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姓名	高銘澤(Ming-Tse Kao)  查詢紙本館藏	畢業系所	生物醫學工程研究所
論文名稱	靜磁場於癌細胞的生物效應 (The static magnetic field-mediated biological effects on cancer cells)
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 (2025-1-1以後開放)
摘要(中)	許多文獻指出，細胞生理會受到電場和磁場的電磁力影響。另外，細胞會受磁場不同的 物理參數而影響癌細胞的生長，如磁場頻率、梯度和強度等。靜磁場常被用於研究特定 磁場強度下的生物效應，然而靜磁場影響細胞的生理機制仍懸而待解且存在爭議。因此， 本研究要探討靜磁場如何調控癌細胞生理機制。在本研究中，細胞實驗結果顯示靜磁場 會調控癌細胞的生長速率及細胞週期。根據細胞生長速率的實驗結果指出，受磁組細胞 的數量增加一倍所需時間比對照組長。此外，細胞週期的實驗結果顯示在靜磁場(static magnetic field，SMF)下暴露 24 小時後，與對照組相比受磁組有更多累積於分裂期的 比例（% of G2/M，SMF：控制組= 5.50 : 0.25）。在免疫螢光染色及西方點墨法的結 果發現，受磁組的細胞素 B1 和 E1 表現量上升且受磁組 ATM-NBS1-CHK 信號傳導途徑也 因磁場而活化。在次世代定序的結果發現，靜磁場主要影響了細胞移動、免疫和發育相 關基因表現。在活細胞影像分析的結果中發現，暴露於靜磁場下的癌細胞有較多細胞累 積在有絲分裂期，細胞型態較收縮且周圍突起較短，細胞的移動頻率較高，這顯示靜磁 場可能影響細胞中微管絲與機動蛋白的組合，使受磁組的細胞附著能力較差。在斑馬魚 生物毒性測試結果中也發現，靜磁場影響了黑色素的移動和生成，但控制組和受磁組於 受孕後 96 小時之生長率，以及幼魚的外型並沒有明顯差異。本研究意旨在理解靜磁場 調控的癌細胞效應，並評估利用此生物效應的特點，作為輔助性療法的潛能
摘要(英)	Previous reports have demonstrated that exposure of electromagnetic force could affect cellular physiology. Others have shown that static magnetic field (SMF) has impacts on cell proliferation, particularly in cancer cells. Several physical parameters, such as magnetic frequency, gradient, and magnitude, were reported to affect the biological consequences. However, discrepancies exist between the SMF and cancer cell responses and the mechanisms underlying the SMF-mediated effects remained largely unexplored. The main purpose of this study is to investigate the mechanisms of SMF-mediated effects in cancer cells. Our results showed that the exposure of SMF affected cancer cell proliferation and cell cycle distribution. The doubling time for cells exposed to SMF was longer than that of control group. The results of flow cytometry showed that SMF induced higher percentage of cells accumulated in the mitotic phase compared to that of control group after 24-hour exposures (% of G2/M，SMF： control= 5.50 : 0.25). Results of immune-fluorescent staining and western blotting found higher expressions of cyclin B1 and cyclin E1 SMF-treated cells. Furthermore, the activation of ATM-NBS1-CHK signaling pathway was enhanced. The results of Next Generation Sequencing (NGS) analysis showed that the SMF primarily regulated genes involved in functions of motility, immune and embryonic development related pathways. From the time-lapse fluorescent microscope observations, more cancer cells exposed to SMF were accumulated in mitotic phase. The SMF-treated cells exhibited a shrinkage phenotype, faster motion frequency, and shorter peripheral protrusions. These observations indicate that the v SMF may affect polymerizations of microtubules and F-actin, as well as cell adhesion. To test the SMF-mediated effects on development, we used zebrafish as the model and evaluated the phenotypic alterations during development. We found that SMF exposures evidently affected the distribution of melanin. Some embryonic malformations were also observed under SMF treatment. However, there’s no difference on the survival ratio between SMF-treated group and control group. The presented study helps to understand more molecular mechanisms of the SMF-mediated effects on cancer cells. This may provide an opportunity to utilize the features of SMF to tailor therapeutic strategy.
