(44.192.66.171) 您好!臺灣時間:2021/05/18 01:27
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:李宣信
研究生(外文):Shiuan-Shinn
論文名稱:抗氧化蛋白在嚼食檳榔引發口腔鱗狀細胞癌之研究
論文名稱(外文):The study of antioxidant proteins expression in areca quid chewing-associated oral squamous cell carcinomas
指導教授:張育超
指導教授(外文):Yu-Chao Chang
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:125
相關次數:
  • 被引用被引用:0
  • 點閱點閱:107
  • 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
口腔鱗狀細胞癌是最常見的口腔癌,嚼食檳榔嚼塊被認為是造成口腔癌的主要原因之一。文獻指出,抗氧化蛋白如金屬硫蛋白 (metallothioneins; MTs)、第一型血基質氧化酵素(heme oxygenase-1; HO-1)及熱休克蛋白70 (heat shock protein 70; HSP70)等,在許多癌症有明顯表現的現象,但是鮮少有研究探討抗氧化蛋白在嚼食檳榔嚼塊所引發之口腔鱗狀細胞癌中所扮演的角色。在本研究中,我們利用免疫組織化學染色法來分析正常口腔上皮組織與嚼食檳榔嚼塊引發之口腔鱗狀細胞癌組織切片,並探討其表現強度與臨床特徵及TNM stage之相關性。另培養口腔上皮細胞株GNM細胞以反轉錄聚合脢連鎖反應(reverse transcription polymerase chain reaction, RT-PCR)及西方點墨法(western blotting)探討檳榔素(arecoline)引發口腔鱗狀細胞癌可能的致病機轉。實驗結果發現在口腔鱗狀細胞癌的組織中MT-1、HO-1及HSP70的表現明顯高於正常的口腔上皮組織(p<0.05),MT-1及HO-1的表現強度與淋巴結轉移成正相關(p<0.05),而HSP70表現強度與淋巴結轉移成負相關(p=0.005)。香菸中主要的致癌物benzo[a]pyrene則可以增加arecoline對GNM細胞誘發MT-1及HO-1的表現(p<0.05)。抗氧化劑N-acetyl-L-cysteine則可以抑制MT-1、HO-1及HSP70的表現(p<0.05)。curcumin、PD98059及staurosporine可以抑制arecoline對GNM細胞誘發HSP70蛋白的表現(p<0.05)。由實驗結果顯示檳榔嚼塊誘發MT-1、HO-1及HSP70的表現可能是造成口腔鱗狀細胞癌的致病機轉之一,benzo[a]pyrene對於造成口腔鱗狀細胞癌有加成作用,這可說明臨床上嚼食檳榔且吸菸者會有較多機會得到口腔癌,且檳榔誘發HSP70的表現可能是經由extracellular signal-regulated kinase inhibitor、activating protein-1及protein kinase C的傳導路徑來調控。

Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer. Previous studies have shown that antioxidant proteins such as metallothionein-1 (MT-1), heme oxygenase-1 (HO-1), and heat shock protein 70 (HSP70) were overexpressed in various cancers. Little is known about the role of antioxidant proteins in the pathogenesis of areca quid chewing-associated OSCC. In the present study, we examined MT-1, HO-1, and HSP70 expression in normal oral epithelium specimens from non-areca quid chewers and OSCC specimens from areca quid chewers by immunohistochemistry. To verify whether arecoline could affect the MT-1, HO-1, and HSP70 production by oral epithelial cell line GNM cells, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were used. Furthermore, glutathione precursor N-acetyl-L-cysteine (NAC), tobacco smoke carcinogen benzo[a]pyrene (BaP), extracellular signal-regulated kinase (ERK) inhibitor PD98059, activating protein-1 (AP-1) inhibitor curcumin, and protein kinase C (PKC) inhibitor staurosporine were added to find the possible regulatory mechanism. MT-1, HO-1 and HSP70 expression were higher in OSCC specimens than normal epithelium specimens (p<0.05). NAC was found to reduce MT-1, HO-1, and HSP70 expression induced by arecoline (p<0.05). BaP was found to enhance MT-1 and HO-1 expression induced by arecoline (p<0.05). Curcumin, PD98059, and staurosporine were found to markly inhibit the HSP70 protein expression induced by arecoline (p<0.05). These results suggest that areca quid chewing may activate MT-1, HO-1, and HSP70 expression that may play an important role on pathogensis of OSCC. BaP may act synergistically in the pathogenesis of OSCC in areca quid chewers. HSP70 expression induced by arecoline in GNM cells may be mediated by ERK inhibitor activation, AP-1, and PKC inhibitor signal transduction pathway.

