請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69986完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 翁昭旼 | |
| dc.contributor.author | Hao-Wei Cheng | en |
| dc.contributor.author | 鄭皓薇 | zh_TW |
| dc.date.accessioned | 2021-06-17T03:37:27Z | - |
| dc.date.available | 2023-03-12 | |
| dc.date.copyright | 2018-03-12 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-02-09 | |
| dc.identifier.citation | 1 Siegel, R. L., Miller, K. D. & Jemal, A. Cancer Statistics, 2017. CA: a cancer journal for clinicians 67, 7-30 (2017).
2 Ridge, C. A., McErlean, A. M. & Ginsberg, M. S. Epidemiology of lung cancer. Semin Intervent Radiol 30, 93-98 (2013). 3 Samet, J. M. et al. Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clinical cancer research 15, 5626-5645 (2009). 4 Mattson, M. E., Pollack, E. S. & Cullen, J. W. What are the odds that smoking will kill you? Am J Public Health 77, 425-431 (1987). 5 Smith, C. J., Perfetti, T. A., Rumple, M. A., Rodgman, A. & Doolittle, D. J. 'IARC group 2A Carcinogens' reported in cigarette mainstream smoke. Food Chem Toxicol 38, 371-383 (2000). 6 Smith, C. J., Perfetti, T. A., Mullens, M. A., Rodgman, A. & Doolittle, D. J. 'IARC group 2B Carcinogens' reported in cigarette mainstream smoke. Food Chem Toxicol 38, 825-848 (2000). 7 Dela Cruz, C. S., Tanoue, L. T. & Matthay, R. A. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med 32, 605-644 (2011). 8 Vineis, P. et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96, 99-106 (2004). 9 Pfeifer, G. P. et al. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 21, 7435-7451 (2002). 10 Sun, S., Schiller, J. H. & Gazdar, A. F. Lung cancer in never smokers--a different disease. Nat Rev Cancer 7, 778-790 (2007). 11 Yang, P. Lung cancer in never smokers. Semin Respir Crit Care Med 32, 10-21 (2011). 12 Brenner, D. R. et al. Lung cancer risk in never-smokers: a population-based case-control study of epidemiologic risk factors. BMC Cancer 10, 285 (2010). 13 Le Marchand, L. et al. Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States). Cancer Causes Control 14, 339-346 (2003). 14 Le Calvez, F. et al. TP53 and KRAS mutation load and types in lung cancers in relation to tobacco smoke: distinct patterns in never, former, and current smokers. Cancer research 65, 5076-5083 (2005). 15 Herbst, R. S., Heymach, J. V. & Lippman, S. M. Lung cancer. The New England journal of medicine 359, 1367-1380 (2008). 16 Beadsmoore, C. J. & Screaton, N. J. Classification, staging and prognosis of lung cancer. Eur J Radiol 45, 8-17 (2003). 17 Pearlberg, J. L., Sandler, M. A., Lewis, J. W., Jr., Beute, G. H. & Alpern, M. B. Small-cell bronchogenic carcinoma: CT evaluation. AJR Am J Roentgenol 150, 265-268 (1988). 18 Travis, W. D. Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Modern pathology 25 Suppl 1, S18-30 (2012). 19 Onuki, N. et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 85, 600-607 (1999). 20 Travis, W. D. et al. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol 10, 1243-1260 (2015). 21 Chaudhuri, M. R. Primary pulmonary cavitating carcinomas. Thorax 28, 354-366 (1973). 22 Shin, M. S., Jackson, L. K., Shelton, R. W., Jr. & Greene, R. E. Giant cell carcinoma of the lung. Clinical and roentgenographic manifestations. Chest 89, 366-369 (1986). 23 Goldstraw, P. et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2, 706-714 (2007). 24 Nyberg, P., Salo, T. & Kalluri, R. Tumor microenvironment and angiogenesis. Frontiers in bioscience : a journal and virtual library 13, 6537-6553 (2008). 25 Chen, P., Cescon, M. & Bonaldo, P. Collagen VI in cancer and its biological mechanisms. Trends in molecular medicine 19, 410-417 (2013). 26 Mao, Y., Keller, E. T., Garfield, D. H., Shen, K. & Wang, J. Stromal cells in tumor microenvironment and breast cancer. Cancer metastasis reviews 32, 303-315 (2013). 27 Shiga, K. et al. Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth. Cancers (Basel) 7, 2443-2458 (2015). 28 Mantovani, A., Schioppa, T., Porta, C., Allavena, P. & Sica, A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer metastasis reviews 25, 315-322 (2006). 29 Yuan, A. et al. Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression. Sci Rep 5, 14273 (2015). 30 Chen, F. et al. New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med 13, 45 (2015). 