請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94783完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 華國泰 | zh_TW |
| dc.contributor.advisor | Kuo-Tai Hua | en |
| dc.contributor.author | 吳晉睿 | zh_TW |
| dc.contributor.author | Chin-Jui Wu | en |
| dc.date.accessioned | 2024-08-19T16:23:24Z | - |
| dc.date.available | 2024-08-20 | - |
| dc.date.copyright | 2024-08-19 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-18 | - |
| dc.identifier.citation | [1] U. Güth, D. J. Huang, G. Bauer, M. Stieger, E. Wight, and G. Singer, “Metastatic patterns at autopsy in patients with ovarian carcinoma,” Cancer, vol. 110, no. 6, pp. 1272–1280, 2007, doi: 10.1002/cncr.22919.
[2] M. A. Bookman et al., “Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup,” J Clin Oncol, vol. 27, no. 9, pp. 1419–1425, 2009, doi: 10.1200/jco.2008.19.1684. [3] L. A. Baldwin et al., “Ten-year relative survival for epithelial ovarian cancer,” Obstet. Gynecol., vol. 120, no. 3, pp. 612–8, 2012, doi: 10.1097/aog.0b013e318264f794. [4] R. A. Burger et al., “Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer,” New Engl J Medicine, vol. 365, no. 26, pp. 2473–2483, 2011, doi: 10.1056/nejmoa1104390. [5] W. P. Tew et al., “PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline,” J Clin Oncol, vol. 38, no. 30, pp. 3468–3493, 2020, doi: 10.1200/jco.20.01924. [6] W. T. Hwang, S. F. Adams, E. Tahirovic, I. S. Hagemann, and G. Coukos, “Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis,” Gynecol. Oncol., vol. 124, no. 2, pp. 192–8, 2012, doi: 10.1016/j.ygyno.2011.09.039. [7] M. Yarchoan, A. Hopkins, and E. M. Jaffee, “Tumor Mutational Burden and Response Rate to PD-1 Inhibition,” N. Engl. J. Med., vol. 377, no. 25, pp. 2500–2501, 2017, doi: 10.1056/nejmc1713444. [8] Y. S. Lee et al., “Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers,” Exp. Mol. Med., vol. 34, no. 1, pp. 18–26, 2002, doi: 10.1038/emm.2002.3. [9] L. Zhang et al., “Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer,” New Engl J Medicine, vol. 348, no. 3, pp. 203–213, 2003, doi: 10.1056/nejmoa020177. [10] E. Sato et al., “Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer,” Proc National Acad Sci, vol. 102, no. 51, pp. 18538–18543, 2005, doi: 10.1073/pnas.0509182102. [11] X. Luo, J. Xu, J. Yu, and P. Yi, “Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer,” Front. Immunol., vol. 12, p. 692360, 2021, doi: 10.3389/fimmu.2021.692360. [12] T. J. Curiel et al., “Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival,” Nat Med, vol. 10, no. 9, pp. 942–949, 2004, doi: 10.1038/nm1093. [13] X. Yuan et al., “Prognostic significance of tumor-associated macrophages in ovarian cancer: A meta-analysis,” Gynecol Oncol, vol. 147, no. 1, pp. 181–187, 2017, doi: 10.1016/j.ygyno.2017.07.007. [14] T. Condamine, I. Ramachandran, J.-I. Youn, and D. I. Gabrilovich, “Regulation of Tumor Metastasis by Myeloid-derived Suppressor Cells,” Annu Rev Med, vol. 66, no. 1, pp. 1–14, 2015, doi: 10.1146/annurev-med-051013-052304. [15] L. E. Kandalaft, K. Odunsi, and G. Coukos, “Immunotherapy in Ovarian Cancer: Are We There Yet?,” J Clin Oncol, vol. 37, no. 27, pp. 2460–2471, 2019, doi: 10.1200/jco.19.00508. [16] S. Yamagoe, Y. Yamakawa, Y. Matsuo, J. Minowada, S. Mizuno, and K. Suzuki, “Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2,” Immunol. Lett., vol. 52, no. 1, pp. 9–13, 1996, doi: 10.1016/0165-2478(96)02572-2. [17] S. Yamagoe et al., “Expression of a neutrophil chemotactic protein