跳到主要內容

臺灣博碩士論文加值系統

(44.220.44.148) 您好!臺灣時間:2024/06/14 09:35
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:高嘉宜
研究生(外文):Kao, Chia-Yi
論文名稱:M13 噬菌體作為細胞的基因載體應用於癌症治療
論文名稱(外文):Optimization of M13 Bacteriophage-mediated Gene Delivery for Cancer Therapy
指導教授:牟昀
指導教授(外文):Mou, Kurt Yun
口試委員:陶秘華牟昀李家偉蔡明翰陳紀如
口試委員(外文):Tao, Mi-HuaMou, Kurt YunLi, Chia-WeiTsai, Ming-HanChen, Chi-Ju
口試日期:2023-1-6
學位類別:博士
校院名稱:國立陽明交通大學
系所名稱:分子醫學博士學位學程
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2023
畢業學年度:111
語文別:英文
論文頁數:162
中文關鍵詞:基因治療M13噬菌體腺相關病毒載體表皮生長因子癌症治療PrimPol蛋白DMBT1蛋白
外文關鍵詞:gene therapyM13 bacteriophageadeno-associated virusepidermal growth factorcancer therapyPrimPolDMBT1
相關次數:
  • 被引用被引用:0
  • 點閱點閱:200
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
Table of Contents
Acknowledgements i
Chinese Abstract ii
English Abstract iii
Table of Contents iv
List of Figures ix
List of Tables xiii
List of Appendices xiv
List of Abbreviations xv
Chapter 1 Introduction 1
1.1 Gene therapy 1
1.1.1 Gene therapy drugs 1
1.1.2 Approaches for gene delivery 2
1.2 M13 filamentous bacteriophage 6
1.2.1 Phage display technology 7
1.2.2 Advantages of M13 bacteriophage as therapeutic tools 8
1.3 Phage transduction of mammalian cells 9
1.3.1 Filamentous phage for gene delivery 9
1.3.2 Mechanism of M13 bacteriophage internalization of mammalian cells 10
1.4 Rationale and purpose 11
Chapter 2 Materials and Methods 15
2.1 Plasmid construction 15
2.1.1 Helper phage 15
2.1.2 Phagemid construction for the M13 bacteriophage genome 16
2.1.3 Construction of the PrimPol gene into a lentiviral vector 16
2.2 M13 bacteriophage production and purification 17
2.3 Enzyme-linked immunosorbent assay (ELISA) 17
2.4 Cell culture 18
2.5 Sample preparation for confocal microscope image 19
2.6 Negative staining for transmission electron microscopy (TEM) 19
2.7 AAV production and purification 20
2.8 M13 bacteriophage and AAV transduction of mammalian cells 20
2.9 Immunofluorescence staining 21
2.10 Stable cell line establishment 21
2.11 Generation of the DMBT1-KO cell line 22
2.12 Cell sorting (GFP/mCherry-PrimPol-HeLa) 22
2.13 Mixture of ssDNA for transfection 23
2.14 pVIII mutant library engineering and screening 23
2.15 Fluorination of phage 24
2.16 S- and I-form bacteriophage formation 24
2.17 FITC labeling of EGF-pIII phages 25
2.18 Camptothecin (CPT) treatment 25
2.19 Cell cycle arrest test 26
2.20 Gefitinib treatment 26
2.21 Gefitinib and cisplatin-resistant cell line 26
2.22 qPCR for PrimPol mRNA expression level 27
2.23 RNA-seq experiments 27
2.24 Luciferin assay 28
2.25 Cell viability assay 29
2.26 Natural killer cell (NK)-cell killing assay 29
2.27 Mice experiment 30
Chapter 3 Results 31
3.1 Various modulations of M13 bacteriophage gene expression in mammalian cells 31
3.1.1 Intracellular gene delivery using M13 bacteriophage displaying various proteins 31
3.1.2 M13 bacteriophage transduction of PrimPol-overexpressing HeLa cells 40
3.1.3 Genetic modification of phage for gene expression optimization in cells 42
3.1.4 Capsid disassembly: pVIII mutant library screening 54
3.1.5 Fluorination of M13 bacteriophage for gene delivery 64
3.1.6 I-, S-form of M13 bacteriophage for gene delivery 66
3.1.7 ssDNA from M13 bacteriophage mixed with primers for transfection 68
3.2 Production of pure and shorter-length phage to enhance transduction efficiency 71
3.2.1 Inverse correlation between the M13 bacteriophage length and transduction efficiency 71
3.2.2 Shorter phage design with an additional domain B 74
3.2.3 Pure phage production from the deleted M13 ori helper 77
3.2.4 Phage transduction in the sorting cells increases transduction efficiency 78
