請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18330
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊泮池,余忠仁 | |
dc.contributor.author | Wei-Yu Liao | en |
dc.contributor.author | 廖唯昱 | zh_TW |
dc.date.accessioned | 2021-06-08T01:00:04Z | - |
dc.date.copyright | 2015-03-12 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2015-01-09 | |
dc.identifier.citation | Aberle, D.R., Adams, A.M., Berg, C.D., Black, W.C., Clapp, J.D., Fagerstrom, R.M., Gareen, I.F., Gatsonis, C., Marcus, P.M., Sicks, J.D., 2011. Reduced lung-cancer mortality with low-dose computed tomographic screening. The New England Journal of Medicine 365, 395-409.
Afonso, P.V., Parent, C.A., 2011. PI3K and chemotaxis: a priming issue? Science Signaling 4, pe22. Aihara, K., 2010. Heparin cofactor II attenuates vascular remodeling in humans and mice. Circulation Journal : official journal of the Japanese Circulation Society 74, 1518-1523. Aihara, K., Azuma, H., Takamori, N., Kanagawa, Y., Akaike, M., Fujimura, M., Yoshida, T., Hashizume, S., Kato, M., Yamaguchi, H., Kato, S., Ikeda, Y., Arase, T., Kondo, A., Matsumoto, T., 2004. Heparin cofactor II is a novel protective factor against carotid atherosclerosis in elderly individuals. Circulation 109, 2761-2765. Baglin, T.P., Carrell, R.W., Church, F.C., Esmon, C.T., Huntington, J.A., 2002. Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proceedings of the National Academy of Sciences of the United States of America 99, 11079-11084. Bepler, G., Olaussen, K.A., Vataire, A.L., Soria, J.C., Zheng, Z., Dunant, A., Pignon, J.P., Schell, M.J., Fouret, P., Pirker, R., Filipits, M., Brambilla, E., 2011. ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis. The American Journal of Pathology 178, 69-78. Bid, H.K., Roberts, R.D., Manchanda, P.K., Houghton, P.J., 2013. RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Molecular Cancer Therapeutics 12, 1925-1934. Blinder, M.A., Tollefsen, D.M., 1990. Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II. The Journal of Biological Chemistry 265, 286-291. Boon, K., Osorio, E.C., Greenhut, S.F., Schaefer, C.F., Shoemaker, J., Polyak, K., Morin, P.J., Buetow, K.H., Strausberg, R.L., De Souza, S.J., Riggins, G.J., 2002. An anatomy of normal and malignant gene expression. Proceedings of the National Academy of Sciences of the United States of America 99, 11287-11292. Borsig, L., 2010. Antimetastatic activities of heparins and modified heparins. Experimental evidence. Thrombosis Research 125 Suppl 2, S66-71. Cadranel, J., Ruppert, A.M., Beau-Faller, M., Wislez, M., 2013. Therapeutic strategy for advanced EGFR mutant non-small-cell lung carcinoma. Critical Reviews in Oncology/Hematology 88, 477-493. Cain, R.J., Ridley, A.J., 2009. Phosphoinositide 3-kinases in cell migration. Biology of the cell / under the auspices of the European Cell Biology Organization 101, 13-29. Chaffer, C.L., Weinberg, R.A., 2011. A perspective on cancer cell metastasis. Science (New York, N.Y.) 331, 1559-1564. Chen, H.Y., Yu, S.L., Chen, C.H., Chang, G.C., Chen, C.Y., Yuan, A., Cheng, C.L., Wang, C.H., Terng, H.J., Kao, S.F., Chan, W.K., Li, H.N., Liu, C.C., Singh, S., Chen, W.J., Chen, J.J., Yang, P.C., 2007. A five-gene signature and clinical outcome in non-small-cell lung cancer. The New England Journal of Medicine 356, 11-20. Chu, Y.W., Yang, P.C., Yang, S.C., Shyu, Y.C., Hendrix, M.J., Wu, R., Wu, C.W., 1997. Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. American Journal of Respiratory Cell and Molecular Biology 17, 353-360. Chung, C.Y., Funamoto, S., Firtel, R.A., 2001. Signaling pathways controlling cell polarity and chemotaxis. Trends in Biochemical Sciences 26, 557-566. Church, F.C., Pratt, C.W., Hoffman, M., 1991. Leukocyte chemoattractant peptides from the serpin heparin cofactor II. The Journal of Biological Chemistry 266, 704-709. Couraud, S., Zalcman, G., Milleron, B., Morin, F., Souquet, P.J., 2012. Lung cancer in never smokers--a review. European Journal of Cancer (Oxford, England : 1990) 48, 1299-1311. Cuevas, B.D., Lu, Y., Mao, M., Zhang, J., LaPushin, R., Siminovitch, K., Mills, G.B., 2001. Tyrosine phosphorylation of p85 relieves its inhibitory activity on phosphatidylinositol 3-kinase. The Journal of Biological Chemistry 276, 27455-27461. Davenport, R.W., Dou, P., Rehder, V., Kater, S.B., 1993. A sensory role for neuronal growth cone filopodia. Nature 361, 721-724. Di, Y.P., 2011. Functional roles of SPLUNC1 in the innate immune response against Gram-negative bacteria. Biochemical Society Transactions 39, 1051-1055. Dumstrei, K., Mennecke, R., Raz, E., 2004. Signaling pathways controlling primordial germ cell migration in zebrafish. Journal of Cell Science 117, 4787-4795. Dunzendorfer, S., Kaneider, N., Rabensteiner, A., Meierhofer, C., Reinisch, C., Romisch, J., Wiedermann, C.J., 2001. Cell-surface heparan sulfate proteoglycan-mediated regulation of human neutrophil migration by the serpin antithrombin III. Blood 97, 1079-1085. Durand, M.K., Bodker, J.S., Christensen, A., Dupont, D.M., Hansen, M., Jensen, J.K., Kjelgaard, S., Mathiasen, L., Pedersen, K.E., Skeldal, S., Wind, T., Andreasen, P.A., 2004. Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis. Thrombosis and Haemostasis 91, 438-449. Etienne-Manneville, S., Hall, A., 2002. Rho GTPases in cell biology. Nature 420, 629-635. Faix, J., Rottner, K., 2006. The making of filopodia. Current Opinion in Cell Biology 18, 18-25. Falanga, A., Vignoli, A., Diani, E., Marchetti, M., 2011. Comparative assessment of low-molecular-weight heparins in cancer from the perspective of patient outcomes and survival. Patient Related Outcome Measures 2, 175-188. Friboulet, L., Olaussen, K.A., Pignon, J.P., Shepherd, F.A., Tsao, M.S., Graziano, S., Kratzke, R., Douillard, J.Y., Seymour, L., Pirker, R., Filipits, M., Andre, F., Solary, E., Ponsonnailles, F., Robin, A., Stoclin, A., Dorvault, N., Commo, F., Adam, J., Vanhecke, E., Saulnier, P., Thomale, J., Le Chevalier, T., Dunant, A., Rousseau, V., Le Teuff, G., Brambilla, E., Soria, J.C., 2013. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. The New England Journal of Medicine 368, 1101-1110. Gainor, J.F., Shaw, A.T., 2013. Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 31, 3987-3996. Galbraith, C.G., Yamada, K.M., Galbraith, J.A., 2007. Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science (New York, N.Y.) 315, 992-995. Gambardella, L., Vermeren, S., 2013. Molecular players in neutrophil chemotaxis--focus on PI3K and small GTPases. Journal of Leukocyte Biology 94, 603-612. Gerotziafas, G.T., Papageorgiou, C., Hatmi, M., Samama, M.M., Elalamy, I., 2008. Clinical studies with anticoagulants to improve survival in cancer patients. Pathophysiology of Haemostasis and Thrombosis 36, 204-211. Gettins, P.G., 2002. Serpin structure, mechanism, and function. Chemical Reviews 102, 4751-4804. Hallberg, B., Palmer, R.H., 2013. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nature Reviews. Cancer 13, 685-700. Hanahan, D., Weinberg, R.A., 2011. Hallmarks of cancer: the next generation. Cell 144, 646-674. He, L., Giri, T.K., Vicente, C.P., Tollefsen, D.M., 2008. Vascular dermatan sulfate regulates the antithrombotic activity of heparin cofactor II. Blood 111, 4118-4125. He, L., Vicente, C.P., Westrick, R.J., Eitzman, D.T., Tollefsen, D.M., 2002. Heparin cofactor II inhibits arterial thrombosis after endothelial injury. The Journal of Clinical Investigation 109, 213-219. Hoffman, M., Loh, K.L., Bond, V.K., Palmieri, D., Ryan, J.L., Church, F.C., 2003. Localization of heparin cofactor II in injured human skin: a potential role in wound healing. Experimental and Molecular Pathology 75, 109-118. Hoffman, M., Pratt, C.W., Brown, R.L., Church, F.C., 1989. Heparin cofactor II-proteinase reaction products exhibit neutrophil chemoattractant activity. Blood 73, 1682-1685. Hsu, T.H., Liao, W.Y., Yang, P.C., Wang, C.C., Xiao, J.L., Lee, C.H., 2007. Dynamics of cancer cell filopodia characterized by super-resolution bright-field optical microscopy. Optics Express 15, 76-82. Hsu, T.H., Yen, M.H., Liao, W.Y., Cheng, J.Y., Lee, C.H., 2009. Label-free quantification of asymmetric cancer-cell filopodium activities in a multi-gradient chip. Lab on a Chip 9, 884-890. Huang, S.W., Mong, H.Y., Lee, C.H., 2004. Super-resolution bright-field optical microscopy based on nanometer topographic contrast. Microscopy Research and Technique 65, 180-185. Humphrey, L.L., Deffebach, M., Pappas, M., Baumann, C., Artis, K., Mitchell, J.P., Zakher, B., Fu, R., Slatore, C.G., 2013. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive services task force recommendation. Annals of Internal Medicine 159, 411-420. Huntington, J.A., 2011. Serpin structure, function and dysfunction. Journal of Thrombosis and Haemostasis : JTH 9 Suppl 1, 26-34. Ikeda, Y., Aihara, K., Yoshida, S., Iwase, T., Tajima, S., Izawa-Ishizawa, Y., Kihira, Y., Ishizawa, K., Tomita, S., Tsuchiya, K., Sata, M., Akaike, M., Kato, S., Matsumoto, T., Tamaki, T., 2012. Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway. The Journal of Biological Chemistry 287, 34256-34263. Janicke, F., Prechtl, A., Thomssen, C., Harbeck, N., Meisner, C., Untch, M., Sweep, C.G., Selbmann, H.K., Graeff, H., Schmitt, M., 2001. Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. Journal of the National Cancer Institute 93, 913-920. Kakkar, A.K., Levine, M.N., Kadziola, Z., Lemoine, N.R., Low, V., Patel, H.K., Rustin, G., Thomas, M., Quigley, M., Williamson, R.C., 2004. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 22, 1944-1948. Kalle, M., Papareddy, P., Kasetty, G., Tollefsen, D.M., Malmsten, M., Morgelin, M., Schmidtchen, A., 2013. Proteolytic activation transforms heparin cofactor II into a host defense molecule. Journal of Immunology (Baltimore, Md. : 1950) 190, 6303-6310. Kalle, M., Papareddy, P., Kasetty, G., van der Plas, M.J., Morgelin, M., Malmsten, M., Schmidtchen, A., 2014. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection. PloS One 9, e102577. Kamp, P., Strathmann, A., Ragg, H., 2001. Heparin cofactor II, antithrombin-beta and their complexes with thrombin in human tissues. Thrombosis Research 101, 483-491. Kang, Y., Pantel, K., 2013. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 23, 573-581. Kavanaugh, W.M., Klippel, A., Escobedo, J.A., Williams, L.T., 1992. Modification of the 85-kilodalton subunit of phosphatidylinositol-3 kinase in platelet-derived growth factor-stimulated cells. Molecular and Cellular Biology 12, 3415-3424. Kim, B., Lee, H.J., Choi, H.Y., Shin, Y., Nam, S., Seo, G., Son, D.S., Jo, J., Kim, J., Lee, J., Kim, J., Kim, K., Lee, S., 2007. Clinical validity of the lung cancer biomarkers identified by bioinformatics analysis of public expression data. Cancer Research 67, 7431-7438. Kim, S.H., Turnbull, J., Guimond, S., 2011. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. The Journal of Endocrinology 209, 139-151. Knelson, E.H., Nee, J.C., Blobe, G.C., 2014. Heparan sulfate signaling in cancer. Trends in Biochemical Sciences 39, 277-288. Knight, M.M., Roberts, S.R., Lee, D.A., Bader, D.L., 2003. Live cell imaging using confocal microscopy induces intracellular calcium transients and cell death. Am. J. Physiol. Cell Physiol. 284, C1083-C1089. Kovbasnjuk, O., Mourtazina, R., Baibakov, B., Wang, T., Elowsky, C., Choti, M.A., Kane, A., Donowitz, M., 2005. The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer. Proceedings of the National Academy of Sciences of the United States of America 102, 19087-19092. Kuderer, N.M., Khorana, A.A., Lyman, G.H., Francis, C.W., 2007. A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications. Cancer 110, 1149-1161. Lal, A., Lash, A.E., Altschul, S.F., Velculescu, V., Zhang, L., McLendon, R.E., Marra, M.A., Prange, C., Morin, P.J., Polyak, K., Papadopoulos, N., Vogelstein, B., Kinzler, K.W., Strausberg, R.L., Riggins, G.J., 1999. A public database for gene expression in human cancers. Cancer Research 59, 