請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/27501
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳青周 | |
dc.contributor.author | Jun-Jie Chen | en |
dc.contributor.author | 陳俊杰 | zh_TW |
dc.date.accessioned | 2021-06-12T18:07:25Z | - |
dc.date.available | 2013-02-19 | |
dc.date.copyright | 2008-02-19 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-12-26 | |
dc.identifier.citation | Reference
Adams J (2004) The Proteasome: a Suitable Antineoplastic Target. Nat Rev Cancer 4:349-360. Adams J (2003) The Proteasome: Structure, Function, and Role in the Cell. Cancer Treat Rev 29 Suppl 1:3-9. Aggarwal BB (2000) Apoptosis and Nuclear Factor-Kappa B: a Tale of Association and Dissociation. Biochem Pharmacol 60:1033-1039. Agre P, Johnson P F and McKnight S L (1989) Cognate DNA Binding Specificity Retained After Leucine Zipper Exchange Between GCN4 and C/EBP. Science 246:922-926. Almond JB and Cohen G M (2002) The Proteasome: a Novel Target for Cancer Chemotherapy. Leukemia 16:433-443. Ashkenazi A and Dixit V M (1999) Apoptosis Control by Death and Decoy Receptors. Curr Opin Cell Biol 11:255-260. Bode AM and Dong Z (2004) Post-Translational Modification of P53 in Tumorigenesis. Nat Rev Cancer 4:793-805. Bradbury DA, Newton R, Zhu Y M, El-Haroun H, Corbett L and Knox A J (2003) Cyclooxygenase-2 Induction by Bradykinin in Human Pulmonary Artery Smooth Muscle Cells Is Mediated by the Cyclic AMP Response Element Through a Novel Autocrine Loop Involving Endogenous Prostaglandin E2, E-Prostanoid 2 (EP2), and EP4 Receptors. J Biol Chem 278:49954-49964. Castelao JE, Bart R D, III, DiPerna C A, Sievers E M and Bremner R M (2003) Lung Cancer and Cyclooxygenase-2. Ann Thorac Surg 76:1327-1335. Cavo M (2006) Proteasome Inhibitor Bortezomib for the Treatment of Multiple Myeloma. Leukemia 20:1341-1352. Chang YJ, Wu M S, Lin J T, Sheu B S, Muta T, Inoue H and Chen C C (2004) Induction of Cyclooxygenase-2 Overexpression in Human Gastric Epithelial Cells by Helicobacter Pylori Involves TLR2/TLR9 and C-Src-Dependent Nuclear Factor-KappaB Activation. Mol Pharmacol 66:1465-1477. Chauhan D, Hideshima T and Anderson K C (2005) Proteasome Inhibition in Multiple Myeloma: Therapeutic Implication. Annu Rev Pharmacol Toxicol 45:465-476. Chen CC, Chiu K T, Chan S T and Chern J W (2001) Conjugated Polyhydroxybenzene Derivatives Block Tumor Necrosis Factor-Alpha-Mediated Nuclear Factor-KappaB Activation and Cyclooxygenase-2 Gene Transcription by Targeting IkappaB Kinase Activity. Mol Pharmacol 60:1439-1448. Chen JJ, Huang W C and Chen C C (2005) Transcriptional Regulation of Cyclooxygenase-2 in Response to Proteasome Inhibitors Involves Reactive Oxygen Species-Mediated Signaling Pathway and Recruitment of CCAAT/Enhancer-Binding Protein Delta and CREB-Binding Protein. Mol Biol Cell 16:5579-5591. Chen X, Kandasamy K and Srivastava R K (2003) Differential Roles of RelA (P65) and C-Rel Subunits of Nuclear Factor Kappa B in Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling. Cancer Res 63:1059-1066. Chinery R, Brockman J A, Dransfield D T and Coffey R J (1997) Antioxidant-Induced Nuclear Translocation of CCAAT/Enhancer-Binding Protein Beta. A Critical Role for Protein Kinase A-Mediated Phosphorylation of Ser299. J Biol Chem 272:30356-30361. Ciechanover A (1998) The Ubiquitin-Proteasome Pathway: on Protein Death and Cell Life. EMBO J 17:7151-7160. Crofford LJ (1997) COX-1 and COX-2 Tissue Expression: Implications and Predictions. J Rheumatol Suppl 49:15-19. Dai Y, Rahmani M and Grant S (2003) Proteasome Inhibitors Potentiate Leukemic Cell Apoptosis Induced by the Cyclin-Dependent Kinase Inhibitor Flavopiridol Through a SAPK/JNK- and NF-KappaB-Dependent Process. Oncogene 22:7108-7122. Delic J, Masdehors P, Omura S, Cosset J M, Dumont J, Binet J L and Magdelenat H (1998) The Proteasome Inhibitor Lactacystin Induces Apoptosis and Sensitizes Chemo- and Radioresistant Human Chronic Lymphocytic Leukaemia Lymphocytes to TNF-Alpha-Initiated Apoptosis. Br J Cancer 77:1103-1107. DuBois RN, Giardiello F M and Smalley W E (1996) Nonsteroidal Anti-Inflammatory Drugs, Eicosanoids, and Colorectal Cancer Prevention. Gastroenterol Clin North Am 25:773-791. Dutta J, Fan Y, Gupta N, Fan G and Gelinas C (2006) Current Insights into the Regulation of Programmed Cell Death by NF-KappaB. Oncogene 25:6800-6816. Fennell DA, Chacko A and Mutti L (2007) BCL-2 Family Regulation by the 20S Proteasome Inhibitor Bortezomib. Oncogene. Fletcher BS, Kujubu D A, Perrin D M and Herschman H R (1992) Structure of the Mitogen-Inducible TIS10 Gene and Demonstration That the TIS10-Encoded Protein Is a Functional Prostaglandin G/H