請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81626完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡孟勳(Mong-Hsun Tsai) | |
| dc.contributor.author | Shin-Her Huang | en |
| dc.contributor.author | 黃信和 | zh_TW |
| dc.date.accessioned | 2022-11-24T09:24:53Z | - |
| dc.date.available | 2022-11-24T09:24:53Z | - |
| dc.date.copyright | 2021-09-11 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-09-04 | |
| dc.identifier.citation | 1. Sung, H., et al., Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021. 2. SEER Cancer Stat Facts: Lung and Bronchus Cancer. National Cancer Institute. Bethesda, MD. 3. Liu, J., et al., Multi-subtype classification model for non-small cell lung cancer based on radiomics: SLS model. Med Phys, 2019. 46(7): p. 3091-3100. 4. Gurda, G.T., et al., Utility of five commonly used immunohistochemical markers TTF-1, Napsin A, CK7, CK5/6 and P63 in primary and metastatic adenocarcinoma and squamous cell carcinoma of the lung: a retrospective study of 246 fine needle aspiration cases. Clin Transl Med, 2015. 4: p. 16. 5. Kargi, A.M.G., Duygu MD; Tuna, Burçin MD, The Diagnostic Value of TTF-1, CK 5/6, and p63 Immunostaining in Classification of Lung Carcinomas. Appl Immunohistochem Mol Morphol, 2007. 15(4): p. 415-520. 6. Ordóñez, N.G.M., Value of Thyroid Transcription Factor-1 Immunostaining in Tumor Diagnosis: A Review and Update. Appl Immunohistochem Mol Morphol, 2012. 20(5): p. 429-444. 7. Mukhopadhyay, S.M.K., Anna-Luise A. MD, Subclassification of Non-small Cell Lung Carcinomas Lacking Morphologic Differentiation on Biopsy Specimens. Am J Surg Pathol, 2011. 35(1): p. 15-25. 8. Argon, A., D. Nart, and A. Veral, The Value of Cytokeratin 5/6, p63 and Thyroid Transcription Factor-1 in Adenocarcinoma, Squamous Cell Carcinoma and Non-Small-Cell Lung Cancer of the Lung. Turk Patoloji Derg, 2015. 31(2): p. 81-8. 9. Momcilovic, M., et al., The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma. Cancer Cell, 2018. 33(5): p. 905-921 e5. 10. Wei Li, J.Z., Yuqing Chen, Gengyan Zhang, Peng Jiang, Lei Hong, Yuangbing Shen, Xiaojing Wang, and Xiaomeng Gong, Cigarette smoke enhances initiation and progression of lung cancer by mutating Notch1/2 and dysregulating downstream signaling molecules. Oncotarget, 2017. 8(70): p. 115128-115139. 11. Barta, J.A., C.A. Powell, and J.P. Wisnivesky, Global Epidemiology of Lung Cancer. Ann Glob Health, 2019. 85(1). 12. Bade, B.C. and C.S. Dela Cruz, Lung Cancer 2020: Epidemiology, Etiology, and Prevention. Clin Chest Med, 2020. 41(1): p. 1-24. 13. Wakelee, H.A., et al., Lung cancer incidence in never smokers. J Clin Oncol, 2007. 25(5): p. 472-8. 14. Okazaki, I., et al., Lung Adenocarcinoma in Never Smokers: Problems of Primary Prevention from Aspects of Susceptible Genes and Carcinogens. Anticancer Res, 2016. 36(12): p. 6207-6224. 15. El-Telbany, A. and P.C. Ma, Cancer genes in lung cancer: racial disparities: are there any? Genes Cancer, 2012. 3(7-8): p. 467-80. 16. Mascaux, C., et al., The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer, 2005. 92(1): p. 131-9. 17. Beau-Faller, M., et al., Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol, 2014. 25(1): p. 126-31. 18. Camidge, D.R., et al., Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol, 2012. 13(10): p. 1011-1019. 19. Paik, P.K., et al., Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol, 2011. 29(15): p. 2046-51. 20. Oxnard, G.R., et al., New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer. Clin Cancer Res, 2011. 17(17): p. 5530-7. 21. Garon, E.B., et al., Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med, 2015. 