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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄧哲明 | |
dc.contributor.author | Min-Wu Chao | en |
dc.contributor.author | 趙敏吾 | zh_TW |
dc.date.accessioned | 2021-05-14T17:44:50Z | - |
dc.date.available | 2020-09-24 | |
dc.date.available | 2021-05-14T17:44:50Z | - |
dc.date.copyright | 2015-09-24 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-07-24 | |
dc.identifier.citation | Aldana-Masangkay, G. I. and K. M. Sakamoto (2011). 'The role of HDAC6 in cancer.' J Biomed Biotechnol 2011: 875824.
Ali, I. K., L. McKendrick, S. J. Morley and R. J. Jackson (2001). 'Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation.' EMBO J 20(15): 4233-4242. Armengol, G., F. Rojo, J. Castellvi, C. Iglesias, M. Cuatrecasas, B. Pons, J. Baselga and S. Ramon y Cajal (2007). '4E-binding protein 1: a key molecular 'funnel factor' in human cancer with clinical implications.' Cancer Res 67(16): 7551-7555. Bacus, S. S., A. V. Gudkov, M. Lowe, L. Lyass, Y. Yung, A. P. Komarov, K. Keyomarsi, Y. Yarden and R. Seger (2001). 'Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53.' Oncogene 20(2): 147-155. Bali, P., M. Pranpat, J. Bradner, M. Balasis, W. Fiskus, F. Guo, K. Rocha, S. Kumaraswamy, S. Boyapalle, P. Atadja, E. Seto and K. Bhalla (2005). 'Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors.' J Biol Chem 280(29): 26729-26734. Bali, P., M. Pranpat, R. Swaby, W. Fiskus, H. Yamaguchi, M. Balasis, K. Rocha, H. G. Wang, V. Richon and K. Bhalla (2005). 'Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2.' Clin Cancer Res 11(17): 6382-6389. Blagosklonny, M. V., R. Robey, D. L. Sackett, L. Du, F. Traganos, Z. Darzynkiewicz, T. Fojo and S. E. Bates (2002). 'Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest, and cytotoxicity.' Mol Cancer Ther 1(11): 937-941. Bloom, J. and F. R. Cross (2007). 'Multiple levels of cyclin specificity in cell-cycle control.' Nat Rev Mol Cell Biol 8(2): 149-160. Bots, M. and R. W. Johnstone (2009). 'Rational combinations using HDAC inhibitors.' Clin Cancer Res 15(12): 3970-3977. Boyault, C., K. Sadoul, M. Pabion and S. Khochbin (2007). 'HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination.' Oncogene 26(37): 5468-5476. Braunstein, S., K. Karpisheva, C. Pola, J. Goldberg, T. Hochman, H. Yee, J. Cangiarella, R. Arju, S. C. Formenti and R. J. Schneider (2007). 'A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer.' Mol Cell 28(3): 501-512. Breuninger, L. M., S. Paul, K. Gaughan, T. Miki, A. Chan, S. A. Aaronson and G. D. Kruh (1995). 'Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution.' Cancer Res 55(22): 5342-5347. Brocato, J., Y. Chervona and M. Costa (2014). 'Molecular responses to hypoxia-inducible factor 1alpha and beyond.' Mol Pharmacol 85(5): 651-657. Bruggemann, E. P., S. J. Currier, M. M. Gottesman and I. Pastan (1992). 'Characterization of the azidopine and vinblastine binding site of P-glycoprotein.' J Biol Chem 267(29): 21020-21026. Brunelle, J. K. and A. Letai (2009). 'Control of mitochondrial apoptosis by the Bcl-2 family.' J Cell Sci 122(Pt 4): 437-441. Bulinski, J. C., J. E. Richards and G. Piperno (1988). 'Posttranslational modifications of alpha tubulin: detyrosination and acetylation differentiate populations of interphase microtubules in cultured cells.' J Cell Biol 106(4): 1213-1220. Castedo, M., J. L. Perfettini, T. Roumier, K. Andreau, R. Medema and G. Kroemer (2004). 'Cell death by mitotic catastrophe: a molecular definition.' Oncogene 23(16): 2825-2837. Chen, L., W. Fischle, E. Verdin and W. C. Greene (2001). 