3.2.5 Nanophage design (TransPhage) of domain B and loop B-C 83
3.3 Cellular factors affecting phage transduction efficiency 86
3.3.1 EGF-pIII phage and EGFR distribution in HeLa cells 86
3.3.2 M13 bacteriophage transduction of mutant EGFR-HEK293T 89
3.3.3 Cell cycle analysis of phage transduction 90
3.3.4 Drug (gefitinib, filipin) treatment or drug-resistant cells for transduction 94
3.3.5 PrimPol protein is an enhancer for phage transduction efficiency 98
3.3.6 DMBT1 protein is an inhibitor of phage transduction efficiency 101
3.4 Application of engineered phage for gene delivery 105
3.4.1 Delivery of different genes using the engineered EGF-phage 105
3.4.2 Immunogene therapy delivered by TransPhage suppressed the xenograft tumors in nude mice 110
3.4.3 Comparable TransPhage transduction efficiency to the AAV vectors 115
Chapter 4 Discussion 118
Chapter 5 Conclusion and future perspectives 128
References 139
Appendices 147


1. Rodrigues GA, Shalaev E, Karami TK, Cunningham J, Slater NK, Rivers HM. Pharmaceutical development of AAV-based gene therapy products for the eye. Pharmaceutical research. 2019;36(2):1-20.
2. Ma C-C, Wang Z-L, Xu T, He Z-Y, Wei Y-Q. The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnology advances. 2020;40:107502.
3. Stein CA, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Molecular Therapy. 2017;25(5):1069-1075.
4. Kassner U, Hollstein T, Grenkowitz T, et al. Gene therapy in lipoprotein lipase deficiency: case report on the first patient treated with alipogene tiparvovec under daily practice conditions. Human gene therapy. 2018;29(4):520-527.
5. Senior M. After Glybera's withdrawal, what's next for gene therapy? Nature Biotechnology. 2017;35(6):491-493.
6. Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. Gene therapy clinical trials worldwide to 2017: An update. The journal of gene medicine. 2018;20(5):e3015.
7. Shim G, Kim D, Park GT, Jin H, Suh S-K, Oh Y-K. Therapeutic gene editing: delivery and regulatory perspectives. Acta Pharmacologica Sinica. 2017;38(6):738-753.
8. Bulcha JT, Wang Y, Ma H, Tai PW, Gao G. Viral vector platforms within the gene therapy landscape. Signal transduction and targeted therapy. 2021;6(1):1-24.
9. Salameh JW, Zhou L, Ward SM, Santa Chalarca CF, Emrick T, Figueiredo ML. Polymer‐mediated gene therapy: Recent advances and merging of delivery techniques. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2020;12(2):e1598.
10. Chen YH, Keiser MS, Davidson BL. Viral vectors for gene transfer. Current protocols in mouse biology. 2018;8(4):e58.
11. Shinagawa M, Padmanabhan R, Padmanabhan R. The nucleotide sequence of the right-hand terminal SmaI-K fragment of adenovirus type 2 DNA. Gene. 1980;9(1-2):99-114.
12. Crystal RG. Adenovirus: the first effective in vivo gene delivery vector. Human gene therapy. 2014;25(1):3-11.
13. Lee CS, Bishop ES, Zhang R, et al. Adenovirus-mediated gene delivery: potential applications for gene and cell-based therapies in the new era of personalized medicine. Genes & diseases. 2017;4(2):43-63.
14. Mast TC, Kierstead L, Gupta SB, et al. International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: correlates of high Ad5 titers and implications for potential HIV vaccine trials. Vaccine. 2010;28(4):950-957.
15. Barouch DH, Kik SV, Weverling GJ, et al. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine. 2011;29(32):5203-5209.
16. Hacker UT, Bentler M, Kaniowska D, Morgan M, Büning H. Towards clinical implementation of adeno-associated virus (AAV) vectors for cancer gene therapy: current status and future perspectives. Cancers. 2020;12(7):1889.
