使用具有臨床應用性的紙基裝置改善外泌體以及外泌體衍生材料純化之研究

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：11

、訪客IP：3.133.134.121

姓名

武雲筑(Van-Truc Vu) 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

使用具有臨床應用性的紙基裝置改善外泌體以及外泌體衍生材料純化之研究
(Strategies to improve extraction of exosomes and exosome-derived materials by paper-based device with clinical applicability)

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
★ 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	★ 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

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 (2027-1-1以後開放)

摘要(中)

癌症是全球重大的公共衛生問題之一。根據 GLOBOCAN 2020 的數據，在全球所有年齡層中大腸直腸癌（CRC）佔的病例和死亡人數排名第三，而其生存率低很大程度是因為缺乏早期診斷和精準醫療。外泌體是由細胞分泌到體液中的細胞外囊泡，其大小介於 30 至 200nm 且內部含有許多的功能性生物分子，如蛋白質、脂質及核酸等，並具有在細胞間傳遞訊息的功能。exosomal miR-21 和癌胚胎抗原（CEA）雖然已被證明可調節大腸直腸癌和多種疾病的發病機制，但早期診斷和個人化治療的非侵入性方法對分離和分析這些循環生物標誌物是一種挑戰。
本研究利用免疫親和法獲得純外泌體或分離潛在細胞外囊泡亞群的能力，並結合紙基裝置的優勢，提出了一種紙基免疫親和裝置。該裝置是通過將 Whatman 紙表面改質上對外泌體的雙層磷脂質表面 CD63 蛋白含有高專一性的 anti-CD63 抗體開發而成的。為了檢測該裝置是否能被有效應用，這邊分別使用紙基酵素結合免疫吸附分析法（P-ELISA）和掃描電子顯微鏡（SEM）評估捕獲的外泌體的數量和形態。在確認此裝置能獲取外泌體後，接著設計更進階的實驗，針對的外泌體裂解時所含有的核酸和蛋白質進行分析。實驗上我們使用高溫超純水來裂解外泌體，並使釋放出的核酸被二氧化矽吸附，然後通過 RT-qPCR 檢測 exosomal miR-21。此外，在實驗上也將外泌體裂解後的裂解液直接進行 ELISA，用於外泌體 CEA 的檢測和定量。首先，我們使用來自 HCT116（人類結腸癌細胞系）細胞培養基的外泌體標準品來確認實驗中對外泌體分離、萃取和定量上整個過程的可行性。接著，使用生物樣品，如血漿、慢性傷口組織液等，來證明所設計的方法對於臨床上的適用性。最後，還研究此方法具有的特性，例如專一性、與商業試劑盒相比的 miRNA 萃取效率以及抗體修飾的紙基對時間的穩定性。
由結果證明了本研究可從不同樣品中分離和純化外泌體，甚至具有對裝置上外泌體定量的能力。而後，也成功進行紙基對 exosomal miR-21 的萃取和外泌體 CEA 定量之實驗，並在研究結果中顯示，使用高溫超純水可成功應用於外泌體 miRNA 萃取，但在針對外泌體 CEA 檢測研究目前還在進行程序上的優化。此外，傷口組織液中外泌體 miRNA 的實驗結果也顯示了慢性傷口癒合與 miRNA-21 含量之間的關聯。此設計的程序不僅穫取了更多的 exosomal miR-21，而且與商業試劑盒相比所需樣品量更少。此方法除了適用於不同的樣本檢測，如血漿、慢性傷口組織液和細胞培養基等，也對外泌體內部成分分析存在優勢。

摘要(英)

Cancer is a great worldwide public health concern with steadily rising incidence, especially in developing countries. According to GLOBOCAN 2020 data, colorectal cancer (CRC) ranks third in estimated number of incident cases and deaths worldwide, both sexes, all ages. The poor survival rate is largely because of lacking early diagnosis and precision medicine. Exosome is extracellular vesicle with diameter from 30 to 200 nm, secreted by all cells to body fluids, transporting functional biomolecules (nucleic acids, proteins, lipids, etc.) of normal physiology and acquired abnormalities. Namely, exosomal miRNA-21 and Carcinoembryonic antigen (CEA) have been revealed to regulate the pathogenesis of colorectal cancer and numerous diseases. However, non-invasive methods for early diagnoses and personalized treatments are hindered by challenges of isolating and profiling these circulating biomarkers.
Leveraging the capacity to obtain pure exosomes of immunoaffinity method and advantages of paper platform – an ideal candidate for point-of-care testing (POCT), this study presents a paper-based immunoaffinity device developed by fabricating Whatman paper surface with anti-CD63 antibodies to specifically target CD63 protein on exosome membrane. Number and morphology of captured exosomes were evaluated using paper-based enzyme-linked immunosorbent assays (P-ELISA) and scanning electron microscopy (SEM), respectively. Following initial successes, we designed further procedures for exosomal nucleic acids and proteins to be analyzed. First, we used high temperature double-distilled water, a highly purified and easily accessible laboratory water for biochemistry, to lyse the exosome and released nucleic acids were absorbed by silica particles before extracted miRNA-21 was evaluated by RT-qPCR. Otherwise, lysed solution of exosomes was directly performed ELISA for detection and quantification of exosomal CEA. At first, we used the standard exosomes from cell culture media of HCT116 (a human colorectal carcinoma cell line) to clarify the feasibility of the whole process from exosome isolation to extraction and quantification of exosomal nucleic acids and proteins. Afterward, biological samples (plasma, chronic wound fluids) were applied to demonstrate the clinical applicability of the designed methods. Finally, some properties of these approaches such as specificity, miRNA extraction efficiency compared with commercial kit as well as the stability of modified paper were also investigated.
The first success achieved was to demonstrate the feasibility of isolating and purifying exosomes from diverse samples and the ability to distinguish the number of captured exosomes. Thereafter, paper-based designed procedures for exosomal miRNA-21 extraction and exosomal CEA quantification were successfully experimented. Interestingly, the empirical results indicate that using high temperature double-distilled water as a lysis buffer was successfully applied for exosomal miRNA extraction, but not as effective as commercial lysis buffer in exosomal CEA study. Moreover, experimental results on wound fluids exposed an association between prolongation of healing and exosomal miRNA-21 reduction. Our designed procedure not only harvested more copious amount of exosomal miRNA but also consumed less sample volume than by commercial kit. These approaches feasibly adopt for different samples (plasma, chronic wound fluids, cell culture media) and manifest advantages for deeper inquiry on exosome-derived constituents.