'Duration of nuclear NF-kappaB action regulated by reversible acetylation.' Science 293(5535): 1653-1657. Choi, J. H., H. J. Kwon, B. I. Yoon, J. H. Kim, S. U. Han, H. J. Joo and D. Y. Kim (2001). 'Expression profile of histone deacetylase 1 in gastric cancer tissues.' Jpn J Cancer Res 92(12): 1300-1304. Chou, T. C. (2006). 'Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.' Pharmacol Rev 58(3): 621-681. Crazzolara, R., A. Cisterne, M. Thien, J. Hewson, R. Baraz, K. F. Bradstock and L. J. Bendall (2009). 'Potentiating effects of RAD001 (Everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia.' Blood 113(14): 3297-3306. Demidenko, Z. N. and M. V. Blagosklonny (2011). 'The purpose of the HIF-1/PHD feedback loop: to limit mTOR-induced HIF-1alpha.' Cell Cycle 10(10): 1557-1562. Dhillon, A. S., S. Hagan, O. Rath and W. Kolch (2007). 'MAP kinase signalling pathways in cancer.' Oncogene 26(22): 3279-3290. Dilling, M. B., G. S. Germain, L. Dudkin, A. L. Jayaraman, X. Zhang, F. C. Harwood and P. J. Houghton (2002). '4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin.' J Biol Chem 277(16): 13907-13917. Dowling, M., K. R. Voong, M. Kim, M. K. Keutmann, E. Harris and G. D. Kao (2005). 'Mitotic spindle checkpoint inactivation by trichostatin a defines a mechanism for increasing cancer cell killing by microtubule-disrupting agents.' Cancer Biol Ther 4(2): 197-206. Dubois, L., M. G. Magagnin, A. H. Cleven, S. A. Weppler, B. Grenacher, W. Landuyt, N. Lieuwes, P. Lambin, T. A. Gorr, M. Koritzinsky and B. G. Wouters (2009). 'Inhibition of 4E-BP1 sensitizes U87 glioblastoma xenograft tumors to irradiation by decreasing hypoxia tolerance.' Int J Radiat Oncol Biol Phys 73(4): 1219-1227. Ducker, G. S., C. E. Atreya, J. P. Simko, Y. K. Hom, M. R. Matli, C. H. Benes, B. Hann, E. K. Nakakura, E. K. Bergsland, D. B. Donner, J. Settleman, K. M. Shokat and R. S. Warren (2014). 'Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors.' Oncogene 33(12): 1590-1600. Dumontet, C. and M. A. Jordan (2010). 'Microtubule-binding agents: a dynamic field of cancer therapeutics.' Nat Rev Drug Discov 9(10): 790-803. Easton, J. B. and P. J. Houghton (2006). 'mTOR and cancer therapy.' Oncogene 25(48): 6436-6446. Edwards, M. S., S. D. Chadda, Z. Zhao, B. L. Barber and D. P. Sykes (2012). 'A systematic review of treatment guidelines for metastatic colorectal cancer.' Colorectal Disease 14(2): e31-e47. Eichhorn, J. M., N. Sakurikar, S. E. Alford, R. Chu and T. C. Chambers (2013). 'Critical role of anti-apoptotic Bcl-2 protein phosphorylation in mitotic death.' Cell Death Dis 4: e834. Eot-Houllier, G., G. Fulcrand, L. Magnaghi-Jaulin and C. Jaulin (2009). 'Histone deacetylase inhibitors and genomic instability.' Cancer Lett 274(2): 169-176. Eot-Houllier, G., G. Fulcrand, Y. Watanabe, L. Magnaghi-Jaulin and C. Jaulin (2008). 'Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister chromatid cohesion.' Genes Dev 22(19): 2639-2644. Faivre, S., G. Kroemer and E. Raymond (2006). 'Current development of mTOR inhibitors as anticancer agents.' Nat Rev Drug Discov 5(8): 671-688. Fojo, A. T. and M. Menefee (2005). 'Microtubule targeting agents: basic mechanisms of multidrug resistance (MDR).' Semin Oncol 32(6 Suppl 7): S3-8. Gascoigne, K. E. and S. S. Taylor (2008). 'Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs.' Cancer Cell 14(2): 111-122. Gascoigne, K. E. and S. S. Taylor (2009). 'How do anti-mitotic drugs kill cancer cells?' J Cell Sci 122(Pt 15): 2579-2585. George, M. L., M. G. Tutton, F. Janssen, A. Arnaout, A. M. Abulafi, S. A. Eccles and R. I. Swift (2001). 'VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression.' Neoplasia 3(5): 420-427. Halkidou, K., L. Gaughan, S. Cook, H. Y. Leung, D. E. Neal and C. N. Robson (2004). 'Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.' Prostate 59(2): 177-189. Harris, A. L. (2002). 'Hypoxia--a key regulatory factor in tumour growth.' Nat Rev Cancer 2(1): 38-47. Heinicke, U. and S. Fulda (2014). 'Chemosensitization of rhabdomyosarcoma cells by the histone deacetylase inhibitor SAHA.' Cancer Letters 351(1): 50-58. Holohan, C., S. Van Schaeybroeck, D. B. Longley and P. G. Johnston (2013). 'Cancer drug resistance: an evolving paradigm.' Nat Rev Cancer 13(10): 714-726. Hsu, H. S., M. H. Lin, Y. H. Jang, T. T. Kuo, C. C. Liu and T. H. Cheng (2015). 'The 4E-BP1/eIF4E ratio is a determinant for rapamycin response in esophageal cancer cells.' J Thorac Cardiovasc Surg 149(1): 378-385. Huang, L., Q. Ao, Q. Zhang, X. Yang, H. Xing, F. Li, G. Chen, J. Zhou, S. Wang, G. Xu, L. Meng, Y. Lu and D. Ma (2010). 'Hypoxia induced paclitaxel resistance in human ovarian cancers via hypoxia-inducible factor 1alpha.' J Cancer Res Clin Oncol 136(3): 447-456. Hubbert, C., A. Guardiola, R. Shao, Y. Kawaguchi, A. Ito, A. Nixon, M. Yoshida, X. F. Wang and T. P. Yao (2002). 'HDAC6 is a microtubule-associated deacetylase.' Nature 417(6887): 455-458. Huisman, M. T., A. A. Chhatta, O. van Tellingen, J. H. Beijnen and A. H. Schinkel (2005). 'MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid.' Int J Cancer 116(5): 824-829. Inoki, K., M. N. Corradetti and K. L. Guan (2005). 'Dysregulation of the TSC-mTOR pathway in human disease.' Nat Genet 37(1): 19-24. Jordan, M. A., D. Thrower and L. Wilson (1992). 'Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis.' J Cell Sci 102 ( Pt 3): 401-416. Kang, J. and H. Yu (2009). 'Kinase signaling in the spindle checkpoint.' J Biol Chem 284(23): 15359-15363. Kang, J. and H. Yu (2009). 'Kinase Signaling in the Spindle Checkpoint.' Journal of Biological Chemistry 284(23): 15359-15363. Karlsson, E., G. Perez-Tenorio, R. Amin, J. Bostner, L. Skoog, T. Fornander, D. C. Sgroi, B. Nordenskjold, A. L. Hallbeck and O. Stal (2013). 'The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials.' Breast Cancer Res 15(5): R96. Keen, N. and S. Taylor (2009). 'Mitotic drivers--inhibitors of the Aurora B Kinase.' Cancer Metastasis Rev 28(1-2): 185-195. Kim, R., M. Emi and K. Tanabe (2006). 'Role of mitochondria as the gardens of cell death.' Cancer Chemotherapy and Pharmacology 57(5): 545-553. Kizaka-Kondoh, S., M. Inoue, H. Harada and M. Hiraoka (2003). 'Tumor hypoxia: a target for selective cancer therapy.' Cancer Sci 94(12): 1021-1028. Kramer, O. H., S. Mahboobi and A. Sellmer (2014). 'Drugging the HDAC6-HSP90 interplay in malignant cells.' Trends Pharmacol Sci 35(10): 501-509. Kremer, C. L., R. R. Klein, J. Mendelson, W. Browne, L. K. Samadzedeh, K. Vanpatten, L. Highstrom, G. A. Pestano and R. B. Nagle (2006). 'Expression of mTOR signaling pathway markers in prostate cancer progression.' Prostate 66(11): 1203-1212. Kufe, D. W. and J. F. Holland (2006). Holland-Frei cancer medicine. London, BC Decker. Kurmasheva, R. T., S. Huang and P. J. Houghton (2006). 'Predicted mechanisms of resistance to mTOR inhibitors.' Br J Cancer 95(8): 955-960. Lai, C. Y., S. L. Pan, X. M. Yang, L. H. Chang, Y. L. Chang, P. C. Yang, K. H. Lee and C. M. Teng (2013). 