請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56393
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳青周(Ching-Chow Chen) | |
dc.contributor.author | Li-Yu Chen | en |
dc.contributor.author | 陳力宇 | zh_TW |
dc.date.accessioned | 2021-06-16T05:26:30Z | - |
dc.date.available | 2019-10-15 | |
dc.date.copyright | 2014-10-15 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-14 | |
dc.identifier.citation | Aparicio, L. A., Valladares, M., et al. (2012). 'Biological influence of Hakai in cancer: a 10-year review'. Cancer metastasis reviews 31(1-2):375-386.
Bean, J., Riely, G. J., et al. (2008). 'Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma'. Clinical cancer research : an official journal of the American Association for Cancer Research 14(22):7519-7525. Bird, A. (2002). 'DNA methylation patterns and epigenetic memory'. Genes & development 16(1):6-21. Blakely, C. M. and Bivona, T. G. (2012). 'Resiliency of lung cancers to EGFR inhibitor treatment unveiled, offering opportunities to divide and conquer EGFR inhibitor resistance'. Cancer discovery 2(10):872-875. Bolden, Jessica E., Peart, Melissa J., et al. (2006). 'Anticancer activities of histone deacetylase inhibitors'. Nature reviews. Drug discovery 5(9):769-784. Brambilla, E., Travis, W. D., et al. (2001). 'The new World Health Organization classification of lung tumours'. The European respiratory journal 18(6):1059-1068. Brose, M. S., Volpe, P., et al. (2002). 'BRAF and RAS mutations in human lung cancer and melanoma'. Cancer research 62(23):6997-7000. Bruce, W. R. and Van Der Gaag, H. (1963). 'A QUANTITATIVE ASSAY FOR THE NUMBER OF MURINE LYMPHOMA CELLS CAPABLE OF PROLIFERATION IN VIVO'. Nature 199:79-80. Chan, K. K., Oza, A. M., et al. (2003). 'The statins as anticancer agents'. Clinical cancer research : an official journal of the American Association for Cancer Research 9(1):10-19. Charafe-Jauffret, E., Monville, F., et al. (2008). 'Cancer stem cells in breast: current opinion and future challenges'. Pathobiology : journal of immunopathology, molecular and cellular biology 75(2):75-84. Chen, J. B., Chern, T. R., et al. (2013a). 'Design and synthesis of dual-action inhibitors targeting histone deacetylases and 3-hydroxy-3-methylglutaryl coenzyme A reductase for cancer treatment'. Journal of medicinal chemistry 56(9):3645-3655. Chen, J., Bi, H., et al. (2013b). 'Atorvastatin overcomes gefitinib resistance in KRAS mutant human non-small cell lung carcinoma cells'. Cell death & disease 4:e814. Chen, J., Hou, J., et al. (2012). 'Atorvastatin synergizes with IFN-gamma in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity'. European journal of pharmacology 682(1-3):161-170. Chen, Y. T., Chen, Y. F., et al. (2013c). 'Microtubule-associated histone deacetylase 6 supports the calcium store sensor STIM1 in mediating malignant cell behaviors'. Cancer research 73(14):4500-4509. Clevers, H. (2011). 'The cancer stem cell: premises, promises and challenges'. Nature medicine 17(3):313-319. Costa, D. B., Schumer, S. T., et al. (2008). 'Differential responses to erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancers with acquired resistance to gefitinib carrying the L747S or T790M secondary mutations'. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 26(7):1182-1184; author reply 1184-1186. De Ruijter, Annemieke J M, van Gennip, Albert H, et al. (2003). 'Histone deacetylases (HDACs): characterization of the classical HDAC family'. Biochem. J. 370(3):737-749. Demierre, Marie-France, Higgins, Peter D. R., et al. (2005). 'Statins and cancer prevention'. Nature reviews. Cancer 5(12):930-942. Engelman, J. A., Zejnullahu, K., et al. (2007). 'MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling'. Science (New York, N.Y.) 316(5827):1039-1043. Finnin, M. S., Donigian, J. R., et al. (1999). 'Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors'. Nature 401(6749):188-193. Fodde, R. and Brabletz, T. (2007). 