關鍵字(中)

★ 外泌體
★ 大腸癌
★ miRNA-21
★ CEA

關鍵字(英)

★ exosome
★ colorectal cancer
★ miRNA-21
★ CEA

論文目次

摘要 i
Abstract iii
Acknowledgements v
Table of Contents vi
List of Figures ix
List of Tables xii
Chapter 1. Introduction 1
1.1 Motivations 1
1.2 Objectives 3
1.3 Structure 4
Chapter 2. Research background and Literature review 6
2.1 Nucleic acids 6
2.1.1 Nucleic acid molecules 6
2.1.2 Deoxyribonucleic acid 7
2.1.3 Ribonucleic acid 8
2.1.4 Microribonucleic acid 9
2.1.5 Micro RNA-21 10
2.1.6 Reverse transcription polymerase chain reaction (RT-qPCR) 11
2.2 Proteins 15
2.2.1 History and biogenesis 15
2.2.2 General structures 16
2.2.3 Biological function 18
2.2.4 Carcinoembryonic antigen (CEA) 19
2.2.5 Enzyme-linked immunosorbent assay (ELISA) 19
2.3 Exosome 21
2.3.1 History of Extracellular vesicles and Exosome 21
2.3.2 Biogenesis of Exosomes 21
2.3.3 Biological functions of exosomes 22
2.3.4 Isolation methods 24
2.3.5 Characterization techniques 25
2.4 Paper-based strategies 27
2.4.1 Paper-based immunoaffinity device 27
2.4.2 Paper-based ELISA for exosome quantification 28
2.4.3 Paper-based nucleic acid extraction procedure 28
2.4.4 Exosomal protein study 29
Chapter 3. Materials and Methods 30
3.1 Materials 30
3.1.1 Chemicals 30
3.1.2 Apparatuses and instruments 32
3.2 Methods 33
3.2.1 Sample preparations 33
3.2.2 Paper modification for exosome isolation 36
3.2.3 Paper-based ELISA (P-ELISA) for exosome detection and quantification 37
3.2.4 Paper-based procedure for exosomal nucleic acid extraction 37
3.2.5 Exosomal nucleic acid extraction using miRNeasy Mini kit 38
3.2.6 RT-qPCR for nucleic acid quantification 39
3.2.7 Paper-based procedure for exosomal protein study 41
3.2.8 ELISA for exosomal CEA detection 41
Chapter 4. Results and Discussion 42
4.1 Anti-CD63-modified paper for exosome isolation 42
4.1.1 P-ELISA confirms and quantifies captured exosomes on modified paper 43
4.1.2 SEM images of captured exosomes under different lysis conditions 45
4.2 Paper-based procedure designed for exosomal nucleic acid extraction 47
4.2.1 Exosome lysis methods 48
4.2.2 Free miRNA-21 captured by anti-CD63-modified paper 49
4.2.3 Clinical applicability of exosomal nucleic acid extraction procedure 50
4.2.4 Comparison of designed extraction procedure with miRNeasy Mini Kit 53
4.2.5 Operability of anti-CD63-modified paper under various storage conditions 54
4.3 Exosomal protein detection and quantification via paper-based device 55
4.3.1 Free-CEA captured by anti-CD63-modified paper 55
4.3.2 CEA detection in lyophilized exosomes under different lysis buffers 56
4.3.3 Exosomal CEA quantification in variously concentrated cell culture media 59
Chapter 5. Conclusions and Outlook 64
5.1 Conclusions 64
5.2 Outlook 65
Chapter 6. References 66

