請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95104完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊家榮 | zh_TW |
| dc.contributor.advisor | Chia-Ron Yang | en |
| dc.contributor.author | 蔡宇鈞 | zh_TW |
| dc.contributor.author | Yu-Chun Tsai | en |
| dc.date.accessioned | 2024-08-28T16:17:11Z | - |
| dc.date.available | 2024-08-29 | - |
| dc.date.copyright | 2024-08-28 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-26 | - |
| dc.identifier.citation | 1.Louis, D.N., Perry, A., Wesseling, P., Brat, D.J., Cree, I.A., Figarella-Branger, D., Hawkins, C., Ng, H., Pfister, S.M., and Reifenberger, G., The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-Oncology, 2021. 23(8): p. 1231–1251.
2.McNamara, C., Mankad, K., Thust, S., Dixon, L., Limback-Stanic, C., D’Arco, F., Jacques, T.S., and Löbel, U., 2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist. Neuroradiology, 2022. 64(10): p. 1919–1950. 3.Torp, S.H., Solheim, O., and Skjulsvik, A.J., The WHO 2021 Classification of Central Nervous System tumours: a practical update on what neurosurgeons need to know—a minireview. Acta Neurochirurgica, 2022. 164(9): p. 2453–2464. 4.Salari, N., Ghasemi, H., Fatahian, R., Mansouri, K., Dokaneheifard, S., Shiri, M.H., Hemmati, M., and Mohammadi, M., The global prevalence of primary central nervous system tumors: a systematic review and meta-analysis. European Journal of Medical Research, 2023. 28(1): p. 39. 5.Czarnywojtek, A., Borowska, M., Dyrka, K., Van Gool, S., Sawicka-Gutaj, N., Moskal, J., Kościński, J., Graczyk, P., Hałas, T., and Lewandowska, A.M., Glioblastoma multiforme: the latest diagnostics and treatment techniques. Pharmacology, 2023. 108(5): p. 423–431. 6.Alexopoulos, G., Zhang, J., Karampelas, I., Patel, M., Kemp, J., Coppens, J., Mattei, T.A., and Mercier, P., Long-term time series forecasting and updates on survival analysis of glioblastoma multiforme: a 1975–2018 population-based study. Neuroepidemiology, 2022. 56(2): p. 75–89. 7.Brown, N.F., Ottaviani, D., Tazare, J., Gregson, J., Kitchen, N., Brandner, S., Fersht, N., and Mulholland, P., Survival outcomes and prognostic factors in glioblastoma. Cancers, 2022. 14(13): p. 3161. 8.Wu, W., Klockow, J.L., Zhang, M., Lafortune, F., Chang, E., Jin, L., Wu, Y., and Daldrup-Link, H.E., Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacological Research, 2021. 171: p. 105780. 9.Hatoum, A., Mohammed, R., and Zakieh, O., The unique invasiveness of glioblastoma and possible drug targets on extracellular matrix. Cancer Management and Research, 2019: p. 1843–1855. 10.Valdebenito, S., D'Amico, D., and Eugenin, E., Novel approaches for glioblastoma treatment: Focus on tumor heterogeneity, treatment resistance, and computational tools. Cancer Reports, 2019. 2(6): p. e1220. 11.Fisher, J.P. and Adamson, D.C., Current FDA-approved therapies for high-grade malignant gliomas. Biomedicines, 2021. 9(3): p. 324. 12.Damato, A.R., Luo, J., Katumba, R.G., Talcott, G.R., Rubin, J.B., Herzog, E.D., and Campian, J.L., Temozolomide chronotherapy in patients with glioblastoma: a retrospective single-institute study. Neuro-Oncology Advances, 2021. 3(1): p. vdab041. 13.Hottinger, A.F., Pacheco, P., and Stupp, R., Tumor treating fields: a novel treatment modality and its use in brain tumors. Neuro-Oncology, 2016. 18(10): p. 1338–1349. 