請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78026
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡孟勳 | |
dc.contributor.author | Cheng-Ying Shen | en |
dc.contributor.author | 沈政瑩 | zh_TW |
dc.date.accessioned | 2021-07-11T14:40:02Z | - |
dc.date.available | 2022-02-21 | |
dc.date.copyright | 2017-02-21 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-01-23 | |
dc.identifier.citation | 1. Parshin, V.D., et al., [Diagnosis and treatment of lung cancer in polyneoplasia]. Probl Tuberk Bolezn Legk, 2008(11): p. 11-4.
2. Tsao, A.S. and J. Heymach, Mesothelioma and small cell lung cancer. J Thorac Oncol, 2011. 6(11 Suppl 4): p. S1825-6. 3. Nugent, W.C., et al., Non-small cell lung cancer at the extremes of age: impact on diagnosis and treatment. Ann Thorac Surg, 1997. 63(1): p. 193-7. 4. Molina, J.R., et al., Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc, 2008. 83(5): p. 584-94. 5. Wood, M.E., et al., The inherited nature of lung cancer: a pilot study. Lung Cancer, 2000. 30(2): p. 135-44. 6. Samet, J.M., et al., Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clin Cancer Res, 2009. 15(18): p. 5626-45. 7. Chen, C.J., et al., Epidemiologic characteristics and multiple risk factors of lung cancer in Taiwan. Anticancer Res, 1990. 10(4): p. 971-6. 8. Wu, A.H., et al., Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States. Am J Epidemiol, 1996. 143(6): p. 535-42. 9. Wu, A.H., et al., Personal and family history of lung disease as risk factors for adenocarcinoma of the lung. Cancer Res, 1988. 48(24 Pt 1): p. 7279-84. 10. Alavanja, M.C., et al., Saturated fat intake and lung cancer risk among nonsmoking women in Missouri. J Natl Cancer Inst, 1993. 85(23): p. 1906-16. 11. De Stefani, E., et al., Dietary fat and lung cancer: a case-control study in Uruguay. Cancer Causes Control, 1997. 8(6): p. 913-21. 12. Wood, S.L., et al., Molecular histology of lung cancer: from targets to treatments. Cancer Treat Rev, 2015. 41(4): p. 361-75. 13. Couraud, S., et al., Lung cancer in never smokers--a review. Eur J Cancer, 2012. 48(9): p. 1299-311. 14. Bradbury, P.A. and F.A. Shepherd, Chemotherapy and surgery for operable NSCLC. Lancet, 2007. 369(9577): p. 1903-4. 15. Herrmann, M.K., et al., Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC--treatment results after long-term follow-up and literature overview. Cancer Radiother, 2011. 15(2): p. 81-8. 16. Lawen, A., Apoptosis-an introduction. Bioessays, 2003. 25(9): p. 888-96. 17. Walsh, C.M., Grand challenges in cell death and survival: apoptosis vs. necroptosis. Front Cell Dev Biol, 2014. 2: p. 3. 18. Garg, A.D., et al., Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta, 2010. 1805(1): p. 53-71. 19. Cappuzzo, F., et al., Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst, 2005. 97(9): p. 643-55. 20. Liang, H., et al., Differential expression of RBM5, EGFR and KRAS mRNA and protein in non-small cell lung cancer tissues. J Exp Clin Cancer Res, 2012. 31: p. 36. 21. Brognard, J., et al., Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res, 2001. 61(10): p. 3986-97. 22. Yuan, T.L. and L.C. Cantley, PI3K pathway alterations in cancer: variations on a theme. Oncogene, 2008. 27(41): p. 5497-510. 23. Carpten, J.D., et al., A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature, 2007. 448(7152): p. 439-44. 24. Hotchkiss, R.S., et al., Cell death. N Engl J Med, 2009. 361(16): p. 1570-83. 