博碩士論文 107324041 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:24 、訪客IP:75.101.211.110
姓名 賴祈宏(Chi-Hung Lai)  查詢紙本館藏   畢業系所 化學工程與材料工程學系
論文名稱 立體紙基外泌體核酸萃取裝置應用於檢測不同微環境下癌細胞所釋放之外泌體與外泌體微小核醣核酸之表現量
(Three-dimensional paper-based exosomal nucleic acid extraction device for detection of exosomes and exosomal miRNAs released by cancer cell cultured in different microenvironment)
相關論文
★ 類澱粉胜肽聚集行為之電腦模擬★ 溶解度參數計算及量測於HPLC純化胜肽程序之最佳化研究
★ 利用恆溫滴定微卡計量測蛋白質分子於溶液中之第二維里係數與自我聚集之行為★ 利用SPRi探討中性DNA探針相較於一般DNA探針在低鹽雜交環境下之優勢
★ 矽奈米線場效電晶體多點之核酸檢測研究★ 使用不帶電中性核酸探針於矽奈米線場效電晶體檢測去氧核醣核酸與微核醣核酸之研究
★ 運用nDNA 修飾引子於PCR及qPCR平台以提升專一性之研究★ 設計中性DNA引子及探針以提升PCR與qPCR專一性之研究
★ 使用中性不帶電去氧核醣核酸探針於矽奈米線場效電晶體檢測微核醣核酸之研究★ 使用不帶電中性核酸探針於原位雜交技術檢測微核醣核酸之研究
★ 設計不帶電中性核酸探針於矽奈米線場效電晶體來改善富含GC鹼基核醣核酸之檢測專一性★ 合成5’-MeNPOC-2’-deoxynucleoside p-methoxy phosphoramidite以作為應用於原位合成之新穎性中性核苷酸之研究
★ 利用抗原結合區段之抗體片段探針於矽奈米線場效電晶體來改善抗原檢測濃度極限之研究★ 利用表面電漿共振影像儀驗證最適化之抗非專一性吸附場效電晶體表面於血清環境下之免疫測定
★ 使用混合自組裝單層膜於矽奈米線場效電晶體檢測微小核醣核酸之研究★ 利用核適體作為訊號放大器於矽奈米線場效電晶體免疫感測器對生物標記物進行定量分析
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 ( 永不開放)
摘要(中) 由細胞分泌的外泌體(exosome)含有細胞特異的核酸及蛋白質,已被證實參與腫瘤的發展、擴散及轉移的發生過程。其中微核醣核酸(microRNA) 在許多疾病的診斷以及治療上為一個非常具有潛力的生物標靶分子,藉由和其目標信使核糖核酸(messanger RNA)的互補序列結合誘發mRNA的降解以調節基因的表現。因為這些特性與功能,外泌體非常有潛力成為疾病檢測用的工具之一,尤其是腫瘤外泌體可能成為癌症早期診斷或術後檢測的判斷依據。由於外泌體能夠穩定存在於人體體液之中且帶有來自母細胞的生物分子,相較於傳統的組織切片(traditional biopsy),從體液分析外泌體這類的液態切片(liquid biopsy)不僅降低了侵入風險,也能夠更即時的反應出腫瘤當下的情況,雖然目前外泌體的應用還停留在科學研究,尚未普遍於疾病的常規檢測上,但由於外泌體於臨床應用的潛力,有發展出相當多的外泌體的應用技術。但現今對於外泌體的分離純化或是生物分子的分析皆需要專業的操作人員、特殊的藥品、費時及昂貴的儀器,鑒於以上原因,使得外泌體及核酸檢測比較無法於一般檢驗室操作,更無法落實於Point-of-care testing。
在此研究中,本實驗室欲發展一套外泌體核酸萃取裝置,結合本實驗室對於核酸萃取的研究,以取代過往對於外泌體純化及核酸萃取繁瑣的操作流程。我們在裝置表面改植上特殊蛋白質,作為分離外泌體的機制;接著在裝置表面塗布上核酸吸附顆粒,藉此分離外泌體中的核酸。我們利用此外泌體核酸萃取裝置於檢測HCT116人類結腸癌細胞株於不同微環境(microenvironment)下外泌體釋放量及核酸表現量。實驗結果顯示在相同的實驗條件下,酸性環境下具有較多外泌體釋放量,也能成功地辨識不同樣品之間核酸表現量。
最後也將裝置應用於慢性傷口組織液的臨床檢測上並得到初步有意義的結果。期望藉由此外泌體核酸萃取裝置能夠使外泌體及核酸檢測,能夠更貼近POCT的應用。
摘要(英) A rapid, microfluidic- extraction device was developed for the extraction of the exosomal nucleic acids of HCT116 colon cancer cell cultured in different microenvironment. Nucleic acid testing (NAT) has been widely used for disease diagnosis, food safety control and environmental monitoring. And currently require laborious off-chip exosome separation, nucleic acid extraction prior to detection. With advances in point-of-care testing (POCT) has been explored for nucleic acid detection. We definitely need to develop an inexpensive, robust, easy-to-use and compatible with downstream nucleic acid detection to replace the traditional method that need the expensive infrastructure and time-consuming process. Here, we have extracted nucleic acid