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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳漢忠 | |
dc.contributor.author | Yi-Hsuan Chi | en |
dc.contributor.author | 紀怡亘 | zh_TW |
dc.date.accessioned | 2021-06-08T01:38:35Z | - |
dc.date.copyright | 2017-02-24 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-16 | |
dc.identifier.citation | 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016;66(1):7-30.
2. Vinay Kumar AKA, Jon C. Aster. Robbins & Cotran Pathologic Basis of Disease. 9th ed: Elsevier Press; 2014. 3. American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society. 2016. 4. Yu YH, Liao CC, Hsu WH, Chen HJ, Liao WC, Muo CH, et al. Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2011;6(1):32-7. 5. Oxnard GR, Binder A, Janne PA. New targetable oncogenes in non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013;31(8):1097-104. 6. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nature reviews Cancer. 2014;14(8):535-46. 7. The Clinical Lung Cancer Genome Project (CLCGP), Network Genomic Medicine (NGM). A genomics-based classification of human lung tumors. Science translational medicine. 2013;5(209):209ra153. 8. Bunn PA, Jr., Franklin W, Doebele RC. The evolution of tumor classification: a role for genomics? Cancer cell. 2013;24(6):693-4. 9. William WN, Jr., Glisson BS. Novel strategies for the treatment of small-cell lung carcinoma. Nature reviews Clinical oncology. 2011;8(10):611-9. 10. Chong CR, Janne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nature medicine. 2013;19(11):1389-400. 11. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. The New England journal of medicine. 2005;353(2):123-32. 12. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561-6. 13. Chen Z, Cheng K, Walton Z, Wang Y, Ebi H, Shimamura T, et al. A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response. Nature. 2012;483(7391):613-7. 14. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nature medicine. 2008;14(12):1351-6. 15. Janne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. The Lancet Oncology. 2013;14(1):38-47. 16. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. 17. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(21):3543-51. 18. Joshi M, Ayoola A, Belani CP. Small-cell lung cancer: an update on targeted therapies. Advances in experimental medicine and biology. 2013;779:385-404. 19. Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Science translational medicine. 2012;4(120):120ra17. 20. Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. The New England journal of medicine. 2005;352(8):786-92. 21. Heldin CH, Rubin K, Pietras K, Ostman A. High interstitial fluid pressure - an obstacle in cancer therapy. Nature reviews Cancer. 2004;4(10):806-13. Epub 2004/10/29. 22. Provenzano Paolo P, Cuevas C, Chang Amy E, Goel Vikas K, Von Hoff Daniel D, Hingorani Sunil R. Enzymatic Targeting of the Stroma Ablates Physical Barriers to Treatment of Pancreatic Ductal Adenocarcinoma. Cancer cell. 2012;21(3):418-29. 23. Hambley TW, Hait WN. Is anticancer drug development heading in the right direction? Cancer Res. 2009;69(4):1259-62. Epub 2009/02/12. 24. Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nature reviews Cancer. 2006;6(8):583-92. 25. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006;5(3):219-34. 26. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145-60. 27. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release. 2000;65(1–2):271-84. 28. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46(12 Pt 1):6387-92. 29. Fang J, Nakamura H, Maeda H. The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Advanced drug delivery reviews. 2011;63(3):136-51. 30. Kohlschutter J, Michelfelder S, Trepel M. Drug delivery in acute myeloid leukemia. Expert Opin Drug Deliv. 2008;5(6):653-63. 31. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Advanced drug delivery reviews. 