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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐麗芬 | zh_TW |
| dc.contributor.advisor | Lie-Fen Shyur | en |
| dc.contributor.author | 沈安娜 | zh_TW |
| dc.contributor.author | Biljana Cvetanova | en |
| dc.date.accessioned | 2021-07-11T14:56:13Z | - |
| dc.date.available | 2024-12-01 | - |
| dc.date.copyright | 2020-03-13 | - |
| dc.date.issued | 2020 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Alsaab, H. O., Sau, S., Alzhrani, R., Tatiparti, K., Bhise, K., Kashaw, S. K., & Iyer, A. K. (2017). PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front Pharmacol, 8, 561. doi:10.3389/fphar.2017.00561
Azimi, A., Caramuta, S., Seashore‐Ludlow, B., Boström, J., Robinson, J. L., Edfors, F., et al. (2018). Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors. Molecular Systems Biology, 14(3), e7858. doi:10.15252/msb.20177858 Becker, M. R., Siegelin, M. D., Rompel, R., Enk, A. H., & Gaiser, T. (2009). COX-2 expression in malignant melanoma: a novel prognostic marker? Melanoma Res, 19(1), 8-16. doi:10.1097/CMR.0b013e32831d7f52 Berwick, M., Buller, D. B., Cust, A., Gallagher, R., Lee, T. K., Meyskens, F., et al. (2016). Melanoma Epidemiology and Prevention. Cancer Treat Res, 167, 17-49. doi:10.1007/978-3-319-22539-5_2 Berwick, M., MacArthur, J., Orlow, I., Kanetsky, P., Begg, C. B., Luo, L., et al. (2014). MITF E318K's effect on melanoma risk independent of, but modified by, other risk factors. Pigment Cell Melanoma Res, 27(3), 485-488. doi:10.1111/pcmr.12215 Cerezo, M., Lehraiki, A., Millet, A., Rouaud, F., Plaisant, M., Jaune, E., et al. (2016). Compounds Triggering ER Stress Exert Anti-Melanoma Effects and Overcome BRAF Inhibitor Resistance. Cancer Cell, 29(6), 805-819. doi:10.1016/j.ccell.2016.04.013 Cerezo, M., & Rocchi, S. (2017). New anti-cancer molecules targeting HSPA5/BIP to induce endoplasmic reticulum stress, autophagy and apoptosis. Autophagy, 13(1), 216-217. doi:10.1080/15548627.2016.1246107 Chan, C. K., Chan, G., Awang, K., & Abdul Kadir, H. (2016). Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest. Molecules, 21(3), 385. doi:10.3390/molecules21030385 Chao, W. W., Cheng, Y. W., Chen, Y. R., Lee, S. H., Chiou, C. Y., & Shyur, L. F. (2019). Phyto-sesquiterpene lactone deoxyelephantopin and cisplatin synergistically suppress lung metastasis of B16 melanoma in mice with reduced nephrotoxicity. Phytomedicine, 56, 194-206. doi:10.1016/j.phymed.2018.11.005 Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., et al. (2011). Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med, 364(26), 2507-2516. doi:10.1056/NEJMoa1103782 Cheng, Y. T., Yang, C. C., & Shyur, L. F. (2016). Phytomedicine-Modulating oxidative stress and the tumor microenvironment for cancer therapy. Pharmacol Res, 114, 128-143. doi:10.1016/j.phrs.2016.10.022 Chiang, Y. M., Lo, C. P., Chen, Y. P., Wang, S. Y., Yang, N. S., Kuo, Y. H., & Shyur, L. F. (2005). Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin. Br J Pharmacol, 146(3), 352-363. doi:10.1038/sj.bjp.0706343 Cochran, A. J., Huang, R. R., Lee, J., Itakura, E., Leong, S. P., & Essner, R. (2006). Tumour-induced immune modulation of sentinel lymph nodes. Nat Rev Immunol, 6(9), 659-670. doi:10.1038/nri1919 Corcoran, R. B., Rothenberg, S. M., Hata, A. N., Faber, A. C., Piris, A., Nazarian, R. M., et al. (2013). TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma. Sci Transl Med, 5(196), 196ra198. doi:10.1126/scitranslmed.3005753 Crawford, A. B., Nessim, C., Weaver, J., & van Walraven, C. (2018). Wait Times for Melanoma Surgery: Is There an Association with Overall Survival? Ann Surg Oncol, 25(1), 265-270. doi:10.1245/s10434-017-6146-2 Damsky, W. E., & Bosenberg, M. (2017). Melanocytic nevi and melanoma: unraveling a complex relationship. Oncogene, 36(42), 5771-5792. doi:10.1038/onc.2017.189 Delyon, J., Lebbe, C., & Dumaz, N. (2019). Targeted therapies in melanoma beyond BRAF: targeting NRAS-mutated and KIT-mutated melanoma. Curr Opin Oncol. doi:10.1097/CCO.0000000000000606 DePinto, W., Chu, X. J., Yin, X., Smith, M., Packman, K., Goelzer, P., et al. (2006). In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol Cancer Ther, 5(11), 2644-2658. doi:10.1158/1535-7163.MCT-06-0355 Duggan, M. C., Stiff, A. R., Bainazar, M., Regan, K., Olaverria Salavaggione, G. N., Maharry, S., et al. (2017). Identification of NRAS isoform 2 overexpression as a mechanism facilitating BRAF inhibitor resistance in malignant melanoma. Proc Natl Acad Sci U S A, 114(36), 9629-9634. doi:10.1073/pnas.1704371114 Eggermont, A. M. M., Spatz, A., & Robert, C. (2014). Cutaneous melanoma. The Lancet, 383(9919), 816-827. doi:10.1016/s0140-6736(13)60802-8 Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol., 35(4), 495-516. doi: 10.1080/01926230701320337 Enninga, E. A. L., Moser, J. C., Weaver, A. L., Markovic, S. N., Brewer, J. D., Leontovich, A. A., et al. (2017). Survival of cutaneous melanoma based on sex, age, and stage in the United States, 1992-2011. Cancer Med, 6(10), 2203-2212. doi:10.1002/cam4.1152 Farha, A. K., Dhanya, S. R., Mangalam, S. N., Geetha, B. S., Latha, P. G., & Remani, P. (2014). Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways. Cell Biol Toxicol, 30(6), 331-343. doi:10.1007/s10565-014-9288-z Feng, J. H., Nakagawa-Goto, K., Lee, K. H., & Shyur, L. F. (2016). A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice. Mol Cancer Ther, 15(6), 1163-1176. doi:10.1158/1535-7163.mct-15-0973 Gach, K., Dlugosz, A., & Janecka, A. (2015). The role of oxidative stress in anticancer activity of sesquiterpene lactones. Naunyn Schmiedebergs Arch Pharmacol, 388(5), 477-486. doi:10.1007/s00210-015-1096-3 Georgieva, J., Sinha, P., & Schadendorf, D. (2001). Expression of cyclins and cyclin dependent kinases in human benign and malignant melanocytic lesions. J Clin Pathol, 54(3), 229-235. Ghantous, A., Gali-Muhtasib, H., Vuorela, H., Saliba, N. A., & Darwiche, N. (2010). What made sesquiterpene lactones reach cancer clinical trials? Drug Discov Today, 15(15-16), 668-678. doi:10.1016/j.drudis.2010.06.002 Giglio, P., Fimia, G. M., Lovat, P. E., Piacentini, M., & Corazzari, M. (2015). Fateful music from a talented orchestra with a wicked conductor: Connection between oncogenic BRAF, ER stress, and autophagy in human melanoma. Mol Cell Oncol, 2(3), e995016. doi:10.4161/23723556.2014.995016 Gong, H. Z., Zheng, H. Y., & Li, J. (2018). The clinical significance of KIT mutations in melanoma: a meta-analysis. Melanoma Res, 28(4), 259-270. doi:10.1097/cmr.0000000000000454 Gorrini, C., Harris, I. S., & Mak, T. W. (2013). Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov, 12(12), 931-947. doi:10.1038/nrd4002 Heinzerling, L., Kuhnapfel, S., Meckbach, D., Baiter, M., Kaempgen, E., Keikavoussi, P., et al. (2013). Rare BRAF mutations in melanoma patients: implications for molecular testing in clinical practice. Br J Cancer, 108(10), 2164-2171. doi:10.1038/bjc.2013.143 Hsan, K. M., Chen, C. C., & Shyur, L. F. (2010). Current research and development of chemotherapeutic agents for melanoma. Cancers (Basel), 2(2), 397-419. doi:10.3390/cancers2020397 Huang, C.-C., Lin, K.-J., Cheng, Y.-W., Hsu, C.-A., Yang, S.-S., & Shyur, L.-F. (2013). Hepatoprotective effect and mechanistic insights of deoxyelephantopin, a phyto-sesquiterpene lactone, against fulminant hepatitis. The Journal of Nutritional Biochemistry, 24(3), 516-530. doi:10.1016/j.jnutbio.2012.01.013 Huang, C. C., Lo, C. P., Chiu, C. Y., & Shyur, L. F. (2010). Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice. Br J Pharmacol, 159(4), 856-871. doi:10.1111/j.1476-5381.2009.00581.x Jafarian, A. H., Mohamadian Roshan, N., Gharib, M., Moshirahmadi, V., Tasbandi, A., Ayatollahi, A. A., & Ayatollahi, H. (2019). Evaluation of Cyclooxygenase-2 Expression in Association with Clinical-Pathological Factors in Malignant Melanoma. Iran J Pathol, 14(2), 96-103. doi:10.30699/IJP.14.2.96 Jiang, R., Dong, J., Li, X., Du, F., Jia, W., Xu, F., et al.. (2015). Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3. Br J Pharmacol, 172(4), 1059-1073. doi:10.1111/bph.12971 Jie Huang Du, L. Z., Xuehua Chen, Changyu He, Yingyan Yu, Ying Qu, Bingya Liu, Jianfang Li, Jianian Zhang and Zhenggang Zhu. (2014). Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer. Oncotarget, 6(3), 1652–1665. doi:doi: 10.18632/oncotarget.2936 Joseph, E. W., Pratilas, C. A., Poulikakos, P. I., Tadi, M., Wang, W., Taylor, B. S., et al. (2010). The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner. Proc Natl Acad Sci U S A, 107(33), 14903-14908. doi:10.1073/pnas.1008990107 Kabeer, F. A., Rajalekshmi, D. S., Nair, M. S., & Prathapan, R. (2017). Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells. Integr Med Res, 6(2), 190-206. doi:10.1016/j.imr.2017.03.004 Kalyanaraman, B., Cheng, G., Hardy, M., Ouari, O., Bennett, B., & Zielonka, J. (2018). Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies. Redox Biol, 15, 347-362. doi:10.1016/j.redox.2017.12.012 Katz, L., & Baltz, R. H. (2016). Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol, 43(2-3), 155-176. doi:10.1007/s10295-015-1723-5 Khazir, J., Mir, B. A., Pilcher, L., & Riley, D. L. (2014). Role of plants in anticancer drug discovery. Phytochemistry Letters, 7, 173-181. doi:10.1016/j.phytol.2013.11.010 Kim, J., & Bae, J. S. (2016). Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment. Mediators Inflamm, 2016, 6058147. doi:10.1155/2016/6058147 Klionsky, D. J. (2007). Autophagy: from phenomenology to molecular understanding in less than a decade. Nature Reviews Molecular Cell Biology, 8(11), 931-937. doi:10.1038/nrm2245 Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., et al. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1), 1-222. doi:10.1080/15548627.2015.1100356 Kurimoto, S.-I., Kashiwada, Y., Lee, K.-H., & Takaishi, Y. (2011). Triterpenes and a triterpene glucoside from Dysoxylum cumingianum. Phytochemistry, 72(17), 2205-2211. doi:10.1016/j.phytochem.2011.08.002 Lagoutte, R., Serba, C., Abegg, D., Hoch, D. G., Adibekian, A., & Winssinger, N. (2016). Divergent synthesis and identification of the cellular targets of deoxyelephantopins. Nat Commun, 7, 12470. doi:10.1038/ncomms12470 Lee, K.-H., Cowherd, C. M., & Wolo, M. T. (1975). Antitumor agents. XV: Deoxyelephantopin, an antitumor principle from Elephantopus carolinianus Willd. J Pharm Sci, 64(9), 1572-1573. doi:10.1002/jps.2600640938 Lee, W. L., & Shyur, L. F. (2012). Deoxyelephantopin impedes mammary adenocarcinoma cell motility by inhibiting calpain-mediated adhesion dynamics and inducing reactive oxygen species and aggresome formation. Free Radic Biol Med, 52(8), 1423-1436. doi:10.1016/j.freeradbiomed.2012.01.020 Leotlela, P. D., Wade, M. S., Duray, P. H., Rhode, M. J., Brown, H. F., Rosenthal, D. T., et al. (2007). Claudin-1 overexpression in melanoma is regulated by PKC and contributes to melanoma cell motility. Oncogene, 26(26), 3846-3856. doi:10.1038/sj.onc.1210155 Lesiak, K., Koprowska, K., Zalesna, I., Nejc, D., Duchler, M., & Czyz, M. (2010). Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro. Melanoma Res, 20(1), 21-34. doi:10.1097/CMR.0b013e328333bbe4 Li, X., Zhu, H., Huang, H., Jiang, R., Zhao, W., Liu, Y., et al. (2012). Study on the effect of IRE1a on cell growth and apoptosis via modulation PLK1 in ER stress response. Mol Cell Biochem, 365(1-2), 99-108. doi:10.1007/s11010-012-1248-4 Lim, S. Y., Menzies, A. M., & Rizos, H. (2017). Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma. Cancer, 123(S11), 2118-2129. doi:10.1002/cncr.30435 Linares, M. A., Zakaria, A., & Nizran, P. (2015). Skin Cancer. Prim Care, 42(4), 645-659. doi:10.1016/j.pop.2015.07.006 Lito, P., Pratilas, C. A., Joseph, E. W., Tadi, M., Halilovic, E., Zubrowski, M., et al. (2012). Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell, 22(5), 668-682. doi:10.1016/j.ccr.2012.10.009 Liu, J., & Debnath, J. (2016). The Evolving, Multifaceted Roles of Autophagy in Cancer. Adv Cancer Res, 130, 1-53. doi:10.1016/bs.acr.2016.01.005 Liu, Z., Liu, S., Xie, Z., Pavlovicz, R. E., Wu, J., Chen, P., et al. (2009). Modulation of DNA methylation by a sesquiterpene lactone parthenolide. J Pharmacol Exp Ther, 329(2), 505-514. doi:10.1124/jpet.108.147934 Luan, Q., Jin, L., Jiang, C. C., Tay, K. H., Lai, F., Liu, X. Y., et al. (2015). RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy. Autophagy, 11(7), 975-994. doi:10.1080/15548627.2015.1049800 Luo, H., Vong, C. T., Chen, H., Gao, Y., Lyu, P., Qiu, L., et al. (2019). Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine. Chin Med, 14, 48. doi:10.1186/s13020-019-0270-9 Martin, S., Dudek-Peric, A. M., Garg, A. D., Roose, H., Demirsoy, S., Van Eygen, S., et al. (2017). An autophagy-driven pathway of ATP secretion supports the aggressive phenotype of BRAFV600E inhibitor-resistant metastatic melanoma cells. Autophagy, 13(9), 1512-1527. doi:10.1080/15548627.2017.1332550 Masaki, T., Wang, Y., DiGiovanna, J. J., Khan, S. G., Raffeld, M., Beltaifa, S., et al. (2014). High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients. Pigment Cell Melanoma Res, 27(3), 454-464. doi:10.1111/pcmr.12226 Maio, M. (2012). Melanoma as a model tumour for immuno-oncology. Ann Oncol, 23 Suppl 8, viii10-14. doi:10.1093/annonc/mds257 Meitzler, J. L., Antony, S., Wu, Y., Juhasz, A., Liu, H., Jiang, G., et al. (2014). NADPH oxidases: a perspective on reactive oxygen species production in tumor biology. Antioxid Redox Signal, 20(17), 2873-2889. doi:10.1089/ars.2013.5603 Menzies, A. M., & Long, G. V. (2014). Systemic treatment for BRAF-mutant melanoma: where do we go next? The Lancet Oncology, 15(9), e371-e381. doi:10.1016/s1470-2045(14)70072-5 Meyskens, F. L., & Yang, S. (2011). Thinking about the role (largely ignored) of heavy metals in cancer prevention: hexavalent chromium