25. Kerr, J.F., C.M. Winterford, and B.V. Harmon, Apoptosis. Its significance in cancer and cancer therapy. Cancer, 1994. 73(8): p. 2013-26. 26. Mukherjee, T.K., K. Paul, and S. Mukhopadhyay, Cell signaling molecules as drug targets in lung cancer: an overview. Curr Opin Pulm Med, 2011. 17(4): p. 286-91. 27. Le Chevalier, T., Non-small cell lung cancer: the challenges of the next decade. Front Oncol, 2011. 1: p. 29. 28. Blagosklonny, M.V., Antiangiogenic therapy and tumor progression. Cancer Cell, 2004. 5(1): p. 13-7. 29. Blagosklonny, M.V., Carcinogenesis, cancer therapy and chemoprevention. Cell Death Differ, 2005. 12(6): p. 592-602. 30. Blagosklonny, M.V., How Avastin potentiates chemotherapeutic drugs: action and reaction in antiangiogenic therapy. Cancer Biol Ther, 2005. 4(12): p. 1307-10. 31. Tomasz, M., Mitomycin C: small, fast and deadly (but very selective). Chem Biol, 1995. 2(9): p. 575-9. 32. Deans, A.J. and S.C. West, DNA interstrand crosslink repair and cancer. Nat Rev Cancer, 2011. 11(7): p. 467-80. 33. Huang, Y. and L. Li, DNA crosslinking damage and cancer - a tale of friend and foe. Transl Cancer Res, 2013. 2(3): p. 144-154. 34. Babiak, A., et al., Mitomycin C and Vinorelbine for second-line chemotherapy in NSCLC--a phase II trial. Br J Cancer, 2007. 96(7): p. 1052-6. 35. Lu, T.P., et al., Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women. Cancer Epidemiol Biomarkers Prev, 2010. 19(10): p. 2590-7. 36. Ruckdeschel, J.C., et al., Chemotherapy for metastatic non-small cell bronchogenic carcinoma: cyclophosphamide, doxorubicin, and etoposide versus mitomycin and vinblastine (EST 2575, generation IV). Cancer Treat Rep, 1984. 68(11): p. 1325-9. 37. Zacche, M.M., S. Srikrishna, and L. Cardozo, Novel targeted bladder drug-delivery systems: a review. Res Rep Urol, 2015. 7: p. 169-78. 38. Lustberg, M.B., et al., Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol, 2010. 5(5): p. 713-8. 39. Booton, R., et al., A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol, 2006. 17(7): p. 1111-9. 40. Seve, P. and C. Dumontet, Chemoresistance in non-small cell lung cancer. Curr Med Chem Anticancer Agents, 2005. 5(1): p. 73-88. 41. Chen, T.C., et al., Mitomycin C retardation of corneal fibroblast migration via sustained dephosphorylation of paxillin at tyrosine 118. Invest Ophthalmol Vis Sci, 2012. 53(3): p. 1539-47. 42. Chu, Y.W., et al., Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol, 1997. 17(3): p. 353-60. 43. Kang, Y., et al., A microarray study of radiation-induced transcriptional responses and the role of Jagged 1 in two closely-related lung cancer cell lines. Transl Cancer Res, 2015. 4(4): p. 314-323. 44. Fojo, T., Cancer, DNA repair mechanisms, and resistance to chemotherapy. J Natl Cancer Inst, 2001. 93(19): p. 1434-6. 45. Harris, A.L., DNA repair and resistance to chemotherapy. Cancer Surv, 1985. 4(3): p. 601-24. 46. Bouwman, P. and J. Jonkers, The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer, 2012. 12(9): p. 587-98. 47. Hinz, J.M., Role of homologous recombination in DNA interstrand crosslink repair. Environ Mol Mutagen, 2010. 51(6): p. 582-603. 48. Mathew, C.G., Fanconi anaemia genes and susceptibility to cancer. Oncogene, 2006. 25(43): p. 5875-84. 49. Liu, L.Z., et al., AKT1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of rapamycin/p70S6K1 pathway. Cancer Res, 2007. 67(13): p. 6325-6332. 50. Toulany, M. and H.P. Rodemann, Potential of Akt mediated DNA repair in radioresistance of solid tumors overexpressing erbB-PI3K-Akt pathway. Transl Cancer Res, 2013. 