Synthase. J Biol Chem 267:4338-4344. Fribley A, Zeng Q and Wang C Y (2004) Proteasome Inhibitor PS-341 Induces Apoptosis Through Induction of Endoplasmic Reticulum Stress-Reactive Oxygen Species in Head and Neck Squamous Cell Carcinoma Cells. Mol Cell Biol 24:9695-9704. Ghosh S and Karin M (2002) Missing Pieces in the NF-KappaB Puzzle. Cell 109 Suppl:S81-S96. Gibson SB, Oyer R, Spalding A C, Anderson S M and Johnson G L (2000) Increased Expression of Death Receptors 4 and 5 Synergizes the Apoptosis Response to Combined Treatment With Etoposide and TRAIL. Mol Cell Biol 20:205-212. Gilmour PS, Rahman I, Donaldson K and MacNee W (2003) Histone Acetylation Regulates Epithelial IL-8 Release Mediated by Oxidative Stress From Environmental Particles. Am J Physiol Lung Cell Mol Physiol 284:L533-L540. Gloire G, Legrand-Poels S and Piette J (2006) NF-KappaB Activation by Reactive Oxygen Species: Fifteen Years Later. Biochem Pharmacol 72:1493-1505. Goetzl EJ, An S and Smith W L (1995) Specificity of Expression and Effects of Eicosanoid Mediators in Normal Physiology and Human Diseases. FASEB J 9:1051-1058. Hershko A (2005) The Ubiquitin System for Protein Degradation and Some of Its Roles in the Control of the Cell Division Cycle. Cell Death Differ 12:1191-1197. Hideshima T, Richardson P, Chauhan D, Palombella V J, Elliott P J, Adams J and Anderson K C (2001) The Proteasome Inhibitor PS-341 Inhibits Growth, Induces Apoptosis, and Overcomes Drug Resistance in Human Multiple Myeloma Cells. Cancer Res 61:3071-3076. Higuchi H, Grambihler A, Canbay A, Bronk S F and Gores G J (2004) Bile Acids Up-Regulate Death Receptor 5/TRAIL-Receptor 2 Expression Via a C-Jun N-Terminal Kinase-Dependent Pathway Involving Sp1. J Biol Chem 279:51-60. Hinz B and Brune K (2002) Cyclooxygenase-2--10 Years Later. J Pharmacol Exp Ther 300:367-375. Hla T and Neilson K (1992) Human Cyclooxygenase-2 CDNA. Proc Natl Acad Sci U S A 89:7384-7388. Hu HM, Tian Q, Baer M, Spooner C J, Williams S C, Johnson P F and Schwartz R C (2000) The C/EBP BZIP Domain Can Mediate Lipopolysaccharide Induction of the Proinflammatory Cytokines Interleukin-6 and Monocyte Chemoattractant Protein-1. J Biol Chem 275:16373-16381. Huang WC, Chen J J, Inoue H and Chen C C (2003) Tyrosine Phosphorylation of I-Kappa B Kinase Alpha/Beta by Protein Kinase C-Dependent C-Src Activation Is Involved in TNF-Alpha-Induced Cyclooxygenase-2 Expression. J Immunol 170:4767-4775. Hung JH, Su I J, Lei H Y, Wang H C, Lin W C, Chang W T, Huang W, Chang W C, Chang Y S, Chen C C and Lai M D (2004) Endoplasmic Reticulum Stress Stimulates the Expression of Cyclooxygenase-2 Through Activation of NF-KappaB and Pp38 Mitogen-Activated Protein Kinase. J Biol Chem 279:46384-46392. Imhof A, Yang X J, Ogryzko V V, Nakatani Y, Wolffe A P and Ge H (1997) Acetylation of General Transcription Factors by Histone Acetyltransferases. Curr Biol 7:689-692. Iniguez MA, Rodriguez A, Volpert O V, Fresno M and Redondo J M (2003) Cyclooxygenase-2: a Therapeutic Target in Angiogenesis. Trends Mol Med 9:73-78. Inoue H, Yokoyama C, Hara S, Tone Y and Tanabe T (1995) Transcriptional Regulation of Human Prostaglandin-Endoperoxide Synthase-2 Gene by Lipopolysaccharide and Phorbol Ester in Vascular Endothelial Cells. Involvement of Both Nuclear Factor for Interleukin-6 Expression Site and CAMP Response Element. J Biol Chem 270:24965-24971. Insinga A, Monestiroli S, Ronzoni S, Gelmetti V, Marchesi F, Viale A, Altucci L, Nervi C, Minucci S and Pelicci P G (2005) Inhibitors of Histone Deacetylases Induce Tumor-Selective Apoptosis Through Activation of the Death Receptor Pathway. Nat Med 11:71-76. Ishii Y, Waxman S and Germain D (2007) Targeting the Ubiquitin-Proteasome Pathway in Cancer Therapy. Anticancer Agents Med Chem 7:359-365. Jackson PK, Eldridge A G, Freed E, Furstenthal L, Hsu J Y, Kaiser B K and Reimann J D (2000) The Lore of the RINGs: Substrate Recognition and Catalysis by Ubiquitin Ligases. Trends Cell Biol 10:429-439. Janelle ME, Gravel A, Gosselin J, Tremblay M J and Flamand L (2002) Activation of Monocyte Cyclooxygenase-2 Gene Expression by Human Herpesvirus 6. Role for Cyclic AMP-Responsive Element-Binding Protein and Activator Protein-1. J Biol Chem 277:30665-30674. Johnson PF and McKnight S L (1989) Eukaryotic Transcriptional Regulatory Proteins. Annu Rev Biochem 58:799-839. Joshi-Barve S, Barve S S, Butt W, Klein J and McClain C J (2003) Inhibition of Proteasome Function Leads to NF-KappaB-Independent IL-8 Expression in Human Hepatocytes. Hepatology 38:1178-1187. Jung EM, Lim J H, Lee T J, Park J W, Choi K S and Kwon T K (2005) Curcumin Sensitizes Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis Through Reactive Oxygen Species-Mediated Upregulation of Death Receptor 5 (DR5). Carcinogenesis 26:1905-1913. Jung EM, Park J W, Choi K S, Park J W, Lee H I, Lee K S and Kwon T K (2006) Curcumin Sensitizes Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Apoptosis Through CHOP-Independent DR5 Upregulation. Carcinogenesis 27:2008-2017. Karim S, Habib A, Levy-Toledano S and Maclouf J (1996) Cyclooxygenase-1 and -2 of Endothelial Cells Utilize Exogenous or Endogenous Arachidonic Acid for Transcellular Production of Thromboxane. J Biol Chem 271:12042-12048. Kim H, Kim E H, Eom Y W, Kim W H, Kwon T K, Lee S J and Choi K S (2006) Sulforaphane Sensitizes Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Resistant Hepatoma Cells to TRAIL-Induced Apoptosis Through Reactive Oxygen Species-Mediated Up-Regulation of DR5. Cancer Res 66:1740-1750. Kim Y and Seol D W (2003) TRAIL, a Mighty Apoptosis Inducer. Mol Cells 15:283-293. Kim YH, Park J W, Lee J Y and Kwon T K (2004) Sodium Butyrate Sensitizes TRAIL-Mediated Apoptosis by Induction of Transcription From the DR5 Gene Promoter Through Sp1 Sites in Colon Cancer Cells. Carcinogenesis 25:1813-1820. Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E and Tanabe T (1994) Characterization of the Human Gene (PTGS2) Encoding Prostaglandin-Endoperoxide Synthase 2. Eur J Biochem 221:889-897. Kraemer SA, Meade E A and DeWitt D L (1992) Prostaglandin Endoperoxide Synthase Gene Structure: Identification of the Transcriptional Start Site and 5'-Flanking Regulatory Sequences. Arch Biochem Biophys 293:391-400. Kreuz S, Siegmund D, Scheurich P and Wajant H (2001) NF-KappaB Inducers Upregulate CFLIP, a Cycloheximide-Sensitive Inhibitor of Death Receptor Signaling. Mol Cell Biol 21:3964-3973. Kuhnel F, Zender L, Paul Y, Tietze M K, Trautwein C, Manns M and Kubicka S (2000) NFkappaB Mediates Apoptosis Through Transcriptional Activation of Fas (CD95) in Adenoviral Hepatitis. J Biol Chem 275:6421-6427. Landschulz WH, Johnson P F, Adashi E Y, Graves B J and McKnight S L (1988) Isolation of a Recombinant Copy of the Gene Encoding C/EBP. Genes Dev 2:786-800. Landschulz WH, Johnson P F and McKnight S L (1989) The DNA Binding Domain of the Rat Liver Nuclear Protein C/EBP Is Bipartite. Science 243:1681-1688. Lavrik I, Golks A and Krammer P H (2005) Death Receptor Signaling. J Cell Sci 118:265-267. Lee AH, Iwakoshi N N, Anderson K C and Glimcher L H (2003a) Proteasome Inhibitors Disrupt the Unfolded Protein Response in Myeloma Cells. Proc Natl Acad Sci U S A 100:9946-9951. Lee DH and Goldberg A L (1998) Proteasome Inhibitors: Valuable New Tools for Cell Biologists. Trends Cell Biol 8:397-403. Lee JY, Kim N A, Sanford A and Sullivan K E (2003b) Histone Acetylation and Chromatin Conformation Are Regulated Separately at the TNF-Alpha Promoter in Monocytes and Macrophages. J Leukoc Biol 73:862-871. Leverkus M, Sprick M R, Wachter T, Mengling T, Baumann B, Serfling E, Brocker E B, Goebeler M, Neumann M and Walczak H (2003) Proteasome Inhibition Results in TRAIL Sensitization of Primary Keratinocytes by Removing the Resistance-Mediating Block of Effector Caspase Maturation. Mol Cell Biol 23:777-790. Li M, Luo J, Brooks C L and Gu W (2002) Acetylation of P53 Inhibits Its Ubiquitination by Mdm2. J Biol Chem 277:50607-50611. Lin FT and Lane M D (1992) Antisense CCAAT/Enhancer-Binding Protein RNA Suppresses Coordinate Gene Expression and Triglyceride Accumulation During Differentiation of 3T3-L1 Preadipocytes. Genes Dev 6:533-544. Ling YH, Liebes L, Zou Y and Perez-Soler R (2003) Reactive Oxygen Species Generation and Mitochondrial Dysfunction in the Apoptotic Response to Bortezomib, a Novel Proteasome Inhibitor, in Human H460 Non-Small Cell Lung Cancer Cells. J Biol Chem 278:33714-33723. Liu X, Yue P, Khuri F R and Sun S Y (2004) P53 Upregulates Death Receptor 4 Expression Through an Intronic P53 Binding Site. Cancer Res 64:5078-5083. Liu X, Yue P, Khuri F R and Sun S Y (2005) Decoy Receptor 2 (DcR2) Is a P53 Target Gene and Regulates Chemosensitivity. Cancer Res 65:9169-9175. Liu YC (2004) Ubiquitin Ligases and the Immune Response. Annu Rev Immunol 22:81-127. Lyss G, Knorre A, Schmidt T J, Pahl H L and Merfort I (1998) The Anti-Inflammatory Sesquiterpene Lactone Helenalin Inhibits the Transcription Factor NF-KappaB by Directly Targeting P65. J Biol Chem 273:33508-33516. Mani A and Gelmann E P (2005) The Ubiquitin-Proteasome Pathway and Its Role in Cancer. J Clin Oncol 23:4776-4789. Marmorstein R (2001) Structure and Function of Histone Acetyltransferases. Cell Mol Life Sci 58:693-703. Marnett LJ and DuBois R N (2002) COX-2: a Target for Colon Cancer