參考文獻

References
[1]
C. E. Meacham and S. J. Morrison, "Tumor heterogeneity and cancer cell plasticity," Nature, vol. 501, no. 7467, pp. 328 - 337, 2013.
[2]
R. Fisher, L. Pusztai and C. Swanton, "Cancer heterogeneity: implications for targeted therapeutics," British Journal of Cancer, vol. 108, p. 479–485, 2013.
[3]
J. Ferlay, M. Ervik, F. Lam, M. Colombet, L. Mery, M. Piñeros, A. Znaor, I. Soerjomataram and F. Bray, "Global Cancer Observatory: Cancer Today," International Agency for Research on Cancer, 2020. [Online]. Available: https://gco.iarc.fr/today. [Accessed 15 March 2021].
[4]
"The WHITE HOUSE. PRESIDENT BARACK OBAMA," 25 February 2016. [Online]. Available: https://obamawhitehouse.archives.gov/the-press-office/2016/02/25/fact-sheet-obama-administration-announces-key-actions-accelerate. [Accessed 15 March 2021].
[5]
D. Levenson, "American Association for Clinical Chemistry (AACC)," 01 November 2020. [Online]. Available: https://www.aacc.org/cln/articles/2020/november/a-new-era-for-liquid-biopsy. [Accessed 15 March 2021].
[6]
B. Zhou, K. Xu, X. Zheng, T. Chen, J. Wang, Y. Song, Y. Shao and S. Zheng, "Application of exosomes as liquid biopsy in clinical diagnosis," Signal Transduction and Targeted Therapy, vol. 5, no. 1, 2020.
[7]
A. Makler and W. Asghar, "Exosomal biomarkers for cancer diagnosis and patient monitoring," Expert Rev Mol Diagn, vol. 20, no. 4, pp. 387-400, 2020.
[8]
C.-h. Hong and Y.-c. Chen, "Clinical significance of exosomes as potential biomarkers in cancer," World Journal of Clinical Cases, vol. 7, no. 2, pp. 171-190, 2019.
[9]
Y. Xie, W. Dang, S. Zhang, W. Yue, L. Yang, X. Zhai, Q. Yan and J. Lu, "The role of exosomal noncoding RNAs in cancer," Molecular Cancer, vol. 18, no. 37, 2019.
[10]
W. Li, C. Li, T. Zhou, X. Liu, X. Liu, X. Li and D. Chen, "Role of exosomal proteins in cancer diagnosis," Molecular Cancer, vol. 16, no. 145, 2017.
[11]
A. Li, T. Zhang, M. Zheng, Y. Liu and Z. Chen, "Exosomal proteins as potential markers of tumor diagnosis," Journal of Hematology & Oncology, vol. 10, no. 175, 2017.
[12]
L.-h. Sun, D. Tian, Z.-c. Yang and J.-l. Li, "Exosomal miR-21 promotes proliferation, invasion and therapy resistance of colon adenocarcinoma cells through its target PDCD4," Scientific Reports, vol. 10, no. 8271, 2020.
[13]
S. Yokoyama, A. Takeuchi, S. Yamaguchi, Y. Mitani, T. Watanabe, K. Matsuda, T. Hotta, J. E. Shively and H. Yamaue, "Clinical implications of carcinoembryonic antigen distribution in serum exosomal fraction—Measurement by ELISA," Plos One, vol. 12, no. 8, 2017.
67
[14]
C. S. Kosack, A.-L. Page and P. R. Klatser, "World Health Organization," 26 June 2017. [Online]. Available: https://www.who.int/bulletin/volumes/95/9/16-187468/en/. [Accessed 15 March 2021].
[15]
H. Grosjean, "Nucleic Acids Are Not Boring Long Polymers of Only Four Types of Nucleotides: A Guided Tour," in DNA and RNA Modification Enzymes: Structure, Mechanism, Function and Evolution, Landes Bioscience, 2009.
[16]
J. D. Watson and F. H. Crick, "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid," Nature, vol. 171, no. 4356, pp. 737-738, 1953.
[17]
H. Lodish, A. Berk, S. L. Zipursky, P. Matsudaira, D. Baltimore and J. Darnell, "Structure of Nucleic Acids," in Molecular Cell Biology, 4th ed., New York, W. H. Freeman, 2000.
[18]
M. Mitra, "Elements of RNA, its Techniques and Applications," American Journal of Current Microbiology, vol. 7, no. 1, pp. 34-39, 2019.
[19]
M. McCarty and O. T. Avery, "Studies on the chemical nature of the substance inducing transformation of pneumococcal types; effect of desoxyribonuclease on the biological activity of the transforming substance," Journal of Experimental Medicine, vol. 83, pp. 89-96, 1946.
[20]
A. G. Leslie, S. Arnott, R. Chandrasekaran and R. L. Ratliff, "Polymorphism of DNA double helices," J Mol Biol, vol. 143, no. 1, pp. 49-72, 1980.
[21]
R. Hardison, "B-Form, A-Form, and Z-Form of DNA.," 15 August 2020. [Online]. Available: https://bio.libretexts.org/@go/page/307 . [Accessed 15 March 2021].
[22]
W. Fuller, F. Hutchinson, M. Spencer and M. Wilkins, "Molecular and crystal structures of double-helical RNA: I. An X-ray diffraction study of fragmented yeast RNA and a preliminary double-helical RNA model," Journal of Molecular Biology, vol. 27, no. 3, pp. 507-512, 1967.
[23]
R. C. Lee, R. L. Feinbaum and V. J. 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.
[24]
M. Ha and V. Kim, "Regulation of microRNA biogenesis," Nat Rev Mol Cell Biol, vol. 15, p. 509–524, 2014.
[25]
D. P. Bartel, "MicroRNAs: genomics, biogenesis, mechanism, and function," Cell, vol. 116, no. 2, pp. 281-297, 2004.
[26]
J. S. Mattick and I. V. Makunin, "Non-coding RNA," Human Molecular Genetics, vol. 15, no. 1, pp. R17-R29, 2006.
[27]
L.-A. MacFarlane and P. R. Murphy, "MicroRNA: biogenesis, function and role in cancer," Current Genomics, vol. 11, no. 7, pp. 537-561, 2010.
[28]
C. Chou, N. Chang, S. Shrestha, S. Hsu, Y. Lin, W. Lee, C. Yang, H. Hong, T. Wei, S. Tu, T. Tsai, S. Ho, T. Jian, H. Wu, P. Chen, N. Lin, H. Huang, T. Yang, C. Pai, C. Tai, W. Chen, C. Huang, C. Liu, S. Weng, K. Liao, W. Hsu and H. Huang, "miRTarBase 2020: updates to the experimentally
68
validated microRNA–target interaction database," Nucleic Acids Res, vol. 44, no. D1, pp. D239-D247, 2016.
[29]
Y. Peng and C. M. Croce, "The role of MicroRNAs in human cancer," Signal Transduction and Targeted Therapy, vol. 1, no. 15004, 2016.
[30]
G. Shafi, N. Aliya and A. Munshi, "MicroRNA signatures in neurological disorders," Can J Neurol Sci, vol. 37, no. 2, pp. 177-185, 2010.
[31]
R. R. Wong, N. Abd-Aziz, S. Affendi and C. Poh, "Role of microRNAs in antiviral responses to dengue infection," J Biomed Sci, vol. 27, no. 1, 2020.
[32]
A. Roberts, A. Lewis and C. Jopling, "The role of microRNAs in viral infection," Prog Mol Biol Transl Sci, vol. 102, pp. 101-139, 2011.