'Depletion of 4E-BP1 and regulation of autophagy lead to YXM110-induced anticancer effects.' Carcinogenesis 34(9): 2050-2060. Laird, P. W. (2005). 'Cancer epigenetics.' Hum Mol Genet 14 Spec No 1: R65-76. Lang, K. J., A. Kappel and G. J. Goodall (2002). 'Hypoxia-inducible factor-1alpha mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia.' Mol Biol Cell 13(5): 1792-1801. Leontieva, O. V., V. Natarajan, Z. N. Demidenko, L. G. Burdelya, A. V. Gudkov and M. V. Blagosklonny (2012). 'Hypoxia suppresses conversion from proliferative arrest to cellular senescence.' Proc Natl Acad Sci U S A 109(33): 13314-13318. Li, Y., G. D. Kao, B. A. Garcia, J. Shabanowitz, D. F. Hunt, J. Qin, C. Phelan and M. A. Lazar (2006). 'A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity.' Genes Dev 20(18): 2566-2579. Lin, R. J., T. Sternsdorf, M. Tini and R. M. Evans (2001). 'Transcriptional regulation in acute promyelocytic leukemia.' Oncogene 20(49): 7204-7215. Loong, H. H. and W. Yeo (2014). 'Microtubule-targeting agents in oncology and therapeutic potential in hepatocellular carcinoma.' Onco Targets Ther 7: 575-585. Luo, J., F. Su, D. Chen, A. Shiloh and W. Gu (2000). 'Deacetylation of p53 modulates its effect on cell growth and apoptosis.' Nature 408(6810): 377-381. Martin, M. E., M. I. Perez, C. Redondo, M. I. Alvarez, M. Salinas and J. L. Fando (2000). '4E binding protein 1 expression is inversely correlated to the progression of gastrointestinal cancers.' Int J Biochem Cell Biol 32(6): 633-642. Martineau, Y., R. Azar, C. Bousquet and S. Pyronnet (2013). 'Anti-oncogenic potential of the eIF4E-binding proteins.' Oncogene 32(6): 671-677. Martinez-Balbas, M. A., U. M. Bauer, S. J. Nielsen, A. Brehm and T. Kouzarides (2000). 'Regulation of E2F1 activity by acetylation.' EMBO J 19(4): 662-671. Matson, D. R. and P. T. Stukenberg (2011). 'Spindle poisons and cell fate: a tale of two pathways.' Mol Interv 11(2): 141-150. Matsuyama, A., T. Shimazu, Y. Sumida, A. Saito, Y. Yoshimatsu, D. Seigneurin-Berny, H. Osada, Y. Komatsu, N. Nishino, S. Khochbin, S. Horinouchi and M. Yoshida (2002). 'In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation.' EMBO J 21(24): 6820-6831. Mollinedo, F. and C. Gajate (2003). 'Microtubules, microtubule-interfering agents and apoptosis.' Apoptosis 8(5): 413-450. Morfoisse, F., A. Kuchnio, C. Frainay, A. Gomez-Brouchet, M. B. Delisle, S. Marzi, A. C. Helfer, F. Hantelys, F. Pujol, J. Guillermet-Guibert, C. Bousquet, M. Dewerchin, S. Pyronnet, A. C. Prats, P. Carmeliet and B. Garmy-Susini (2014). 'Hypoxia induces VEGF-C expression in metastatic tumor cells via a HIF-1alpha-independent translation-mediated mechanism.' Cell Rep 6(1): 155-167. Muller, A., C. Zang, C. Chumduri, B. Dorken, P. T. Daniel and C. W. Scholz (2013). 'Concurrent inhibition of PI3K and mTORC1/mTORC2 overcomes resistance to rapamycin induced apoptosis by down-regulation of Mcl-1 in mantle cell lymphoma.' Int J Cancer 133(8): 1813-1824. Nagata, K., A. Puls, C. Futter, P. Aspenstrom, E. Schaefer, T. Nakata, N. Hirokawa and A. Hall (1998). 'The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3.' EMBO J 17(1): 149-158. Noh, E. J. and J. S. Lee (2003). 'Functional interplay between modulation of histone deacetylase activity and its regulatory role in G2-M transition.' Biochem Biophys Res Commun 310(2): 267-273. Nowak, S. J. and V. G. Corces (2004). 'Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation.' Trends Genet 20(4): 214-220. Park, S., N. Chapuis, J. Tamburini, V. Bardet, P. Cornillet-Lefebvre, L. Willems, A. Green, P. Mayeux, C. Lacombe and D. Bouscary (2010). Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia. Petroulakis, E., Y. Mamane, O. Le Bacquer, D. Shahbazian and N. Sonenberg (2006). 'mTOR signaling: implications for cancer and anticancer therapy.' British Journal of Cancer 94(2): 195-199. Pringels, S., N. Van Damme, B. De Craene, P. Pattyn, W. Ceelen, M. Peeters and J. Grooten (2012). 'Clinical procedure for colon carcinoma tissue sampling directly affects the cancer marker-capacity of VEGF family members.' BMC Cancer 12: 515. Ray, M. E., Z. Q. Yang, D. Albertson, C. G. Kleer, J. G. Washburn, J. A. Macoska and S. P. Ethier (2004). 'Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines.' Cancer Res 64(1): 40-47. Richon, V. M., J. Garcia-Vargas and J. S. Hardwick (2009). 'Development of vorinostat: current applications and future perspectives for cancer therapy.' Cancer Lett 280(2): 201-210. Risinger, A. L., F. J. Giles and S. L. Mooberry (2009). 'Microtubule dynamics as a target in oncology.' Cancer Treat Rev 35(3): 255-261. Rojo, F., L. Najera, J. Lirola, J. Jimenez, M. Guzman, M. D. Sabadell, J. Baselga and S. Ramon y Cajal (2007). '4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis.' Clin Cancer Res 13(1): 81-89. Ruvolo, P. P., X. Deng and W. S. May (2001). 'Phosphorylation of Bcl2 and regulation of apoptosis.' Leukemia 15(4): 515-522. Sandor, V., A. Senderowicz, S. Mertins, D. Sackett, E. Sausville, M. V. Blagosklonny and S. E. Bates (2000). 'P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228.' Br J Cancer 83(6): 817-825. Semenza, G. L. (2003). 'Targeting HIF-1 for cancer therapy.' Nat Rev Cancer 3(10): 721-732. Seton-Rogers, S. (2008). 'Translation - Switching to cap-independence.' Nature Reviews Cancer 8(1). She, Q. B., E. Halilovic, Q. Ye, W. Zhen, S. Shirasawa, T. Sasazuki, D. B. Solit and N. Rosen (2010). '4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors.' Cancer Cell 18(1): 39-51. Sherr, C. J. and J. M. Roberts (1999). 'CDK inhibitors: positive and negative regulators of G1-phase progression.' Genes Dev 13(12): 1501-1512. Sherrill, K. W., M. P. Byrd, M. E. Van Eden and R. E. Lloyd (2004). 'BCL-2 translation is mediated via internal ribosome entry during cell stress.' J Biol Chem 279(28): 29066-29074. Shitashige, M., M. Toi, T. Yano, M. Shibata, Y. Matsuo and F. Shibasaki (2001). 'Dissociation of Bax from a Bcl-2/Bax heterodimer triggered by phosphorylation of serine 70 of Bcl-2.' J Biochem 130(6): 741-748. Shtil, A. A., S. Mandlekar, R. Yu, R. J. Walter, K. Hagen, T. H. Tan, I. B. Roninson and A. N. Kong (1999). 'Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells.' Oncogene 18(2): 377-384. Siegel, R. L., K. D. Miller and A. Jemal (2015). 'Cancer statistics, 2015.' CA: A Cancer Journal for Clinicians 65(1): 5-29. Silvera, D., S. C. Formenti and R. J. Schneider (2010). 'Translational control in cancer.' Nat Rev Cancer 10(4): 254-266. Simms-Waldrip, T., A. Rodriguez-Gonzalez, T. Lin, A. K. Ikeda, C. Fu and K. M. Sakamoto (2008). 'The aggresome pathway as a target for therapy in hematologic malignancies.' Mol Genet Metab 94(3): 283-286. Soubrane, C., R. Mouawad, V. Sultan, J. Spano, D. Khayat and O. Rixe (2006). 'Soluble VEGF-A and lymphangiogenesis in metastatic malignant melanoma patients.' J Clin Oncol (Meeting Abstracts) 24(18_suppl): 8049-. Stone, A. A. and T. C. Chambers (2000). 'Microtubule inhibitors elicit differential effects on MAP kinase (JNK, ERK, and p38) signaling pathways in human KB-3 carcinoma cells.' Exp Cell Res 254(1): 110-119. Sullivan, R., G. C. Pare, L. J. Frederiksen, G. L. Semenza and C. H. Graham (2008). 'Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity.' Mol Cancer Ther 7(7): 1961-1973. Tasian, S. K., D. T. Teachey and S. R. Rheingold (2014). 