目錄
目 錄
中文摘要
英文摘要
壹、 文獻回顧…………………………………………………………1
一、口腔癌之定義……………………………………………………2-3
二、口腔癌之流行病學………………………………………………4-7
三、口腔癌之臨床分期………………………………………………8-9
四、檳榔成份………………………………………………………10-12
五、檳榔與活性氧分子……………………………………………13-16
六、抗氧化蛋白……………………………………………………17-26
七、探討致癌機轉所使用之藥品…………………………………27-32
貳、研究動機………………………………………………………33-34
叁、材料及方法……………………………………………………35-62
肆、結果……………………………………………………………63-68
伍、討論……………………………………………………………69-78
陸、參考文獻……………………………………………………79-108
柒、圖表…………………………………………………………109-125
捌、附錄………………………………………………………………126



Ames BN, Gold LS. Too many rodent carcinogens: mitogenesis increases mutagenesis. Science 1990;249:970-971.
Andrews GK. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol 2000;59: 95-104.
Aschner M. Metallothionein (MT) isoforms in the central nervous system (CNS): regional and cell-specific distribution and potential functions as an antioxidant. Neurotoxicol 1998;19:653-660.
Ashby J, Styles JA, Boyland E. Betel nuts, arecaidine and oral cancer. Lancet 1979;1:112-115.
Asthana S, Greig NH, Holloway HW, Raffaele KC, Berardi A, Schapiro MB, Rapoport SI, Soncrant TT. Clinical pharmacokinetics of arecoline in subjects with Alzheimer''s disease. Clin Pharmacol Ther 1996;60:276-282.
Baranano DE, Baranano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proc. Natl Acad Sci USA 2002;99:16093-16098.
Bast A , Haenen GR, Doelman CJ. Oxidants and antioxidants: state of the art. Am J Med 1991;91:2-13.
Bowler RP, Crapo JD. Oxidative stress in airways: is there a role for extracellular superoxide dismutase? Am J Respir Crit Care Med 2002;166:38-43.
Bonwick GA, Fielden PR, Gordon JD. Metallothionein–like proteins in the livers of qualoed and carcharhinid sharks. Mar Pollut Bull 1990; 21:567-570.
Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AM, Soares MP. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 2000;192: 1015-1026
Burdon RH , Gill V, Rice-Evans C. Cell proliferation and oxidative stress. Free RAd Res Commun 1989;7:149-159.
Carraway MS, Ghio AJ, Carter JD, Piantadosi CA. Expression of heme oxygenase-1 in the lung in chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 2000;278:806-812.
Camhi SL, Lee P, Choi AM. The oxidative stress response. New Horiz 1995;3:170-182.
Cardoso SV, Barbosa HM, Candellori IM, Loyola AM, Aguiar MC. Prognostic impact of metallothionein on oral squamous cell carcinoma. Virchows Arch 2002;441:174-178.
Cerutti PA. Prooxidant states and tumor promotion. Science 1985;227:375-381.
Chang KM. Experimental production of lesions on cheek pouch of the hamster by betel quid. J Formosan Med Assoc 1964;65:125-131.
Chang KW, Lee TC, Yeh WI, Chung MY, Liu CJ, Chi LY, Lin SC. Polymorphism in heme oxygenase-1 (HO-1) promoter is related to the risk of oral squamous cell carcinoma occurring on male areca chewers. Br J Cancer 2004;91:1551-1555.
Chang YC, Lai CC, Lin LF, Ni WF, Tsai CH. The up-regulation of heme oxygenase-1 expression in human gingival fibroblasts stimulated with nicotine. J Periodontal Res 2005;40:252-257.
