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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蕭寧馨(Ning-Sing Shaw) | |
| dc.contributor.author | Jia-Ching Mao | en |
| dc.contributor.author | 毛嘉慶 | zh_TW |
| dc.date.accessioned | 2021-06-15T13:27:17Z | - |
| dc.date.available | 2026-12-31 | |
| dc.date.copyright | 2016-02-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2016-02-16 | |
| dc.identifier.citation | (1) Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. 'Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity.' Pharmacological Reviews 2004, 56, 185-229.
(2) Weiss, R. B. 'The anthracyclines: Will we ever find a better doxorubicin?' Seminars in Oncology 1992, 19, 670-686. (3) Pai, V. B.; Nahata, M. C. 'Cardiotoxicity of chemotherapeutic agents. Incidence, treatment and prevention.' Drug Safety 2000, 22, 263-302. (4) Lenaz, L.; Page, J. A. 'Cardiotoxicity of adriamycin and related anthracyclines.' Cancer Treatment Reviews 1976, 3, 111-120. (5) Gullotti, E.; Yeo, Y. 'Extracellularly activated nanocarriers: a new paradigm of tumor targeted drug delivery.' Molecular Pharmaceutics 2009, 6, 1041-1051. (6) Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R. 'Nanocarriers as an emerging platform for cancer therapy.' Nature Nanotechnology 2007, 2, 751-760. (7) Moghimi, S. M.; Hunter, A. C.; Murray, J. C. 'Long-circulating and target-specific nanoparticles: Theory to practice.' Pharmacological Reviews 2001, 53, 283-318. (8) Safra, T. 'Cardiac safety of liposomal anthracyclines.' The oncologist 2003, 8, 17-24. (9) Allen, T. M.; Cullis, P. R. 'Drug delivery systems: entering the mainstream.' Science 2004, 303, 1818-1822. (10) Bae, Y. H.; Park, K. 'Targeted drug delivery to tumors: myths, reality and possibility.' Journal of Controlled Release 2011, 153, 198-205. (11) Matsumura, Y.; Maeda, H. 'A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.' Cancer Research 1986, 46, 6387-6392. (12) Panyam, J.; Labhasetwar, V. 'Biodegradable nanoparticles for drug and gene delivery to cells and tissue.' Advanced Drug Delivery Reviews 2003, 55, 329-347. (13) Bangham, A.; Standish, M.; Weissmann, G. 'The action of steroids and streptolysin S on the permeability of phospholipid structures to cations.' Journal of Molecular Biology 1965, 13, 253-IN228. (14) Juliano, D.; Wang, Y.; Marcinkiewicz, C.; Rosenthal, L. A.; Stewart, G. J.; Niewiarowski, S. 'Disintegrin interaction with α v β 3 integrin on human umbilical vein endothelial cells: Expression of ligand-induced binding site on β 3 subunit.' Experimental Cell Research 1996, 225, 132-142. (15) Muqbil, I.; Masood, A.; Sarkar, F. H.; Mohammad, R. M.; Azmi, A. S. 'Progress in nanotechnology based approaches to enhance the potential of chemopreventive agents.' Cancers (Basel) 2011, 3, 428-445. (16) Wicki, A.; Witzigmann, D.; Balasubramanian, V.; Huwyler, J. 'Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.' Journal of Controlled Release 2015, 200, 138-157. (17) Woodbury, D. J.; Richardson, E. S.; Grigg, A. W.; Welling, R. D.; Knudson, B. H. 'Reducing liposome size with ultrasound: bimodal size distributions.' Journal of Liposome Research 2006, 16, 57-80. (18) Olson, F.; Hunt, C. A.; Szoka, F. C.; Vail, W. J.; Papahadjopoulos, D. 'Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes.' Biochimica et Biophysica Acta (BBA) - Biomembranes 1979, 557, 9-23. (19) Liu, D.; Mori, A.; Huang, L. 'Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GM1-containing liposomes.' Biochimica et Biophysica Acta (BBA) - Biomembranes 1992, 1104, 95-101. (20) Maruyama, K. 'Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects.' Advanced Drug Delivery Reviews 2011, 63, 161-169. (21) Kraft, J. C.; Freeling, J. P.; Wang, Z.; Ho, R. J. Y. 