'Wnt/beta-catenin signaling in cancer stemness and malignant behavior'. Current opinion in cell biology 19(2):150-158. Frederick, B. A., Helfrich, B. A., et al. (2007). 'Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma'. Molecular cancer therapeutics 6(6):1683-1691. Gottlicher, M., Minucci, S., et al. (2001). 'Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells'. The EMBO journal 20(24):6969-6978. Grego-Bessa, J., Diez, J., et al. (2004). 'Notch and epithelial-mesenchyme transition in development and tumor progression: another turn of the screw'. Cell cycle (Georgetown, Tex.) 3(6):718-721. Gupta, P. B., Onder, T. T., et al. (2009). 'Identification of selective inhibitors of cancer stem cells by high-throughput screening'. Cell 138(4):645-659. Haslinger-Loffler, Bettina (2008). 'Multiple effects of HMG-CoA reductase inhibitors (statins) besides their lipid-lowering function'. Kidney Int 74(5):553-555. Huber, M. A., Kraut, N., et al. (2005). 'Molecular requirements for epithelial-mesenchymal transition during tumor progression'. Current opinion in cell biology 17(5):548-558. Hynes, N. E. and Lane, H. A. (2005). 'ERBB receptors and cancer: the complexity of targeted inhibitors'. Nature reviews. Cancer 5(5):341-354. Itamochi, H. (2010). 'Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action'. World journal of biological chemistry 1(7):209-220. Jackson, S. M., Ericsson, J., et al. (1997). 'Signaling molecules derived from the cholesterol biosynthetic pathway'. Sub-cellular biochemistry 28:1-21. Jaggupilli, A. and Elkord, E. (2012). 'Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity'. Clinical & developmental immunology 2012:708036. Jenuwein, T. and Allis, C. D. (2001). 'Translating the histone code'. Science (New York, N.Y.) 293(5532):1074-1080. Johnstone, Ricky W. (2002). 'Histone-deacetylase inhibitors: novel drugs for the treatment of cancer'. Nature reviews. Drug discovery 1(4):287-299. Kaartinen, V., Voncken, J. W., et al. (1995). 'Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction'. Nature genetics 11(4):415-421. Karhadkar, S. S., Bova, G. S., et al. (2004). 'Hedgehog signalling in prostate regeneration, neoplasia and metastasis'. Nature 431(7009):707-712. Kawano, O., Sasaki, H., et al. (2006). 'PIK3CA mutation status in Japanese lung cancer patients'. Lung cancer (Amsterdam, Netherlands) 54(2):209-215. Konishi, J., Kawaguchi, K. S., et al. (2007). 'Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers'. Cancer research 67(17):8051-8057. Kris, M. G., Natale, R. B., et al. (2003). 'Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial'. JAMA : the journal of the American Medical Association 290(16):2149-2158. Kurtze, Sonnemann, et al. (2011). 'KRAS-mutated non-small cell lung cancer cells are responsive to either co-treatment with erlotinib or gefitinib and histone deacetylase inhibitors or single treatment with lapatinib'. Oncology Reports 25(4):1021-1029. Lapidot, T., Sirard, C., et al. (1994). 'A cell initiating human acute myeloid leukaemia after transplantation into SCID mice'. Nature 367(6464):645-648. Leung, E. L., Fiscus, R. R., et al. (2010). 'Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties'. PloS one 5(11):e14062. Lin, Y. C., Lin, J. H., et al. (2008). 'Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2'. Cancer research 68(7):2375-2383. Loprevite, M., Tiseo, M., et al. (2005). 'In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines'. Oncology research 15(1):39-48. Lynch, T. J., Bell, D. W., et al. (2004). 'Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib'. The New England journal of medicine 350(21):2129-2139. Makino, S. (1956). 'Further evidence favoring the concept of the stem cell in ascites tumors of rats'. Annals of the New York Academy of Sciences 63(5):818-830. Mani, S. A., Guo, W., et al. (2008). 