from cell culture medium and clinical chronic wound samples using exosomal nucleic acid extraction devices. Captured exosomes were analyzed by SEM and qNano to check the morphology and size, respectively. Assessing the amount of exosomes captured using P-ELISA using antibodies conjugated to horseradish peroxidase to produce a colorimetric readout was accomplished within 30 min. Nucleic acid can be extracted by exosomal nucleic acid extraction devices and analyzed by real-time polymerase chain reaction (qPCR) to provide information for disease management. As a whole, we have already developed a exosomal nucleic acid extraction device to extract nucleic acid from HCT116 cultured in different microenvironment and chronic wound samples from the different patients in the different stages that employ an user-friendly procedure and encourage a quicker adoption of this technology in POCT.
關鍵字(中) ★ 外泌體
★ 微小核糖核酸
★ 反轉錄及時聚合酶鍊式反應
★ HCT116癌細胞
★ 紙基微流道
★ 慢性傷口
關鍵字(英) ★ exosome
★ microRNA
★ qPCR
★ HCT116 cancer cell line
★ Paper microfluidic
★ Chronic wound
論文目次 摘要 i
ABSTRACT iii
誌謝 iv
目錄 v
圖目錄 ix
表目錄 xiii
一、 緒論 1
1.1 研究背景 1
1.2 論文架構 3
二、 文獻回顧 4
2.1 核酸介紹 4
2.1.1 核酸分子 4
2.1.2 去氧核醣核酸 5
2.1.3 核醣核酸 6
2.1.4 微小核醣核酸 8
2.2 分子生物檢測平台 9
2.2.1 聚合酶鏈鎖反應(Polymerase chain reaction, PCR) 9
2.2.2 即時定量聚合酶鏈鎖反應(Quantitative real time polymerase chain reaction, qPCR)檢測miRNA原理 11
2.3 酵素結合免疫吸附分析法(Enzyme-linked immunosorbent assay, ELISA) 15
2.4 細胞外囊泡(Extracellular vesicles) 介紹 16
2.4.1 外泌體(Exosome) 17
2.5 Exosome分離方式 20
2.5.1 超速離心法(Ultracentrifugation-based isolation techniques) 20
2.5.2 沉澱法(Precipitation) 21
2.5.3 免疫法(Immunoaffinity capture-based techniques) 22
2.5.4 粒徑篩析法(Size-based isolation techniques) 22
2.6 Paper-based device 24
2.6.1 Paper-based immunoaffinity device 25
2.6.2 Paper-based ELISA 26
2.6.3 Paper-based nucleic acid extraction device 27
三、 實驗藥品、儀器及方法 28
3.1 實驗藥品 28
3.1.1 細胞培養 28
3.1.2 外泌體純化濃縮 28
3.1.3 Paper-based immunoaffinity device 28
3.1.4 Paper-based ELISA 29
3.1.5 Paper-based nucleic acid extraction device 29
3.1.6 核酸萃取 29
3.1.7 即時聚合酶鏈式反應 30
3.2 儀器設備 31
3.3 實驗方法 32
3.3.1 細胞解凍 32
3.3.2 細胞培養 33
3.3.3 細胞培養於不同pH細胞培養液 34
3.3.4 細胞冷凍保存 36
3.3.5 微小核糖核酸萃取 37
3.3.6 外泌體純化濃縮 39
3.3.7 qNano 40
3.3.8 Paper-based immunoaffinity device 42
3.3.9 Paper-based ELISA 44
3.3.10 Paper-based nucleic acid extraction device 46
3.3.11 反轉錄及時聚合酶鍊式反應(qRT-PCR) 48
四、 結果與討論 52
4.1 建立立體紙基外泌體核酸萃取裝置 52
4.1.1 Paper-based immunoaffinity device 應用於捕獲HCT116癌細胞之exosome 54
4.1.2 Paper-based nucleic acid extraction device應用於萃取HCT116 exosome之核酸 60
4.2 HCT116癌細胞培養於不同微環境 64
4.2.1 利用P-ELISA檢測HCT116癌細胞於不同微環境中exosome釋放量 65
4.2.2 HCT116癌細胞培養於不同微環境中外泌體微小核醣核酸表現量69