LECT2 in human hepatocytes revealed by immunochemical studies using polyclonal and monoclonal antibodies to a recombinant LECT2,” Biochem. Biophys. Res. Commun., vol. 237, no. 1, pp. 116–20, 1997, doi: 10.1006/bbrc.1997.7095. [18] T. Saito et al., “Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis,” J. Immunol., vol. 173, no. 1, pp. 579–85, 2004, doi: 10.4049/jimmunol.173.1.579. [19] S. Yamagoe, Y. Kameoka, K. Hashimoto, S. Mizuno, and K. Suzuki, “Molecular Cloning, Structural Characterization, and Chromosomal Mapping of the Human LECT2 Gene,” Genomics, vol. 48, no. 3, pp. 324–329, 1998, doi: 10.1006/geno.1997.5198. [20] X. J. Lu et al., “LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor,” J. Exp. Med., vol. 210, no. 1, pp. 5–13, 2013, doi: 10.1084/jem.20121466. [21] T. Uchida et al., “Expression pattern of a newly recognized protein, LECT2, in hepatocellular carcinoma and its premalignant lesion,” Pathol Int, vol. 49, no. 2, pp. 147–151, 1999, doi: 10.1046/j.1440-1827.1999.00836.x. [22] H. T. Ong, P. K. Tan, S. M. Wang, D. T. H. Low, L. L. Ooi, and K. M. Hui, “The tumor suppressor function of LECT2 in human hepatocellular carcinoma makes it a potential therapeutic target,” Cancer Gene Ther., vol. 18, no. 6, pp. 399–406, 2011, doi: 10.1038/cgt.2011.5. [23] C. K. Chen et al., “Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment,” Hepatology, vol. 59, no. 3, pp. 974–85, 2014, doi: 10.1002/hep.26738. [24] M. Anson et al., “Oncogenic β-catenin triggers an inflammatory response that determines the aggressiveness of hepatocellular carcinoma in mice,” J Clin Invest, vol. 122, no. 2, pp. 586–599, 2012, doi: 10.1172/jci43937. [25] A. L’Hermitte et al., “Lect2 Controls Inflammatory Monocytes to Constrain the Growth and Progression of Hepatocellular Carcinoma,” Hepatology, vol. 69, no. 1, pp. 160–178, 2019, doi: 10.1002/hep.30140. [26] F. Balkwill and A. Mantovani, “Inflammation and cancer: back to Virchow?,” Lancet, vol. 357, no. 9255, pp. 539–545, 2001, doi: 10.1016/s0140-6736(00)04046-0. [27] R. S. Freedman et al., “Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma.,” Clin. cancer Res. : Off. J. Am. Assoc. Cancer Res., vol. 6, no. 6, pp. 2268–78, 2000. [28] A. Mantovani, S. Sozzani, M. Locati, P. Allavena, and A. Sica, “Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes,” Trends Immunol, vol. 23, no. 11, pp. 549–555, 2002, doi: 10.1016/s1471-4906(02)02302-5. [29] J. Lortet-Tieulent, J. Ferlay, F. Bray, and A. Jemal, “International Patterns and Trends in Endometrial Cancer Incidence, 1978–2013,” Jnci J National Cancer Inst, vol. 110, no. 4, pp. 354–361, 2017, doi: 10.1093/jnci/djx214. [30] C.-Y. Huang et al., “Nationwide surveillance in uterine cancer: survival analysis and the importance of birth cohort: 30-year population-based registry in Taiwan.,” Plos One, vol. 7, no. 12, p. e51372, 2012, doi: 10.1371/journal.pone.0051372. [31] K. Lindemann, L. J. Vatten, M. Ellstrom-Engh, and A. Eskild, “Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study,” British journal of cancer, vol. 98, no. 9, pp. 1582–5, 2008, doi: 10.1038/sj.bjc.6604313. [32] E. Weiderpass, I. Persson, H. O. Adami, C. Magnusson, A. Lindgren, and J. A. Baron, “Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden),” Cancer Causes Control, vol. 11, pp. 185–92, 2000, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/10710204 [33] K. Esposito, P. Chiodini, A. Colao, A. Lenzi, and D. Giugliano, “Metabolic Syndrome and Risk of Cancer A