372(21): p. 2018-28. 22. Islam, K.M., et al., Patient preferences of chemotherapy treatment options and tolerance of chemotherapy side effects in advanced stage lung cancer. BMC Cancer, 2019. 19(1): p. 835. 23. Ruiz-Cordero, R. and W.P. Devine, Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer. Surg Pathol Clin, 2020. 13(1): p. 17-33. 24. Lu, X., et al., Targeting EGFR(L858R/T790M) and EGFR(L858R/T790M/C797S) resistance mutations in NSCLC: Current developments in medicinal chemistry. Med Res Rev, 2018. 38(5): p. 1550-1581. 25. Hong, D.S., et al., KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med, 2020. 383(13): p. 1207-1217. 26. Couzin-Frankel, J., Cancer Immunotherapy. Science, 2013. 342(6165): p. 1432-1433. 27. Reck, M., et al., Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med, 2016. 375(19): p. 1823-1833. 28. Langer, C.J., et al., Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol, 2016. 17(11): p. 1497-1508. 29. Passive Immunotherapy, in Encyclopedic Reference of Immunotoxicology, H.-W. Vohr, Editor. 2005, Springer Berlin Heidelberg: Berlin, Heidelberg. p. 493-494. 30. Chodon, T., R.C. Koya, and K. Odunsi, Active Immunotherapy of Cancer. Immunol Invest, 2015. 44(8): p. 817-36. 31. Papaioannou, N.E., et al., Harnessing the immune system to improve cancer therapy. Ann Transl Med, 2016. 4(14): p. 261. 32. Raju R Raval, A.B.S., Amanda J Walker, Charles G Drake Padmanee Sharma, Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer. J Immunother Cancer, 2014. 2: p. 14. 33. Vivier, E., et al., Functions of natural killer cells. Nat Immunol, 2008. 9(5): p. 503-10. 34. Maher, J. and E.T. Davies, Targeting cytotoxic T lymphocytes for cancer immunotherapy. Br J Cancer, 2004. 91(5): p. 817-21. 35. Mitchell, R.E., et al., IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation. Sci Rep, 2017. 7(1): p. 11315. 36. Kumar, S., et al., Dendritic Cell-Mediated Th2 Immunity and Immune Disorders. Int J Mol Sci, 2019. 20(9). 37. Vignali, D.A., L.W. Collison, and C.J. Workman, How regulatory T cells work. Nat Rev Immunol, 2008. 8(7): p. 523-32. 38. Galli, F., et al., Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy. J Exp Clin Cancer Res, 2020. 39(1): p. 89. 39. Lin, A., et al., Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations, in Mol Cancer. 2019. p. 139. 40. Whiteside, T.L., The tumor microenvironment and its role in promoting tumor growth. Oncogene, 2008. 27(45): p. 5904-12. 41. McNally, A., et al., CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proc Natl Acad Sci U S A, 2011. 108(18): p. 7529-7534. 42. Mantovani, A., et al., Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol, 2017. 14(7): p. 399-416. 43. DiLillo, D.J., K. Yanaba, and T.F. Tedder, B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice. J Immunol, 2010. 184(7): p. 4006-16. 44. Bejarano, L., M.J.C. Jordao, and J.A. Joyce, Therapeutic Targeting of the Tumor Microenvironment. Cancer Discov, 2021. 11(4): p. 933-959. 45. Sadelain, J.-B.L.M., Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells. Nat Biotechnol, 2000. 18: p. 405-409. 46. Guillerey, C., N.D. Huntington, and M.J. Smyth, Targeting natural killer cells in cancer immunotherapy. Nat Immunol, 2016. 17(9): p. 1025-36. 47. Oh, S., et al., Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors. Cancers, 2019. 11(10). 48. Qu, J., et al., Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives. Cancer Immunol Immunother, 2020. 49. Edward A. Hirschowitz, D.M.H., John R. Yannelli, Vaccines for Lung Cancer. J Thorac Oncol., 2006. 1: p. 93-104. 