benzofuran. Archives Internationales de Pharmacodynamie et de Therapie, 139:255-264. Chen, Y.H., Lee, H.C., Hsu, R.J., Chen, T.Y., Huang, Y.K., Lo, H.C., Hu, S.C., Harn, H.J., Jeng, J.R., Sun, C.K., Lin, S.Z., and Tsai, H.J. (2012). The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos. Reproductive Toxicology, 33:233-244. Chua, K.N., Sim, W.J., Racine, V., Lee, S.Y., Goh, B.C., and Thiery, J.P. (2012). A cell-based small molecule screening method for identifying inhibitors of epithelial-mesenchymal transition in carcinoma. PLoS One, 7:e33183. Citri, A., and Yarden, Y. (2006). EGF-ERBB signalling: towards the systems level. Nature Reviews Molecular Cell Biology, 7:505-516. Cross, L.M., Cook, M.A., Lin, S., Chen, J.N., and Rubinstein, A.L. (2003). Rapid analysis of angiogenesis drugs in a live fluorescent zebrafish assay. Arteriosclerosis, Thrombosis, and Vascular Biology, 23:911-912. Deltour, G., Binon, F., Tondeur, R., Goldenberg, C., Henaux, F., Sion, R., Deray, E., and Charlier, R. (1962). Studies in the benzofuran series. VI. Coronary-dilating activity of alkylated and aminoalkylated derivatives of 3-benzoylbenzofuran. Archives Internationales de Pharmacodynamie et de Therapie, 139:247-254. Domenzain-Reyna, C., Hernández, D., Miquel-Serra, L., Docampo, M.J., Badenas, C., Fabra, A., and Bassols, A. (2009). Structure and regulation of the versican promoter: the versican promoter is regulated by AP-1 and TCF transcription factors in invasive human melanoma cells. The Journal of Biological Chemistry, 284:12306-12317. Du, W.W., Fang, L., Yang, X., Sheng, W., Yang, B.L., Seth, A., Zhang, Y., Yang, B.B., and Yee, A.J. (2013). The role of versican in modulating breast cancer cell self-renewal. Molecular Cancer Research, 11:443-455. Du, W.W., Yang, B.B., Shatseva, T.A., Yang, B.L., Deng, Z., Shan, S.W., Lee, D.Y., Seth, A., and Yee, A.J. (2010). Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis by influencing EGF receptor signaling. PLoS One, 5:e13828. Engelman, J.A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J.O., Lindeman, N., Gale, C.M., Zhao, X., Christensen, J., Kosaka, T., Holmes, A.J., Rogers, A.M., Cappuzzo, F., Mok, T., Lee, C., Johnson, B.E., Cantley, L.C., and Jänne, P.A. (2007). MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science, 316:1039-1043. Fang, J.Y., and Richardson, B.C. (2005). The MAPK signalling pathways and colorectal cancer. The Lancet Oncology, 6:322-327. Fidler, I.J. (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature Reviews Cancer, 3:453-458. Frei, E.3rd., and Canellos, G.P. (1980). Dose: a critical factor in cancer chemotherapy. The American Journal of Medicine, 69:585-594. Frumin, H., Kerin, N.Z., and Rubenfire, M. (1989). Classification of antiarrhythmic drugs. The Journal of Clinical Pharmacology, 29:387-394. Grille, S.J., Bellacosa, A., Upson, J., Klein-Szanto, A.J., van Roy, F., Lee-Kwon, W., Donowitz, M., Tsichlis, P.N., and Larue, L. (2003). The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Research, 63:2172-2178. Hanahan, D., and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell, 144:646-674. Hernández, D., Miquel-Serra, L., Docampo, M.J., Marco-Ramell, A., Cabrera, J., Fabra, A., and Bassols, A. (2011). V3 versican isoform alters the behavior of human melanoma cells by interfering with CD44/ErbB-dependent signaling. The Journal of Biological Chemistry, 286:1475-1485. Hugo, H., Ackland, M.L., Blick, T., Lawrence, M.G., Clements, J.A., Williams, E.D., and Thompson, E.W. (2007). Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. Journal of Cellular Physiology, 213:374-383. Kallergi, G., Agelaki, S., Kalykaki, A., Stournaras, C., Mavroudis, D., and Georgoulias, V. (2008). Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Breast Cancer Research, 10:R80. Kalluri, R., and Weinberg, R.A. (2009). The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation, 119:1420-1428. Kasai, H., Allen, J.T., Mason, R.M., Kamimura, T., and Zhang, Z. (2005). TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respiratory Research, 6:56-70. Kiang, D.T., Frenning, D.H., Goldman, A.I., Ascensao, V.F., and Kennedy, B.J. (1978) Estrogen receptors and responses to chemotherapy and hormonal therapy in advanced breast cancer. The New England Journal of Medicine, 14:1330-1334. Kim, K.K., Lee, J.J., Yang, Y., You, K.H., and Lee, J.H. (2008). Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells. Carcinogenesis, 29:704-712. Kischel, P., Waltregny, D., Dumont, B., Turtoi, A., Greffe, Y., Kirsch, S., De Pauw, E., and Castronovo, V. (2010). Versican overexpression in human breast cancer lesions: Known and new isoforms for stromal tumor targeting. International Journal of Cancer, 126:640-650. Kobayashi, S., Boggon, T.J., Dayaram, T., Jänne, P.A., Kocher, O., Meyerson, M., Johnson, B.E., Eck, M.J., Tenen, D.G., and Halmos, B. (2005). EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. The New England Journal of Medicine, 352:786-792. Kodama, I., Kamiya, K., and Toyama, J. (1999). Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. The American Journal of Cardiology, 84:20-28. Kuo, T.C., Tan, C.T., Chang, Y.W., Hong, C.C., Lee, W.J., Chen, M.W., Jeng, Y.M., Chiou, J., Yu, P., Chen, P.S., Wang, M.Y., Hsiao, M., Su, J.L., and Kuo, M.L. (2013). Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility. The Journal of Clinical Investigation, 123:1082-1095. Leber, M.F., and Efferth, T. (2009). Molecular principles of cancer invasion and metastasis (review). International Journal of Oncology, 34:881-895. Lee, M.Y., Chou, C.Y., Tang, M.J., and Shen, M.R. (2008). Epithelial-mesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation. Clinical Cancer Research, 14:4743-4750. Lee, W.R., Hanks, G.E., Schultheiss, T.E., Corn, B.W., and Hunt, M.A. (1995). Localized prostate cancer treated by external-beam radiotherapy alone: serum prostate-specific antigen-driven outcome analysis. Journal of Clinical Oncology, 13:464-469. Lee-Hoeflich, S.T., Crocker, L., Yao, E., Pham, T., Munroe, X., Hoeflich, K.P., Sliwkowski, M.X., and Stern, H.M. (2008). A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Research, 68:5878-5887. Li, D., Wang, X., Wu, J.L., Quan, W.Q., Ma, L., Yang, F., Wu, K.Y., and Wan, H.Y. (2013). Tumor-produced versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and vitamin D3 signaling to promote ovarian cancer progression in vitro. PLoS One, 8:e56616. Lin, C.Y., Lee, H.C., Fu, C.Y., Ding, Y.Y., Chen, J.S., Lee, M.H., Huang, W.J., and Tsai HJ. (2013). MiR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos. Nature Communications, 4:2829-2839. Lin, C.Y., Tsai, P.H., Kandaswami, C.C., Chang, G.D., Cheng, C.H., Huang, C.J., Lee, P.P., Hwang, J.J., and