systematic review and meta-analysis,” Diabetes Care, vol. 35, no. 11, pp. 2402-2411–2411, 2012, doi: 10.2337/dc12-0336. [34] C. M. Friedenreich et al., “Case–Control Study of the Metabolic Syndrome and Metabolic Risk Factors for Endometrial Cancer,” Cancer Epidemiology Prev Biomarkers, vol. 20, no. 11, pp. 2384-2395–2395, 2011, doi: 10.1158/1055-9965.epi-11-0715. [35] V. Rosato et al., “Metabolic syndrome and endometrial cancer risk,” Ann Oncol, vol. 22, no. 4, pp. 884-889–889, 2011, doi: 10.1093/annonc/mdq464. [36] B. Trabert, N. Wentzensen, A. S. Felix, H. P. Yang, M. E. Sherman, and L. A. Brinton, “Metabolic Syndrome and Risk of Endometrial Cancer in the United States: A Study in the SEER–Medicare Linked Database,” Cancer Epidemiology Prev Biomarkers, vol. 24, no. 1, pp. 261-267–267, 2015, doi: 10.1158/1055-9965.epi-14-0923. [37] Y. Zhang et al., “The association between metabolic abnormality and endometrial cancer: A large case-control study in China,” Gynecologic oncology, vol. 117, no. 1, pp. 41-46–46, 2010, doi: 10.1016/j.ygyno.2009.12.029. [38] E. Anastasi, T. Filardi, S. Tartaglione, A. Lenzi, A. Angeloni, and S. Morano, “Linking type 2 diabetes and gynecological cancer: an introductory overview,” Clin Chem Laboratory Medicine Cclm, vol. 56, no. 9, pp. 1413–1425, 2018, doi: 10.1515/cclm-2017-0982. [39] A. S. Furberg and I. Thune, “Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort,” International journal of cancer. Journal international du cancer, vol. 104, no. 6, pp. 669–76, 2003, doi: 10.1002/ijc.10974. [40] Z. Khitan and D. H. Kim, “Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension,” J Nutrition Metabolism, vol. 2013, pp. 1-12–12, 2013, doi: 10.1155/2013/682673. [41] J.-P. Drouin-Chartier et al., “Changes in Consumption of Sugary Beverages and Artificially Sweetened Beverages and Subsequent Risk of Type 2 Diabetes: Results From Three Large Prospective U.S. Cohorts of Women and Men,” Diabetes Care, vol. 42, no. 12, pp. 2181–2189, 2019, doi: 10.2337/dc19-0734. [42] M. I. Goran, S. J. Ulijaszek, and E. E. Ventura, “High fructose corn syrup and diabetes prevalence: A global perspective,” Glob Public Health, vol. 8, no. 1, pp. 55–64, 2013, doi: 10.1080/17441692.2012.736257. [43] P. Bu et al., “Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis,” Cell Metab, vol. 27, no. 6, pp. 1249-1262 e4, 2018, doi: 10.1016/j.cmet.2018.04.003. [44] X. Fan, H. Liu, M. Liu, Y. Wang, L. Qiu, and Y. Cui, “Increased utilization of fructose has a positive effect on the development of breast cancer,” Peerj, vol. 5, p. e3804, 2017, doi: 10.7717/peerj.3804. [45] H. Liu, D. Huang, D. L. McArthur, L. G. Boros, N. Nissen, and A. P. Heaney, “Fructose induces transketolase flux to promote pancreatic cancer growth,” Cancer research, vol. 70, no. 15, pp. 6368–76, 2010, doi: 10.1158/0008-5472.can-09-4615. [46] M. Inoue-Choi, K. Robien, A. Mariani, J. R. Cerhan, and K. E. Anderson, “Sugar-Sweetened Beverage Intake and the Risk of Type I and Type II Endometrial Cancer among Postmenopausal Women,” Cancer Epidemiology Prev Biomarkers, vol. 22, no. 12, pp. 2384–2394, 2013, doi: 10.1158/1055-9965.epi-13-0636. [47] W. Gao, N. Li, Z. Li, J. Xu, and C. Su, “Ketohexokinase is involved in fructose utilization and promotes tumor progression in glioma,” Biochem. Biophys. Res. Commun., vol. 503, no. 3, pp. 1298–1306, 2018, doi: 10.1016/j.bbrc.2018.07.040. [48] X. Yang et al., “Prognostic Impact of Metabolism Reprogramming Markers Acetyl-CoA Synthetase 2 