2(3): p. 190-202. 51. Franke, T.F., et al., PI3K/Akt and apoptosis: size matters. Oncogene, 2003. 22(56): p. 8983-98. 52. Nakashio, A., et al., Prevention of phosphatidylinositol 3'-kinase-Akt survival signaling pathway during topotecan-induced apoptosis. Cancer Res, 2000. 60(18): p. 5303-9. 53. Crowell, J.A., V.E. Steele, and J.R. Fay, Targeting the AKT protein kinase for cancer chemoprevention. Mol Cancer Ther, 2007. 6(8): p. 2139-48. 54. Sheppard, K., et al., Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit Rev Oncog, 2012. 17(1): p. 69-95. 55. 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. Mol Cancer Ther, 2010. 9(7): p. 1956-67. 56. Chen, G.G. and P.B. Lai, Apoptosis in carcinogenesis and cancer therapy. Curr Cancer Drug Targets, 2010. 10(6): p. 554. 57. Lowe, S.W. and A.W. Lin, Apoptosis in cancer. Carcinogenesis, 2000. 21(3): p. 485-95. 58. Thompson, C.B., Apoptosis in the pathogenesis and treatment of disease. Science, 1995. 267(5203): p. 1456-62. 59. Kerr, J.F., A.H. Wyllie, and A.R. Currie, Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 1972. 26(4): p. 239-57. 60. Frisch, S.M. and H. Francis, Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol, 1994. 124(4): p. 619-26. 61. Lavrik, I., A. Golks, and P.H. Krammer, Death receptor signaling. J Cell Sci, 2005. 118(Pt 2): p. 265-7. 62. Capparuccia, L. and L. Tamagnone, Semaphorin signaling in cancer cells and in cells of the tumor microenvironment--two sides of a coin. J Cell Sci, 2009. 122(Pt 11): p. 1723-36. 63. Tran, T.S., A.L. Kolodkin, and R. Bharadwaj, Semaphorin regulation of cellular morphology. Annu Rev Cell Dev Biol, 2007. 23: p. 263-92. 64. Yaron, A., et al., Differential requirement for Plexin-A3 and -A4 in mediating responses of sensory and sympathetic neurons to distinct class 3 Semaphorins. Neuron, 2005. 45(4): p. 513-23. 65. Winberg, M.L., et al., Plexin A is a neuronal semaphorin receptor that controls axon guidance. Cell, 1998. 95(7): p. 903-16. 66. Li, X. and A.Y. Lee, Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase. J Biol Chem, 2010. 285(42): p. 32436-45. 67. Kumanogoh, A. and H. Kikutani, Roles of the semaphorin family in immune regulation. Adv Immunol, 2003. 81: p. 173-98. 68. Feiner, L., et al., Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ. Neuron, 1997. 19(3): p. 539-45. 69. Tamagnone, L. and P.M. Comoglio, To move or not to move? Semaphorin signalling in cell migration. EMBO Rep, 2004. 5(4): p. 356-61. 70. Neufeld, G., et al., Semaphorins in angiogenesis and tumor progression. Cold Spring Harb Perspect Med, 2012. 2(1): p. a006718. 71. Basile, J.R., et al., Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis. Proc Natl Acad Sci, 2006. 103(24): p. 9017-22. 72. Swiercz, J.M., R. Kuner, and S. Offermanns, Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol, 2004. 165(6): p. 869-80. 73. Artigiani, S., et al., Plexin-B3 is a functional receptor for semaphorin 5A. EMBO Rep, 2004. 5(7): p. 710-4. 74. Director's Challenge Consortium for the Molecular Classification of Lung, A., et al., Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med, 2008. 14(8): p. 822-7. 75. Bild, A.H., et al., Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature, 2006. 439(7074): p. 353-7. 76. Catalano, A., et al., The plexin-A1 receptor activates vascular endothelial growth factor-receptor 2 and nuclear factor-kappaB to mediate survival and anchorage-independent growth of malignant mesothelioma cells. Cancer Res, 2009. 