Prevention. Annu Rev Pharmacol Toxicol 42:55-80. Masferrer JL, Leahy K M, Koki A T, Zweifel B S, Settle S L, Woerner B M, Edwards D A, Flickinger A G, Moore R J and Seibert K (2000) Antiangiogenic and Antitumor Activities of Cyclooxygenase-2 Inhibitors. Cancer Res 60:1306-1311. Matsui TA, Sowa Y, Yoshida T, Murata H, Horinaka M, Wakada M, Nakanishi R, Sakabe T, Kubo T and Sakai T (2006) Sulforaphane Enhances TRAIL-Induced Apoptosis Through the Induction of DR5 Expression in Human Osteosarcoma Cells. Carcinogenesis 27:1768-1777. Meriin AB, Gabai V L, Yaglom J, Shifrin V I and Sherman M Y (1998) Proteasome Inhibitors Activate Stress Kinases and Induce Hsp72. Diverse Effects on Apoptosis. J Biol Chem 273:6373-6379. Miller C, Zhang M, He Y, Zhao J, Pelletier J P, Martel-Pelletier J and Di Battista J A (1998) Transcriptional Induction of Cyclooxygenase-2 Gene by Okadaic Acid Inhibition of Phosphatase Activity in Human Chondrocytes: Co-Stimulation of AP-1 and CRE Nuclear Binding Proteins. J Cell Biochem 69:392-413. Milosavljevic TS, Petrovic M V, Cvetkovic I D and Grigorov I I (2002) DNA Binding Activity of C/EBPbeta and C/EBPdelta for the Rat Alpha2-Macroglobulin Gene Promoter Is Regulated in an Acute-Phase Dependent Manner. Biochemistry (Mosc ) 67:918-926. Nagane M, Pan G, Weddle J J, Dixit V M, Cavenee W K and Huang H J (2000) Increased Death Receptor 5 Expression by Chemotherapeutic Agents in Human Gliomas Causes Synergistic Cytotoxicity With Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Vitro and in Vivo. Cancer Res 60:847-853. Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto M, Kishimoto T and Akira S (1993) Phosphorylation at Threonine-235 by a Ras-Dependent Mitogen-Activated Protein Kinase Cascade Is Essential for Transcription Factor NF-IL6. Proc Natl Acad Sci U S A 90:2207-2211. Nakayama K, Furusu A, Xu Q, Konta T and Kitamura M (2001) Unexpected Transcriptional Induction of Monocyte Chemoattractant Protein 1 by Proteasome Inhibition: Involvement of the C-Jun N-Terminal Kinase-Activator Protein 1 Pathway. J Immunol 167:1145-1150. Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H and Kishimoto T (1992) Macrophage Differentiation-Specific Expression of NF-IL6, a Transcription Factor for Interleukin-6. Blood 79:460-466. Nencioni A, Grunebach F, Patrone F, Ballestrero A and Brossart P (2007) Proteasome Inhibitors: Antitumor Effects and Beyond. Leukemia 21:30-36. Nie M, Pang L, Inoue H and Knox A J (2003) Transcriptional Regulation of Cyclooxygenase 2 by Bradykinin and Interleukin-1beta in Human Airway Smooth Muscle Cells: Involvement of Different Promoter Elements, Transcription Factors, and Histone H4 Acetylation. Mol Cell Biol 23:9233-9244. Ogasawara A, Arakawa T, Kaneda T, Takuma T, Sato T, Kaneko H, Kumegawa M and Hakeda Y (2001) Fluid Shear Stress-Induced Cyclooxygenase-2 Expression Is Mediated by C/EBP Beta, CAMP-Response Element-Binding Protein, and AP-1 in Osteoblastic MC3T3-E1 Cells. J Biol Chem 276:7048-7054. Pahl HL (1999) Activators and Target Genes of Rel/NF-KappaB Transcription Factors. Oncogene 18:6853-6866. Perez-Galan P, Roue G, Villamor N, Montserrat E, Campo E and Colomer D (2006) The Proteasome Inhibitor Bortezomib Induces Apoptosis in Mantle-Cell Lymphoma Through Generation of ROS and Noxa Activation Independent of P53 Status. Blood 107:257-264. Podar K, Shringarpure R, Tai Y T, Simoncini M, Sattler M, Ishitsuka K, Richardson P G, Hideshima T, Chauhan D and Anderson K C (2004) Caveolin-1 Is Required for Vascular Endothelial Growth Factor-Triggered Multiple Myeloma Cell Migration and Is Targeted by Bortezomib. Cancer Res 64:7500-7506. Poli V (1998) The Role of C/EBP Isoforms in the Control of Inflammatory and Native Immunity Functions. J Biol Chem 273:29279-29282. Potter S, Mitchell M D, Hansen W R and Marvin K W (2000) NF-IL6 and CRE Elements Principally Account for Both Basal and Interleukin-1 Beta-Induced Transcriptional Activity of the Proximal 528bp of the PGHS-2 Promoter in Amnion-Derived AV3 Cells: Evidence for Involvement of C/EBP Beta. Mol Hum Reprod 6:771-778. Pritts TA, Hungness E S, Hershko D D, Robb B W, Sun X, Luo G J, Fischer J E, Wong H R and Hasselgren P O (2002) Proteasome Inhibitors Induce Heat Shock Response and Increase IL-6 Expression in Human Intestinal Epithelial Cells. Am J Physiol Regul Integr Comp Physiol 282:R1016-R1026. Radhakrishnan SK and Kamalakaran S (2006) Pro-Apoptotic Role of NF-KappaB: Implications for Cancer Therapy. Biochim Biophys Acta 1766:53-62. Rahman I (2002b) Oxidative Stress, Transcription Factors and Chromatin Remodelling in Lung Inflammation. Biochem Pharmacol 64:935-942. Rahman I (2002a) Oxidative