Chen GS, Chen CH. A statistical analysis of oral squamous cell carcinoma. Gaoxiong Yi Xue Ke Xue Za Zhi 1995; 11:582-588.
Chen CL, Chi CW, Liu TY. Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo. J Toxicol Enviro Health A 2002;65:327-336.
Chen YK, Huang HC, Lin LM, Lin CC. Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan. Oral Oncol 1999;35:173-179.
Cherian MG, Howell SB, Imura N, Klaassen CD, Koropatnick J, Lazo, JS, Waalkes MP. Role of metallothionein in carcinogenesis. Toxicol Appl Pharmacol 1994;126:1-5.
Cherian MG, Huang PC, Klaassen CD, Liu YP, Longfellow DG, Waalkes MP. National Cancer Institute workshop on the possible roles of metallothionein in carcinogenesis. Cancer Res 1993;53:922-925.
Chiang CP, Lang MJ, Liu BY, Wang JT, Leu JS, Hahn LJ, Kuo MYP. Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan. Oral Oncol 2000;36:353-359.
Ciocca DR, Oesterreich S, Chamness GC, McGuire WL, Fuqua SAW: Biological and clinical implication of heat shock protein 27000 (Hsp27): a review. J Nat Cancer Inst 1993;85:1558-1570.
Chou AY, Archdeacon J, Kado CI. Agrobacterium transcriptional regulator Ros is a prokaryotic zinc finger protein that regulates the plant oncogene ipt. Proc Natl Acad Sci U S A 1998;95:5293-5298.
Clark JE, Foresti R, Sarathchandra P, Kaur H, Green CJ, Motterlini R. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am J Physiol Heart Circ Physiol 2000;278:643-651.
Cousins RJ, Leinart AS. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J 1988;2:2884-2890.
Craig EA, Gambill BD, Nelson RJ. Heat shock proteins, molecular chaperones of protein biogenesis. Microbiol Rev 1993;57:402-414.
Deng DX, Chakrabarti S, Waalkes MP, Cherian MG. Metallothionein and apoptosis in primary human hepatocellular carcinoma and metastatic adenocarcinoma. Histopathol 1998;32:340-347.
Dennery PA, Rodgers PA, Lum MA, Jennings BC, Shokoohi V. Hyperoxic regulation of lung heme oxygenase in neonatal rats. Pediatr Res 1996;40:815-21.
Department of Health. Cancer registry annual report in Taiwan area, 2003. Taipei: Department of Health. The Executive Yuan, ROC; 2007.
de Silva GK, Jayamaha JM, Gabriel A. Pattern and prevalence of oral carcinoma in a surgical unit at Cancer Institute Maharagama, 1985 to 1994. Ceylon Med J 1995;40:146-147.
Dipple A, Pigott MA, Agarwal SK, Yagi H, Sayer JM, Jerina DM. Optically active benzo[c]phenanthrene diol epoxides bind extensively to adenine in DNA. Nature 1987;327: 535-536.
Dong Z, Lavrovsky Y, Venkatachalam MA, Roy AK. Heme oxygenase-1 in tissue pathology. Am J Pathol 2000;156:1485-1488.
Dulak J, Jozkowicz A. Carbon monoxide - a new gaseous modulator of gene expression. Acta Biochim Pol 2003;50:31-47.
Eisenstein R, Garcia-Mayol D, Pettingell W, Munroe H. Regulation of ferritin and heme oxygenase in rat fibroblasts by different forms of iron. Proc Natl Acad Sci USA 1991;88:688-692.
Erdos G, Lee YJ. Effect of staurosporine on the transcription of HSP70 heat shock gene in HT-29 cells. Biochem Biophys Res Commun 1994;202:476-483.
Ericson T, Bratt P. Interactions between peroxide and salivary glycoprotein: protection by peroxidase. J Oral Pathol 1987;16:421-424.
Ernst H, Ohshima H, Bartsch H, Mohr U, Reichart P. Tumorigenicity study in Syrian hamsters fed areca nut together with nitrite. Carcinogenesis 1987;8:1843-1845.