50. Ramlogan-Steel, C.A., J.C. Steel, and J.C. Morris, Lung cancer vaccines: current status and future prospects. Transl Lung Cancer Res, 2014. 3(1): p. 46-52. 51. Onoi, K., et al., Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review. J Clin Med, 2020. 9(5). 52. C.S Goodman, A.L.K., Y Luo, A.W Püschel, J.A Raper, Unified Nomenclature for the Semaphorins/Collapsins. Cell, 1999. 97(5): p. 551-552. 53. Janssen, B.J., et al., Structural basis of semaphorin-plexin signalling. Nature, 2010. 467(7319): p. 1118-22. 54. Pasterkamp, R.J. and A.L. Kolodkin, Semaphorin junction: making tracks toward neural connectivity. Curr Opin Neurobiol, 2003. 13(1): p. 79-89. 55. Alex L. Kolodkin, D.J.M., Corey S.Goodman, The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell, 1993. 75: p. 1389-1399. 56. Takamatsu, H., T. Okuno, and A. Kumanogoh, Regulation of immune cell responses by semaphorins and their receptors. Cell Mol Immunol, 2010. 7(2): p. 83-8. 57. Hu, S. and L. Zhu, Semaphorins and Their Receptors: From Axonal Guidance to Atherosclerosis. Front Physiol, 2018. 9: p. 1236. 58. Fujisawa, H., Discovery of semaphorin receptors, neuropilin and plexin, and their functions in neural development. J Neurobiol, 2004. 59(1): p. 24-33. 59. Raimondi, C. and C. Ruhrberg, Neuropilin signalling in vessels, neurons and tumours. Semin Cell Dev Biol, 2013. 24(3): p. 172-8. 60. Chenghua Gu, Y.Y., Jean Livet, Dorothy V. Reimert, Fanny Mann, Janna Merte,Christopher E. Henderson, Thomas M. Jessell, Alex L. Kolodkin, and D.D. Ginty, Semaphorin 3E and Plexin-D1 Control Vascular Pattern Independently of Neuropilins. Science, 2005. 307(5707): p. 265-268. 61. Jongbloets, B.C. and R.J. Pasterkamp, Semaphorin signalling during development. Development, 2014. 141(17): p. 3292-7. 62. 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. 63. Gurrapu, S. and L. Tamagnone, Transmembrane semaphorins: Multimodal signaling cues in development and cancer. Cell Adh Migr, 2016. 10(6): p. 675-691. 64. Emely Castro-Rivera, S.R., [...], and John D. Minna, Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. PNAS, 2003. 101(31): p. 11432-11437. 65. Rolny, C., et al., The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment. J Exp Med, 2008. 205(5): p. 1155-71. 66. Roodink, I., et al., Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression. Am J Pathol, 2008. 173(6): p. 1873-81. 67. Ofra Kessler, N.S.-H., Tali Lange, Noga Gutmann-Raviv, Edmond Sabo, Limor Baruch, Marcelle Machluf and Gera Neufeld, Semaphorin-3F Is an Inhibitor of Tumor Angiogenesis. cancer res, 2004. 64: p. 1008-1015. 68. Kusy, S., et al., Selective suppression of in vivo tumorigenicity by semaphorin SEMA3F in lung cancer cells. Neoplasia, 2005. 7(5): p. 457-65. 69. John R. Basile, R.M.C., Vanessa P. Williams, and J. Silvio Gutkind, Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis. PNAS, 2006. 103(24): p. 9017-9022. 70. Zhang, Y., et al., Plexin-B1: a potential diagnostic biomarker for glioma and a future target for glioma immunotherapy. J Neuroimmunol, 2012. 252(1-2): p. 113-7. 71. Audrey P. Le, Y.H., Sandeep C. Pingle, Santosh Kesari, Huaien Wang, Raymund L. Yong, Hongyan Zou and Roland H. Friedel, Plexin-B2 promotes invasive growth of malignant glioma. Oncotarget, 2015. 6(9): p. 7293-7304. 72. Ko, P.H., et al., Semaphorin 5A suppresses the proliferation and migration of lung adenocarcinoma cells. Int J Oncol, 2020. 56(1): p. 165-177. 73. Chen, L.H. and E.Y. Cuang, Importance of semaphorins in cancer immunity. Transl Lung Cancer Res, 2019. 8(Suppl 4): p. S468-S470. 74. Casazza, A., et al., Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell, 2013. 24(6): p. 695-709. 