[33]
M. Cui, H. Wang, X. Yao, D. Zhang, Y. Xie, R. Cui and X. Zhang, "Circulating MicroRNAs in Cancer: Potential and Challenge," Front Genet, vol. 10, no. 626, 2019.
[34]
M. Wang, F. Yu, H. Ding, Y. Wang, P. Li and K. Wang, "Emerging Function and Clinical Values of Exosomal MicroRNAs in Cancer," Mol Ther Nucleic Acids, vol. 16, pp. 791-804, 2019.
[35]
S. Tan, L. Xia, P. Yi, Y. Han, L. Tang, Q. Pan, Y. Tian, S. Rao, L. Oyang, J. Liang, J. Lin, M. Su, Y. Shi, D. Cao, Y. Zhou and Q. Liao, "Exosomal miRNAs in tumor microenvironment," J Exp Clin Cancer Res, vol. 39, no. 1, 2020.
[36]
M. Tsukamoto, H. Iinuma, T. Yagi, K. Matsuda and Y. Hashiguchi, "Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer," Oncology, vol. 92, no. 6, pp. 360-370, 2017.
[37]
Q. Liu, Z. Yu, S. Yuan, W. Xie, C. Li, Z. Hu, Y. Xiang, N. Wu, L. Wu, L. Bai and Y. Li, "Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer," Oncotarget, vol. 8, no. 8, p. 13048–13058, 2017.
[38]
X. Li, Z. Ren, J. Tang and Q. Yu, "Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer," Cell Physiol Biochem, vol. 44, no. 5, pp. 1741-1748, 2017.
[39]
M. Lagos-Quintana, R. Rauhut, W. Lendeckel and T. Tuschl, "Identification of novel genes coding for small expressed RNAs," Science, vol. 294, no. 5593, pp. 853-858, 2001.
[40]
V. Jazbutyte and T. Thum, "MicroRNA-21: From cancer to cardiovascular disease," Curr Drug Targets, vol. 11, pp. 926-935, 2010.
[41]
C. You, L. Jin, Q. Xu, B. Shen, X. Jiao and X. Huang, "Expression of miR-21 and miR-138 in colon cancer and its effect on cell proliferation and prognosis," Oncology letters, vol. 17, no. 2, p. 2271–2277, 2019.
[42]
T. Wang, Y. Feng, H. Sun, L. Zhang, L. Hao, C. Shi, J. Wang, R. Li, X. Ran, Y. Su and Z. Zou, "miR-21 regulates skin wound healing by targeting multiple aspects of the healing process," Am
69
J Pathol, vol. 181, no. 6, pp. 1911-1920, 2012.
[43]
X. Yang, J. Wang, S. Guo, K. Fan, J. Li, Y. Wang, Y. Teng and X. Yang, "miR-21 Promotes Keratinocyte Migration and Re-epithelialization During Wound Healing," Int J Biol Sci, vol. 7, no. 5, pp. 685-690, 2011.
[44]
R. Saiki, S. Scharf, F. Faloona, K. Mullis and G. Horn, "Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia," Science, vol. 230, no. 4732, pp. 1350-1354, 1985.
[45]
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.
[46]
R. K. Saiki, D. H. Gelfand, S. Stoffel, S. J. Scharf, R. Higuchi, G. T. Horn, K. B. Mullis and H. A. Erlich, "Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase," Science, vol. 239, p. 487–491, 1988.
[47]
"Polymerase Chain Reaction (PCR)," U.S. National Library of Medicine, 09 November 2017. [Online]. Available: https://www.ncbi.nlm.nih.gov/probe/docs/techpcr/. [Accessed 15 March 2021].
[48]
"Real-Time qRT-PCR," U.S. National Library of Medicine, 09 November 2017. [Online]. Available: https://www.ncbi.nlm.nih.gov/probe/docs/techqpcr/. [Accessed 15 March 2021].
[49]
J. Kuang, X. Yan, A. Genders, C. Granata and D. Bishop, "An overview of technical considerations when using quantitative real-time PCR analysis of gene expression in human exercise research," Plos One, vol. 13, no. 5, 2018.
[50]
M. L. Wong and J. F. Medrano, "Real-time PCR for mRNA quantitation," Biotechniques, vol. 39, no. 1, pp. 75-85, 2005.
[51]
M. J. Wacker and M. P. Godard, "Analysis of one-step and two-step real-time RT-PCR using SuperScript III," J Biomol Tech, vol. 16, no. 3, pp. 266-271, 2005.
[52]
M. J. Holden and L. Wang, "Quantitative Real-Time PCR: Fluorescent Probe Options and Issues," in Standardization and Quality Assurance in Fluorescence Measurements II, Berlin, Heidelberg, Springer, 2008, pp. 489-508.
[53]
T. D. Schmittgen, B. A. Zakrajsek, A. G. Mills, V. Gorn, M. J. Singer and M. W. Reed, "Quantitative reverse transcription-polymerase chain reaction to study mRNA decay: comparison of endpoint and real-time methods," Anal. Biochem., vol. 285, no. 2, p. 194–204, 2000.
[54]
M. S. Rajeevan, S. D. Vernon, N. Taysavang and E. R. Unger, "Validation of array-based gene expression profiles by real-time (kinetic) RT-PCR," J Mol Diagn, vol. 3, no. 1, pp. 26-31, 2001.
[55]
S. A. Deepak, K. R. Kottapalli, R. Rakwal, G. Oros, K. S. Rangappa, H. Iwahashi, Y. Masuo and G. K. Agrawal, "Real-Time PCR: Revolutionizing Detection and Expression Analysis of Genes," Curr Genomics, vol. 8, no. 4, p. 234–251, 2007.
70
[56]
D.-K. Yang, C.-H. Kweon, B.-H. Kim, S.-I. Lim, S.-H. Kim, J.-H. Kwon and H.-R. Han, "TaqMan reverse transcription polymerase chain reaction for the detection of Japanese encephalitis virus," Journal of Veterinary Science, vol. 5, no. 4, p. 345–351, 2004.
[57]
C. J. Smith and A. M. Osborn, "Advantages and limitations of quantitative PCR (Q-PCR)-based approaches in microbial ecology," FEMS Microbiology Ecology, vol. 67, pp. 6-20, 2009.
[58]
M. Labrenz, I. Brettar, R. Christen, S. Flavier, J. Bötel and M. G. Höfle, "Development and application of a real-time PCR approach for quantification of uncultured bacteria in the central Baltic Sea," Appl Environ Microbiol, vol. 70, no. 8, pp. 4971-4979, 2004.
[59]
P. Chhalliyil, H. Ilves, S. A. Kazakov, S. J. Howard, B. H. Johnston and J. Fagan, "A Real-Time Quantitative PCR Method Specific for Detection and Quantification of the First Commercialized Genome-Edited Plant," Foods, vol. 9, no. 9, 2020.
[60]
M. A. A. Valones, R. L. Guimarães, L. A. C. Brandão, P. R. E. de Souza, A. d. A. T. Carvalho and S. Crovela, "Principles and applications of polymerase chain reaction in medical diagnostic fields: a review," Brazilian Journal of Microbiology, vol. 40, pp. 1-11, 2009.
[61]
H. Hartley, "Origin of the word ′protein′," Nature, vol. 168, 1951.
[62]
F. Sanger, "The terminal peptides of insulin," The Biochemical Journal, vol. 45, no. 5, pp. 563-574, 1949.
[63]
