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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧哲明(Che-Ming Teng) | |
| dc.contributor.author | Yi-Chiu Kuo | en |
| dc.contributor.author | 郭憶萩 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:19:40Z | - |
| dc.date.copyright | 2010-09-13 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-21 | |
| dc.identifier.citation | Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S, Lorca T, Cleveland DW & Labbe JC (2001) Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106, 83-93.
ACOG. (2002) The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. Gynecol Oncol 87, 237-239. ACOG. (2007) ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol 110, 201-214. Acquaviva C & Pines J (2006) The anaphase-promoting complex/cyclosome: APC/C. J Cell Sci 119, 2401-2404. Allan LA & Clarke PR (2007) Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis. Mol Cell 26, 301-310. Allan LA, Morrice N, Brady S, Magee G, Pathak S & Clarke PR (2003) Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK. Nat Cell Biol 5, 647-654. Bain J, McLauchlan H, Elliott M & Cohen P (2003) The specificities of protein kinase inhibitors: an update. Biochem J 371, 199-204. Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL & Korsmeyer SJ (1985) Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 41, 899-906. Barney SP, Muller CY & Bradshaw KD (2008) Pelvic masses. Med Clin North Am 92, 1143-1161, xi. Bast RC, Jr., Hennessy B & Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 9, 415-428. Becker M, Stolz A, Ertych N & Bastians H (2010) Centromere localization of INCENP-aurora B is sufficient to support spindle checkpoint function. Cell Cycle 9. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM & Anderson DW (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A 98, 13681-13686. Brenner D & Mak TW (2009) Mitochondrial cell death effectors. Curr Opin Cell Biol 21, 871-877. Brito DA & Rieder CL (2006) Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol 16, 1194-1200. Campbell IG, Russell SE, Choong DY, Montgomery KG, Ciavarella ML, Hooi CS, Cristiano BE, Pearson RB & Phillips WA (2004) Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64, 7678-7681. Caspari T (2000) How to activate p53. Curr Biol 10, R315-317. Castedo M, Perfettini JL, Roumier T & Kroemer G (2002) Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe. Cell Death Differ 9, 1287-1293. Chan YW, Ma HT, Wong W, Ho CC, On KF & Poon RY (2008) CDK1 inhibitors antagonize the immediate apoptosis triggered by spindle disruption but promote apoptosis following the subsequent rereplication and abnormal mitosis. Cell Cycle 7, 1449-1461. Chang L, Kamata H, Solinas G, Luo JL, Maeda S, Venuprasad K, Liu YC & Karin M (2006) The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 124, 601-613. Chaparro M, Gonzalez Moreno L, Trapero-Marugan M, Medina J & Moreno-Otero R (2008) Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents. Aliment Pharmacol Ther 28, 1269-1277. Chen TH, Pan SL, Guh JH, Liao CH, Huang DY, Chen CC & Teng CM (2008) Moscatilin induces apoptosis in human colorectal cancer cells: a crucial role of c-Jun NH2-terminal protein kinase activation caused by tubulin depolymerization and DNA damage. Clin Cancer Res 14, 4250-4258. Cheng EH, Sheiko TV, Fisher JK, Craigen WJ & Korsmeyer SJ (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301, 513-517. Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T & Korsmeyer SJ (2001) BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8, 705-711. Chetoui N, Sylla K, Gagnon-Houde JV, Alcaide-Loridan C, Charron D, Al-Daccak R & Aoudjit F (2008) Down-regulation of mcl-1 by small interfering RNA sensitizes resistant melanoma cells to fas-mediated apoptosis. Mol Cancer Res 6, 42-52. Clarke PR & Allan LA (2009) Cell-cycle control in the face of damage--a matter of life or death. Trends Cell Biol 19, 89-98. Cleary ML, Smith SD & Sklar J (1986) Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47, 19-28. Cory S & Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2, 647-656. Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, Zhou H, Sen S, Allis CD & Sassone-Corsi P (2002) Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol 22, 874-885. D'Amelio M, Tino E & Cecconi F (2008) The apoptosome: emerging insights and new potential targets for drug design. Pharm Res 25, 740-751. D'Angiolella V, Mari C, Nocera D, Rametti L & Grieco D (2003) The spindle checkpoint requires cyclin-dependent kinase activity. Genes Dev 17, 2520-2525. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y & Greenberg ME (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231-241. Davis FM, Tsao TY, Fowler SK & Rao PN (1983) Monoclonal antibodies to mitotic cells. Proc Natl Acad Sci U S A 80, 2926-2930. Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103, 239-252. DeLuca JG, Gall WE, Ciferri C, Cimini D, Musacchio A & Salmon ED (2006) Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. Cell 127, 969-982. Deng Y, Ren X, Yang L, Lin Y & Wu X (2003) A JNK-dependent pathway is required for TNFalpha-induced apoptosis. Cell 115, 61-70. Dewson G, Kratina T, Sim HW, Puthalakath H, Adams JM, Colman PM & Kluck RM (2008) To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3:groove interactions. Mol Cell 30, 369-380. Dhillon AS, Hagan S, Rath O & Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26, 3279-3290. Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N & Taylor SS (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 161, 267-280. Downing KH & Nogales E (1999) Crystallographic structure of tubulin: implications for dynamics and drug binding. Cell Struct Funct 24, 269-275. Du L, Lyle CS & Chambers TC (2005) Characterization of vinblastine-induced Bcl-xL and Bcl-2 phosphorylation: evidence for a novel protein kinase and a coordinated phosphorylation/dephosphorylation cycle associated with apoptosis induction. Oncogene 24, 107-117. Dy GK & Adjei AA (2009) Emerging therapeutic targets in non-small cell lung cancer. Proc Am Thorac Soc 6, 218-223. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35, 495-516. Engelman JA, Luo J & Cantley LC (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7, 606-619. Ernest NJ, Habela CW & Sontheimer H (2008) Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death. J Cell Sci 121, 290-297. Fan M, Goodwin M, Vu T, Brantley-Finley C, Gaarde WA & Chambers TC (2000) Vinblastine-induced phosphorylation of Bcl-2 and Bcl-XL is mediated by JNK and occurs in parallel with inactivation of the Raf-1/MEK/ERK cascade. J Biol Chem 275, 29980-29985. Fu Z & Tindall DJ (2008) FOXOs, cancer and regulation of apoptosis. Oncogene 27, 2312-2319. Furukawa Y, Iwase S, Kikuchi J, Terui Y, Nakamura M, Yamada H, Kano Y & Matsuda M (2000) Phosphorylation of Bcl-2 protein by CDC2 kinase during G2/M phases and its role in cell cycle regulation. J Biol Chem 275, 21661-21667. Gascoigne KE & Taylor SS (2008) Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell 14, 111-122. Gershenson DM (1994) Management of early ovarian cancer: germ cell and sex cord-stromal tumors. Gynecol Oncol 55, S62-72. Gu L, Zheng H, Murray SA, Ying H & Jim Xiao ZX (2003) Deregulation of Cdc2 kinase induces caspase-3 activation and apoptosis. Biochem Biophys Res Commun 302, 384-391. Guillem V & Poveda A (2007) Germ cell tumours of the ovary. Clin Transl Oncol 9, 237-243. Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B & Davis RJ (1996) Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15, 2760-2770. Gynecologists. ACoOa (2002) The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. Gynecol Oncol 87, 237-239. Gynecologists. ACoOa (2007) ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol 110, 201-214. Haldar S, Jena N & Croce CM (1995) Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci U S A 92, 4507-4511. Halilovic E & Solit DB (2008) Therapeutic strategies for inhibiting oncogenic BRAF signaling. Curr Opin Pharmacol 8, 419-426. Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL & Peters JM (2003) The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol 161, 281-294. Hengartner MO & Horvitz HR (1994) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76, 665-676. Hu L, Hofmann J, Lu Y, Mills GB & Jaffe RB (2002) Inhibition of phosphatidylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res 62, 1087-1092. Huang C, Jacobson K & Schaller MD (2004) MAP kinases and cell migration. J Cell Sci 117, 4619-4628. Igney FH & Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2, 277-288. Jeffers JR, Parganas E, Lee Y, Yang C, Wang J, Brennan J, MacLean KH, Han J, Chittenden T, Ihle JN, McKinnon PJ, Cleveland JL & Zambetti GP (2003) Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell 4, 321-328. Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH & Kops GJ (2008) Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 132, 233-246. Jones MH, Huneycutt BJ, Pearson CG, Zhang C, Morgan G, Shokat K, Bloom K & Winey M (2005) Chemical genetics reveals a role for Mps1 kinase in kinetochore attachment during mitosis. Curr Biol 15, 160-165. Jordan MA & Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4, 253-265. Kang J & Yu H (2009) Kinase signaling in the spindle checkpoint. J Biol Chem 284, 15359-15363. Kim EK & Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802, 396-405. Kim H, Tu HC, Ren D, Takeuchi O, Jeffers JR, Zambetti GP, Hsieh JJ & Cheng EH (2009) Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell 36, 487-499. Kim HE, Du F, Fang M & Wang X (2005a) Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc Natl Acad Sci U S A 102, 17545-17550. Kim M, Murphy K, Liu F, Parker SE, Dowling ML, Baff W & Kao GD (2005b) Caspase-mediated specific cleavage of BubR1 is a determinant of mitotic progression. Mol Cell Biol 25, 9232-9248. Kiyokawa H & Ray D (2008) In vivo roles of CDC25 phosphatases: biological insight into the anti-cancer therapeutic targets. Anticancer Agents Med Chem 8, 832-836. Kuwana T & Newmeyer DD (2003) Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol 15, 691-699. Lan W, Zhang X, Kline-Smith SL, Rosasco SE, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Walczak CE & Stukenberg PT (2004) Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. Curr Biol 14, 273-286. Lavrik I, Golks A & Krammer PH (2005) Death receptor signaling. J Cell Sci 118, 265-267. Li H, Zhu H, Xu CJ & Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501. Li J & Yuan J (2008) Caspases in apoptosis and beyond. Oncogene 27, 6194-6206. Ling YH, Tornos C & Perez-Soler R (1998) Phosphorylation of Bcl-2 is a marker of M phase events and not a determinant of apoptosis. J Biol Chem 273, 18984-18991. Liu D, Vader G, Vromans MJ, Lampson MA & Lens SM (2009) Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science 323, 1350-1353. Lomonosova E & Chinnadurai G (2008) BH3-only proteins in apoptosis and beyond: an overview. Oncogene 27 Suppl 1, S2-19. Lynch HT & de la Chapelle A (2003) Hereditary colorectal cancer. N Engl J Med 348, 