'Emerging Research and Clinical Development Trends of Liposome and Lipid Nanoparticle Drug Delivery Systems.' Journal of Pharmaceutical Sciences 2014, 103, 29-52. (22) Torchilin, V. 'Tumor delivery of macromolecular drugs based on the EPR effect.' Advanced Drug Delivery Reviews 2011, 63, 131-135. (23) Mosca, M.; Ceglie, A.; Ambrosone, L. 'Effect of membrane composition on lipid oxidation in liposomes.' Chemistry and Physics of Lipids 2011, 164, 158-165. (24) Diederichs, J. E. 'Plasma protein adsorption patterns on liposomes: establishment of analytical procedure.' Electrophoresis 1996, 17, 607-611. (25) Ho, J. A.; Fan, N. C.; Jou, A. F.; Wu, L. C.; Sun, T. P. 'Monitoring the subcellular localization of doxorubicin in CHO-K1 using MEKC-LIF: liposomal carrier for enhanced drug delivery.' Talanta 2012, 99, 683-688. (26) Kibria, G.; Hatakeyama, H.; Ohga, N.; Hida, K.; Harashima, H. 'Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery.' Journal of Controlled Release 2011, 153, 141-148. (27) Guo, P.; You, J. O.; Yang, J.; Jia, D.; Moses, M. A.; Auguste, D. T. 'Inhibiting metastatic breast cancer cell migration via the synergy of targeted, pH-triggered siRNA delivery and chemokine axis blockade.' Molecular Pharmaceutics 2014, 11, 755-765. (28) Handa, T.; Sakano, M.; Naito, S.; Hiramatsu, M.; Tsuboi, M. 'Thermal SiO and H13CO+ Line Observations of the Dense Molecular Cloud G0.11–0.11 in the Galactic Center Region.' The Astrophysical Journal 2006, 636, 261. (29) Deamer, D.; Bangham, A. D. 'Large volume liposomes by an ether vaporization method.' Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis 1976, 443, 629-634. (30) Schieren, H.; Rudolph, S.; Finkelstein, M.; Coleman, P.; Weissmann, G. 'Comparison of large unilamellar vesicles prepared by a petroleum ether vaporization method with multilamellar vesicles: ESR, diffusion and entrapment analyses.' Biochimica et Biophysica Acta (BBA) - General Subjects 1978, 542, 137-153. (31) Szoka, F.; Papahadjopoulos, D. 'Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation.' Proceedings of the National Academy of Sciences of the United States of America 1978, 75, 4194-4198. (32) Batzri, S.; Korn, E. D. 'Single bilayer liposomes prepared without sonication.' Biochimica et Biophysica Acta (BBA) - Biomembranes 1973, 298, 1015-1019. (33) Hood, J. D.; Bednarski, M.; Frausto, R.; Guccione, S.; Reisfeld, R. A.; Xiang, R.; Cheresh, D. A. 'Tumor regression by targeted gene delivery to the neovasculature.' Science 2002, 296, 2404-2407. (34) Pangburn, T. O.; Petersen, M. A.; Waybrant, B.; Adil, M. M.; Kokkoli, E. 'Peptide- and aptamer-functionalized nanovectors for targeted delivery of therapeutics.' Journal of Biomechanical Engineering 2009, 131. (35) Sardan, M.; Kilinc, M.; Genc, R.; Tekinay, A. B.; Guler, M. O. 'Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of anticancer drugs to tumor cells.' Faraday Discussions 2013, 166, 269-283. (36) Arabi, L.; Badiee, A.; Mosaffa, F.; Jaafari, M. R. 'Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin.' Journal of Controlled Release 2015, 220, 275-286. (37) Erdogan, S.; Medarova, Z. O.; Roby, A.; Moore, A.; Torchilin, V. P. 