17. Li C, Samulski RJ. Engineering adeno-associated virus vectors for gene therapy. Nature Reviews Genetics. 2020;21(4):255-272.
18. Hay ID, Lithgow T. Filamentous phages: masters of a microbial sharing economy. EMBO reports. 2019;20(6):e47427.
19. Rakonjac J, Russel M, Khanum S, Brooke SJ, Rajič M. Filamentous phage: structure and biology. Recombinant Antibodies for Infectious Diseases. 2017:1-20.
20. Rakonjac J, Bennett NJ, Spagnuolo J, Gagic D, Russel M. Filamentous bacteriophage: biology, phage display and nanotechnology applications. Current issues in molecular biology. 2011;13(2):51-76.
21. Haase M, Tessmer L, Köhnlechner L, Kuhn A. The M13 Phage Assembly Machine Has a Membrane-Spanning Oligomeric Ring Structure. Viruses. 2022;14(6):1163.
22. Marvin D, Symmons M, Straus S. Structure and assembly of filamentous bacteriophages. Progress in biophysics and molecular biology. 2014;114(2):80-122.
23. Wen J, Yuan K. Research Progress of Phage Display System. 2021.
24. Velappan N, Fisher HE, Pesavento E, et al. A comprehensive analysis of filamentous phage display vectors for cytoplasmic proteins: an analysis with different fluorescent proteins. Nucleic acids research. 2010;38(4):e22-e22.
25. Sidhu SS, Weiss GA, Wells JA. High copy display of large proteins on phage for functional selections. Journal of molecular biology. 2000;296(2):487-495.
26. Petrenko VA. Landscape phage: Evolution from phage display to nanobiotechnology. Viruses. 2018;10(6):311.
27. Petrenko V, Smith G, Gong X, Quinn T. A library of organic landscapes on filamentous phage. Protein Engineering, Design and Selection. 1996;9(9):797-801.
28. Enshell-Seijffers D, Smelyanski L, Gershoni JM. The rational design of a ‘type 88’genetically stable peptide display vector in the filamentous bacteriophage fd. Nucleic acids research. 2001;29(10):e50-e50.
29. Ranjibar F, Habibi-Anbouhi M, Kazemi-Lomedasht F, Aghaee-Bakhtiyari SH, Alirahimi E, Behdani M. Cell-specific targeting by engineered M13 bacteriophage expressing VEGFR2 nanobody. Iranian Journal of Basic Medical Sciences. 2018;21(9):884.
30. KHALAJKONDORI M, Kavoosi M, Rahmati-Yamchi M, Kadivar M. Preparation of a transferrin-targeted M13-based gene nanocarrier and evaluation of its efficacy for gene delivery and expression in eukaryote cells. Turkish Journal of Biology. 2016;40(3):561-570.
31. Poul M-A, Marks JD. Targeted gene delivery to mammalian cells by filamentous bacteriophage. Journal of molecular biology. 1999;288(2):203-211.
32. Larocca D, Jensen-Pergakes K, Burg MA, Baird A. Receptor-targeted gene delivery using multivalent phagemid particles. Molecular therapy. 2001;3(4):476-484.
33. Larocca D, Witte A, Johnson W, Pierce GF, Baird A. Targeting bacteriophage to mammalian cell surface receptors for gene delivery. Human gene therapy. 1998;9(16):2393-2399.
34. Kim A, Shin T-H, Shin S-M, et al. Cellular internalization mechanism and intracellular trafficking of filamentous M13 phages displaying a cell-penetrating transbody and TAT peptide. PloS one. 2012;7(12):e51813.
35. Hoffmann K, Milech N, Juraja SM, et al. A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery. Scientific reports. 2018;8(1):1-16.
36. Kwaśnikowski P, Kristensen P, Markiewicz WT. Multivalent display system on filamentous bacteriophage pVII minor coat protein. Journal of immunological methods. 2005;307(1-2):135-143.
37. Specthrie L, Bullitt E, Horiuchi K, Model P, Russel M, Makowski L. Construction of a microphage variant of filamentous bacteriophage. Journal of Molecular Biology. 1992;228(3):720-724.
38. Chen C-C, Sun C-P, Ma H-I, et al. Comparative study of anti-hepatitis B virus RNA interference by double-stranded adeno-associated virus serotypes 7, 8, and 9. Molecular Therapy. 2009;17(2):352-359.