2013;65(1):36-48. 32. Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, et al. Drug delivery systems: An updated review. International journal of pharmaceutical investigation. 2012;2(1):2-11. 33. Ashley CE, Carnes EC, Phillips GK, Padilla D, Durfee PN, Brown PA, et al. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nat Mater. 2011;10(5):389-97. 34. Lu RM, Chang YL, Chen MS, Wu HC. Single chain anti-c-Met antibody conjugated nanoparticles for in vivo tumor-targeted imaging and drug delivery. Biomaterials. 2011;32(12):3265-74. 35. Svensen N, Walton JGA, Bradley M. Peptides for cell-selective drug delivery. Trends in Pharmacological Sciences. 2012;33(4):186-92. 36. Torchilin V. Antibody-modified liposomes for cancer chemotherapy. Expert Opin Drug Deliv. 2008;5(9):1003-25. 37. Lo A, Lin CT, Wu HC. Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery. Mol Cancer Ther. 2008;7(3):579-89. 38. Lau D, Guo L, Liu R, Marik J, Lam K. Peptide ligands targeting integrin alpha3beta1 in non-small cell lung cancer. Lung cancer. 2006;52(3):291-7. 39. Chang DK, Lin CT, Wu CH, Wu HC. A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer. PloS one. 2009;4(1):e4171. 40. McGuire MJ, Gray BP, Li S, Cupka D, Byers LA, Wu L, et al. Identification and characterization of a suite of tumor targeting peptides for non-small cell lung cancer. Scientific reports. 2014;4:4480. 41. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine. 2006;1(3):297-315. 42. Wu HC, Chi, Y.H., and Wu, C.H. Targeting liposomes for drug delivery in cancer therapy. In: Souto EB, editor. Lipid Nanocarriers in Cancer Diagnosis and Therapy. iSmithers Press; 2011. pp. 85-136. 43. Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol. 2006;24(10):1211-7. 44. Depierre A, Lemarie E, Dabouis G, Garnier G, Jacoulet P, Dalphin JC. A phase II study of Navelbine (vinorelbine) in the treatment of non-small-cell lung cancer. American journal of clinical oncology. 1991;14(2):115-9. 45. Faller BA, Pandit TN. Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer. Clinical Medicine Insights Oncology. 2011;5:131-44. 46. Zhigaltsev IV, Maurer N, Akhong QF, Leone R, Leng E, Wang J, et al. Liposome-encapsulated vincristine, vinblastine and vinorelbine: a comparative study of drug loading and retention. Journal of controlled release : official journal of the Controlled Release Society. 2005;104(1):103-11. 47. Yang SH, Lin CC, Lin ZZ, Tseng YL, Hong RL. A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor. Investigational new drugs. 2012;30(1):282-9. 48. Drummond DC, Noble CO, Guo Z, Hayes ME, Park JW, Ou CJ, et al. Improved pharmacokinetics and efficacy of a highly stable nanoliposomal vinorelbine. The Journal of pharmacology and experimental therapeutics. 2009;328(1):321-30. 49. Li CL, Cui JX, Wang CX, Zhang L, Li YH, Zhang L, et al. Development of pegylated liposomal vinorelbine formulation using 'post-insertion' technology. International journal of pharmaceutics. 2010;391(1-2):230-6. 50. Li SD, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Molecular pharmaceutics. 2008;5(4):496-504. 51. Wu C-H, Kuo Y-H, Hong R-L, Wu H-C. α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer. Science translational medicine. 2015;7(290):290ra91. 52. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. The New England journal of medicine. 2011;365(5):395-409. 53. Sodickson A, Baeyens PF, Andriole KP, Prevedello LM, Nawfel RD, Hanson R, et al. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009;251(1):175-84. 54. Frush DP, Applegate K. Computed tomography and radiation: understanding the issues. Journal of the American College of Radiology : JACR. 2004;1(2):113-9. 55. Ost D, Fein AM, Feinsilver SH. Clinical practice. The solitary pulmonary nodule. The New England journal of medicine. 2003;348(25):2535-42. 56. Winer-Muram HT. The solitary pulmonary nodule. Radiology. 2006;239(1):34-49. 