H. Muirhead and M. Perutz, "Structure of hemoglobin. A three-dimensional fourier synthesis of reduced human hemoglobin at 5.5 Å resolution," Nature, vol. 199, no. 4894, pp. 633-638, 1963.
[64]
J. C. Kendrew, G. Bodo, H. M. Dintzis, R. G. Parrish, H. Wyckoff and D. C. Phillips, "A three-dimensional model of the myoglobin molecule obtained by x-ray analysis," Nature, vol. 181, no. 4610, pp. 662-666, 1958.
[65]
"A Structural View of Biology," RCSB Protein Data Bank, 18 April 2015. [Online]. Available: https://web.archive.org/web/20150418160606/http://www.rcsb.org/pdb/home/home.do. [Accessed 19 January 2021].
[66]
D. L. Nelson and M. M. Cox, Lehninger′s Principles of Biochemistry, 4th ed., New York: New York : W.H. Freeman, 2005, pp. 622-629.
[67]
F. Sanger, "The Arrangement of Amino Acids in Proteins," in Advances in Protein Chemistry, vol. 7, Elsevier, 1952, pp. 1-67.
[68]
L. Pauling, R. B. Corey and H. R. Branson, "The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain," Proc Natl Acad Sci USA, vol. 37, no. 4, pp. 205-211, 1951.
[69]
A. D. McNaught and A. Wilkinson, Eds., Compendium of Chemical Terminology (the Gold Book), 2nd ed., International Union of Pure and Applied Chemistry, 1997.
[70]
C. Branden and J. Tooze, Introduction to Protein Structure, New York: Garland, 1990.
71
[71]
J. M. Berg, J. L. Tymoczko and L. Stryer, "Quaternary Structure: Polypeptide Chains Can Assemble Into Multisubunit Structures," in Biochemistry, 5th ed., New York, W. H. Freeman, 2002.
[72]
N. Rifai, M. Gillette and S. Carrs, "Protein biomarker discovery and validation: the long and uncertain path to clinical utility," Nat Biotechnol, vol. 24, pp. 971-983, 2006.
[73]
A. K. Chan, D. C. Lockhart, W. von Bernstorff, R. A. Spanjaard, H. G. Joo, T. J. Eberlein and P. S. Goedegebuure, "Soluble MUC1 secreted by human epithelial cancer cells mediates immune suppression by blocking T-cell activation," International Journal of Cancer, vol. 82, pp. 721-772, 1999.
[74]
C. Kirmiz, B. Li, H. J. An, B. H. Clowers, H. K. Chew, K. S. Lam, A. Ferrige, R. Alecio, A. D. Borowsky, S. Sulaimon, C. B. Lebrilla and S. Miyamoto, "A serum glycomics approach to breast cancer biomarkers," Mol Cell Proteomics, pp. 43-45, 2007.
[75]
R. C. Bast, F. J. Xu, Y. H. Yu, S. Barnhill, Z. Zhang and G. B. Mills, "CA 125: the past and the future," Int J Biol Markers, vol. 13, pp. 179-187, 1998.
[76]
G. M. Clark, "Interpreting and integrating risk factors for patients with primary breast cancer," J Natl Cancer Inst Monogr, vol. 17, no. 2, 2001.
[77]
Z. Yu, X. Chen, L. Cui, H. Si, H. Lu and S. Liu, "Prediction of lung cancer based on serum biomarkers by gene expression programming methods," Asian Pac. J. Cancer Prev, vol. 15, p. 9367–9373, 2014.
[78]
B. Sandfeld-Paulsen, N. Aggerholm-Pedersen, R. Bæk, K. R. Jakobsen, P. Meldgaard, B. H. Folkersen, T. R. Rasmussen, K. Varming, M. M. Jørgensen and B. S. Sorensen, "Exosomal proteins as prognostic biomarkers in non-small cell lung cancer," Molecular oncology, vol. 10, no. 10, pp. 1595-1602, 2016.
[79]
S. A. Melo, L. B. Luecke, C. Kahlert, A. F. Fernandez, S. T. Gammon, J. Kaye, V. S. LeBleu, E. A. Mittendorf, J. Weitz, N. Rahbari, C. Reissfelder, C. Pilarsky, M. F. Fraga, D. Piwnica-Worms and R. Kalluri, "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer," Nature, vol. 523, no. 7559, pp. 177-182, 2015.
[80]
C. Hall, L. Clarke, A. Pal, P. Buchwald, T. Eglinton, C. Wakeman and F. Frizelle, "A Review of the Role of Carcinoembryonic Antigen in Clinical Practice," Ann Coloproctol, vol. 35, no. 6, pp. 294-305, 2019.
[81]
M. J. Goldstein and E. P. Mitchell, "Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer," Cancer Invest., vol. 23, no. 4, pp. 338-351, 2005.
[82]
K. Björkman, S. Jalkanen, M. Salmi, H. Mustonen, T. Kaprio, H. Kekki, K. Pettersson, C. Böckelman and C. Haglund, "A prognostic model for colorectal cancer based on CEA and a 48-multiplex serum biomarker panel," Sci Rep, vol. 11, 2021.
[83]
L.-H. Gam, "Breast cancer and protein biomarkers," World J Exp Med, vol. 2, no. 5, pp. 86-91,
72
2012.
[84]
M. Grunnet and J. B. Sorensen, "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer," Lung Cancer, vol. 76, no. 2, pp. 138-143, 2012.
[85]
S. S. Sørensen and B. J. Mosgaard, "Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis," Dan Med Bull, vol. 58, no. 11, 2011.
[86]
M. A. Gerber and S. N. Thung, "Carcinoembryonic antigen in normal and diseased liver tissue," Am J Pathol, vol. 92, no. 3, pp. 671-679, 1978.
[87]
S. K. Khoo and I. R. Mackay, "Carcinoembryonic antigen in serum in diseases of the liver and pancreas," J Clin Pathol, vol. 26, no. 7, pp. 470-475, 1973.
[88]
T. H. Weber and Y. Kerttula, "Carcinoembryonic antigen (CEA) in blood in cases of pneumonia," Scand J Infect Dis, vol. 18, no. 6, pp. 547-550, 1986.
[89]
I. Fukuda, M. Yamakado and H. Kiyose, "Influence of smoking on serum carcinoembryonic antigen levels in subjects who underwent multiphasic health testing and services," J Med Syst, vol. 22, no. 2, pp. 89-93, 1998.
[90]
J. Li, Y. Chen, X. Guo, L. Zhou, Z. Jia, Z. Peng, Y. Tang, W. Liu, B. Zhu, L. Wang and C. Ren, "GPC1 exosome and its regulatory miRNAs are specific markers for the detection and target therapy of colorectal cancer," J Cell Mol Med, vol. 21, no. 5, pp. 838-847, 2017.
[91]
R. S. Yalow and S. A. Berson, "Assay of plasma insulin in human subjects by immunological methods," Nature, vol. 184, pp. 1648-1649, 1959.
[92]
J. M. Walker and R. Rapley, Molecular Biomethods Handbook, Humana Press, 2008, pp. 375-376.
[93]
S. D. Gan and K. R. Patel, "Enzyme immunoassay and enzyme-linked immunosorbent assay," J Invest Dermatol, vol. 133, no. 9, 2013.
[94]
S. X. Leng, J. E. McElhaney, J. D. Walston, D. Xie, N. S. Fedarko and G. A. Kuchel, "ELISA and multiplex technologies for cytokine measurement in inflammation and aging research," J Gerontol A Biol Sci Med Sci, vol. 63, no. 8, pp. 879-884, 2008.
