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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 病理學科所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95041
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dc.contributor.advisor李力行zh_TW
dc.contributor.advisorLi-Shing Leeen
dc.contributor.author黃微溱zh_TW
dc.contributor.authorWei-Chen Huangen
dc.date.accessioned2024-08-26T16:24:01Z-
dc.date.available2024-08-27-
dc.date.copyright2024-08-26-
dc.date.issued2024-
dc.date.submitted2024-08-06-
dc.identifier.citationSung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71(3), 209-249. https://doi.org/10.3322/caac.21660
Cancer Statistics. (n.d.). Taiwan Cancer Registry Center. Retrieved March 5, 2024, from https://twcr.tw/?page_id=1855&lang=en
Symptoms of Breast Cancer. (2024, February 21). Breast Cancer. https://www.cdc.gov/breast-cancer/symptoms/index.html
Orrantia‐Borunda, E., Anchondo-Nuñez, P., Acuña-Aguilar, L. E., Gómez-Valles, F. O., & Ramírez-Valdespino, C. A. (2022). Subtypes of Breast Cancer. In Exon Publications eBooks (pp. 31–42). https://doi.org/10.36255/exon-publications-breast-cancer-subtypes
Allison, K. H., Hammond, M. E. H., Dowsett, M., McKernin, S. E., Carey, L. A., Fitzgibbons, P. L., Hayes, D. F., Lakhani, S. R., Chavez-MacGregor, M., Perlmutter, J., Perou, C. M., Regan, M. M., Rimm, D. L., Symmans, W. F., Torlakovic, E. E., Varella, L., Viale, G., Weisberg, T. F., McShane, L. M., & Wolff, A. C. (2020). Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 38(12), 1346–1366. https://doi.org/10.1200/JCO.19.02309
Wolff, A. C., Hammond, M. E. H., Allison, K. H., Harvey, B. E., Mangu, P. B., Bartlett, J. M. S., Bilous, M., Ellis, I. O., Fitzgibbons, P., Hanna, W., Jenkins, R. B., Press, M. F., Spears, P. A., Vance, G. H., Viale, G., McShane, L. M., & Dowsett, M. (2018). Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 36(20), 2105–2122. https://doi.org/10.1200/JCO.2018.77.8738
Yao-Lung, K., Dar-Ren, C. & Tsai-Wang, C. Clinicopathological features of triple-negative breast cancer in Taiwanese women. Int J Clin Oncol 16, 500–505 (2011). https://doi.org/10.1007/s10147-011-0211-9
Zagami, P., Carey, L.A. Triple negative breast cancer: Pitfalls and progress. npj Breast Cancer 8, 95 (2022). https://doi.org/10.1038/s41523-022-00468-0
Foulkes, W. D., Smith, I. E., & Reis-Filho, J. S. (2010). Triple-negative breast cancer. The New England journal of medicine, 363(20), 1938–1948. https://doi.org/10.1056/NEJMra1001389
Grote, I., Poppe, A., Lehmann, U., Christgen, M., Kreipe, H., & Bartels, S. (2024). Frequency of genetic alterations differs in advanced breast cancer between metastatic sites. Genes, chromosomes & cancer, 63(1), e23199. https://doi.org/10.1002/gcc.23199
Dvorak H. F. (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. The New England journal of medicine, 315(26), 1650–1659. https://doi.org/10.1056/NEJM198612253152606
Rodrigues, M., Kosaric, N., Bonham, C. A., & Gurtner, G. C. (2019). Wound Healing: A Cellular Perspective. Physiological reviews, 99(1), 665–706. https://doi.org/10.1152/physrev.00067.2017
Darby, I. A., Laverdet, B., Bonté, F., & Desmoulière, A. (2014). Fibroblasts and myofibroblasts in wound healing. Clinical, cosmetic and investigational dermatology, 7, 301–311. https://doi.org/10.2147/CCID.S50046
Schreier, T., Degen, E., & Baschong, W. (1993). Fibroblast migration and proliferation during in vitro wound healing. A quantitative comparison between various growth factors and a low molecular weight blood dialysate used in the clinic to normalize impaired wound healing. Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie, 193(4), 195–205. https://doi.org/10.1007/BF02576227
McCann, J. V., Xiao, L., Kim, D. J., Khan, O. F., Kowalski, P. S., Anderson, D. G., Pecot, C. V., Azam, S. H., Parker, J. S., Tsai, Y. S., Wolberg, A. S., Turner, S. D., Tatsumi, K., Mackman, N., & Dudley, A. C. (2019). Endothelial miR-30c suppresses tumor growth via inhibition of TGF-β-induced Serpine1. The Journal of clinical investigation, 129(4), 1654–1670. https://doi.org/10.1172/JCI123106
Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013
Hanahan D. (2022). Hallmarks of Cancer: New Dimensions. Cancer discovery, 12(1), 31–46. https://doi.org/10.1158/2159-8290.CD-21-1059
Paget, S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 8, 98–101 (1989).