Phosphorylation and Ketohexokinase-A Expression in Non-Small-Cell Lung Carcinoma,” Frontiers Oncol, vol. 9, p. 1123, 2019, doi: 10.3389/fonc.2019.01123. [49] J. Kim et al., “Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer,” Nat Commun, vol. 11, no. 1, p. 5436, 2020, doi: 10.1038/s41467-020-19263-1. [50] C. P. Diggle et al., “Both isoforms of ketohexokinase are dispensable for normal growth and development,” Physiol Genomics, vol. 42A, no. 4, pp. 235–43, 2010, doi: 10.1152/physiolgenomics.00128.2010. [51] C. P. Diggle et al., “Ketohexokinase: Expression and Localization of the Principal Fructose-metabolizing Enzyme,” J Histochem Cytochem, vol. 57, no. 8, pp. 763-774–774, 2009, doi: 10.1369/jhc.2009.953190. [52] X. Li et al., “A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation,” Nat. Cell Biol., vol. 18, no. 5, pp. 561–71, 2016, doi: 10.1038/ncb3338. [53] Z. Shen et al., “GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer,” Cancer Lett, vol. 534, p. 215617, May 2022, doi: 10.1016/j.canlet.2022.215617. [54] Y.-L. Kang, J. Kim, S.-B. Kwak, Y.-S. Kim, J. Huh, and J.-W. Park, “The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer,” Exp. Mol. Med., pp. 1–15, 2024, doi: 10.1038/s12276-023-01153-3. [55] D. Huntsman, J. H. Resau, E. Klineberg, and N. Auersperg, “Comparison of c-met Expression in Ovarian Epithelial Tumors and Normal Epithelia of the Female Reproductive Tract by Quantitative Laser Scan Microscopy,” Am J Pathology, vol. 155, no. 2, pp. 343–348, 1999, doi: 10.1016/s0002-9440(10)65130-9. [56] K. Sawada et al., “c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion,” Cancer Res., vol. 67, no. 4, pp. 1670–1679, 2007, doi: 10.1158/0008-5472.can-06-1147. [57] A. Lorenzato et al., “Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion,” Cancer Res, vol. 62, pp. 7025–30, 2002, [Online]. Available: https://www.ncbi.nlm.nih.gov/pubmed/12460923 [58] A. Lorenzato et al., “Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion.,” Cancer Res, vol. 62, no. 23, pp. 7025–30, 2002. [59] 陳季青, “探討第二型白血球趨化因子在卵巢癌惡性進程之角色,” 國立臺灣大學, 2015. [60] M.-T. Ko, “Evaluation of the Roles of Ketohexokinase in Endometrioid Adenocarcinoma Progression,” 2019. [61] D. A. Levine et al., “Integrated genomic characterization of endometrial carcinoma,” Nature, vol. 497, no. 7447, pp. 67–73, 2013, doi: 10.1038/nature12113. [62] J. R. Sierra and M.-S. Tsao, “c-MET as a potential therapeutic target and biomarker in cancer,” Ther. Adv. Méd. Oncol., vol. 3, no. 1_suppl, pp. S21--S35, 2011, doi: 10.1177/1758834011422557. [63] X. Li et al., “LECT 2 Antagonizes FOXM1 Signaling via Inhibiting MET to Retard PDAC Progression,” Front. Cell Dev. Biol., vol. 9, p. 661122, 2021, doi: 10.3389/fcell.2021.661122. [64] W. Y. Hung et al., “Leukocyte Cell-Derived Chemotaxin 2 Retards Non-Small Cell Lung Cancer Progression Through Antagonizing MET and EGFR Activities,” Cell. Physiol. Biochem., vol. 51, no. 1, pp. 337–355, 2018, doi: 10.1159/000495233. [65] M. E. Gerritsen, J. E. Tomlinson, C. Zlot, M. Ziman, and S. Hwang, “Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells,” Br. J. Pharmacol., vol. 140, no. 4, pp. 595–610, 2003, doi: 10.1038/sj.bjp.0705494. [66] C. K. Chen et al., “Inhibition of VEGF165/VEGFR2-dependent signaling by LECT2 suppresses hepatocellular carcinoma angiogenesis,” Sci. Rep., vol. 6, no. 1, p. 31398, 2016, doi: 10.1038/srep31398. [67] M. Xu et al., “LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis,” Cell, vol. 178, no. 