'Enhanced tumor MR imaging with gadolinium-loaded polychelating polymer-containing tumor-targeted liposomes.' Journal of Magnetic Resonance Imaging 2008, 27, 574-580. (38) Matsumura, Y.; Gotoh, M.; Muro, K.; Yamada, Y.; Shirao, K.; Shimada, Y.; Okuwa, M.; Matsumoto, S.; Miyata, Y.; Ohkura, H. 'Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer.' Annals of Oncology 2004, 15, 517-525. (39) Lu, Y.; Low, P. S. 'Folate-mediated delivery of macromolecular anticancer therapeutic agents.' Advanced Drug Delivery Reviews 2002, 54, 675-693. (40) Wang, S.; Lee, R. J.; Cauchon, G.; Gorenstein, D. G.; Low, P. S. 'Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol.' Proceedings of the National Academy of Sciences of the United States of America 1995, 92, 3318-3322. (41) Lee, R. J.; Huang, L. 'Folate-targeted, anionic liposome-entrapped polylysine-condensed DNA for tumor cell-specific gene transfer.' Journal of Biological Chemistry 1996, 271, 8481-8487. (42) Gabizon, A.; Martin, F. 'Polyethylene Glycol-Coated (Pegylated) Liposomal Doxorubicin.' Drugs 1997, 54, 15-21. (43) Hood, R. R.; Shao, C.; Omiatek, D. M.; Vreeland, W. N.; DeVoe, D. L. 'Microfluidic Synthesis of PEG- and Folate-Conjugated Liposomes for One-Step Formation of Targeted Stealth Nanocarriers.' Pharmaceutical Research 2013, 30, 1597-1607. (44) Gabizon, A.; Shmeeda, H.; Horowitz, A. T.; Zalipsky, S. 'Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid–PEG conjugates.' Advanced Drug Delivery Reviews 2004, 56, 1177-1192. (45) Park, J. W.; Hong, K.; Kirpotin, D. B.; Colbern, G.; Shalaby, R.; Baselga, J.; Shao, Y.; Nielsen, U. B.; Marks, J. D.; Moore, D. 'Anti-HER2 immunoliposomes enhanced efficacy attributable to targeted delivery.' Clinical Cancer Research 2002, 8, 1172-1181. (46) Gabizon, A.; Horowitz, A. T.; Goren, D.; Tzemach, D.; Shmeeda, H.; Zalipsky, S. 'In vivo fate of folate-targeted polyethylene-glycol liposomes in tumor-bearing mice.' Clinical Cancer Research 2003, 9, 6551-6559. (47) Brooks, H.; Lebleu, B.; Vivès, E. 'Tat peptide-mediated cellular delivery: Back to basics.' Advanced Drug Delivery Reviews 2005, 57, 559-577. (48) Duchardt, F.; Fotin-Mleczek, M.; Schwarz, H.; Fischer, R.; Brock, R. 'A Comprehensive Model for the Cellular Uptake of Cationic Cell-penetrating Peptides.' Traffic 2007, 8, 848-866. (49) Torchilin, V. P. 'Recent advances with liposomes as pharmaceutical carriers.' Nature Reviews Drug Discovery 2005, 4, 145-160. (50) Tamkun, J. W.; DeSimone, D. W.; Fonda, D.; Patel, R. S.; Buck, C.; Horwitz, A. F.; Hynes, R. O. 'Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin.' Cell 1986, 46, 271-282. (51) Hynes, R. O. 'Integrins: Versatility, modulation, and signaling in cell adhesion.' Cell 1992, 69, 11-25. (52) Huttenlocher, A.; Horwitz, A. R. 'Integrins in cell migration.' Cold Spring Harbor Perspectives in Biology 2011, 3, a005074. (53) Hynes, R. O. 'Integrins: Bidirectional, Allosteric Signaling Machines.' Cell 2002, 110, 673-687. (54) Kuperwasser, C.; Dessain, S.; Bierbaum, B.; Garnet, D.; Sperandio, K.; Gauvin, G.; Naber, S.; Weinberg, R.; Rosenblatt, M. 'A mouse model of human breast cancer metastasis to human bone.' Cancer Research 2005, 65, 6130 - 6138. (55) Sloan, E. K.; Pouliot, N.; Stanley, K. L.; Chia, J.; Moseley, J. M.; Hards, D. K.; Anderson, R. L. 