Stress and Gene Transcription in Asthma and Chronic Obstructive Pulmonary Disease: Antioxidant Therapeutic Targets. Curr Drug Targets Inflamm Allergy 1:291-315. Ramji DP and Foka P (2002) CCAAT/Enhancer-Binding Proteins: Structure, Function and Regulation. Biochem J 365:561-575. Ramji DP, Vitelli A, Tronche F, Cortese R and Ciliberto G (1993) The Two C/EBP Isoforms, IL-6DBP/NF-IL6 and C/EBP Delta/NF-IL6 Beta, Are Induced by IL-6 to Promote Acute Phase Gene Transcription Via Different Mechanisms. Nucleic Acids Res 21:289-294. Ravi R, Bedi G C, Engstrom L W, Zeng Q, Mookerjee B, Gelinas C, Fuchs E J and Bedi A (2001) Regulation of Death Receptor Expression and TRAIL/Apo2L-Induced Apoptosis by NF-KappaB. Nat Cell Biol 3:409-416. Ray A and Ray B K (1994) Serum Amyloid A Gene Expression Under Acute-Phase Conditions Involves Participation of Inducible C/EBP-Beta and C/EBP-Delta and Their Activation by Phosphorylation. Mol Cell Biol 14:4324-4332. rias-Negrete S, Keller K and Chadee K (1995) Proinflammatory Cytokines Regulate Cyclooxygenase-2 MRNA Expression in Human Macrophages. Biochem Biophys Res Commun 208:582-589. Riedl SJ and Shi Y (2004) Molecular Mechanisms of Caspase Regulation During Apoptosis. Nat Rev Mol Cell Biol 5:897-907. Ristimaki A, Honkanen N, Jankala H, Sipponen P and Harkonen M (1997) Expression of Cyclooxygenase-2 in Human Gastric Carcinoma. Cancer Res 57:1276-1280. Roccaro AM, Hideshima T, Raje N, Kumar S, Ishitsuka K, Yasui H, Shiraishi N, Ribatti D, Nico B, Vacca A, Dammacco F, Richardson P G and Anderson K C (2006) Bortezomib Mediates Antiangiogenesis in Multiple Myeloma Via Direct and Indirect Effects on Endothelial Cells. Cancer Res 66:184-191. Rockwell P, Yuan H, Magnusson R and Figueiredo-Pereira M E (2000) Proteasome Inhibition in Neuronal Cells Induces a Proinflammatory Response Manifested by Upregulation of Cyclooxygenase-2, Its Accumulation As Ubiquitin Conjugates, and Production of the Prostaglandin PGE(2). Arch Biochem Biophys 374:325-333. Ruiz de AC, Ruiz-Ruiz C, Rodriguez A, Ortiz-Ferron G, Redondo J M and Lopez-Rivas A (2004) Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Decoy Receptor TRAIL-R3 Is Up-Regulated by P53 in Breast Tumor Cells Through a Mechanism Involving an Intronic P53-Binding Site. J Biol Chem 279:4093-4101. Sakaguchi K, Sakamoto H, Lewis M S, Anderson C W, Erickson J W, Appella E and Xie D (1997) Phosphorylation of Serine 392 Stabilizes the Tetramer Formation of Tumor Suppressor Protein P53. Biochemistry 36:10117-10124. Sano H, Kawahito Y, Wilder R L, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M and Hla T (1995) Expression of Cyclooxygenase-1 and -2 in Human Colorectal Cancer. Cancer Res 55:3785-3789. Saunders MA, Sansores-Garcia L, Gilroy D W and Wu K K (2001) Selective Suppression of CCAAT/Enhancer-Binding Protein Beta Binding and Cyclooxygenase-2 Promoter Activity by Sodium Salicylate in Quiescent Human Fibroblasts. J Biol Chem 276:18897-18904. Sayers TJ, Brooks A D, Koh C Y, Ma W, Seki N, Raziuddin A, Blazar B R, Zhang X, Elliott P J and Murphy W J (2003) The Proteasome Inhibitor PS-341 Sensitizes Neoplastic Cells to TRAIL-Mediated Apoptosis by Reducing Levels of C-FLIP. Blood 102:303-310. Sayers TJ and Murphy W J (2006) Combining Proteasome Inhibition With TNF-Related Apoptosis-Inducing Ligand (Apo2L/TRAIL) for Cancer Therapy. Cancer Immunol Immunother 55:76-84. Schroer K, Zhu Y, Saunders M A, Deng W G, Xu X M, Meyer-Kirchrath J and Wu K K (2002) Obligatory Role of Cyclic Adenosine Monophosphate Response Element in Cyclooxygenase-2 Promoter Induction and Feedback Regulation by Inflammatory Mediators. Circulation 105:2760-2765. Schumm K, Rocha S, Caamano J and Perkins N D (2006) Regulation of P53 Tumour Suppressor Target Gene Expression by the P52 NF-KappaB Subunit. EMBO J 25:4820-4832. Schwartz AL and Ciechanover A (1999) The Ubiquitin-Proteasome Pathway and Pathogenesis of Human Diseases. Annu Rev Med 50:57-74. Sheridan JP, Marsters S A, Pitti R M, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray C L, Baker K, Wood W I, Goddard A D, Godowski P and Ashkenazi A (1997) Control of TRAIL-Induced Apoptosis by a Family of Signaling and Decoy Receptors. Science 277:818-821. Shetty S, Gladden J B, Henson E S, Hu X, Villanueva J, Haney N and Gibson S B (2002) Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) Up-Regulates Death Receptor 5 (DR5) Mediated by NFkappaB Activation in Epithelial Derived Cell Lines. Apoptosis 7:413-420. Shetty S, Graham B A, Brown J G, Hu X, Vegh-Yarema N, Harding G, Paul J T and Gibson S B (2005) Transcription Factor NF-KappaB Differentially Regulates Death Receptor 5 Expression