'The epithelial-mesenchymal transition generates cells with properties of stem cells'. Cell 133(4):704-715. Margueron, R., Trojer, P., et al. (2005). 'The key to development: interpreting the histone code?'. Current opinion in genetics & development 15(2):163-176. Markowitz, S., Wang, J., et al. (1995). 'Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability'. Science (New York, N.Y.) 268(5215):1336-1338. Marks, J. L., Broderick, S., et al. (2008). 'Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma'. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 3(2):111-116. Marks, Paul A., Rifkind, Richard A., et al. (2001). 'Histone deacetylases and cancer: causes and therapies'. Nature reviews. Cancer 1(3):194-202. Minucci, S. and Pelicci, P. G. (2006). 'Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer'. Nature reviews. Cancer 6(1):38-51. Nakayama, J., Rice, J. C., et al. (2001). 'Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly'. Science (New York, N.Y.) 292(5514):110-113. Okamoto, W., Okamoto, I., et al. (2010). 'TAK-701, a humanized monoclonal antibody to hepatocyte growth factor, reverses gefitinib resistance induced by tumor-derived HGF in non-small cell lung cancer with an EGFR mutation'. Molecular cancer therapeutics 9(10):2785-2792. Palacios, F., Tushir, J. S., et al. (2005). 'Lysosomal targeting of E-cadherin: a unique mechanism for the down-regulation of cell-cell adhesion during epithelial to mesenchymal transitions'. Molecular and cellular biology 25(1):389-402. Pao, W. and Chmielecki, J. (2010). 'Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer'. Nature reviews. Cancer 10(11):760-774. Pao, W. and Girard, N. (2011). 'New driver mutations in non-small-cell lung cancer'. The lancet oncology 12(2):175-180. Pao, W., Wang, T. Y., et al. (2005). 'KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib'. PLoS medicine 2(1):e17. Park, I. H., Kim, J. Y., et al. (2010). 'Lovastatin overcomes gefitinib resistance in human non-small cell lung cancer cells with K-Ras mutations'. Investigational new drugs 28(6):791-799. Pece, S. and Gutkind, J. S. (2002). 'E-cadherin and Hakai: signalling, remodeling or destruction?'. Nature cell biology 4(4):E72-74. Perini, G., Diolaiti, D., et al. (2005). 'In vivo transcriptional regulation of N-Myc target genes is controlled by E-box methylation'. Proceedings of the National Academy of Sciences of the United States of America 102(34):12117-12122. Pierce, G. B. and Speers, W. C. (1988). 'Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation'. Cancer research 48(8):1996-2004. Polyak, K. and Weinberg, R. A. (2009). 'Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits'. Nature reviews. Cancer 9(4):265-273. Rao, Sharmila, Porter, Donald C., et al. (1999). 'Lovastatin-mediated G1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase'. Proceedings of the National Academy of Sciences 96(14):7797-7802. Reya, T. and Clevers, H. (2005). 'Wnt signalling in stem cells and cancer'. Nature 434(7035):843-850. Reya, T., Morrison, S. J., et al. (2001). 'Stem cells, cancer, and cancer stem cells'. Nature 414(6859):105-111. Romano, L. A. and Runyan, R. B. (2000). 'Slug is an essential target of TGFbeta2 signaling in the developing chicken heart'. Developmental biology 223(1):91-102. Schotta, G., Lachner, M., et al. (2004). 'A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin'. Genes & development 18(11):1251-1262. Serrano, D., Bleau, A. M., et al. (2011). 'Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer'. Molecular cancer 10:96. Sharma, S. V., Bell, D. W., et al. (2007). 'Epidermal growth factor receptor mutations in lung cancer'. Nature reviews. Cancer 7(3):169-181. Shen, Y., Hirsch, D. S., et al. (2008). 'Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal growth factor receptor to Src-mediated pathway'. The Journal of biological chemistry 283(8):5127-5137. Shi, Y., Fu, X., et al. (2012). 