and melanoma as a case in point. Recent Results Cancer Res, 188, 65-74. doi:10.1007/978-3-642-10858-7_5 Michaelis, M., Rothweiler, F., Nerreter, T., van Rikxoort, M., Zehner, R., Dirks, W. G., et al. (2014). Association between acquired resistance to PLX4032 (vemurafenib) and ATP-binding cassette transporter expression. BMC Res Notes, 7, 710. doi:10.1186/1756-0500-7-710 Mishra, H., Mishra, P. K., Ekielski, A., Jaggi, M., Iqbal, Z., & Talegaonkar, S. (2018). Melanoma treatment: from conventional to nanotechnology. J Cancer Res Clin Oncol, 144(12), 2283-2302. doi:10.1007/s00432-018-2726-1 Moosavi, M. A., Haghi, A., Rahmati, M., Taniguchi, H., Mocan, A., Echeverria, J., et al. (2018). Phytochemicals as potent modulators of autophagy for cancer therapy. Cancer Lett, 424, 46-69. doi:10.1016/j.canlet.2018.02.030 Nakagawa-Goto, K., Chen, J. Y., Cheng, Y. T., Lee, W. L., Takeya, M., Saito, Y., et al. (2016). Novel sesquiterpene lactone analogues as potent anti-breast cancer agents. Mol Oncol, 10(6), 921-937. doi:10.1016/j.molonc.2016.03.002 Nakhjavani, M., Hardingham, J. E., Palethorpe, H. M., Tomita, Y., Smith, E., Price, T. J., & Townsend, A. R. (2019). Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer. Medicines (Basel), 6(1). doi:10.3390/medicines6010017 Newman, D. J., & Cragg, G. M. (2016). Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod, 79(3), 629-661. doi:10.1021/acs.jnatprod.5b01055 Ouyang, L., Shi, Z., Zhao, S., Wang, F. T., Zhou, T. T., Liu, B., & Bao, J. K. (2012). Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif, 45(6), 487-498. doi:10.1111/j.1365-2184.2012.00845.x DeSimone, P., Valiante, M., & Silipo, V. (2017). Familial melanoma and multiple primary melanoma. G Ital Dermatol Venereol, 152(3), 262-265. doi:10.23736/s0392-0488.17.05554-7 Pasquali, E., Garcia-Borron, J. C., Fargnoli, M. C., Gandini, S., Maisonneuve, P., Bagnardi, V., et al. (2015). MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. Int J Cancer, 136(3), 618-631. doi:10.1002/ijc.29018 Patrick, R. J., Fenske, N. A., & Messina, J. L. (2007). Primary mucosal melanoma. J Am Acad Dermatol, 56(5), 828-834. doi:10.1016/j.jaad.2006.06.017 Podolak, I., Galanty, A., & Sobolewska, D. (2010). Saponins as cytotoxic agents: a review. Phytochem Rev, 9(3), 425-474. doi:10.1007/s11101-010-9183-z Potrony, M., Badenas, C., Aguilera, P., Puig-Butille, J. A., Carrera, C., Malvehy, J., & Puig, S. (2015). Update in genetic susceptibility in melanoma. Ann Transl Med, 3(15), 210. doi:10.3978/j.issn.2305-5839.2015.08.11 Prakash, O., Kumar, A., Kumar, P., & Ajeet, A. (2013). Anticancer Potential of Plants and Natural Products: A Review. American Journal of Pharmacological Sciences, 1(6), 104-115. doi:10.12691/ajps-1-6-1 Puthalakath, H., O'Reilly, L. A., Gunn, P., Lee, L., Kelly, P. N., Huntington, N. D., et al. (2007). ER stress triggers apoptosis by activating BH3-only protein Bim. Cell, 129(7), 1337-1349. doi:10.1016/j.cell.2007.04.027 Rashid, H. O., Yadav, R. K., Kim, H. R., & Chae, H. J. (2015). ER stress: Autophagy induction, inhibition and selection. Autophagy, 11(11), 1956-1977. doi:10.1080/15548627.2015.1091141 Ribas, A. (2015). Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discov, 5(9), 915-919. doi:10.1158/2159-8290.CD-15-0563 Rizos, H., Menzies, A. M., Pupo, G. M., Carlino, M. S., Fung, C., Hyman, J., et al. (2014). BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res, 20(7), 1965-1977. doi:10.1158/1078-0432.CCR-13-3122 Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., et al (2011). Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med, 364(26), 2517-2526. doi:10.1056/NEJMoa1104621 Schadendorf, D., Fisher, D. E., Garbe, C., Gershenwald, J. E., Grob, J. J., Halpern, A., et al. (2015). Melanoma. Nat Rev Dis Primers, 1, 15003. doi:10.1038/nrdp.2015.3 Schadendorf, D., van Akkooi, A. C. J., Berking, C., Griewank, K. G., Gutzmer, R., Hauschild, A., et al. (2018). Melanoma. Lancet, 392(10151), 971-984. doi:10.1016/s0140-6736(18)31559-9 Schonthal, A. H. (2012). Endoplasmic reticulum stress: its role in disease and novel prospects for therapy. Scientifica (Cairo), 2012, 857516. doi:10.6064/2012/857516 Schumacker, P. T. (2006). Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell, 10(3), 175-176. doi:10.1016/j.ccr.2006.08.015 Shain, A. H., & Bastian, B. C. (2016). From melanocytes to melanomas. Nat Rev Cancer, 16(6), 345-358. doi:10.1038/nrc.2016.37 Sharma, K., Ishaq, M., Sharma, G., Khan, M. A., Dutta, R. K., & Majumdar, S. (2016). Pentoxifylline triggers autophagy via ER stress response that interferes with Pentoxifylline induced apoptosis in human melanoma cells. Biochem Pharmacol, 103, 17-28. doi:10.1016/j.bcp.2015.12.018 Shiau, J. Y., Chang, Y. Q., Nakagawa-Goto, K., Lee, K. H., & Shyur, L. F. (2017). Phytoagent Deoxyelephantopin and Its Derivative Inhibit Triple Negative Breast Cancer Cell Activity through ROS-Mediated Exosomal Activity and Protein Functions. Front Pharmacol, 8, 398. doi:10.3389/fphar.2017.00398 Shiau, J. Y., Nakagawa-Goto, K., Lee, K. H., & Shyur, L. F. (2017). Phytoagent deoxyelephantopin derivative inhibits triple negative breast cancer cell activity by inducing oxidative stress-mediated paraptosis-like cell death. Oncotarget, 8(34), 56942-56958. doi:10.18632/oncotarget.18183 Kurimoto, S.I., Kashiwada, Y., Morris-Natschke, S.L., Lee, K.H., & Takaishi, Y. (2011). Dyscusins A-C, three new steroids from the leaves of Dysoxylum cumingianum. Chemical and Pharmaceutical Bullitin, 59(10), 1303-1306. Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA Cancer J Clin, 69(1), 7-34. doi:10.3322/caac.21551 Singh, S., Davis, R., Alamanda, V., Pireddu, R., Pernazza, D., Sebti, S., et al. (2010). Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine. Mol Cancer Ther, 9(12), 3330-3341. doi:10.1158/1535-7163.MCT-10-0442 Smalley, K. S., Lioni, M., Dalla Palma, M., Xiao, M., Desai, B., Egyhazi, S., et al. (2008). Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther, 7(9), 2876-2883. doi:10.1158/1535-7163.MCT-08-0431 Soura, E., Eliades, P. J., Shannon, K., Stratigos, A. J., & Tsao, H. (2016). Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling. J Am Acad Dermatol, 74(3), 411-420; quiz 421-412. doi:10.1016/j.jaad.2015.08.037 Sun, M., Ye, Y., Xiao, L., Duan, X., Zhang, Y., & Zhang, H. (2017). Anticancer effects of ginsenoside Rg3 (Review). Int J Mol Med, 39(3), 507-518. doi:10.3892/ijmm.2017.2857 Tarhini, A. A., Zahoor, H., Yearley, J. H., Gibson, C., Rahman, Z., Dubner, R., et al. (2015). Tumor associated PD-L1 expression pattern in microscopically tumor positive sentinel lymph nodes in patients with melanoma. J Transl Med, 13, 319. doi:10.1186/s12967-015-0678-7 Tentori, L., Lacal, P. M., & Graziani, G. (2013). Challenging resistance mechanisms to therapies for metastatic melanoma. Trends Pharmacol Sci, 34(12), 656-666. doi:10.1016/j.tips.2013.10.003 Topalian, S. L., Sznol, M., McDermott, D. F., Kluger, H. M., Carvajal, R. D., Sharfman, W. H., et al. (2014). Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol, 32(10), 1020-1030. doi:10.1200/JCO.2013.53.0105 Toshihiro, F., Mihashi, K., Kashiwada, Y., Chen, I.S., & Lee, K.H. (1997a). Antitumor agents. 168. Dysoxylum cumingianum. 4. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines. Chemical and Pharmaceutical Bullitin, 45(1), 68-74. Toshihiro, F., Mihashi, K., Kashiwada, Y., Chen, I.S., & Lee, K.H. (1997b). Antitumor agents. 169. Dysoxylum cumingianum. 5. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum. Chemical and Pharmaceutical Bullitin, 45(1), 202-206. Tsai, J., Lee, J. T., Wang, W., Zhang, J., Cho, H., Mamo, S., et al. (2008). Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A, 105(8), 3041-3046. doi:10.1073/pnas.0711741105 Varghese, F., Bukhari, A. B., Malhotra, R., & De, A. (2014). IHC Profiler: an open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS One, 9(5), e96801. doi:10.1371/journal.pone.0096801 Verfaillie, T., Garg, A. D., & Agostinis, P. (2013). Targeting ER stress induced apoptosis and inflammation in cancer. Cancer Lett, 332(2), 249-264. doi:10.1016/j.canlet.2010.07.016 Vermeulen, K., Van Bockstaele, D. R., & Berneman, Z. N. (2003). The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Proliferation, 36(3), 131-149. doi:DOI 10.1046/j.1365-2184.2003.00266.x Wagle, N., Van Allen, E. M., Treacy, D. J., Frederick, D. T., Cooper, Z. A., Taylor-Weiner, A., et al. (2014). MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov, 4(1), 61-68. doi:10.1158/2159-8290.CD-13-0631 Wai-Leng Lee, T.-N. W., Jeng-Yuan Shiau, and Lie-Fen Shyur. (2010). Differential Proteomic Profiling Identifies Novel Molecular Targets of Paclitaxel and Phytoagent Deoxyelephantopin against Mammary Adenocarcinoma Cells. Journal of Proteome Research, 9, 237-253. doi.org/10.1021/pr900543e Wang, X., Chen, L., Wang, T., Jiang, X., Zhang, H., Li, P., et al. (2015). Ginsenoside Rg3 antagonizes adriamycin-induced cardiotoxicity by improving endothelial dysfunction from oxidative stress via upregulating the Nrf2-ARE pathway through the activation of akt. Phytomedicine, 22(10), 875-884. doi:10.1016/j.phymed.2015.06.010 Weber, J., Mandala, M., Del Vecchio, M., Gogas, H. J., Arance, A. M., Cowey, C. L., et al. (2017). Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med, 377(19), 1824-1835. doi:10.1056/NEJMoa1709030 Wu, S., Han, J., Laden, F., & Qureshi, A. A. (2014). Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: a cohort study. Cancer Epidemiol Biomarkers Prev, 23(6), 1080-1089. doi:10.1158/1055-9965.epi-13-0821 Wu, S., Han, J., Vleugels, R. A., Puett, R., Laden, F., Hunter, D. J., & Qureshi, A. A. (2014). Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women. Br J Cancer, 110(7), 1855-1861. doi:10.1038/bjc.2014.43 Xu, T., Ding, W., Ji, X., Ao, X., Liu, Y., Yu, W., & Wang, J. (2019). Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med, 23(8), 4900-4912. doi:10.1111/jcmm.14511 Xu, W., & McArthur, G. (2016). Cell Cycle Regulation and Melanoma. Curr Oncol Rep, 18(6), 34. doi:10.1007/s11912-016-0524-y Yoshiki, K., Chang, J.J, Chen, I.S., Mihashi, K., & Lee, K.H. (1992). Antitumor agents. 136. Cumingianosides A-F, potent antileukemic new triterpene glucosides, and cumindysoside-A and cumindysoside-B, trisnortriterpene and tetranortriterpene glucosides with a 14,18-cycloapoeuphane-type skeleton from Dysoxylum cumingianum. Journal of Organic Chemistry, 57, 6946-6953. Yoshiki, K., Mihashi, K., Chen, I.S, Katayama, H., & Lee, K.H.. (1997). Antitumor Agents. 180.1 Chemical Studies and Cytotoxic Evaluation of Cumingianosides and Cumindysoside A, Antileukemic Triterpene Glucosides with a 14,18-Cycloapotirucallane Skeleton. Journal of Natural Products, 60, 1105-1114. Yoshinaga, S., Mabuchi, K., Sigurdson, A. J., Doody, M. M., & Ron, E. (2004). Cancer risks among radiologists and radiologic technologists: review of epidemiologic studies. Radiology, 233(2), 313-321. doi:10.1148/radiol.2332031119 Zhang, H., Nakajima, S., Kato, H., Gu, L., Yoshitomi, T., Nagai, K., et al. (2013). Selective, potent blockade of the IRE1 and ATF6 pathways by 4-phenylbutyric acid analogues. Br J Pharmacol, 170(4), 822-834. doi:10.1111/bph.12306 Zhang, M., Qureshi, A. A., Geller, A. C., Frazier, L., Hunter, D. J., & Han, J. (2012). Use of tanning beds and incidence of skin cancer. J Clin Oncol, 30(14), 1588-1593. doi:10.1200/jco.2011.39.3652 Zhang, Q., Kang, X., Yang, B., Wang, J., & Yang, F. (2008). Antiangiogenic effect of capecitabine combined with ginsenoside Rg3 on breast cancer in mice. Cancer Biother Radiopharm, 23(5), 647-653. doi:10.1089/cbr.2008.0532 Zou, G., Gao, Z., Wang, J., Zhang, Y., Ding, H., Huang, J., et al. (2008). Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARgamma. Biochem Pharmacol, 75(6), 1381-1392. doi:10.1016/j.bcp.2007.11.021 Zou, J., Zhang, Y., Sun, J., Wang, X., Tu, H., Geng, S., et al. (2017). Deoxyelephantopin Induces Reactive Oxygen Species-Mediated Apoptosis and Autophagy in Human Osteosarcoma Cells. Cell Physiol Biochem, 42(5), 1812-1821. doi:10.1159/000479537 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78423 | - |
| dc.description.abstract | 突變的原癌基因BRAF為治療黑色素瘤藥物之標的。可惜的是，黑色素瘤對BRAF抑制劑藥物如vemurafenib (PLX4032) 所產生的抗藥性使得此一標靶治療策略受到質疑，因而目前帶有BRAF突變基因的轉移性黑色素瘤的治療目前仍是一大挑戰，且對於能夠耐久的藥物反應或是減緩標靶藥物副作用的新穎治療策略仍有迫切需求。本論文旨在探討皂素cumingianoside A (CUMA)、倍半萜內酯DET及其半有機合成衍生物DETD-35針對抗PLX4032之BRAF突變黑色素瘤或轉移性黑色素瘤的抑制效果，並了解背後的分子機制。首先，我們建立從楝科(Meliaceae) 蘭嶼樫木 (Dysoxylum cumingianum) 葉子及枝條萃取三萜類皂素CUMA的方法，並探討CUMA在活體內及細胞實驗中抑制抗PLX4032之BRAF突變黑色素瘤細胞(A375-R)的活性。
我們的結果顯示CUMA處理能夠抑制A375-R生長，且此活性隨CUMA濃度與處理時間增加。CUMA亦能抑制A375-R細胞中CDK1/cyclin B1的表現而造成細胞生長週期G2/M期的停滯。再者，CUMA能夠透過增進caspase 3及caspase 7的活性和PARP的水解促進細胞凋亡。我們也觀察到CUMA會在A375-R誘發類細胞自噬，其中包含自噬相關的基因表現上升以及自噬小體的生成。我們更發現CUMA會誘發細胞內質網壓力，且與內質網壓力抑制劑(4-PBA)共同處理A375-R細胞時能夠延緩細胞的凋亡。更重要的是，在異種移植的抗PLX4032之BRAF突變黑色素瘤小鼠模式中，不管是以口服方式給予單一處理CUMA或是共同給予CUMA與PLX4032皆能在不影響正常器官的狀況下有效抑制腫瘤生長。本論文是第一篇探討CUMA在活體內及體外試驗中抗黑色素瘤活性及機制的研究，儘管仍需更進一步的研究，我們目前的結果顯示開發此三萜類皂素做為抗癌藥物的潛。 在我們研究室先前利用同一異種移植的BRAF突變且抗PLX4032之黑色素瘤小鼠 模式中，從菊科 (Asteraceae) 草藥地膽草 (Elephantopus scaber L.) 所萃取出的DET及其衍生物DETD-35能夠增進抗PLX4032腫瘤對PLX4032的敏感性。另外，DET及DETD-35能夠在異種移植小鼠模式中抑制A375LM5IF4g/Luc黑色素瘤細胞的肺轉移。本論文活體試驗結果研究DET及DETD-35抑制黑色素瘤肺轉移活性的相關機轉。我們發現自由基螯合劑N-acetylcysteine (NAC)的預處理能夠壓制DET及DETD-35所誘發的細胞毒性及細胞凋亡。再者，DET及DETD-35能夠破壞A375LM5IF4g/Luc細胞的粒線體構形並導致粒線體功能喪失。更重要的是，DET及DETD-35能抑制轉移相關的分子標記N-cadherin 的表現量，而在NAC預處理後，能阻斷此現象，且在肺轉移密切相關的分子標記integrin 4亦可觀察到表現量下降，但NAC僅稍微阻斷。我們在細胞實驗觀察到DET及DETD-35的抗轉移活性也在活體試驗結果得到證實，其中包含在DET及DETD-35處理後的小鼠黑色素瘤轉移之肺臟組織觀察到N-cadherin的減少，以及細胞緊密連接蛋白claudin-1和ZO-1及血管新生標記CD31的表現量顯著減少。DET及DETD-35並抑制腫瘤細胞在肺臟所引發的巨噬細胞及嗜中性白血球的浸潤。DET及DETD-35的免疫調節潛力也能夠透過減低的肺臟組織中COX-2及PD-L1表現量受到證實。本研究揭露了DET及DETD-35抑制肺轉移黑色素瘤的活性，其中一部分是透過影響活性氧類相關的細胞凋亡、轉移型態的調控以及肺腫瘤微環境的調節。 總結來說，此篇論文所研究的內容揭露了植物皂素CUMA及倍半萜內酯DET/DETD-35被開發做為抑制黑色素瘤藥物的潛力。 | zh_TW |