31 Wood, S. L., Pernemalm, M., Crosbie, P. A. & Whetton, A. D. The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev 40, 558-566 (2014). 32 Calon, A., Tauriello, D. V. & Batlle, E. TGF-beta in CAF-mediated tumor growth and metastasis. Seminars in cancer biology 25, 15-22 (2014). 33 Lu, P., Weaver, V. M. & Werb, Z. The extracellular matrix: a dynamic niche in cancer progression. The Journal of cell biology 196, 395-406 (2012). 34 Chaffer, C. L. & Weinberg, R. A. A perspective on cancer cell metastasis. Science 331, 1559-1564 (2011). 35 Cirri, P. & Chiarugi, P. Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression. Cancer metastasis reviews 31, 195-208 (2012). 36 Gridley, T. Notch signaling during vascular development. Proceedings of the National Academy of Sciences 98, 5377-5378 (2001). 37 Gay, L. J. & Felding-Habermann, B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 11, 123-134 (2011). 38 Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nature medicine 19, 1423-1437 (2013). 39 Schumacher, D., Strilic, B., Sivaraj, K. K., Wettschureck, N. & Offermanns, S. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer cell 24, 130-137 (2013). 40 Psaila, B., Lyden, D. & Roberts, I. Megakaryocytes, malignancy and bone marrow vascular niches. J Thromb Haemost 10, 177-188 (2012). 41 Erler, J. T. & Weaver, V. M. Three-dimensional context regulation of metastasis. Clinical & experimental metastasis 26, 35-49 (2009). 42 Tomasini, P., Khobta, N., Greillier, L. & Barlesi, F. Ipilimumab: its potential in non-small cell lung cancer. Ther Adv Med Oncol 4, 43-50 (2012). 43 Hellmann, M. D. et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. The Lancet. Oncology 18, 31-41 (2017). 44 Folkman, J. Tumor angiogenesis: therapeutic implications. The New England journal of medicine 285, 1182-1186 (1971). 45 Watnick, R. S. The role of the tumor microenvironment in regulating angiogenesis. Cold Spring Harbor perspectives in medicine 2, a006676 (2012). 46 Vasudev, N. S. & Reynolds, A. R. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 17, 471-494 (2014). 47 Ye, W. The Complexity of Translating Anti-angiogenesis Therapy from Basic Science to the Clinic. Dev Cell 37, 114-125 (2016). 48 Nogales, E. Structural insights into microtubule function. Annual review of biochemistry 69, 277-302 (2000). 49 Jordan, M. A. & Wilson, L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 4, 253-265 (2004). 50 Mitchison, T. J. Microtubule dynamics and kinetochore function in mitosis. Annu Rev Cell Biol 4, 527-549 (1988). 51 Jackson, J. R., Patrick, D. R., Dar, M. M. & Huang, P. S. Targeted anti-mitotic therapies: can we improve on tubulin agents? Nat Rev Cancer 7, 107-117 (2007). 52 Dumontet, C. & Jordan, M. A. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nature reviews. Drug discovery 9, 790-803 (2010). 53 Canta, A., Chiorazzi, A. & Cavaletti, G. Tubulin: a target for antineoplastic drugs into the cancer cells but also in the peripheral nervous system. Curr Med Chem 16, 1315-1324 (2009). 54 Rowinsky, E. K. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu Rev Med 48, 353-374 (1997). 55 Chen, F., Wang, W. & El-Deiry, W. S. Current strategies to target p53 in cancer. Biochemical pharmacology 80, 724-730 (2010). 56 Staples, O. D., Steele, R. J. & Lain, S. p53 as a therapeutic target. Surgeon 6, 240-243 (2008). 57 Zilfou, J. T. & Lowe, S. W. Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol 1, a001883 (2009). 58 Olivier, M., Hollstein, M. & Hainaut, P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2, a001008 (2010). 59 Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R. & Lane, D. P. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 9, 862-873 (2009). 60 Kato, S. et al. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proceedings of the National Academy of Sciences 100, 8424-8429 (2003). 61 Duffy, M. J. et al. p53 as a target for the treatment of cancer. Cancer Treat Rev 40, 1153-1160 (2014). 62 Nemunaitis, J. & Nemunaitis, J. Head and neck cancer: response to p53-based therapeutics. Head & neck 33, 131-134 (2011). 63 Ries, S. & Korn, W. M. ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus. British journal of cancer 86, 5-11 (2002). 64 Wade, M., Li, Y. C. & Wahl, G. M. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 13, 83-96 (2013). 