Involving Histone Deacetylase 1. Mol Cell Biol 25:5404-5416. Shibata T, Imaizumi T, Tamo W, Matsumiya T, Kumagai M, Cui X F, Yoshida H, Takaya S, Fukuda I and Satoh K (2002) Proteasome Inhibitor MG-132 Enhances the Expression of Interleukin-6 in Human Umbilical Vein Endothelial Cells: Involvement of MAP/ERK Kinase. Immunol Cell Biol 80:226-230. Shiraishi T, Yoshida T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T and Sakai T (2005) Tunicamycin Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Prostate Cancer Cells. Cancer Res 65:6364-6370. Sidransky D and Hollstein M (1996) Clinical Implications of the P53 Gene. Annu Rev Med 47:285-301. Sizemore N, Lerner N, Dombrowski N, Sakurai H and Stark G R (2002) Distinct Roles of the Ikappa B Kinase Alpha and Beta Subunits in Liberating Nuclear Factor Kappa B (NF-Kappa B) From Ikappa B and in Phosphorylating the P65 Subunit of NF-Kappa B. J Biol Chem 277:3863-3869. Smith WL (1992) Prostanoid Biosynthesis and Mechanisms of Action. Am J Physiol 263:F181-F191. Stenger JE, Tegtmeyer P, Mayr G A, Reed M, Wang Y, Wang P, Hough P V and Mastrangelo I A (1994) P53 Oligomerization and DNA Looping Are Linked With Transcriptional Activation. EMBO J 13:6011-6020. Sun SY, Yue P, Hong W K and Lotan R (2000) Augmentation of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis by the Synthetic Retinoid 6-[3-(1-Adamantyl)-4-Hydroxyphenyl]-2-Naphthalene Carboxylic Acid (CD437) Through Up-Regulation of TRAIL Receptors in Human Lung Cancer Cells. Cancer Res 60:7149-7155. Svotelis A, Doyon G, Bernatchez G, Desilets A, Rivard N and Asselin C (2005) IL-1 Beta-Dependent Regulation of C/EBP Delta Transcriptional Activity. Biochem Biophys Res Commun 328:461-470. Takimoto R and El-Deiry W S (2000) Wild-Type P53 Transactivates the KILLER/DR5 Gene Through an Intronic Sequence-Specific DNA-Binding Site. Oncogene 19:1735-1743. Tamura M, Sebastian S, Yang S, Gurates B, Fang Z, Okamura K and Bulun S E (2003) Induction of Cyclooxygenase-2 in Human Endometrial Stromal Cells by Malignant Endometrial Epithelial Cells: Evidence for the Involvement of Extracellularly Regulated Kinases and CCAAT/Enhancer Binding Proteins. J Mol Endocrinol 31:95-104. Tanabe T and Tohnai N (2002) Cyclooxygenase Isozymes and Their Gene Structures and Expression. Prostaglandins Other Lipid Mediat 68-69:95-114. Tang Q, Chen W, Gonzales M S, Finch J, Inoue H and Bowden G T (2001b) Role of Cyclic AMP Responsive Element in the UVB Induction of Cyclooxygenase-2 Transcription in Human Keratinocytes. Oncogene 20:5164-5172. Tang Q, Chen W, Gonzales M S, Finch J, Inoue H and Bowden G T (2001a) Role of Cyclic AMP Responsive Element in the UVB Induction of Cyclooxygenase-2 Transcription in Human Keratinocytes. Oncogene 20:5164-5172. Tani E, Kitagawa H, Ikemoto H and Matsumoto T (2001) Proteasome Inhibitors Induce Fas-Mediated Apoptosis by C-Myc Accumulation and Subsequent Induction of FasL Message in Human Glioma Cells. FEBS Lett 504:53-58. Toledo F and Wahl G M (2006) Regulating the P53 Pathway: in Vitro Hypotheses, in Vivo Veritas. Nat Rev Cancer 6:909-923. Tomasetti M, Andera L, Alleva R, Borghi B, Neuzil J and Procopio A (2006) Alpha-Tocopheryl Succinate Induces DR4 and DR5 Expression by a P53-Dependent Route: Implication for Sensitisation of Resistant Cancer Cells to TRAIL Apoptosis. FEBS Lett 580:1925-1931. Traenckner EB, Wilk S and Baeuerle P A (1994) A Proteasome Inhibitor Prevents Activation of NF-Kappa B and Stabilizes a Newly Phosphorylated Form of I Kappa B-Alpha That Is Still Bound to NF-Kappa B. EMBO J 13:5433-5441. Trautwein C, Caelles C, van der G P, Hunter T, Karin M and Chojkier M (1993) Transactivation by NF-IL6/LAP Is Enhanced by Phosphorylation of Its Activation Domain. Nature 364:544-547. Tripathi P and Hildeman D (2004) Sensitization of T Cells to Apoptosis--a Role for ROS? Apoptosis 9:515-523. Tsuji S, Tsujii M, Kawano S and Hori M (2001) Cyclooxygenase-2 Upregulation As a Perigenetic Change in Carcinogenesis. J Exp Clin Cancer Res 20:117-129. Tsujii M and DuBois R N (1995) Alterations in Cellular Adhesion and Apoptosis in Epithelial Cells Overexpressing Prostaglandin Endoperoxide Synthase 2. Cell 83:493-501. Turini ME and DuBois R N (2002) Cyclooxygenase-2: a Therapeutic Target. Annu Rev Med 53:35-57. Voortman J, Resende T P, bou El Hassan M A, Giaccone G and Kruyt F A (2007) TRAIL Therapy in Non-Small Cell Lung Cancer Cells: Sensitization to Death Receptor-Mediated Apoptosis by Proteasome Inhibitor Bortezomib. Mol Cancer Ther 6:2103-2112. Vousden KH and Lu X (2002) Live or Let Die: the Cell's Response to P53. Nat Rev Cancer 2:594-604. Walczak H, gli-Esposti M A, Johnson R