'The side population in human lung cancer cell line NCI-H460 is enriched in stem-like cancer cells'. PloS one 7(3):e33358. Siegel, R., Naishadham, D., et al. (2013). 'Cancer statistics, 2013'. CA: a cancer journal for clinicians 63(1):11-30. Singh, A. and Settleman, J. (2010). 'EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer'. Oncogene 29(34):4741-4751. Soria, J. C., Mok, T. S., et al. (2012). 'EGFR-mutated oncogene-addicted non-small cell lung cancer: current trends and future prospects'. Cancer treatment reviews 38(5):416-430. Sos, M. L., Koker, M., et al. (2009). 'PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR'. Cancer research 69(8):3256-3261. Stadtman, E. R. and Barker, H. A. (1949). 'Fatty acid synthesis by enzyme preparations of Clostridium kluyveri; a consideration of postulated 4-carbon intermediates in butyrate synthesis'. The Journal of biological chemistry 181(1):221-235. Takebe, N., Harris, P. J., et al. (2011). 'Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways'. Nature reviews. Clinical oncology 8(2):97-106. Thiery, J. P. (2002). 'Epithelial-mesenchymal transitions in tumour progression'. Nature reviews. Cancer 2(6):442-454. Thiery, J. P. and Sleeman, J. P. (2006). 'Complex networks orchestrate epithelial-mesenchymal transitions'. Nature reviews. Molecular cell biology 7(2):131-142. Uramoto, H., Iwata, T., et al. (2010). 'Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma'. Anticancer research 30(7):2513-2517. Valent, Peter, Bonnet, Dominique, et al. (2012). 'Cancer stem cell definitions and terminology: the devil is in the details'. Nature reviews. Cancer 12(11):767-775. Valenzuela-Fernandez, A., Cabrero, J. R., et al. (2008). 'HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions'. Trends in cell biology 18(6):291-297. Wang, B. Y., Huang, J. Y., et al. (2013). 'Lung cancer and prognosis in taiwan: a population-based cancer registry'. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 8(9):1128-1135. Wang, J., Li, Z. H., et al. (2014). 'Lung Cancer Stem Cells and Implications for Future Therapeutics'. Cell biochemistry and biophysics. Wei, J., Xu, G., et al. (2008). 'Overexpression of vimentin contributes to prostate cancer invasion and metastasis via src regulation'. Anticancer research 28(1A):327-334. Wong, W. W., Dimitroulakos, J., et al. (2002). 'HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis'. Leukemia 16(4):508-519. Wu, J. Y., Wu, S. G., et al. (2008). 'Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response'. Clinical cancer research : an official journal of the American Association for Cancer Research 14(15):4877-4882. Wu, Y. and Wu, P. Y. (2009). 'CD133 as a marker for cancer stem cells: progresses and concerns'. Stem cells and development 18(8):1127-1134. Yang, J. and Weinberg, R. A. (2008). 'Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis'. Developmental cell 14(6):818-829. Yano, S., Wang, W., et al. (2008). 'Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations'. Cancer research 68(22):9479-9487. Yeh, C. T., Wu, A. T., et al. (2012). 'Trifluoperazine, an antipsychotic agent, inhibits cancer stem cell growth and overcomes drug resistance of lung cancer'. American journal of respiratory and critical care medicine 186(11):1180-1188. Yoo, C. B. and Jones, P. A. (2006). 'Epigenetic therapy of cancer: past, present and future'. Nature reviews. Drug discovery 5(1):37-50. Yoshida, T., Okamoto, I., et al. (2010). 'Effects of Src inhibitors on cell growth and epidermal growth factor receptor and MET signaling in gefitinib-resistant non-small cell lung cancer cells with acquired MET amplification'. Cancer science 101(1):167-172. Yun, C. H., Mengwasser, K. E., et al. (2008). 'The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP'. Proceedings of the National Academy of Sciences of the United States of America 105(6):2070-2075. Zhou, C., Wu, Y. L., et al. (2011). 'Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study'. The lancet oncology 12(8):735-742. Zhu, Q. S., Rosenblatt, K., et al. (2011). 'Vimentin is a novel AKT1 target mediating motility and invasion'. Oncogene 30(4):457-470. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56393 | - |