關鍵字(中)	★ 靜磁場 ★ 鼻咽癌癌細胞	關鍵字(英)	★ static magnetic field ★ nasopharyngeal carcinoma
論文目次	目錄 中文摘要 ………………………………………………………………………… iii 英文摘要 ………………………………………………………………………… iv 誌謝 ………………………………………………………………………… vi 目錄 ………………………………………………………………………… vii 縮寫一覽表 ………………………………………………………………………… x Chapter 1 Introduction…………………………………………………………… 1 1-1 Electromagnetic fields in nature……………………………………… 1 1-1-1 Tumor treating fields………………………………………………… 2 1-1-2 Electromagnetic field in environments……………………………… 3 1-1-3 Static magnetic field and human health……………………………… 4 1-2 Static magnetic field at the cellular level……………………………… 6 1-2-1 Static magnetic field and cellproliferation………………………… 6 1-2-2 The potential mechanisms of static magnetic field…………………… 7 Chapter 2 Materials and Methods……………………………………………… 9 2-1 Static magnetic field generated by Neodymium magnet…………… 9 2-2 Cell culture and treatment method…………………………………… 9 2-3 Cell cycle analysis…………………………………………………… 9 2-4 Time-lapse live cell imaging………………………………………… 10 2-5 Wound healing assay………………………………………………… 10 2-6 Real-time proliferation assay………………………………………… 11 2-7 Western blotting……………………………………………………… 11 2-8 Immunofluorescent staining………………………………………… 12 2-9 RNA sequencing and quantification………………………………… 12 2-9-1 RNA extraction and RNA sequencing………………………………… 12 2-9-2 Transcriptome analysis……………………………………………… 13 2-9-3 Real time quantitative polymerase chain reaction…………………… 13 2-10 Zebrafish toxicity assay……………………………………………… 14 2-11 Statistics analysis…………………………………………………… 14 Chapter 3 Results………………………………………………………………… 16 3-1 Distribution of Neodymium magnet flux…………………………… 16 3-2 SMF decreases cancer cell proliferation……………………………… 16 3-3 SMF induces cell cycle redistribution and M phase arrest…………… 17 3-4 SMF induces DNA damage response………………………………… 17 3-5 The top scoring pathways dysregulated by SMF……………………… 18 3-6 Validation of selected genes involved in cell motility………………… 18 3-7 SMF affects cell mobility…………………………………………… 19 3-8 SMF reduces melanin production and migration during development of zebrafish…………………………………………………………… 20 Chapter 4 Discussion…………………………………………………………… 21 4-1 Possible mechanisms under SMF exposures………………………… 21 4-1-1 SMF induces DNA damage response in NPC cells…………………… 21 4-1-2 SMF exposure results in M phase arrest……………………………… 22 4-1-3 SMF regulates cell proliferation………………………………… 22 4-1-4 SMF decreases the cell motility……………………………………… 23 4-1-5 Zebrafish as a model for SMF toxicity tests……………………… 24 4-2 Future perspectives…………………………………………………… 24 Figures ………………………………………………………………………… 26 Figure 1 Characterization of SMF flux………………………………………… 26 Figure 2 The vectors of SMF distribution……………………………………… 27 Figure 3 SMF decreases cancer cell proliferation…………………………… 28 Figure 4 SMF induces cell cycle redistribution and M phase arrest…………… 29 Figure 5 SMF activates DNA damage response……………………………… 30 Figure 6 The top scoring pathways dysregulated by SMF…………………… 31 Figure 7 Expression patterns of genes under SMF exposures………………… 32 Figure 8 Validation of selected genes involved in cell motility……………… 33 Figure 9 SMF affects cell mobility…………………………………………… 34 Figure 10 SMF reduces melanin production and migration during development of zebrafish…………………………………………………………… 35 Appendix Housing of zebrafish for toxicity assay………………………36 References ………………………………………………………………………… 37
參考文獻	Reference 1. Zakharchenko, A., Guz, N., Laradji, A.M., Katz, E., and Minko, S. 2018. Magnetic field remotely controlled selective biocatalysis. Nature Catalysis 1:73. 2. Wong, W., Gan, W.L., Teo, Y.K., and Lew, W.S. 2018. Interplay of cell death signaling pathways mediated by alternating magnetic field gradient. Cell death discovery 4:49-49. 3. Colbert, A.P., Markov, M.S., and Souder, J.S. 2008. Static magnetic field therapy: dosimetry considerations. The Journal of Alternative and Complementary Medicine 14:577-582. 4. Zhang, Y., Wei, F., Poh, Y.