跳到主要內容

臺灣博碩士論文加值系統

(44.192.48.196) 您好!臺灣時間:2024/06/14 17:25
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:孫上禾
研究生(外文):Shang-Ho Sun
論文名稱:COX-2基因啟動區突變點檢測以及快速篩檢的方法之研究
論文名稱(外文):The Rapid Method of Scanning Mutation in COX-2 Gene Promoter Region
指導教授:藍萬烘藍萬烘引用關係
指導教授(外文):Wan-Hong Lan
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床牙醫學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:111
中文關鍵詞:DNACOX-2聚合酶連鎖反應巢狀聚合酶連鎖反應high-resolution儀器分析
外文關鍵詞:DNACOX-2PCRnested PCRhigh-resolution melting analysis
相關次數:
  • 被引用被引用:0
  • 點閱點閱:240
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
隨著人類基因體計畫的進展,人們發現個體基因的多型性有助於解釋個體的表型差異、不同群體和個體對疾病,特別是對複雜疾病的易感性、以及對各種藥物的耐受性和對環境因素的反應。但因我們所能取得的樣本有限,因此以微量的樣本所萃取出DNA來做各種鑑定及研究,有其重要性。
我們研究的重點就是簡單、容易地把微量DNA萃取出來,並利用些特殊方法,將所萃取的微量DNA大量複製出我們想要的片段來,又因有相關證據表示COX-2的表現與癌症具有關聯。所以我們藉著最新的分析技術,試著從大量樣品中,來篩選出可能有COX-2基因變異的個體。
本論文可分三部分,首先我們利用牙科紙針從10位台大醫院病人的口腔中吸取唾液及洗牙後於牙齦溝滲出之血液,所取之紙針利用QIAamp DNA Micro kit 抽取出其中之DNA,並以IL-1β基因引子進行聚合酶連鎖反應(PCR),最後再以洋菜膠(agarose)電泳顯示出結果。
第二部分,樣品取自台大醫院牙科就診的201位病人,其中187位是沒得過口腔癌的人,14位為現在口腔癌的病人或有口腔癌病史的人,以萃取之DNA來複製長片段的COX-2基因啟動區,使用更精密的巢狀聚合酶連鎖反應(nest PCR),並測試此方法複製長片段基因之成功率。最後,利用最新的high-resolution儀器來分析篩選出COX-2基因啟動區可能有變異的樣品。
結果顯示,所有的唾液及血液之微量DNA皆能由QIAamp的方式來萃取出來,並且IL-1β基因(249 b.p)經過PCR的放大後,都可以在電泳膠上清楚的顯示。在使用nested PCR,來複製長片段COX-2基因啟動區方面有95%以上的成功率。而且我們用high-resolution儀器分析也能迅速地將全部的樣品基因分出兩種波形,並藉由這兩種波形的差異來篩選出可能有變異的樣品,進而以核酸定序來證實之。
往後我們可用紙針蒐集血液和唾液方式來替代較具侵入性之檢驗法,這不但有容易操作、容易取得、不佔空間、節省成本等優點,並且可以降低受檢者之恐懼感及不適,大大地提升其接受檢驗之意願。nested PCR可以有95%以上的成功率將長片段基因複製出來,如此可以用非常微小的量來大大地增加DNA複製的效率。利用最新的high-resolution儀器分析,將來我們不需花時間將所有的樣品定序,而且不需花很多金錢來做real-time PCR分析,只需要一組primer,一點LC Green dye和一台PCR儀器及HR-1儀器,就可以簡單、不貴且迅速地分析出DNA的基因型和變異型。 High-resolution儀器分析將會是未來檢測DNA變異的主流方法之一。
Background Data: Since the marked advance of Human Genome Project, analysis of genetic polymorphism has been popularly used to explain the individual difference in susceptibility to various diseases, such as infection of complicated diseases, sensitivity of medication and environment. However, analysis of gene polymorphisms is sometimes not feasible due to limited DNA available.
Objective: A simple and easy method to extract DNA from minimal amount of saliva and blood for PCR amplification of gene is necessary. Some studies indicated the relation between COX-2 expression and cancer. Thus, we try to design an analytical technique to compare the COX-2 promoter region polymorphism in clinical healthy and oral cancer patients.
Materials and Methods: This study divided three parts. First, we collected saliva and blood with paper points after full mouth scaling in NTUH. The tips of paper points were used to extract DNA using QIAamp DNA Micro kit. PCR was used to amplified IL-1βgene from isolated DNA, subjected to agarose gel electrophoresis, stained with ethidium bromide.