'Tumor-specific expression of alphavbeta3 integrin promotes spontaneous metastasis of breast cancer to bone.' Breast Cancer Research 2006, 8, R20. (56) Shen, B.; Zhao, X.; O/'Brien, K. A.; Stojanovic-Terpo, A.; Delaney, M. K.; Kim, K.; Cho, J.; Lam, S. C. T.; Du, X. 'A directional switch of integrin signalling and a new anti-thrombotic strategy.' Nature 2013, 503, 131-135. (57) Teitelbaum, S. L. 'Osteoporosis and Integrins.' The Journal of Clinical Endocrinology & Metabolism 2005, 90, 2466-2468. (58) Arnaout, M. 'Structure and function of the leukocyte adhesion molecules CD11/CD18.' Blood 1990, 75, 1037-1050. (59) Eliceiri, B. P. 'Integrin and growth factor receptor crosstalk.' Circulation Research 2001, 89, 1104-1110. (60) Desgrosellier, J. S.; Cheresh, D. A. 'Integrins in cancer: biological implications and therapeutic opportunities.' Nature Reviews Cancer 2010, 10, 9-22. (61) Lössner, D.; Abou-Ajram, C.; Benge, A.; Reuning, U. 'Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells.' The International Journal of Biochemistry & Cell Biology 2008, 40, 2746-2761. (62) Brooks, P. C.; Clark, R.; Cheresh, D. A. 'Requirement of vascular integrin alpha v beta 3 for angiogenesis.' Science 1994, 264, 569-571. (63) Petitclerc, E.; Strömblad, S.; von Schalscha, T. L.; Mitjans, F.; Piulats, J.; Montgomery, A. M.; Cheresh, D. A.; Brooks, P. C. 'Integrin αvβ3 promotes M21 melanoma growth in human skin by regulating tumor cell survival.' Cancer Research 1999, 59, 2724-2730. (64) Brooks, P. C.; Strömblad, S.; Klemke, R.; Visscher, D.; Sarkar, F. H.; Cheresh, D. A. 'Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin.' Journal of Clinical Investigation 1995, 96, 1815. (65) Brooks, P. C.; Clark, R. A. F.; Cheresh, D. A. 'Requirement of vascular integrin αvβ3 for angiogenesis.' Science 1994, 264, 569-571. (66) Brooks, P. C.; Montgomery, A. M. P.; Rosenfeld, M.; Reisfeld, R. A.; Hu, T.; Klier, G.; Cheresh, D. A. 'Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels.' Cell 1994, 79, 1157-1164. (67) Hofmann, U. B.; Westphal, J. R.; Van Muijen, G. N. P.; Ruiter, D. J. 'Matrix metalloproteinases in human melanoma.' Journal of Investigative Dermatology 2000, 115, 337-344. (68) Brooks, P. C.; Strömblad, S.; Sanders, L. C.; von Schalscha, T. L.; Aimes, R. T.; Stetler-Stevenson, W. G.; Quigley, J. P.; Cheresh, D. A. 'Localization of Matrix Metalloproteinase MMP-2 to the Surface of Invasive Cells by Interaction with Integrin αvβ3.' Cell 1996, 85, 683-693. (69) Yu, Y. P.; Wang, Q.; Liu, Y. C.; Xie, Y. 'Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3.' Biomaterials 2014, 35, 1667-1675. (70) Danhier, F.; Breton, A. L.; Préat, V. 'RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis.' Molecular Pharmaceutics 2012, 9, 2961-2973. (71) Jiang, J.; Yang, S.-j.; Wang, J.-c.; Yang, L.-j.; Xu, Z.-z.; Yang, T.; Liu, X.-y.; Zhang, Q. 'Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin.' European Journal of Pharmaceutics and Biopharmaceutics 2010, 76, 170-178. (72) Naik, S.; Patel, D.; Chuttani, K.; Mishra, A. K.; Misra, A. 'In vitro mechanistic study of cell death and in vivo performance evaluation of RGD grafted PEGylated docetaxel liposomes in breast cancer.' Nanomedicine: Nanotechnology, Biology and Medicine 2012, 8, 951-962. (73) Xiong, X.-B.; Huang, Y.; Lu, W.-l.; Zhang, X.; Zhang, H.; Nagai, T.; Zhang, Q. 'Enhanced intracellular delivery and improved antitumor efficacy of doxorubicin by sterically stabilized liposomes modified with a synthetic RGD mimetic.' Journal of Controlled Release 2005, 107, 262-275. (74) Xiong, X.