[95]
N. Aziz, P. Nishanian, R. Mitsuyasu, R. Detels and J. L. Fahey, "Variables that affect assays for plasma cytokines and soluble activation markers," Clinical and diagnostic laboratory immunology, vol. 6, no. 1, pp. 89-95, 1999.
[96]
C. M. Cheng, A. W. Martinez, J. Gong, C. R. Mace, S. T. Phillips, E. Carrilho, K. A. Mirica and G. M. Whitesides, "Paper-based ELISA," Angew Chem Int Ed Engl, vol. 49, no. 28, pp. 4771-4774, 2010.
[97]
J. C. Contreras-Naranjo, H.-J. Wu and . V. M. Ugaz, "Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine," Lab Chip, vol. 17, no. 21, pp. 3558-3577, 2017.
73
[98]
A. V. Vlassov, S. Magdaleno and R. Sette, "Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials," Biochim Biophys Acta, vol. 1820, no. 7, pp. 940-948, 2012.
[99]
I. V. Miller and T. G. P. Grunewald, "Tumour‐derived exosomes: Tiny envelopes for big stories," Biol Cell, vol. 107, no. 9, pp. 287-305, 2015.
[100]
J. C. Akers, D. Gonda, R. Kim, B. S. Carter and C. C. Chen, "Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies," J Neurooncol, vol. 113, no. 1, pp. 1-11, 2013.
[101]
M. Mathieu, L. Martin-Jaular, G. Lavieu and C. Théry, "Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication," Nature Cell Biology, vol. 21, pp. 9-17, 2019.
[102]
S. I. Buschow, E. N. Nolte-′t Hoen, G. van Niel, M. S. Pols, T. ten Broeke, M. Lauwen, F. Ossendorp, C. J. Melief, G. Raposo, R. Wubbolts, M. H. Wauben and W. Stoorvogel, "MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways," Traffic, vol. 10, no. 10, pp. 1528-1542, 2009.
[103]
G. Turturici, R. Tinnirello, G. Sconzo and F. Geraci, "Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages," Am J Physiol Cell Physiol, vol. 306, no. 7, pp. C621-C633, 2014.
[104]
K. M. McAndrews and R. Kalluri, "Mechanisms associated with biogenesis of exosomes in cancer," Mol Cancer, vol. 18, no. 1, 2019.
[105]
H. Shao, H. Im, C. M. Castro, X. Breakefield, R. Weissleder and H. Lee, "New Technologies for Analysis of Extracellular Vesicles," Chem Rev, vol. 118, no. 4, pp. 1917-1950, 2018.
[106]
B. S. Batista, W. S. Eng, K. T. Pilobello, K. D. Hendricks-Munoz and L. K. Mahal, "Identification of a conserved glycan signature for microvesicles," J. Proteome Res, vol. 10, p. 4624–4633, 2011.
[107]
J. Kowal, J. Vigneron, P. Benaroch, N. Manel, L. F. Moita, C. Théry and G. Raposo, "Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles," J.Cell Sci, vol. 126, p. 5553–5565, 2013.
[108]
N. P. Hessvik and A. Llorente, "Current knowledge on exosome biogenesis and release," Cell Mol. Life Sci, vol. 75, p. 193–208, 2018.
[109]
W. M. Henne, H. Stenmark and S. D. Emr, "Molecular mechanisms of the membrane sculpting ESCRT pathway," Cold Spring Harb Perspect Biol, vol. 5, no. 9, 2013.
[110]
S. Atay, C. Gercel-Taylor, M. Kesimer and D. D. Taylor, "Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells," Exp Cell Res, vol. 317, no. 8, pp. 1192-1202, 2011.
[111]
T. Skotland, K. Sagini, K. Sandvig and A. Llorente, "An emerging focus on lipids in extracellular
74
vesicles," Adv Drug Deliv Rev, vol. 159, pp. 308-321, 2020.
[112]
M. Frydrychowicz, A. Kolecka-Bednarczyk, M. Madejczyk, S. Yasar and G. Dworacki, "Exosomes - structure, biogenesis and biological role in non-small-cell lung cancer," Scand J Immunol, vol. 81, no. 1, pp. 2-10, 2015.
[113]
J. Conde-Vancells, E. Rodriguez-Suarez, N. Embade, D. Gil, R. Matthiesen, M. Valle, F. Elortza, S. C. Lu, J. M. Mato and J. M. Falcon-Perez, "Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes," J. Proteome Res, vol. 7, p. 5157–5166, 2008.
[114]
C. Subra, D. Grand, K. Laulagnier, A. Stella, G. Lambeau, M. Paillasse, P. De Medina, B. Monsarrat, B. Perret, S. Silvente-Poirot, M. Poirot and M. Record, "Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins," J. Lipid Res, vol. 51, p. 2105–2120, 2010.
[115]
L. Alvarez-Erviti, Y. Seow, H. Yin, C. Betts, S. Lakhal and M. J. Wood, "Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes," Nat. Biotechnol, vol. 29, pp. 341-345, 2011.
[116]
M. Colombo, G. Raposo and C. Théry, "Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles," Annu Rev Cell Dev Biol, vol. 30, pp. 255-289, 2014.
[117]
A. Y. Wu, K. Ueda and C. P. Lai, "Proteomic Analysis of Extracellular Vesicles for Cancer Diagnostics," Proteomics, vol. 19, no. 1-2, 2019.
[118]
C. Théry, L. Zitvogel and S. Amigorena, "Exosomes: composition, biogenesis and function," Nat Rev Immunol 2, pp. 569-579, 2002.
[119]
G. Raposo and W. Stoorvogel, "Extracellular vesicles: exosomes, microvesicles, and friends," J Cell Biol, vol. 200, no. 4, pp. 373-383, 2013.
[120]
G. Bellin, C. Gardin, L. Ferroni, J. C. Chachques, M. Rogante, D. Mitrečić, R. Ferrari and B. Zavan, "Exosome in Cardiovascular Diseases: A Complex World Full of Hope," Cells, vol. 8, no. 2, 2019.
[121]
S. Rastogi, V. Sharma, P. S. Bharti, K. Rani, G. P. Modi, F. Nikolajeff and S. Kumar, "The Evolving Landscape of Exosomes in Neurodegenerative Diseases: Exosomes Characteristics and a Promising Role in Early Diagnosis," Int J Mol Sci, vol. 22, no. 1, 2021.
[122]
W. Liu, X. Bai, A. Zhang, J. Huang, S. Xu and J. Zhang, "Role of Exosomes in Central Nervous System Diseases," Frontiers in Molecular Neuroscience, vol. 12, 2019.
[123]
W. Chang and J. Wang, "Exosomes and Their Noncoding RNA Cargo Are Emerging as New Modulators for Diabetes Mellitus," Cells, vol. 8, no. 8, 2019.
[124]
C. Castaño, A. Novials and M. Párrizas, "Exosomes and diabetes," Diabetes Metab Res Rev, vol. 35, no. 3, 2019.
[125]
C. Liu, J. Zhao, F. Tian, L. Cai, W. Zhang, Q. Feng, J. Chang, F. Wan, Y. Yang, B. Dai, Y. Cong,
75
B. Ding, J. Sun and W. Tan, "Low-cost thermophoretic profiling of extracellular-vesicle surface proteins for the early detection and classification of cancers," Nat Biomed Eng, vol. 3, pp. 183-193, 2019.
[126]