4.3 立體紙基外泌體核酸萃取裝置應用於慢性傷口(chronic wound)檢體 76
五、 結論 83
六、 未來展望 85
七、 參考文獻 86
八、 附錄 92
8.1 Paper-based nucleic acid extraction device 實驗參數 92
8.2 利用P-ELISA檢測慢性傷口組織液 95
參考文獻 [1] R. J. H. g. Dahm, "Discovering DNA: Friedrich Miescher and the early years of nucleic acid research," Human genetics, vol. 122, no. 6, pp. 565-581, 2008.
[2] J. D. Watson and F. H. J. J.-A. M. A. Crick, "Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid," Jama, vol. 269, pp. 1966-1966, 1993.
[3] A. Leslie, S. Arnott, R. Chandrasekaran, and R. J. J. o. m. b. Ratliff, "Polymorphism of DNA double helices," Journal of molecular biology, vol. 143, no. 1, pp. 49-72, 1980.
[4] A. Herbert and A. J. J. o. B. C. Rich, "The biology of left-handed Z-DNA," Journal of Biological Chemistry, vol. 271, no. 20, pp. 11595-11598, 1996.
[5] R. C. Lee, R. L. Feinbaum, and V. J. c. Ambros, "The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14," cell, vol. 75, no. 5, pp. 843-854, 1993.
[6] L.-A. MacFarlane and P. J. C. g. R Murphy, "MicroRNA: biogenesis, function and role in cancer," Current genomics, vol. 11, no. 7, pp. 537-561, 2010.
[7] G. A. Calin and C. M. J. N. r. c. Croce, "MicroRNA signatures in human cancers," Nature reviews cancer, vol. 6, no. 11, pp. 857-866, 2006.
[8] S. Lin and R. I. J. N. r. c. Gregory, "MicroRNA biogenesis pathways in cancer," Nature reviews cancer, vol. 15, no. 6, pp. 321-333, 2015.
[9] L. S. Beese, V. Derbyshire, and T. A. J. S. Steitz, "Structure of DNA polymerase I Klenow fragment bound to duplex DNA," Science, vol. 260, no. 5106, pp. 352-355, 1993.
[10] J. C. Akers, D. Gonda, R. Kim, B. S. Carter, and C. C. J. J. o. n.-o. Chen, "Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies," Journal of Neuro-Oncology, vol. 113, no. 1, pp. 1-11, 2013.
[11] M. Mathieu, L. Martin-Jaular, G. Lavieu, and C. J. N. c. b. Thery, "Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication," Nature cell biology, vol. 21, no. 1, pp. 9-17, 2019.
[12] E. G. Trams, C. J. Lauter, J. N. Salem, and U. J. B. e. B. A.-B. Heine, "Exfoliation of membrane ecto-enzymes in the form of micro-vesicles," Biochimica et Biophysica Acta, vol. 645, no. 1, pp. 63-70, 1981.
[13] K. M. McAndrews and R. J. M. c. Kalluri, "Mechanisms associated with biogenesis of exosomes in cancer," Molecular cancer, vol. 18, no. 1, p. 52, 2019.
[14] J. C. Contreras-Naranjo, H.-J. Wu, and V. M. J. L. o. a. C. Ugaz, "Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine," Lab on a Chip, vol. 17, no. 21, pp. 3558-3577, 2017.
[15] J. R. J. B. b. Edgar, "Q&A: What are exosomes, exactly?," BMC biology, vol. 14, no. 1, p. 46, 2016.