57. Simon S. New Lung Cancer Screening Guidelines for Heavy Smokers 2013. Available from: http://www.cancer.org/cancer/news/new-lung-cancer-screening-guidelines-for-heavy-smokers. 58. Papathanassiou D, Bruna-Muraille C, Liehn JC, Nguyen TD, Cure H. Positron Emission Tomography in oncology: present and future of PET and PET/CT. Critical reviews in oncology/hematology. 2009;72(3):239-54. 59. Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nature reviews Cancer. 2002;2(9):683-93. 60. Harris RS, Schuster DP. Visualizing lung function with positron emission tomography. Journal of applied physiology. 2007;102(1):448-58. 61. Degen CL, Poggio M, Mamin HJ, Rettner CT, Rugar D. Nanoscale magnetic resonance imaging. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(5):1313-7. 62. Buxton RB. Introduction to Functional Magnetic Resonance Imaging: Principles and Techniques. 2nd ed: Cambridge University Press; 2002. 63. Kozlowska D, Foran P, MacMahon P, Shelly MJ, Eustace S, O'Kennedy R. Molecular and magnetic resonance imaging: The value of immunoliposomes. Advanced drug delivery reviews. 2009;61(15):1402-11. 64. Shokrollahi H. Contrast agents for MRI. Materials science & engineering C, Materials for biological applications. 2013;33(8):4485-97. 65. Gao Z, Ma T, Zhao E, Docter D, Yang W, Stauber RH, et al. Small is Smarter: Nano MRI Contrast Agents - Advantages and Recent Achievements. Small. 2016;12(5):556-76. 66. Kobayashi H, Brechbiel MW. Nano-sized MRI contrast agents with dendrimer cores. Advanced drug delivery reviews. 2005;57(15):2271-86. 67. Penfield JG, Reilly RF, Jr. What nephrologists need to know about gadolinium. Nature clinical practice Nephrology. 2007;3(12):654-68. 68. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. Journal of the American Society of Nephrology : JASN. 2006;17(9):2359-62. 69. Pouliquen D, Le Jeune JJ, Perdrisot R, Ermias A, Jallet P. Iron oxide nanoparticles for use as an MRI contrast agent: pharmacokinetics and metabolism. Magnetic resonance imaging. 1991;9(3):275-83. 70. Weinstein JS, Varallyay CG, Dosa E, Gahramanov S, Hamilton B, Rooney WD, et al. Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2010;30(1):15-35. 71. Kim BH, Lee N, Kim H, An K, Park YI, Choi Y, et al. Large-scale synthesis of uniform and extremely small-sized iron oxide nanoparticles for high-resolution T1 magnetic resonance imaging contrast agents. Journal of the American Chemical Society. 2011;133(32):12624-31. 72. Huang G, Li H, Chen J, Zhao Z, Yang L, Chi X, et al. Tunable T1 and T2 contrast abilities of manganese-engineered iron oxide nanoparticles through size control. Nanoscale. 2014;6(17):10404-12. 73. Zhao Z, Zhou Z, Bao J, Wang Z, Hu J, Chi X, et al. Octapod iron oxide nanoparticles as high-performance T(2) contrast agents for magnetic resonance imaging. Nature communications. 2013;4:2266. 74. Lee N, Choi Y, Lee Y, Park M, Moon WK, Choi SH, et al. Water-dispersible ferrimagnetic iron oxide nanocubes with extremely high r(2) relaxivity for highly sensitive in vivo MRI of tumors. Nano letters. 2012;12(6):3127-31. 75. Zhou Z, Wu C, Liu H, Zhu X, Zhao Z, Wang L, et al. Surface and interfacial engineering of iron oxide nanoplates for highly efficient magnetic resonance angiography. ACS nano. 2015;9(3):3012-22. 76. Bakhtiary Z, Saei AA, Hajipour MJ, Raoufi M, Vermesh O, Mahmoudi M. Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges. Nanomedicine : nanotechnology, biology, and medicine. 2016;12(2):287-307. 77. Yang CC, Yang SY, Chieh JJ, Horng HE, Hong CY, Yang HC, et al. Biofunctionalized magnetic nanoparticles for specifically detecting biomarkers of Alzheimer's disease in vitro. ACS chemical neuroscience. 2011;2(9):500-5. 78. Yang CC, Yang SY, Ho CS, Chang JF, Liu BH, Huang KW. Development of antibody functionalized magnetic nanoparticles for the immunoassay of carcinoembryonic antigen: a feasibility study for clinical use. Journal of nanobiotechnology. 