39. Manning M, Chrysogelos S, Griffith J. Mechanism of coliphage M13 contraction: intermediate structures trapped at low temperatures. Journal of virology. 1981;40(3):912-919.
40. Ngo-Duc T-T, Alibay Z, Plank JM, Cheeney JE, Haberer ED. Gold-decorated M13 I-forms and S-forms for targeted photothermal lysis of bacteria. ACS Applied Materials & Interfaces. 2019;12(1):126-134.
41. Burg MA, Jensen-Pergakes K, Gonzalez AM, Ravey P, Baird A, Larocca D. Enhanced phagemid particle gene transfer in camptothecin-treated carcinoma cells. Cancer research. 2002;62(4):977-981.
42. Zheng J, Yu J, Yang M, Tang L. Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition. Experimental and Therapeutic Medicine. 2019;18(3):1823-1830.
43. Béchohra L, Laraba-Djebari F, Hammoudi-Triki D. Cytotoxic activity of Androctonus australis hector venom and its toxic fractions on human lung cancer cell line. Journal of venomous animals and toxins including tropical diseases. 2016;22.
44. Hansen JE, Tse C-M, Chan G, Heinze ER, Nishimura RN, Weisbart RH. Intranuclear protein transduction through a nucleoside salvage pathway. Journal of Biological Chemistry. 2007;282(29):20790-20793.
45. Hansen JE, Fischer LK, Chan G, et al. Antibody-mediated p53 protein therapy prevents liver metastasis in vivo. Cancer research. 2007;67(4):1769-1774.
46. Weisbart RH, Chan G, Jordaan G, et al. DNA-dependent targeting of cell nuclei by a lupus autoantibody. Scientific Reports. 2015;5(1):1-6.
47. Im S-W, Pravinsagar P, Im S-R, Jang Y-J. Variable heavy chain domain derived from a cell-penetrating anti-DNA monoclonal antibody for the intracellular delivery of biomolecules. Immunological Investigations. 2017;46(5):500-517.
48. Faria JA, de Andrade C, Goes AM, Rodrigues MA, Gomes DA. Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation. Biochemical and biophysical research communications. 2016;478(1):39-45.
49. Reilly JF, Maher PA. Importin β–mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation. The Journal of cell biology. 2001;152(6):1307-1312.
50. Reilly JF, Mizukoshi E, Maher PA. Ligand dependent and independent internalization and nuclear translocation of fibroblast growth factor (FGF) receptor 1. DNA and cell biology. 2004;23(9):538-548.
51. Gasparian M, Elistratov P, Drize N, Nifontova I, Dolgikh D, Kirpichnikov M. Overexpression in Escherichia coli and purification of human fibroblast growth factor (FGF-2). Biochemistry (Moscow). 2009;74(2):221-225.
52. Dvorak P, Bednar D, Vanacek P, et al. Computer‐assisted engineering of hyperstable fibroblast growth factor 2. Biotechnology and bioengineering. 2018;115(4):850-862.
53. Kuo H-H, Gao X, DeKeyser J-M, et al. Negligible-cost and weekend-free chemically defined human iPSC culture. Stem Cell Reports. 2020;14(2):256-270.
54. García-Gómez S, Reyes A, Martínez-Jiménez MI, et al. PrimPol, an archaic primase/polymerase operating in human cells. Molecular cell. 2013;52(4):541-553.
55. Díaz-Talavera A, Calvo PA, González-Acosta D, et al. A cancer-associated point mutation disables the steric gate of human PrimPol. Scientific reports. 2019;9(1):1-13.
56. Wang X, Xu Z, Tian Z, et al. The EF‐1α promoter maintains high‐level transgene expression from episomal vectors in transfected CHO‐K1 cells. Journal of cellular and molecular medicine. 2017;21(11):3044-3054.
57. Prieto Y, Sánchez O. Self-complementary sequences induce the formation of double-stranded filamentous phages. Biochimica et Biophysica Acta (BBA)-General Subjects. 2007;1770(8):1081-1084.
58. Hlavaty J, Schittmayer M, Stracke A, et al. Effect of posttranscriptional regulatory elements on transgene expression and virus production in the context of retrovirus vectors. Virology. 2005;341(1):1-11.