14.Stupp, R., Taillibert, S., Kanner, A., Read, W., Steinberg, D.M., Lhermitte, B., Toms, S., Idbaih, A., Ahluwalia, M.S., and Fink, K., Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. The Journal of the American Medical Association, 2017. 318(23): p. 2306–2316. 15.Cruz, J.V.R., Batista, C., Afonso, B.d.H., Alexandre-Moreira, M.S., Dubois, L.G., Pontes, B., Moura Neto, V., and Mendes, F.d.A., Obstacles to glioblastoma treatment two decades after temozolomide. Cancers, 2022. 14(13): p. 3203. 16.Seker-Polat, F., Pinarbasi Degirmenci, N., Solaroglu, I., and Bagci-Onder, T., Tumor cell infiltration into the brain in glioblastoma: from mechanisms to clinical perspectives. Cancers, 2022. 14(2): p. 443. 17.Uyar, R., Glioblastoma microenvironment: The stromal interactions. Pathology-Research and Practice, 2022. 232: p. 153813. 18.Zhang, H., Zhou, Y., Cui, B., Liu, Z., and Shen, H., Novel insights into astrocyte-mediated signaling of proliferation, invasion and tumor immune microenvironment in glioblastoma. Biomedicine & Pharmacotherapy, 2020. 126: p. 110086. 19.Parker, J.J., Dionne, K.R., Massarwa, R., Klaassen, M., Foreman, N.K., Niswander, L., Canoll, P., Kleinschmidt-Demasters, B., and Waziri, A., Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma. Neuro-Oncology, 2013. 15(8): p. 1048–1057. 20.Anderson, S.M., Kelly, M., and Odde, D.J., Glioblastoma cells use an integrin-and CD44-mediated motor-clutch mode of migration in brain tissue. Cellular and Molecular Bioengineering, 2024: p. 1–15. 21.Mohiuddin, E. and Wakimoto, H., Extracellular matrix in glioblastoma: Opportunities for emerging therapeutic approaches. American Journal of Cancer Research, 2021. 11(8): p. 3742. 22.Sharma, P., Sonawane, P., Herpai, D., D’Agostino, R., Rossmeisl, J., Tatter, S., and Debinski, W., Multireceptor targeting of glioblastoma. Neuro-Oncology Advances, 2020. 2(1): p. vdaa107. 23.Whitehead, C.A., Morokoff, A.P., Kaye, A.H., Drummond, K.J., Mantamadiotis, T., and Stylli, S.S., Invadopodia associated Thrombospondin-1 contributes to a post-therapy pro-invasive response in glioblastoma cells. Experimental Cell Research, 2023. 431(1): p. 113743. 24.Zhao, W., Wu, Y., Wang, S., Zhao, F., Liu, W., Xue, Z., Zhang, L., Wang, J., Han, M., Li, X., and Huang, B., HTRA1 promotes EMT through the HDAC6/Ac-α-tubulin pathway in human GBM cells. CNS Neuroscience & Therapeutics, 2024. 30(2): p. e14605. 25.Ge, L.-P., Jin, X., Yang, Y.-S., Liu, X.-Y., Shao, Z.-M., Di, G.-H., and Jiang, Y.-Z., Tektin4 loss promotes triple-negative breast cancer metastasis through HDAC6-mediated tubulin deacetylation and increases sensitivity to HDAC6 inhibitor. Oncogene, 2021. 40(12): p. 2323-2334. 26.Ahir, B.K., Engelhard, H.H., and Lakka, S.S., Tumor development and angiogenesis in adult brain tumor: glioblastoma. Molecular Neurobiology, 2020. 57: p. 2461–2478. 27.Valiathan, R.R., Marco, M., Leitinger, B., Kleer, C.G., and Fridman, R., Discoidin domain receptor tyrosine kinases: new players in cancer progression. Cancer and Metastasis Reviews, 2012. 31: p. 295–321. 28.Chen, L., Kong, X., Fang, Y., Paunikar, S., Wang, X., Brown, J.A., Bourke, E., Li, X., and Wang, J., Recent advances in the role of discoidin domain receptor tyrosine Kinase 1 and discoidin domain receptor tyrosine Kinase 2 in breast and ovarian cancer. Frontiers in Cell and Developmental Biology, 2021. 9: p. 747314. 29.Leitinger, B., Discoidin domain receptor functions in physiological and pathological conditions. International Review of Cell and Molecular Biology, 2014. 