69(4): p. 1485-93. 77. Kitsukawa, T., et al., Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron, 1997. 19(5): p. 995-1005. 78. Guttmann-Raviv, N., et al., Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis. J Biol Chem, 2007. 282(36): p. 26294-305. 79. Tomizawa, Y., et al., Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci , 2001. 98(24): p. 13954-9. 80. Roche, J., et al., Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin. Oncogene, 1996. 12(6): p. 1289-97. 81. Xiang, R.H., et al., Isolation of the human semaphorin III/F gene (SEMA3F) at chromosome 3p21, a region deleted in lung cancer. Genomics, 1996. 32(1): p. 39-48. 82. Xiang, R., et al., Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice. Cancer Res, 2002. 62(9): p. 2637-43. 83. Kigel, B., et al., Successful inhibition of tumor development by specific class-3 semaphorins is associated with expression of appropriate semaphorin receptors by tumor cells. PLoS One, 2008. 3(9): p. e3287. 84. Roodink, I., et al., Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression. Am J Pathol, 2008. 173(6): p. 1873-81. 85. Fukushima, Y., et al., Sema3E-PlexinD1 signaling selectively suppresses disoriented angiogenesis in ischemic retinopathy in mice. J Clin Invest, 2011. 121(5): p. 1974-85. 86. Toyofuku, T., et al., Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. EMBO J, 2007. 26(5): p. 1373-84. 87. Nogi, T., et al., Structural basis for semaphorin signalling through the plexin receptor. Nature, 2010. 467(7319): p. 1123-7. 88. Dhanabal, M., et al., Recombinant semaphorin 6A-1 ectodomain inhibits in vivo growth factor and tumor cell line-induced angiogenesis. Cancer Biol Ther, 2005. 4(6): p. 659-68. 89. Suto, F., et al., Plexin-a4 mediates axon-repulsive activities of both secreted and transmembrane semaphorins and plays roles in nerve fiber guidance. J Neurosci, 2005. 25(14): p. 3628-37. 90. Suto, F., et al., Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron, 2007. 53(4): p. 535-47. 91. Xu, X.M., et al., The transmembrane protein semaphorin 6A repels embryonic sympathetic axons. J Neurosci, 2000. 20(7): p. 2638-48. 92. Runker, A.E., et al., Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology. PLoS ONE, 2011. 6(11): p. e26488. 93. Runker, A.E., et al., Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points. Neural Dev, 2008. 3: p. 34. 94. Klostermann, A., et al., The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain. J Biol Chem, 2000. 275(50): p. 39647-53. 95. Belinsky, S.A., Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev Cancer, 2004. 4(9): p. 707-17. 96. Wilson, N.S., V. Dixit, and A. Ashkenazi, Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol, 2009. 10(4): p. 348-55. 97. McIlwain, D.R., T. Berger, and T.W. Mak, Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol, 2013. 5(4): p. a008656. 98. Thorburn, A., Death receptor-induced cell killing. Cell Signal, 2004. 16(2): p. 139-44. 99. Chinnaiyan, A.M., et al., FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell, 1995. 81(4): p. 505-12. 100. Ashkenazi, A. and V.M. Dixit, Death receptors: signaling and modulation. Science, 1998. 281(5381): p. 1305-8. 101. Yeh, W.C., et al., FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science, 1998. 279(5358): p. 1954-8. 102. Hsu, H., et al., TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell, 1996. 84(2): p. 299-308. 103. Raponi, M., et al., Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res, 2006. 