75. Atsushi Kumanogoh, S.M., Kazuhiro Suzuki,, C.W. Noriko Takegahara, EweSeng Ch’ng, Isao Ishida,, and S.S. Harutoshi Fujimura, Kanji Yoshida Hitoshi Kikutani, Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature, 2002. 419: p. 629-633. 76. Meda, C., et al., Semaphorin 4A exerts a proangiogenic effect by enhancing vascular endothelial growth factor-A expression in macrophages. J Immunol, 2012. 188(8): p. 4081-92. 77. Eissler, N. and C. Rolny, The role of immune semaphorins in cancer progression. Exp Cell Res, 2013. 319(11): p. 1635-43. 78. Kumanogoh, A., et al., Requirement for CD100-CD72 interactions in fine-tuning of B-cell antigen receptor signaling and homeostatic maintenance of the B-cell compartment. Int Immunol, 2005. 17(10): p. 1277-82. 79. Takegahara, N., et al., Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol, 2006. 8(6): p. 615-22. 80. Suzuki, K., A. Kumanogoh, and H. Kikutani, Semaphorins and their receptors in immune cell interactions. Nat Immunol, 2008. 9(1): p. 17-23. 81. Morote-Garcia, J.C., et al., Endothelial Semaphorin 7A promotes neutrophil migration during hypoxia. Proc Natl Acad Sci U S A, 2012. 109(35): p. 14146-51. 82. Zhou, Y., R.A. Gunput, and R.J. Pasterkamp, Semaphorin signaling: progress made and promises ahead. Trends Biochem Sci, 2008. 33(4): p. 161-70. 83. Chen, L.H., et al., Semaphorin 6A Attenuates the Migration Capability of Lung Cancer Cells via the NRF2/HMOX1 Axis. Sci Rep, 2019. 9(1): p. 13302. 84. Zhao, J., et al., SEMA6A is a prognostic biomarker in glioblastoma. Tumor Biol, 2015. 36(11): p. 8333-8340. 85. Urbich, C., et al., MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A. Blood, 2012. 119(6): p. 1607-16. 86. Zhou, Q., et al., Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters. Proc Natl Acad Sci U S A, 2011. 108(20): p. 8287-92. 87. 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. 88. Shen, C.Y., et al., The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells. Oncogenesis, 2018. 7(12): p. 95. 89. St Clair, R.M., et al., PKC induces release of a functional ectodomain of the guidance cue semaphorin6A. FEBS Lett, 2019. 593(21): p. 3015-3028. 90. Lee, H., et al., Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins. Cell, 2020. 182(2): p. 345-356 e16. 91. Alex L. Kolodkin, D.V.L., Erica G. Rowe, Yu-Tzu Tai, Roman J. Giger, and David D. Ginty, Neuropilin Is a Semaphorin III Receptor. Cell, 1997. 90: p. 753-762. 92. Schwarz, Q., et al., Plexin A3 and plexin A4 convey semaphorin signals during facial nerve development. Dev Biol, 2008. 324(1): p. 1-9. 93. Catalano, A., et al., Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function. Blood, 2006. 107(8): p. 3321-9. 94. Yamamoto, M., et al., Plexin-A4 negatively regulates T lymphocyte responses. Int Immunol, 2008. 20(3): p. 413-20. 95. Catalano, A., The neuroimmune semaphorin-3A reduces inflammation and progression of experimental autoimmune arthritis. J Immunol, 2010. 185(10): p. 6373-83. 96. Leclerc, M., et al., Regulation of antitumour CD8 T-cell immunity and checkpoint blockade immunotherapy by Neuropilin-1. Nat Commun, 2019. 10(1): p. 3345. 97. Malkinson, A.M., The genetic basis of susceptibility to lung tumors in mice. Toxicology, 1989. 54: p. 241-271. 98. Cekanova, M. and K. Rathore, Animal models and therapeutic molecular targets of cancer: utility and limitations. Drug Des Devel Ther, 2014. 8: p. 1911-21. 99. Yokohira, M., et al., Establishment of a bioassay model for lung cancer chemoprevention initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice. Exp Toxicol Pathol, 2008. 60(6): p. 469-73. 