請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63204
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李財坤(Tsai-Kun Li) | |
dc.contributor.author | Yu-Chen Yang | en |
dc.contributor.author | 楊育臻 | zh_TW |
dc.date.accessioned | 2021-06-16T16:28:06Z | - |
dc.date.available | 2013-03-04 | |
dc.date.copyright | 2013-03-04 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2013-01-11 | |
dc.identifier.citation | 1. Akhtar MW, Sunico CR, Nakamura T, Lipton SA. Redox Regulation of Protein Function via Cysteine S-Nitrosylation and Its Relevance to Neurodegenerative Diseases. Int J Cell Biol 2012: 463756, 2012.
2. Arnold J, Hamer MJ, Irving M. Hepatic phosphofructokinase-1 activity and fructose 2,6-bisphosphate levels in patients with abdominal sepsis. Clin Sci (Lond) 80: 213-7, 1991. 3. Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF. Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A 104: 11014-9, 2007. 4. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 392: 245-52, 1998. 5. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434: 864-70, 2005. 6. Benesch RE, Lardy HA, Benesch R. The sulfhydryl groups of crystalline proteins. I. Some albumins, enzymes, and hemoglobins. J Biol Chem 216: 663-76, 1955. 7. Calmels S, Hainaut P, Ohshima H. Nitric oxide induces conformational and functional modifications of wild-type p53 tumor suppressor protein. Cancer Res 57: 3365-9, 1997. 8. Castiglione N, Rinaldo S, Giardina G, Stelitano V, Cutruzzola F. Nitrite and nitrite reductases: from molecular mechanisms to significance in human health and disease. Antioxid Redox Signal 17: 684-716, 2012. 9. Chazotte-Aubert L, Hainaut P, Ohshima H. Nitric oxide nitrates tyrosine residues of tumor-suppressor p53 protein in MCF-7 cells. Biochem Biophys Res Commun 267: 609-13, 2000. 10. Chazotte-Aubert L, Oikawa S, Gilibert I, Bianchini F, Kawanishi S, Ohshima H. Cytotoxicity and site-specific DNA damage induced by nitroxyl anion (NO(-)) in the presence of hydrogen peroxide. Implications for various pathophysiological conditions. J Biol Chem 274: 20909-15, 1999. 11. Chen BJ, Cui X, Sempowski GD, Domen J, Chao NJ. Hematopoietic stem cell dose correlates with the speed of immune reconstitution after stem cell transplantation. Blood 103: 4344-52, 2004. 12. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30: 1073-81, 2009. 13. D'Antuono M, Biagini G, Tancredi V, Avoli M. Electrophysiology of regular firing cells in the rat perirhinal cortex. Hippocampus 11: 662-72, 2001. 14. Deweese JE, Osheroff N. The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing. Nucleic Acids Res 37: 738-48, 2009. 15. Egeblad M, Nakasone ES, Werb Z. Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 18: 884-901, 2010. 16. Fan JR, Peng AL, Chen HC, Lo SC, Huang TH, Li TK. Cellular processing pathways contribute to the activation of etoposide-induced DNA damage responses. DNA Repair (Amst) 7: 452-63, 2008. 17. Feng CW, Wang LD, Jiao LH, Liu B, Zheng S, Xie XJ. Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features. BMC Cancer 2: 8, 2002. 18. Feng Z, Hu W, Tang MS. Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci U S A 101: 8598-602, 2004. 19. Fortune JM, Osheroff N. Topoisomerase II as a target for anticancer drugs: when enzymes stop being nice. Prog Nucleic Acid Res Mol Biol 64: 221-53, 2000. 20. Gaston BM, Carver J, Doctor A, Palmer LA. S-nitrosylation signaling in cell biology. Mol Interv 3: 253-63, 2003. 21. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RA, Jr., Kastrinakis NG, Levy B, Kletsas D, Yoneta A, Herlyn M, Kittas C, Halazonetis TD. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434: 907-13, 2005. 22. Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB. Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid Redox Signal 16: 1295-322, 2012. 23. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144: 646-74, 2011. 24. Harker WG, Slade DL, Parr RL, Holguin MH. Selective use of an alternative stop codon and polyadenylation signal within intron sequences leads to a truncated topoisomerase II alpha messenger RNA and protein in human HL-60 leukemia cells selected for resistance to mitoxantrone. Cancer Res 55: 4962-71, 1995. 25. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56: 549-80, 2004. 26. Hofseth LJ, Saito S, Hussain SP, Espey MG, Miranda KM, Araki Y, Jhappan C, Higashimoto Y, He P, Linke SP, Quezado MM, Zurer I, Rotter V, Wink DA, Appella E, Harris CC. Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc Natl Acad Sci U S A 100: 143-8, 2003. 27. Hotamisligil GS. Inflammation and metabolic disorders. Nature 444: 860-7, 2006. 28. Huang TH, Chen HC, Chou SM, Yang YC, Fan JR, Li TK. Cellular processing determinants for the activation of damage signals in response to topoisomerase I-linked DNA breakage. Cell Res 20: 1060-75, 2010. 29. Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer 3: 276-85, 2003. 30. Janeway CA, Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol 20: 197-216, 2002. 31. Jungwirth U, Kowol CR, Keppler BK, Hartinger CG, Berger W, Heffeter P. Anticancer activity of metal complexes: involvement of redox processes. Antioxid Redox Signal 15: 1085-127, 2011. 32. Kusari S, Zuhlke S, Spiteller M. An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J Nat Prod 72: 2-7, 2009. 33. Land H, Chen AC, Morgenstern JP, Parada LF, Weinberg RA. Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts. Mol Cell Biol 6: 1917-25, 1986. 34. Li S, Yi Y, Wang Y, Zhang Z, Beasley RS. Camptothecin accumulation and variations in camptotheca. Planta Med 68: 1010-6, 2002. 35. Li TK, Chen AY, Yu C, Mao Y, Wang H, Liu LF. Activation of topoisomerase II-mediated excision of chromosomal DNA loops during oxidative stress. Genes Dev 13: 1553-60, 1999. 36. Li TK, Houghton PJ, Desai SD, Daroui P, Liu AA, Hars ES, Ruchelman AL, LaVoie EJ, Liu LF. Characterization of ARC-111 as a novel topoisomerase I-targeting anticancer drug. Cancer Res 63: 8400-7, 2003. 37. Li TK, Liu LF. Tumor cell death induced by topoisomerase-targeting drugs. Annu Rev Pharmacol Toxicol 41: 53-77, 2001. 38. Lorusso G, Ruegg C. The tumor microenvironment and its contribution to tumor evolution toward metastasis. Histochem Cell Biol 130: 1091-103, 2008. 39. Lu H, Gorman E, McKnight TD. Molecular characterization of two anthranilate synthase alpha subunit genes in Camptotheca acuminata. Planta 221: 352-60, 2005. 40. Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, Liu LF. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res 67: 8839-46, 2007. 41. Lyu YL, Wang JC. Aberrant lamination in the cerebral cortex of mouse embryos lacking DNA topoisomerase IIbeta. Proc Natl Acad Sci U S A 100: 7123-8, 2003. 42. Maiti D, Sarkar TS, Ghosh S. Detection of S-nitrosothiol and nitrosylated proteins in Arachis hypogaea functional nodule: response of the nitrogen fixing symbiont. PLoS One 7: e45526, 2012. 43. Melillo RM, Castellone MD, Guarino V, De Falco V, Cirafici AM, Salvatore G, Caiazzo F, Basolo F, Giannini R, Kruhoffer M, Orntoft T, Fusco A, Santoro M. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest 115: 1068-81, 2005. 44. Milde-Langosch K, Karn T, Muller V, Witzel I, Rody A, Schmidt M, Wirtz RM. Validity of the proliferation markers Ki67, TOP2A, and RacGAP1 in molecular subgroups of breast cancer. Breast Cancer Res Treat, 2012. 45. Monacelli B, Valletta A, Rascio N, Moro I, Pasqua G. Laticifers in Camptotheca acuminata Decne: distribution and structure. Protoplasma 226: 155-61, 2005. 46. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109-42, 1991. 