66(15): p. 7466-72. 104. Tomida, S., et al., Relapse-related molecular signature in lung adenocarcinomas identifies patients with dismal prognosis. J Clin Oncol, 2009. 27(17): p. 2793-9. 105. Mitomycin C. IARC Monogr Eval Carcinog Risk Chem Man, 1976. 10: p. 171-9. 106. Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl, 1987. 7: p. 1-440. 107. Buitenhuis, M., The role of PI3K/protein kinase B (PKB/c-akt) in migration and homing of hematopoietic stem and progenitor cells. Curr Opin Hematol, 2011. 18(4): p. 226-30. 108. Zhou, G.L., et al., Opposing roles for Akt1 and Akt2 in Rac/Pak signaling and cell migration. J Biol Chem, 2006. 281(47): p. 36443-53. 109. Liao, J., et al., Growth factor-dependent AKT activation and cell migration requires the function of c-K(B)-Ras versus other cellular ras isoforms. J Biol Chem, 2006. 281(40): p. 29730-8. 110. Hovelmann, S., T.L. Beckers, and M. Schmidt, Molecular alterations in apoptotic pathways after PKB/Akt-mediated chemoresistance in NCI H460 cells. Br J Cancer, 2004. 90(12): p. 2370-2377. 111. Kandel, E.S., et al., Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage. Mol Cell Biol, 2002. 22(22): p. 7831-41. 112. Datta, S.R., et al., Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 1997. 91(2): p. 231-41. 113. Downward, J., How BAD phosphorylation is good for survival. Nat Cell Biol, 1999. 1(2): p. E33-5. 114. Bai, D., L. Ueno, and P.K. Vogt, Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. Int J Cancer, 2009. 125(12): p. 2863-70. 115. Liang, Y., et al., Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer, 2004. 111(4): p. 484-93. 116. Gingis-Velitski, S., et al., Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice. Cancer Res, 2011. 71(22): p. 6986-6996. 117. Daenen, L.G., et al., Chemotherapy enhances metastasis formation via VEGFR-1-expressing endothelial cells. Cancer Res, 2011. 71(22): p. 6976-6985. 118. Tang, Y.A., et al., Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer. Nucleic acids research, 2015. 43(3): p. 1593-1608. 119. Katso, R., et al., Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol, 2001. 17: p. 615-675. 120. Musa, F. and R. Schneider, Targeting the PI3K/AKT/mTOR pathway in ovarian cancer. Transl Cancer Res, 2015. 4(1): p. 97-106. 121. Qiao, M., J.D. Iglehart, and A.B. Pardee, Metastatic potential of 21T human breast cancer cells depends on Akt/protein kinase B activation. Cancer Res, 2007. 67(11): p. 5293-5299. 122. Moldovan, G.L. and A.D. D'Andrea, How the fanconi anemia pathway guards the genome. Annu Rev Genet, 2009. 43: p. 223-249. 123. Sakoda, L.C., et al., Germ line variation in nucleotide excision repair genes and lung cancer risk in smokers. Int J Mol Epidemiol Genet, 2012. 3(1): p. 1-17. 124. Hou, S.M., et al., The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis, 2002. 23(4): p. 599-603. 125. Renaud, J., et al., Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nat Neurosci, 2008. 11(4): p. 440-9. 126. Mauti, O., et al., Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system. Neural Dev, 2007. 2: p. 28. 127. Debatin, K.M. and P.H. Krammer, Death receptors in chemotherapy and cancer. Oncogene, 2004. 23(16): p. 2950-66. 128. Henningsen, J., et al., Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation. Mol Cell Proteomics, 2010. 9(11): p. 2482-2496. 129. Gras, C., et al., Secreted semaphorin 5A activates immune effector cells and is a biomarker for rheumatoid arthritis. Arthritis Rheumatol, 2014. 