Lee, M.T. (2011). Role of tissue transglutaminase 2 in the acquisition of a mesenchymal-like phenotype in highly invasive A431 tumor cells. Molecular Cancer, 21:87-99. Liotta, L.A., and Kohn, E.C. (2001). The microenvironment of the tumour-host interface. Nature, 411:375–379. Martin, R.T., and Bartman, T. (2009). Analysis of heart valve development in larval zebrafish. Developmental Dynamics, 238:1796-1802. Martino, E., Bartalena, L., Bogazzi, F., and Braverman, L.E. (2001). The effects of amiodarone on the thyroid. Endocrine Reviews, 22:240-254. Maruyama, K., Okabayashi, K., and Kinoshita, T. (1987). Progress in gastric cancer surgery in Japan and its limits of radicality. World Journal of Surgery, 11:418-425. Maseki, S., Ijichi, K., Tanaka, H., Fujii, M., Hasegawa, Y., Ogawa, T., Murakami, S., Kondo, E., and Nakanishi, H. (2012). Acquisition of EMT phenotype in the gefitinib-resistant cells of a head and neck squamous cell carcinoma cell line through Akt/GSK-3beta/snail signalling pathway. British Journal of Cancer, 106:1196-1204. Mason, J.W. (1987). Amiodarone. The New England Journal of Medicine, 316:455-466. Matsumoto, K., Shionyu, M., Go, M., Shimizu, K., Shinomura, T., Kimata, K., and Watanabe, H. (2003). Distinct interaction of versican/PG-M with hyaluronan and link protein. The Journal of Biological Chemistry, 278:41205-41212. Mauri, P., Scarpa, A., Nascimbeni, A.C., Benazzi, L., Parmagnani, E., Mafficini, A., Della Peruta, M., Bassi, C., Miyazaki, K., and Sorio, C. (2005). Identification of proteins released by pancreatic cancer cells by multidimensional protein identification technology: a strategy for identification of novel cancer markers. Journal of The Federation of American Societies for Experimental Biology, 19:1125–1127. Miquel-Serra, L., Serra, M., Hernández, D., Domenzain, C., Docampo, M.J., Rabanal, R.M., de Torres, I., Wight, T.N., Fabra, A., and Bassols, A. (2006). V3 versican isoform expression has a dual role in human melanoma tumor growth and metastasis. Laboratory Investigation, 86:889–901. Mukaratirwa, S., Koninkx, J.F., Gruys, E., and Nederbragt, H. (2005). Mutual paracrine effects of colorectal tumour cells and stromal cells: modulation of tumour and stromal cell differentiation and extracellular matrix component production in culture. International Journal of Experimental Pathology, 86:219–229. Murai, R., Yoshida, Y., Muraguchi, T., Nishimoto, E., Morioka, Y., Kitayama, H., Kondoh, S., Kawazoe, Y., Hiraoka, M., Uesugi, M., and Noda, M. (2010). A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs. Oncotarget, 1:252-264. Nagarajan, D., Melo, T., Deng, Z., Almeida, C., and Zhao, W. (2012). ERK/GSK3beta/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition. Free Radical Biology and Medicine, 52:983-992. Narisawa-Saito, M., and Kiyono, T. (2007). Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Science, 98:1505-1511. Nguyenm, A.T., Emelyanov, A., Koh, C.H., Spitsbergen, J.M., Parinov, S., and Gong, Z. (2012). An inducible kras(V12) transgenic zebrafish model for liver tumorigenesis and chemical drug screening. Disease Models & Mechanisms, 5:63-72. Nguyen, D.X., and Massagué, J. (2007). Genetic determinants of cancer metastasis. Nature Reviews Genetics, 8:341-352. Nikitovic, D., Zafiropoulos, A., Katonis, P., Tsatsakis, A., Theocharis, A.D., Karamanos, N.K., and Tzanakakis, G.N. (2006). Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase- 2 and synthesis of hyaluronan in malignant osteosarcoma cells. International Union of Biochemistry and Molecular Biology Life, 58:47–53. Ogiso, H., Ishitani, R., Nureki, O., Fukai, S., Yamanaka, M., Kim, J.H., Saito. K., Sakamoto, A., Inoue, M., Shirouzu, M., and Yokoyama, S. (2002). Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell, 110:775-787. Olayioye, M.A., Neve, R.M., Lane, H.A., and Hynes, N.E. (2000). The ErbB signaling network: receptor heterodimerization in development and cancer. The EMBO Journal, 19:3159-3167. Olin, A.I., Morgelin, M., Sasaki, T., Timpl, R., Heinegard, D., and Aspberg, A. (2001). The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding. The Journal of Biological Chemistry, 276:1253-1261. Pao, W., Miller, V.A., Politi, K.A., Riely, G.J., Somwar, R., Zakowski, M.F., Kris, M.G., and Varmus, H. (2005). Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Medicine, 2:e73. Paris, S., Sesboue, R., Chauzy, C., Maingonnat, C., and Delpech, B. (2006). Hyaluronectin modulation of lung metastasis in nude mice. European Journal of Cancer, 42:3253–3259. Paulus, W., Baur, I., Dours-Zimmermann, M.T., and Zimmermann, D.R. (1996). Differential expression of versican isoforms in brain tumors. Journal of Neuropathology and Experimental Neurology, 55:528–533. Pirinen, R., Leinonen, T., Bohm, J., Johansson, R., Ropponen, K., Kumpulainen, E., and Kosma VM. (2005). Versican in nonsmall cell lung cancer: relation to hyaluronan, clinicopathologic factors, and prognosis. Human Pathology, 36:44–50. Psaila, B., Kaplan, R.N., Port, E.R., and Lyden, D. (2006-2007). Priming the 'soil' for breast cancer metastasis: the pre-metastatic niche. Breast Disease, 26:65-74. Pukkila, M., Kosunen, A., Ropponen, K., Virtaniemi, J., Kellokoski, J., Kumpulainen, E., Pirinen, R., Nuutinen, J., Johansson, R., and Kosma, V.M. (2007). High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma. Journal of Clinical Pathology, 60:267–272. Rahmani, M., Wong, B.W., Ang, L., Cheung, C.C., Carthy, J.M., Walinski, H., and McManus, B.M. (2006). Versican: signaling to transcriptional control pathways. Canadian Journal of Physiology and Pharmacology, 84:77-92. Ricciardelli, C., Brooks, J.H., Suwiwat, S., Sakko, A.J., Mayne, K., Raymond, W.A., Seshadri, R., LeBaron, R.G., and Horsfall, D.J. (2002). Regulation of stromal versican expression by breast cancer cells and importance to relapse-free survival in patients with node-negative primary breast cancer. Clinical Cancer Research, 8:1054–1060. Ricciardelli, C., Mayne, K., Sykes, P. J., Raymond, W. A., McCaul, K., Marshall, V. R., and Horsfall, D.J. (1998). Elevated levels of versican but not decorin predict disease progression in earlystage prostate cancer. Clinical Cancer Research, 4:963–997. Roden, D.M. (2000). Antiarrhythmic drugs: from mechanisms to clinical practice. Heart, 84:339-346. Rosenberg, S.A., Yang, J.C., and Restifo, N.P. (2004). Cancer immunotherapy: moving beyond current vaccines. Nature Medicine, 10:909-915. Rottiers, P., Verfaillie, T., Contreras, R., Revets, H., Desmedt, M., Dooms, H., Fiers, W., and Grooten, J. (1998). Differentiation of EL4 lymphoma cells by tumoral environment is associated with inappropriate expression of the large chondroitin sulfate proteoglycan PG-M and the tumor-associated