59. Klein R, Ruttkowski B, Knapp E, Salmons B, Günzburg WH, Hohenadl C. WPRE-mediated enhancement of gene expression is promoter and cell line specific. Gene. 2006;372:153-161.
60. Hajitou A, Trepel M, Lilley CE, et al. A hybrid vector for ligand-directed tumor targeting and molecular imaging. Cell. 2006;125(2):385-398.
61. Martínez-Jiménez MI, Calvo PA, García-Gómez S, Guerra-González S, Blanco L. The Zn-finger domain of human PrimPol is required to stabilize the initiating nucleotide during DNA priming. Nucleic acids research. 2018;46(8):4138-4151.
62. Mahon MJ. Vectors bicistronically linking a gene of interest to the SV40 large T antigen in combination with the SV40 origin of replication enhance transient protein expression and luciferase reporter activity. Biotechniques. 2011;51(2):119-126.
63. Akuta T, Eguchi A, Okuyama H, et al. Enhancement of phage-mediated gene transfer by nuclear localization signal. Biochemical and biophysical research communications. 2002;297(4):779-786.
64. Hübner S, Xiao C-Y, Jans DA. The protein kinase CK2 site (Ser111/112) enhances recognition of the simian virus 40 large T-antigen nuclear localization sequence by importin. Journal of Biological Chemistry. 1997;272(27):17191-17195.
65. Girod A, Wobus CE, Zádori Z, et al. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. Journal of General Virology. 2002;83(5):973-978.
66. Grieger JC, Snowdy S, Samulski RJ. Separate basic region motifs within the adeno-associated virus capsid proteins are essential for infectivity and assembly. Journal of virology. 2006;80(11):5199-5210.
67. Grieger JC, Johnson JS, Gurda-Whitaker B, Agbandje-McKenna M, Samulski RJ. Surface-exposed adeno-associated virus Vp1-NLS capsid fusion protein rescues infectivity of noninfectious wild-type Vp2/Vp3 and Vp3-only capsids but not that of fivefold pore mutant virions. Journal of virology. 2007;81(15):7833-7843.
68. Ellis BL, Hirsch ML, Barker JC, Connelly JP, Steininger RJ, Porteus MH. A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype. Virology journal. 2013;10(1):1-10.
69. Canaan S, Zádori Z, Ghomashchi F, et al. Interfacial enzymology of parvovirus phospholipases A2. Journal of Biological Chemistry. 2004;279(15):14502-14508.
70. Zádori Z, Szelei J, Lacoste M-C, et al. A viral phospholipase A2 is required for parvovirus infectivity. Developmental cell. 2001;1(2):291-302.
71. Rossi A, Dupaty L, Aillot L, et al. Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity. Scientific reports. 2019;9(1):1-14.
72. Iannolo G, Minenkova O, Petruzzelli R, Cesareni G. Modifying filamentous phage capsid: limits in the size of the major capsid protein. Journal of molecular biology. 1995;248(4):835-844.
73. Wang M, Liu H, Li L, Cheng Y. A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios. Nature communications. 2014;5(1):1-8.
74. Zhang Z, Shen W, Ling J, Yan Y, Hu J, Cheng Y. The fluorination effect of fluoroamphiphiles in cytosolic protein delivery. Nature Communications. 2018;9(1):1377.
75. Lv J, Chang H, Wang Y, et al. Fluorination on polyethylenimine allows efficient 2D and 3D cell culture gene delivery. Journal of Materials Chemistry B. 2015;3(4):642-650.
76. Olofsson L, Ankarloo J, Andersson PO, Nicholls IA. Filamentous bacteriophage stability in non-aqueous media. Chemistry & Biology. 2001;8(7):661-671.
77. Lopez J, Webster RE. Minor coat protein composition and location of the A protein in bacteriophage f1 spheroids and I-forms. Journal of Virology. 1982;42(3):1099-1107.
78. Hornstein BD, Roman D, Arévalo-Soliz LM, Engevik MA, Zechiedrich L. Effects of circular DNA length on transfection efficiency by electroporation into HeLa cells. PloS one. 2016;11(12):e0167537.
79. Xu Dh, Wang Xy, Jia Yl, et al. SV40 intron, a potent strong intron element that effectively increases transgene expression in transfected Chinese hamster ovary cells. Journal of cellular and molecular medicine. 2018;22(4):2231-2239.