dc.description.abstract | 目前針對表現過度活化epidermal growth factor receptor (EGFR) 之非小細胞肺癌治療主要是使用小分子藥物EGFR tyrosine kinase inhibitor (TKI),如gefitinib 或是erlotinib。然而,因治療數月後對TKI產生抗藥性而導致腫瘤復發,稱為acquired resistance (secondary resistance),已漸漸成為主要克服的議題。另外,因對傳統化療藥物產生抗藥性而提出癌幹細胞為主要造成癌症發生,維持和轉移,也成為是否造成對標把藥物譬如TKI產生抗藥性主因。本實驗中,發現非小細胞肺癌細胞株HCC827因長時間給與gefitinib後而形成癌細胞HCC827/IR,不但容易培養出癌幹細胞而且大量表現CD24low/CD44high和ALDH1A1。除此之外,這群癌幹細胞明顯表現epithelial mesenchymal transition (EMT)特徵且EMT影響癌幹細胞生成。因此尋找新一代藥物來對付此種抗藥性癌細胞是刻不容緩課題。除了化療和標把治療外,HDAC和HMG-CoA抑制劑也在癌症治療上占著舉足輕重的地位。我們研發出一種具有抑制HDAC 和HMG-CoA效果之抑制劑JMF3086,不但能有效降低肺癌細胞和肺癌幹細胞產生還能恢復此兩種細胞E-cadherin表現。因此,JMF3086為具潛能應用於對抗EGFR-TKI產生抗藥性之肺癌幹細胞。 | zh_TW |
dc.description.abstract | Inhibition of EGFR tyrosine kinase by small molecule inhibitor, such as gefitinib or erlotinib, is an important treatment strategy for NSCLC with EGFR activating mutations. Currently, acquired resistance to EGFR TKI in NSCLC is becoming a critical problem to solve. Cancer stem cell (CSC) is a rare population in tumor to initiate tumor initiation, maintenance and metastasis, and confers resistance to chemotherapy. However, the role of CSC in TKI resistance needed investigation. We found that gefitinib acquired resistant NSCLC cell, HCC827/Iressa resistance (IR), had more CSC population, called spheroids with CD24low/CD44high feature and increased ALDH1A1 activity. Besides, these spheroids had strong epithelial mesenchymal transition (EMT) feature and EMT was related to their formation. Therefore, the aim of the present study was to find a new drug to overcome stemness-related EGFR TKI resistance. In addition to chemotherapy and targeted therapy, both of HDAC and HMG-CoA inhibition play vital role in cancer therapies. We generated a dual HDAC and HMG-CoA reductase (HMGR) inhibitor JMF3086 which inhibited HCC827/IR growth and its spheroid formation. Moreover, JMF3086 restored E-cadherin expression in HCC827/IR and its spheroid. Our results indicated that JMF3086 had a potential to overcome stemness-related EGFR TKI resistance. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T05:26:30Z (GMT). No. of bitstreams: 1 ntu-103-R01443009-1.pdf: 8071128 bytes, checksum: 5f82fd6ba821b38cbcb4aef6ae143baf (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | Abbreviation 1
中文摘要 4 Abstract 5 Chapter1. Introduction 6 Section1. Cancer stem cell 7 Section2. Epithelial mesenchymal transition and Cancer stem cell 24 Section3. Non-small cell lung cancer and Tyrosine kinase inhibitor 38 Section4. Histone Deacetylase Inhibitor and HMG-CoA inhibitor 46 Study Motivation 59 Chapter2. Material and Methods 60 Chapter3. Results 65 Chapter4. Discussion 83 References 89 | |
dc.language.iso | en | |
dc.title | 新穎HDAC抑制劑對Gefitinib抗藥性之非小細胞肺癌幹細胞之研究 | zh_TW |
dc.title | Effect of A Novel HDAC Inhibitor on Gefitinib Resistant Non-Small Cell Lung Cancer Stem Cell | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 吳明賢(MING-SHIANG WU),黃偉謙(Wei-Chien Huang) | |
dc.subject.keyword | 新穎HDAC抑制劑,肺癌幹細胞, | zh_TW |
dc.subject.keyword | A Novel HDAC Inhibitor,Non-Small Cell Lung Cancer Stem Cell, | en |
dc.relation.page | 97 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-08-14 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
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 | 7.88 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。