66(6): p. 1461-71. 130. Henningsen, J., et al., Quantitative proteomics for investigation of secreted factors: focus on muscle secretome. Clin Proteomics, 2012. 9: p. 2. 131. Lee, E.W., et al., The roles of FADD in extrinsic apoptosis and necroptosis. BMB Rep, 2012. 45(9): p. 496-508. 132. Kischkel, F.C., et al., Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J, 1995. 14(22): p. 5579-88. 133. Cotter, T.G., Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer, 2009. 9(7): p. 501-7. 134. Ueno, K., et al., Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer. Hum Genet, 1998. 102(1): p. 63-8. 135. Cullinan, S.B., et al., Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol, 2003. 23(20): p. 7198-209. 136. Lamb, J., et al., The connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Sci Signal, 2006. 313: p. 1929. 137. Ushijima, M., et al., Development of a gene expression database and related analysis programs for evaluation of anticancer compounds. Cancer Sci, 2013. 104(3): p. 360-8. 138. Liu, C., et al., Compound signature detection on LINCS L1000 big data. Mol Biosyst, 2015. 11(3): p. 714-22. 139. Vicini, F.A., et al., Long-term impact of young age at diagnosis on treatment outcome and patterns of failure in patients with ductal carcinoma in situ treated with breast-conserving therapy. Breast J, 2013. 19(4): p. 365-73. 140. Hsu, Y.-C., et al., A simple gene set-based method accurately predicts the synergy of drug pairs. BMC Syst Biol, 2016. 10(3): p. 66. 141. Lu, X., et al., The SNP rs402710 in 5p15.33 Is Associated with Lung Cancer Risk: A Replication Study in Chinese Population and a Meta-Analysis. PLoS One, 2013. 8(10): p. e76252. 142. Ren, Y.W., et al., P53 Arg72Pro and MDM2 SNP309 Polymorphisms Cooperate to Increase Lung Adenocarcinoma Risk in Chinese Female Non-smokers: A Case Control Study. Asian Pac J Cancer Prev, 2013. 14(9): p. 5415-20. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78026 | - |
dc.description.abstract | 肺癌是世界上持續高踞癌症死亡主因的前幾位。肺癌同時也造成了癌症患友的家庭與社會的沉重負擔。在癌症細胞的發生過程中,癌症細胞內的訊息傳導,如有利於存活的磷酸化Akt與關掉能誘發細胞凋亡的路徑是需要的。許多化療藥物也是針對這些相關的訊息傳導路徑來設計。但是,有些抗癌藥物還是會引發一些藥物的不良反應,例如抗藥性的產生與癌症轉移。在本論文中,我們將利用兩篇研究來探討肺癌細胞面對化療藥物時的可能細胞訊息反應,與最新發現的semaphorin 6A對細胞凋亡的控制機制。
我們發現與同源母細胞株CL1-0相比,較惡性肺癌子細胞株CL1-5對mitomycin C (MMC)的抵抗能力較強。並且發現MMC會透過磷酸化Akt (p-Akt)的活化來增強CL1-5的細胞移動。在共同處理p-Akt 抑制劑與MMC之後則可以減低MMC產生的不良效應,並增加MMC的細胞毒性。因此磷酸化的Akt (p-Akt) 是造成MMC抗藥性與增強細胞移動的主因。 除此之外,本論文也將描述semaphorin 6A經由其細胞質內的蛋白質區與FADD結合所引發的細胞凋亡現象。此FADD與semaphorin 6A胞質內蛋白質區之結合現象更可藉由semaphorin 6A自身之胞質外蛋白質區(extracellular domain)來控制,進而降低胞質蛋白區所誘發之細胞凋亡的現象。 藉由本研究發現合併使用磷酸化Akt抑制劑與抗癌藥物能增進對惡性肺癌細胞的療效,與全新關於semaphorin 6A對細胞凋亡的調控,可以在未來於肺癌的臨床治療上有更好的貢獻。 | zh_TW |
dc.description.abstract | Lung cancer is the major cause of cancer-related death worldwide and brings significant socioeconomic effects to patients and their families. Cell signaling such as p-Akt activation for survival and silencing of cell death related pathways for evading senescence and apoptosis are required during lung carcinogenesis. Many drugs were developed against these signaling proteins for cancer therapy. Unfortunately, some anticancer-agents might induce adverse effects such as drug resistance or metastasis. In this thesis, two studies were used to elucidate the potential signaling within lung cancer cells in response to chemotherapeutic agents induced adverse effects, and the discovered activation of apoptosis in semaphorin 6A dependent regulation.