919-932. Malumbres M & Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9, 153-166. Masters SC, Yang H, Datta SR, Greenberg ME & Fu H (2001) 14-3-3 inhibits Bad-induced cell death through interaction with serine-136. Mol Pharmacol 60, 1325-1331. Matsumura S, Toyoshima F & Nishida E (2007) Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1. J Biol Chem 282, 15217-15227. Maurer U, Charvet C, Wagman AS, Dejardin E & Green DR (2006) Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell 21, 749-760. McGrogan BT, Gilmartin B, Carney DN & McCann A (2008) Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta 1785, 96-132. Micheau O & Tschopp J (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114, 181-190. Mitchison T & Kirschner M (1984) Dynamic instability of microtubule growth. Nature 312, 237-242. Miura M, Zhu H, Rotello R, Hartwieg EA & Yuan J (1993) Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75, 653-660. Modur V, Nagarajan R, Evers BM & Milbrandt J (2002) FOXO proteins regulate tumor necrosis factor-related apoptosis inducing ligand expression. Implications for PTEN mutation in prostate cancer. J Biol Chem 277, 47928-47937. Morrow CJ, Tighe A, Johnson VL, Scott MI, Ditchfield C & Taylor SS (2005) Bub1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20. J Cell Sci 118, 3639-3652. Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A, Smotkin D, Ben-David Y, Rosenblatt J, Russo D, Schwartz P, Tung N, Warner E, Rosen B, Friedman J, Brunet JS & Narod SA (2000) BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 66, 1259-1272. Musacchio A & Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8, 379-393. O'Connor DS, Wall NR, Porter AC & Altieri DC (2002) A p34(cdc2) survival checkpoint in cancer. Cancer Cell 2, 43-54. Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ & Campbell IG (1998) Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 58, 2095-2097. Obexer P, Geiger K, Ambros PF, Meister B & Ausserlechner MJ (2007) FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells. Cell Death Differ 14, 534-547. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T & Tanaka N (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288, 1053-1058. Oza AM, Eisenhauer EA, Elit L, Cutz JC, Sakurada A, Tsao MS, Hoskins PJ, Biagi J, Ghatage P, Mazurka J, Provencher D, Dore N, Dancey J & Fyles A (2008) Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. J Clin Oncol 26, 4319-4325. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE & Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497-1500. Perera D & Freire R (2005) Human spindle checkpoint kinase Bub1 is cleaved during apoptosis. Cell Death Differ 12, 827-830. Pinsky BA & Biggins S (2005) The spindle checkpoint: tension versus attachment. Trends Cell Biol 15, 486-493. Rodriguez J & Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13, 3179-3184. Roett MA & Evans P (2009) Ovarian cancer: an overview. Am Fam Physician 80, 609-616. Ryerson AB, Eheman C, Burton J, McCall N, Blackman D, Subramanian S & Richardson LC (2007) Symptoms, diagnoses, and time to key diagnostic procedures among older U.S. women with ovarian cancer. Obstet Gynecol 109, 1053-1061. Sanchez-Perez T, Ortiz-Ferron G & Lopez-Rivas A (2010) Mitotic arrest and JNK-induced proteasomal degradation of FLIP and Mcl-1 are key events in the sensitization of breast tumor cells to TRAIL by antimicrotubule agents. Cell Death Differ 17, 883-894. Savill J & Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407, 784-788. Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH & Peter ME (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17, 1675-1687. Schmidt M, Budirahardja Y, Klompmaker R & Medema RH (2005) Ablation of the spindle assembly checkpoint by a compound targeting Mps1. EMBO Rep 6, 866-872. Schubbert S, Shannon K & Bollag G (2007) Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 7, 295-308. Seidman JD & Kurman RJ (2000) Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol 31, 539-557. Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB & Gray JW (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21, 99-102. Shen SC, Huang TS, Jee SH & Kuo ML (1998) Taxol-induced p34cdc2 kinase activation and apoptosis inhibited by 12-O-tetradecanoylphorbol-13-acetate in human breast MCF-7 carcinoma cells. Cell Growth Differ 9, 23-29. Sherr CJ & Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13, 1501-1512. Shitashige M, Toi M, Yano T, Shibata M, Matsuo Y & Shibasaki F (2001) Dissociation of Bax from a Bcl-2/Bax heterodimer triggered by phosphorylation of serine 70 of Bcl-2. J Biochem 130, 741-748. Sliedrecht T, Zhang C, Shokat KM & Kops GJ (2010) Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis. PLoS One 5, e10251. Smith LH, Morris CR, Yasmeen S, Parikh-Patel A, Cress RD & Romano PS (2005) Ovarian cancer: can we make the clinical diagnosis earlier? Cancer 104, 1398-1407. Sorensen CS, Syljuasen RG, Falck J, Schroeder T, Ronnstrand L, Khanna KK, Zhou BB, Bartek J & Lukas J (2003) Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell 3, 247-258. Srivastava RK, Mi QS, Hardwick JM & Longo DL (1999) Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis. Proc Natl Acad Sci U S A 96, 3775-3780. Stirling D, Evans DG, Pichert G, Shenton A, Kirk EN, Rimmer S, Steel CM, Lawson S, Busby-Earle RM, Walker J, Lalloo FI, Eccles DM, Lucassen AM & Porteous ME (2005) Screening for familial ovarian cancer: failure of current protocols to detect ovarian cancer at an early stage according to the international Federation of gynecology and obstetrics system. J Clin Oncol 23, 5588-5596. Sudakin V, Chan GK & Yen TJ (2001) Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol 154, 925-936. Sudo T, Nitta M, Saya H & Ueno NT (2004) Dependence of paclitaxel sensitivity on a functional spindle assembly checkpoint. Cancer Res 64, 2502-2508. Suhara T, Kim HS, Kirshenbaum LA & Walsh K (2002) Suppression of Akt signaling induces Fas ligand expression: involvement of caspase and Jun kinase activation in Akt-mediated Fas ligand regulation. Mol Cell Biol 22, 680-691. Suzuki M, Youle RJ & Tjandra N (2000) Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103, 645-654. Taylor SS & McKeon F (1997) Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell 89, 727-735. Terrano DT, Upreti M & Chambers TC (2010) Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol 30, 640-656. Thigpen T, Brady MF, Omura GA, Creasman WT, McGuire WP, Hoskins WJ & Williams S (1993) Age as a prognostic factor in ovarian carcinoma. The Gynecologic Oncology Group experience. Cancer 71, 606-614. Tsai AC, Pan SL, Liao CH, Guh JH, Wang SW, Sun HL, Liu YN, Chen CC, Shen CC, Chang YL & Teng CM (2010) Moscatilin, a bibenzyl derivative from the India orchid Dendrobrium loddigesii, suppresses tumor angiogenesis and growth in vitro and in vivo. Cancer Lett 292, 163-170. Tsujimoto Y, Cossman J, Jaffe E & Croce CM (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science 228, 1440-1443. van Vugt MA, van de Weerdt BC, Vader G, Janssen H, Calafat J, Klompmaker R, Wolthuis RM & Medema RH (2004) Polo-like kinase-1 is required for bipolar spindle formation but is dispensable for anaphase promoting complex/Cdc20 activation and initiation of cytokinesis. J Biol Chem 279, 36841-36854. Villedieu M, Louis MH, Dutoit S, Brotin E, Lincet H, Duigou F, Staedel C, Gauduchon P & Poulain L (2007) Absence of Bcl-xL down-regulation in response to cisplatin is associated with chemoresistance in ovarian carcinoma cells. Gynecol Oncol 105, 31-44. Vivanco I & Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2, 489-501. Voisin L, Julien C, Duhamel S, Gopalbhai K, Claveau I, Saba-El-Leil MK, Rodrigue-Gervais IG, Gaboury L, Lamarre D, Basik M & Meloche S (2008) Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors. BMC Cancer 8, 337. Wang L, Du F & Wang X (2008) TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133, 693-703. Wang XT, Pei DS, Xu J, Guan QH, Sun YF, Liu XM & Zhang GY (2007) Opposing effects of Bad phosphorylation at two distinct sites by Akt1 and JNK1/2 on ischemic brain injury. Cell Signal 19, 1844-1856. Warr MR & Shore GC (2008) Unique biology of Mcl-1: therapeutic opportunities in cancer. Curr Mol Med 8, 138-147. Weaver BA & Cleveland DW (2005) Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. Cancer Cell 8, 7-12. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB & Korsmeyer SJ (2000) tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14, 2060-2071. Wei SH, Dong K, Lin F, Wang X, Li B, Shen JJ, Zhang Q, Wang R & Zhang HZ (2008) Inducing apoptosis and enhancing chemosensitivity to gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell. Cancer Chemother Pharmacol 62, 1055-1064. Weston CR & Davis RJ (2007) The JNK signal transduction pathway. Curr Opin Cell Biol 19, 142-149. Wyllie AH, Kerr JF & Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68, 251-306. Yamaguchi H & Wang HG (2001) The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change. Oncogene 20, 7779-7786. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS & Workman P (2008) Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol 8, 393-412. Youle RJ & Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9, 47-59. Yuan J & Horvitz HR (1992) The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 116, 309-320. Yue P, Zhou Z, Khuri FR & Sun SY (2006) Depletion of intracellular glutathione contributes to JNK-mediated death receptor 5 upregulation and apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me). Cancer Biol Ther 5, 492-497. Zou W, Liu X, Yue P, Zhou Z, Sporn MB, Lotan R, Khuri FR & Sun SY (2004) c-Jun NH2-terminal kinase-mediated up-regulation of death receptor 5 contributes to induction of apoptosis by the novel synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1, 9-dien-28-oate in human lung cancer cells. Cancer Res 64, 7570-7578. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22515 | - |
| dc.description.abstract | 卵巢癌病人當被診斷出時大多已是後期，導致卵巢癌病人的存活率極差，目前卵巢癌的死亡率在女性排名為第八位。為了研究環草石斛成分 moscatilin 之衍生物 MT-6 是否在卵巢癌細胞具有抑制作用，及探討可能之作用機轉，我們做了以下實驗。利用 SRB 和 MTT 試驗發現 MT-6 在48 小時有濃度依賴性的抑制癌細胞的增生與生長，在 SKOV3 和 OVCAR3 細胞株的 GI50 分別為 0.041 μM 和 0.062 μM，在 SKOV3 和OVCAR3 細胞株的 IC50 分別為 0.073 μM 和 0.192 μM。接著我們利用 PI 染色合併流式細胞儀分析，發現 MT-6 有濃度及時間依賴性地使細胞聚集到 G2/M 期，伴隨 sub-G1 細胞比例的增加，此現象可能是 MT-6 影響微管的動態所造成。在許多微管抑制藥物皆會造成細胞停滯在 M 期而非 G2 期，所以我們檢查 M 期的指標蛋白MPM2 及 Histone-3 ser10 磷酸化的現象。在卵巢癌細胞加入 MT-6 後，的確可以看到 MPM2 及 Histone-3 ser10 磷酸化增加的現象。另一方面因為 MT-6 使 caspase-3、-7、-8、-9 及 -10 活化，所以代表其不僅活化細胞凋亡的內生性途徑也活化了外生性途徑。因此我們往細胞凋亡途徑的上游尋找，像是死亡受體與 Bcl-2 家族蛋白，結果發現 MT-6 能增加卵巢癌細胞 DR5 的表達，引起 Bid cleavage，另外促使 Bcl-2 磷酸化，及降低 Mcl-1 及 Bcl-xL 的表達。同時我們也確認 Akt 及 MAPK 在 MT-6 造成的細胞凋亡所扮演的角色，發現 MT-6 能同時在 SKOV3 及 OVCAR3 細胞造成 JNK 活化，因此在 MT-6 所造成的細胞凋亡中，JNK的角色相對於 Akt、Erk 及 p38 可能較為重要。最後我們發現 JNK 抑制劑 SP600125 能避免 MT-6 所造成的細胞凋亡及 M 期滯留，而這抑制現象也會出現在 taxol 及 vincristine 處理過的細胞，此與我們的 MT-6 作用相呼應。綜合以上結果，MT-6 改變微管蛋白的動態，使細胞週期停留在 M 期，造成 JNK 活化，並經由活化 caspase 來造成細胞凋亡，所以 MT-6 具有潛力發展成新的抗癌藥物。 | zh_TW |