2014;12:44. 79. Yang SY, Chiu MJ, Lin CH, Horng HE, Yang CC, Chieh JJ, et al. Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles. Journal of nanobiotechnology. 2016;14(1):41. 80. Chiu MJ, Chen YF, Chen TF, Yang SY, Yang FP, Tseng TW, et al. Plasma tau as a window to the brain-negative associations with brain volume and memory function in mild cognitive impairment and early Alzheimer's disease. Human brain mapping. 2014;35(7):3132-42. 81. Cheng WW, Allen TM. The use of single chain Fv as targeting agents for immunoliposomes: an update on immunoliposomal drugs for cancer treatment. Expert Opin Drug Deliv. 2010;7(4):461-78. 82. Chu YW, Yang PC, Yang SC, Shyu YC, Hendrix MJ, Wu R, et al. Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol. 1997;17(3):353-60. 83. Lee TY, Wu HC, Tseng YL, Lin CT. A novel peptide specifically binding to nasopharyngeal carcinoma for targeted drug delivery. Cancer Res. 2004;64(21):8002-8. 84. Lee TY, Lin CT, Kuo SY, Chang DK, Wu HC. Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery. Cancer Res. 2007;67(22):10958-65. 85. Edelman RR, Hesselink JR, Zlatkin MB, Crues JV. Clinical magnetic resonance imaging. 3rd ed. Philadelphia: Saunders Press; 2006. 86. Chavhan GB, Babyn PS, Thomas B, Shroff MM, Haacke EM. Principles, techniques, and applications of T2*-based MR imaging and its special applications. Radiographics : a review publication of the Radiological Society of North America, Inc. 2009;29(5):1433-49. 87. Blake BL, Wing MR, Zhou JY, Lei Q, Hillmann JR, Behe CI, et al. G beta association and effector interaction selectivities of the divergent G gamma subunit G gamma 13. The Journal of biological chemistry. 2001;276(52):49267-74. 88. Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, et al. A transient receptor potential channel expressed in taste receptor cells. Nature neuroscience. 2002;5(11):1169-76. 89. Hirabayashi J. Lectin-based structural glycomics: glycoproteomics and glycan profiling. Glycoconjugate journal. 2004;21(1-2):35-40. 90. Raman R, Raguram S, Venkataraman G, Paulson JC, Sasisekharan R. Glycomics: an integrated systems approach to structure-function relationships of glycans. Nature methods. 2005;2(11):817-24. 91. Claus-Wilhelm von der Lieth, Thomas Lütteke, Martin Frank. Bioinformatics for Glycobiology and Glycomics: An Introduction. 1st ed. John Wiley & Sons, Ltd Press; 2009. 92. Yamamoto K, Konami Y, Kusui K, Osawa T. Purification and characterization of a carbohydrate-binding peptide from Bauhinia purpurea lectin. FEBS letters. 1991;281(1-2):258-62. 93. Yamamoto K, Konami Y, Osawa T, Irimura T. Carbohydrate-binding peptides from several anti-H(O) lectins. Journal of biochemistry. 1992;111(4):436-9. 94. Loris R, De Greve H, Dao-Thi MH, Messens J, Imberty A, Wyns L. Structural basis of carbohydrate recognition by lectin II from Ulex europaeus, a protein with a promiscuous carbohydrate-binding site. Journal of molecular biology. 2000;301(4):987-1002. 95. Stowell SR, Ju T, Cummings RD. Protein glycosylation in cancer. Annual review of pathology. 2015;10:473-510. 96. American Cancer Society. Lung Cancer (Non-Small Cell). 2016 American Cancer Society, Inc. 16 May 2016. Available: http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer 97. Chen X. Molecular Imaging Probes for Cancer Research. Singapore: World Scientific Publishing Press; 2012. 1083 p. 98. Laurent S, Dutz S, Hafeli UO, Mahmoudi M. Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. Advances in colloid and interface science. 2011;166(1-2):8-23. 99. Yu J, Yang C, Li J, Ding Y, Zhang L, Yousaf MZ, et al. Multifunctional Fe5C2 nanoparticles: a targeted theranostic platform for magnetic resonance imaging and photoacoustic tomography-guided photothermal therapy. Advanced materials. 2014;26(24):4114-20. 