Second, we followed the same method to collect samples and the samples were 201 patients in NTUH, including 187 healthy control subjects and 14 patients who had oral cancer or medical history of oral caner. DNA was isolated and used to amplified the promoter region of COX-2 gene by more sensitive method “nested PCR”. Finally, we utilized the latest analytical technique “high-resolution melting analysis” and nucleotide sequencing to screen some doubtful samples with mutation of COX-2 promoter region.
Results: We successfully extracted DNA from all blood and saliva samples by QIAamp DNA isolation kits. After PCR amplification of IL-1β genes (249 b.p), the specific DNA bands were clearly identified on agarose gels after ethidium bromide staining. Moreover, by using Nested PCR, the successful rates to amplify long genetic section of COX-2 promoter region were above 95%. We further utilized high-resolution melting analysis to detect two patterns of the melting curves. According to these two types of curves, we could screen doubtful samples and make further confirmation of gene polymorphism sites by DNA nucleotide sequencing.


Conclusion: The results indicate that we can use paper point to substitute the invasive methods for collecting blood and saliva for DNA analysis in the future. The advantage is easy to operate and obtain, not to occupy the space, and the economical cost. Futhermore, people can reduce fear and receive examination by this method. We can amplify long genetic section above 95% by nested PCR which can greatly increase efficiency to amplify tiny amount of DNA. Utilizing high-resolution melting analysis, we can not spend time to sequence all samples, and can not spend money to do real-time PCR. SNP genotyping will be simple, rapid, and inexpensive, requiring only one pair of primers, a little LC Green dye, one PCR machine, and one HR-1 machine. High-resolution melting analysis will be the best methods of SNP genotyping in the future.
中文摘要 ---------------------------------------------------------------------i
英文摘要 --------------------------------------------------------------------iv
壹、緒論
第一章:DNA鑑定法
第一節:DNA簡介 -------------------------------------------------------1
第二節:DNA定量法 ----------------------------------------------------2
第二章:PCR系統之鑑定
第一節:PCR發展背景 --------------------------------------------------6
第二節:PCR的原理 -----------------------------------------------------8
第三節:PCR之應用 -----------------------------------------------------9
第四節:巢狀聚合酶連鎖反應 ---------------------------------------10
第五節:污染防治措施 ------------------------------------------------11
第六節:以PCR系統鑑定DNA之種類 -----------------------------12
第三章:單核苷酸多型性(SNP)之鑑定法
第一節:SNP簡介 ------------------------------------------------------13
第二節:同型合子與異型合子 ---------------------------------------14
第三節:SNP分析的應用 ---------------------------------------------14
第四節:定序法 ---------------------------------------------------------16
第五節:High-resolution儀器分析 -----------------------------------18
第四章:第二型環氧酵素(COX-2)與口腔癌
第一節:第二型環氧酵素簡介 ---------------------------------------20
第二節:COX-2與IL-1β的關係 ------------------------------------21
第三節:口腔癌簡介 ---------------------------------------------------22
第四節:COX-2在癌症所扮演的角色 ------------------------------24
貳、實驗動機與目的
第一章:實驗動機 ------------------------------------------------------28
第二章:實驗目的 ------------------------------------------------------29
參、實驗材料與儀器
第一章:儀器 -------------------------------------------------------------30
第二章:材料 -------------------------------------------------------------32
肆、實驗方法
第一章:利用QIAamp的技術從血液及唾液中萃取DNA並測出樣本的量
第一節:微量樣本的取得 ---------------------------------------------35
第二節:萃取微量DNA ------------------------------------------------35
第三節:DNA濃度的檢測 --------------------------------------------36
第四節:聚合酶連鎖反應 ---------------------------------------------37
第五節:電泳 ------------------------------------------------------------38
第二章:利用巢狀聚合酶連鎖反應的技術複製COX-2基因啟動區的成功率
第一節:血液和唾液樣本的蒐集 ------------------------------------39
第二節:血液DNA的萃取 --------------------------------------------39
第三節:唾液DNA的萃取 --------------------------------------------40
第四節:聚合酶連鎖反應與電泳 ------------------------------------42
第五節:巢狀聚合酶連鎖反應與電泳 ------------------------------43