100. Guang-yu Yang, Z.L., Darren N.Seril, Jie Liao, Wei Ding, Sungbin Kim, lordeliza Bondoc and Chung S.Yang, Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Carcinogenesis, 1997. 18(12): p. 2361-2365. 101. Kellar, A., C. Egan, and D. Morris, Preclinical Murine Models for Lung Cancer: Clinical Trial Applications. Biomed Res Int, 2015. 2015: p. 621324. 102. Franklin, M., LL/2: an immunosuppressive murine tumor model. 2019. 103. Sakai, Y., et al., Conjugated linoleic acid reduced metastasized LL2 tumors in mouse peritoneum. Virchows Arch, 2006. 449(3): p. 341-7. 104. De Vlaeminck, Y., et al., Targeting Neuropilin-1 with Nanobodies Reduces Colorectal Carcinoma Development. Cancers, 2020. 12(12). 105. Chuckran, C.A., et al., Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy. J Immunother Cancer, 2020. 8(2). 106. Jung, K., et al., A Neuropilin-1 Antagonist Exerts Antitumor Immunity by Inhibiting the Suppressive Function of Intratumoral Regulatory T Cells. Cancer Immunol Res, 2020. 8(1): p. 46-56. 107. 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. 108. 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. 109. Gautier, G., et al., The class 6 semaphorin SEMA6A is induced by interferon-gamma and defines an activation status of langerhans cells observed in pathological situations. Am J Pathol, 2006. 168(2): p. 453-65. 110. Bruder, D., et al., Neuropilin-1: a surface marker of regulatory T cells. Eur J Immunol, 2004. 34(3): p. 623-630. 111. Sidaway, P., Immunotherapy: Neuropilin-1 is required for Treg stability. Nat Rev Clin Oncol, 2017. 14(8): p. 458. 112. Narumi, K., et al., Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery. Sci Rep, 2019. 9(1): p. 5562. 113. Holliger, P. and P.J. Hudson, Engineered antibody fragments and the rise of single domains. Nat Biotechnol, 2005. 23(9): p. 1126-36. 114. Konig, L., et al., Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer. BMC Cancer, 2019. 19(1): p. 120. 115. Xu, X., et al., Adeno-associated virus (AAV)-based gene therapy for glioblastoma. Cancer Cell Int, 2021. 21(1): p. 76. 116. Ma, H.I., et al., Intratumoral decorin gene delivery by AAV vector inhibits brain glioblastomas and prolongs survival of animals by inducing cell differentiation. Int J Mol Sci, 2014. 15(3): p. 4393-414. 117. Shi, W., et al., Adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo. Cancer Gene Ther, 2002. 9(6): p. 513-21. 118. Wu, J.Q., et al., Adeno-associated virus mediated gene transfer into lung cancer cells promoting CD40 ligand-based immunotherapy. Virology, 2007. 368(2): p. 309-16. 119. Jun Yoshida, M.M., Norimoto Nakahara, Peter Colosi, Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma. Jpn J Cancer Res, 2002. 93: p. 223-228. 120. Mohr, A., et al., AAV-encoded expression of TRAIL in experimental human colorectal cancer leads to tumor regression. Gene Ther, 2004. 11(6): p. 534-43. 121. S Beissert, J.H., S Grabbe, A Asahina and R D Granstein, IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells. J Immunol, 1995. 154(1): p. 1280-1286. 122. Suyun Huang, S.E.U., and Menashe Bar-Eli, Regulation of Tumor Growth and Metastasis by Interleukin-10: The Melanoma Experience. J Interferon Res, 1999. 19(7): p. 697-703. 123. Sakamoto, T., et al., Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancer. Int J Cancer, 2006. 118(8): p. 1909-14. 124. Hatanaka, H., et al., Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer. Ann Oncol, 2000. 11(7): p. 815-9. 125. Li, J., et al., Prognostic value of TGF-beta in lung cancer: systematic review and meta-analysis. BMC Cancer, 2019. 19(1): p. 691. 126. Tang, F. and P. Zheng, Tumor cells versus host immune cells: whose PD-L1 contributes to PD-1/PD-L1 blockade mediated cancer immunotherapy? Cell Biosci, 2018. 