Kalluri, R. & LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science 367, eaau6977 (2020).
Maman, S. & Witz, I. P. A history of exploring cancer in context. Nat. Rev. Cancer 18, 359–376 (2018).
Anderson, N. M., & Simon, M. C. (2020). The tumor microenvironment. Current biology: CB, 30(16), R921–R925. https://doi.org/10.1016/j.cub.2020.06.081
Jin, M. Z., & Jin, W. L. (2020). The updated landscape of tumor microenvironment and drug repurposing. Signal transduction and targeted therapy, 5(1), 166. https://doi.org/10.1038/s41392-020-00280-x
Truffi, M., Sorrentino, L., & Corsi, F. (2020). Fibroblasts in the Tumor Microenvironment. Advances in experimental medicine and biology, 1234, 15–29. https://doi.org/10.1007/978-3-030-37184-5_2
Antonio, N., Bønnelykke-Behrndtz, M. L., Ward, L. C., Collin, J., Christensen, I. J., Steiniche, T., Schmidt, H., Feng, Y., & Martin, P. (2015). The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. The EMBO journal, 34(17), 2219–2236. https://doi.org/10.15252/embj.201490147
Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., Vonderheide, R. H., Pittet, M. J., Jain, R. K., Zou, W., Howcroft, T. K., Woodhouse, E. C., Weinberg, R. A., & Krummel, M. F. (2018). Understanding the tumor immune microenvironment (TIME) for effective therapy. Nature medicine, 24(5), 541–550. https://doi.org/10.1038/s41591-018-0014-x
Lei, X., Lei, Y., Li, J. K., Du, W. X., Li, R. G., Yang, J., Li, J., Li, F., & Tan, H. B. (2020). Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer letters, 470, 126–133. https://doi.org/10.1016/j.canlet.2019.11.009
Younesi, F.S., Miller, A.E., Barker, T.H. et al. Fibroblast and myofibroblast activation in normal tissue repair and fibrosis. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-024-00716-0
Yoon, H., Tang, CM., Banerjee, S. et al. TGF-β1-mediated transition of resident fibroblasts to cancer-associated fibroblasts promotes cancer metastasis in gastrointestinal stromal tumor. Oncogenesis 10, 13 (2021). https://doi.org/10.1038/s41389-021-00302-5
Yang, D., Liu, J., Qian, H. et al. Cancer-associated fibroblasts: from basic science to anticancer therapy. Exp Mol Med 55, 1322–1332 (2023). https://doi.org/10.1038/s12276-023-01013-0
Glentis, A., Oertle, P., Mariani, P. et al. Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane. Nat Commun 8, 924 (2017). https://doi.org/10.1038/s41467-017-00985-8
Larouche, J., Sheoran, S., Maruyama, K., & Martino, M. M. (2018). Immune Regulation of Skin Wound Healing: Mechanisms and Novel Therapeutic Targets. Advances in wound care, 7(7), 209–231. https://doi.org/10.1089/wound.2017.0761
Pakyari, M., Farrokhi, A., Maharlooei, M. K., & Ghahary, A. (2013). Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing. Advances in wound care, 2(5), 215–224. https://doi.org/10.1089/wound.2012.0406
Shi, X., Yang, J., Deng, S., Xu, H., Wu, D., Zeng, Q., Wang, S., Hu, T., Wu, F., & Zhou, H. (2022). TGF-β signaling in the tumor metabolic microenvironment and targeted therapies. Journal of hematology & oncology, 15(1), 135. https://doi.org/10.1186/s13045-022-01349-6
Pickup, M., Novitskiy, S., & Moses, H. L. (2013). The roles of TGFβ in the tumour microenvironment. Nature reviews. Cancer, 13(11), 788–799. https://doi.org/10.1038/nrc3603
Ciardiello, D., Elez, E., Tabernero, J., & Seoane, J. (2020). Clinical development of therapies targeting TGFβ: current knowledge and future perspectives. Annals of oncology: official journal of the European Society for Medical Oncology, 31(10), 1336–1349. https://doi.org/10.1016/j.annonc.2020.07.009