65 Lain, S. et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer cell 13, 454-463 (2008). 66 Mutka, S. C. et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer research 69, 510-517 (2009). 67 Foster, B. A., Coffey, H. A., Morin, M. J. & Rastinejad, F. Pharmacological rescue of mutant p53 conformation and function. Science 286, 2507-2510 (1999). 68 Friedler, A. et al. A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants. Proceedings of the National Academy of Sciences 99, 937-942 (2002). 69 Lambert, J. M. et al. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer cell 15, 376-388 (2009). 70 Liu, P., Cheng, H., Roberts, T. M. & Zhao, J. J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nature reviews. Drug discovery 8, 627-644 (2009). 71 Fruman, D. A. & Rommel, C. PI3K and cancer: lessons, challenges and opportunities. Nature reviews. Drug discovery 13, 140-156 (2014). 72 Thorpe, L. M., Yuzugullu, H. & Zhao, J. J. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer 15, 7-24 (2015). 73 Nitulescu, G. M. et al. Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review). International journal of oncology 48, 869-885 (2016). 74 Kumar, C. C. & Madison, V. AKT crystal structure and AKT-specific inhibitors. Oncogene 24, 7493-7501 (2005). 75 Hirai, H. et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Molecular cancer therapeutics 9, 1956-1967 (2010). 76 Hilgard, P. et al. D-21266, a new heterocyclic alkylphospholipid with antitumour activity. Eur J Cancer 33, 442-446 (1997). 77 Torre, L. A. et al. Global cancer statistics, 2012. CA: a cancer journal for clinicians 65, 87-108 (2015). 78 Reymond, N., d'Agua, B. B. & Ridley, A. J. Crossing the endothelial barrier during metastasis. Nat Rev Cancer 13, 858-870 (2013). 79 Laska, M. J. et al. Expression of the RAI gene is conducive to apoptosis: studies of induction and interference. Experimental cell research 313, 2611-2621 (2007). 80 Sullivan, A. & Lu, X. ASPP: a new family of oncogenes and tumour suppressor genes. British journal of cancer 96, 196-200 (2007). 81 Gorina, S. & Pavletich, N. P. Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science 274, 1001-1005 (1996). 82 Yang, J. P., Hori, M., Sanda, T. & Okamoto, T. Identification of a novel inhibitor of nuclear factor-kappaB, RelA-associated inhibitor. The Journal of biological chemistry 274, 15662-15670 (1999). 83 Bergamaschi, D. et al. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat Genet 33, 162-167 (2003). 84 Jia, Y. et al. Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation. FASEB journal 28, 2816-2827 (2014). 85 Falik-Zaccai, T. C. et al. Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome. EMBO molecular medicine 9, 319-336 (2017). 86 Notari, M. et al. iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death. Proceedings of the National Academy of Sciences 112, E973-981 (2015). 87 Chikh, A. et al. iASPP is a novel autophagy inhibitor in keratinocytes. Journal of cell science 127, 3079-3093 (2014). 88 Wilson, A. M. et al. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is required for neuronal survival after axonal injury. PloS one 9, e94175 (2014). 89 Cai, Y., Qiu, S., Gao, X., Gu, S. Z. & Liu, Z. J. iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes. Apoptosis 17, 777-783 (2012). 90 Chen, J., Xie, F., Zhang, L. & Jiang, W. G. iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway. BMC Cancer 10, 694 (2010). 91 Wang, L. L., Xu, Z., Peng, Y., Li, L. C. & Wu, X. L. Downregulation of inhibitor of apoptosisstimulating protein of p53 inhibits proliferation and promotes apoptosis of gastric cancer cells. Molecular medicine reports 12, 1653-1658 (2015). 92 Dong, P. et al. Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124. Sci Rep 6, 35480 (2016). 93 Kong, F. et al. Increased expression of iASPP correlates with poor prognosis in FIGO IA2-IIA cervical adenocarcinoma following a curative resection. Am J Cancer Res 5, 1217-1224 (2015). 94 Wu, Z. et al. Inhibitory member of the apoptosis-stimulating protein of p53 is overexpressed in bladder cancer and correlated to its progression. Medicine (Baltimore) 96, e6640 (2017). 95 Gan, W., Zhao, H., Li, T., Liu, K. & Huang, J. CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway. Oncotarget 11, 71618-71629 (2017). 