'Targeting the PI3K/mTOR Pathway in Pediatric Hematologic Malignancies.' Front Oncol 4: 108. Teachey, D. T., S. A. Grupp and V. I. Brown (2009). 'mTOR Inhibitors and Their Potential Role in Therapy in Leukemia and Other Haematologic Malignancies.' British journal of haematology 145(5): 569-580. Vu, C. and D. A. Fruman (2010). 'Target of Rapamycin Signaling in Leukemia and Lymphoma.' Clinical Cancer Research 16(22): 5374-5380. Vu, C. and D. A. Fruman (2010). 'Target of rapamycin signaling in leukemia and lymphoma.' Clin Cancer Res 16(22): 5374-5380. Wada, T. and J. M. Penninger (0000). 'Mitogen-activated protein kinases in apoptosis regulation.' Oncogene 23(16): 2838-2849. Walther, A., E. Johnstone, C. Swanton, R. Midgley, I. Tomlinson and D. Kerr (2009). 'Genetic prognostic and predictive markers in colorectal cancer.' Nat Rev Cancer 9(7): 489-499. Wang, J., Q. Ye and Q. B. She (2014). 'New insights into 4E-BP1-regulated translation in cancer progression and metastasis.' Cancer Cell Microenviron 1(5). Wang, T. H., D. M. Popp, H. S. Wang, M. Saitoh, J. G. Mural, D. C. Henley, H. Ichijo and J. Wimalasena (1999). 'Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun N-terminal kinase (JNK)-dependent and -independent pathways in ovarian cancer cells.' J Biol Chem 274(12): 8208-8216. Wang, T. H., H. S. Wang, H. Ichijo, P. Giannakakou, J. S. Foster, T. Fojo and J. Wimalasena (1998). 'Microtubule-interfering agents activate c-Jun N-terminal kinase/stress-activated protein kinase through both Ras and apoptosis signal-regulating kinase pathways.' J Biol Chem 273(9): 4928-4936. Weaver, B. A. and D. W. Cleveland (2005). 'Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death.' Cancer Cell 8(1): 7-12. Wertz, I. E., S. Kusam, C. Lam, T. Okamoto, W. Sandoval, D. J. Anderson, E. Helgason, J. A. Ernst, M. Eby, J. Liu, L. D. Belmont, J. S. Kaminker, K. M. O'Rourke, K. Pujara, P. B. Kohli, A. R. Johnson, M. L. Chiu, J. R. Lill, P. K. Jackson, W. J. Fairbrother, S. Seshagiri, M. J. Ludlam, K. G. Leong, E. C. Dueber, H. Maecker, D. C. Huang and V. M. Dixit (2011). 'Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7.' Nature 471(7336): 110-114. West, A. C. and R. W. Johnstone (2014). 'New and emerging HDAC inhibitors for cancer treatment.' J Clin Invest 124(1): 30-39. Wilson, A. J., D. S. Byun, N. Popova, L. B. Murray, K. L'Italien, Y. Sowa, D. Arango, A. Velcich, L. H. Augenlicht and J. M. Mariadason (2006). 'Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer.' J Biol Chem 281(19): 13548-13558. Witzig, T. E., S. M. Geyer, I. Ghobrial, D. J. Inwards, R. Fonseca, P. Kurtin, S. M. Ansell, R. Luyun, P. J. Flynn, R. F. Morton, S. R. Dakhil, H. Gross and S. H. Kaufmann (2005). 'Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma.' J Clin Oncol 23(23): 5347-5356. Xu, W. S., G. Perez, L. Ngo, C. Y. Gui and P. A. Marks (2005). 'Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects.' Cancer Res 65(17): 7832-7839. Yamamoto, K., H. Ichijo and S. J. Korsmeyer (1999). 'BCL-2 Is Phosphorylated and Inactivated by an ASK1/Jun N-Terminal Protein Kinase Pathway Normally Activated at G(2)/M.' Molecular and Cellular Biology 19(12): 8469-8478. Zhang, Y., N. Li, C. Caron, G. Matthias, D. Hess, S. Khochbin and P. Matthias (2003). 'HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo.' EMBO J 22(5): 1168-1179. Zhang, Y. and X. F. Zheng (2012). 'mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors.' Cell Cycle 11(3): 594-603. Zhang, Z., H. Yamashita, T. Toyama, H. Sugiura, Y. Omoto, Y. Ando, K. Mita, M. Hamaguchi, S. Hayashi and H. Iwase (2004). 'HDAC6 expression is correlated with better survival in breast cancer.' Clin Cancer Res 10(20): 6962-6968. Zhu, P., E. Martin, J. Mengwasser, P. Schlag, K. P. Janssen and M. Gottlicher (2004). 'Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis.' Cancer Cell 5(5): 455-463. Ziello, J. E., I. S. Jovin and Y. Huang (2007). 'Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia.' Yale J Biol Med 80(2): 51-60. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/4661 | - |
dc.description.abstract | 目前最新的世界衛生組織統計,癌症是世界上致死率與發病率的主要原因之一,在 2012 年有八百二十萬的人口死於癌症相關疾病,且預測在未來的 20年裡,新的案例會以每年成長 57% 的速率增加。而且根據台灣衛生福利部的統計結果,在過去的三十年裡,癌症在台灣的十大死因中始終位於首位。尋求理想的合併療法以降低抗癌藥物的毒性和減少抗藥性的產生,發展新的小分子藥物來改善目前臨床上抗癌藥物使用的瓶頸,以及建立重要的癌症預後因子並根據其研發新穎的分子標拔藥物一直是治療癌症的最終目標。在此篇論文中,我們將研究 (1) vincristine 和 vorinostat 合併使用在人類急性淋巴性白血病的作用機轉,(2) 探討 MPT0B392 在人類急性白血病中的抗癌機轉,和 (3) 評估 eIF4E binding protein 1 (4E-BP1) 對於人類大腸直腸癌在臨床上的重要性。
Vincristine 是一種傳統的微管抑制劑,在臨床上常用於治療急性淋巴性白血病的合併療法中;vorinostat,俗稱SAHA,是第一個被 FDA 認可使用在 T 細胞淋巴瘤的廣泛型組織蛋白去乙醯酶抑制劑 (HDAC inhibitor)。在此論文的第一部分中,我們將著重 vincristine 和 vorinostat 合併使用之抗白血病機轉探討,由實驗結果發現當合併使用 vincristine 和 vorinostat後使得白血病細胞加成性的停留在 G2M 期,並隨之明顯地累積在 subG1 期;低濃度的 vincristine 會影響微管的動態平衡,在加入 vorinostat 之後會增加此現象,主要是因為 vorinostat 會藉由抑制 HDAC6 的活性因而促進微管蛋白的乙醯化進而使得微管的動態平衡改變;且在當我們併用 vincristine 和 HDAC6 專一性抑制劑 (tubastatin A 和 Acy1215) 也觀察到此加成的現象。除此之外, vincristine-vorinostat 的合併使用在小鼠體內異種移植的動物實驗中也具有較佳的療效且耐受性良好。根據這些結果,合併使用微管抑制劑和組織蛋白去乙醯酶抑制劑可以做為臨床上治療急性淋巴性白血病的基礎概念。 在第二部分中,我們探討一個全新可口服的 quinoline 衍生物-MPT0B392 (B392) 在急性白血病的抗癌機轉。B392 會使得人類急性白血球細胞滯留在 G2M 期,但最終還是會進行細胞凋亡,從小鼠異體移植的切片染色得知,投與 B392 會增加 cleavage-caspase 3的表現。B392 也會抑制微管的聚合作用,並且不會影響 P-gp 的活性,同時會活化 mitotic spindle checkpoint 以及 c-Jun-N-terminal-kinase (JNK),而 JNK 的磷酸化會進一步流失粒線體的膜電位以及各種 caspases 的活化和 PARP cleavage。另外,我們也發現 B392 在對 sirolimus (mTOR 抑制劑) 具有抗性的細胞中會增強sirolimus 的細胞毒性。因此,由以上結果可知,不論是單獨使用或是合併療法,B392 是個具有發展潛力的抗白血病藥物。 4E-BP1 (eIF4E binding protein 1) 在 cap-dependent 以及 cap-independent 轉譯的路徑中扮演著關鍵的調控角色,也因此控制了蛋白質的生合成。在第三部分,我們認為 4E-BP1 在大腸直腸癌中是個重要的預後因子。在人類大腸直腸癌細胞株與癌化的組織中4E-BP1 蛋白質的表現量遠高於正常的大腸細胞株和組織,且藉由分析臨床病人的病理參數發現 4E-BP1 蛋白的表現量與疾病進程具有統計上的相關性。在缺氧的情況下,4E-BP1 在 cap-independent 轉譯過程中更顯重要;此外,cryptopleurine 衍生物 YXM110 也已被證實會藉由抑制 4E-BP1 的表現來達到腫瘤抑制作用,因此,我們更進一步去研究在缺氧情況下 YXM110 抑制蛋白質生合成的情況。由結果得知,YXM110 可以經由抑制 HIF-1 | zh_TW |
dc.description.abstract | Cancer is the leading causes of mortality and morbidity worldwide with approximately 8.2 million cancer related deaths in 2012 and is expected that annual new cases will rise 57% within the next two decades as reported by World Health Worldwide. According to the statistics from Taiwan’s Ministry of Health and Welfare, cancer has taken the first position in causes of death in Taiwan in the past three decades. Searching for the optimal combination therapeutic approaches to decrease drugs toxicities and resistance, developing novel small molecular agents to improve current treatments and identifying the important prognostic factors to design the targeted therapies are our ultimate goals of eliminating cancers. In this thesis, we investigated (1) the effect of vincristine-vorinostat combination on human acute lymphoblastic leukemia (ALL), (2) the mechanism underlying anticancer activity of MPT0B392 on human acute leukemia and (3) the clinical importance of eIF4E binding protein 1 (4E-BP1) on human colorectal cancer (CRC).