47. Montoro P, Maldini M, Piacente S, Macchia M, Pizza C. Metabolite fingerprinting of Camptotheca acuminata and the HPLC-ESI-MS/MS analysis of camptothecin and related alkaloids. J Pharm Biomed Anal 51: 405-15, 2010. 48. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8: 958-69, 2008. 49. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29: 71-109, 2011. 50. Pedersen-Bjergaard J, Andersen MK, Christiansen DH, Nerlov C. Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. Blood 99: 1909-12, 2002. 51. Pommier Y. Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints. Curr Med Chem Anticancer Agents 4: 429-34, 2004. 52. Pommier Y, Zwelling LA, Schwartz RE, Mattern MR, Kohn KW. Absence of a requirement for long-range DNA torsional strain in the production of protein-associated DNA strand breaks in isolated mammalian cell nuclei by the DNA intercalating agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA). Biochem Pharmacol 33: 3909-12, 1984. 53. Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270: 7420-6, 1995. 54. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett 256: 137-65, 2007. 55. Ratain MJ. Therapeutic relevance of pharmacokinetics and pharmacodynamics. Semin Oncol 19: 8-13, 1992. 56. Rosenberg L, Palmer JR, Zauber AG, Warshauer ME, Stolley PD, Shapiro S. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. J Natl Cancer Inst 83: 355-8, 1991. 57. Rowley JD. The critical role of chromosome translocations in human leukemias. Annu Rev Genet 32: 495-519, 1998. 58. Salk JJ, Salipante SJ, Risques RA, Crispin DA, Li L, Bronner MP, Brentnall TA, Rabinovitch PS, Horwitz MS, Loeb LA. Clonal expansions in ulcerative colitis identify patients with neoplasia. Proc Natl Acad Sci U S A 106: 20871-6, 2009. 59. Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19: 59-70, 2003. 60. Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O'Neill LA, Perretti M, Rossi AG, Wallace JL. Resolution of inflammation: state of the art, definitions and terms. FASEB J 21: 325-32, 2007. 61. Shi WG, Zu YG, Yang L, Zhao CJ, Li JH. [Isolation and purification of 10-hydroxycamptothecin and vincoside-lactam from Camptotheca acuminata seed by polyamide]. Zhongguo Zhong Yao Za Zhi 33: 2486-9, 2008. 62. Spagnoli LG, Bonanno E, Sangiorgi G, Mauriello A. Role of inflammation in atherosclerosis. J Nucl Med 48: 1800-15, 2007. 63. Wall ME, Wani MC, Natschke SM, Nicholas AW. Plant antitumor agents. 22. Isolation of 11-hydroxycamptothecin from Camptotheca acuminata Decne: total synthesis and biological activity. J Med Chem 29: 1553-5, 1986. 64. Wang H, Mao Y, Chen AY, Zhou N, LaVoie EJ, Liu LF. Stimulation of topoisomerase II-mediated DNA damage via a mechanism involving protein thiolation. Biochemistry 40: 3316-23, 2001. 65. Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3: 430-40, 2002. 66. Wu CC, Li TK, Farh L, Lin LY, Lin TS, Yu YJ, Yen TJ, Chiang CW, Chan NL. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 333: 459-62, 2011. 67. Xiao H, Li TK, Yang JM, Liu LF. Acidic pH induces topoisomerase II-mediated DNA damage. Proc Natl Acad Sci U S A 100: 5205-10, 2003. 68. Yamazaki F, Okamoto H, Matsumura Y, Tanaka K, Kunisada T, Horio T. Development of a new mouse model (xeroderma pigmentosum a-deficient, stem cell factor-transgenic) of ultraviolet B-induced melanoma. J Invest Dermatol 125: 521-5, 2005. 69. Zaki MH, Vogel P, Malireddi RK, Body-Malapel M, Anand PK, Bertin J, Green DR, Lamkanfi M, Kanneganti TD. The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. Cancer Cell 20: 649-60, 2011. 70. Zhang Y, Strissel P, Strick R, Chen J, Nucifora G, Le Beau MM, Larson RA, Rowley JD. Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia. Proc Natl Acad Sci U S A 99: 3070-5, 2002. 71. Zhou N, Xiao H, Li TK, Nur EKA, Liu LF. DNA damage-mediated apoptosis induced by selenium compounds. J Biol Chem 278: 29532-7, 2003. 72. Zwelling LA, Kerrigan D, Michaels S, Kohn KW. Cooperative sequestration of m-AMSA in L1210 cells. Biochem Pharmacol 31: 3269-77, 1982. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63204 | - |
