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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳漢忠 | |
| dc.contributor.author | Chun-Ting Yeh | en |
| dc.contributor.author | 葉俊廷 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:11:31Z | - |
| dc.date.available | 2024-08-28 | |
| dc.date.copyright | 2019-08-28 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-06 | |
| dc.identifier.citation | Adams, S.F., Marsh, E.B., Elmasri, W., Halberstadt, S., Vandecker, S., Sammel, M.D., Bradbury, A.R., Daly, M., Karlan, B., and Rubin, S.C. (2011). A high response rate to liposomal doxorubicin is seen among women with BRCA mutations treated for recurrent epithelial ovarian cancer. Gynecol Oncol 123, 486-491.
Ahn, J., Miura, Y., Yamada, N., Chida, T., Liu, X., Kim, A., Sato, R., Tsumura, R., Koga, Y., Yasunaga, M., et al. (2015). Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer. Biomaterials 39, 23-30. Akhtar, R., Chandel, S., Sarotra, P., and Medhi, B. (2014). Current status of pharmacological treatment of colorectal cancer. World J Gastrointest Oncol 6, 177-183. Allen, T.M., and Martin, F.J. (2004). Advantages of liposomal delivery systems for anthracyclines. Semin Oncol 31, 5-15. Ashok, B., Arleth, L., Hjelm, R.P., Rubinstein, I., and Onyuksel, H. (2004). In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: effects of PEG chain length and PC incorporation. J Pharm Sci 93, 2476-2487. Bardania, H., Tarvirdipour, S., and Dorkoosh, F. (2017). Liposome-targeted delivery for highly potent drugs. Artif Cells Nanomed Biotechnol 45, 1478-1489. Berchuck, A., Kamel, A., Whitaker, R., Kerns, B., Olt, G., Kinney, R., Soper, J.T., Dodge, R., Clarke-Pearson, D.L., Marks, P., et al. (1990). Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50, 4087-4091. Brandt-Rauf, P.W., Pincus, M.R., and Carney, W.P. (1994). The c-erbB-2 protein in oncogenesis: molecular structure to molecular epidemiology. Crit Rev Oncog 5, 313-329. Burger, R.A., Sill, M.W., Monk, B.J., Greer, B.E., and Sorosky, J.I. (2007). Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 25, 5165-5171. Cai, Y., Wang, J., Zhang, L., Wu, D., Yu, D., Tian, X., Liu, J., Jiang, X., Shen, Y., Zhang, L., et al. (2015). Expressions of fatty acid synthase and HER2 are correlated with poor prognosis of ovarian cancer. Med Oncol 32, 391. Carter, J.S., and Downs, L.S., Jr. (2011). Ovarian Cancer Tests and Treatment. Female Patient (Parsippany) 36, 30-35. Chames, P., Van Regenmortel, M., Weiss, E., and Baty, D. (2009). Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 157, 220-233. Chatterjee, K., Zhang, J., Honbo, N., and Karliner, J.S. (2010). Doxorubicin cardiomyopathy. Cardiology 115, 155-162. Chiang, C.J., Lo, W.C., Yang, Y.W., You, S.L., Chen, C.J., and Lai, M.S. (2016). Incidence and survival of adult cancer patients in Taiwan, 2002-2012. J Formos Med Assoc 115, 1076-1088. Chudecka-Glaz, A.M. (2015). ROMA, an algorithm for ovarian cancer. Clin Chim Acta 440, 143-151. Cortez, A.J., Tudrej, P., Kujawa, K.A., and Lisowska, K.M. (2018). Advances in ovarian cancer therapy. Cancer Chemother Pharmacol 81, 17-38. Deen, K.I., Silva, H., Deen, R., and Chandrasinghe, P.C. (2016). Colorectal cancer in the young, many questions, few answers. World J Gastrointest Oncol 8, 481-488. Delavari, A., Mardan, F., Salimzadeh, H., Bishehsari, F., Khosravi, P., Khanehzad, M., Nasseri-Moghaddam, S., Merat, S., Ansari, R., Vahedi, H., et al. (2014). Characteristics of colorectal polyps and cancer; a retrospective review of colonoscopy data in iran. Middle East J Dig Dis 6, 144-150. Deonarain, M.P. (2018). Miniaturised 'antibody'-drug conjugates for solid tumours? Drug Discov Today Technol 30, 47-53. Devouassoux-Shisheboran, M., and Genestie, C. (2015). Pathobiology of ovarian carcinomas. Chin J Cancer 34, 50-55. Duggan, S.T., and Keating, G.M. (2011). Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma. Drugs 71, 2531-2558. Elbayoumi, T.A., and Torchilin, V.P. (2009). Tumor-specific anti-nucleosome antibody improves therapeutic efficacy of doxorubicin-loaded long-circulating liposomes against primary and metastatic tumor in mice. Mol Pharm 6, 246-254. Faller, B.A., and Pandit, T.N. (2011). Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer. Clin Med Insights Oncol 5, 131-144. Fu, Z., Shrubsole, M.J., Smalley, W.E., Wu, H., Chen, Z., Shyr, Y., Ness, R.M., and Zheng, W. (2012). Lifestyle factors and their combined impact on the risk of colorectal polyps. Am J Epidemiol 176, 766-776. Gabizon, A., Catane, R., Uziely, B., Kaufman, B., Safra, T., Cohen, R., Martin, F., Huang, A., and Barenholz, Y. (1994). Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res 54, 987-992. Gabizon, A.A., Lyass, O., Berry, G.J., and Wildgust, M. (2004). Cardiac safety of pegylated liposomal doxorubicin (Doxil/Caelyx) demonstrated by endomyocardial biopsy in patients with advanced malignancies. Cancer Invest 22, 663-669. Gabizon, A.A., Patil, Y., and La-Beck, N.M. (2016). New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy. Drug Resist Updat 29, 90-106. Gewirtz, D.A. (1999). A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 57, 727-741. Gibson, J.M., Alzghari, S., Ahn, C., Trantham, H., and La-Beck, N.M. (2013). The role of pegylated liposomal doxorubicin in ovarian cancer: a meta-analysis of randomized clinical trials. Oncologist 18, 1022-1031. Gordon, A.N., Tonda, M., Sun, S., Rackoff, W., and Doxil Study, I. (2004). Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 95, 1-8. Gorumlu, G., Kucukzeybek, Y., Kemal-Gul, M., Karaca, B., Cosan-Terek, M., Karabulut, B., Sanli, U.A., Akman, L., Ozsaran, A., Dikmen, Y., et al. (2008). Pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients. J BUON 13, 349-352. Grady, W.M., and Carethers, J.M. (2008). Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 135, 1079-1099. Grady, W.M., and Markowitz, S.D. (2015). The molecular pathogenesis of colorectal cancer and its potential application to colorectal cancer screening. Dig Dis Sci 60, 762-772. Green, A.E., and Rose, P.G. (2006). Pegylated liposomal doxorubicin in ovarian cancer. Int J Nanomedicine 1, 229-239. Gulbake, A., Jain, A., Jain, A., Jain, A., and Jain, S.K. (2016). Insight to drug delivery aspects for colorectal cancer. World J Gastroenterol 22, 582-599. Hamilton, G.S. (2015). Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids. Biologicals 43, 318-332. Herlyn, M., Steplewski, Z., Herlyn, D., and Koprowski, H. (1979). Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. Proc Natl Acad Sci U S A 76, 1438-1442. Hilger, R.A., Richly, H., Grubert, M., Oberhoff, C., Strumberg, D., Scheulen, M.E., and Seeber, S. (2005). Pharmacokinetics (PK) of a liposomal encapsulated fraction containing doxorubicin and of doxorubicin released from the liposomal capsule after intravenous infusion of Caelyx/Doxil. Int J Clin Pharmacol Ther 43, 588-589. Hogdall, E.V., Christensen, L., Kjaer, S.K., Blaakaer, J., Bock, J.E., Glud, E., Norgaard-Pedersen, B., and Hogdall, C.K. (2003). Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study. Cancer 98, 66-73. Hurwitz, H.I., Fehrenbacher, L., Hainsworth, J.D., Heim, W., Berlin, J., Holmgren, E., Hambleton, J., Novotny, W.F., and Kabbinavar, F. (2005). Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23, 3502-3508. Immordino, M.L., Dosio, F., and Cattel, L. (2006). Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1, 297-315. Imrich, S., Hachmeister, M., and Gires, O. (2012). EpCAM and its potential role in tumor-initiating cells. Cell Adh Migr 6, 30-38. Iqbal, N., and Iqbal, N. (2014). Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int 2014, 852748. Jain, A., and Jain (2018). Advances in Tumor Targeted Liposomes. Curr Mol Med 18, 44-57. Jain, V., Jain, S., and Mahajan, S.C. (2015). Nanomedicines based drug delivery systems for anti-cancer targeting and treatment. Curr Drug Deliv 12, 177-191. Kawauchi, T. (2012). Cell adhesion and its endocytic regulation in cell migration during neural development and cancer metastasis. Int J Mol Sci 13, 4564-4590. Klotz, D.M., Nelson, S.A., Kroboth, K., Newton, I.P., Radulescu, S., Ridgway, R.A., Sansom, O.J., Appleton, P.L., and Nathke, I.S. (2012). The microtubule poison vinorelbine kills cells independently of mitotic arrest and targets cells lacking the APC tumour suppressor more effectively. J Cell Sci 125, 887-895. Koutras, A.K., and Evans, T.R. (2008). The epidermal growth factor receptor family in breast cancer. Onco Targets Ther 1, 5-19. Krause, D.S., and Van Etten, R.A. (2005). Tyrosine kinases as targets for cancer therapy. N Engl J Med 353, 172-187. Kuan, II, Liang, K.H., Wang, Y.P., Kuo, T.W., Meir, Y.J., Wu, S.C., Yang, S.C., Lu, J., and Wu, H.C. (2017). EpEX/EpCAM and Oct4 or Klf4 alone are sufficient to generate induced pluripotent stem cells through STAT3 and HIF2alpha. Sci Rep 7, 41852. Kurman, R.J., and Shih Ie, M. (2010). The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 34, 433-443. Leoz, M.L., Carballal, S., Moreira, L., Ocana, T., and Balaguer, F. (2015). The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet 8, 95-107. Li, D. (2018). Recent advances in colorectal cancer screening. Chronic Dis Transl Med 4, 139-147. Li, J., Liu, H., Yu, J., and Yu, H. (2015). Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factor beta signaling in HCT116 colon cancer cells. Mol Med Rep 12, 192-198. Li, M., Du, C., Guo, N., Teng, Y., Meng, X., Sun, H., Li, S., Yu, P., and Galons, H. (2019). Composition design and medical application of liposomes. Eur J Med Chem 164, 640-653. Liang, K.H., Tso, H.C., Hung, S.H., Kuan, II, Lai, J.K., Ke, F.Y., Chuang, Y.T., Liu, I.J., Wang, Y.P., Chen, R.H., et al. (2018). Extracellular domain of EpCAM enhances tumor progression through EGFR signaling in colon cancer cells. Cancer Lett 433, 165-175. Liao, M.Y., Lai, J.K., Kuo, M.Y., Lu, R.M., Lin, C.W., Cheng, P.C., Liang, K.H., and Wu, H.C. (2015). An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer. Oncotarget 6, 24947-24968. Lin, C.W., Liao, M.Y., Lin, W.W., Wang, Y.P., Lu, T.Y., and Wu, H.C. (2012). Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer. J Biol Chem 287, 39449-39459. Lowe, K.A., Chia, V.M., Taylor, A., O'Malley, C., Kelsh, M., Mohamed, M., Mowat, F.S., and Goff, B. (2013). An international assessment of ovarian cancer incidence and mortality. Gynecol Oncol 130, 107-114. Lu, R.M., Chang, Y.L., Chen, M.S., and Wu, H.C. (2011). Single chain anti-c-Met antibody conjugated nanoparticles for in vivo tumor-targeted imaging and drug delivery. Biomaterials 32, 3265-3274. Lu, T.Y., Lu, R.M., Liao, M.Y., Yu, J., Chung, C.H., Kao, C.F., and Wu, H.C. (2010). Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem 285, 8719-8732. Luo, H., Xu, X., Ye, M., Sheng, B., and Zhu, X. (2018). The prognostic value of HER2 in ovarian cancer: A meta-analysis of observational studies. PLoS One 13, e0191972. Makaraviciute, A., Jackson, C.D., Millner, P.A., and Ramanaviciene, A. (2016). Considerations in producing preferentially reduced half-antibody fragments. J Immunol Methods 429, 50-56. Mamot, C., Drummond, D.C., Noble, C.O., Kallab, V., Guo, Z., Hong, K., Kirpotin, D.B., and Park, J.W. (2005). Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res 65, 11631-11638. Mano, M. (2006). Vinorelbine in the management of breast cancer: New perspectives, revived role in the era of targeted therapy. Cancer Treat Rev 32, 106-118. Markman, M., Moon, J., Wilczynski, S., Lopez, A.M., Rowland, K.M., Jr., Michelin, D.P., Lanzotti, V.J., Anderson, G.L., and Alberts, D.S. (2010). Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin in recurrent ovarian cancer: final survival results of a SWOG (S0200) phase 3 randomized trial. Gynecol Oncol 116, 323-325. Maso, K., Grigoletto, A., Vicent, M.J., and Pasut, G. (2019). Molecular platforms for targeted drug delivery. Int Rev Cell Mol Biol 346, 1-50. Mencoboni, M., Filiberti, R.A., Taveggia, P., Del Corso, L., Del Conte, A., Covesnon, M.G., Puccetti, C., Donati, S., Auriati, L., Amoroso, D., et al. (2017). Safety of First-line Chemotherapy with Metronomic Single-agent Oral Vinorelbine in Elderly Patients with NSCLC. Anticancer Res 37, 3189-3194. Milla, P., Dosio, F., and Cattel, L. (2012). PEGylation of proteins and liposomes: a powerful and flexible strategy to improve the drug delivery. Curr Drug Metab 13, 105-119. Mittica, G., Ghisoni, E., Giannone, G., Genta, S., Aglietta, M., Sapino, A., and Valabrega, G. (2018). PARP Inhibitors in Ovarian Cancer. Recent Pat Anticancer Drug Discov 13, 392-410. Momenimovahed, Z., Tiznobaik, A., Taheri, S., and Salehiniya, H. (2019). Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health 11, 287-299. Nelson, A.L. (2010). Antibody fragments: hope and hype. MAbs 2, 77-83. Ohhara, Y., Fukuda, N., Takeuchi, S., Honma, R., Shimizu, Y., Kinoshita, I., and Dosaka-Akita, H. (2016). Role of targeted therapy in metastatic colorectal cancer. World J Gastrointest Oncol 8, 642-655. Ohradanova-Repic, A., Nogueira, E., Hartl, I., Gomes, A.C., Preto, A., Steinhuber, E., Muhlgrabner, V., Repic, M., Kuttke, M., Zwirzitz, A., et al. (2018). Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells. Nanomedicine 14, 123-130. Olusanya, T.O.B., Haj Ahmad, R.R., Ibegbu, D.M., Smith, J.R., and Elkordy, A.A. (2018). Liposomal Drug Delivery Systems and Anticancer Drugs. Molecules 23. Pisano, C., Cecere, S.C., Di Napoli, M., Cavaliere, C., Tambaro, R., Facchini, G., Scaffa, C., Losito, S., Pizzolorusso, A., and Pignata, S. (2013). Clinical trials with pegylated liposomal Doxorubicin in the treatment of ovarian cancer. J Drug Deliv 2013, 898146. Quintero-Hernandez, V., Juarez-Gonzalez, V.R., Ortiz-Leon, M., Sanchez, R., Possani, L.D., and Becerril, B. (2007). The change of the scFv into the Fab format improves the stability and in vivo toxin neutralization capacity of recombinant antibodies. Mol Immunol 44, 1307-1315. Rader, C. (2009). Overview on concepts and applications of Fab antibody fragments. Curr Protoc Protein Sci Chapter 6, Unit 6 9. Rafiyath, S.M., Rasul, M., Lee, B., Wei, G., Lamba, G., and Liu, D. (2012). Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis. Exp Hematol Oncol 1, 10. Reid, B.M., Permuth, J.B., and Sellers, T.A. (2017). Epidemiology of ovarian cancer: a review. Cancer Biol Med 14, 9-32. Riaz, M.K., Riaz, M.A., Zhang, X., Lin, C., Wong, K.H., Chen, X., Zhang, G., Lu, A., and Yang, Z. (2018). Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review. Int J Mol Sci 19. Richards, D.A. (2018). Exploring alternative antibody scaffolds: Antibody fragments and antibody mimics for targeted drug delivery. Drug Discov Today Technol 30, 35-46. Rivankar, S. (2014). An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther 10, 853-858. Rothlisberger, D., Honegger, A., and Pluckthun, A. (2005). Domain interactions in the Fab fragment: a comparative evaluation of the single-chain Fv and Fab format engineered with variable domains of different stability. J Mol Biol 347, 773-789. Rudnick, S.I., Lou, J., Shaller, C.C., Tang, Y., Klein-Szanto, A.J., Weiner, L.M., Marks, J.D., and Adams, G.P. (2011). Influence of affinity and antigen internalization on the uptake and penetration of Anti-HER2 antibodies in solid tumors. Cancer Res 71, 2250-2259. Safra, T., Groshen, S., Jeffers, S., Tsao-Wei, D.D., Zhou, L., Muderspach, L., Roman, L., Morrow, C.P., Burnett, A., and Muggia, F.M. (2001). Treatment of patients with ovarian carcinoma with pegylated liposomal doxorubicin: analysis of toxicities and predictors of outcome. Cancer 91, 90-100. Salani, R., Backes, F.J., Fung, M.F., Holschneider, C.H., Parker, L.P., Bristow, R.E., and Goff, B.A. (2011). Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol 204, 466-478. Sawant, R.R., and Torchilin, V.P. (2012). Challenges in development of targeted liposomal therapeutics. AAPS J 14, 303-315. Schnell, U., Cirulli, V., and Giepmans, B.N. (2013). EpCAM: structure and function in health and disease. Biochim Biophys Acta 1828, 1989-2001. Schoch, A., Kettenberger, H., Mundigl, O., Winter, G., Engert, J., Heinrich, J., and Emrich, T. (2015). Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics. Proc Natl Acad Sci U S A 112, 5997-6002. Scott, C.L., Swisher, E.M., and Kaufmann, S.H. (2015). Poly (ADP-ribose) polymerase inhibitors: recent advances and future development. J Clin Oncol 33, 1397-1406. Seimetz, D., Lindhofer, H., and Bokemeyer, C. (2010). Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev 36, 458-467. Serrano-Olvera, A., Duenas-Gonzalez, A., Gallardo-Rincon, D., Candelaria, M., and De la Garza-Salazar, J. (2006). Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer. Cancer Treat Rev 32, 180-190. Shade, C.W. (2016). Liposomes as Advanced Delivery Systems for Nutraceuticals. Integr Med (Encinitas) 15, 33-36. Siontorou, C.G. (2013). Nanobodies as novel agents for disease diagnosis and therapy. Int J Nanomedicine 8, 4215-4227. Sriraman, S.K., Aryasomayajula, B., and Torchilin, V.P. (2014). Barriers to drug delivery in solid tumors. Tissue Barriers 2, e29528. Steinke, V., Engel, C., Buttner, R., Schackert, H.K., Schmiegel, W.H., and Propping, P. (2013). Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. Dtsch Arztebl Int 110, 32-38. Stintzing, S. (2014). Management of colorectal cancer. F1000Prime Rep 6, 108. Stylianopoulos, T., Munn, L.L., and Jain, R.K. (2018). Reengineering the Physical Microenvironment of Tumors to Improve Drug Delivery and Efficacy: From Mathematical Modeling to Bench to Bedside. Trends Cancer 4, 292-319. Tacar, O., Sriamornsak, P., and Dass, C.R. (2013). Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65, 157-170. Tambaro, R., Greggi, S., Iaffaioli, R.V., Rossi, A., Pisano, C., Manzione, L., Ferrari, E., Di Maio, M., Iodice, F., Casella, G., et al. (2003). An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer. Ann Oncol 14, 1406-1411. Tetin, S.Y., Prendergast, F.G., and Venyaminov, S.Y. (2003). Accuracy of protein secondary structure determination from circular dichroism spectra based on immunoglobulin examples. Anal Biochem 321, 183-187. Thorn, C.F., Oshiro, C., Marsh, S., Hernandez-Boussard, T., McLeod, H., Klein, T.E., and Altman, R.B. (2011). Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics 21, 440-446. Torchilin, V.P. (2005). Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4, 145-160. Torre, L.A., Trabert, B., DeSantis, C.E., Miller, K.D., Samimi, G., Runowicz, C.D., Gaudet, M.M., Jemal, A., and Siegel, R.L. (2018). Ovarian cancer statistics, 2018. CA Cancer J Clin 68, 284-296. Tuefferd, M., Couturier, J., Penault-Llorca, F., Vincent-Salomon, A., Broet, P., Guastalla, J.P., Allouache, D., Combe, M., Weber, B., Pujade-Lauraine, E., et al. (2007). HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS One 2, e1138. van Vught, R., Pieters, R.J., and Breukink, E. (2014). Site-specific functionalization of proteins and their applications to therapeutic antibodies. Comput Struct Biotechnol J 9, e201402001. Vetter, M.H., and Hays, J.L. (2018). Use of Targeted Therapeutics in Epithelial Ovarian Cancer: A Review of Current Literature and Future Directions. Clin Ther 40, 361-371. Vugmeyster, Y., Entrican, C.A., Joyce, A.P., Lawrence-Henderson, R.F., Leary, B.A., Mahoney, C.S., Patel, H.K., Raso, S.W., Olland, S.H., Hegen, M., et al. (2012). Pharmacokinetic, biodistribution, and biophysical profiles of TNF nanobodies conjugated to linear or branched poly(ethylene glycol). Bioconjug Chem 23, 1452-1462. Wang, C.X., Li, C.L., Zhao, X., Yang, H.Y., Wei, N., Li, Y.H., Zhang, L., and Zhang, L. (2010). [Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride]. Yao Xue Xue Bao 45, 1565-1569. White, A., Joseph, D., Rim, S.H., Johnson, C.J., Coleman, M.P., and Allemani, C. (2017). Colon cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer 123 Suppl 24, 5014-5036. Winter, M.J., Nagtegaal, I.D., van Krieken, J.H., and Litvinov, S.V. (2003). The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. Am J Pathol 163, 2139-2148. Wolfram, J., Suri, K., Yang, Y., Shen, J., Celia, C., Fresta, M., Zhao, Y., Shen, H., and Ferrari, M. (2014). Shrinkage of pegylated and non-pegylated liposomes in serum. Colloids Surf B Biointerfaces 114, 294-300. Wolpin, B.M., and Mayer, R.J. (2008). Systemic treatment of colorectal cancer. Gastroenterology 134, 1296-1310. Wu, C.H., Kuo, Y.H., Hong, R.L., and Wu, H.C. (2015). alpha-Enolase-binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer. Sci Transl Med 7, 290ra291. Xing, M., Yan, F., Yu, S., and Shen, P. (2015). Efficacy and Cardiotoxicity of Liposomal Doxorubicin-Based Chemotherapy in Advanced Breast Cancer: A Meta-Analysis of Ten Randomized Controlled Trials. PLoS One 10, e0133569. Zahednezhad, F., Saadat, M., Valizadeh, H., Zakeri-Milani, P., and Baradaran, B. (2019). Liposome and immune system interplay: Challenges and potentials. J Control Release 305, 194-209. Zhai, J., Scoble, J.A., Li, N., Lovrecz, G., Waddington, L.J., Tran, N., Muir, B.W., Coia, G., Kirby, N., Drummond, C.J., et al. (2015). Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity. Nanoscale 7, 2905-2913. Zhang, M., Zhuang, G., Sun, X., Shen, Y., Zhao, A., and Di, W. (2015). Risk prediction model for epithelial ovarian cancer using molecular markers and clinical characteristics. J Ovarian Res 8, 67. Zhang, Y., Chen, Z., and Li, J. (2017). The current status of treatment for colorectal cancer in China: A systematic review. Medicine (Baltimore) 96, e8242. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78676 | - |