96 Lu, W. et al. FHL2 interacts with iASPP and impacts the biological functions of leukemia cells. Oncotarget 8, 40885-40895 (2017). 97 Li, G. et al. RNA interference-mediated silencing of iASPP induces cell proliferation inhibition and G0/G1 cell cycle arrest in U251 human glioblastoma cells. Molecular and cellular biochemistry 350, 193-200 (2011). 98 Morris, E. V. et al. Nuclear iASPP may facilitate prostate cancer progression. Cell Death Dis 5, e1492 (2014). 99 Lu, M. et al. Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer cell 23, 618-633 (2013). 100 Xiong, Y. et al. iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling. J Exp Clin Cancer Res 36, 48 (2017). 101 Bell, H. S. et al. A p53-derived apoptotic peptide derepresses p73 to cause tumor regression in vivo. J Clin Invest 117, 1008-1018 (2007). 102 Qiu, S., Cai, Y., Gao, X., Gu, S. Z. & Liu, Z. J. A small peptide derived from p53 linker region can resume the apoptotic activity of p53 by sequestering iASPP with p53. Cancer Lett 356, 910-917 (2015). 103 Liu, H. et al. A novel all-trans retinoic acid derivative 4-amino2trifluoromethyl-phenyl retinate inhibits the proliferation of human hepatocellular carcinoma HepG2 cells by inducing G0/G1 cell cycle arrest and apoptosis via upregulation of p53 and ASPP1 and downregulation of iASPP. Oncology reports 36, 333-341 (2016). 104 Liang, X. G. et al. MicroRNA-184 Modulates Human Central Nervous System Lymphoma Cells Growth and Invasion by Targeting iASPP. J Cell Biochem 118, 2645-2653 (2016). 105 Liu, K. et al. The miR-124-p63 feedback loop modulates colorectal cancer growth. Oncotarget 8, 29101-29115 (2017). 106 Zhao, H. et al. The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting iASPP. Arch Biochem Biophys 610, 1-7 (2016). 107 Wang, S. P. et al. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nat Cell Biol 11, 694-704 (2009). 108 Chen, Y. L. et al. In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells. Biochemical pharmacology 72, 308-319 (2006). 109 Marcon, E. et al. Assessment of a method to characterize antibody selectivity and specificity for use in immunoprecipitation. Nat Methods 12, 725-731 (2015). 110 Mellacheruvu, D. et al. The CRAPome: a contaminant repository for affinity purification-mass spectrometry data. Nat Methods 10, 730-736 (2013). 111 Chiu, J. & Dawes, I. W. Redox control of cell proliferation. Trends in cell biology 22, 592-601 (2012). 112 Hans, F. & Dimitrov, S. Histone H3 phosphorylation and cell division. Oncogene 20, 3021-3027 (2001). 113 Mollinedo, F. & Gajate, C. Microtubules, microtubule-interfering agents and apoptosis. Apoptosis 8, 413-450 (2003). 114 Dunphy, W. G. The decision to enter mitosis. Trends in cell biology 4, 202-207 (1994). 115 Romagnoli, R. et al. 2-Arylamino-4-amino-5-aroylthiazoles. 'One-pot' synthesis and biological evaluation of a new class of inhibitors of tubulin polymerization. Journal of medicinal chemistry 52, 5551-5555 (2009). 116 Lynch, T. J. et al. 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, 2129-2139 (2004). 117 Paez, J. G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (2004). 118 Ma, C., Wei, S. & Song, Y. T790M and acquired resistance of EGFR TKI: a literature review of clinical reports. J Thorac Dis 3, 10-18 (2011). 119 Lippi, G., Salvagno, G. L., Montagnana, M., Brocco, G. & Guidi, G. C. Influence of hemolysis on routine clinical chemistry testing. Clinical chemistry and laboratory medicine 44, 311-316 (2006). 120 Rivlin, N., Brosh, R., Oren, M. & Rotter, V. Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis. Genes & cancer 2, 466-474 (2011). 121 Houben, R. et al. High-level expression of wild-type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays. PloS one 6, e22096 (2011). 122 Selivanova, G. Wild type p53 reactivation: from lab bench to clinic. FEBS letters 588, 2628-2638 (2014). 123 Bykov, V. J. N. & Wiman, K. G. Mutant p53 reactivation by small molecules makes its way to the clinic. FEBS letters 588, 2622-2627 (2014). 124 Zhao, Y., Aguilar, A., Bernard, D. & Wang, S. Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment. Journal of medicinal chemistry 58, 1038-1052 (2015). 125 Vousden, K. H. & Prives, C. Blinded by the Light: The Growing Complexity of p53. Cell 137, 413-431 (2009). 