100. Thorek DL, Ulmert D, Diop NF, Lupu ME, Doran MG, Huang R, et al. Non-invasive mapping of deep-tissue lymph nodes in live animals using a multimodal PET/MRI nanoparticle. Nature communications. 2014;5:3097. 101. Zeng J, Jia B, Qiao R, Wang C, Jing L, Wang F, et al. In situ 111In-doping for achieving biocompatible and non-leachable 111In-labeled Fe3O4 nanoparticles. Chemical communications. 2014;50(17):2170-2. 102. Hatabu H, Alsop DC, Listerud J, Bonnet M, Gefter WB. T2* and proton density measurement of normal human lung parenchyma using submillisecond echo time gradient echo magnetic resonance imaging. European journal of radiology. 1999;29(3):245-52. 103. Kuethe DO, Adolphi NL, Fukushima E. Short data-acquisition times improve projection images of lung tissue. Magnetic resonance in medicine. 2007;57(6):1058-64. 104. Branca RT, Cleveland ZI, Fubara B, Kumar CS, Maronpot RR, Leuschner C, et al. Molecular MRI for sensitive and specific detection of lung metastases. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(8):3693-7. 105. Pombo Garcia K, Zarschler K, Barbaro L, Barreto JA, O'Malley W, Spiccia L, et al. Zwitterionic-coated 'stealth' nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system. Small. 2014;10(13):2516-29. 106. Murthy AK, Stover RJ, Hardin WG, Schramm R, Nie GD, Gourisankar S, et al. Charged gold nanoparticles with essentially zero serum protein adsorption in undiluted fetal bovine serum. Journal of the American Chemical Society. 2013;135(21):7799-802. 107. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006;24(28):4539-44. 108. Thatcher N, Eckardt J, Green M. Options for first- and second-line therapy in small cell lung cancer--a workshop discussion. Lung cancer. 2003;41 Suppl 4:S37-41. 109. Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1997;15(5):2090-6. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18889 | - |
dc.description.abstract | 背景:
肺癌位居全世界癌症死亡率之首。目前已有的肺癌標靶藥物主要是針對肺腺癌的表皮細胞生長因子 (EGFR) 或間變性淋巴瘤激酶 (ALK) 所設計的的酪胺酸激酶抑制劑 (TKIs) 。到目前為止,還沒有針對大細胞癌和小細胞肺癌有效的標靶藥物。因此,我們的研究目標希望尋找能廣泛辨識小細胞肺癌和非小細胞肺癌各種亞型的標的胜肽,可應用於肺癌的偵檢和治療。 結果: 由於近期的研究將大細胞癌歸類為各種肺癌亞型中“未分化”的腫瘤型態。因此我們運用噬菌體顯現法,針對H460大細胞癌細胞株,期望篩選出廣效型的肺癌標的胜肽。三條標的胜肽 (HSP1、HSP2和HSP4) 及其所對應的的噬菌體 (HPC1、HPC2和HPC4) 可以結合小細胞肺癌和非小細胞肺癌的細胞株和臨床病人檢體,且不會與正常細胞結合。在活體的噬菌體光學照影及胜肽接合超順磁氧化鐵奈米粒子的磁振照影實驗顯示,HSP1最適合發展為多重模式的分子影像探針。HSP1可以導引氧化鐵在H460腫瘤中累積並造成T2磁振訊號下降42%。在T2的磁振造影模式中,HSP2的水分子自旋子吸引效應及其卓越的腫瘤標的能力造成奈米粒子周圍局部磁場不均勻的現象,使HSP2-HDex-Fe3O4奈米粒子成為有前景的顯影劑,可以將細微的腫瘤結構顯像並可運用於未來臨床中於低信號的肺實質中偵測肺癌病灶。HSP1可與肺癌細胞表面緊密結合,相反的,HSP4則傾向於導引內噬作用與細胞內的藥物傳輸,因此顯著的增進活體的治療指數。在非小細胞肺癌 (H460和H1993) 的動物模式中,HSP1、HSP2和HSP4接合的小紅莓微脂體顯著地增進非標的微脂體藥物的療效。在更惡性的A549原位癌移植動物模式中,HSP4接合的穩定型長春瑞濱微脂體及HSP4接合的小紅莓微脂體的複合式療法能更近一步地增進非標的微脂體藥物的中位存活率,由84天延長至131天( P值0.0248)。 結論: 總結而言,在未來的應用上,這三條標的胜肽可以導引針對各樣的肺癌亞型特製之“治療診斷試劑”,對於發展標靶治療、非侵入式照影、小細胞肺癌和非小細胞肺癌的偵檢極具臨床潛力。 | zh_TW |
dc.description.abstract | Background:
Lung cancer is the leading cause of cancer-related death worldwide. Most targeting drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) of EGFR or ALK, mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC); we therefore aimed to identify targeting peptides with broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC) for diagnostic and therapeutic purposes. Results: We performed phage display biopanning of H460 LCC cells to select “broad-spectrum” lung cancer-binding peptides, since LCC has recently been categorized as an undifferentiated tumor type within other histological subcategories of lung cancer. Three targeting phage (HPC1, HPC2, and HPC4) and their respective displayed peptides (HSP1, HSP2, and HSP4) were able to bind to both SCLC and NSCLC cell lines and clinical specimens, but not to normal pneumonic tissues. In vivo optical imaging of phage homing and magnetic resonance imaging (MRI) of peptide-SPIONs revealed that HSP1 was the most favorable probe for multimodal molecular imaging, which resulted in a decrease of T2-weighted MR signal of up to 42% in H460 xenografts. The water spin collection effect and