6, pp. 1478-1492 e20, 2019, doi: 10.1016/j.cell.2019.07.021. [68] S. Huang et al., “Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice,” JNCI: J. Natl. Cancer Inst., vol. 94, no. 15, pp. 1134–42, 2002, doi: 10.1093/jnci/94.15.1134. [69] A. Mantovani, F. Marchesi, A. Malesci, L. Laghi, and P. Allavena, “Tumour-associated macrophages as treatment targets in oncology,” Nat. Rev. Clin. Oncol., vol. 14, no. 7, pp. 399–416, 2017, doi: 10.1038/nrclinonc.2016.217. [70] N. Nishikoba et al., “HGF-MET Signaling Shifts M1 Macrophages Toward an M2-Like Phenotype Through PI3K-Mediated Induction of Arginase-1 Expression,” Front. Immunol., vol. 11, p. 2135, 2020, doi: 10.3389/fimmu.2020.02135. [71] M. Y. Zhang et al., “A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients,” J. Ovarian Res., vol. 7, no. 1, p. 19, 2014, doi: 10.1186/1757-2215-7-19. [72] I. Kryczek et al., “B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma,” J. Exp. Med., vol. 203, no. 4, pp. 871–81, 2006, doi: 10.1084/jem.20050930. [73] C. E. Gottlieb, A. M. Mills, J. V. Cross, and K. L. Ring, “Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors,” Gynecol. Oncol., vol. 144, no. 3, pp. 607–612, 2017, doi: 10.1016/j.ygyno.2016.12.021. [74] T. Baert et al., “Myeloid Derived Suppressor Cells: Key Drivers of Immunosuppression in Ovarian Cancer,” Front. Immunol., vol. 10, p. 1273, 2019, doi: 10.3389/fimmu.2019.01273. [75] D. Vasquez-Dunddel et al., “STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients,” J. Clin. Investig., vol. 123, no. 4, pp. 1580–9, 2013, doi: 10.1172/jci60083. [76] P. L. Raber et al., “Subpopulations of myeloid‐derived suppressor cells impair T cell responses through independent nitric oxide‐related pathways,” Int. J. Cancer, vol. 134, no. 12, pp. 2853--2864, 2014, doi: 10.1002/ijc.28622. [77] C. A. Corzo et al., “Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells,” J. Immunol., vol. 182, no. 9, pp. 5693–701, 2009, doi: 10.4049/jimmunol.0900092. [78] B. Bierie and H. L. Moses, “Transforming growth factor beta (TGF-beta) and inflammation in cancer,” Cytokine Growth Factor Rev., vol. 21, no. 1, pp. 49–59, 2010, doi: 10.1016/j.cytogfr.2009.11.008. [79] K. M. Hart, K. T. Byrne, M. J. Molloy, E. M. Usherwood, and B. Berwin, “IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer,” Front. Immunol., vol. 2, p. 29, 2011, doi: 10.3389/fimmu.2011.00029. [80] T. J. Curiel et al., “Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity,” Nat. Med., vol. 9, no. 5, pp. 562–7, 2003, doi: 10.1038/nm863. [81] P. C. Rodriguez et al., “Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses,” Cancer Res., vol. 64, no. 16, pp. 5839–49, 2004, doi: 10.1158/0008-5472.can-04-0465. [82] M. Z. Noman et al., “PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation,” J. Exp. Med., vol. 211, no. 5, pp. 781--790, 2014, doi: 10.1084/jem.20131916. [83] J. Yang et al., “KHK-A promotes the proliferation of oesophageal squamous cell carcinoma through the up-regulation of PRPS1,” Arab J Gastroenterol, 2020, doi: 10.1016/j.ajg.2020.08.007. [84] I. Guccini et al., “Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development,” iScience, vol. 26, no. 8, p. 107368, 2023, doi: 10.1016/j.isci.2023.107368. [85] H. Wang, M. Guo, H. Wei, and Y. Chen, “Targeting p53 pathways: mechanisms, structures, and advances in therapy,” Signal Transduct. Target. Ther., vol. 8, no. 1, p. 92, 2023, doi: 10.1038/s41392-023-01347-1. [86] B. Aral et al., “Mutations in PDX1, the