S, Smolak P J, Waugh J Y, Boiani N, Timour M S, Gerhart M J, Schooley K A, Smith C A, Goodwin R G and Rauch C T (1997) TRAIL-R2: a Novel Apoptosis-Mediating Receptor for TRAIL. EMBO J 16:5386-5397. Wang CY, Mayo M W, Korneluk R G, Goeddel D V and Baldwin A S, Jr. (1998) NF-KappaB Antiapoptosis: Induction of TRAF1 and TRAF2 and C-IAP1 and C-IAP2 to Suppress Caspase-8 Activation. Science 281:1680-1683. Wang ND, Finegold M J, Bradley A, Ou C N, Abdelsayed S V, Wilde M D, Taylor L R, Wilson D R and Darlington G J (1995) Impaired Energy Homeostasis in C/EBP Alpha Knockout Mice. Science 269:1108-1112. Wen J, Ramadevi N, Nguyen D, Perkins C, Worthington E and Bhalla K (2000) Antileukemic Drugs Increase Death Receptor 5 Levels and Enhance Apo-2L-Induced Apoptosis of Human Acute Leukemia Cells. Blood 96:3900-3906. Wu GS, Burns T F, McDonald E R, III, Meng R D, Kao G, Muschel R, Yen T and el-Deiry W S (1999) Induction of the TRAIL Receptor KILLER/DR5 in P53-Dependent Apoptosis but Not Growth Arrest. Oncogene 18:6411-6418. Xie W, Fletcher B S, Andersen R D and Herschman H R (1994) V-Src Induction of the TIS10/PGS2 Prostaglandin Synthase Gene Is Mediated by an ATF/CRE Transcription Response Element. Mol Cell Biol 14:6531-6539. Yan H, Wang Y C, Li D, Wang Y, Liu W, Wu Y L and Chen G Q (2007) Arsenic Trioxide and Proteasome Inhibitor Bortezomib Synergistically Induce Apoptosis in Leukemic Cells: the Role of Protein Kinase Cdelta. Leukemia 21:1488-1495. Yoshida T, Maeda A, Tani N and Sakai T (2001) Promoter Structure and Transcription Initiation Sites of the Human Death Receptor 5/TRAIL-R2 Gene. FEBS Lett 507:381-385. Yoshida T, Shiraishi T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T and Sakai T (2005) Proteasome Inhibitor MG132 Induces Death Receptor 5 Through CCAAT/Enhancer-Binding Protein Homologous Protein. Cancer Res 65:5662-5667. Zhang HG, Wang J, Yang X, Hsu H C and Mountz J D (2004) Regulation of Apoptosis Proteins in Cancer Cells by Ubiquitin. Oncogene 23:2009-2015. Zhu Y, Saunders M A, Yeh H, Deng W G and Wu K K (2002) Dynamic Regulation of Cyclooxygenase-2 Promoter Activity by Isoforms of CCAAT/Enhancer-Binding Proteins. J Biol Chem 277:6923-6928. Zimmermann KC, Sarbia M, Weber A A, Borchard F, Gabbert H E and Schror K (1999) Cyclooxygenase-2 Expression in Human Esophageal Carcinoma. Cancer Res 59:198-204. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/27501 | - |
dc.description.abstract | 抑制泛素-蛋白解體路徑有希望成為治療發炎及癌症的明日之星,蛋白解體抑制劑MG132除了可透過泛素-蛋白解體路徑調節蛋白轉化作用外,也被報導可經由mitogenic activated kinases (MAPKs)活化activating protein (AP-1),並引發許多發炎基因如monocyte chemoattractant protein-1(MCP-1)、IL-8及IL-6。然而,蛋白解體抑制劑啟動發炎基因的詳細機制仍未完全清楚。在本論文中,我們發現在人類肺泡上皮癌細胞NCI-H292、A549及胃上皮癌細胞AGS中,蛋白解體抑制劑MG132、PSI-1及lactacystin引發COX-2表現是透過增加基因轉錄而非阻止蛋白分解的機制而來。COX-2 promoter上NF-IL6與CRE結合位參與此基因轉錄是必須的,而NF-kB結合位則不參與此機制。CCAAT/enhancer結合蛋白(C/EBPb)和C/EBPd結合到NF-IL6和CRE位置,並且MG132可增加組蛋白H3和H4乙醯化並引發CBP徵召到COX-2 promoter上。然而,C/EBPb和C/EBPd之蛋白質總量則不受MG132改變。MG132所引發C/EBPd而非C/EBPb之DNA結合活性是透過p38、PI3K、Src和PKC所調節的。C/EBPd之小片段干擾RNA (siRNA)抑制COX-2表現進一步證明C/EBPd在COX-2基因轉錄的角色。此外,MAPKs及Akt參與MG132刺激細胞內反應性氧化物種(ROS)之生成。這些發現顯示蛋白解體抑制劑引發COX-2轉錄必須透過ROS-dependent蛋白激酶的活化及之後C/EBPd和CBP之徵召。
在非小細胞肺癌中,蛋白解體抑制劑PS-341可致敏TRAIL媒介之細胞凋亡。MG132已被報導可透過CHOP的增加而引發DR5。Lactacystin在人類神經膠細胞中可增進Fas媒介之細胞凋亡,這些研究顯示蛋白解體抑制劑可透過增加死亡受器的表現而誘導細胞凋亡,然而其詳細機轉仍然未知。 以調節TRAIL受器-2 (DR5)路徑作為標的有希望成為根除癌細胞之治療策略,臨床研究顯示蛋白解體抑制劑增進TRAIL引發之細胞凋亡,但其機轉仍未完全了解。本論文中,我們發現在肺部上皮細胞中蛋白解體抑制劑致敏TRAIL媒介之細胞凋亡是透過引發DR5表現而來。Reporter assay顯示在 DR5第一intron區域的p53和NF-kB位置參與此過程是必須的。p53 siRNA和NF-kB抑制劑可壓制DR5表現,更進一步證實了p53和NF-kB在DR5轉錄中所扮演的角色。我們也發現MG132可增加p53表現和穩定度、Ser392磷酸化及Lys373/382乙醯化。同時,可觀察到IkBa的分解和NF-kB轉位的現象。DAPA及ChIP assay顯示p53及p65可結合到DR5第一intron的區域,MG132增加細胞內氧化活性物種(ROS)之生成,可導致p53而非p65的核轉位和DNA結合活性。ROS scavenger可明顯抑制蛋白解體抑制劑併用TRAIL所引發之細胞凋亡。這些發現顯示蛋白解體抑制劑所媒介的NF-kB和ROS-dependent p53活化參與了DR5轉錄之intronic調節作用,並増進TRAIL-所誘發之細胞凋亡。 總結,本論文對蛋白解體抑制劑在COX-2及DR5轉錄作用之調控提供詳細機轉之探討,並進一步釐清氧化活性物種及下游轉錄因子在蛋白解體抑制劑活化基因轉錄過程中所扮演的角色,而根據此論文我們可了解蛋白解體抑制劑對發炎及細胞凋亡基因之調控作用及其功能之相關性,以期望對未來蛋白解體抑制劑之藥物研究及臨床治療提供一個參考。 | zh_TW |
dc.description.abstract | Inhibition of ubiquitin-proteasome pathway has been shown to be a promising strategy for the treatment of inflammation and cancer. In addition to the regulation of protein turnover via ubiquitin-proteasome pathway, the proteasome inhibitor MG132 had been reported to activate activator protein-1 (AP-1) through the mitogenic activated protein kinases (MAPKs) pathway and induce the expressions of several inflammatory genes, such as monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-6. However, the precise mechanism by which proteasome inhibitor triggers the expression of inflammatory genes is not fully clear.