Ewing JF, Maines MD. Rapid induction of heme oxygenase-1 mRNA and protein by hyperthermia in rat brain: heme oxygenase-2 is not a heat shock protein. Proc Natl Acad Sci USA 1991;88:5364-5368.
Fang J, Akaike T, Maeda H. Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment. Apoptosis 2004;9:27-35
Field JK, Yiagnisis M, Spandidos DA, Gosney JR, Papadimitriou K, Vaughan ED, Stell PM. Low levels of ras p21 oncogene expression correlates with clinical outcome in head and neck squamous cell carcinoma. Eur J Surg Oncol 1992;18:168-176.
Foresti R, Goatly H, Green CJ, Motterlini R. Role of heme oxygenase–1 in hypoxia–reoxygenation: Requirement of substrate heme to promote cardioprotection. Am J Physiol 2001;281:1976-1984.
Fujita-Yamaguchi Y, Kathuria S. Characterization of receptor tyrosine-specific protein kinases by the use of inhibitors. Staurosporine is a 100-times more potent inhibitor of insulin receptor than IGF-I receptor. Biochem Biophys Res Commun 1988;157:955-962.
Galbraith R. Heme oxygenase: who needs it?Proc Soc Exp Biol Med 1999;222:299-305.
Georgopoulos C, Welch WJ: Role of the major heat shock proteins as molecular chaperons. Annu Rev Cell Biol 1993;9:601-634.
Gillissen A, Novak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Res Med 1998;2:609-623.
Gourley GR. Bilirubin metabolism and kernicterus. Adv Pediatr 1997;44:173-229.
Hall M, Parker DK, Grover PL, Lu JY, Hopkins NE, Alworth WL. Effects of 1-ethynylpyrene and related inhibitors of P450 isozymes upon benzo[a]pyrene metabolism by liver microsomes. Chemico-Biological Interactions 1990;76:181-192.
Hamer DH. Metallothionein. Annu Rev Biochem 1986;55,913-951.
Hancock JT, Desikan R, Neill S. Role of reactive oxygen species in cell signaling pathways. J Biochem Soc Trans 2001;29:345-350.
Halliwell B, Gutteridge JMC. In “Free radicals, ageing and disease. In “Free radicals in Biology and Medicine.” Clarendon Press; Oxford 1989:484-487.
Hatayama T, Tsukimi Y, Wakatsuki T, Kitamura T, Imahara H. Different induction of 70,000-Da heat shock protein and metallothionein in HeLa cells by copper. J Biochem 1991;110:726-731.
Higuchi Y. Glutathione depletion-induced chromosomal DNA fragmentation associated with apoptosis and necrosis. J Cell Mol Med 2004;8:455-464.
Hirayama T. An epidemiological study of oral and pharyngeal cancer in central and south-east Asia. Bull. World Health Organ 1966;34:41-69.
Huang MT, Wang ZY, Georgiadis CA, Laskin JD, Conney AH. Inhibitory effect of curcumin on tumor initiation by benzo[a]pyrene and 7,12-dimethyl-benz[a]anthracene. Carcinogenesis 1992;13:947-954
Huang MT, Ma W, Lu YP, Chang RL, Fischer C, Manchand PS, Newmark HL, Conney AH. Effect of curcumin, 52 demethoxycurcumin, bisdemethoxy-curcumin and tetrahydrocurcumin on TPA-induced tumor promotion. Carcinogenesis 1995;16:2493-2497.
Huang MT, Smart RC, Wong CQ, Conney AH. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 1988;48:5941-5946.
IARC. Betal quid and areca-nut chewing. International Agency for Research on Cancer. Lyon, Monographs 1985;37:141-291.
IARC. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 2004;85:1-334.
Jacquier-Sarlin MR, Jornot L, Polla BS. Differential expression and regulation of hsp70 and hsp90 by phorbol esters and heat shock. J Biol Chem 1995;270:14094-4099.
Jacquier-Sarlin MR, Polla BS. Dual regulation of heat-shock transcription factor (HSF) activation and DNA-binding activity by H2O2: role of thioredoxin. Biochem J 1996;318:187-193.