Human Lipoyl-Containing Component X of the Pyruvate Dehydrogenase–Complex Gene on Chromosome 11p1, in Congenital Lactic Acidosis,” Am. J. Hum. Genet., vol. 61, no. 6, pp. 1318–1326, 1997, doi: 10.1086/301653. [87] J. Inoue, M. Kishikawa, H. Tsuda, Y. Nakajima, T. Asakage, and J. Inazawa, “Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma,” Cancer Sci, vol. 112, no. 7, pp. 2792–2802, 2021, doi: 10.1111/cas.14938. [88] S. C. Eastlack, S. Dong, C. Ivan, and S. K. Alahari, “Suppression of PDHX by microRNA-27b deregulates cell metabolism and promotes growth in breast cancer,” Mol. Cancer, vol. 17, no. 1, p. 100, 2018, doi: 10.1186/s12943-018-0851-8. [89] C. Yang et al., “Brain-Type Glycogen Phosphorylase (PYGB) in the Pathologies of Diseases: A Systematic Review,” Cells, vol. 13, no. 3, p. 289, 2024, doi: 10.3390/cells13030289. [90] L. Ren et al., “Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target,” J. Cancer Res. Clin. Oncol., vol. 150, no. 3, p. 127, 2024, doi: 10.1007/s00432-024-05644-2. [91] Q. Huang, S. Yang, H. Yan, H. Chen, Y. Wang, and Y. Wang, “Development and validation of a combined glycolysis and immune prognostic signature for lung squamous cell carcinoma,” Front. Genet., vol. 13, p. 907058, 2022, doi: 10.3389/fgene.2022.907058. [92] D. Zhang et al., “Identification of a glycolysis‐related gene signature for survival prediction of ovarian cancer patients,” Cancer Med., vol. 10, no. 22, pp. 8222–8237, 2021, doi: 10.1002/cam4.4317. [93] K. Kotowski et al., “Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets,” Cancers, vol. 13, no. 4, p. 909, 2021, doi: 10.3390/cancers13040909. [94] T. Dai et al., “Hypoxic activation of PFKFB4 in breast tumor microenvironment shapes metabolic and cellular plasticity to accentuate metastatic competence,” Cell Reports, vol. 41, no. 10, p. 111756, 2022, doi: 10.1016/j.celrep.2022.111756. [95] J. Zhou, Y. Lin, X. Kang, Z. Liu, J. Zou, and F. Xu, “Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the EZH2/FBXL7/PFKFB4 axis,” Cell Death Dis., vol. 14, no. 5, p. 326, 2023, doi: 10.1038/s41419-023-05795-z. [96] C. S. Kam et al., “PFKFB4 Drives the Oncogenicity in TP53-Mutated Hepatocellular Carcinoma in a Phosphatase-Dependent Manner,” Cell. Mol. Gastroenterol. Hepatol., vol. 15, no. 6, pp. 1325–1350, 2023, doi: 10.1016/j.jcmgh.2023.02.004. [97] S. Dasgupta et al., “Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer,” Nature, vol. 556, no. 7700, pp. 249–254, 2018, doi: 10.1038/s41586-018-0018-1. [98] D. Hanahan, “Hallmarks of Cancer: New Dimensions,” Cancer Discov, vol. 12, no. 1, pp. 31–46, 2022, doi: 10.1158/2159-8290.cd-21-1059. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94783 | - |
| dc.description.abstract | 婦科惡性腫瘤包卵巢癌、子宮癌、子宮頸癌、外陰癌等數種分佈於女性生殖器官，其中卵巢癌的診斷通常在晚期且具有高復發率，而子宮癌雖多為早期，但一旦診斷為末期或是復發則無良好的治療方式。面對這些不易治療的婦癌，新穎的生物標的在早期檢測、預後評估和標靶治療等有其重要的一面。我們研究強調了白血球細胞趨化素2 (Leukocyte cell-derived chemotaxin 2, LECT2) 和己酮糖磷酸激酶 (Ketohexokinase, KHK) 作為這些惡性腫瘤的潛在生物標的的重要性。我們實驗證實在上皮性卵巢癌中，血清 LECT2 的濃度降低與疾病進展和腫瘤免疫抑制微環境相關， 我們利用細胞與小鼠上皮性卵巢癌模型驗證LECT2除了會透過調節 c-Met 路徑，另一方面也會通過調節腫瘤細胞與免疫細胞的腫瘤微環境來促進卵巢癌進展，這種調節會影響免疫檢查點抑制療法的效果，這項發現將可化為補充LECT2 作為協同免疫治療抑制劑。而在子宮內膜癌，我們發現KHK有兩種異構體KHK-A及KHK-C，其中高KHK-A的表達與不良預後和較晚期疾病有關，過表現KHK-A會促使腫瘤細胞增殖、集落形成和幹細胞特性的增強。此外，我們也發現KHK-A 與 TP53 基因突變和拷貝數變異有關，表明其在代謝調節和致癌途徑中可能發揮作用。KHK抑制劑已被運用在糖尿病的治療上，在子宮內膜癌的代謝調控和腫瘤進展中也可能發揮關鍵作用，為新療法提供潛在的治療機會。這些新興的生物標的LECT2 和 KHK-A，為婦科癌症的發病機制提供了新發現，並有望在診斷、預後及治療策略有益。 | zh_TW |