第三章:利用HR-1儀器來分析COX-2基因啟動區之變異
第一節:High-resolution儀器分析 -----------------------------------45
第二節:純化 ------------------------------------------------------------46
第三節:定序 ------------------------------------------------------------47
伍、實驗結果
第一章:利用QIAamp的技術從血液及唾液中萃取DNA並測出樣本的量
第一節:經Nano drop ND-1000超微量高精度光度計所測出來的唾液和血液之DNA量 -------------------------------------48
第二節:利用PCR將IL-1β基因複製出來的結果 ----------------48
第二章:利用巢狀聚合酶連鎖反應的技術複製COX-2基因啟動區的成功率
第一節:使用PCR將COX-2基因啟動區複製的結果表現 -----50
第二節:使用nested PCR將COX-2基因啟動區複製的結果表現 ------------------------------------------------------------------50
第三章:利用HR-1儀器來分析COX-2基因啟動區之變異
第一節:HR-1儀器分析 -----------------------------------------------52
第二節:COX-2基因啟動區前段經HR-1儀器分析的結果表現 ------------------------------------------------------------------52
第三節:COX-2基因啟動區段後經HR-1分析儀器的結果表現 ------------------------------------------------------------------54
第四節:COX-2基因啟動區定序之結果 ---------------------------56
陸、討論
第一章:利用QIAamp的技術從血液及唾液中萃取DNA並測出樣本的量 -----------------------------------------------59
第二章:利用巢狀聚合酶連鎖反應的技術複製COX-2基因啟動區的成功率 -------------------------------------------64
第三章:利用HR-1儀器來分析COX-2基因啟動區之變異 -----------------------------------------------------------66
柒、結論 --------------------------------------------------------------------71
捌、參考文獻 ------------------------------------------------------------72
玖、實驗表 ---------------------------------------------------------------78
拾、實驗圖 ----------------------------------------------------------------82
1.Andrisin TE, Humma LM, Johnson JA (2002) Collection of genomic DNA by the noninvasive mouthwash method for use in pharmacogenetic studies. Pharmacotherapy 22(8):954-960
2.Angel Carracedo, Paula Sanchez-Diz. (2004) Forensic DNA-typing technologies. Methods Mol Biol 297: 1-11
3.Atsushi Akane, Satoko Seki, Hiroshi Shiono et al. (1992) Sex determination of forensic samples by dual PCR amplification of an X-Y homologous gene. Forensic Sci Int 52:143-148
4.Belvisi MG, Saunders MA, Haddad el-B, Hirst SJ, et al. (1997) Induction of cyclo-oxygenase-2 by cytokines in human cultured airway smooth muscle cells: novel inflammatory role of this cell type. Br J Pharmacol. 120(5):910-6.
5.Brion C. Smith (2001) Introduction to DNA analysis. Dental Clinics of North America 45(2):229-235.
6.Chan G, Boyle JO, Yang EK, Zhang F, Sacks PG, Edelstein D, Soslow RA, Koki AT, Woerner BM, Masferrer JL and Dannenberg AJ (1999a) Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res 59:991-994
7.Chen C (1987) An epidemiological study of oral squamous cell carcinoma in southern Taiwan. J Formosan Dent Assoc 10:268-274.
8.Chien A, Edgar DB, Trela JM.(1976) Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus. J Bacteriol. 127(3):1550-7
9.Daniel P.K. Ng, David Koh, Serena G.L. Choo, Vivian Ng,Qiuyun Fu. (2004) Effect of storage conditions on the extraction of PCR-quality genomic DNA from saliva. Clinica Chimica Acta 343:191-194
10.Dannenberg AJ, Altorki NK, Boyle JO, Dang C, Howe LR, Weksler BB and Subbaramaiah K (2001) Cyclooxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2:544-551.
11.Dixon DA, Kaplan CD, McIntyre TM, Zimmerman GA and Prescott SM (2000) Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3''-untranslated region. J Biol Chem 275:11750-11757.
12.Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, and Lipsky PE (1998) Cyclooxygenase in biology and disease. FASEB J 12:1063–1073
13.Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, and DuBois RN (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183–1188
14.Ellen Fritsche, Seung Joon Baek, Lorraine M. King, Darryl C. Zeldin, et al. (2001) Functional characterization of cyclooxygenase-2 polymorphisms. JPET 299:468–476
15.Fosslien E (2000) Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 30:3-21.
16.Francoise Fridez, Raphael Coquoz (1996) PCR DNA typing of stamps: evaluation of the DNA extraction. Forensic Sci Int 78:103-110
17.Hogaboam CM, Steinhauser ML, Chensue SW, Kunkel SI (1998) Novel roles for chemokines and fibroblasts in interstitial fibrosis. Kidney Int 54; 2152-9
18.Howe LR, Subbaramaiah K, Brown AM and Dannenberg AJ (2001b) Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8:97-114.