310: p. 39–87. 30.Kothiwale, S., Borza, C.M., Lowe Jr, E.W., Pozzi, A., and Meiler, J., Discoidin domain receptor 1 (DDR1) kinase as target for structure-based drug discovery. Drug Discovery Today, 2015. 20(2): p. 255–261. 31.Carafoli, F. and Hohenester, E., Collagen recognition and transmembrane signalling by discoidin domain receptors. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2013. 1834(10): p. 2187–2194. 32.Multhaupt, H.A., Leitinger, B., Gullberg, D., and Couchman, J.R., Extracellular matrix component signaling in cancer. Advanced Drug Delivery Reviews, 2016. 97: p. 28–40. 33.Vogel, W.F., Aszódi, A., Alves, F., and Pawson, T., Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Molecular and Cellular Biology, 2001. 21(8): p. 2906–2917. 34.Yeh, Y.-C., Lin, H.-H., and Tang, M.-J., Dichotomy of the function of DDR1 in cells and disease progression. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2019. 1866(11): p. 118473. 35.Henriet, E., Sala, M., Abou Hammoud, A., Tuariihionoa, A., Di Martino, J., Ros, M., and Saltel, F., Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer. Cell Adhesion & Migration, 2018. 12(4): p. 363–377. 36.Dagamajalu, S., Rex, D., Suchitha, G., Rai, A.B., Kumar, S., Joshi, S., Raju, R., and Prasad, T.K., A network map of discoidin domain receptor 1 (DDR1)-mediated signaling in pathological conditions. Journal of Cell Communication and Signaling, 2023. 17(3): p. 1081–1088. 37.Vehlow, A., Klapproth, E., Jin, S., Hannen, R., Hauswald, M., Bartsch, J.-W., Nimsky, C., Temme, A., Leitinger, B., and Cordes, N., Interaction of discoidin domain receptor 1 with a 14-3-3-Beclin-1-Akt1 complex modulates glioblastoma therapy sensitivity. Cell Reports, 2019. 26(13): p. 3672–3683. e3677. 38.Rammal, H., Saby, C., Magnien, K., Van-Gulick, L., Garnotel, R., Buache, E., El Btaouri, H., Jeannesson, P., and Morjani, H., Discoidin domain receptors: potential actors and targets in cancer. Frontiers in Pharmacology, 2016. 7: p. 55. 39.Moll, S., Desmoulière, A., Moeller, M.J., Pache, J.-C., Badi, L., Arcadu, F., Richter, H., Satz, A., Uhles, S., and Cavalli, A., DDR1 role in fibrosis and its pharmacological targeting. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2019. 1866(11): p. 118474. 40.Çataltepe, S. and Cox, L.A., DDR1 Deficiency in Mice: A Spontaneous Model of Bronchopulmonary Dysplasia-associated Pulmonary Hypertension? American Thoracic Society, 2022. 67(5): p. 518–519. 41.Toy, K.A., Valiathan, R.R., Núñez, F., Kidwell, K.M., Gonzalez, M.E., Fridman, R., and Kleer, C.G., Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer. Breast Cancer Research and Treatment, 2015. 150: p. 9–18. 42.Zhong, X., Zhang, W., and Sun, T., DDR1 promotes breast tumor growth by suppressing antitumor immunity. Oncology Reports, 2019. 42(6): p. 2844–2854. 43.Koh, M., Woo, Y., Valiathan, R.R., Jung, H.Y., Park, S.Y., Kim, Y.N., Kim, H.R.C., Fridman, R., and Moon, A., Discoidin domain receptor 1 is a novel transcriptional target of ZEB 1 in breast epithelial cells undergoing H‐R as‐induced epithelial to mesenchymal transition. International Journal of Cancer, 2015. 136(6): p. E508–E520. 44.Takai, K., Drain, A.P., Lawson, D.A., Littlepage, L.E., Karpuj, M., Kessenbrock, K., Le, A., Inoue, K., Weaver, V.M., and Werb, Z., Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers. Genes & Development, 2018. 32(3-4): p. 244–257. 45.Juin, A., Di Martino, J., Leitinger, B., Henriet, E., Gary, A.