8: p. 34. 127. Pavlin, D., et al., Local and systemic antitumor effect of intratumoral and peritumoral IL-12 electrogene therapy on murine sarcoma. Cancer Biol Ther, 2009. 8(22): p. 2114-22. 128. Grépin, R. and G. Pagès, Measurement of Cytokines. Bio Protoc, 2012. 2(22): p. e290. 129. Smyth, M.J., et al., CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol, 2006. 176(3): p. 1582-7. 130. Ghiringhelli, F., et al., Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med, 2005. 202(7): p. 919-29. 131. Tanaka, A. and S. Sakaguchi, Regulatory T cells in cancer immunotherapy. Cell Res, 2017. 27(1): p. 109-118. 132. Shimizu, J., et al., Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol, 2002. 3(2): p. 135-42. 133. ChauVert, F.G.C.M.P.E.P.S.L.S.R.F.M.E.S.A.L.C.L.Z.B., Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother, 2007. 56: p. 641-648. 134. Hatanaka, Y., et al., Semaphorin 6A-Plexin A2/A4 Interactions with Radial Glia Regulate Migration Termination of Superficial Layer Cortical Neurons. iScience, 2019. 21: p. 359-374. 135. Kuo, Y.C., et al., Cryo-EM structure of the PlexinC1/A39R complex reveals inter-domain interactions critical for ligand-induced activation. Nat Commun, 2020. 11(1): p. 1953. 136. 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. 137. Ito, D., et al., mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells. J Immunol, 2015. 195(3): p. 934-43. 138. Ge, G.Z., T.R. Xu, and C. Chen, Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms. Acta Biochim Biophys Sin (Shanghai), 2015. 47(7): p. 477-87. 139. Desai, D., et al., Chemopreventive efficacy of suberoylanilide hydroxamic acid (SAHA) against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Anticancer Res, 2003. 23: p. 499-503. 140. Razani-Boroujerdi, S. and M.L. Sopori, Early manifestations of NNK-induced lung cancer: role of lung immunity in tumor susceptibility. Am J Respir Cell Mol Biol, 2007. 36(1): p. 13-9. 141. Goud, S.N. and A.M. Kaplan, Inhibition of natural killer cell activity in mice treated with tobacco specific carcinogen NNK. J Toxicol Environ Health A, 1999(1528-7394 (Print)). 142. Sun, Z. and Z. Xiao, 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) regulates CTL activation and memory programming. Biochem Biophys Res Commun, 2013. 435(3): p. 472-6. 143. Granville, C.A., et al., A central role for Foxp3+ regulatory T cells in K-Ras-driven lung tumorigenesis. PLoS One, 2009. 4(3): p. e5061. 144. Lin, L., et al., Additional evidence that the K-ras protooncogene is a candidate for the major mouse pulmonary adenoma susceptibility (Pas-1) gene. Exp Lung Res, 1998. 24(4): p. 481-97. 145. Ryan, J., et al., KRAS2 as a genetic marker for lung tumor susceptibility in inbred mice. JNCI, 1987(0027-8874 (Print)). 146. Davis, R., et al., Nicotine promotes tumor growth and metastasis in mouse models of lung cancer. PLoS One, 2009. 4(10): p. e7524. 147. Miller, Y.E., et al., Induction of a high incidence of lung tumors in C57BL/6 mice with multiple ethyl carbamate injections. Cancer Lett, 2003. 198(2): p. 139-144. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81626 | - |