[16] A. V. Vlassov, S. Magdaleno, R. Setterquist, and R. J. B. e. B. A.-G. S. Conrad, "Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials,"Biochimica et Biophysica Acta (BBA)- General Subjects, vol. 1820, no. 7, pp. 940-948, 2012.
[17] I. V. Miller and T. G. J. B. o. t. C. Grunewald, "Tumour‐derived exosomes: Tiny envelopes for big stories," Biology of the Cell, vol. 107, no. 9, pp. 287-305, 2015.
[18] M.-P. Caby, D. Lankar, C. Vincendeau-Scherrer, G. Raposo, and C. J. I. i. Bonnerot, "Exosomal-like vesicles are present in human blood plasma," International immunology, vol. 17, no. 7, pp. 879-887, 2005.
[19] C. Lässer et al., "Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages," Journal of Translational Medicine, vol. 9, no. 1, p. 9, 2011.
[20] C. Admyre et al., "Exosomes with immune modulatory features are present in human breast milk,"The journal of immunology, vol. 179, no. 3, pp. 1969-1978, 2007.
[21] D. A. Raj, I. Fiume, G. Capasso, and G. J. K. i. Pocsfalvi, "A multiplex quantitative proteomics strategy for protein biomarker studies in urinary exosomes," Kidney international, vol. 81, no. 12, pp. 1263-1272, 2012.
[22] I. J. J. N. r. c. Fidler, "The pathogenesis of cancer metastasis: the′seed and soil′hypothesis revisited," Nature reviews cancer, vol. 3, no. 6, pp. 453-458, 2003.
[23] A. Hoshino et al., "Tumour exosome integrins determine organotropic metastasis," Nature, vol. 527, no. 7578, pp. 329-335, 2015.
[24] G. Raposo et al., "B lymphocytes secrete antigen-presenting vesicles," Journal of Experimental Medicine, vol. 183, no. 3, pp. 1161-1172, 1996.
[25] L. Zitvogel et al., "Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes," Nature medicine, vol. 4, no. 5, pp. 594-600, 1998.
[26] M. Simons and G. J. C. o. i. c. b. Raposo, "Exosomes–vesicular carriers for intercellular communication," Current opinion in cell biology, vol. 21, no. 4, pp. 575-581, 2009.
[27] C. Théry, M. Ostrowski, and E. J. N. r. i. Segura, "Membrane vesicles as conveyors of immune responses," Nature reviews immunology, vol. 9, no. 8, pp. 581-593, 2009.
[28] J. Conde-Vancells et al., "Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes," Journal of proteome research, vol. 7, no. 12, pp. 5157-5166, 2008.
[29] K. Trajkovic et al., "Ceramide triggers budding of exosome vesicles into multivesicular endosomes," Science, vol. 319, no. 5867, pp. 1244-1247, 2008.
[30] C. Théry, L. Zitvogel, and S. J. N. r. i. Amigorena, "Exosomes: composition, biogenesis and function," Nature reviews immunology, vol. 2, no. 8, pp. 569-579, 2002.
[31] L. Qing, H. Chen, J. Tang, X. J. N. Jia, and n. repair, "Exosomes and their MicroRNA cargo: new players in peripheral nerve regeneration," Neurorehabilitation and neural repair, vol. 32, no. 9, pp. 765-776, 2018.
[32] J. Ratajczak, M. Wysoczynski, F. Hayek, A. Janowska-Wieczorek, and M. J. L. Ratajczak, "Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication," Leukemia, vol. 20, no. 9, pp. 1487-1495, 2006.
[33] S. A. Bellingham, B. M. Coleman, and A. F. J. N. a. r. Hill, "Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells," Nucleic acids research, vol. 40, no. 21, pp. 10937-10949, 2012.
[34] C. Yang, S.-H. Kim, N. R. Bianco, and P. D. J. P. o. Robbins, "Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model," PloS one, vol. 6, no. 8, 2011.
[35] H. W. King, M. Z. Michael, and J. M. J. B. c. Gleadle, "Hypoxic enhancement of exosome release by breast cancer cells," BMC cancer, vol. 12, no. 1, p. 421, 2012.
[36] X. Xiao et al., "Exosomes: decreased sensitivity of lung cancer A549 cells to cisplatin," PloS one, vol. 9, no. 2, 2014.