| dc.description.abstract | Gynecologic malignancies, including epithelial ovarian cancer (EOC) and endometrial cancer, present significant challenges due to their often advanced-stage diagnosis, high recurrence rates, and complex tumor microenvironments. Novel biomarkers are critical for early detection, prognostic assessment, and targeted therapy. Recent investigations have highlighted the importance of human leukocyte cell-derived chemotaxin 2 (LECT2) and ketohexokinase (KHK) as promising biomarkers for these malignancies. In EOC, reduced serum LECT2 levels correlate with disease progression and an immunosuppressive microenvironment, suggesting a pivotal role in regulating metastasis via the c-Met pathway. Using the murine EOC model, we discovered that loss of Lect2 promotes EOC progression by modulating both tumor cells and the tumor microenvironment. This modulation impacts the effectiveness of immune checkpoint blockade therapies, emphasizing LECT2's potential as a target for synergistic immunotherapy. For endometrial cancer, KHK has two splicing alternative isoforms, KHK-A and KHK-C, respectively. High KHK-A expression is linked to poor prognosis and advanced stage, driving tumor cell proliferation, colony formation, and stem cell properties. Moreover, KHK-A's association with TP53 mutations and copy number variations indicates a potential role in metabolic regulation and oncogenic pathways. KHK-A may play a vital role in the metabolic regulation and tumor progression of endometrial cancer, offering potential targets for new therapeutic strategies. These emerging biomarkers, LECT2 and KHK-A, offer new insights into the pathogenesis of gynecologic cancers, providing potential avenues for innovative diagnostic, prognostic, and therapeutic strategies. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-19T16:23:24Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-19T16:23:24Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
誌謝 II 中文摘要 III 英文摘要 IV Background 1 Material and Methods 7 Results 16 Part. I: LECT2 in ovarian cancer 16 Part. II: KHK-A in endometrial cancer 25 Discussion 29 Future perspective 37 Tables 38 Figures and legends 42 Reference 76 | - |
| dc.language.iso | en | - |
| dc.subject | 白血球趨化蛋白2 | zh_TW |
| dc.subject | 婦癌 | zh_TW |
| dc.subject | 腫瘤代謝 | zh_TW |
| dc.subject | 腫瘤免疫 | zh_TW |
| dc.subject | 己酮糖磷酸酶 | zh_TW |
| dc.subject | Gynecologic oncology | en |
| dc.subject | Leukocyte cell-derived chemotaxin 2 | en |
| dc.subject | Cancer metabolism | en |
| dc.subject | Cancer immunity | en |
| dc.subject | Ketohexokinase | en |
| dc.title | 婦癌中新蛋白標的與相關代謝調節及免疫調控功能 | zh_TW |
| dc.title | The novel biomarkers of gynecologic cancer in cellular metabolism and immune regulatory mechanism | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 魏凌鴻 | zh_TW |
| dc.contributor.coadvisor | Lin-Hung Wei | en |
| dc.contributor.oralexamcommittee | 楊順發;簡銘賢;湯智昕 | zh_TW |
| dc.contributor.oralexamcommittee | Shun-Fa Yang;Ming-Hsien Chien;Chih-Hsin Tang | en |
| dc.subject.keyword | 婦癌,白血球趨化蛋白2,己酮糖磷酸酶,腫瘤免疫,腫瘤代謝, | zh_TW |
| dc.subject.keyword | Gynecologic oncology,Leukocyte cell-derived chemotaxin 2,Ketohexokinase,Cancer immunity,Cancer metabolism, | en |
| dc.relation.page | 85 | - |
| dc.identifier.doi | 10.6342/NTU202401812 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-07-18 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 毒理學研究所 | - |
| 顯示於系所單位： | 毒理學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf 未授權公開取用 | 11.13 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。