| dc.description.abstract | HER2蛋白質是EGFR酪氨酸激酶受體家族之一，其在細胞度過度表現在腫瘤細胞增殖和轉移中扮演重要作用。許多卵巢癌患者都具有極高HER2蛋白質的表達，同時伴隨不良的預後。儘管臨床上對於卵巢癌患者的治療多為傳統手術切除或合併化療，但大多數的患者在五年內會因為產生抗藥性而復發，於是目前的藥物開發研究主要著重在如何利用標靶治療的方式有效解決抗藥性。
上皮細胞粘附分子（EpCAM）是一種穿膜醣蛋白，其在結腸癌患者中具有高表達現象，目前上皮細胞粘附分子的細胞外結構（EpEX）已知會促進結腸癌細胞增殖。透過標靶治療的方式，可以避免化療藥物對正常細胞的損害並提升化療藥物的治療效率。 在本研究中，我們運用先前由噬菌體展示技術挑選出與HER2或EpEX專一性結合的抗原呈現片段（Fab），接著透過酵素連結免疫吸附分析法（ELISA）和免疫螢光染色證實它們各自的專一性與結合強度。我們進而將HER2或EpEX抗體結合區片段接於微脂體藥物之外膜，發現HER2或EpEX抗體結合區片段皆可提升微脂體藥物對細胞的結合能力與吞噬作用。最後，我們用接上抗原呈現片段的微脂體藥物運用於治療異體移植免疫缺陷小鼠，並比較帶有標靶的微脂體藥物與一般微脂體藥物兩者之療效與存活率，發現帶有抗原呈現片段的微脂體藥物具有較佳的存活率，且結合不同種類的微脂體藥物有更好的療效。綜合上述結果，HER2與EpEX抗原呈現片段可應用於標靶藥物傳輸系統，透過其對腫瘤細胞的高專一性與對生物體的低毒性之兩大優勢，可望提升癌症患者的整體存活率。 | zh_TW |
| dc.description.abstract | HER2 belongs to EGFR tyrosine kinase receptor family, the overexpression of HER2 plays an important role in tumor cell proliferation and metastasis. Many ovarian cancer patients have a high expression level of HER2 and are associated with poor prognosis. Although the combination of traditional surgery and chemotherapy is commonly used for the treatment of ovarian cancer patients, most of the patients would relapse within five years because of drug resistance. Therefore, many targeted therapies have been developed to solve drug resistance and improve the patient’s outcome.
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein which is frequently overexpressed in colon cancer patients, and the extracellular domain of EpCAM (EpEX) is associated with colon cancer cell proliferation. Through treating targeted therapies to patients with cancer, the damage caused by chemo drugs can be avoided, and the therapeutic efficacy of chemo drugs can be promoted as well. In this study, we synthesized anti-HER2 Fab and anti-EpEX Fab which was selected by phage display technology. The specificity and binding affinity of anti-HER2 or anti-EpEX Fab were confirmed by ELISA and immunofluorescence. Next, we found that the conjugation of anti-HER2 or anti-EpEX Fab onto liposomal drugs could effectively improve the binding and targeting ability of liposomal drugs to cancer cell line. Eventually, in NOD/SCID tumor-bearing mice model, targeting liposomal drugs and non-targeting liposomal drugs were used to evaluate the therapeutic efficacy and the survival rate. The results revealed that Fab-conjugated liposomal drugs could prolong the survival rate. Furthermore, the combination of different liposomal drugs can harvested the better therapeutic efficacy. In summary, both anti-HER2 Fab and anti-EpEX Fab can be applied to targeting drug delivery system. With the advantages of high specificity and low cytotoxicity, anti-HER2 Fab and anti-EpEX Fab have the potential to prolong the survival of patients. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:11:31Z (GMT). No. of bitstreams: 1 ntu-108-R05444003-1.pdf: 2571376 bytes, checksum: 0e4f69fa881c9c8fcbe7686cf90be889 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 誌謝-I
中文摘要-II Abstract-III Contents-V Content of figures-IX List of abbreviations-XI Introduction-1 1.1 Epidemiology of colorectal cancer-1 1.2 Pathogenesis of colorectal cancer-2 1.3 Treatment of colorectal cancer-3 1.4 Introduction of EpCAM and EpEX-4 1.5 Epidemiology of ovarian cancer-6 1.6 Pathogenesis of ovarian cancer-7 1.7 Treatment of ovarian cancer-7 1.8 Introduction of HER2-10 1.9 Anti-cancer drug delivery system-10 1.10 Doxorubicin-12 1.11 Vinorelbine-13 1.12 Fab fragments-14 Materials and Methods-17 2.1 Cell lines and cell culture conditions-17 2.2 Generation of anti-HER2 Fab and anti-EpEX Fab-17 2.3 Western blotting-18 2.4 Binding affinity analysis by ELISA-19 