19.Hwang D, Scollard D, Byrne J, and Levine E (1998) Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 90:455–460.
20.Irwin MH, Moffatt RJ, Pinkert CA (1996) Identification of transgenic mice by PCR analysis of saliva. Nature Biotechnology 14:1146-1148
21.J. Brøns-Poulsen, N. E. Petersen, M. Hørder, K. Kristiansen (1998) An improved PCR-based method for site directed mutagenesis using megaprimers. Molecular and Cellular Probes 12:345–348
22.J.P. Whitaker, T.M. Clayton, A.J. Urquhar, E.S. Millican, T.J. Downes, et al. (1995) Short tandem repeat typing of bodies from a mass disaster: high success rate and characteristic amplification patterns in highly degraded samples. BioTechniques 18(4):670-677
23.Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA, and Jothy S (1995) Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 55:2556–2559
24.Kathryn Sinclair, Victoria M. McKechnie (2000) DNA extraction from stamps and enveliope flaps using QIAamp and QIAshredder. J Forensic Sci 45(1):229-230
25.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
26.Kujubu DA, Fletcher BS, Varnum BC, Lim RW, and Herschman HR (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266:12866–12872
27.Kutchera W, Jones DA, Matsunami N, Groden J, McIntyre TM, Zimmerman GA, White RL, and Prescott SM (1996) Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: Evidence for a transcriptional effect. Proc Natl Acad Sci USA 93:4816–4820
28.Lederberg J. (1994) The transformation of genetics by DNA: an anniversary celebration of Avery, MacLeod and McCarty (1944). Genetics. 136(2):423-6.
29.Leung WK, To KF, Ng YP, Lee TL, Lau JY, Chan FK, Ng EK, Chung SC and Sung JJ (2001) Association between cyclooxygenase-2 overexpression and missense p53 mutations in gastric cancer. Br J Cancer 84:335-339
30.Liew M, Pryor R, Palais R, Meadows C, et al. (2004) Genotyping of single-nucleotide polymorphisms by high-resolution melting of small amplicons. Clin Chem 50(7):1156-1164
31.Mark KS, Trickler WJ, Miller DW (2001) Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. J Pharmacol Exp Ther. 297(3):1051-8.
32.Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci U S A. 74(2):560-4
33.McOrist AL, Jackson M, Bird AR (2002) A comparison of five methods for extraction of bacterial DNA from human faecal samples. J Microbiol Methods 50(2):131–139
34.Mitchell JA, Belvisi MG, Akarasereenont P, Robbins RA, et al. (1994) Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: regulation by dexamethasone. Br J Pharmacol. 113(3):1008-14
35.Mutri PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS (1995) Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 24: 145-52
36.Pang L, Knox AJ. (1997) Effect of interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma on the induction of cyclo-oxygenase-2 in cultured human airway smooth muscle cells. Br J Pharmacol. 121(3):579-87.
37.R. K. Saiki, D.H.Gelfand, S. Stoffel, S. Scharf, R. Higuchi, et al. (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 39: 487-491.
38.R. K. Saiki, S. Scharf, F. Faloona, K. B. Mullis, G. Horn, et al. (1985) Enzymatic amplification of β-globin genomic sequences and restriction site analysis of sickle cell anemia. Science 230: 1350-1354.
39.Renkonen J, Wolff H and Paavonen T (2002) Expression of cyclooxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch 440:594-597
40.Rimarachin JA, Jacobson JA, Szabo P, Maclouf J, Creminon C, and Weksler BB (1994) Regulation of cyclooxygenase-2 expression in aortic smooth muscle cells. Arterioscler Thromb 14:1021–1031
41.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
42.Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H and Isola J (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62:632-635
43.Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, KatoH, Kondo M, and Hla T (1995) Expression of Cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55:3785–3789.
44.Shao J, Sheng H, Inoue H, Morrow JD and DuBois RN (2000) Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem 275:33951-33956.
45.Sheng H, Shao J, Dixon DA, Williams CS, Prescott SM, DuBois RN and Beauchamp RD (2000) Transforming growth factor-beta 1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA. J Biol Chem 275:6628-6635.
46.Shiota G, Okubo M, Noumi T, Noguchi N, Oyama K, Takano Y, Yashima K, Kishimoto Y, and Kawasaki H (1999) Cyclooxygenase-2 expression in hepatocellular carcinoma. Hepato-gastroenterology 46:407–412.