We found that the malignant lung cancer cells, CL1-5, were more resistant to mitomycin C than were the parental CL1-0 cells. Furthermore, cell migration was enhanced by MMC in CL1-5 cells. Administering a p-Akt inhibitor reduced the mitomycin C resistance, demonstrating that p-Akt is important in the mitomycin C resistance of CL1-5 cells. Our data suggest that in CL1-5 cells, the activity of p-Akt, may underlie the resistance to mitomycin C and enhance the cells’ migration abilities after drug treatment. Moreover, we described the discovered functions of semaphorin 6A in regulating apoptosis via its cytosolic region through interaction with FADD, and the SEMA domain might act as a safety pin by attenuating the interaction between FADD to prevent cytosolic domain of semaphorin 6A induced apoptosis. Overall, this thesis provides insights on an improved efficacy of chemotherapy by combining mitomycin C with a p-Akt inhibitor, and a newly discovered semaphorin 6A-regulated apoptosis signaling. We expect that the findings of this thesis can make contributions to lung cancer therapy. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:40:02Z (GMT). No. of bitstreams: 1 ntu-106-D96642006-1.pdf: 10931736 bytes, checksum: 74c5c681650c1584b64e24714434ec99 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | Contents
誌謝 ii Contents iii Table list ix Abbreviations x 中文摘要 12 Abstract 13 Chpater 1. General background 15 1.1. Lung cancer overview 16 1.2. Cell signaling in lung cancer 17 1.2.1 Survival signaling in cells 17 1.2.2. Apoptosis in cells 18 1.3. Cell signaling molecules as chemotherapeutic targets and the challenges of chemotherapy in lung cancer 18 1.4. Specific aims of this thesis 20 Chpater 2. The activation of p-Akt is needed for Mitomycin C induced signaling in aggressive lung cancer cells 21 2.1. Introduction 22 2.2. CL1-2 and CL1-5 cells were more resistant to MMC than were CL1-0 and CL1-1 cells 22 2.2.1. MMC induced longer G2/M arrest in CL1-0 cells 23 2.2.2. Asynchronous cells can be used to investigate MMC induced cell responses 24 2.3. DNA repair signaling are eliminated in the MMC induced drug resistance 24 2.3.1 Several DNA repaired signaling cannot be activate by MMC 24 2.3.2. MMC induced Fanconi anaemia and non-homologous end-joining repair signalling in CL1-0 but not CL1-5 cells 25 2.4. Survival signaling is a key factor to private the MMC induced cytotoxicity 25 2.4.1. Activation of p-Akt in CL1-5 cells reduced the MMC-induced cytotoxicity 26 2.5. MMC increased the migration abilities of CL1-5 but not CL1-0 cells 27 2.6. Material and method 27 2.6.1. Cell culture 28 2.6.2. Immunoblotting 28 2.6.3. MTT assay 29 2.6.4. Clonogenic assay 29 2.6.5. Double thymidine block and flow cytometry analysis 29 2.6.6. Immunofluorescence staining 30 2.6.7. Transwell assay 30 2.6.8. Statistical analysis 31 Chpater 3. Semaphorin 6A induces apoptosis via its cytosolic signaling through interaction with FADD 32 3.1 Introduction 33 3.1.1. Mechanism of apoptosis induced by membrane proteins 34 3.1.2. The roles of semaphorins in modulating of tumor progression 35 3.2. SEMA6A is down-regulated in lung tumor tissues and lung cancer cells 39 3.2.1. The potential mechanism of down-regulation of SEMA6A in lung cancer cells 41 3.3. The functions of SEMA6A in lung cancer cells 42 3.3.1. SEMA6A decreases the growth of lung cancer cells in vitro 43 3.3.2. Expression of SEMA6A induces changes in cellular motility 43 3.3.3. SEMA6A decreases the growth of lung cancer cells in vivo 43 3.3.4. SEMA6A induces apoptosis through its cytosolic domain 44 3.3.5. The cytosolic region of SEMA6A can induce apoptosis in vitro 44 3.3.6. The cytosolic region of SEMA6A can induce apoptosis in vivo 45 3.3.7. The SEMA domain regulates the induction of apoptosis 45 3.3.8. The 6Asema-induced apoptosis can be attenuated by reintroduced SEMA domain 45 3.3.9. The cytosolic domain of SEMA6A interacts with FADD 47 3.3.10. 