[37] H. Ogata-Kawata et al., "Circulating exosomal microRNAs as biomarkers of colon cancer," PloS one, vol. 9, no. 4, 2014.
[38] S. Yan et al., "Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer," Oncotarget, vol. 8, no. 36, p. 60149, 2017.
[39] R. Bryant et al., "Changes in circulating microRNA levels associated with prostate cancer," British journal of cancer, vol. 106, no. 4, pp. 768-774, 2012.
[40] R. Que, G. Ding, J. Chen, and L. J. W. j. o. s. o. Cao, "Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma," World journal of surgical oncology, vol. 11, no. 1, p. 219, 2013.
[41] N. Yanaihara et al., "Unique microRNA molecular profiles in lung cancer diagnosis and prognosis," Cancer cell, vol. 9, no. 3, pp. 189-198, 2006.
[42] E. Zeringer, T. Barta, M. Li, and A. V. J. C. S. H. P. Vlassov, "Strategies for isolation of exosomes," Cold Spring Harbor Protocols, vol. 2015, no. 4, p. pdb. top074476, 2015.
[43] P. Li, M. Kaslan, S. H. Lee, J. Yao, and Z. J. T. Gao, "Progress in exosome isolation techniques," Theranostics, vol. 7, no. 3, p. 789, 2017.
[44] B. J. Tauro et al., "Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes," Methods, vol. 56, no. 2, pp. 293-304, 2012.
[45] C. Théry, S. Amigorena, G. Raposo, and A. J. C. p. i. c. b. Clayton, "Isolation and characterization of exosomes from cell culture supernatants and biological fluids," Current protocols in cell biology, vol. 30, no. 1, pp. 3.22. 1-3.22. 29, 2006.
[46] L. Zhao, J. Yu, J. Wang, H. Li, J. Che, and B. J. J. o. C. Cao, "Isolation and Identification of miRNAs in exosomes derived from serum of colon cancer patients," Journal of Cancer, vol. 8, no. 7, p. 1145, 2017.
[47] C. S. Hong, L. Muller, M. Boyiadzis, and T. L. J. P. o. Whiteside, "Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia," PloS one, vol. 9, no. 8, 2014.
[48] K. Ueda, N. Ishikawa, A. Tatsuguchi, N. Saichi, R. Fujii, and H. J. S. r. Nakagawa, "Antibody-coupled monolithic silica microtips for highthroughput molecular profiling of circulating exosomes," Scientific reports, vol. 4, p. 6232, 2014.
[49] S. Mathivanan et al., "Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature," Molecular & Cellular Proteomics, vol. 9, no. 2, pp. 197-208, 2010.
[50] A. Cheruvanky et al., "Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator," American Journal of Physiology-Renal Physiology, vol. 292, no. 5, pp. F1657-F1661, 2007.
[51] C.-S. Hong, S. Funk, L. Muller, M. Boyiadzis, and T. L. J. J. o. e. v. Whiteside, "Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer," Journal of extracellular vesicles, vol. 5, no. 1, p. 29289, 2016.
[52] A. W. Martinez, S. T. Phillips, G. M. Whitesides, and E. Carrilho, "Diagnostics for the developing world: microfluidic paper-based analytical devices," ed: ACS Publications, 2010.
[53] E. Carrilho, S. T. Phillips, S. J. Vella, A. W. Martinez, and G. M. J. A. c. Whitesides, "Paper microzone plates," Analytical chemistry, vol. 81, no. 15, pp. 5990-5998, 2009.
[54] E. Carrilho, A. W. Martinez, and G. M. J. A. c. Whitesides, "Understanding wax printing: a simple micropatterning process for paper-based microfluidics," Analytical chemistry, vol. 81, no. 16, pp. 7091-7095, 2009.
[55] A. W. Martinez et al., "Programmable diagnostic devices made from paper and tape," Lab on a Chip, vol. 10, no. 19, pp. 2499-2504, 2010.
[56] A. K. Yetisen, M. S. Akram, and C. R. J. L. o. a. C. Lowe, "based microfluidic point-of-care diagnostic devices," Lab on a Chip, vol. 13, no. 12, pp. 2210-2251, 2013.
[57] D. M. Cate, J. A. Adkins, J. Mettakoonpitak, and C. S. J. A. c. Henry, "Recent developments in paper-based microfluidic devices," Analytical chemistry, vol. 87, no. 1, pp. 19-41, 2015.