5403-5407. Lane, D.A., Philippou, H., Huntington, J.A., 2005. Directing thrombin. Blood 106, 2605-2612. Lappano, R., Maggiolini, M., 2012. GPCRs and cancer. Acta Pharmacologica Sinica 33, 351-362. Lash, A.E., Tolstoshev, C.M., Wagner, L., Schuler, G.D., Strausberg, R.L., Riggins, G.J., Altschul, S.F., 2000. SAGEmap: a public gene expression resource. Genome Research 10, 1051-1060. Law, R.H., Zhang, Q., McGowan, S., Buckle, A.M., Silverman, G.A., Wong, W., Rosado, C.J., Langendorf, C.G., Pike, R.N., Bird, P.I., Whisstock, J.C., 2006. An overview of the serpin superfamily. Genome Biology 7, 216. Lebeau, B., Chastang, C., Brechot, J.M., Capron, F., Dautzenberg, B., Delaisements, C., Mornet, M., Brun, J., Hurdebourcq, J.P., Lemarie, E., 1994. Subcutaneous heparin treatment increases survival in small cell lung cancer. 'Petites Cellules' Group. Cancer 74, 38-45. Lee, C.H., Mong, H.Y., Lin, W.C., 2002. Noninterferometric wide-field optical profilometry with nanometer depth resolution. Optics letters 27, 1773-1775. Lee, C.J., Ansell, J.E., 2011. Direct thrombin inhibitors. British Journal of Clinical Pharmacology 72, 581-592. Lee, S.Y., Meier, R., Furuta, S., Lenburg, M.E., Kenny, P.A., Xu, R., Bissell, M.J., 2012. FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice. The Journal of Clinical Investigation 122, 3211-3220. Levy-Adam, F., Ilan, N., Vlodavsky, I., 2010. Tumorigenic and adhesive properties of heparanase. Seminars in Cancer Biology 20, 153-160. Liao, W.Y., Chen, J.H., Wu, M., Shih, J.Y., Chen, K.Y., Ho, C.C., Yang, J.C., Yu, C.J., 2013. Neoadjuvant chemotherapy with docetaxel-cisplatin in patients with stage III N2 non-small-cell lung cancer. Clinical Lung Cancer 14, 418-424. Liou, Y.-R., Torng, W., Kao, Y.-C., Sung, K.-B., Lee, C.-H., Kuo, P.-L., 2014. Substrate stiffness regulates filopodial activities in lung cancer cells. PloS One 9, e89767. Look, M.P., van Putten, W.L., Duffy, M.J., Harbeck, N., Christensen, I.J., Thomssen, C., Kates, R., Spyratos, F., Ferno, M., Eppenberger-Castori, S., Sweep, C.G., Ulm, K., Peyrat, J.P., Martin, P.M., Magdelenat, H., Brunner, N., Duggan, C., Lisboa, B.W., Bendahl, P.O., Quillien, V., Daver, A., Ricolleau, G., Meijer-van Gelder, M.E., Manders, P., Fiets, W.E., Blankenstein, M.A., Broet, P., Romain, S., Daxenbichler, G., Windbichler, G., Cufer, T., Borstnar, S., Kueng, W., Beex, L.V., Klijn, J.G., O'Higgins, N., Eppenberger, U., Janicke, F., Schmitt, M., Foekens, J.A., 2002. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. Journal of the National Cancer Institute 94, 116-128. Machesky, L.M., 2008. Lamellipodia and filopodia in metastasis and invasion. FEBS Letters 582, 2102-2111. Maillard, L., Saito, N., Hlawaty, H., Friand, V., Suffee, N., Chmilewsky, F., Haddad, O., Laguillier, C., Guyot, E., Ueyama, T., Oudar, O., Sutton, A., Charnaux, N., 2014. RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCalpha signaling pathway. Biology Open 3, 995-1004. Mattila, P.K., Lappalainen, P., 2008. Filopodia: molecular architecture and cellular functions. Nature reviews. Molecular Cell Biology 9, 446-454. Morgan, M.R., Humphries, M.J., Bass, M.D., 2007. Synergistic control of cell adhesion by integrins and syndecans. Nature reviews. Molecular Cell Biology 8, 957-969. Nierodzik, M.L., Karpatkin, S., 2006. Thrombin induces tumor growth, metastasis, and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10, 355-362. Noda, A., Wada, H., Kusiya, F., Sakakura, M., Onishi, K., Nakatani, K., Gabazza, E.C., Asahara, N., Tsukada, M., Nobori, T., Shiku, H., 2002. Plasma levels of heparin cofactor II (HCII) and thrombin-HCII complex in patients with disseminated intravascular coagulation. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 8, 265-271. Nurnberg, A., Kitzing, T., Grosse, R., 2011. Nucleating actin for invasion. Nature reviews. Cancer 11, 177-187. O'Keeffe, D., Olson, S.T., Gasiunas, N., Gallagher, J., Baglin, T.P., Huntington, J.A., 2004. The heparin binding properties of heparin cofactor II suggest an antithrombin-like activation mechanism. The Journal of Biological Chemistry 279, 50267-50273. O'Reilly, M.S., 2007. Antiangiogenic antithrombin. Seminars in Thrombosis and Hemostasis 33, 660-666. O'Reilly, M.S., Pirie-Shepherd, S., Lane, W.S., Folkman, J., 1999. Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. Science (New York, N.Y.) 285, 1926-1928. Olson, S.T., Richard, B., Izaguirre, G., Schedin-Weiss, S., Gettins, P.G., 2010. Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitors. Biochimie 92, 1587-1596. Ossandon, F.J., Villarroel, C., Aguayo, F., Santibanez, E., Oue, N., Yasui, W., Corvalan, A.H., 2008. In silico analysis of gastric carcinoma Serial Analysis of Gene Expression libraries reveals different profiles associated with ethnicity. Molecular Cancer 7, 22. Oxnard, G.R., Binder, A., Janne, P.A., 2013. New targetable oncogenes in non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 31, 1097-1104. Padda, S.K., Burt, B.M., Trakul, N., Wakelee, H.A., 2014. Early-stage non-small cell lung cancer: surgery, stereotactic radiosurgery, and individualized adjuvant therapy. Seminars in Oncology 41, 40-56. Papareddy, P., Kalle, M., Singh, S., Morgelin, M., Schmidtchen, A., Malmsten, M., 2014. An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo. Biochimica et Biophysica Acta 1838, 1225-1234. Pike, R.N., Buckle, A.M., le Bonniec, B.F., Church, F.C., 2005. Control of the coagulation system by serpins. Getting by with a little help from glycosaminoglycans. The FEBS Journal 272, 4842-4851. Polyak, K., Riggins, G.J., 2001. Gene discovery using the serial analysis of gene expression technique: implications for cancer research. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 19, 2948-2958. Porter, D., Yao, J., Polyak, K., 2006. SAGE and related approaches for cancer target identification. Drug Discovery Today 11, 110-118. Raftopoulou, M., Hall, A., 2004. Cell migration: Rho GTPases lead the way. Developmental Biology 265, 23-32. Randall, D.R., Colobong, K.E., Hemmelgarn, H., Sinclair, G.B., Hetty, E., Thomas, A., Bodamer, O.A., Volkmar, B., Fernhoff, P.M., Casey, R., Chan, A.K., Mitchell, G., Stockler, S., Melancon, S., Rupar, T., Clarke, L.A., 2008. Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Molecular Genetics and Metabolism 94, 456-461. Sadeghi, N., Gerber, D.E., 2012. Targeting the PI3K pathway for cancer therapy. Future Medicinal Chemistry 4, 1153-1169. Sahai, E., Marshall, C.J., 2002. RHO-GTPases and cancer. Nature Reviews Cancer 2, 133-142. Sarrazin, S., Lamanna, W.C., Esko, J.D., 2011. Heparan sulfate proteoglycans. Cold Spring Harbor Perspectives in Biology 3. Saxena, M., Christofori, G., 2013. Rebuilding cancer metastasis in the mouse. Molecular Oncology 7, 283-296. Schedin-Weiss, S., Richard, B., Hjelm, R., Olson, S.T., 2008. Antiangiogenic forms of antithrombin specifically bind to the anticoagulant heparin sequence. Biochemistry 47, 13610-13619. Shih, J.-Y., Yang, S.-C., Hong, T.-M., Yuan, A., Chen, J.J.W., Yu, C.-J., Chang, Y.-L., Lee, Y.-C., Peck, K., Wu, C.-W., Yang, P.-C., 2001. Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells. J. Natl. Cancer Inst. 93, 1392-1400. Siegel, R., Ma, J., Zou, Z., Jemal, A., 2014. Cancer statistics, 2014. CA: a Cancer Journal for Clinicians 64, 9-29. Siller-Matula, J.M., Schwameis, M., Blann, A., Mannhalter, C., Jilma, B., 2011. Thrombin as a multi-functional enzyme. Focus on in vitro and in vivo effects. Thrombosis and Haemostasis 106, 1020-1033. Skokowa, J., Klimiankou, M., Klimenkova, O., Lan, D., Gupta, K., Hussein, K., Carrizosa, E., Kusnetsova, I., Li, Z., Sustmann, C., Ganser, A., Zeidler, C., Kreipe, H.H., Burkhardt, J., Grosschedl, R., Welte, K., 2012. Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis. Nature Medicine 18, 1550-1559. Speeckaert, M.M., Speeckaert, R., Delanghe, J.R., 2013. Human epididymis protein 4 in cancer diagnostics: a promising and reliable tumor marker. Advances in Clinical Chemistry 59, 1-21. St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K.E., Montgomery, E., Lal, A., Riggins, G.J., Lengauer, C., Vogelstein, B., Kinzler, K.W., 2000. Genes expressed in human tumor endothelium. Science (New York, N.Y.) 289, 1197-1202. Stengel, K., Zheng, Y., 2011. Cdc42 in oncogenic transformation, invasion, and tumorigenesis. Cellular Signalling 23, 1415-1423. Stephens, L., Milne, L., Hawkins, P., 2008. Moving towards a better understanding of chemotaxis. Current Biology : CB 18, R485-494. Sumitomo-Ueda, Y., Aihara, K., Ise, T., Yoshida, S., Ikeda, Y., Uemoto, R., Yagi, S., Iwase, T., Ishikawa, K., Hirata, Y., Akaike, M., Sata, M., Kato, S., Matsumoto, T., 2010. Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice. Hypertension 56, 430-436. Takamori, N., Azuma, H., Kato, M., Hashizume, S., Aihara, K., Akaike, M., Tamura, K., Matsumoto, T., 2004. High plasma heparin cofactor II activity is associated with reduced incidence of in-stent restenosis after percutaneous coronary intervention. Circulation 109, 481-486. Tollefsen, D.M., 2007. Heparin cofactor II modulates the response to vascular injury. Arteriosclerosis, Thrombosis, and Vascular Biology 27, 454-460. Tollefsen, D.M., 2010. Vascular dermatan sulfate and heparin cofactor II. Progress in Molecular Biology and Translational Science 93, 351-372. Tollefsen, D.M., Majerus, D.W., Blank, M.K., 1982. Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. The Journal of Biological Chemistry 257, 2162-2169. Tollefsen, D.M., Pestka, C.A., Monafo, W.J., 1983. Activation of heparin cofactor II by dermatan sulfate. The Journal of Biological Chemistry 258, 6713-6716. Trowbridge, J.M., Gallo, R.L., 2002. Dermatan sulfate: new functions from an old glycosaminoglycan. Glycobiology 12, 117r-125r. Untergasser, G., Koch, H.B., Menssen, A., Hermeking, H., 2002. Characterization of epithelial senescence by serial analysis of gene expression: identification of genes potentially involved in prostate cancer. Cancer Research 62, 6255-6262. Valastyan, S., Weinberg, R.A., 2011. Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275-292. van Doormaal, F.F., Di Nisio, M., Otten, H.M., Richel, D.J., Prins, M., Buller, H.R., 2011. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29, 2071-2076. van Kempen, G.M.P., van der Voort, H.T.M., Bauman, J.G.J., Strasters, K.C., 1996. Comparing Maximum Likelihood Estimation and Constrained Tikhonov-Miller Restoration. IEEE Eng. Med. Biol. 15, 76-83. Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., Bilanges, B., 2010. The emerging mechanisms of isoform-specific PI3K signalling. Nature reviews. Molecular Cell Biology 11, 329-341. Vega, F.M., Ridley, A.J., 2008. Rho GTPases in cancer cell biology. FEBS Letters 582, 2093-2101. Velculescu, V.E., Zhang, L., Vogelstein, B., Kinzler, K.W., 1995. Serial analysis of gene expression. Science (New York, N.Y.) 270, 484-487. Vignjevic, D., Schoumacher, M., Gavert, N., Janssen, K.P., Jih, G., Lae, M., Louvard, D., Ben-Ze'ev, A., Robine, S., 2007. Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Research 67, 6844-6853. von Tempelhoff, G.F., Harenberg, J., Niemann, F., Hommel, G., Kirkpatrick, C.J., Heilmann, L., 2000. Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial. International Journal of Oncology 16, 815-824. Walter-Yohrling, J., Cao, X., Callahan, M., Weber, W., Morgenbesser, S., Madden, S.L., Wang, C., Teicher, B.A., 2003. Identification of genes expressed in malignant cells that promote invasion. Cancer Research 63, 8939-8947. Wang, C.-C., Kao, Y.-C., Chi, P.-Y., Huang, C.-W., Lin, J.-Y., Chou, C.-F., Cheng, J.-Y., Lee, C.-H., 2011. Asymmetric cancer-cell filopodium growth induced by electric-fields in a microfluidic culture chip. Lab on a Chip 11, 695-699. Wang, C.-C., Lee, K.-L., Lee, C.