Vincristine, a traditional microtubule-depolymerizing agent, is one of combination chemotherapy drugs used in treatment of ALL; vorinostat, also called SAHA, was the first approved pan-HDAC inhibitor for T cell lymphoma. In the first study, we investigated the vincristine and vorinostat combined effect and the underlying antileukemic mechanism. Our data showed that combination of vincristine and vorinostat induced cells arrest synergistically in the G2M phase, following by obviously accumulation in the subG1 phase. Low concentration of vincristine caused microtubule dynamic changes, and this phenomenon was enhanced by co-incubated with vorinostat, which inhibited HDAC6, causing tubulin acetylation, also leading to microtubule instabilities. This result was consistent with vincristine in combination with HDAC6 inhibitors, tubastatin A and Acy1215. In vivo xenografting experiments corroborated the in vitro activity and tolerability of the combination. Based on these findings, the combination of microtubule depolymerizing agents and HDAC inhibitors can provide the basis of clinical treatment for ALL. In the second study, we elucidated the underlying mechanisms of a novel quinoline derivative, MTP0B392 (B392), which was specially designed for oral administration. B392 induced acute leukemic cells arrest in the G2M phase and ultimately led to apoptosis, which was corroborated by the observation of cleavaged-caspase 3 by immunohistochemistry staining in B392-treated groups of xenograft experiments. B392 also suppressed microtubule polymerization with less susceptibility to P-gp activity, activated mitotic spindle checkpoint as well as caused activation of c-Jun-N-terminal-kinase (JNK), which further contributing to mitochondrial membrane potential loss, caspases and PARP cleavages. Furthermore, B392 had an ability to enhance the cyototoxicity of sirolimus (mTOR inhibitor) in the sirolimus-resistant cells. Our results suggest that B392 is a potential antileukemic drug that could be applied in mono- and combination therapy. 4E-BP1 (eIF4E binding protein 1) is a key regulator in cap-dependent and independent translation, thereby controlling protein synthesis. In the third study, we identified 4E-BP1 as an important prognostic factor in CRC. We found that the protein expression level of 4E-BP1 was more abundant in colorectal cancer cell lines and patients’ tissues when compared to normal colon cell line and tissues. By the analysis of clinical patients’ pathological parameters, 4E-BP1 expression has statically correlation with disease progression. Under hypoxia, 4E-BP1 is thought to be a crucial factor for cap-independent translation. Additionally, YMX-110, a cryptopleurine derivative, led to tumor suppression by deletion of 4E-BP1. Thus, the inhibition of protein synthesis by YXM110 in hypoxic condition was further evaluated. Our data show that YXM110 decreased hypoxia-inducible factor 1 | en |
dc.description.provenance | Made available in DSpace on 2021-05-14T17:44:50Z (GMT). No. of bitstreams: 1 ntu-104-D98443001-1.pdf: 9393200 bytes, checksum: 680c5fffc47ee9b6f65f513de99bb2dd (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 口試委員會審定書………………………………………………………………….………………I
誌謝……………………………………………………………………………….…………………II Abbreviations……………………………………………………………………….………………IV 中文摘要…………………………………………………………………………….…………..…...1 Abstract ……………………………………………………………………………………………....4 Chapter 1 Introduction………….…………………………………………………….…………..….7 1.1 Research Motivation and Aim………………………..………………..……………………7 1.2 Literature Reviews……………………………………………...……...………..…………..9 Chapter 2 Materials and Methods…………………………………………………………………...47 2.1 Materials……………………………………………………………….……….…………..47 2.2 Methods……………………………………………………………….………….………...49 Chapter 3 The synergic anticancer effect of vincristine and vorinostat in leukemia in vitro and in vivo 中文摘要……………………………………………………………….….….………………..59 Abstract……………………………………………………………….…….………………….60 3.1 Results…………………………………………………….…….……….…...…………….61 3.2 Discussion……………………………………………………..……………………...……67 Chapter 4 An oral quinoline derivative, MPT0B392, causes the mitotic arrest and overcomes sirolimus-resistant human acute leukemic cells 中文摘要…………………………………………………………………………..………...…91 Abstract……………………………………………………………………………..………….92 4.1 Results……………………………………………………………………..…………….....93 4.2 Discussion…………………………………………………………...……..……………....98 Chapter 5 eIF4E binding protein 1 expression is associated with clinical survival outcomes in colorectal cancer patients 中文摘要…………………………………………………………………………..……….....118 Abstract……………………………………………………………………………..………...119 5.1 Results……………………………………………………………………..……………...120 5.2 Discussion…………………………………………………………...……..……………..124 Chapter 6 Conclusion and Perspectives……………………………………….……..……………141 Publications………………..……………………………………………….…………..……….....145 References………………………………………………………………….…………..……….....146 | |
dc.language.iso | en | |
dc.title | 探討 vincristine-vorinostat 合併使用與微管抑制劑 MPT0B392 之抗癌機轉及eIF4E binding protein 1 在癌症中的重要性 | zh_TW |
dc.title | Anticancer mechanisms of vincristine-vorinostat combination and a tubulin-binding agent MPT0B392,and the role of eIF4E binding protein 1 in cancer patients | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 潘秀玲 | |
dc.contributor.oralexamcommittee | 黃德富,顏茂雄,楊春茂,蕭哲志 | |
dc.subject.keyword | vincristine-vorinostat 合併療法,MPT0B392 微管抑制劑,eIF4E binding protein 1 大腸直腸癌, | zh_TW |
dc.subject.keyword | vincristine-vorinostat combination, MPT0B392,tubulin binding agent,eIF4E binding protein 1,colorectal cancer, | en |
dc.relation.page | 158 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2015-07-24 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
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