-S., Paysan, L., Bomo, J., Baffet, G., Gauthier-Rouvière, C., and Rosenbaum, J., Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42–Tuba pathway. Journal of Cell Biology, 2014. 207(4): p. 517–533. 46.Yang, S.H., Baek, H.A., Lee, H.J., Park, H.S., Jang, K.Y., Kang, M.J., Lee, D.G., Lee, Y.C., Moon, W.S., and Chung, M.J., Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung carcinomas. Oncology Reports, 2010. 24(2): p. 311–319. 47.Dawoud, M.M., Salah, M., and Mohamed, A.S.E.D., Clinical significance of immunohistochemical expression of DDR1 and β-catenin in colorectal carcinoma. World Journal of Surgical Oncology, 2023. 21(1): p. 168. 48.Vilella, E., Gas, C., Garcia-Ruiz, B., and Rivera, F.J., Expression of DDR1 in the CNS and in myelinating oligodendrocytes. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2019. 1866(11): p. 118483. 49.Ram, R., Lorente, G., Nikolich, K., Urfer, R., Foehr, E., and Nagavarapu, U., Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2. Journal of Neuro-Oncology, 2006. 76(3): p. 239–248. 50.Vehlow, A. and Cordes, N., DDR1 (discoidin domain receptor tyrosine kinase 1) drives glioblastoma therapy resistance by modulating autophagy. Autophagy, 2019. 15(8): p. 1487–1488. 51.Faisal, S.M., Varela, M., Comba, A., Argento, A., West, M., Brumley, E., Abel II, C., Clewner, J., Stack, B., and Haase, S., TMIC-03. Targeting the collagen receptor ddr1 promotes anti-glioma immunity by remodeling collagen fiber architecture. Neuro-Oncology, 2023. 25(Supplement_5): p. v278. 52.Lu, J., Chen, Y., Wen, L., Zhou, Q., and Yan, S., LncRNA CDKN2B‐AS1 contributes to glioma development by regulating the miR‐199a‐5p/DDR1 axis. The Journal of Gene Medicine, 2022. 24(1): p. e3389. 53.Richter, H., Satz, A.L., Bedoucha, M., Buettelmann, B., Petersen, A.C., Harmeier, A., Hermosilla, R., Hochstrasser, R., Burger, D., and Gsell, B., DNA-encoded library-derived DDR1 inhibitor prevents fibrosis and renal function loss in a genetic mouse model of Alport syndrome. ACS Chemical Biology, 2018. 14(1): p. 37–49. 54.Liu, S., Li, X., Chen, C., Lin, X., Zuo, W., Peng, C., Jiang, Q., Huang, W., and He, G., Design, synthesis, and biological evaluation of novel discoidin domain receptor inhibitors for the treatment of lung adenocarcinoma and pulmonary fibrosis. European Journal of Medicinal Chemistry, 2024. 265: p. 116100. 55.Mo, C., Zhang, Z., Li, Y., Huang, M., Zou, J., Luo, J., Tu, Z.-C., Xu, Y., Ren, X., and Ding, K., Design and Optimization of 3′-(Imidazo [1, 2-a] pyrazin-3-yl)-[1, 1′-biphenyl]-3-carboxamides as Selective DDR1 Inhibitors. ACS Medicinal Chemistry Letters, 2020. 11(3): p. 379–384. 56.Zhavoronkov, A., Ivanenkov, Y.A., Aliper, A., Veselov, M.S., Aladinskiy, V.A., Aladinskaya, A.V., Terentiev, V.A., Polykovskiy, D.A., Kuznetsov, M.D., and Asadulaev, A., Deep learning enables rapid identification of potent DDR1 kinase inhibitors. Nature Biotechnology, 2019. 37(9): p. 1038–1040. 57.Montero, J.C., Seoane, S., Ocaña, A., and Pandiella, A., Inhibition of SRC family kinases and receptor tyrosine kinases by dasatinib: possible combinations in solid tumors. Clinical Cancer Research, 2011. 17(17): p. 5546–5552. 58.Brave, M., Goodman, V., Kaminskas, E., Farrell, A., Timmer, W., Pope, S., Harapanhalli, R., Saber, H., Morse, D., and Bullock, J., Sprycel for chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clinical Cancer Research, 2008. 14(2): p. 352–359. 