-H., 2009. Wide-field optical nano-profilometry using structured illumination. Opt. Lett. 34, 3538-3540. Wang, S.M., 2007. Understanding SAGE data. Trends in Genetics : TIG 23, 42-50. Wells, A., Grahovac, J., Wheeler, S., Ma, B., Lauffenburger, D., 2013. Targeting tumor cell motility as a strategy against invasion and metastasis. Trends in Pharmacological Sciences 34, 283-289. Yanagisawa, K., Tomida, S., Shimada, Y., Yatabe, Y., Mitsudomi, T., Takahashi, T., 2007. A 25-signal proteomic signature and outcome for patients with resected non-small-cell lung cancer. Journal of the National Cancer Institute 99, 858-867. Zhang, W., Swanson, R., Izaguirre, G., Xiong, Y., Lau, L.F., Olson, S.T., 2005. The heparin-binding site of antithrombin is crucial for antiangiogenic activity. Blood 106, 1621-1628. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18330 | - |
dc.description.abstract | 肺癌在台灣以及世界各地是癌症死亡最常見的原因之一,主要分小細胞與非小細胞肺癌,其中大約85%的肺癌為非小細胞肺癌。初次診斷時大約只有15-20%的肺癌病患有機會接受手術治療,而有機會接受手術治療的病患也只有一半可以長期存活,其餘病患往往死於癌症轉移。如何早期診斷肺癌且給予有效的治療,並找出轉移率高的危險群施以有效的輔助性療法,是減少肺癌的死亡率的關鍵。我們利用CGAP(Cancer Genome Anatomy Project)所提供的SAGE(Series Analysis of Gene Expression)Genie工具,找到Heparin cofactor II(肝素第二輔助因子,HCII,又稱為SERPIN D1,serine protease inhibitor,clade D,member 1)在肺癌大量表現且具有分泌功能。我們進一步分析一系列人類非小細胞肺癌細胞株中HCII的表現,發現HCII在侵入性及轉移能力較高的細胞株中表現量較高。我們以75位臨床上可接受手術的非小細胞肺癌患者之腫瘤組織進行免疫組織染色以分析HCII的表現量,結果顯示HCII表現量高的患者,無疾病存活期顯著較短(P=0.011)且整體存活期縮短 (P=0.005)。多變項Cox比例危險迴歸分析顯示,HCII 表現量高、男性及病理分期第 III 期和第 IV 期,與非小細胞肺癌患者的整體存活期降低有關聯性。另外我們檢測57位非小細胞肺癌患者的HCII血漿濃度,發現治療前血漿HCII濃度高的患者,整體存活期顯著縮短(P =0.039)。進一步研究發現,外源性HCII可促進非小細胞肺癌細胞的絲狀偽足動態變化,此外利用過量表現或壓抑HCII表現的實驗證實,HCII會增加癌細胞移動力及侵入性,並在體外及體內促進癌症轉移。而且HCII對於肺癌細胞促進移動作用,與凝血酶的抑制沒有直接相關性。接下來的實驗證實HCII是透過活化Cdc42及Rac1來促進肺癌細胞的絲狀偽足動態變化與移動能力。而HCII對肺癌細胞產生的移動能力提升作用,是透過PI3K而活化下游的Cdc42及Rac1。肝素可阻斷上述HCII作用所造成的癌細胞移動與轉移,且經由HCII肝素結合位置的突變(K185M)證實HCII是透過其肝素結合位置與非小細胞肺癌細胞交互作用。我們的研究證實HCII為非小細胞肺癌的轉移促進因子之一。PI3K、Rac1 及 Cdc42 為HCII誘發肺癌細胞絲狀偽足形成和移動的下游作用因子。HCII的表現,與癌症復發增加及治療結果不佳有關聯性。HCII的表現可能做為預後因子,藉以鑑別非小細胞肺癌手術切除後具有高復發風險而需要立即接受輔助治療的患者。腫瘤組織或血漿檢體中的HCII 濃度,將有可能做為肝素治療非小細胞肺癌時的預測因子。 | zh_TW |
dc.description.abstract | Lung cancer is the leading cause of cancer deaths worldwide. Non-small-cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer. Although there has been progress in the diagnosis and treatment of lung cancer, NSCLC caries a 5-year survival rate of only 17%. Despite the fact that early stage disease may be cured with surgery, only 15%-20% of lung cancer patients were operable at presentation, and about half of them had long-term survival. The remaining almost always died of metastatic disease. Identifying early stage NSCLC with metastatic potential and providing individualized treatment strategies will have a higher probability of truly curing the disease. By using Serial Analysis of Gene Expression (SAGE) database from Cancer Genome Anatomy Project (CGAP), we identified heprain cofactor II (HCII), also named, serine protease inhibitor D1 (SERPIN D1), which is overexpressed in NSCLC. Here, we investigate the clinical significance of HCII and provide molecular evidence to support that HCII could enhance cancer metastasis in NSCLC. HCII expression was higher in NSCLC cell lines with high metastatic ability. We found that high HCII expression in tumor tissue is associated with increased cancer recurrence (P = 0.011) and shorter overall survival times (P=0.005) in 75 clinically operable NSCLC patients. Multivariate Cox proportional hazards regression analysis showed that high HCII expression in tumor tissue, male gender and pathological stage III&IV were associated with reduced overall survival of patients with NSCLC. High pre-treatment plasma concentration of HCII is associated with reduced overall survival in 57 consecutive NSCLC patients. We overexpressed and knockdown HCII expressions in lung cancer cell lines and confirmed that HCII can promote cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro and increased metastatic colonization in an in vivo mouse model. Exogenous treatment of HCII promoted cancer cell migration, and this promigratory effect of HCII was independent of thrombin. We further showed that HCII could upregulate cancer cell migration through activation of PI3K, which acts upstream of Rac1 and Cdc42, and this effect could be blocked by heparin. We also demonstrated that the promigratory and invasion ability of HCII on lung cancer cells were abolished by mutagenesis at heparin binding site (K185M) of HCII. We suggest that HCII is a novel metastasis enhancer and may be used as a predictor for heparin treatment in NSCLC. We propose that HCII expression levels in tumor tissues or plasma samples could be regarded as a predictive factor for heparin treatment in NSCLC patients. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:00:04Z (GMT). No. of bitstreams: 1 ntu-103-D92421008-1.pdf: 13727004 bytes, checksum: f8ad155c46246ea408a87a8d76f34b87 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審定書……………………………………………i
致謝…………………………………………………………ii 中文摘要………………………………………………………iii 英文摘要……………………………………………………v 博士論文內容 第一章 緒論…………………………………………………1 第一節 肺癌的概況………………………………………1 第二節 公共資料庫的資料探勘………………………… 4 第三節 Serine protease inhibitors(serpins)的生物功能……………… 7 第四節 Heparin Cofactor II(HCII,SERPIND1)的生物功能………… 12 第五節 探討HCII與肺癌之相關性………………………19 第二章 研究方法與材料…………………………………… 23 第一節 細胞株及培養條件………………………………23 第二節 西方墨點法分析…………………………………23 第三節 即時定量PCR……………………………………24 第四節 腫瘤組織的免疫組織化學染色…………………25 第五節 HCII的血漿濃度的測定…………………………25 第六節 體外細胞移動及侵入檢測………………………26 第七節 顯微縮時影片……………………………………27 第八節 細胞增生檢測……………………………………27 第九節 利用shRNA壓抑HCII之表現量…………………27 第十節 慢病毒包裝……………………………………… 28 第十一節 慢病毒感染………………………………………29 第十二節 超高解析度明視野光學顯微鏡及絲狀偽足定量 29 第十三節 Rac1 及 Cdc42 Pull Down檢測………………30 第十四節 建構表現載體及轉染……………………………30 第十五節 免疫螢光染色及絲狀偽足測量…………………31 第十六節 顯性負性Cdc42暫時性轉染……………………32 第十七節 引發突變…………………………………………33 第十八節 實驗性轉移………………………………………33 第十九節 統計分析………………………………………… 33 第三章 結果……………………………………………………………35 第一節 HCII在人類非小細胞肺癌細胞株中的表現……35 第二節 HCII在腫瘤組織中的表現量與肺癌患者的存活有關聯性…… 35 第三節 HCII的血漿濃度與肺癌患者的存活有關聯性…36 第四節 外源性的HCII會促進肺癌細胞移動……………37 第五節 HCII促進肺癌細胞移動的作用與thrombin無直接關聯……… 37 第六節 HCII促進肺癌細胞移動與侵襲而調降HCII會降低這些作用… 38 第七節 HCII增強肺癌細胞的絲狀偽足動態變化………38 第八節 Cdc 42及 Rac1為HCII的下游作用因子………40 第九節 受到HCII刺激時PI3K作用於Cdc42及Rac1的上游………… 41 第十節 肝素可阻斷HCII誘發之癌細胞移動及侵襲……41 第十一節 HCII表現促進體內轉移…………………………42 第三章 討論…………………………………………………44 第一節 主要研究成果……………………………………44 第二節 HCII促進肺癌細胞移動能力……………………46 第三節 HCII與肺癌病患存活的相關性…………………48 第四節 HCII促進肺癌細胞移動與Thrombin無關………50 第五節 HCII與絲狀偽足動態……………………………53 第六節 HCII透過Cdc42及Rac1促進絲狀偽足動態及肺癌細胞移動… 56 第七節 HCII透過PI3K的作用來活化Cdc42及Rac1……58 第八節 肝素影響HCII促進肺癌細胞移動的作用………59 第九節 結論………………………………………………63 第三章 展望…………………………………………………64 第一節 非小細胞肺癌治療的現況………………………64 第二節 肝素用於抑制癌症轉移的治療…………………67 第三節 探討HCII與肺癌細胞作用可能之機轉…………70 論文英文簡述……………………………………………………………74 參考文獻………………………………………………… 87 圖一、………………………………………………………102 圖二、………………………………………………………103 圖三、………………………………………………………104 圖四、………………………………………………………105 圖五、………………………………………………………106 圖六、………………………………………………………107 圖七、………………………………………………………108 圖八、………………………………………………………109 圖九、………………………………………………………110 圖十、………………………………………………………111 圖十一、……………………………………………………112 圖十二、……………………………………………………113 圖十三、……………………………………………………114 圖十四、……………………………………………………115 圖十五、……………………………………………………116 圖十六、……………………………………………………117 圖十七、……………………………………………………118 圖十八、……………………………………………………120 圖十九、……………………………………………………122 圖二十、…………………………………………………… 123 圖二十一、………………………………………………124 圖二十二、…………………………………………………125 圖二十三、…………………………………………… 126 圖二十四、…………………………………………………127 圖二十五、…………………………………………………128 圖二十六、…………………………………………………129 圖二十七、…………………………………………………130 圖二十八、…………………………………………………131 圖二十九、…………………………………………………132 表一、………………………………………………………133 表二、………………………………………………… 135 表三、………………………………………………… 136 表四、………………………………………………… 137 | |
dc.language.iso | zh-TW | |
dc.title | 肝素第二輔助因子促進非小細胞肺癌轉移之研究 | zh_TW |
dc.title | Heparin Cofactor II Promotes Metastasis in Non-Small-Cell Lung Cancer | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李超煌,楊偉勛,劉俊人,陳健尉 | |
dc.subject.keyword | 肝素第二輔助因子,非小細胞肺癌,細胞移動能力,癌症轉移,絲狀偽足動態, | zh_TW |
dc.subject.keyword | Heparin cofactor II (HCII),Non-small-cell lung cancer,Cell motility,Metastasis,Filopodium dynamics, | en |
dc.relation.page | 137 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2015-01-09 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 13.41 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。