126 Gibbons, D. L., Byers, L. A. & Kurie, J. M. Smoking, p53 mutation, and lung cancer. Molecular cancer research 12, 3-13 (2014). 127 Carmeliet, P. Angiogenesis in health and disease. Nature medicine 9 (2003). 128 Hoeben, A. et al. Vascular endothelial growth factor and angiogenesis. Pharmacological reviews 56, 549-580 (2004). 129 Folkman, J. Role of angiogenesis in tumor growth and metastasis. Seminars in oncology 29, 15-18 (2002). 130 Weis, S. M. & Cheresh, D. A. Tumor angiogenesis: molecular pathways and therapeutic targets. Nature medicine 17, 1359-1370 (2011). 131 Hicklin, D. J. & Ellis, L. M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of clinical oncology 23, 1011-1027 (2005). 132 Sang, Q. X. Complex role of matrix metalloproteinases in angiogenesis. Cell Res 8, 171-177 (1998). 133 Rundhaug, J. E. Matrix metalloproteinases and angiogenesis. Journal of cellular and molecular medicine 9, 267-285 (2005). 134 Deryugina, E. I. & Quigley, J. P. Tumor angiogenesis: MMP-mediated induction of intravasation- and metastasis-sustaining neovasculature. Matrix Biol 44-46, 94-112 (2015). 135 Zheng, C. L. et al. Prognostic impact of elevation of vascular endothelial growth factor family expression in patients with non-small cell lung cancer: an updated meta-analysis. Asian Pac J Cancer Prev 16, 1881-1895 (2015). 136 Jusufovic, E. et al. let-7b and miR-126 are down-regulated in tumor tissue and correlate with microvessel density and survival outcomes in non--small--cell lung cancer. PloS one 7, e45577 (2012). 137 Kadota, K. et al. The clinical significance of lymphangiogenesis and angiogenesis in non-small cell lung cancer patients. Eur J Cancer 44, 1057-1067 (2008). 138 Ucuzian, A. A., Gassman, A. A., East, A. T. & Greisler, H. P. Molecular mediators of angiogenesis. J Burn Care Res 31, 158-175 (2010). 139 Holmes, D. I. & Zachary, I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol 6, 209 (2005). 140 Otrock, Z. K., Makarem, J. A. & Shamseddine, A. I. Vascular endothelial growth factor family of ligands and receptors: review. Blood Cells Mol Dis 38, 258-268 (2007). 141 Soker, S., Takashima, S., Miao, H. Q., Neufeld, G. & Klagsbrun, M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92, 735-745 (1998). 142 Gerwins, P., Skoldenberg, E. & Claesson-Welsh, L. Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. Critical reviews in oncology/hematology 34, 185-194 (2000). 143 Xue, L. & Greisler, H. P. Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system. Surgery 132, 259-267 (2002). 144 Kanda, S., Landgren, E., Ljungstrom, M. & Claesson-Welsh, L. Fibroblast growth factor receptor 1-induced differentiation of endothelial cell line established from tsA58 large T transgenic mice. Cell Growth Differ 7, 383-395 (1996). 145 Papapetropoulos, A. et al. Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. The Journal of biological chemistry 275, 9102-9105 (2000). 146 Brindle, N. P., Saharinen, P. & Alitalo, K. Signaling and functions of angiopoietin-1 in vascular protection. Circulation research 98, 1014-1023 (2006). 147 Collo, G. & Pepper, M. S. Endothelial cell integrin alpha5beta1 expression is modulated by cytokines and during migration in vitro. Journal of cell science 112, 569-578 (1999). 148 Li, J., Zhang, Y. P. & Kirsner, R. S. Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech 60, 107-114 (2003). 149 Sainson, R. C. et al. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood 111, 4997-5007 (2008). 150 Rodon, J., Dienstmann, R., Serra, V. & Tabernero, J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nature reviews. Clinical oncology 10, 143-153 (2013). 151 Gerber, H. P. et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. The Journal of biological chemistry 273, 30336-30343 (1998). 152 Shiojima, I. & Walsh, K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circulation research 90, 1243-1250 (2002). 153 Dayanir, V., Meyer, R. D., Lashkari, K. & Rahimi, N. Identification of tyrosine residues in vascular endothelial growth factor receptor-2/FLK-1 involved in activation of phosphatidylinositol 3-kinase and cell proliferation. The Journal of biological chemistry 276, 17686-17692 (2001). 154 Augustin, H. G., Koh, G. Y., Thurston, G. & Alitalo, K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nature reviews. Molecular cell biology 10, 165-177 (2009). 