6Acyto induced the cleavage forms of caspase-8 48 3.3.11. 6Acyto interacts with HSP 70 and GRP 78 49 3.3.12. The cytosolic domain of SEMA6A induces apoptosis via interaction with FADD 49 3.3.13. The reintroduction of SEMA domain reduced the association of FA DD and 6Asema 50 3.4. Material and method 51 3.4.1. Quantitative reverse transcriptase-PCR 51 3.4.2. Microarray data analysis 51 3.4.3. Survival analyses of two independent cohorts 52 3.4.4. DNA methylation sequencing 52 3.4.5. Immunohistochemistry (IHC) staining 52 3.4.6. SEMA6A, 6Asema, 6Acyto and 6Aect constructs 53 3.4.7. Cell culture 53 3.4.8. Immunoblotting 54 3.4.9. MTT assay 54 3.4.10. Clonogenic assay 55 3.4.11. Virus production and cell infection 55 3.4.12. Annexin V analysis for apoptosis 55 3.4.13. Xenograft tumor models 56 3.4.14. Purification of 6Asema protein 56 3.4.15. Coimmunoprecipitation assay 57 3.4.16. Silencing of and SEMA6A and FADD 57 3.4.17. Co-culture assay 57 3.4.18. Statistical analysis 58 Chpater 4. Conclusion 59 Chpater 5. General Discussion 61 5.1. Overview 62 5.2. The MMC-enhanced migration abilities in aggressive lung cancer cells are reduced by p-Akt inhibitor 62 5.3. The enriched p-Akt promote CL1-5 to go through cell cycle fast without DNA repair activation 63 5.4. Survival signaling activated by p-Akt might compensate MMC induced cytotoxicity in CL1-5 cells 64 5.5. MMC-induced p-Akt promotes the migration of CL1-5 cells. 64 5.6. p-Akt is more important than activated DNA repair mechanisms in the development of resistance to MMC treatment in CL1-5 cells. 65 5.7. Overview of SEMA6A in regulation of apoptosis 66 5.8. SEMA domain of SEMA6A acts as a safety pin for reducing SEMA6A-induced apoptosis 66 5.9. SEMA6A might be a new discovered death receptor 67 5.10. FADD related signaling is not the only apoptosis pathway induced by 6Acyto in lung cancer cells 68 5.11. Highly methylated SEMA6A and somatic deletion of SEMA6A in lung cancer cells 68 5.12. Overexpressed SEMA6A can induce ER stress in lung cancer cells 69 Chpater 6. Future work 71 6.1. To identify MLCAs induced adverse effects in CL1-5 cells 72 6.2. To identify the other cell responses activated by SEMA6A 75 List of tables 77 List of Figures 84 Reference list 130 Appendix 140 | |
dc.language.iso | en | |
dc.title | 研究肺癌細胞內信息傳導之調控
1. 磷酸化Akt於Mitomycin C引起之不良反應所扮演的角色 2. Semaphorin 6A於細胞凋亡之自我調控 | zh_TW |
dc.title | To study the regulations of cell signaling in lung cancer cells:
1. The role of phosphorylated Akt in mitomycin C induced adverse responses. 2. Self-regulation of semaphorin 6A in apoptosis. | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 莊曜宇,賴亮全,李心予,阮雪芬,李宜靜 | |
dc.subject.keyword | 磷酸化Akt,MMC化療藥物,肺癌細胞,semaphorin 6A膜蛋白,細胞凋亡,semaphorin 6A胞質外蛋白質區, | zh_TW |
dc.subject.keyword | p-Akt,MMC,lung cancer cells,semaphorin 6A,apoptosis,SEMA domain of semaphorin 6A, | en |
dc.relation.page | 140 | |
dc.identifier.doi | 10.6342/NTU201700179 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-01-24 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-D96642006-1.pdf 目前未授權公開取用 | 10.68 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。