antigen HTgp-175. International Journal of Cancer, 78:503–510. Sheng, W., Wang, G., Wang, Y., Liang, J., Wen, J., Zheng, P.S., Wu, Y., Lee. V., Slingerland, J., Dumont, D., and Yang, B.B. (2005). The roles of versican V1 and V2 isoforms in cell proliferation and apoptosis. Molecular Biology of the Cell, 16:1330–1340. Slamon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A., and McGuire, W.L. (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 235:177-182. Sugarbaker, E.V. (1979). Cancer metastasis: a product of tumor-host interactions. Current Problems in Cancer, 3:1-59. Suwiwat, S., Ricciardelli, C., Tammi, R., Tammi, M., Auvinen, P., Kosma, V.M., LeBaron, R.G., Raymond, W.A., Tilley, W.D., and Horsfall, D.J. (2004). Expression of extracellularmatrix components versican, chondroitin sulfate, tenascin, andhyaluronan, and their association with disease outcome in nodenegativebreast cancer. Clinical Cancer Research, 10:2491–2498. Thiery, J.P., Acloque, H., Huang, R.Y., and Nieto, M.A. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139:871-890. Thiery J.P., and Sleeman J.P. (2006). Complex networks orchestrate epithelial -mesenchymal transitions. Nature Reviews Molecular Cell Biology, 7:131-142. Ullrich, A., and Schlessinger, J. (1990). Signal transduction by receptors with tyrosine kinase activity. Cell, 61:203-212. Vivanco, I., and Sawyers, C.L. (2002). The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nature Reviews Cancer, 2:489-501. Voulgari, A., and Pintzas, A. (2009). Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochimica et Biophysica Acta, 1796:75-90. Voutilainen, K., Anttila, M., Sillanpaa, S., Tammi, R., Tammi, M., Saarikoski, S., and Kosma, V.M. (2003). Versican in epithelial ovarian cancer: relation to hyaluronan, clinicopathologic factors and prognosis. International Journal of Cancer, 107:359–364. Wasa, J., Nishida, Y., Shinomura, T., Isogai, Z., Futamura, N., Urakawa, H., Arai, E., Kozawa, E., Tsukushi, S., and Ishiguro, N. (2012). Versican V1 isoform regulates cell-associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells. International Journal of Cancer, 130:2271-2281. Wight, T.N. (2002). Versican: a versatile extracellular matrix proteoglycan in cell biology. Current Opinion in Cell Biology, 14:617-623. Wyckoff, J.B., Jones, J.G., Condeelis, J.S., and Segall, J.E. (2000). A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Research, 60:2504-2511. Yamagata, M., Yamada, K.M., Yoneda, M., Suzuki, S., and Kimata, K. (1986). Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin. The Journal of Biological Chemistry, 261:13526-13535. Yang, B.L., Zhang, Y., Cao, L., and Yang, B.B. (1999). Cell adhesion and proliferation mediated through the G1 domain of versican. Journal of Cellular Biochemistry, 72:210-220. Yang, J., Mani, S.A., Donaher, J.L., Ramaswamy, S., Itzykson, R.A., Come, C., Savagner, P., Gitelman, I., Richardson, A., and Weinberg, R.A. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117:927-939. Yang, J., and Weinberg, R.A. (2008). Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Developmental Cell, 14:818-829 Yarden, Y. (2001). The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. European Journal of Cancer, 37 Suppl 4:S3-S8. Yee, A.J., Akens, M., Yang, B.L., Finkelstein, J., Zheng, P.S., Deng, Z., and Yang, B. (2007). The effect of versican G3 domain on local breast cancer invasiveness and bony metastasis. Breast Cancer Research, 9:R47. Yilmaz, M., and Christofori, G. (2009). EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Reviews, 28:15-33. Zeisberg M., and Neilson E.G. (2009). Biomarkers for epithelial-mesenchymal transitions. The Journal of Clinical Investigation, 119:1429-1437. Zhang, Y., Cao, L., Yang, B.L., and Yang, B.B. (1998). The G3 domain of versican enhances cell proliferation via epidermial growth factor-like motifs. The Journal of Biological Chemistry, 273:21342-21351. Zheng, P.S., Wen, J., Ang, L.C., Sheng, W., Viloria-Petit, A., Wang, Y., Wu, Y., Kerbel, R.S., and Yang, B.B.(2004). Versican/PG-M G3 domain promotes tumor growth and angiogenesis. Journal of The Federation of American Societies for Experimental Biology, 18:754-756. Zhou, B.P., Deng, J., Xia, W., Xu, J., Li, Y.M., Gunduz, M., and Hung, M.C. (2004). Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesench ymal transition. Nature Cell Biology, 6:931-940. Zimmermann, D.R., and Ruoslahti, E. (1989). Multiple domains of the large fibroblast proteoglycan, versican. The EMBO Journal, 8:2975-2981. Zuo, J.H., Zhu, W., Li, M.Y., Li, X.H., Yi, H., Zeng, G.Q., Wan, X.X., He, Q.Y., Li, J.H., Qu, J.Q., Chen, Y., and Xiao Z.Q. (2011). Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin. Journal of Cellular Biochemistry, 112:2508-2517. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18738 | - |
dc.description.abstract | 癌症領域中尋找治癒癌症的藥物至今仍然是一大挑戰,目前研究指出癌症導致死亡有 90% 是因為癌症轉移,而上皮細胞-間質細胞轉變 (EMT) 是癌細胞得到侵襲能力的關鍵。所以,建立一個新穎的活體平台以快速尋找可能抑制癌細胞轉移的藥物及機轉是必要的。本實驗欲利用斑馬魚胚胎做為快速篩選抑制癌細胞轉移藥物的活體平台。首先,先確認斑馬魚的心臟瓣膜形成的 invagination 與癌細胞 EMT 的訊息傳遞路徑是否相同。為釐清此問題,本實驗利用已知會抑制斑馬魚心內皮細胞進行 invagination 的藥物 Amiodarone,探討其可否以相同訊息傳遞路徑抑制癌細胞的 EMT。我們利用傷口癒合法與 Transwell 侵襲實驗觀察,發現 Amiodarone 會造成癌細胞 (B16/OVA、JC、4T-1) 移動與侵襲能力的下降。接著,利用西方浸漬法分析,結果顯示 Amiodarone 會增加癌細胞中 Versican V2 蛋白質的表現量。進一步地發現 Amiodarone 也會降低癌細胞中 Snail 與 Twist 蛋白質表現,而使得 E-cadherin 蛋白質表現量上升但 N-cadherin 蛋白質表現量下降。當利用 siRNA 降低 Versican V2 蛋白表現量後,小鼠癌細胞侵襲能力會提升,且 Amiodarone 抑制 Snail 表現的能力會下降。而本實驗同時也發現癌細胞處理 Amiodarone 後,癌細胞中 epidermal growth factor receptor (EGFR) 磷酸化程度會下降,且AKT、ERK 以及 GSK3β 磷酸化程度都下降。當利用 epithelial growth factor 或 BIO 干擾 Amiodarone 對 EGFR 或 GSK3β 的影響時,Amiodarone 促使 E-cadherin 表現的能力皆受阻。但當利用 myr-AKT 與 MEK1 質體轉染,干擾 Amiodarone 抑制 AKT 與 ERK 磷酸化程度,卻發現只有轉染 MEK1 會降低 Amiodarone 抑制 Snail 表現的能力。因此,證明了 Amiodarone 會增加 Versican V2表現量,並抑制癌細胞株中 EGFR 訊息傳遞路徑,導致 ERK 訊息傳遞路徑受阻,進而增加 GSK3β 活性,使得 Snail 無法抑制 E-cadherin 的表現量,達到抑制癌細胞移動與侵襲的結果。這表示 Amiodarone 可抑制癌細胞進行 EMT,且其調控機制與抑制斑馬魚胚胎瓣膜形成相同。為了證明此現象並非只適合 Amiodarone,本實驗利用另一個會導致斑馬魚心內皮細胞 versican 異位性過量表現的藥物 4-Amiopyridine,發現其也可抑制 B16/OVA 的移動能力,而其他不影響斑馬魚心內皮細胞 versican 表現的藥物,則不影響 B16/OVA 的移動。因此,我們總結本實驗成功建立了以斑馬魚心臟專一發螢光的基因轉殖品系 Tg(cmlc2:HcRFP) 胚胎,可作為快速篩選會影響 EMT 藥物的活體新式動物平台。 | zh_TW |
dc.description.abstract | To find a drug that cures cancer is still a challenge. It has been reported that approximately 90% reasons caused death by cancer are metastasis, and the key step of cancer cells that acquires invasion ability is epithelial-mesenchymal transition (EMT). Therefore, it is necessary and helpful if we could establish a novel in vivo platform for rapid screening drugs and understanding the mechanism of inhibiting cancer metastasis. To accomplish this goal, in this study, we employed zebrafish embryo as an alternative study