155 Graupera, M. et al. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature 453, 662-666 (2008). 156 Herbert, S. P. et al. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science 326, 294-298 (2009). 157 Hong, C. C., Peterson, Q. P., Hong, J. Y. & Peterson, R. T. Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling. Current biology 16, 1366-1372 (2006). 158 Yoshioka, K. et al. Endothelial PI3K-C2alpha, a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nature medicine 18, 1560-1569 (2012). 159 Coyne, D. W., Nickols, M., Bertrand, W. & Morrison, A. R. Regulation of mesangial cell cyclooxygenase synthesis by cytokines and glucocorticoids. Am J Physiol 263, F97-102 (1992). 160 Williams, C. S., Tsujii, M., Reese, J., Dey, S. K. & DuBois, R. N. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest 105, 1589-1594 (2000). 161 Ruegg, C., Dormond, O. & Mariotti, A. Endothelial cell integrins and COX-2: mediators and therapeutic targets of tumor angiogenesis. Biochim Biophys Acta 1654, 51-67 (2004). 162 Dormond, O., Bezzi, M., Mariotti, A. & Ruegg, C. Prostaglandin E2 promotes integrin alpha Vbeta 3-dependent endothelial cell adhesion, rac-activation, and spreading through cAMP/PKA-dependent signaling. The Journal of biological chemistry 277, 45838-45846 (2002). 163 Chu, Y. W. et al. Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. American journal of respiratory cell and molecular biology 17, 353-360 (1997). 164 Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4, 44-57 (2009). 165 Rousseaux, S. et al. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med 5, 186ra166 (2013). 166 Dimmeler, S. & Zeiher, A. M. Endothelial cell apoptosis in angiogenesis and vessel regression. Circulation research 87, 434-439 (2000). 167 Heasman, S. J. & Ridley, A. J. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nature reviews. Molecular cell biology 9, 690-701 (2008). 168 Hall, A. Rho GTPases and the actin cytoskeleton. Science 279, 509-514 (1998). 169 Small, J. V., Stradal, T., Vignal, E. & Rottner, K. The lamellipodium: where motility begins. Trends in cell biology 12, 112-120 (2002). 170 Hanahan, D. & Coussens, L. M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer cell 21, 309-322 (2012). 171 Liotta, L. A. & Kohn, E. C. The microenvironment of the tumour-host interface. Nature 411, 375-379 (2001). 172 Xiong, Y. Q. et al. Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells. Clinical cancer research 15, 4838-4846 (2009). 173 Tu, M. L. et al. Involvement of Akt1/protein kinase Balpha in tumor conditioned medium-induced endothelial cell migration and survival in vitro. Journal of cancer research and clinical oncology 135, 1543-1550 (2009). 174 Shijubo, N. et al. Tumor angiogenesis of non-small cell lung cancer. Microsc Res Tech 60, 186-198 (2003). 175 Manna, S. K. & Ramesh, G. T. Interleukin-8 induces nuclear transcription factor-kappaB through a TRAF6-dependent pathway. The Journal of biological chemistry 280, 7010-7021 (2005). 176 Sprague, A. H. & Khalil, R. A. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochemical pharmacology 78, 539-552 (2009). 177 Bialkowska, K. et al. Evidence that beta3 integrin-induced Rac activation involves the calpain-dependent formation of integrin clusters that are distinct from the focal complexes and focal adhesions that form as Rac and RhoA become active. The Journal of cell biology 151, 685-696 (2000). 178 Kovac, B., Teo, J. L., Makela, T. P. & Vallenius, T. Assembly of non-contractile dorsal stress fibers requires alpha-actinin-1 and Rac1 in migrating and spreading cells. Journal of cell science 126, 263-273 (2013). 179 Dianzani, C. et al. Celecoxib modulates adhesion of HT29 colon cancer cells to vascular endothelial cells by inhibiting ICAM-1 and VCAM-1 expression. Br J Pharmacol 153, 1153-1161 (2008). 180 Catalano, V. et al. Tumor and its microenvironment: a synergistic interplay. Seminars in cancer biology 23, 522-532 (2013). 181 Salvado, M. D., Alfranca, A., Haeggstrom, J. Z. & Redondo, J. M. Prostanoids in tumor angiogenesis: therapeutic intervention beyond COX-2. Trends in molecular medicine 18, 233-243 (2012). 182 Wang, D. & DuBois, R. N. Cyclooxygenase 2-derived prostaglandin E2 regulates the angiogenic switch. Proceedings of the National Academy of Sciences 101, 415-416 (2004). 