-B.; Huang, Y.; Lu, W.-L.; Zhang, X.; Zhang, H.; Nagai, T.; Zhang, Q. 'Intracellular delivery of doxorubicin with RGD-modified sterically stabilized liposomes for an improved antitumor efficacy: In vitro and in vivo.' Journal of Pharmaceutical Sciences 2005, 94, 1782-1793. (75) Mei, L.; Fu, L.; Shi, K.; Zhang, Q.; Liu, Y.; Tang, J.; Gao, H.; Zhang, Z.; He, Q. 'Increased tumor targeted delivery using a multistage liposome system functionalized with RGD, TAT and cleavable PEG.' International Journal of Pharmaceutics 2014, 468, 26-38. (76) Haubner, R.; Wester, H. J.; Weber, W. A.; Mang, C.; Ziegler, S. I.; Goodman, S. L.; Senekowitsch-Schmidtke, R.; Kessler, H.; Schwaiger, M. 'Noninvasive imaging of αvβ3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography.' Cancer Research 2001, 61, 1781-1785. (77) Maubant, S.; Saint-Dizier, D.; Boutillon, M.; Perron-Sierra, F.; Casara, P. J.; Hickman, J. A.; Tucker, G. C.; Van Obberghen-Schilling, E. 'Blockade of αvβ3 and αvβ5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells.' Blood 2006, 108, 3035-3044. (78) Bloch, S.; Xu, B.; Ye, Y.; Liang, K.; Achilefu, S. In Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2006. (79) Pedchenko, V.; Zent, R.; Hudson, B. G. 'αvβ3 and αvβ5 Integrins Bind Both the Proximal RGD Site and Non-RGD Motifs within Noncollagenous (NC1) Domain of the α3 Chain of Type IV Collagen: IMPLICATION FOR THE MECHANISM OF ENDOTHELIAL CELL ADHESION.' Journal of Biological Chemistry 2004, 279, 2772-2780. (80) Lin, H. Y.; Lansing, L.; Merillon, J. M.; Davis, F. B.; Tang, H. Y.; Shih, A.; Vitrac, X.; Krisa, S.; Keating, T.; Cao, H. J.; Bergh, J.; Quackenbush, S.; Davis, P. J. 'Integrin alphaVbeta3 contains a receptor site for resveratrol.' The FASEB Journal 2006, 20, 1742-1744. (81) Leonard, S. S.; Xia, C.; Jiang, B. H.; Stinefelt, B.; Klandorf, H.; Harris, G. K.; Shi, X. 'Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses.' Biochemical and Biophysical Research Communications 2003, 309, 1017-1026. (82) De La Lastra, C. A.; Villegas, I. 'Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications.' Molecular Nutrition and Food Research 2005, 49, 405-430. (83) Gao, X.; Xu, Y. X.; Janakiraman, N.; Chapman, R. A.; Gautam, S. C. 'Immunomodulatory activity of resveratrol: Suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production.' Biochemical Pharmacology 2001, 62, 1299-1308. (84) Bhat, K. P. L.; Pezzuto, J. M. In Annals of the New York Academy of Sciences, 2002, pp 210-229. (85) Delmas, D.; Jannin, B.; Latruffe, N. 'Resveratrol: Preventing properties against vascular alterations and ageing.' Molecular Nutrition and Food Research 2005, 49, 377-395. (86) Baur, J. A.; Sinclair, D. A. 'Therapeutic potential of resveratrol: The in vivo evidence.' Nature Reviews Drug Discovery 2006, 5, 493-506. (87) Siemann, E.; Creasy, L. 'Concentration of the phytoalexin resveratrol in wine.' American Journal of Enology and Viticulture 1992, 43, 49-52. (88) Liu, B.-l.; Zhang, X.; Zhang, W.; Zhen, H.-n. 'New enlightenment of French paradox: Resveratrol's potential for cancer chemoprevention and anti-cancer therapy.' Cancer Biology & Therapy 2007, 6, 1833-1836. (89) Renaud, S.; de Lorgeril, M. 