-C., Jia, Q., Chen, J., Chen, J., Luo, J., Yao, W., Zhou, W., and Huang, W. 2017. Interfacing 3D magnetic twisting cytometry with confocal fluorescence microscopy to image force responses in living cells. Nature protocols 12:1437. 5. Bininda-Emonds, O.R., Cardillo, M., Jones, K.E., MacPhee, R.D., Beck, R.M., Grenyer, R., Price, S.A., Vos, R.A., Gittleman, J.L., and Purvis, A. 2007. The delayed rise of present-day mammals. Nature 446:507. 6. Clarke, D., Whitney, H., Sutton, G., and Robert, D. 2013. Detection and learning of floral electric fields by bumblebees. Science 340:66-69. 7. Liang, C.-H., Chuang, C.-L., Jiang, J.-A., and Yang, E.-C. 2016. Magnetic sensing 38 through the abdomen of the honey bee. Scientific reports 6:23657. 8. Foley, L.E., Gegear, R.J., and Reppert, S.M. 2011. Human cryptochrome exhibits light-dependent magnetosensitivity. Nature communications 2:356. 9. Aragonès, A.C., Haworth, N.L., Darwish, N., Ciampi, S., Bloomfield, N.J., Wallace, G.G., Diez-Perez, I., and Coote, M.L. 2016. Electrostatic catalysis of a Diels–Alder reaction. Nature 531:88. 10. Mehta, M., Wen, P., Nishikawa, R., Reardon, D., and Peters, K. 2017. Critical review of the addition of tumor treating fields (TTFields) to the existing standard of care for newly diagnosed glioblastoma patients. Critical reviews in oncology/hematology 111:60-65. 11. Kessler, A.F., Frömbling, G.E., Gross, F., Hahn, M., Dzokou, W., Ernestus, R.-I., Löhr, M., and Hagemann, C. 2018. Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition. Cell death discovery 5:12. 12. Long, Y., Wei, H., Li, J., Yao, G., Yu, B., Ni, D., Gibson, A.L., Lan, X., Jiang, Y., and Cai, W. 2018. Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators. ACS nano 12:12533-12540. 13. Stupp, R., Taillibert, S., Kanner, A., Read, W., Steinberg, D.M., Lhermitte, B., Toms, S., Idbaih, A., Ahluwalia, M.S., and Fink, K. 2017. Effect of tumor-treating fields plus 39 maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. Jama 318:2306-2316. 14. Sienkiewicz, Z. 2013. International Workshop on Non‐Ionizing Radiation Protection in Medicine. Medical physics 40. 15. Lu, Y., Worrell, G.A., Zhang, H.C., Yang, L., Brinkmann, B., Nelson, C., and He, B. 2014. Noninvasive imaging of the high frequency brain activity in focal epilepsy patients. IEEE Transactions on Biomedical Engineering 61:1660-1667. 16. Brain, J.D., Kavet, R., McCormick, D.L., Poole, C., Silverman, L.B., Smith, T.J., Valberg, P.A., Van Etten, R., and Weaver, J.C. 2003. Childhood leukemia: electric and magnetic fields as possible risk factors. Environmental Health Perspectives 111:962-970. 17. Tao, R., and Huang, K. 2011. Reducing blood viscosity with magnetic fields. Physical Review E 84:011905. 18. Vallbona, C., Hazlewood, C.F., and Jurida, G. 1997. Response of pain to static magnetic fields in postpolio patients: a double-blind pilot study. Archives of physical medicine and rehabilitation 78:1200-1203. 19. Alfano, A.P., Taylor, A.G., Foresman, P.A., Dunkl, P.R., McConnell, G.G., Conaway, M.R., and Gillies, G.T. 2001. Static magnetic fields for treatment of fibromyalgia: a randomized controlled trial. The Journal of Alternative & Complementary Medicine 40 7:53-64. 20. Juhász, M., Nagy, V.L., Székely, H., Kocsis, D., Tulassay, Z., and László, J.F. 2014. Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self-and placebo-controlled, double-blind, single centre, pilot study. Journal of The Royal Society Interface 11:20140601. 21. Colbert, A.P., Wahbeh, H., Harling, N., Connelly, E., Schiffke, H.C., Forsten, C., Gregory, W.L., Markov, M.S., Souder, J.J., and Elmer, P. 2009. Static magnetic field therapy: a critical review of treatment parameters. Evidence-based complementary and alternative medicine 6:133-139. 22. Polyakova, T., Zablotskii, V., and Dejneka, A. 2017. Cell membrane pore formation and change in ion channel activity in high-gradient magnetic fields. IEEE Magnetics Letters 8:1-5. 23. Ghibelli, L., Cerella, C., Cordisco, S., Clavarino, G., Marazzi, S., De Nicola, M., Nuccitelli, S., D′alessio, M., Magrini, A., and Bergamaschi, A. 2006. NMR exposure sensitizes tumor cells to apoptosis. Apoptosis 11:359-365. 