prominent tumor homing capability of HSP2 contribute to an inhomogeneous local magnetic field around the nanoparticles, making HSP2-HDex-Fe3O4 a promising contrast agent for visualizing subtle tumor structures and for detecting foci of lung cancer in hypointense lung parenchyma clinically by using common T2 MRI. Contrary to the tight binding of HSP1 to cancer cell surfaces, HSP4 favors endocytosis and intracellular drug delivery, thereby significantly improving the therapeutic index in vivo. Liposomal doxorubicin (LD) conjugated to HSP1, HSP2, or HSP4 had significantly greater therapeutic efficacy than non-targeting liposomal drugs in NSCLC (H460 and H1993) animal models. Combined therapy with an HSP4-conjugated stable formulation of liposomal vinorelbine (sLV) further improved median overall survival (131 vs. 84 days; P = 0.0248), even in aggressive A549 orthotopic models. Conclusions: Overall, these peptides have the potential to guide a wide variety of tailored “theranostic agents” for targeting therapy, non-invasive imaging, and clinical detection of SCLC and NSCLC. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:38:35Z (GMT). No. of bitstreams: 1 ntu-105-F96444002-1.pdf: 12435754 bytes, checksum: c9d2b9fbdbe947cfd3937faf32365d6f (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書...........................................................................................................1
中文摘要...........................................................................................................................2 Abstract............................................................................................................................4 Abbreviations...................................................................................................................6 Table of content................................................................................................................9 Chapter 1. Introduction................................................................................................15 1-1 Epidemiology and etiology of lung cancer....................................................15 1-2 Lung cancer classification.............................................................................16 1-3 Current treatment for lung cancer..................................................................18 1-4 Drug Delivery Systems (DDS)......................................................................20 1-5 Early detection of lung cancer.......................................................................23 1-6 Magnetic Resonance Imaging (MRI)............................................................25 Chapter 2. Materials and Methods..............................................................................29 2-1 Cell lines and cultures...................................................................................29 2-2 Peptide synthesis and labeling......................................................................29 2-3 Flow cytometry analysis...............................................................................30 2-4 Immunohistochemical staining of human surgical specimens......................30 2-5 Ethics Statement for animal experiments......................................................31 2-6 In vivo tumor homing assay and optical imaging..........................................32 2-7 Synthesis and characterization of peptide-conjugated, hydroxyl-rich, dextran-coated SPIONs................................................................................33 2-8 In vivo MR imaging using targeting peptide-HDex-Fe3O4 NPs for tumor Tracing..........................................................................................................33 2-9 Prussian blue staining and histological analysis...........................................34 2-10 Preparation of liposomal