dc.description.abstract | 在慢性發炎反應中與氧自由基或氮自由基相關的分子(ROS & RNOS)已經被證實在癌症產生的過程中扮演重要的角色。而在我們實驗室以往的研究中指出,第二型拓樸異構酶(topoisomerase II, TOP2)會因為氧自由基的反應下,產生DNA與第二型拓樸異構酶複合體(topoisomerase II cleavage complex, TOP2cc),導致DNA斷裂。因此在本篇的研究中,我們想要解釋在發炎的環境下,氮自由基中的一氧化氮(Nitric oxide, NO)會因為誘導TOP2參與的DNA損傷和染色體基因組的不穩定,而提高細胞癌化的風險。我們利用兩階段小鼠皮膚黑色素瘤形成的動物試驗模型來證明NO提供者,S-亞硝基穀胱甘肽(GSNO)與第二型拓樸異構酶藥物,Etoposide (VP-16)的處理下,可以誘發黑色素瘤的形成。另外,我們也發展細胞共培養系統來證實活化的巨噬細胞因為大量表現誘導型一氧化氮合成酶(iNOS),使得標的細胞染色體DNA斷裂與細胞訊息的活化(γ-H2AX & p53-ser15P)。在有無抑制藥物的條件下,也可以觀察到NO與TOP2的重要性。細胞毒性試驗則對於NO所誘發的反應提供一個有力的證據:在細胞可以忍受的NO毒性下,細胞可以對於NO產生的DNA斷裂進行修補的反應。因此,進一步我們利用DNA重組試驗,觀察到由於NO可以誘發TOP2參與的DNA斷裂,因此提高了DNA重組的頻率。最後我們利用TOP2β基因剔除小鼠來檢查TOP2同工異構酶在NO的處理下,確實可以降低因為NO誘發TOP2引起的DNA損傷和染色體基因組的不穩定,也因此降低小鼠皮膚黑色素瘤產生的風險。在本篇研究中,我們提供了第一個實驗證據證明NO誘導TOP2參與的DNA損傷,會提高DNA突變和細胞癌化的風險。這些研究有助於以分子生物學的角度解釋慢性發炎反應與癌症之間的關係。 | zh_TW |
dc.description.abstract | Aims: Both cancer-suppressing and cancer-promoting properties of reactive nitrogen and oxygen species (RNOS) have been suggested to play a role in tumor pathology, particularly those activities associated with chronic inflammation. Here, we address the impact of nitric oxide (NO) on the induction of DNA damage and genome instability with a specific focus on the involvement of topoisomerase II (TOP2). We also investigate the contribution of NO to the formation of skin melanoma in mice.
Results: Similar to the TOP2-targeting drug, etoposide (VP-16), the NO-donor, S-nitrosoglutathione (GSNO), induces skin melanomas formation in 7,12-dimethyl- benz[a]anthracene (DMBA)-initiated mice. To explore the mechanism(s) underlying this NO-induced tumorigenesis, we use a co-culture model system to demonstrated that inflamed macrophages with inducible NO synthase (iNOS) expression cause γ-H2AX activation, p53 phosphorylation and chromosome DNA breaks in the target cells. Inhibitor experiments revealed that NO and TOP2 isozymes are responsible for the described above cellular phenotypes. Notably, NO unlike VP-16 preferentially induces the formation of TOP2β cleavable complexes (TOP2βcc) in cells. Moreover, GSNO induced TOP2-dependent DNA sequence rearrangements and cytotoxicity. Furthermore, the incidences of GSNO- and VP-16-induced skin melanomas were also observed to be lower in the skin-specific top2β-knockout mice. Our results suggest that TOP2 isozymes contribute to NO-induced mutagenesis and subsequent cancer development during chronic inflammation. Innovation and Conclusions: Here, we provide the first experimental evidence for the functional role of TOP2 in NO-caused DNA damage, mutagenesis and carcinogenesis. Notably, these studies contribute, in part, to our molecular understanding of the cancer-promoting actions of RNOS during chronic inflammation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T16:28:06Z (GMT). No. of bitstreams: 1 ntu-101-D96445009-1.pdf: 2176730 bytes, checksum: 8a996f4222bde212734466d267bfa6b2 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 口試委員會審定書……………………………………………………………………i
Acknowledgements…………………………………………………………………ii 中文摘要……………………………………………………………………………iii Abstract……………………………………………………………………………iv Content………………………………………………………………………………vi Introduction…………………………………………………………………………1 1. Inflammatory response…………………………………………………………….1 2. The correction between inflammation and carcinogenesis (CRI)………………....3 3. Topoisomerase……………………………………………………………………..7 4. Specific aim………………………………………………………………………12 Materials and Methods…………………………………………………..13 1. Chemicals, antibodies and immunoblotting analysis……………………………13 2. Cell lines and cytotoxicity assays……………………………………………….13 3. Mouse genotyping………………………………………………………………14 4. The two-stage mouse skin carcinogenesis model and IHC analysis…………….15 5. Co-culture conditions and Griess assay…………………………………………16 6. Experimental assays for TOP2-linked DNA breaks and TOP2 cleavable complexes (TOP2cc)……………………………………………………….