In this thesis, we show that proteasome inhibitors MG132, PSI-1 and lactacystin induce COX-2 expression via enhancing gene transcription rather than preventing protein degradation in the human alveolar NCI-H292 and A549, and gastric AGS epithelial cells. NF-IL6 and CRE, but not NF-kB elements on the COX-2 promoter were involved in the gene transcription event. The binding of CCAAT/enhancer binding protein (C/EBP)b and C/EBPd to the CRE and NF-IL6 elements, as well as the recruitment of CBP and the enhancement of histone H3 and H4 acetylation on the COX-2 promoter was enhanced by MG132. However, it did not affect the total protein levels of C/EBPb and C/EBPd. MG132-induced DNA-binding activity of C/EBPd but not C/EBPb was regulated by p38, PI3K, Src and PKC. Small interfering RNA of C/EBPd suppressed COX-2 expression, further strengthening the role of C/EBPd in COX-2 gene transcription. In addition, the generation of intracellular reactive oxygen species (ROS) in response to MG132 contributed to the activation of MAPKs and Akt. These findings reveal that the induction of COX-2 transcription induced by proteasome inhibitors requires ROS-dependent protein kinases activation and the subsequent recruitments of C/EBPd and CBP. Proteasome inhibitor PS-341 sensitized TRAIL-mediated apoptosis in non-small cell lung cancer cells. It has been reported that MG132 induced DR5 expression through CHOP up-regulation. Lactacystin enhanced Fas-mediated apoptosis by induction of Fas and Fas ligand in human glioma cells. These studies imply that proteasome inhibitors may enhance apoptosis through the up-regulation of death receptor. However, the underlying mechanism of this enhancement is still unclear. Manipulation of TRAIL receptor-2 (DR5) pathway is a promising therapeutic strategy to eradicate cancer cells. Preclinical studies have shown that proteasome inhibitors enhance TRAIL-induced apoptosis, but the underlying mechanism has not been fully elucidated. In this thesis, we show that proteasome inhibitors sensitize TRAIL-mediated apoptosis by inducing DR5 expression in human alveolar cells. Reporter assay demonstrated the involvement of p53 and NF-kB elements on DR5 first intron region. Both p53 siRNA and NF-kB inhibitor suppressed DR5 expression, strengthening the role of p53 and NF-kB in DR5 transcription. p53 expression and stability, Ser392 phosphorylation and Lys373/382 acetylation were enhanced by MG132. Meanwhile, IkBa degradation and NF-kB translocation were also observed. DAPA and ChIP assays demonstrated the occupancy of p53 and p65 on the first intron of DR5. Intracellular reactive oxygen species (ROS) generated after MG132 treatment contributed to p53 but not p65 nuclear translocation and DNA-binding activity. ROS scavenger dramatically inhibited the apoptosis induced by proteasome inhibitors plus TRAIL. These findings reveal that proteasome inhibitors-mediated NF-kB and ROS-dependent p53 activation are attributed to intronic regulation of DR5 transcription, and resulted in the subsequent enhancement of TRAIL-induced apoptosis. Taken together, all the results provide a mechanistic insight into the crucial role of proteasome inhibitors on COX-2 and DR5 transcription, and further elucidate the role of ROS and downstream transcription factor in the process of proteasome inhibitors induced gene transcription. According to this thesis, we shed the light on the relationship between the regulation and function of inflammatory and apoptotic gene in response to proteasome inhibitors. | en |
dc.description.provenance | Made available in DSpace on 2021-06-12T18:07:25Z (GMT). No. of bitstreams: 1 ntu-96-D91443001-1.pdf: 5674002 bytes, checksum: 19b7e0a74dc31908e688ff397e0c957a (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 縮寫表 (Abbreviations).......................... i
中文摘要 (Abstract in Chinese).................... iii 英文摘要 (Abstract in English)......................v 第一章、 緒論 (Introduction)....................... 1 第一節、泛素-蛋白解體系統(Ubiquitin-Proteasome System ;UPS)之代謝及功能........................................1 第二節、蛋白解體抑制劑(Proteasome inhibitors) 之分類與功能....................................... 8 第三節、第二型環氧化酶(Cyclooxygenase-2, COX-2)之結構、表 現與功能........................................... 15 第四節、TNF-related apoptosis-inducing ligand (TRAIL)與其受 之功能............................................. 23 第五節、CCAAT/enhancer binding protein (C/EBP)家族之調控與功能..................................................28 第六節、p53與NF-kB活化路徑與細胞凋亡之調控......... 33 研究動機........................................... 39 第二章、 實驗材料與方法 (Materials and Methods).... 40 第三章、 蛋白解體抑制劑在肺細胞引發環氧化酶表現之探討 (Proteasome inhibitors-induced COX-2 gene expression in lung cells).........................................51 第四章、 蛋白解體抑制劑增進TRAIL誘導細胞凋亡之探討 (Proteasome inhibitors enhance TRAIL-induced apoptosis) ....................................................71 第五章、 結論與未來展望 (Conclusions and Perspectives) ....................................................91 參考文獻 (References)...............................93 著作發表與奬項(Publications and Honors)............109 | |
dc.language.iso | zh-TW | |
dc.title | 蛋白解體抑制劑引發基因轉錄與細胞凋亡之探討 | zh_TW |
dc.title | Regulatory mechanism of proteasome inhibitors-induced gene transcription and apoptosis | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 吳明賢,徐立中,楊春茂,顏茂雄 | |
dc.subject.keyword | 蛋白解體抑制劑,環氧化酶,-2,死亡受體-5, | zh_TW |
dc.subject.keyword | Proteasome inhibitor,cyclooxygenase-2,death receptor-5, | en |
dc.relation.page | 108 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-12-27 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-96-1.pdf 目前未授權公開取用 | 5.54 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。