Park, H., Otte, A., & Park, K. (2022). Evolution of drug delivery systems: From 1950 to 2020 and beyond. Journal of controlled release: official journal of the Controlled Release Society, 342, 53–65. https://doi.org/10.1016/j.jconrel.2021.12.030
Zhang, Y., Chan, H. F., & Leong, K. W. (2013). Advanced materials and processing for drug delivery: the past and the future. Advanced drug delivery reviews, 65(1), 104–120. https://doi.org/10.1016/j.addr.2012.10.003
Vargason, A.M., Anselmo, A.C. & Mitragotri, S. The evolution of commercial drug delivery technologies. Nat Biomed Eng 5, 951–967 (2021). https://doi.org/10.1038/s41551-021-00698-w
Lü, J. M., Wang, X., Marin-Muller, C., Wang, H., Lin, P. H., Yao, Q., & Chen, C. (2009). Current advances in research and clinical applications of PLGA-based nanotechnology. Expert review of molecular diagnostics, 9(4), 325–341. https://doi.org/10.1586/erm.09.15
Lin, H. R., Kuo, C. J., Yang, C. Y., Shaw, S. Y., & Wu, Y. J. (2002). Preparation of macroporous biodegradable PLGA scaffolds for cell attachment with the use of mixed salts as porogen additives. Journal of biomedical materials research, 63(3), 271–279. https://doi.org/10.1002/jbm.10183
Zhang, J., Zheng, Y., Lee, J. et al. A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing. Nat Commun 12, 1670 (2021). https://doi.org/10.1038/s41467-021-21964-0
Ryu, S., Park, S., Lee, H. Y., Lee, H., Cho, C. W., & Baek, J. S. (2021). Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced
Encapsulation Efficiency and Controlled Release of Hydrophilic Drug. International journal of molecular sciences, 22(6), 2792. https://doi.org/10.3390/ijms22062792
Grierson, I., Joseph, J., Miller, M., & Day, J. E. (1988). Wound repair: the fibroblast and the inhibition of scar formation. Eye (London, England), 2 (Pt 2), 135–148. https://doi.org/10.1038/eye.1988.27
Park, M. K., Lee, C. H., & Lee, H. (2018). Mouse models of breast cancer in preclinical research. Laboratory animal research, 34(4), 160–165. https://doi.org/10.5625/lar.2018.34.4.160
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95041-
dc.description.abstract乳癌是在世界各國都很常見的一種癌症。治療乳癌的主要方式是透過手術切除腫瘤,但部分患者可能會面臨術後復發的問題,這對病人來說是一大威脅。而手術造成的傷口會改變改變周圍組織,形成如腫瘤微環境(TME)般,可以促進腫瘤發展的環境。因此,可以促進組織修復的物質,可能也有助於腫瘤復發,無論是在原位或遠端。乙型轉化生長因子(TGFβ)是關鍵的細胞因子,在多種傷口癒合,以及腫瘤發展的過程中發揮作用。本研究探討了利用藥物釋放平台裝載並在特定時間釋放乙型轉化生長因子抑制劑(TGFβ inhibitor)是否能減少復發。在進行體內研究前,我們先將纖維母細胞(3T3-L1)與乳腺癌細胞(4T1)共同培養,試圖模擬一個簡易的腫瘤微環境。再將乳腺癌細胞注射到小鼠乳腺腺體,以建立復發模型。手術過程中,我們在切除部位應用了含或不含乙型轉化生長因子抑制劑的脈衝式藥物釋放平台。結果顯示,接受乙型轉化生長因子抑制劑治療的小鼠,其肝臟和肺部的轉移病灶明顯減少,且纖維化區域亦較小。因此,這種藥物釋放系統可能是減少遠端復發(轉移)的潛在治療方法,值得進一步研究。zh_TW
dc.description.abstractBreast cancer is a global health concern where surgery is the primary treatment, yet post-surgery recurrence remains a significant threat. Surgical wounds create an environment. This is reported to be similar to the tumor microenvironment (TME), potentially promoting tumor growth. Transforming growth factor β (TGFβ) is a pivotal cytokine participates in wound healing, which also influences tumor recurrence, no matter local or distant recurrence (metastasis). This study explores the potential of utilization of a drug-releasing platform to reduce recurrence. Prior to in vivo experiments, co-cultured fibroblasts (3T3-L1) and breast cancer cells (4T1) simulated a simplified TME. Mice models injected with these cells demonstrated reduced metastasis and fibrotic areas when treated with a TGFβ inhibitor embedded in a hydrogel during surgery. This approach shows promise in mitigating distant recurrence (metastasis), warranting further investigation.en
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dc.description.tableofcontents口試委員會審定書 …………………………………………………… i