material. First, we studied whether the pathway involved in the invagination of cardiac valves formation during zebrafish heart development is similar to that of EMT involved in cancer cells. We used Amiodarone, a drug has been reported to inhibit invagination of endocardial cells during zebrafish cardiogenesis, to investigate its effect on cancer cells. Using wound healing assay and matrigel invasion assay, we found that Amiodarone did inhibit migration and invasion of cancer cell lines B16/OVA, JC and 4T-1. Western blot demonstrated that Amiodarone induced Versican V2 and E-cadherin proteins’ level but reduced Snail, Twist and N-cadherin proteins’ level. Knockdown of Versican V2 by specific siRNA induced cancer cell invasion and lost the inhibition Snail expression mediated by Amiodarone. Signaling pathway analyses demonstrated that Amiodarone treatment reduced the phosphorylation levels of EGFR, AKT, ERK and GSK3β in cell lines B16/OVA, JC and 4T-1. However, Amiodarone failed to induce E-cadherin in cells treated with either epithelial growth factor or GSK3β inhibitor, BIO. Moreover, Amiodarone failed to repress Snail in the MEK1- transfected cells but not in the myr-AKT- transfected cells. The line of evidences suggested that Amiodarone increases Versican V2, blocks EGFR and ERK pathways, and elevates GSK3β activity by decreasing its phosphorylation, then causes E-cadherin overexpression through inhibiting Snail, which in turn, inhibits the migration and invasion of cell lines B16/OVA, JC and 4T-1. Taken together, we demonstrated that Amiodarone inhibits EMT of cancer cells through the signaling pathways which are similar to those of inhibiting the cardiac valve formation of zebrafish embryos. Additionally, to prove this phenomenon is not particularly specific to Amiodarone, we employed another drug, 4-Amiopyridine, which is known to induce versican overexpression in zebrafish endocardial cells, and found that 4-Amiopyridine could inhibit B16/OVA migration. However, Lidocaine and Nifedipine, which could not affect versican expreesion, could not influence B16/OVA migration. Therefore, we clearly demonstrated that using zebrafish embryo derived from transgenic line Tg(cmlc2:HcRFP) is a highly potential in vivo platform for rapid screening putative drugs that could affect EMT. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:22:48Z (GMT). No. of bitstreams: 1 ntu-103-R01b43016-1.pdf: 2251335 bytes, checksum: 617dc44952764e3fe33ef6ffe32b78ed (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 中文摘要 •••••••••••••••••••••1
英文摘要 •••••••••••••••••••••3 文獻回顧 •••••••••••••••••••••5 前言 •••••••••••••••••••••••13 材料與方法 ••••••••••••••••••••17 結果 •••••••••••••••••••••••25 討論 •••••••••••••••••••••••36 參考文獻 •••••••••••••••••••••40 圖表 •••••••••••••••••••••••58 | |
dc.language.iso | zh-TW | |
dc.title | 建立一個利用斑馬魚胚胎篩選影響 EMT 藥物的活體平台 | zh_TW |
dc.title | Zebrafish Embryo as an Alternative in vivo Platform to Screen Putative Drugs Affecting EMT Process | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 張敏政,林芸薇,戴明燊 | |
dc.subject.keyword | 斑馬魚胚胎,上皮細胞-間質細胞轉換,篩藥平台, | zh_TW |
dc.subject.keyword | Zebrafish Embryo,EMT,in vivo Platform, | en |
dc.relation.page | 72 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2014-08-05 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
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