P. Sharma, S. Ludwig, L. Muller, C. S. Hong, J. M. Kirkwood, S. Ferrone and T. L. Whiteside, "Immunoaffinity-based isolation of melanoma cell-derived exosomes from plasma of patients with melanoma," J Extracell Vesicles, vol. 7, no. 1, 2018.
[127]
V. Domenyuk, Z. Zhong, A. Stark, N. Xiao, H. A. O′Neill, X. Wei, J. Wang, T. T. Tinder, S. Tonapi, J. Duncan, T. Hornung, A. Hunter, M. R. Miglarese, J. Schorr, D. D. Halbert, J. Quackenbush and G. Post, "Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach," Sci Rep, vol. 7, 2017.
[128]
T. Huang and C. X. Deng, "Current Progresses of Exosomes as Cancer Diagnostic and Prognostic Biomarkers," Int J Biol Sci, vol. 15, no. 1, pp. 1-11, 2019.
[129]
S. Gurunathan, M. H. Kang, M. Jeyaraj, M. Qasim and J. H. Kim, "Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes," Cells, vol. 8, no. 4, 2019.
[130]
M. Lafitte, C. Lecointre and S. Roche, "Roles of exosomes in metastatic colorectal cancer," Am J Physiol Cell Physiol, vol. 317, p. C869–C880, 2019.
[131]
L. Bracci, F. Lozupone and I. Parolini, "The role of exosomes in colorectal cancer disease progression and response to therapy," Cytokine & Growth Factor Reviews, vol. 51, pp. 84-91, 2020.
[132]
L. Ruiz-López, I. Blancas, J. M. Garrido, N. Mut-Salud, M. Moya-Jódar, A. Osuna and F. Rodríguez-Serrano, "The role of exosomes on colorectal cancer: A review," J Gastroenterol Hepatol, vol. 33, no. 4, pp. 792-799, 2018.
[133]
P. Goodarzi, B. Larijani, S. Alavi-Moghadam, A. Tayanloo-Beik, F. Mohamadi-Jahani, N. Ranjbaran, M. Payab, K. Falahzadeh, M. Mousavi and B. Arjmand, "Mesenchymal Stem Cells-Derived Exosomes for Wound Regeneration," Adv Exp Med Biol, vol. 1119, pp. 119-131, 2018.
[134]
B. F. Hettich, M. B.-Y. Greenwald, S. Werner and J.-C. Leroux, "Exosomes for Wound Healing: Purification Optimization and Identification of Bioactive Components," Adv. Sci, vol. 7, 2020.
[135]
J. Xu, S. Bai, Y. Cao, L. Liu, Y. Fang, J. Du, L. Luo, M. Chen, B. Shen and Q. Zhang, "miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice," Diabetes Metab Syndr Obes, vol. 13, pp. 1259-1270, 2020.
[136]
S. Gao, T. Chen, Y. Hao, F. Zhang, X. Tang, D. Wang, Z. Wei and J. Qi, "Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression," Stem Cell Res Ther, vol. 11, no. 56, 2020.
[137]
A. Cheruvanky, H. Zhou, T. Pisitkun, J. B. Kopp, M. A. Knepper, P. S. Yuen and R. A. Star,
76
"Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator," Am J Physiol Renal Physiol, vol. 292, no. 5, pp. F1657-F1661, 2007.
[138]
C. Théry, S. Amigorena, G. Raposo and A. Clayton, "Isolation and characterization of exosomes from cell culture supernatants and biological fluids," Curr Protoc Cell Biol, 2006.
[139]
J. V. Deun, P. Mestdagh, R. Sormunen, V. Cocquyt, K. Vermaelen, J. Vandesompele, M. Bracke, O. D. Wever and A. Hendrix, "The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling," J. Extracell. Vesicles, vol. 3, 2014.
[140]
E. I. B. L. T. B. A. B. L. Kenneth W Witwer, J. Lötvall, E. N. N.-′. Hoen, M. G. Piper, S. Sivaraman, J. Skog, C. Théry, M. H. Wauben and F. Hochberg, "Standardization of sample collection, isolation and analysis methods in extracellular vesicle research," J. Extracell. Vesicles, vol. 2, 2013.
[141]
P. Li, M. Kaslan, S. H. Lee, J. Yao and Z. Gao, "Progress in exosome isolation techniques," Theranostics, vol. 7, no. 3, pp. 789-804, 2017.
[142]
P. E. Chugh, S.-H. Sin, S. Ozgur, D. H. Henry, P. Menezes, J. Griffith, J. J. Eron, B. Damania and D. P. Dittmer, "Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies," Plos Pathogens, vol. 9, no. 7, 2013.
[143]
A. Clayton, J. Court, H. Navabi, M. Adams, M. D. Mason, J. A. Hobot, G. R. Newman and B. Jasani, "Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry," J Immunol Methods, vol. 247, no. 1-2, pp. 136-174, 2001.
[144]
E. Zeringer, T. Barta, M. Li and A. V. Vlassov, "Strategies for isolation of exosomes," Cold Spring Harb Protoc, vol. 4, pp. 319-323, 2015.
[145]
L. Dong, R. C. Zieren, K. Horie, C.-J. Kim, E. Mallick, Y. Jing, M. Feng, M. D. Kuczler, J. Green, S. R. Amend, K. W. Witwer, T. M. d. Reijke, Y.-K. Cho, K. J. Pienta and W. Xue, "Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium," J Extracell Vesicles, vol. 10, no. 2, 2020.
[146]
R. A. Dragovic, C. Gardiner, A. S. Brooks, D. S. Tannetta, D. J. P. Ferguson, P. Hole, B. Carr, C. W. G. Redman, A. L. Harris, P. J. Dobson, P. Harrison and I. L. Sargent, "Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis," Nanomedicine: Nanotechnology, Biology and Medicine, vol. 7, no. 6, pp. 780-788, 2011.
[147]
V. Filipe, A. Hawe and W. Jiskoot, "Critical Evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the Measurement of Nanoparticles and Protein Aggregates," Pharmaceutical Research, vol. 27, no. 5, pp. 796-810, 2010.
[148]
R. Szatanek, M. Baj-Krzyworzeka, J. Zimoch, M. Lekka, M. Siedlar and J. Baran, "The Methods of Choice for Extracellular Vesicles (EVs) Characterization," Int J Mol Sci, vol. 18, no. 6, 2017.
[149]
D. McMullan, "Scanning electron microscopy 1928–1965," Scanning, vol. 17, pp. 175-185, 1995.
77
[150]
J. M. Hyosun Choi, "Structural Analysis of Exosomes Using Different Types of Electron Microscopy," Applied Microspcopy, vol. 47, no. 3, pp. 171-175, 2017.
[151]
D. Enderle, A. Spiel, C. M. Coticchia, E. Berghoff, R. Mueller, M. Schlumpberger, M. Sprenger-Haussels, J. M. Shaffer, E. Lader, J. Skog and M. Noerholm, "Characterization of RNA from exosomes and other extracellular vesicles isolated by a novel spin column-based method," Plos One, vol. 10, no. 8, 2015.
[152]
C. Théry, M. Ostrowski and E. Segura, "Membrane vesicles as conveyors of immune responses," Nat. Rev. Immunol., vol. 9, no. 8, pp. 581-593, 2009.
[153]
Y. Wu, W. Deng and D. J. Klinke, "xosomes: improved methods to characterize their morphology, RNA content, and surface protein biomarkers," Analyst, vol. 140, no. 19, pp. 6631-6642, 2015.