doxorubicin (LD) and liposomal SRB (LSRB)....35 2-11 Preparation of stable liposomal formulation of vinorelbine (sLV)...............36 2-12 Synthesis of targeted peptide-PEG-DSPE conjugates and incorporation into liposomal nanoparticles.........................................................................37 2-13 Characterization of liposomal nanoparticles.................................................38 2-14 Uptake of targeting peptide-conjugated LSRB or LD by human lung cancer cells...................................................................................................38 2-15 Animal models for the study of ligand-targeted therapy...............................39 2-16 Pharmacokinetic and biodistribution studies................................................40 2-17 Statistical analysis.........................................................................................41 Chapter 3. Results..........................................................................................................42 3-1 Identification of three novel peptides that bind to several histopathological subtypes of human lung cancer.....................................................................42 3-2 Binding activities of HPC1, HPC2, and HPC4 to clinical surgical specimens of human lung cancer....................................................................................45 3-3 In vivo tumor homing and optical imaging of HPC1, HPC2, and HPC4......46 3-4 In vivo MR imaging of HSP1-, HSP2-, and HSP4-conjugated hydroxyl-rich, dextran-coated SPIONs for tumor tracing....................................................47 3-5 Water (proton) spin collection effects of HSP2- and HSP4-conjugated hydroxyl-rich, dextran-coated SPIONs on T2-weighted MR images..........51 3-6 HSP1, HSP2, and HSP4 improve liposomal drug binding, intracellular delivery, and cytotoxicity..............................................................................53 3-7 HSP1-, HSP2-, and HSP4-mediated drug delivery systems enhance biodistribution and therapeutic efficacy in vivo...........................................55 3-8 Characterization and comparison of HSP4-conjugated LD and sLV............57 3-9 Targeting liposome-based combination therapy further improved overall Survival.........................................................................................................59 3-10 Target molecule prediction for HSP1, HSP2, and HSP4..............................61 Chapter 4. Discussion....................................................................................................64 Acknowledgments..........................................................................................................71 References.......................................................................................................................72 Tables..............................................................................................................................89 Figures............................................................................................................................98 | |
dc.language.iso | en | |
dc.title | 適用於多種亞型的肺癌標的胜肽於複合式藥物傳輸與分子磁振照影之應用 | zh_TW |
dc.title | Lung Cancer-Targeting Peptides with Multi-subtype Indication for Combinatorial Drug Delivery and Molecular Magnetic Resonance Imaging | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 張程,李美賢,李文山,李賢明 | |
dc.subject.keyword | 小細胞肺癌,非小細胞肺癌,標的胜?,微脂體藥物,分子磁振照影, | zh_TW |
dc.subject.keyword | Small cell lung cancer (SCLC),non-small cell lung cancer (NSCLC),targeting peptides,liposomal drugs,molecular magnetic resonance imaging, | en |
dc.relation.page | 131 | |
dc.identifier.doi | 10.6342/NTU201602814 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2016-08-16 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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