Jafarey NA, Mahmood Z, Zaidi SHM. Habits and dietary pattern of cases of carcinoma of oral cavity and oropharynx. J Pakistan Med Assoc 1977;27:340-343.
Johnston GA, Krogsgaard-Larsen P, Stephanson A. Betel nut constituents as inhibitors of gamma-aminobutyric acid uptake. Nature 1975;258:627-628.
Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu KK, Chau LY. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001;104:1519-1525.
Jussawalla DJ, Deshpande VA. Evaluation of cancer risk in tobacco chewers and smokers: an epidemiological assessment. Cancer 1971; 28:244-252.
Kagi JH. Overview of metallothionein. Methods Enzymol 1991; 205:613-626.
Kang YJ, Li Y, Sun X. Antiapoptotic effect and inhibition of ischemia/reperfusion-induced myocardial injury in metallothionein-overexpressing transgenic mice. Am J Pathol 2003;163:1579-1586.
Kang YJ, Zhou ZX, Wang GW, Buridi A, Klein JB. Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogen-activated protein kinases. J Biol Chem 2000;275:13690-13698.
Katsuragi H, Hasegawa A, Saito K. Distribution of metallothionein in cigarette smokers and non-smokers in advanced periodontitis patients. J Periodontol 1997;68:1005-1009.
Kaur J, Ralhan R. Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int J Cancer 1995;63:774-779.
Kaur J, Srivastava A, Ralhan R. Expression of 70-kDa heat shock protein in oral lesions: marker of biological stress or pathogenicity. Oral Oncol 1998a;34:496-501.
Kaur J, Das SN, Srivastava A. Cell surface expression of 70 KDa heat shock protein in human oral dysplasia and squamous cell carcinoma: correlation with clinicopathological features. Oral Oncol 1998b;34:93-98.
Kazzaz JA, Xu J, Palaia TA, Mantell L, Fein AM, Horowitz S. Cellular oxygen toxicity. J Biol Chem 1996;271:15182-15186.
Keyse SM, Tyrrell RM. Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32–kDa stress protein in normal human skin fibroblast. J Biol Chem 1987;262:14821-14825.
Keyse SM, Tyrrell RM. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci USA 1989;86:99-103.
Ko YC, Chiang TA, Chang SJ, Hsieh SF. Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. J Oral Pathol Med 1992;21:261-264.
Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM, Tsai CC. Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 1995;24:450-453.
Kong S, Davison AJ. The role of interactions between O2,H2O2 , and O2- in free radical damage to biological systems. Arch Biochem Biophys 1980;204:18-29.
Kuchino Y, Mori F, Kasai H, Inoue H, Iwai S, Miura K, Ohtsuka E, Nishimura S. Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature 1987;327:77-79.
Kunchandy E, Rao MNA. Oxygen radical scavenging activity of curcumin. Int''l J Pharm 1990;38:239-240.
Kuo MY, Jeng JH, Chiang CP, Hahn LJ. Mutations of Ki-ras oncogene codon 12 in betel quid chewing-related human oral squamous cell carcinoma in Taiwan. J Oral Pathol Med 1994;23:70-74.
Kutty RK, Kutty G, Rodriguez IR, Chader GJ, Wiggert B. Chromosomal localization of the human heme oxygenase genes: heme oxygenase-1 (HMOX1) maps to chromosome 22q12 and heme oxygenase-2 (HMOX2) maps to chromosome 16p13.3. Genomics 1994;20:513-516.
Kwan HW:A statistical study on oral carcinomas in Taiwan with emphasis on the relationship with betel nut chewing:A preliminary report. J Formosan Med Assoc 1976;75:497-505.
Lazo JS, Kuo SM, Woo ES, Pitt BR. The protein thiol metallothionein as an antioxidant and protectant against antineoplastic drugs. Chem Biol Interact 1998;111:255-262.
Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002;8:240-246.
Lewis JG, Adams DO. Inflammation, oxidative DNA damage, and carcinogenesis. Environ Health Perspect 1987;76:19-27.
Lin SK, Kok SH, Yeh FT. MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum 2004;50:785-793.
Liu J, Kershaw WC, Klaassen CD. The protective effect of metallothionein on the toxicity of various metals in rat primary hepatocyte culture. Toxicol Appl Pharmacol 1991;107:27-34.
Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W. Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 2002;55:396-405.
Lin SK, Kok SH, Yeh FT. MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Arthritis Rheum 2004;50:785-793.
Liu TY, Chen CL, Chi CW. Oxidative damage to DNA induced by areca nut extract. Mutat Res 1996;367:25-31.
Lodish B, Matsudaira K, Krieger S, Zipursky D. Molecular cell biology 2004 ; fifteenth by W. H. Freeman.
Lombet A, Zujovic V, Kandouz M, Billardon C, Carvajal-Gonzalez S, Gompel A, Rostène W. Resistance to induced apoptosis in the human neuroblastoma cell line SK-N-SH in relation to neuronal differentiation. Role of Bcl-2 protein family. Eur J Bio chem 2001;268:1352-1362.
Lu CT, Lan SJ, Yen YY, Ho CS, Hsieh CC, Ko YC. A case-control study of oral cancer in Changhua County, Taiwan. J Oral Pathol Med 1996;25:245-248.
Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997;37:517-54.
Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms , and clinical applications. FASEB J 1988;2:2557-2568.
Maines MD, Abrahamsson PA. Expression of heme oxygenase-1 (HSP32) in human prostate: normal, hyperplastic, and tumor tissue distribution. Urology 1996;47:727-733.
Maines MD, Trakshel GM, Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem 1986;261:411-9.
Maehara Y, Oki E, Abe T, Tokunaga E, Shibahara K, Kakeji Y, Sugimachi K. Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer. Oncol 2000;58:144-151.
Marber MS, Latchman DS, Walker JM, Yellon DM. Cardiac stress protein elevation 24 hours after brief ischemia orheat stress is associated with resistance to myocardial in-fection. Circulation 1993;88:1264-1272.
Margoshea M, Vallee BL. Flame photometry and spectrometry; principles and applications. Methods Biochem Anal 1956;3:353-407.
Mazumder A, Raghavan K, Weinstein J, Kohn KW, Pommier Y. Inhibition of HIV-1 integrase by curcumin. Biochem Pharm 1995;49:1165-1170.
McCoubrey WK, Jr., Huang TJ, Maines MD. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 1997;247:725-732.
McMahon SB, Monroe JG. The role of early growth response gene-1 (egr-1) in regulation of the immune response. J Leukoc Biol 1996;60:159-166.
Mehta FS, Pindborg JJ, Gupta PC, Daftary DK. Epidemiologic and histologic study of oral cancer and leukoplakia among 50,915 villagers in India. Cancer 1969;24:832-849.
Minetti M, Mallozzi C, Di Stasi AM, Pietraforte D. Bilirubin is an effective antioxidant of peroxynitrite-mediated protein oxidation in human blood plasma. Arch Biochem Biophys 1998; 352:165-174.
Moffatt P, Denizeau F. Metallothionein in physiological and physiopathological processes. Drug Metab Rev 1997;29:261-307.
Morimoto. Hemin-induced transcriptional activation of the Hsp70 gene during erythroid maturation in K562 cells is due to a heat shock factor-mediated stress reponse. Mol Cell Biol 1989;9:3166-3173.
Morse D, Choi AM. Heme oxygenase-1: the "emerging molecule" has arrived. Am J Respir Cell Mol Biol 2002;27:8-16.
Muramatsu Y, Hasegawa Y, Fukano H, Ogawa T, Namuba M, Mouri K, Fujimoto Y, Matsuura H, Takai Y, Mori M. Metallothionein immunoreactivity in head and neck carcinomas ; special reference to clinical behaviors and chemotherapy responses. Anticancer Res 2000;20:257-264.
Murti PR, Bhonsle RB, Gupta PC, Daftary DK. Oral health consequences of tobacco use in Ernakulam districr, Kerala, India. Control of Tobacco-related Cancers and other disease. International Symposium, 1990. In: PC Gupta, JE Hamner, PR Murti, eds. Bombay: Oxford University Press 1992;91-105.
Nagel WW, Vallee BL. Cell cycle regulation of metallothionein in human colonic cancer cells. Proc Natl Acad Sci USA 1995;92:579-583.