'Wine, alcohol, platelets, and the French paradox for coronary heart disease.' The Lancet 1992, 339, 1523-1526. (90) Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas, C. F.; Beecher, C. W. W.; Fong, H. H. S.; Farnsworth, N. R.; Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M. 'Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes.' Science 1997, 275, 218-220. (91) Cui, X.; Jin, Y.; Hofseth, A. B.; Pena, E.; Habiger, J.; Chumanevich, A.; Poudyal, D.; Nagarkatti, M.; Nagarkatti, P. S.; Singh, U. P.; Hofseth, L. J. 'Resveratrol suppresses colitis and colon cancer associated with colitis.' Cancer prevention research (Philadelphia, Pa.) 2010, 3, 549-559. (92) Lu, R.; Serrero, G. 'Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells.' Journal of Cellular Physiology 1999, 179, 297-304. (93) Damm, G.; Hao, L.; Ehnert, S.; Blankenstein, A.; Nüssler, A. K.; Knobeloch, D.; Glanemann, M. 'Chemotherapeutic use of Resveratrol on liver cancer cell lines cause damage on primary human hepatocytes.' Z Gastroenterol 2012, 50, P5_11. (94) Shukla, Y.; Singh, R. 'Resveratrol and cellular mechanisms of cancer prevention.' Annals of the New York Academy of Sciences 2011, 1215, 1-8. (95) Kim, T. H.; Shin, Y. J.; Won, A. J.; Lee, B. M.; Choi, W. S.; Jung, J. H.; Chung, H. Y.; Kim, H. S. 'Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.' Biochimica et Biophysica Acta 2014, 1840, 615-625. (96) Osman, A. M.; Bayoumi, H. M.; Al-Harthi, S. E.; Damanhouri, Z. A.; Elshal, M. F. 'Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line.' Cancer Cell International 2012, 12, 47. (97) Huang, F.; Wu, X.-N.; Chen, J. I. E.; Wang, W.-X.; Lu, Z.-F. 'Resveratrol reverses multidrug resistance in human breast cancer doxorubicin-resistant cells.' Experimental and Therapeutic Medicine 2014, 7, 1611-1616. (98) Al-Abd, A. M.; Mahmoud, A. M.; El-Sherbiny, G. A.; El-Moselhy, M. A.; Nofal, S. M.; El-Latif, H. A.; El-Eraky, W. I.; El-Shemy, H. A. 'Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro.' Cell Proliferation 2011, 44, 591-601. (99) Shi, X.-P.; Miao, S.; Wu, Y.; Zhang, W.; Zhang, X.-F.; Ma, H.-Z.; Xin, H.-L.; Feng, J.; Wen, A.-D.; Li, Y. 'Resveratrol Sensitizes Tamoxifen in Antiestrogen-Resistant Breast Cancer Cells with Epithelial-Mesenchymal Transition Features.' International Journal of Molecular Sciences 2013. (100) Chen, L.-C.; Lin, S.-S.; Li, C.-Z.; Hsu, H.-F.; Weng, Y.-J.; Cheng, C.-C. 'Dynamic Structural Transformation of Resveratrol-Modified Stearate Liposomes Led to a Spontaneous Drug Release System.' Journal of the Chinese Chemical Society 2013, 60, 1099-1102. (101) Hortobágyi, G. N. 'Anthracyclines in the Treatment of Cancer.' Drugs 1997, 54, 1-7. (102) Paradise, R. K.; Lauffenburger, D. A.; Van Vliet, K. J. 'Acidic extracellular pH promotes activation of integrin alpha (v) beta (3).' PLoS One 2011, 6, e15746. (103) Cluzel, C.; Saltel, F.; Lussi, J.; Paulhe, F.; Imhof, B. A.; Wehrle-Haller, B. 'The mechanisms and dynamics of (alpha)v(beta)3 integrin clustering in living cells.' Journal of Cell Biology 2005, 171, 383-392. (104) Takagi, J.; Petre, B. M.; Walz, T.; Springer, T. A. 'Global Conformational Rearrangements in Integrin Extracellular Domains in Outside-In and Inside-Out Signaling.' Cell 2002, 110, 599-611. (105) Diaz-Chavez, J.; Fonseca-Sanchez, M. A.; Arechaga-Ocampo, E.; Flores-Perez, A.; Palacios-Rodriguez, Y.; Dominguez-Gomez, G.; Marchat, L. A.; Fuentes-Mera, L.; Mendoza-Hernandez, G.; Gariglio, P.; Lopez-Camarillo, C. 'Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy.' PLoS One 2013, 8, e64378. (106) Marreilha dos Santos, A. P.; Santos, D.; Au, C.; Milatovic, D.; Aschner, M.; Batoréu, M. C. C. 'Antioxidants prevent the cytotoxicity of manganese in RBE4 cells.' Brain Research 2008, 1236, 200-205. (107) Mould, A. P.; Askari, J. A.; Barton, S.; Kline, A. D.; McEwan, P. A.; Craig, S. E.; Humphries, M. J. 'Integrin activation involves a conformational change in the α1 helix of the β subunit A-domain.' Journal of Biological Chemistry 2002, 277, 19800-19805. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51199 | - |