| dc.description.abstract | Mutated proto-oncogene BRAF is a bona fide therapeutic target for melanomas. Regrettably, melanoma acquires resistance to BRAF inhibitors, e.g., vemurafenib (PLX4032) casting doubt on this promising melanoma targeted therapy. BRAF-mutant metastatic melanoma is still challenging and new treatment modalities for advanced melanoma patients are of urgent need to elicit durable response or minimize current adverse effects in therapy. The objective of this dissertation was to investigate the anti-melanoma effect of phyto-saponin cumingianoside A (CUMA) and phyto-sesquiterpene lactone DET and its semi-synthetic derivative DETD-35 against BRAF-mutant PLX4032-resistant or metastatic melanoma, and to explore the molecular mechanisms.
First, in this study we established the protocol to isolate triterpenoid saponin (CUMA) from the leaves and twigs of Dysoxylum cumingianum (Meliaceae) and addressed CUMA effect against PLX4032-resistant BRAFV600E mutant melanoma A375-R in vitro and in vivo. Our data showed that CUMA treatment inhibited A375-R melanoma cell proliferation in a time- and dose-dependent manner. CUMA also suppressed the expression of CDK1/cyclin B1 complex and led to G2/M-phase arrest of A375-R cells. Furthermore, CUMA treatment resulted in induction of apoptosis as shown by the increased activation of caspase 3 and caspase 7, and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). We also observed that CUMA induced autophagy-like activity in A375-R cells, as shown by the increased expression of autophagy-related genes and increased formation of autophagosomes. Moreover, we found that CUMA treatment induced ER stress response and co-treatment with an ER stress inhibitor (4-PBA) could attenuate apoptosis induced by CUMA. Notably, orally administered CUMA as a single agent or in combination with PLX4032 exhibited strong tumor growth inhibition in a PLX4032-resistant A375-R xenograft mouse model, and with little toxicity to organs. This is the first report to explore the anti-melanoma activity of CUMA in vitro and in vivo mechanistically, and albeit further research is required, our results imply that this triterpenoid saponin may be suitable for further research and development. Our lab demonstrated previously that DET isolated from the medicinal herb Elephantopus scaber L. (Asteraceae) and DETD-35 overcome PLX4032 acquired resistance and sensitized PLX4032 in the same xenograft mouse model. Also, DET and DETD-35 significantly suppressed the metastatic potential of A375LM5IF4g/Luc lung-seeking melanoma cells in xenograft mice. As a continuing work, the mechanisms underlying the anti-metastatic activities of DET and DETD-35 against A375LM5IF4g/Luc cells were explored. We observed that pretreatment with ROS scavenger N-acetylcysteine (NAC) blunted DET- and DETD-35 induced cytotoxicity and apoptosis in cells. Moreover, DET and DETD-35 impaired A375LM5IF4g/Luc mitochondrial integrity and caused mitochondrial bioenergetic dysfunction. Furthermore, DET- and DETD-35-treatment lead to down-regulation of EMT-related marker N-cadherin which expression was reversed to the basal level by NAC pretreatment. The level of lung specific metastasis marker integrin 4 was also decreased by both compounds and partially reversed by NAC pretreatment. The anti-metastatic properties of DET and DETD-35 observed in vitro were supported by the decreased N-cadherin expression levels in melanoma metastatic lung tissues of mice treated with DET and DETD-35. Significant decrease in the levels of tight junction proteins claudin-1 and ZO-2 and angiogenesis marker CD31 were also observed in the same treated lung tissues. Furthermore, the significant tumor-elicited macrophage and neutrophils infiltration into mice lungs was suppressed by DET and DETD-35. The immunomodulatory potential of both compounds was also evident by the decreased COX-2 and PD-L1 expression in lung tissues compared to tumor control mice. Altogether, this study gives mechanistic insight into the bio-efficacy of DET and DETD-35 against lung metastatic melanoma which might be in part thorough ROS-related apoptosis and metastatic cell phenotype modulation and lung tumor microenvironment regulation. In summary, the study from this dissertation sheds a light on the potential of phytocompounds saponin CUMA and sesquiterpene lactone DET/DETD-35 in the treatment of melanoma. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:56:13Z (GMT). No. of bitstreams: 1 ntu-109-D00423105-1.pdf: 6167704 bytes, checksum: 32a20e73be28897faf4786b5c12236dc (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | Committee approval i