24. Fanelli, C., Coppola, S., Barone, R., Colussi, C., Gualandi, G., Volpe, P., and Ghibelli, L. 1999. Magnetic fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx. The FASEB journal 13:95-102. 25. Pacini, S., Gulisano, M., Peruzzi, B., Sgambati, E., Gheri, G., Bryk, S.G., Vannucchi, 41 S., Polli, G., and Ruggiero, M. 2003. Effects of 0.2 T static magnetic field on human skin fibroblasts. Cancer detection and prevention 27:327-332. 26. Gioia, L., Saponaro, I., Bernabo, N., Tettamanti, E., Mattioli, M., and Barboni, B. 2013. Chronic exposure to a 2 mT static magnetic field affects the morphology, the metabolism and the function of in vitro cultured swine granulosa cells. Electromagnetic biology and medicine 32:536-550. 27. Wang, J., Xiang, B., Deng, J., Freed, D.H., Arora, R.C., and Tian, G. 2016. Inhibition of viability, proliferation, cytokines secretion, surface antigen expression, and adipogenic and osteogenic differentiation of adipose-derived stem cells by seven-day exposure to 0.5 T static magnetic fields. Stem cells international 2016. 28. Stolfa, S., Skorvanek, M., Stolfa, P., Rosocha, J., Vasko, G., and Sabo, J. 2007. Effects of static magnetic field and pulsed electromagnetic field on viability of human chondrocytes in vitro. Physiological research 56:S45. 29. Martino, C.F., Perea, H., Hopfner, U., Ferguson, V.L., and Wintermantel, E. 2010. Effects of weak static magnetic fields on endothelial cells. Bioelectromagnetics: Journal of the Bioelectromagnetics Society, The Society for Physical Regulation in Biology and Medicine, The European Bioelectromagnetics Association 31:296-301. 30. Chuo, W., Ma, T., Saito, T., Sugita, Y., Maeda, H., Zhang, G., Li, J., Liu, J., and Lu, L. 2013. A preliminary study of the effect of static magnetic field acting on rat bone 42 marrow mesenchymal stem cells during osteogenic differentiation in vitro. Journal of Hard Tissue Biology 22:227-232. 31. Denegre, J.M., Valles, J.M., Lin, K., Jordan, W., and Mowry, K.L. 1998. Cleavage planes in frog eggs are altered by strong magnetic fields. Proceedings of the National Academy of Sciences 95:14729-14732. 32. Sullivan, K., Balin, A.K., and Allen, R.G. 2011. Effects of static magnetic fields on the growth of various types of human cells. Bioelectromagnetics 32:140-147. 33. Papatheofanis, F.J. 1990. Use of calcium channel antagonists as magnetoprotective agents. Radiation research 122:24-28. 34. Prasad, A., Teh, D.B.L., Blasiak, A., Chai, C., Wu, Y., Gharibani, P.M., Yang, I.H., Phan, T.T., Lim, K.L., and Yang, H. 2017. Static magnetic field stimulation enhances oligodendrocyte differentiation and secretion of neurotrophic factors. Scientific reports 7:6743. 35. Luo, Y., Ji, X., Liu, J., Li, Z., Wang, W., Chen, W., Wang, J., Liu, Q., and Zhang, X. 2016. Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and Taxol. Bioelectrochemistry 109:31-40. 36. Zhang, L., Wang, J., Wang, H., Wang, W., Li, Z., Liu, J., Yang, X., Ji, X., Luo, Y., and Hu, C. 2016. Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation. Oncotarget 7:41527. 43 37. Kimmel, C.B., Ballard, W.W., Kimmel, S.R., Ullmann, B., and Schilling, T.F. 1995. Stages of embryonic development of the zebrafish. Developmental dynamics 203:253-310. 38. Tajik, A., Zhang, Y., Wei, F., Sun, J., Jia, Q., Zhou, W., Singh, R., Khanna, N., Belmont, A.S., and Wang, N. 2016. Transcription upregulation via force-induced direct stretching of chromatin. Nature materials 15:1287. 39. Le, H.Q., Ghatak, S., Yeung, C.-Y.C., Tellkamp, F., Günschmann, C., Dieterich, C., Yeroslaviz, A., Habermann, B., Pombo, A., and Niessen, C.M. 2016. Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nature cell biology 18:864. 40. Le, Q.-H. 2016. Mechanisms of force-mediated regulation of transcription, chromatin remodeling and cell fate decisions. Universität zu Köln
指導教授	陳健章 劉淑貞(Chien-Chang Chen Shu-Chen Liu)	審核日期	2020-1-22
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