Nair J, Ohshima H, Freisen M, Croisy A, Bhide SV, Bartsch H. Tobacco specific and betel nut specific N-nitroso compounds: occurrence in saliva and urine of betal quid chewers and formation in vitro by nitrosation of betal quid. Carcinogenesis 1985;6:295-303.
Nair UJ, Floyd RA, Nair J, Bussachini V, Friesen M, Bartsch H. Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients. Chem Biol Interact 1987;63:157-169.
Nair UJ, Friesen M, Richard I, MacLennan R, Thomas S, Bartsch H. Effect of lime composition on the formation of reactive oxygen species from areca nut extract in vitro. Carcinogenesis 1990;11:2145-2148.
Nair UJ, Obe G, Friesen M, Goldberg MT, Bartsch H. Role of lime in the generation of reactive oxygen species from betel-quid ingredients. Environ Health Perspect 1992;98:203-205.
Nair UJ, Nair J, Friesen MD, Bartsch H, Ohshima H. Ortho- and meta-tyrosine formation from phenylalanine in human saliva as a marker of hydroxyl radical generation during betel quid chewing. Carcinogenesis 1995;16:1195-1198.
Nakao A, Otterbein LE, Overhaus M, Sarady JK, Tsung A, Kimizuka K, Nalesnik MA, Kaizu T, Uchiyama T, Liu F, Murase N, Bauer AJ, Bach FH. Biliverdin protects the functional integrity of a transplanted syngeneic small bowel. Gastroenterol 2004;127:595-606.
Nanbu K, Konishi I, Komatsu T, Mandai M, Yamamoto S, Kuroda H, Koshiyama M, Mori T. Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression. Cancer 1996;77:330-338.
Nath R, Prasad R, Palinal VK, Chopra RK. Molecular basis of cadmium toxicity. Prog Food Nutr Sci 1984;8:109-163.
Ng KH, Siar CH, Ramanathan K, Murugasu P, Chelvanayagam PI. Squamous cell carcinoma of the oral mucosa in Malaysia—any change? Southeast Asian J Trop Med Public Health 1985;16:602-606.
Nishimura HM, Emoto, Kimura K, Yoshikai Y. HSP 70 protects macrophages infected with Salmonella choleraesuis against TNF-α-induced cell death. Cell Stress Chaperones 1997;2:50-59.
Noguchi T, Takeno S, Shibata T, Uchida Y, Yokoyama S, Muller W. Expression of heat shock protein 70 in grossly resected esophageal squamous cell carcinoma. Ann Thorac Surg 2002;74:222–226.
Oberle S, Schwartz P, Abate A, Schroder H. The antioxidant defense protein ferritin is a novel and specific target for pentaerithrityl tetranitrate in endothelial cells. Biochem Biophys Res Commun 1999;261:28-34.
Ossola J, Tomaro M. Heme oxygenase induction by UVA radiation. A response to oxidative stress in rat liver. Int J Biochem Cell Biol 1998;30:285-292.
Otterbein L, Sylvester SL, Choi AMK. Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase–1. Am J Respir Cell Mol Biol 1995;13: 595-601.
Otterbein L, Bach F, Alam J, Soares M, Tao Lu H, Wysk M, Davis R, Flavell R, Choi A. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6:422-428.
Otterbein LE, Choi AM. Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 2000;279:1029-1037.
Panigrahi GB, Rao AR. Chromosome-breaking ability of arecoline, a major betel nut alkaloid on mouse bone-marrow cells in vivo. Mutation Res 1982;103:197-204.
Panigrahi GB, Rao AR. Influence of caffeine on arecoline-induced SCE in mouse bone marrow cells in vivo. Mutation Res 1983;122:347-353.
Parsell DA, Lindquist S. The function of heat-shock proteins in stress tolerence: degration and reactivation of damaged proteins. Annu Rev Genet 1993;27:437-496.
Polla BS, Cossarizza A. Stress proteins in inflammation. Ann N Y Acad Sci 1998;77:375-391.
Polte T, Abate A, Dennery PA, Schroder H. Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arterioscler Thromb Vasc Biol 2000;20:1209-1215.