183 Uddin, S. et al. Cyclooxygenase-2 inhibition inhibits PI3K/AKT kinase activity in epithelial ovarian cancer. International journal of cancer. 126, 382-394 (2010). 184 Yuan, T. L. et al. Class 1A PI3K regulates vessel integrity during development and tumorigenesis. Proceedings of the National Academy of Sciences 105, 9739-9744 (2008). 185 Shahid, M. et al. An 8-gene signature for prediction of prognosis and chemoresponse in non-small cell lung cancer. Oncotarget 7, 86561-86572 (2016). 186 Krzystanek, M., Moldvay, J., Szuts, D., Szallasi, Z. & Eklund, A. C. A robust prognostic gene expression signature for early stage lung adenocarcinoma. Biomark Res 4, 4 (2016). 187 Bendell, J. C. et al. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Journal of clinical oncology 30, 282-290 (2012). 188 Vansteenkiste, J. F. et al. Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study. J Thorac Oncol 10, 1319-1327 (2015). 189 Shapiro, G. I. et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245408 (XL147), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. Clinical cancer research 20, 233-245 (2014). 190 Massacesi, C. et al. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design. Onco Targets Ther 9, 203-210 (2016). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69986 | - |
| dc.description.abstract | 在世界各地中，肺癌佔造成癌症死亡的首位，因此尋找具有新穎治療機制的抗癌策略成為一件重要的工作。根據文獻報導，腫瘤微環境、致癌基因和腫瘤抑制基因在癌化過程中扮演著重要角色，因此，在肺癌治療上透過控制腫瘤微環境及致癌、抑癌基因的表現或許是可行的辦法。p53是重要的腫瘤抑制基因，作為一個轉錄因子，它可以維持基因組的穩定性、造成細胞週期停滯、細胞凋亡、衰老及自體吞噬。我們也試著從控制腫瘤微環境的角度切入，看能否透過抑制血管新生來減緩腫瘤生長。受腫瘤微環境調控的血管新生，在肺癌的惡化過程中扮演重要角色，也是癌症的標誌之一。透過分析利用H1975、A549、PC9及PC9IR等四株細胞篩選抗癌藥物的數據，我們證實AS7128可以在細胞層次及動物實驗中抑制腫瘤細胞的生長，是個具有潛力的藥物，其機轉是經由抑制微管蛋白聚合與降低和p53抑制物iASPP的交互作用來恢復p53轉錄因子的活性，可以讓細胞週期停在有絲分裂及造成細胞凋亡。我們也發現，將人類臍帶靜脈內皮細胞(HUVEC)和人類肺癌細胞培養在一起後，會透過PI3K/Akt訊息傳遞路徑及COX-2基因表現來增加臍帶靜脈內皮細胞微血管結構的形成，減少細胞凋亡，進而影響微環境以利腫瘤生長；這樣子的培養過程也會改變內皮細胞的基因表現，而這些表現量有差異的基因，也可以用來預測非小細胞肺癌病人的整體存活與無疾病存活。總結來說，透過解析藥物新的作用機轉及阻斷腫瘤微環境對血管內皮細胞的影響，可加強控制腫瘤生長，這些研究希望能提供肺癌病患在治療上的新策略。 | zh_TW |
| dc.description.abstract | Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing anti-cancer drugs with novel mechanism becomes an important issue. It has been reported that tumor microenvironment, oncogene and tumor suppressor gene play an important role in lung cancer progression. Thus management of the tumor microenvironment or gene expression could be a practical strategy in lung cancer therapy. p53 is an important tumor suppressor gene which acts as a transcriptional factor to maintain genome stability and induce cell cycle arrest, apoptosis, senescence and autophagy. Angiogenesis which is regulated by tumor microenvironment is a hallmark of cancer and plays a critical role in lung cancer progression. Using the data from a high-throughput screening against H1975, A549, PC9 and PC9IR cell lines, we identified AS7128 as a potential compound to inhibit tumor growth in vitro and in vivo. In addition, AS7128 induced cell cycle M phase arrest and cell apoptosis through microtubule polymerization inhibition and p53 transactivation ability restoration, which by decreasing the interaction with p53 inhibitor, iASPP. Furthermore, we found that after co-culture with lung cancer cells, human umbilical vein endothelial cells (HUVECs) showed increased microvessel tube formation ability and a decreased apoptotic percentage through PI3K/Akt signaling pathway and COX-2 expression, and thus changed the microenvironment to benefit tumor growth. Interaction with cancer cells also altered the gene expression of HUVECs, and these gene signatures could predict overall survival and disease-free survival in non-small cell lung cancer (NSCLC) patients. Taken together, we tried to control tumor growth by discovering drugs and blocking the effect of tumor microenvironment on endothelial cells. These findings provide novel strategies to overcome lung cancer in patients. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T03:37:27Z (GMT). No. of bitstreams: 1 ntu-107-D98548017-1.pdf: 4066777 bytes, checksum: da07be84f8dbbb23345cf8ef69b12090 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii 中文摘要 iii Abstract iv Contents vi List of figures x List of tables xiii Chapter one: General introduction 1 1.1 Lung cancer etiology 2 1.2 Histology of lung cancer 4 1.2.1 Small cell lung cancer 4 1.2.2 Adenocarcinoma 5 1.2.3 Squamous carcinoma 6 1.2.4 Large cell carcinoma 6 1.3 Stages of lung cancer 6 1.4 Management of lung cancer 8 1.4.1 Tumor microenvironment in therapy 9 1.4.1.1 Anti-metastasis 10 1.4.1.2 Anti-angiogenesis 12 1.4.2 Microtubule in therapy 13 1.4.3 p53 in therapy 15 1.4.4 PI3K/Akt signaling in therapy 18 1.5 Specific aims of this thesis 20 Chapter two: The 2-anilino-4-amino-5-aroylthiazole-type compound AS7128 inhibits lung cancer growth through decreased iASPP and p53 interaction 22 2.1 Abstract 23 2.2 Introduction 25 2.2.1 iASPP 25 2.2.2 iASPP in cancer 26 2.2.3 iASPP in cancer therapy 27 2.2.4 Drug screening 28 2.2.5 Summary 29 2.3 Material and Methods 30 2.3.1 Cells 30 2.3.2 Plasmid construction, siRNA and transfection 30 2.3.3 Western blot 31 2.3.4 Sulforhodamine B (SRB) assay 32 2.3.5 Flow cytometry 32 2.3.6 Synchronization 33 2.3.7 Immunoflourescence staining 33 2.3.8 Cold treatment assay 34 2.3.9 in vitro tubulin polymerization assay 35 2.3.10 in vivo tubulin polymerization assay 35 2.3.11 Xenograft animal model 36 2.3.12 Mass spectrometry and protein identification 37 2.3.13 Immunoprecipitation and immunoblotting 38 2.3.14 Reporter assay 38 2.3.15 Real-time quantitative PCR 39 2.3.16 Statistical analysis 39 2.4 Results 41 2.4.1 AS7128 was a potential compound in vitro and in vivo 41 2.4.2 AS7128 induced apoptosis and cell cycle G2/M arrest in H1975 cells 42 2.4.3 AS7128 suppressed tubulin polymerization in vitro and in vivo 43 2.4.4 AS7128 arrested H1975 cell in M phase 45 2.4.5 AS7128 activated p53 function through disruption the interaction between p53 and iASPP 47 2.5 Discussion 51 Chapter three: Cancer cells increase endothelial cell tube formation and survival by activating the PI3K/Akt signaling pathway 57 3.1 Abstract 58 3.2 Introduction 60 3.2.1 Angiogenesis in tumor progression 60 3.2.2 Angiogenesis mediators 61 3.2.3 PI3K signaling and COX-2 in endothelial cells 62 3.2.4 Summary 64 3.3 Materials and Methods 65 3.3.1 Cells 65 3.3.2 F-actin staining 66 3.3.3 Migration assay 67 3.3.4 TUNEL assay 67 3.3.5 Tube formation 68 3.3.6 RNA extraction and Real-time quantitative PCR 69 3.3.7 Western blot 70 3.3.8 Rac-1 activity assay 70 3.3.9 Microarray analysis 71 3.3.10 Statistical analysis 72 3.4 Results 74 3.4.1 The phenotype of HUVECs changed after co-culture with CL1-5 cells 74 3.4.2 Gene expression and protein level changes in HUVECs after co-culture with CL1-5 cells 76 3.4.3 Rac-1, lamellipodia and filopodia were activated to promote cell motility in HUVECs after co-culture with CL1-5 cells 78 3.4.4 PI3K and COX-2 inhibitors attenuated the capillary-like tubular formation on Matrigel and promoted the apoptosis of HUVECs after co-culture with CL1-5 cells 78 3.4.5 Cancer cell-stimulated gene signatures were associated with the clinical outcome of NSCLC patients 80 3.5 Discussion 82 Chapter four: Conclusion and future works 89 Abbreviations 92 Figures 96 Tables 149 References 168 | |
| dc.language.iso | en | |
| dc.subject | 肺癌 | zh_TW |
| dc.subject | 內皮細胞 | zh_TW |
| dc.subject | 細胞週期 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 血管新生 | zh_TW |
| dc.subject | 微管 | zh_TW |
| dc.subject | iASPP | zh_TW |
| dc.subject | p53 | zh_TW |
| dc.subject | PI3K/Akt | zh_TW |
| dc.subject | p53 | en |
| dc.subject | lung cancer | en |
| dc.subject | endothelial cell | en |
| dc.subject | iASPP | en |
| dc.subject | PI3K/Akt | en |
| dc.subject | cell cycle | en |
| dc.subject | apoptosis | en |
| dc.subject | angiogenesis | en |
| dc.subject | microtubule | en |
| dc.title | 透過調控p53路徑及血管新生控制肺癌細胞生長 | zh_TW |
| dc.title | Up-regulation of p53 Pathway and Down-regulation of
Angiogenesis in Lung Cancer Cell Growth Control | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 陳健尉,陳惠文,何肇基,魏淑? | |
| dc.subject.keyword | 肺癌,內皮細胞,細胞週期,細胞凋亡,血管新生,微管,iASPP,p53,PI3K/Akt, | zh_TW |
| dc.subject.keyword | lung cancer,endothelial cell,cell cycle,apoptosis,angiogenesis,iASPP,p53,microtubule,PI3K/Akt, | en |
| dc.relation.page | 181 | |
| dc.identifier.doi | 10.6342/NTU201800487 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-02-11 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-1.pdf 未授權公開取用 | 3.97 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。