59.Kim, B.H., Lee, Y., Yoo, H., Cui, M., Lee, S., Kim, S.Y., Cho, J.U., Lee, H., Yang, B.S., and Kwon, Y.G., Anti‐angiogenic activity of thienopyridine derivative LCB 03‐0110 by targeting VEGFR‐2 and JAK/STAT 3 Signalling. Experimental Dermatology, 2015. 24(7): p. 503–509. 60.Gao, M., Duan, L., Luo, J., Zhang, L., Lu, X., Zhang, Y., Zhang, Z., Tu, Z., Xu, Y., and Ren, X., Discovery and optimization of 3-(2-(Pyrazolo [1, 5-a] pyrimidin-6-yl) ethynyl) benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors. Journal of Medicinal Chemistry, 2013. 56(8): p. 3281–3295. 61.Chen, H.-R., Yeh, Y.-C., Liu, C.-Y., Wu, Y.-T., Lo, F.-Y., Tang, M.-J., and Wang, Y.-K., DDR1 promotes E-cadherin stability via inhibition of integrin-β1-Src activation-mediated E-cadherin endocytosis. Scientific Reports, 2016. 6(1): p. 36336. 62.Koga, F., Xu, W., Karpova, T.S., McNally, J.G., Baron, R., and Neckers, L., Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent Akt and Erk activation. Proceedings of the National Academy of Sciences, 2006. 103(30): p. 11318–11322. 63.Dunphy, W.G., The decision to enter mitosis. Trends in Cell Biology, 1994. 4(6): p. 202–207. 64.Qi, B., Zhong, L., He, J., Zhang, H., Li, F., Wang, T., Zou, J., Lin, Y.-X., Zhang, C., and Guo, X., Discovery of inhibitors of Aurora/PLK targets as anticancer agents. Journal of Medicinal Chemistry, 2019. 62(17): p. 7697–7707. 65.Ongusaha, P.P., Kim, J.i., Fang, L., Wong, T.W., Yancopoulos, G.D., Aaronson, S.A., and Lee, S.W., p53 induction and activation of DDR1 kinase counteract p53‐mediated apoptosis and influence p53 regulation through a positive feedback loop. The EMBO Journal, 2003. 22(6): p.1289–1301. 66.Hsieh, Y.-L., Tu, H.-J., Pan, S.-L., Liou, J.-P., and Yang, C.-R., Anti-metastatic activity of MPT0G211, a novel HDAC6 inhibitor, in human breast cancer cells in vitro and in vivo. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2019. 1866(6): p. 992–1003. 67.Roig, B. and Vilella, E., DDR1 (discoidin domain receptor tyrosine kinase 1). http://AtlasGeneticsOncology.org/Genes/DDR1ID40280ch6p21.html 68.Ramachandran, R.K., Sørensen, M.D., Aaberg-Jessen, C., Hermansen, S.K., and Kristensen, B.W., Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas. PLoS One, 2017. 12(2): p. e0172234. 69.Wang, J., Li, Y., Wang, J., Li, C., Yu, K., and Wang, Q., Increased expression of matrix metalloproteinase-13 in glioma is associated with poor overall survival of patients. Medical Oncology, 2012. 29(4): p. 2432–2437. 70.Pointer, K.B., Clark, P.A., Schroeder, A.B., Salamat, M.S., Eliceiri, K.W., and Kuo, J.S., Association of collagen architecture with glioblastoma patient survival. Journal of Neurosurgery, 2016. 126(6): p. 1812–1821. 71.Luo, J., Zou, H., Guo, Y., Tong, T., Ye, L., Zhu, C., Deng, L., Wang, B., Pan, Y., and Li, P., SRC kinase-mediated signaling pathways and targeted therapies in breast cancer. Breast Cancer Research, 2022. 24(1): p. 99. 72.Stettner, M.R., Wang, W., Nabors, L.B., Bharara, S., Flynn, D.C., Grammer, J.R., Gillespie, G.Y., and Gladson, C.L., Lyn kinase activity is the predominant cellular SRC kinase activity in glioblastoma tumor cells. Cancer Research, 2005. 65(13): p. 5535–5543. 73.Ligresti, G., Militello, L., Steelman, L.S., Cavallaro, A., Basile, F., Nicoletti, F., Stivala, F., McCubrey, J.A., and Libra, M., PIK3CA mutations in human solid tumors: role in sensitivity to various therapeutic approaches. Cell Cycle, 2009. 