| dc.description.abstract | Ovarian cancer patients are always diagnosed at an advanced stage resulting in poor survival rates. So far ovarian cancer is the eighth cause of cancer deaths among women. To study the effects of MT-6, a derivative of moscatilin, on human ovarian cancer cells, several experiments were performed. The data showed that MT-6 inhibited cell proliferation in a concentration-dependent manner using sulphorodamine B (SRB) and 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay. After 48 hours of treatment, the GI50 values of SKOV3 and OVCAR3 are 0.041 μM and 0.062 μM, respectively, by SRB assay; the IC50 values are 0.073 μM and 0.192 μM, respectively, by MTT assay. Cell cycle analysis of SKOV3 cells was determined by flow cytometric analysis with propidium iodide (PI) staining. We found that MT-6 induced a concentration- and time-dependent arrest of the cell-cycle at G2/M phase followed by an increase of cell proportion at sub-G1 phase. The effect was caused by alternation of tubulin dynamics by in vitro tubulin assay and confocal microscopic examination. To further determine whether MT-6 induced G2 or mitotic arrest of the cell cycle, the two mitotic markers, MPM2 and Histone-3 ser10 were examined in this study. The data demonstrated that MT-6 induced a dramatic increase of phosphorylation of MPM2 and Histone-3 at ser10. Moreover, both intrinsic and extrinsic apoptosis pathways were activated by the detection of catalytic cleavage of caspase-3, -7, -8, -9, -10, poly (ADP)-ribose polymerase-1 (PARP, the substrate of caspase-3 and -7). We further examined the upstream regulators of apoptotic pathways, such as death receptors and Bcl-2 family proteins. As a result, MT-6 increased DR5 expression and caused bid cleavage. Besides, MT-6 induced Bcl-2 phosphorylation and downregulation of anti-apoptotic protein Bcl-xL and Mcl-1 expression. The role of Akt and MAPK apoptotsis was also examined. The results showd that MT-6 activated JNK, whereas inhibited or had no effect on Akt, Erk and p38 in SKOV3 and OVCAR3 cells, depending on cell types. Of note, the data showed that SP600125, a JNK inhibitor, inhibited MT-6-induced caspase activation and mitotic arrest. Similarly, SP600125 also inhibited taxol- or vincristine-induced mitotic arrest and apoptosis. In summary, the results suggest that MT-6 is able to change tubulin dynamics, leading to mitotic arrest of the cell cycle and JNK activation which ultimately causes apoptosis through the intrinsic and extrinsic apoptotic pathways. The study provides evidence that MT-6 is a potential anticancer agent for further development. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:19:40Z (GMT). No. of bitstreams: 1 ntu-99-R97443009-1.pdf: 4667566 bytes, checksum: b0f3e6a15a92ce0c0b0874a8f74742e0 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 致 謝 i
縮寫表 ii 中文摘要 iii 英文摘要 iv 第一章 緒論 1 第二章 文獻回顧 4 第三章 實驗材料與方法 37 第一節 實驗材料 37 第二節 實驗方法 39 第四章 結果 47 第五章 討論 52 第六章 結論與展望 58 參考文獻 78 著作 92 | |
| dc.language.iso | zh-TW | |
| dc.subject | 卵巢癌 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | apoptosis | en |
| dc.subject | ovarian cancer | en |
| dc.title | Moscatilin 之衍生物 MT-6 在人類卵巢癌細胞引起細胞凋亡之機轉探討 | zh_TW |
| dc.title | The apoptotic mechanisms of MT-6, a derivative of moscatilin, in human ovarian cancer cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃德富(Tur-Fu Huang),顧記華(Jih-Hwa Guh),楊春茂(Chuen-Mao Yang),顏茂雄(Mao-Hsiung Yen),潘秀玲(Shiow-Lin Pan) | |
| dc.subject.keyword | 細胞凋亡,卵巢癌, | zh_TW |
| dc.subject.keyword | apoptosis,ovarian cancer, | en |
| dc.relation.page | 92 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2010-07-21 | |
| 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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