[154]
B. György, T. G. Szabó, M. Pásztói, Z. Pál, P. Misják, B. Aradi, V. László, E. Pállinger, E. Pap, A. Kittel, G. Nagy, A. Falus and E. I. Buzás, "Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles," Cell Mol Life Sci, vol. 16, pp. 2667-2688, 2011.
[155]
H. Shao, J. Chung, L. Balaj, A. Charest, D. D. Bigner, B. S. Carter, F. H. Hochberg, X. O. Breakefield, R. Weissleder and H. Lee, "Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy," Nat Med, vol. 18, no. 12, pp. 1835-1840, 2012.
[156]
L. C. Fowke, "Transmission and Scanning Electron Microscopy for Plant Protoplasts, Cultured Cells and Tissues," in Plant Cell, Tissue and Organ Culture, Berlin, Heidelberg, Springer, 1995, pp. 229-238.
[157]
M. J. Karnovsky, "A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy," Journal of Cell Biology, vol. 27, no. 2, pp. 1A-149A, 1965.
[158]
K. A. Kondratov, T. A. Petrova, V. Y. Mikhailovskii, A. N. Ivanova, A. A. Kostareva and A. V. Fedorov, "A study of extracellular vesicles isolated from blood plasma conducted by low-voltage scanning Electron microscopy," Cell and Tissue Biology, vol. 11, pp. 181-190, 2017.
[159]
B. J. Berne and R. Pecora, Dynamic Light Scattering: With Applications to Chemistry, Biology, and Physics, Mineola: Courier Dover, 2000.
[160]
B. F. Andreasi, G. Arcovito, M. De Spirito, A. Mordente and G. Martorana, "Self-similarity properties of alphacrystallin supramolecular aggregates," Biophys J, vol. 69, no. 6, pp. 2720-2727, 1995.
[161]
T. Parasassi, M. D. Spirito, G. Mei, R. Brunelli, G. Greco, L. Lenzi, G. Maulucci, E. Nicolai, M. Papi, G. Arcovito, S. C. E. Tosatto and F. Ursini, "Low density lipoprotein misfolding and amyloidogenesis," FASEB J, vol. 22, no. 7, pp. 2350-2356, 2008.
[162]
G. Maulucci, M. D. Spirito, G. Arcovito, F. Boffi, A. C. Castellano and G. Briganti, "Particle size distribution in DMPC vesicles solutions undergoing different sonication times," Biophys J, vol. 88, no. 5, pp. 3545-3550, 2005.
78
[163]
V. Filipe, A. Hawe and W. Jiskoot, "Critical evaluation of Nanoparticle tracking analysis (NTA) by nanosight for the measurement of nanoparticles and protein aggregates," Pharmaceut Res, vol. 27, no. 5, p. 796–810, 2010.
[164]
M. Papi, G. Arcovito, M. De Spirito, M. Vassalli and B. Tiribilli, "Fluid viscosity determination by means of uncalibrated atomic force microscopy cantilevers," Appl Phys Lett, vol. 88, no. 19, 2006.
[165]
M. Papi, G. Maulucci, G. Arcovito, P. Paoletti, M. Vassalli and M. De Spirito, "Detection of microviscosity by using uncalibrated atomic force microscopy cantilevers," Appl Phys Lett, vol. 93, no. 12, 2008.
[166]
F. Momen-Heravi, L. Balaj, S. Alian, J. Tigges, V. Toxavidis, M. Ericsson, R. J. Distel, A. R. Ivanov, J. Skog and W. P. Kuo, "Alternative methods for characterization of extracellular vesicles," Front Physiol, vol. 3, no. 354, 2012.
[167]
K. M. McKinnon, "Flow Cytometry: An Overview," Curr Protoc Immunol, vol. 120, pp. 5.1.1-5.1.11, 2018.
[168]
J. L. Zamora and H. C. Aguilar, "Flow virometry as a tool to study viruses," Methods, Vols. 134-135, p. 87–97, 2018.
[169]
J. Picot, C. L. Guerin, V. K. C. Le and C. M. Boulanger, "Flow cytometry: retrospective, fundamentals and recent instrumentation," Cytotechnology, vol. 64, no. 2, pp. 109-130, 2012.
[170]
A. W. Martinez, S. T. Phillips, G. M. Whitesides and E. Carrilho, "Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices," Anal. Chem., vol. 82, no. 1, pp. 3-10, 2010.
[171]
C. Chen, B.-R. Lin, H.-K. Wang, S.-T. Fan, M.-Y. Hsu and C.-M. Cheng, "Paper-based immunoaffinity devices for accessible isolation and characterization of extracellular vesicles," Microfluidics and Nanofluidics, vol. 16, p. 849–856, 2014.
[172]
C.-M. Cheng, A. Martinez, J. Gong, C. Mace, S. Phillips, E. Carrilho, K. Mirica and G. Whitesides, "Paper‐based ELISA," Clinical Analytics, vol. 48, no. 8, pp. 4771-4774, 2010.
[173]
C. Schrader, A. Schielke, L. Ellerbroek and R. Johne, "PCR inhibitors - occurrence, properties and removal," J Appl Microbiol, vol. 113, no. 5, pp. 1014-1026, 2012.
[174]
Y. H. Hsiao and C. Chen, "Paper-based for isolation of extracellular vesicles," Methods Mol. Biol., vol. 1660, pp. 43-54, 2017.
[175]
M.-Y. Hsu, C.-C. Chiu, J.-Y. Wang, C.-T. Huang, Y.-F. Huang, J.-C. Liou, C. Chen, H.-C. Chen and C.-M. Cheng, "Paper-based microfluidic platforms for understanding the role of exosomes in the pathogenesis of major blindness-threatening diseases," Nanomaterials (Basel), vol. 8, no. 5, 2018.
[176]
C.-h. Lai, Three-dimensional paper-based exosomal nucleic acid extraction device for detection
79
of exosomes and exosomal miRNAs released by cancer cell cultured in different microenvironment, Taiwan, 2020.
[177]
M. Lee, J.-J. Ban, W. Im and M. Kim, "Influence of storage condition on exosome recovery," Biotechnology and Bioprocess Engineering, vol. 21, pp. 299-304, 2016.
[178]
T. H. Nguyen and M. Elimelech, "Plasmid DNA Adsorption on Silica: Kinetics and Conformational Changes in Monovalent and Divalent Salts," Biomacromolecules, vol. 8, no. 1, pp. 24-32, 2007.
[179]
X. Li, J. Zhang and H. Gu, "Adsorption and desorption behaviors of DNA with magnetic mesoporous silica nanoparticles," Langmuir, vol. 27, no. 10, pp. 6099-6106, 2011.
[180]
K. A. Melzak, C. S. Sherwood, R. F. B. Turner and C. A. Haynes, "Driving Forces for DNA Adsorption to Silica in Perchlorate Solutions," Journal of Colloid and Interface Science, vol. 181, no. 2, pp. 635-644, 1996.
[181]
W. P. Hu, Y. C. Chen and W. Y. Chen, "Improve sample preparation process for miRNA isolation from the culture cells by using silica fiber membrane," Sci Rep, vol. 10, 2020.
[182]
E. J. Mulholland, N. Dunne and H. O. McCarthy, "MicroRNA as Therapeutic Targets for Chronic Wound Healing," Mol Ther Nucleic Acids, vol. 8, pp. 46-55, 2017.

指導教授

陳文逸(Wen-Yih Chen)

審核日期

2022-1-20

推文