47.Smith WL, DeWitt DL and Garavito RM (2000b) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145-182.
48.Song SH, Jong HS, Choi HH, Inoue H, Tanabe T, Kim NK and Bang YJ (2001) Transcriptional silencing of cyclooxygenase-2 by hyper-methylation of the 5'' CpG island in human gastric carcinoma cells. Cancer Res 61:4628-4635
49.Streckfus CF, Bigler LR. (2002) Saliva as a diagnostic fluid. Oral Dis 8:69-76
50.Subbaramaiah K, Altorki N, Chung WJ, Mestre JR, Sampat A and Dannenberg AJ (1999) Inhibition of cyclooxygenase-2 gene expression by p53. J Biol Chem 274:10911-10915
51.Subbaramaiah K, Cole PA and Dannenberg AJ (2002a) Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and -independent mechanisms. Cancer Res 62:2522-2530.
52.Subbaramaiah K, Norton L, Gerald W and Dannenberg AJ (2002b) Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem 277:18649-18657.
53.Sudbo J and Reith A (2003) Which putatively pre-malignant oral lesions become oral cancers? Clinical relevance of early targeting of high-risk individuals. J Oral Pathol Med 32:63-70.
54.Sudbo J, Ristimaki A, Sondresen JE, Kildal W, Boysen M, Koppang HS, Reith A, Risberg B, Nesland JM and Bryne M (2003) Cyclooxygenase-2 (COX-2) expression in high-risk premalignant oral lesions. Oral Oncol 39:497-505
55.Sumitani K, Kamijo R, Toyoshima T, Nakanishi Y, Takizawa K, Hatori M and Nagumo M (2001) Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production. J Oral Pathol Med 30:41-47.
56.Terakado N, Shintani S, Yano J, Chunnan L, Mihara M, Nakashiro K and Hamakawa H (2004) Overexpression of COX-2 is associated with radioresistance in oral squamous cell carcinoma. Oral Oncol 40:383-389
57.Tsai CH, Chou MY, Chang YC (2003) The up-regulation of cyclooxygenase-2 expression in human buccal mucosal fibroblasts by arecoline: a possible role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med. 32(3):146-53.
58.Turini ME and DuBois RN (2002) Cyclooxygenase-2: a therapeutic target. Annu Rev Med 53:35-57
59.Vadas P, Stefanski E, Wloch M, Grouix B, et al. (1996) Secretory non-pancreatic phospholipase A2 and cyclooxygenase-2 expression by tracheobronchial smooth muscle cells. Eur J Biochem. 235(3):557-63
60.Vane JR, Bakhle YS, and Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120
61.W-P Koh, J-M Yuan, D van den Berg, H-P Lee, et al. (2004) Interaction between cyclooxygenase-2 gene polymorphism and dietary n-6 polyunsaturated fatty acids on colon cancer risk: The Singapore Chinese Health Study. British Journal of Cancer 90, 1760 – 1764
62.Walker AH, Najarian D, White DL, Jaffe JF, et al. (1999) Collection of genomic DNA by buccal swabs for polymerse chain reaction-based biomarker assays. Environ Health Perspect. 107(7):517-521
63.Wittwer CT, Reed GH, Gundry CN, Vandersteen JG, et al. (2003) High-Resolution Genotyping by Amplicon Melting Analysis Using LCGreen. Clin Chem 49(6):853–860
64.Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, and Ristimaki A (1998) Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 58:4997– 5001
65.Yang CY, Meng CL, Liao CL and Wong PY (2003a) Regulation of cell growth by selective COX-2 inhibitors in oral carcinoma cell lines. Prostaglandins Other Lipid Mediat 72:115-130
66.Yokoyama C and Tanabe T (1989) Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme. Biochem Biophys Res Commun 165:888–894
67.Zhang F, Altorki NK, Mestre JR, Subbaramaiah K and Dannenberg AJ (1999) Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis 20:445-451
68.Zhou L, Myers AN, Vandersteen JG, Wang L, et al. (2004) Closed-tube genotyping with unlabeled oligonucleotide probes and a saturating DNA dye. Clin Chem 50(8):1328-1335
69.Zimmermann KC, Sarbia M, Weber AA, Borchard F, Gabbert HE, and Schror K (1999) Cyclooxygenase-2 expression in human esophageal carcinoma. Cancer Res 59:198–204.
70.李俊億 (1995) DNA鑑定-PCR(PCR in Forensic DNA Analysis)
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top