8(9): p. 1352–1358. 74.Wang, Z., Sun, J., Li, X., Yang, S., Yue, S., Zhang, J., Yang, X., Zhu, T., Jiang, R., and Yang, W., Downregulation of Src enhances the cytotoxic effect of temozolomide through AKT in glioma. Oncology Reports, 2013. 29(4): p. 1395–1398. 75.Suleman, M., Chen, A., Ma, H., Wen, S., Zhao, W., Lin, D., Wu, G., and Li, Q., PIR promotes tumorigenesis of breast cancer by upregulating cell cycle activator E2F1. Cell Cycle, 2019. 18(21): p. 2914–2927. 76.Azizi, R., Salemi, Z., Fallahian, F., and Aghaei, M., Inhibition of didscoidin domain receptor 1 reduces epithelial–mesenchymal transition and induce cell‐cycle arrest and apoptosis in prostate cancer cell lines. Journal of Cellular Physiology, 2019. 234(11): p. 19539–19552. 77.Ye, L., Pu, C., Tang, J., Wang, Y., Wang, C., Qiu, Z., Xiang, T., Zhang, Y., and Peng, W., Transmembrane-4 L-six family member-1 (TM4SF1) promotes non-small cell lung cancer proliferation, invasion and chemo-resistance through regulating the DDR1/Akt/ERK-mTOR axis. Respiratory Research, 2019. 20: p. 1–10. 78.Iwamoto, K., Tashima, Y., Hamada, H., Eguchi, Y., and Okamoto, M., Mathematical modeling and sensitivity analysis of G1/S phase in the cell cycle including the DNA-damage signal transduction pathway. Biosystems, 2008. 94(1-2): p. 109–117. 79.Wang, Y., Ji, P., Liu, J., Broaddus, R.R., Xue, F., and Zhang, W., Centrosome-associated regulators of the G 2/M checkpoint as targets for cancer therapy. Molecular Cancer, 2009. 8: p. 1–13. 80.Lu, Q.P., Chen, W.D., Peng, J.R., Xu, Y.D., Cai, Q., Feng, G.K., Ding, K., Zhu, X.F., and Guan, Z., Antitumor activity of 7RH, a discoidin domain receptor 1 inhibitor, alone or in combination with dasatinib exhibits antitumor effects in nasopharyngeal carcinoma cells. Oncology Letters, 2016. 12(5): p. 3598–3608. 81.Dai, W., Liu, S., Wang, S., Zhao, L., Yang, X., Zhou, J., Wang, Y., Zhang, J., Zhang, P., and Ding, K., Activation of transmembrane receptor tyrosine kinase DDR1-STAT3 cascade by extracellular matrix remodeling promotes liver metastatic colonization in uveal melanoma. Signal Transduction and Targeted Therapy, 2021. 6(1): p. 176. 82.Liu, K., Zheng, M., Lu, R., Du, J., Zhao, Q., Li, Z., Li, Y., and Zhang, S., The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review. Cancer Cell International, 2020. 20: p. 1–16. 83.Galusic, D., Lucijanic, M., Livun, A., Radman, M., Lucijanic, J., Drmic Hofman, I., and Kusec, R., CDC25c expression in patients with myelofibrosis is associated with stronger myeloproliferation and shorter overall survival. Wiener klinische Wochenschrift, 2022: p. 1–3. 84.Cho, Y., Park, J., Park, B.C., Kim, J.H., Jeong, D.G., Park, S.G., and Cho, S., Cell cycle-dependent Cdc25C phosphatase determines cell survival by regulating apoptosis signal-regulating kinase 1. Cell Death & Differentiation, 2015. 22(10): p. 1605–1617. 85.Huang, D.-M., Guh, J.-H., Huang, Y.-T., Chueh, S.-C., Chiang, P.-C., and Teng, C.-M., Induction of mitotic arrest and apoptosis in human prostate cancer pc-3 cells by evodiamine. The Journal of Urology, 2005. 173(1): p. 256–261. 86.Rosén, E., Mangukiya, H.B., Elfineh, L., Stockgard, R., Krona, C., Gerlee, P., and Nelander, S., Inference of glioblastoma migration and proliferation rates using single time-point images. Communications Biology, 2023. 6(1): p. 402. 87.Wu, L., Li, X., Li, Z., Cheng, Y., Wu, F., Lv, C., Zhang, W., and Tang, W., HtrA serine proteases in cancers: A target of interest for cancer therapy. Biomedicine & Pharmacotherapy, 2021. 