……17 7. In vitro TOP2-mediated DNA cleavage assay…………………….18 8. Lentivirus-based RNA interference (RNAi) and plasmid-integration assay…….19 9. Quantitative measurement and statistical analysis……………………………...19 Results……………………………………………………………………………...21 1. NO induced TOP2β-mediated DNA breaks……………………………………21 2. NO treatment increased TOP2-mediated cellular recombination repair frequency………………………………………………..26 3. NO induced TOP2β-mediated melanoma formation………………27 Discussions……………………………………………………………………29 Figures……………………………………………………………………………32 Fig.1 Raw264.7 cells were stimulated with LPS, IFN-γ, LPS+IFN-γ then produced NO………………………………………………………………32 Fig.2 Cellular exposure to NO induced in TOP2-linked DNA breaks…………..33 Fig.3 NO induces DNA breakage………………………………………………34 Fig.4 The NO-induced DDR activation is also antagonized by ICRF-193 pre-treatment……………………………………………...……………...35 Fig.5 NO could induce TOP2-mediated DNA breaks…………………………36 Fig.6 NO could induce TOP2cc formation………………………………………37 Fig.7 TOP2αcc, over TOP2βcc, is preferentially formed during chronic inflammation condition………………….…..……..………………..38 Fig.8 GSNO treatment induces TOP2cc formation……………………………39 Fig.9 The GSNO-induced formation of TOP2cc is highly reversible…………...40 Fig.10 The formation of TOP2α, TOP2βcc and TOP1cc are mainly responsible for the DDR activation by GSNO, VP-16 and CPT treatments respectively…………………………………………………...41 Fig.11 GSNO stimulates reversible TOP2-mediated DNA cleavage……………42 Fig.12 GSNO stimulates reversible TOP2-mediated DNA cleavage……………43 Fig.13 GSNO stimulates reversible TOP2-mediated DNA cleavage……………44 Fig.14 The isozyme-specific knockdown efficiency of HL-60 LucKD, TOP2αKD and TOP2βKD cells………………………………………….45 Fig.15 Both TOP2 isozymes contribute to the GSNO-stimulated DNA breaks and mutagenesis………………………………………………………….46 Fig.16 ICRF abolishes both GSNO- and VP-16-stimulated mutagenesis…….47 Fig.17 The GSNO-stimulated cytotoxicity and mutagenesis is mediated mainly through the TOP2β isozyme in HCT116 colorectal cancer cells…………………………………………………...…………………..48 Fig.18 GSNO, unlike VP-16, induces primarily the TOP2β-mediated mutagenesis in HCT116 cells…………………………………………….49 Fig.19 NO promotes formation of melanomas in the mouse skin carcinogenesis model, like TOP2-targeting etoposide (VP-16) does…….50 Fig.20 Representative images of histological and immunohistochemical analyses of the GSNO-, VP-16- and TPA-induced skin melanomas…….51 Fig.21 TOP2β contributes to the formation of NO- and VP-16-induced skin melanomas…………………..………………………………………52 Table.1 Topoisomerase subfamily..........................................54 Reference…………………………………………………………………………..55 | |
dc.language.iso | en | |
dc.title | 探討腫瘤生成相關的發炎反應中一氧化氮活化第二型拓樸異構酶參與之DNA裂解與突變的機制 | zh_TW |
dc.title | Topoisomerase II-mediated DNA cleavage and mutagenesis activated by nitric oxide underlie the inflammation-associated tumorigenesis | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 鄧述諄(Shu-Chun Teng),董馨蓮(Shin-Lian Doong),詹迺立(Nei-Li Chan),賴逸儒(I-Rue Lai) | |
dc.subject.keyword | 發炎反應,一氧化氮,拓樸異構酶,DNA裂解與突變, | zh_TW |
dc.subject.keyword | Topoisomerase II,DNA cleavage and mutagenesis,nitric oxide,inflammation,tumorigenesis, | en |
dc.relation.page | 61 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-01-11 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 微生物學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-101-1.pdf 目前未授權公開取用 | 2.13 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。