| dc.description.abstract | 以化學藥物進行癌症治療時，如何將藥物精確地送至病灶區域是醫療界全心追求的目標。近年來，可以用於運送藥物的奈米粒子陸續被開發出來，具有標靶功能的奈米傳遞系統不但可以有效毒殺腫瘤細胞，還可以降低對人體其他器官的副作用(如：心血管毒性、嘔吐及掉髮等)。標靶載體的設計通常是藉由修飾可辨認腫瘤細胞表面特定的受器(receptor)的配體(ligand)(例如：抗體、醣分子、小片段胺基酸序列或核酸序列等)，因此能將載體內藥物專一地送到病灶。
過去的文獻指出，白藜蘆醇(resveratrol)可藉由乳癌細胞膜上的αvβ3組合蛋白(integrin)進入細胞，活化ERK1/2的訊息傳遞路徑並調控p53ser15的磷酸化，促使乳癌細胞進行凋亡。此外，其它文獻亦指出白藜蘆醇搭配臨床化療用藥阿黴素(doxorubicin)的使用可提高對乳癌細胞的毒殺能力。因此本篇研究擬利用白藜蘆醇(一種非黃酮類的酚類物質，存在於許多植物中，並具有抗氧化功能)作為標靶乳癌細胞的工具。利用白藜蘆醇－硬脂酸合成分子(由嘉義大學應用化學系鄭建中教授實驗室提供)搭配其他適當的磷脂質製備表面修飾有白藜蘆醇－硬脂酸合成分子之微脂體(resveratrol-modified stearate liposome)，並裝載阿黴素，發展為可調控腫瘤細胞訊息傳遞、增強毒殺能力且具安全性之藥物傳遞系統。首先，我們利用流式細胞儀分析MCF7乳癌細胞上活化態的αvβ3組合蛋白的表現，結果發現在Mn2+處理的情況下活化態v3組合蛋白的表現量有提高。利用Mn2+處理活化細胞表面之αvβ3組合蛋白，觀察到MCF7乳癌細胞攝取不同比例RMS修飾之微脂體能力有差異，以7.5% RMS修飾之微脂體被攝取的程度較高且細胞毒殺能力提升。過去研究指出腫瘤微環境的弱酸性(pH~6.5)會促使αvβ3組合蛋白進行活化，我們模擬腫瘤微環境的條件觀察阿黴素與RMS微脂體的功效，發現弱酸性(pH~6.5)與Mn2+處理之組別一樣毒殺能力有提高，從毒性試驗結果發現裝載阿黴素之表面修飾有白藜蘆醇的微脂體(RMS-liposomal doxorubicin)與相等劑量之游離型阿黴素藥物(free doxorubicin)或裝載阿黴素藥物之微脂體(liposomal doxorubicin)更具有毒殺癌細胞的能力。本研究利用白藜蘆醇具有分子標靶在癌細胞會大量表現之活化態的αvβ3組合蛋白的特性，發展成更專一地的定位腫瘤且兼具功能性及安全性之微脂體藥物傳遞系統。 | zh_TW |
| dc.description.abstract | Chemotherapy is a category of medicine treatment that uses chemical substances and usually delivered via intravenous injection. To make sure that enough drug reaches a tumor, very large quantity of drug might have to be given. Precise delivery of drugs to tumor site thus becomes an important issue. Many studies have been done investigating the effects of nanoparticles in the application of drug delivery. Some of the pharmacological properties of free drugs can be manipulated through the utilization of specially designed nanocarriers. Nanocarriers has a number of advantages in drug delivery, including: (i) provide a shelter that prevent rapid metabolism of drugs in circulation; (ii) improve poor solubility of drugs and increase the bioavailability of drugs; (iii) lead to an intensive accumulation of drugs in tumor site (iv) reduce side-effect of free drugs by site-directing nanocarriers. In the light of the potential offered by nanoparticles, the development of a site-directing nanodrug is a promising approach to improve delivery efficiency and efficacy of drugs.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a stilbenoid and a phytoalexin, found naturally in several plants, which suppresses oxidative damage and is known to have anti-inflammatory, antioxidant, antitumor and immunomodulatory capabilities. Resveratrol was reported to exhibit αvβ3 integrin binding ability, and subsequently induce downstream pathway of extracellular regulated kinases 1 and 2 (ERK1/2) and serine-15-p53 dependent phosphorylation, and finally leading to apoptosis. In addition, several studies have been carried out to explore the synergistic effect of resveratrol and chemotherapy agent (e.g., doxorubicin). In this study, resveratrol-modified stearate (provided by Prof. Chien-Chung Cheng at Department of Applied