| dc.description.abstract | 全球肺癌於癌症排名中致死率高居第一、發生率位居第二，五年存活率僅21％。肺癌患者通常接受手術、化學療法、放射療法或標靶療法，而近期較新的免疫療法正蓬勃發展，免疫療法可以藉由刺激抗癌免疫反應或抵消由癌細胞誘導的免疫抑制機制達成治療功效。先前研究證實Semaphorin6A（Sema6A）可以透過競爭Semaphorin3A (Sema3A)與Neuropinlin1（Nrp1）/ Plexin-A4共受體的結合而增強細胞毒殺型T細胞的增生能力同時減少調節型T細胞的增生能力，Sema6A成為免疫治療的潛在目標。由於Sema6A的分子量高、結構複雜且為穿膜蛋白，製程困難，因此，本研究設計兩種Sema6A為基礎的重組蛋白—SEMA-PSI與SEMA，並使用Sema6A基因剔除C57BL/6J小鼠探討Sema6A蛋白、SEMA-PSI重組蛋白及SEMA重組蛋白對於抗癌免疫反應的影響。競爭試驗顯示Sema6A蛋白、SEMA-PSI和SEMA重組蛋白於濃度為5至20 μg/ml時可競爭Sema3A與Nrp1的結合。透過共培養LL/2小鼠肺癌細胞株與來自皮下注射LL/2的Sema6A基因剔除以及野生型小鼠的脾臟細胞，顯示SEMA重組蛋白均可顯著減少調節型T細胞的增生能力，也代表抗癌免疫的提升，SEMA-PSI重組蛋白可降低調節型T細胞的增生能力但未達顯著，而Sema6A蛋白未顯著影響免疫細胞的增生能力。活體實驗顯示，LL/2腫瘤於Sema6A基因剔除小鼠的生長較野生型小鼠快速，且腫瘤浸潤毒殺型T細胞的比例也顯著低於野生型小鼠。為了評估在活體中Sema6A、SEMA-PSI和SEMA重組蛋白治療後的抗癌免疫情形，皮下注射LL/2細胞至Sema6A基因剔除小鼠，每兩天腫瘤周邊皮下注射20μg的蛋白，與對照組相比，SEMA重組蛋白可顯著降低腫瘤的生長，而Sema6A和SEMA-PSI重組蛋白未顯著降低腫瘤的生長，SEMA重組蛋白治療的組別中，腫瘤浸潤毒殺型T細胞無顯著差異，而腫瘤浸潤調節型T細胞有下降趨勢但未達顯著，取其脾臟細胞發現毒殺型T細胞及自然殺手細胞的增生能力有上升趨勢但未達顯著，調節型T細胞的增生能力也有下降但未達顯著。另外於野生型小鼠模型中，SEMA-PSI及SEMA重組蛋白治療後未顯著降低LL/2腫瘤生長，但SEMA重組蛋白治療後的腫瘤浸潤毒殺型T細胞有上升趨勢，且調節型T細胞增生能力也有下降趨勢。為建立化學物質誘導的肺癌致癌模型，本研究將致癌物4-（甲基亞硝胺）-1-（3-吡啶基）-1-丁酮 （NNK）腹腔注射至14隻Sema6A基因剔除及8隻野生型小鼠，觀察第16周及32周時鼠肺中結節的形成，僅一隻Sema6A基因剔除小鼠肺部外觀於第16周出現明顯腫瘤結節，依據病理組織型態判讀為骨肉瘤，而野生型小鼠肺部外觀皆未觀察到明顯腫瘤結節，經蘇木精-伊紅染色後，無論第16周或32周，小鼠肺部損傷程度於Sema6A基因剔除小鼠皆高於野生型小鼠，且未觀察到肺腺癌細胞或鱗狀上皮癌細胞的形成。 總結而論，LL/2腫瘤於Sema6A基因剔除小鼠中生長較野生型小鼠快速，且腫瘤浸潤毒殺型T細胞顯著降低。Sema6A蛋白、SEMA-PSI重組蛋白和SEMA重組蛋白可以競爭Sema3A與Nrp1的結合。活體外共培養結果顯示SEMA重組蛋白可顯著減少調節型T細胞的增生能力，意謂抗癌免疫反應的提升。活體試驗指出SEMA重組蛋白有提升抗癌免疫的趨勢，顯著降低LL/2腫瘤於Sema6A基因剔除小鼠的生長，綜上所述，SEMA重組蛋白的抗癌效果較Sema6A蛋白及SEMA-PSI重組蛋白優異，成為潛在的肺癌免疫治療蛋白。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T09:24:53Z (GMT). No. of bitstreams: 1 U0001-0708202116070300.pdf: 7634580 bytes, checksum: f06b6a61d1d2475acc6de5dd1024e171 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員審定書 I 致謝 II 中文摘要 III Abstract V Contents VIII Table list XII Figure list XIII Chapter 1. Literature review 1 1.1 Lung cancer overview 1 1.1.1. Statistics of lung cancer 1 1.1.2. Types of lung cancer 1 1.1.3. Causes of lung cancer 2 1.1.4. Treatments of lung cancer 2 1.2 Cancer immunotherapy overview 3 1.2.1. Introduction of immunotherapy 3 1.2.2. Mechanism of immune system 4 1.2.3. Tumor microenvironment (TME) 5 1.2.4. Adoptive cytotoxic T cell therapy 7 1.2.5. Adoptive natural killer cell therapy 7 1.2.6. Chimeric antigen receptor (CAR)-T cell therapy 7 1.2.7. Cancer vaccine 7 1.2.8. Immune checkpoint therapy 8 1.3 Semaphorin overview 8 1.3.1. Semaphorin family 8 1.3.2. Semaphorin receptors and signaling 10 1.3.3. Semaphorins in cancer 11 1.3.4. Semaphorin-related immunity 11 1.3.5. Semaphorin6A 12 1.3.6. Semaphorin3A 13 1.4 Animal model for lung cancer 13 1.4.1. Strain of C57BL/6J mice 14 1.4.2. Lung cancer model 14 1.5 Pilot study 15 Chapter 2. Research motivation and aims 16 Chapter 3. Materials and methods 17 3.1 Experimental design 17 3.2 Medium preparation 17 3.3 Cell lines and cell culture 18 3.4 RNA extraction 18 3.5 Reverse transcription qPCR 19 3.6 Cloning of recombinant protein 19 3.7 Protein production and purification 20 3.8 Western blot analysis 22 3.9 Competitive assay 23 3.10 Ex vivo assay 24 3.11 Flow cytometry 25 3.12 Animals 26 3.13 Mouse tail Sema6A genotyping 26 3.14 Protein treatment in Sema6A knockout mice 27 3.15 Protein treatment in wild-type mice 27 3.16 Tumor dissociation 28 3.17 Immunohistochemical (IHC) staining and hematoxylin-eosin (H E) staining 28 3.18 NNK induction mouse model 29 3.19 Statistical analysis 29 Chapter 4. Results 30 4.1 Mouse full-length Sema6A protein, SEMA-PSI recombinant protein, SEMA recombinant protein, and mouse Sema3A protein were manufactured successfully 30 4.2 Mouse full-length Sema6A protein, SEMA-PSI recombinant protein, and SEMA recombinant protein had competitive effect with the binding of Sema3A to Nrp1 30 4.3 SEMA recombinant proteins could significantly reduce proliferation of Treg cells ex vivo 31 4.4 LL/2 tumor growth and proportion of tumor-infiltrating lymphocytes (TILs) in Sema6A KO and WT mice 32 4.5 IL-10, TGF-β, PD-L1, and Foxp3 gene expression among resected LL/2 tumors