2.5 Internalization ability of anti-HER2 Fab and anti-EpEX Fab-20 2.6 Flow cytometric analysis-21 2.7 PEGylation of liposomal drugs-21 2.8 Synthesis of Fab-conjugated liposomal drugs-22 2.9 Binding ability analysis of anti-HER2 Fab-LD and anti-EpEX Fab-LD-23 2.10 Internalization analysis of anti-EpEX Fab-LD and anti-HER2 Fab-LD-23 2.11 Cell viability analysis of anti-EpEX Fab-LD or anti-HER2 Fab-LD-23 2.12 In vivo tumor targeted therapeutic studies of Fab-conjugated liposomal doxorubicin-24 2.13 Therapeutic potential of combination therapy using Fab-conjugated liposomal doxorubicin and Fab-conjugated liposomal vinorelbine-25 2.14 Statistical analysis-26 Results-27 3.1 Expression and purification of different anti-HER2 Fab fragments.-27 3.2 Evaluation of the binding affinity of anti-HER2 Fabs.-27 3.3 Evaluation of the internalization ability of anti-HER2 Fab.-28 3.4 Binding affinity was maintained after PEGylation with DSPE-PEG (2000) Maleimide.-29 3.5 PEGylation of anti-HER2 Fab with maleimide-PEG-DSPE (2000).-29 3.6 Anti-HER2 Fab conjugation enhanced the liposomal drug delivery and cytotoxic effect.-30 3.7 Anti-HER2 Fab-LD prolongs the survival of human ovarian cancer xenograft mice.-31 3.8 Anti-HER2 Fab enhanced the cytotoxic effect of liposomal vinorelbine (sLV) to human ovarian cancer cells in vitro-32 3.9 Combination of anti-HER2 Fab-LD and anti-HER2 Fab-sLV improve the therapeutic efficacy in human ovarian cancer.-33 3.10 Expression and purification of different anti-EpEX Fab.-34 3.11 Evaluation of the binding affinity of anti-EpEX Fab.-35 3.12 Evaluation of the internalization ability of anti-EpEX Fab.-36 3.13 PEGylation of anti-EpEX Fab with maleimide-PEG-DSPE (2000).-36 3.14 Enhancement of liposomal drug delivery and cytotoxic effect in vitro by anti-EpEX Fab.-37 3.15 Therapy efficacy of anti-EpEX Fab-LD of human colon cancer xenograft mice.-39 3.16 Anti-EpEX Fab enhance the liposomal vinorelbine cytotoxic effect to human colon cancer cell in vitro-40 3.17 Therapeutic efficacy of anti-EpEX Fab-LD combines anti-EpEX Fab-sLV in human colon cancer xenograft.-40 Discussion-42 Figure-50 References-67 | |
| dc.language.iso | en | |
| dc.subject | 抗原呈現片段 | zh_TW |
| dc.subject | EpEX | zh_TW |
| dc.subject | EpCAM | zh_TW |
| dc.subject | HER2 | zh_TW |
| dc.subject | 溫諾平 | zh_TW |
| dc.subject | 阿黴素 | zh_TW |
| dc.subject | 微脂體 | zh_TW |
| dc.subject | 藥物傳輸系統 | zh_TW |
| dc.subject | 結腸癌 | zh_TW |
| dc.subject | 卵巢癌 | zh_TW |
| dc.subject | EpEX | en |
| dc.subject | HER2 | en |
| dc.subject | Fab | en |
| dc.subject | colon cancer | en |
| dc.subject | EpCAM | en |
| dc.subject | vinorelbine | en |
| dc.subject | doxorubicin | en |
| dc.subject | liposome | en |
| dc.subject | drug delivery system | en |
| dc.subject | antigen-binding fragment | en |
| dc.subject | ovarian cancer | en |
| dc.title | 研發Fab抗體片段嵌合微脂體藥物運用於抗癌標靶藥物傳輸 | zh_TW |
| dc.title | Development of Fab-conjugated liposomal drugs for cancer targeting drug delivery | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李文山,蕭培文,王逸平 | |
| dc.subject.keyword | 結腸癌,卵巢癌,抗原呈現片段,藥物傳輸系統,微脂體,阿黴素,溫諾平,HER2,EpCAM,EpEX, | zh_TW |
| dc.subject.keyword | HER2,EpCAM,EpEX,colon cancer,ovarian cancer,antigen-binding fragment,drug delivery system,liposome,doxorubicin,vinorelbine,Fab, | en |
| dc.relation.page | 80 | |
| dc.identifier.doi | 10.6342/NTU201902180 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-08-06 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| dc.date.embargo-lift | 2024-08-28 | - |
| 顯示於系所單位： | 病理學科所 | |
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