139: p. 111603. 88.Staudinger, L.A., Spano, S.J., Lee, W., Coelho, N., Rajshankar, D., Bendeck, M.P., Moriarty, T., and McCulloch, C.A., Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen. Biology Open, 2013. 2(11): p. 1148–1159. 89.Coelho, N.M., Arora, P.D., van Putten, S., Boo, S., Petrovic, P., Lin, A.X., Hinz, B., and McCulloch, C.A., Discoidin domain receptor 1 mediates myosin-dependent collagen contraction. Cell Reports, 2017. 18(7): p. 1774–1790. 90.Zeng, J., Zhang, J., Yang, Y.-Z., Wang, F., Jiang, H., Chen, H.-D., Wu, H.-Y., Sai, K., and Hu, W.-M., IL13RA2 is overexpressed in malignant gliomas and related to clinical outcome of patients. American Journal of Translational Research, 2020. 12(8): p. 4702. 91.Tu, M., Wange, W., Cai, L., Zhu, P., Gao, Z., and Zheng, W., IL-13 receptor α2 stimulates human glioma cell growth and metastasis through the Src/PI3K/Akt/mTOR signaling pathway. Tumor Biology, 2016. 37: p. 14701–14709. 92.Huang, G.-H., Du, L., Li, N., Zhang, Y., Xiang, Y., Tang, J.-H., Xia, S., Zhang, E.E., and Lv, S.-Q., Methylation-mediated miR-155-FAM133A axis contributes to the attenuated invasion and migration of IDH mutant gliomas. Cancer Letters, 2018. 432: p. 93–102. 93.Shi, T., Guo, D., Zheng, Y., Wang, W., Bi, J., He, A., Fan, S., Su, G., Zhao, X., and Zhao, Z., Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide. Cell Death & Disease, 2024. 15(1): p. 6. 94.Alves, A.L.V., Gomes, I.N., Carloni, A.C., Rosa, M.N., da Silva, L.S., Evangelista, A.F., Reis, R.M., and Silva, V.A.O., Role of glioblastoma stem cells in cancer therapeutic resistance: A perspective on antineoplastic agents from natural sources and chemical derivatives. Stem Cell Research & Therapy, 2021. 12: p. 1–22. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95104 | - |
| dc.description.abstract | 神經膠質母細胞瘤（GBM）是最常見也最具侵襲能力的成人原發性腦腫瘤。根據世界衛生組織（WHO）分級，神經膠質母細胞瘤被分類為第四級的成人型神經膠質細胞瘤，同時神經膠質母細胞瘤的浸潤和遷移也是導致高侵略性和難以治療的關鍵，因其具有浸潤並擴散到周圍腦組織的能力，經腫瘤經手術切除後，剩餘癌細胞仍可以遷移至附近的健康腦組織，即便進行合併放療和化療等積極的治療方法，患者的預後仍然不佳。因此迫切需要一種新的治療方法來治療神經膠質母細胞瘤。
盤狀結構域受體1（Discoidin Domain Receptor 1, DDR1）是以膠原蛋白作為配體的酪氨酸激酶。在多種癌症中，其異常表現增加會活化細胞內多個下游訊息傳遞，促進癌細胞的存活、增殖、貼附、遷移和細胞外基質重塑。在資料庫分析中，我們發現DDR1的表現量在神經膠質母細胞瘤顯著增加，為了研究DDR1在神經膠質母細胞瘤中扮演的角色，我們利用CRISPR/Cas9將神經膠質母細胞瘤細胞株的DDR1基因進行剔除，發現經DDR1剔除的細胞株顯著抑制了細胞增生與腫瘤生長的能力，同時我們使用RNA-seq分析DDR1剔除後所造成的基因富集差異，發現DDR1 影響細胞貼附及遷移的相關路徑，因此抑制DDR1可能是治療神經膠質母細胞瘤的新策略。 本論文中，我們設計並合成出喹唑啉衍生物作為新穎性DDR1抑制劑且於神經膠質母細胞瘤驗證其療效並詳細探討其相關作用機轉，其中PANDD083對於 DDR1 的抑制活性IC50為3.3 nM。在細胞試驗中，該化合物顯著抑制DDR1的作用並降低了癌細胞的增生、存活及遷移能力。另外在動物實驗中PANDD083也有效抑制了腫瘤細胞的生長，展現其抗腫瘤效果。作用機轉發現PANDD083 可藉由抑制 collagen I誘發的DDR1磷酸化並影響下游蛋白，減少Src及AKT/mTOR的活化，造成細胞週期停滯在G2/M並誘導細胞凋亡；此外，PANDD083會抑制HTRA1和HDAC6的表現量，進而影響癌細胞存活、生長及遷移。綜合以上結果，我們研究說明了DDR1可作為神經膠質母細胞瘤的一個新治療標的，也證實PANDD083在神經膠質母細胞瘤細胞的抗癌效果。 | zh_TW |
| dc.description.abstract | Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. According to the World Health Organization (WHO), GBM is categorized as Grade IV adult-type gliomas. The invasive and migratory capabilities of GBM cells are key factors contributing to their aggressiveness and treatment resistance, as remaining cancer cells can migrate even after surgical resection into surrounding healthy brain tissue. Despite aggressive treatments such as surgery, radiation therapy, and chemotherapy, the prognosis for patients remains poor. Therefore, there is an urgent need for a new treatment approach for GBM.