Acknowledgements ii 摘要 iii Abstract vi Table of contents ix List of Figures xiii List of Tables xv Abbreviations xvi Chapter 1: Background, rationale and significance 1 1.1 Skin cancer: general introduction of melanoma 2 1.2 Current therapies for melanoma 5 1.3 BRAF inhibitors, resistance and combinations 8 1.4. Current status of plant-derived triterpene glucosides and sesquiterpene lactones for cancer therapy 9 1.4.1 Plant triterpene glucosides 10 1.4.2 Bioactive sesquiterpene lactones: a focus on the phyotocompound DET and its derivative DETD-35 12 1.5 General objective and specific aims of the study 16 Chapter 2 Investigation of pharmacological activity and mechanism of phyto-triterpenoid saponin CUMA against acquired BRAF inhibitor resistant melanoma 21 2.1 Introduction 22 2.2 Materials and methods 24 2.2.1 Chemicals and reagents 24 2.2.2 Cell culture 25 2.2.3 Cell viability assay 25 2.2.4 Colony forming assay 26 2.2.5 Cell cycle analysis 26 2.2.6 Apoptosis assay 27 2.2.7 Western blot analysis 27 2.2.8 Animals 28 2.2.9 Experimental A375-R resistant melanoma orthotropic mouse model 28 2.2.10 Pharmacokinetic study of CUMA in mice 29 2.2.11 Histology, immunofluorescence and immunohistochemistry of animal tissues from A375-R resistant orthotropic mouse model 30 2.2.12 RT qPCR analysis 31 2.2.13 Immunofluorescence cell staining 32 2.2.14 Statistical analysis 32 2.3 Results 32 2.3.1 Isolation and identification of CUMA 32 2.3.2 CUMA inhibited melanoma cells proliferation 34 2.3.3 CUMA induced G2/M phase cell cycle arrest in A375-R cells 35 2.3.4 CUMA induced apoptotic cell death in A375-R cells 36 2.3.5 CUMA alone or in combination with PLX4032 inhibited tumor growth in an A375-R melanoma with acquired resistance to PLX4032 in vivo 37 2.3.6 CUMA induced ER-stress related apoptosis and autophagy-like activity in A375-R cells 38 2.4 Discussion 40 Chapter 3: Investigation of the molecular mechanism of DET and its derivative DETD-35 against lung metastatic melanoma 69 3.1 Introduction 70 3.2 Materials and methods 72 3.2.1 Compounds DET and DETD-35 72 3.2.2 Cell culture 72 3.2.3 Cell viability assay 73 3.2.4 ROS measurement 73 3.2.5 Apoptosis assay 74 3.2.6 Western blot analysis 74 3.2.7 Cell mitochondria stress test 75 3.2.8 Immunofluorescence cell staining 76 3.2.9 Animals 76 3.2.10 Experimental A375LM5IF4g/Luc lung metastasis melanoma mouse model 77 3.2.11 Immunofluorescence and immunohistochemistry of lung tissues from A375LM5IF4g/Luc metastatic mouse model 77 3.2.12 Statistical analysis 78 3.3 Results 78 3.3.1 DET- and DETD-35-induced anti-proliferative effect in A375LM5IF4g/Luc lung-seeking melanoma cells is ROS-mediated 78 3.3.2 DET and DETD-35 induced ROS-mediated apoptosis and decrease of metastasis markers in A375LM5IF4g/Luc lung-seeking melanoma cells 79 3.3.3 DET and DETD-35 affected mitochondrial function of A375LM5IF4g/Luc lung-seeking melanoma cells 81 3.3.4 DET and DETD-35 dysregulated metastasis-related markers and TME in lungs from A375LM5IF4g/Luc melanoma lung metastatic xenograft mice 82 3.4 Discussion 85 Chapter 4: Conclusions and Future Perspectives 100 4.1 Conclusions 101 4.2 Future perspectives 103 4.2.1 Therapeutic implications of CUMA 103 4.2.2 Therapeutic implications of DET and DETD-35 105 References 108 Appendices 117 Appendix I 118 | - |
| dc.language.iso | en | - |
| dc.title | 植物化合物 cumingianoside A和 deoxyelephantopin 及其衍生物DETD-35用於抑制抗藥性或轉移性黑色素瘤功效之研究 | zh_TW |
| dc.title | The effect of phytocompounds cumingianoside A and deoxyelephantopin and its derivative DETD-35 on inhibiting drug resistant or metastatic melanoma | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 108-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 沈雅敬 | zh_TW |
| dc.contributor.coadvisor | Ya-Ching Shen | en |
| dc.contributor.oralexamcommittee | 顧記華;鄭源斌;廖憶純;黃啟彰;王升陽 | zh_TW |
| dc.contributor.oralexamcommittee | Jih-Hwa Guh;Yuan-Bin Cheng;Yi-Chun Liao;Chi-Chang Huang;Sheng-Yang Wang | en |
| dc.subject.keyword | BRAF抑制劑之黑色素瘤,轉移性黑色素瘤,三?類皂素,cumingianoside A,內質網壓力相關之細胞凋亡,倍半?內酯,deoxyelephantopin,DETD-35,氧化壓力, | zh_TW |
| dc.subject.keyword | BRAF inhibitor-resistant melanoma,metastatic melanoma,triterpenoid saponin,cumingianoside A,ER stress-related apoptosis,sesquiterpene lactone,deoxyelephantopin,DETD-35,oxidative stress, | en |
| dc.relation.page | 118 | - |
| dc.identifier.doi | 10.6342/NTU202000618 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2020-02-27 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 藥學研究所 | - |
| dc.date.embargo-lift | 2025-03-13 | - |
| 顯示於系所單位： | 藥學系 | |
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