[58] C. Chen et al., "based immunoaffinity devices for accessible isolation and characterization of extracellular vesicles," Microfluidics and nanofluidics, vol. 16, no. 5, pp. 849-856, 2014.
[59] M.-Y. Hsu et al., "Based Microfluidic Platforms for Understanding the Role of Exosomes in the Pathogenesis of Major Blindness-Threatening Diseases," Nanomaterials, vol. 8, no. 5, p. 310, 2018.
[60] C. M. Cheng et al., "Paper‐based ELISA," Angewandte Chemie International Edition, vol. 49, no. 28, pp. 4771-4774, 2010.
[61] K. A. Melzak, C. S. Sherwood, R. F. Turner, C. A. J. J. o. c. Haynes, and i. science, "Driving forces for DNA adsorption to silica in perchlorate solutions," Journal of colloid and interface science, vol. 181, no. 2, pp. 635-644, 1996.
[62] E. Evans, E. F. M. Gabriel, T. E. Benavidez, W. K. T. Coltro, and C. D. J. A. Garcia, "Modification of microfluidic paper-based devices with silica nanoparticles," Analyst, vol. 139, no. 21, pp. 5560-5567, 2014.
[63] I. Balcells, S. Cirera, and P. K. J. B. b. Busk, "Specific and sensitive quantitative RT-PCR of miRNAs with DNA primers," BMC biotechnology, vol. 11, no. 1, p. 70, 2011.
[64] Y. Wu, W. Deng, and D. J. J. A. Klinke II, "Exosomes: improved methods to characterize their morphology, RNA content, and surface protein biomarkers," Analyst, vol. 140, no. 19, pp. 6631-6642, 2015.
[65] 陳昱圻, "改良二氧化矽纖維膜分離程序於培養的細胞中微核醣核酸之純化," 中央大學碩士論文, 2018.
[66] M. G. Vander Heiden, L. C. Cantley, and C. B. J. s. Thompson, "Understanding the Warburg effect: the metabolic requirements of cell proliferation," science, vol. 324, no. 5930, pp. 1029-1033, 2009.
[67] M. Logozzi et al., "Microenvironmental pH and exosome levels interplay in human cancer cell lines of different histotypes," Cancers, vol. 10, no. 10, p. 370, 2018.
[68] X.-P. Tian et al., "Acidic microenvironment up-regulates exosomal miR-21 and miR-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis," Theranostics, vol. 9, no. 7, p. 1965, 2019.
[69] J. Zhao, Y. Zhang, and G. J. C. B. Zhao, "Emerging role of microRNA-21 in colorectal cancer," Cancer Biomarkers, vol. 15, no. 3, pp. 219-226, 2015.
[70] D. D. Taylor and C. J. G. o. Gercel-Taylor, "MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer," Gynecologic oncology, vol. 110, no. 1, pp. 13-21, 2008.
[71] G. Hu, K. M. Drescher, and X. J. F. i. g. Chen, "Exosomal miRNAs: biological properties and therapeutic potential," Frontiers in genetics, vol. 3, p. 56, 2012.
[72] Q. Ge, Y. Zhou, J. Lu, Y. Bai, X. Xie, and Z. J. M. Lu, "miRNA in plasma exosome is stable under different storage conditions," Molecules, vol. 19, no. 2, pp. 1568-1575, 2014.
[73] M. Tsukamoto, H. Iinuma, T. Yagi, K. Matsuda, and Y. J. O. Hashiguchi, "Circulating exosomal microRNA-21 as a biomarker in each tumor stage of colorectal cancer," Oncology, vol. 92, no. 6, pp. 360-370, 2017.
[74] S. Werner and R. J. P. r. Grose, "Regulation of wound healing by growth factors and cytokines," Physiological reviews, vol. 83, no. 3, pp. 835-870, 2003.
[75] T. Wang et al., "miR-21 regulates skin wound healing by targeting multiple aspects of the healing process," The American journal of pathology, vol. 181, no. 6, pp. 1911-1920, 2012.
[76] X. Yang et al., "miR-21 promotes keratinocyte migration and re-epithelialization during wound healing," International journal of biological sciences, vol. 7, no. 5, p. 685, 2011.
指導教授 陳文逸(Wen-Yih Chen) 審核日期 2020-7-21
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明