80. West A, Bulysheva A. Reduction of the Plasmid Vector Backbone Length Enhances Reporter Gene Expression. 2022.
81. Sattar S, Bennett NJ, Wen WX, et al. Ff-nano, short functionalized nanorods derived from Ff (f1, fd, or M13) filamentous bacteriophage. Frontiers in microbiology. 2015;6:316.
82. Dotto GP, Horiuchi K, Zinder ND. The functional origin of bacteriophage f1 DNA replication: Its signals and domains. Journal of molecular biology. 1984;172(4):507-521.
83. Johnston S, Ray DS. Interference between M13 and oriM13 plasmids is mediated by a replication enhancer sequence near the viral strand origin. Journal of Molecular Biology. 1984;177(4):685-700.
84. Vieira J, Messing J. Production of single-stranded plasmid DNA. Recombinant DNA Methodology: Elsevier; 1989.
85. Higashitani N, Higashitani A, Guan ZW, Horiuchi K. Recognition mechanisms of the minus‐strand origin of phage f1 by Escherichia coli RNA polymerase. Genes to Cells. 1996;1(9):829-841.
86. Higashitani A, Higashitani N, Horiuchi K. Minus-strand origin of filamentous phage versus transcriptional promoters in recognition of RNA polymerase. Proceedings of the National Academy of Sciences. 1997;94(7):2909-2914.
87. Schlessinger J. Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell. 2002;110(6):669-672.
88. Campos ACDA, Rodrigues MA, de Andrade C, de Goes AM, Nathanson MH, Gomes DA. Epidermal growth factor receptors destined for the nucleus are internalized via a clathrin-dependent pathway. Biochemical and biophysical research communications. 2011;412(2):341-346.
89. Hsu S-C, Hung M-C. Characterization of a novel tripartite nuclear localization sequence in the EGFR family. Journal of Biological Chemistry. 2007;282(14):10432-10440.
90. Zhang S, Joseph G, Pollok K, et al. G2 cell cycle arrest and cyclophilin A in lentiviral gene transfer. Molecular Therapy. 2006;14(4):546-554.
91. Chen M, Huang J, Yang X, et al. Serum starvation induced cell cycle synchronization facilitates human somatic cells reprogramming. PloS one. 2012;7(4):e28203.
92. Chou T-Y, Chiu C-H, Li L-H, et al. Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non–small cell lung cancer. Clinical cancer research. 2005;11(10):3750-3757.
93. Ono M, Kuwano M. Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clinical cancer research. 2006;12(24):7242-7251.
94. Nishimura Y, Bereczky B, Ono M. The EGFR inhibitor gefitinib suppresses ligand-stimulated endocytosis of EGFR via the early/late endocytic pathway in non-small cell lung cancer cell lines. Histochemistry and cell biology. 2007;127(5):541-553.
95. Sigismund S, Argenzio E, Tosoni D, Cavallaro E, Polo S, Di Fiore PP. Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Developmental cell. 2008;15(2):209-219.
96. Huang W-C, Chen Y-J, Li L-Y, et al. Nuclear translocation of epidermal growth factor receptor by Akt-dependent phosphorylation enhances breast cancer-resistant protein expression in gefitinib-resistant cells. Journal of Biological Chemistry. 2011;286(23):20558-20568.
97. Hsu S-C, Miller SA, Wang Y, Hung M-C. Nuclear EGFR is required for cisplatin resistance and DNA repair. American journal of translational research. 2009;1(3):249.
98. Liccardi G, Hartley JA, Hochhauser D. EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment. Cancer research. 2011;71(3):1103-1114.
99. Peng D, Qian C, Sun Y, Barajas MA, Prieto J. Transduction of hepatocellular carcinoma (HCC) using recombinant adeno-associated virus (rAAV): in vitro and in vivo effects of genotoxic agents. Journal of hepatology. 2000;32(6):975-985.
100. Tsafa E, Bentayebi K, Topanurak S, et al. Doxorubicin Improves Cancer Cell Targeting by Filamentous Phage Gene Delivery Vectors. International journal of molecular sciences. 2020;21(21):7867.
101. Ligtenberg AJ, Karlsson NG, Veerman EC. Deleted in malignant brain tumors-1 protein (DMBT1): a pattern recognition receptor with multiple binding sites. International Journal of Molecular Sciences. 2010;11(12):5212-5233.
102. Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535(7610):111-116.
103. Huang R-S, Shih H-A, Lai M-C, Chang Y-J, Lin S. Enhanced NK-92 cytotoxicity by CRISPR genome engineering using Cas9 ribonucleoproteins. Frontiers in immunology. 2020:1008.
104. Tsedev U, Lin C-W, Hess GT, Sarkaria JN, Lam FC, Belcher AM. Phage Particles of Controlled Length and Genome for In Vivo Targeted Glioblastoma Imaging and Therapeutic Delivery. ACS nano. 2022;16(8):11676-11691.
105. Maruyama IN. Mechanisms of activation of receptor tyrosine kinases: monomers or dimers. Cells. 2014;3(2):304-330.
106. Purba ER, Saita E-i, Maruyama IN. Activation of the EGF receptor by ligand binding and oncogenic mutations: the “rotation model”. Cells. 2017;6(2):13.
107. Schneider MR, Wolf E. The epidermal growth factor receptor ligands at a glance. Journal of cellular physiology. 2009;218(3):460-466.
108. Ogiso H, Ishitani R, Nureki O, et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002;110(6):775-787.
109. Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers. 2017;9(5):52.
110. Yewale C, Baradia D, Vhora I, Patil S, Misra A. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013;34(34):8690-8707.
111. Brand TM, Iida M, Li C, Wheeler DL. The nuclear epidermal growth factor receptor signaling network and its role in cancer. Discovery medicine. 2011;12(66):419.
112. Han W, Lo H-W. Landscape of EGFR signaling network in human cancers: biology and therapeutic response in relation to receptor subcellular locations. Cancer letters. 2012;318(2):124-134.
113. Wang Y-N, Wang H, Yamaguchi H, Lee H-J, Lee H-H, Hung M-C. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport. Biochemical and biophysical research communications. 2010;399(4):498-504.
114. Saksena S, Summers MD, Burks JK, Johnson AE, Braunagel SC. Importin-α-16 is a translocon-associated protein involved in sorting membrane proteins to the nuclear envelope. Nature structural & molecular biology. 2006;13(6):500-508.
115. Lo HW, Ali‐Seyed M, Wu Y, Bartholomeusz G, Hsu SC, Hung MC. Nuclear‐cytoplasmic transport of EGFR involves receptor endocytosis, importin β1 and CRM1. Journal of cellular biochemistry. 2006;98(6):1570-1583.
116. Wang Y-N, Yamaguchi H, Huo L, et al. The translocon Sec61β localized in the inner nuclear membrane transports membrane-embedded EGF receptor to the nucleus. Journal of Biological Chemistry. 2010;285(49):38720-38729.
117. Kobayashi K, Guilliam TA, Tsuda M, et al. Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides. Cell Cycle. 2016;15(15):1997-2008.
118. Bianchi J, Rudd SG, Jozwiakowski SK, et al. PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Molecular cell. 2013;52(4):566-573.
119. Torregrosa-Muñumer R, Forslund JM, Goffart S, et al. PrimPol is required for replication reinitiation after mtDNA damage. Proceedings of the National Academy of Sciences. 2017;114(43):11398-11403.
120. Quinet A, Tirman S, Jackson J, et al. PRIMPOL-mediated adaptive response suppresses replication fork reversal in BRCA-deficient cells. Molecular cell. 2020;77(3):461-474. e469.
121. Mollenhauer J, Wiemann S, Scheurlen W, et al. DMBT1, a new member of the SRCR superfamily, on chromosome 10q25. 3–26.1 is deleted in malignant brain tumours. Nature genetics. 1997;17(1):32-39.
122. Takeshita H, Sato M, Shiwaku HO, et al. Expression of the DMBT1 gene is frequently suppressed in human lung cancer. Japanese journal of cancer research. 1999;90(9):903-908.
123. Mollenhauer J, Herbertz S, Holmskov U, et al. DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer. Cancer research. 2000;60(6):1704-1710.
124. Pan W-Y, Lo C-H, Chen C-C, et al. Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains. Molecular Therapy. 2012;20(5):927-937.
125. Huang C-C, Kuo K-K, Cheng T-C, et al. Development of membrane-bound GM-CSF and IL-18 as an effective tumor vaccine. Plos one. 2015;10(7):e0133470.