Discoidin Domain Receptor 1 (DDR1) is a type of receptor tyrosine kinase (RTK) binding to collagens as its ligand. The abnormal expression of DDR1 is implicated in various cancers, leading to the activation of several downstream signaling pathways that participate in cell survival, proliferation, adhesion, migration, and extracellular matrix remodeling. Database analysis has shown a significant increase in DDR1 expression in GBM. To investigate the role of DDR1 in GBM, we utilized CRISPR/Cas9 to knock out the DDR1 gene in the GBM cell line. We also found that DDR1 knockout significantly inhibited cell proliferation and tumor growth in animal models. Using NGS RNA-seq analysis, we identified significant gene enrichment differences caused by DDR1 knockout, particularly affecting cell adhesion and migration pathways. Therefore, inhibition of DDR1 may represent a novel strategy for treating GBM. In this study, we designed and synthesized a novel DDR1 inhibitor named PANDD083, a quinazoline derivative with an IC50 value of 3.3 nM. PANDD083 also significantly reduced DDR1 activity and inhibited cancer cell proliferation, survival, and migration. Additionally, in animal experiments, PANDD083 suppressed tumor cell growth, demonstrating its anti-tumor effects. Mechanistic studies revealed that PANDD083 inhibits collagen I-induced phosphorylation of DDR1 and affects its downstream proteins, reducing the activation of Src and AKT/mTOR pathways. This inhibition caused cell cycle arrest at the G2/M phase and induced apoptosis. Furthermore, PANDD083 inhibited the expression of HTRA1 and HDAC6, thereby impacting cancer cell survival, growth, and migration. In conclusion, we have developed a novel DDR1 inhibitor for treating GBM and investigated its relevant mechanisms of action. Collectively, our study suggests DDR1 as a novel therapeutic target for GBM and confirms the anti-cancer effects of PANDD083 in GBM cells. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-28T16:17:11Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-28T16:17:11Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iv Contents vi List of Figures ix List of Tables xi List of Abbreviations xii Chapter 1 Introduction 1 1.1 Glioblastoma (GBM) 1 1.2 Standard therapy for GBM 1 1.3 Infiltration and migration in GBM 2 1.4 Discoidin Domain Receptor (DDR) 3 1.4.1 DDR1 in cancers 4 1.4.2 DDR1 in GBM 5 1.4.3 Current DDR1 inhibitors 6 1.5 Purpose 7 Chapter 2 Materials and methods 16 2.1 Cell culture 16 2.2 Generation of DDR1 knockout U87 cells 16 2.3 Next-generation sequencing (NGS) 17 2.4 DDR1 inhibitors 18 2.5 BBB penetration assay 19 2.6 Cell viability and proliferation assay 19 2.7 Colony formation 20 2.8 Flow cytometry 20 2.9 RT-qPCR 21 2.10 Western Blot 21 2.11 Wound healing assay 22 2.12 Animal experiment 22 2.13 Data analysis and Statistics 24 Chapter 3 Results 25 3.1 Development of DDR1-KO U87cell line 25 3.2 NGS and enrichment analysis of DDR1-KO U87 versus parental U87 cells 26 3.3 Development of DDR1 inhibitors 26 3.4 PANDD083 exhibits anti-proliferation, cytotoxicity, and highly BBB penetration 27 3.5 Inhibition of DDR1 phosphorylation by PANDD083 28 3.6 Induction of cell cycle arrest and caspase-dependent apoptosis by PANDD083 29 3.7 PANDD083 inhibited cell migration 30 3.8 PANDD083 inhibited tumor growth in a xenograft model 32 3.9 PANDD083 inhibited tumor growth in an orthotopic xenograft model 33 Chapter 4 Discussion 57 Chapter 5 Conclusion 63 References 64 | - |
| dc.language.iso | en | - |
| dc.subject | 抑制劑 | zh_TW |
| dc.subject | 喹唑啉衍生物 | zh_TW |
| dc.subject | 神經膠質母細胞瘤 | zh_TW |
| dc.subject | inhibitor | en |
| dc.subject | quinazoline derivatives | en |
| dc.subject | glioblastoma | en |
| dc.title | 喹唑啉衍生物作為人類神經膠質母細胞瘤抗癌藥物之評估 | zh_TW |
| dc.title | Evaluation of quinazoline derivatives as anticancer agents for human glioblastoma | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 潘秀玲;許凱程;顧記華;許麗卿 | zh_TW |
| dc.contributor.oralexamcommittee | Shiow-Lin Pan;Kai-Cheng Hsu;Jih-Hwa Guh;Lih-Ching Hsu | en |
| dc.subject.keyword | 喹唑啉衍生物,神經膠質母細胞瘤,抑制劑, | zh_TW |
| dc.subject.keyword | quinazoline derivatives,glioblastoma,inhibitor, | en |
| dc.relation.page | 72 | - |
| dc.identifier.doi | 10.6342/NTU202402223 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-07-26 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 藥學研究所 | - |
| 顯示於系所單位： | 藥學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf 未授權公開取用 | 3.32 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。