誌謝 …………………………………………………………………… ii
中文摘要 ……………………………………………………………… iii
Abstract ……………………………………………………………… iv
Content ………………………………………………………………… v
Chapter 1 Introduction ……...……………………………………………….… 1
1.1 Breast Cancer ………………………………………………… 1
1.1.1 Epidemiology ………………………………………… 1
1.1.2 Breast Cancer Subtypes ……………………………… 1
1.1.3 Treatments for Breast Cancer ………………………… 2
1.2 Presence of Wound Could Create an Environment for Cancer Metastasis ……………………………………………………… 3
1.2.1 Wound Healing Processes …………………………… 3
1.2.2 Wound Healing and Cancer Have Shared Hallmarks …. 4
1.2.3 Tumor Microenvironment …………………………… 6
1.2.3.1 Immune Cells ……………………………… 6
1.2.3.2 Cancer-Associated Fibroblasts ……………… 7
1.2.4 Wound Healing Microenvironment ………………… 7
1.3 Transforming Growth Factor β (TGFβ) is a Cytokine Participating in Multiple Processes ………………………………………… 8
1.3.1 Transforming Growth Factor β (TGFβ) Signaling Pathway ……………………………………………… 8
1.3.2 Current Treatments Targeting Transforming Growth Factor β (TGFβ) ……………………………………… 8
1.4 Drug-Releasing Platforms …………………………………… 9
1.4.1 Poly(lactic-co-glycolic) acid (PLGA)-Fabricated Microcapsule ………………………………………… 9
1.4.2 Current Application of PLGA-Fabricated Microcapsule in Wound Healing ……………………………………… 9
Chapter 2 Motivation and Specific Aims ………………………........ 11
2.1 Motivation …………………………………………………. … 11
2.2 Specific Aims ………………………………………………… 11
Chapter 3 Methods and Materials …………………………………… 12
3.1 Cell Lines, Cell Culture, and Cell Count ……………………… 12
3.2 Wound Healing Assay ………………………………………… 13
3.3 ELISA ………………………………………………………… 13
3.4 Drug-Releasing Platform ……………………………………… 14
3.5 Recurrence Model and Surgical Procedure …………………… 14
3.6 Histopathology ………………………………………………… 15
Chapter 4 Results …………………………………………………… 17
4.1 In Vitro Examinations ………………………………………… 17
4.1.1 Breast cancer cells affect fibroblast proliferation and migration in vitro. …………………………………… 17
4.1.2 Transforming growth factor β (TGFβ) could adjust the properties of cells in vitro. …………………………… 18
4.2 In Vivo Application …………………………………………… 19
4.2.1 Development of a breast cancer post-surgery recurrence model. ………………………………………………… 19
4.2.2 Locally delayed inhibition of TGFβ decreased number of metastatic foci in distant organs. …………………… 20
Chapter 5 Discussion ………………………………………………… 22
Figures ………………………………………………………………… 28
Reference ……………………………………………………………… 35
Supplementary Information …………………………………………… 44
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dc.language.isoen-
dc.subject腫瘤微環境zh_TW
dc.subject乳癌zh_TW
dc.subject傷口癒合zh_TW
dc.subject藥物釋放平台zh_TW
dc.subject乙型轉化生長因子zh_TW
dc.subject癌症復發zh_TW
dc.subjectCancer recurrenceen
dc.subjectBreast canceren
dc.subjectTransforming growth factor β (TGFβ)en
dc.subjectTumor microenvironment (TME)en
dc.subjectDrug-releasing platformen
dc.subjectWound healingen
dc.title利用藥物載體延後抑制乙型轉化生長因子對乳癌轉移的影響zh_TW
dc.titleImpact of Delayed Inhibition of Transforming Growth Factor β via a Drug-Releasing Platform on Breast Cancer Metastasisen
dc.typeThesis-
dc.date.schoolyear112-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee連晃駿;謝明書;林季宏zh_TW
dc.contributor.oralexamcommitteeHuang-Chun Lien;Min-Shu Hsieh;Ching-Hung Linen
dc.subject.keyword乳癌,傷口癒合,癌症復發,腫瘤微環境,乙型轉化生長因子,藥物釋放平台,zh_TW
dc.subject.keywordBreast cancer,Wound healing,Cancer recurrence,Tumor microenvironment (TME),Transforming growth factor β (TGFβ),Drug-releasing platform,en
dc.relation.page45-
dc.identifier.doi10.6342/NTU202403482-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2024-08-07-
dc.contributor.author-college醫學院-
dc.contributor.author-dept病理學研究所-
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