126. Lin S-Y, Makino K, Xia W, et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nature cell biology. 2001;3(9):802-808.
127. Lo H-W, Xia W, Wei Y, Ali-Seyed M, Huang S-F, Hung M-C. Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer research. 2005;65(1):338-348.
128. Lipponen P, Eskelinen M. Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. British journal of cancer. 1994;69(6):1120-1125.
129. Kamio T, Shigematsu K, Sou H, Kawai K, Tsuchiyama H. Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma. Human pathology. 1990;21(3):277-282.
130. Psyrri A, Yu Z, Weinberger PM, et al. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clinical Cancer Research. 2005;11(16):5856-5862.
131. Díaz-Talavera A, Montero-Conde C, Leandro-García LJ, Robledo M. PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy. Biomolecules. 2022;12(2):248.
132. Cao H, Lei Z, Bian L, Rao CV. Functional nuclear epidermal growth factor receptors in human choriocarcinoma JEG-3 cells and normal human placenta. Endocrinology. 1995;136(7):3163-3172.
133. Marti U, Burwen SJ, Wells A, et al. Localization of epidermal growth factor receptor in hepatocyte nuclei. Hepatology. 1991;13(1):15-20.
134. Wang J, Lamolinara A, Conti L, et al. HER2-Displaying M13 Bacteriophages induce Therapeutic Immunity against Breast Cancer. Cancers. 2022;14(16):4054.
135. Hashiguchi S, Yamaguchi Y, Takeuchi O, Akira S, Sugimura K. Immunological basis of M13 phage vaccine: Regulation under MyD88 and TLR9 signaling. Biochemical and biophysical research communications. 2010;402(1):19-22.
136. Dong X, Pan P, Ye J-J, Zhang Q-L, Zhang X-Z. Hybrid M13 bacteriophage-based vaccine platform for personalized cancer immunotherapy. Biomaterials. 2022;289:121763.
137. Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. Journal of clinical oncology. 2015;33(25):2780-2788.
138. Doniņa S, Strēle I, Proboka G, et al. Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study. Melanoma research. 2015;25(5):421.
139. Liang M. Oncorine, the world first oncolytic virus medicine and its update in China. Current cancer drug targets. 2018;18(2):171-176.
140. Liu T, Zhao N, Shi M, Shen Y, Mao C, Zhou X. Phage‐Derived Oncolytic Viruses with 3C from Seneca Valley Virus for Targeted Therapy of Cervical Cancer. Advanced Therapeutics. 2022;5(8):2200059.
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
1. 藉著孔洞的演化研究壓應力對3D IC銅-銅接合可靠度的影響
2. 銠金屬催化2-芳基苯並咪唑與順丁烯二醯亞胺進行結構控制的 (4+2) 和 (4+1) 環化反應/ 銠金屬催化2-芳基苯並咪唑與炔酸酯進行 (4+1) 碳-氫鍵活化反應/ 銠金屬催化吡唑啉酮與重氮化合物進行碳-氫鍵活化反應
3. 雙極性接面電晶體PNP元件集射極崩潰電壓改善之研究
4. 在台外籍生與台灣新興之雙語環境:挑戰、影響與解決方案
5. 母親聲音結合搖籃曲介入減緩早產兒對足跟血穿刺疼痛反應之成效
6. 護理長的角色壓力與影響因素之探討: 史洛斯伯格轉換理論觀點
7. 以虛擬主播角色創作關懷當代年輕群體的集體焦慮
8. 噴淋式降膜應用於板式熱交換器之海水淡化研究
9. 超音波振動輔助壓縮對選擇性雷射熔融316L不鏽鋼之疲勞強度效應
10. 應用仿生二頭肌超輕型機械手臂
11. 一種利用可自我校正磁共振無線傳輸系統來讀取電容式感測器的方法
12. 應用在低軌道衛星且可阻抗單一事件反轉和單一事件脈衝及抑制 PVTA 變異的抗輻射正反器設計
13. 聯邦深度加強式學習於太赫茲波束成型之 智慧反射面板輔助無線網路之最佳化與分析
14. 基於WiFi 通道狀態資訊及時間選擇性所設計異質遷移學習之非接觸式呼吸暫停檢測系統
15. 非線性後補償與預失真運用於延時分複用6G類比前傳網路鏈結