from Sema6A KO and WT mice 32 4.6 Treatment efficacy of mouse full-length Sema6A protein, SEMA-PSI recombinant protein, and SEMA recombinant protein on LL/2 tumor growth in Sema6A KO mice 33 4.7 The proportion of tumor-infiltrating lymphocytes (TILs) were examined after treatment of mouse full-length Sema6A protein, SEMA-PSI recombinant protein, and SEMA recombinant protein in Sema6A KO mice 34 4.8 IL-10, TGF-β, PD-L1, and Foxp3 gene expression among resected LL/2 tumors from PBS-, Sema6A FL-, SEMA-PSI-, and SEMA-treated Sema6A KO mice 35 4.9 Percentage of proliferating Tc, Th, NK, and Treg were examined after treatment of full-length Sema6A protein, SEMA-PSI recombinant protein, and SEMA recombinant protein in Sema6A KO mice 35 4.10 Treatment efficacy of SEMA-PSI and SEMA recombinant proteins on LL/2 tumor growth in WT mice 36 4.11 The proportion of tumor-infiltrating lymphocytes (TILs) were examined after treatment of SEMA-PSI and SEMA recombinant proteins in WT mice 36 4.12 IL-10, TGF-β, PD-L1, and Foxp3 gene expression among resected LL/2 tumors from PBS-, SEMA-PSI-, and SEMA-treated WT mice 37 4.13 Percentage of proliferating Tc, Th, NK, and Treg were examined after treatment of SEMA-PSI recombinant protein and SEMA recombinant protein in WT mice 37 4.14 NNK induced higher degree of lesions in Sema6A KO mice lungs than in WT mice lungs 38 Chapter 5. Discussion and conclusion 40 5.1 Different competitive ability of full-length Sema6A, SEMA-PSI, and SEMA recombinant proteins on the binding of Sema3A to Nrp1 40 5.2 Antitumor immune response triggered by full-length Sema6A, SEMA-PSI, or SEMA recombinant protein ex vivo 41 5.3 Antitumor efficacy of full-length Sema6A, SEMA-PSI, and SEMA recombinant proteins on the proportion of tumor-infiltrating lymphocytes in Sema6A KO mice ............................................................................................................................42 5.4 Immunosuppressive mRNA expression in LL/2 tumors after treatment of Sema6A FL, SEMA-PSI, and SEMA recombinant proteins in Sema6A KO mice 44 5.5 Antitumor immunity of SEMA recombinant protein treatment 45 5.6 Influence of host Sema6A gene expression on antitumor immunity 46 5.7 Influence of NNK induction on lungs of Sema6A KO and WT C57BL/6J mice 47 5.8 Conclusion 49 Chapter 6. Future work 50 Tables 52 Figures 54 Reference 92" | |
| dc.language.iso | en | |
| dc.subject | NNK | zh_TW |
| dc.subject | 免疫療法 | zh_TW |
| dc.subject | 肺癌 | zh_TW |
| dc.subject | Semaphorin3A | zh_TW |
| dc.subject | 基因剔除 | zh_TW |
| dc.subject | Semaphorin6A | zh_TW |
| dc.subject | Lung cancer | en |
| dc.subject | Semaphorin6A | en |
| dc.subject | NNK | en |
| dc.subject | immunotherapy | en |
| dc.subject | Semaphorin3A | en |
| dc.subject | knockout | en |
| dc.title | 利用Semaphorin6A基因剔除小鼠模型探討Semaphorin6A為基礎之重組蛋白於肺癌免疫治療的效果 | zh_TW |
| dc.title | Using Semaphorin6A Knockout Mouse Model to Examine Antitumor Immune Response Triggered by Semaphorin6A-Based Recombinant Proteins in Lung Cancer Immunotherapy | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 賴亮全(Hsin-Tsai Liu),莊曜宇(Chih-Yang Tseng),陳立涵 | |
| dc.subject.keyword | 肺癌,免疫療法,Semaphorin6A,Semaphorin3A,基因剔除,NNK, | zh_TW |
| dc.subject.keyword | Lung cancer,immunotherapy,Semaphorin6A,Semaphorin3A,knockout,NNK, | en |
| dc.relation.page | 103 | |
| dc.identifier.doi | 10.6342/NTU202102173 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2021-09-06 | |
| 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 | |
|---|---|---|---|
| U0001-0708202116070300.pdf 未授權公開取用 | 7.46 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。