Chemistry, National Chia-Yi University) was used to prepare resveratrol-modified liposomal doxorubicin (RML/Dox) that possessed capability of targeting αvβ3 integrin on the surface of tumor cells. Our results showed that, at the same drug dosage, resveratrol-modified liposomal doxorubicin demonstrated better efficacy when compare to conventional forms of free drug and liposomal drug. This might be due to the existence of resveratrol that concurrently upregulated downstream apoptosis pathway, resulting in the synergistic effect of doxorubicin chemotherapy and resveratrol treatment on killing breast cancer cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T13:27:17Z (GMT). No. of bitstreams: 1 ntu-104-R02b22044-1.pdf: 2195893 bytes, checksum: 363e43e20ec9ae86318685766b4c14f0 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
謝誌 I 中文摘要 II ABSTRACT III 目錄 V 圖目錄 VIII 表目錄 X 附錄目錄 XI 第一章 緒論 1 1.1 前言 1 1.2 奈米載體(nanocarriers) 2 1.2.1 微脂體(liposome) 3 1.2.2 微脂體的製備 5 1.2.3 微脂體的功能性修飾 6 1.2.4 微脂體與細胞的交互作用 8 1.3 組合蛋白(Integrin) 9 1.3.1 組合蛋白αvβ3在癌症中扮演的角色 10 1.3.2 組合蛋白αvβ3靶向治療(targeting therapy) 11 1.4 白藜蘆醇 (resveratrol) 11 1.4.1 白藜蘆醇的功效 12 1.4.2 白藜蘆醇的抗癌效果 12 1.4.3 白藜蘆醇與抗癌藥物的協同性作用 12 1.5 Doxorubicin (Dox) 13 1.6 研究目的 15 第二章 實驗材料、儀器與方法 16 2.1 實驗藥品 16 2.2 抗體 17 2.3 脂質載體 17 2.4 細胞株 18 2.5 實驗儀器 18 2.6 細胞培養 19 2.6.1 培養條件 19 2.6.2 細胞繼代 19 2.6.3 細胞冷凍 19 2.6.4 細胞解凍 19 2.6.5 細胞計數 20 2.7 流式細胞儀分析 20 2.7.1 Integrin αvβ3活化與偵測 20 2.8 蛋白質膠體電泳分析 21 2.8.1 蛋白質萃取及電泳樣品前處理 21 2.8.2 膠體製備及蛋白質電泳(Electrophoresis) 21 2.8.3 轉印(Electrotransfer) 22 2.8.4 免疫墨點法(Immunoblotting) 22 2.9 微脂體製備與鑑定 23 2.9.1 微脂體製備 23 2.9.2 微脂體鑑定 24 2.10 細胞毒性實驗 24 2.11 細胞攝取實驗(Cellular uptake) 24 第三章 實驗結果 26 3.1 細胞表面αvβ3組合蛋白之鑑定 26 3.2 Doxorubicin細胞毒殺能力 27 3.3 微脂體鑑定 27 3.4 微脂體細胞毒殺能力 28 3.5 細胞表面組合蛋白αvβ3的活化與RMS liposome的效率 29 3.5.1 錳離子(Mn2+)對細胞的影響 29 3.5.2 偵測以錳離子活化的組合蛋白αvβ3 31 3.5.3 偵測以錳離子活化的組合蛋白β3單元 32 3.5.4 錳離子活化的組合蛋白αvβ3與微脂體效率 33 3.5.5 以抗體結合組合蛋白αvβ3可以降低毒殺效率 36 3.6 RMS liposome與細胞死亡之關係 38 第四章 實驗結果與討論 42 附錄 44 參考文獻 46 | |
| dc.language.iso | zh-TW | |
| dc.subject | 藥物傳遞 | zh_TW |
| dc.subject | 組合蛋白αvβ3 | zh_TW |
| dc.subject | 藥物傳遞 | zh_TW |
| dc.subject | 組合蛋白αvβ3 | zh_TW |
| dc.subject | 微脂體 | zh_TW |
| dc.subject | 阿黴素 | zh_TW |
| dc.subject | 白藜蘆醇-硬脂酸合成物 | zh_TW |
| dc.subject | 阿黴素 | zh_TW |
| dc.subject | 白藜蘆醇-硬脂酸合成物 | zh_TW |
| dc.subject | 微脂體 | zh_TW |
| dc.subject | Integrin αvβ3 | en |
| dc.subject | Doxorubicin | en |
| dc.subject | Resveratrol-modified stearate | en |
| dc.subject | Liposome | en |
| dc.subject | Drug delivery | en |
| dc.subject | Integrin αvβ3 | en |
| dc.subject | Doxorubicin | en |
| dc.subject | Resveratrol-modified stearate | en |
| dc.subject | Liposome | en |
| dc.subject | Drug delivery | en |
| dc.title | 藉由白藜蘆醇-硬脂酸合成物發展具標靶αvβ3組合蛋白能力之微脂體型藥物傳遞系統 | zh_TW |
| dc.title | Using resveratrol-modified stearate to develop a liposome-based drug delivery system by targeting integrin αvβ3 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 何佳安(Ja-An Ho) | |
| dc.contributor.oralexamcommittee | 楊家銘(Chia-Min Yang),吳立真(Li-Chen Wu),徐士蘭(Shih-Lan Hsu) | |
| dc.subject.keyword | 組合蛋白αvβ3,藥物傳遞,微脂體,白藜蘆醇-硬脂酸合成物,阿黴素, | zh_TW |
| dc.subject.keyword | Integrin αvβ3,Drug delivery,Liposome,Resveratrol-modified stearate,Doxorubicin, | en |
| dc.relation.page | 62 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-02-16 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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