Presta A, Green AR, Zelazowski A. Stillman MJ. Copper binding to rabbit liver metallothionein. Formation of a continuum of copper(I)-thiolate stoichiometric species. Eur J Biochem 1995;227:226-240.
Ralhan R, Kaur J. Differential expression of Mr 70,000 heat shock protein in normal, premalignant, and malignant human uterine cervix. Clin Cancer Res 1995;1:1217-1222.
Ranadive KJ, Gothoskar SV, Rao AR, Tezabwala BU, Ambaye RY. Experimental evidence of betel nut and tobacco carcinogenicity. Intl J Cancer 1976;17:469-476.
Rao TK, Young JA, Lijinsky W, Epler JL. Mutagenicity of N-nitrosopiperazine derivatives in Salmonella typhimurium. Mutat Res 1978;57:127-134.
Reichart PA. Oral cancer and precancer related to betel and miang chewing in Thailand: a review. J Oral Pathol Med 1995;24:241-243.
Roesijadi G. Metallothioneins in metal regulation and toxicity in aquatic animals . Aquat Toxicol 1992;22:23-49.
Rosin MP. The influence of pH on the convertogenic activity of plant phenolics. Mutat Res 1984;135:109-113.
Rosenberg L, Louik C, Shapiro S. Nonsteroidal anti-inflammatory drug use and reduced risk of large bowel carcinoma. Cancer 1998;82:2326-2333.
Sato M, Bremner I. Oxygen free radicals and metallothionein. Free Radic Biol Med 1993;14:325-337.
Shacter E, Beecham EJ, Covey JM, Kohn KW, Potter M. Activated neutrophils induce prolonged DNA damage in neighboring cells. Carcinogenesis 1988;9:2297-2304.
Shafer et al. 關學婉校閱,許輝吉編譯,林正仲校對,口腔病理學,環球書社,中華民國八十一年三月初版八印。
Shanta V, Krishnamurthy S. Further study in aetiology of carcinomas of the upper alimentary tract. Br J Cancer 1963;17:8-23.
Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995;270:24995-25000.
Sohal RS, Dubey A. Mitochondrial oxidative damage, hydrogen peroxide release, and aging. Free Radic Biol Med 1994;16:621-626.
Stich HF, Rosin MP, Brunnemann KD. Oral lesions, genotoxicity and nitrosamines in betel quid chewers with no obvious increase in oral cancer risk. Cancer Lett 1986;31:15-25.
Stocker R, Yamamoto Y, McDonagh A, Glazer A, Ames B. Bilirubin is an antioxidant of possible physiological importance. Science 1987;235:1043-1045.
Stocker R. Induction of haem oxygenase as a defense against oxidative stress. Free Rad Res Commun 1990;9:101-112.
Sundelin K, Jadner M, Norberg-Spaak L, Davidsson A, Hellquist HB. Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue. Eur J Cancer 1997; 33:1860-1864.
Sunamura M, Duda DG, Ghattas MH, Lozonschi L, Motoi F, Yamauchi. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer. Angiogenesis 2003;6:15-24.
Tamaoki T, Nomoto H, Takahashi I, Kato Y, Morimoto M, Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun 1986;135:397-402.
Tanaka S, Akaike T, Fang J, Beppu T, Ogawa M, Tamura F, Miyamoto Y, Maeda H. Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour. Br J Cancer 2003;88:902-909.
Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 1968;61:748-755.
Tenhunen R, Marver HS, Schmid R. Microsomal heme oxygenase. Characterization of the enzyme. J Biol Chem 1969;244:6388-6394.
Thomas SJ, MacLennan R. Slaked lime and betel nut cancer in Papua New Guinea. Lancet 1992;340:577-578.
Thornalley PJ, Vasak M. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta 1985;827:36-44.
Torronteguy C, Frasson A, Zerwes F, Winnikov E, da Silva VD, Menoret A, Bonorino C. Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors. Cell Stress Chaperones 2006;1:34-43.
Trivedy C, Baldwin D, Warnakulasuriya S, Johnson NW, Peters TJ. Copper content in areca catechu (betel nut) products and oral submucous fibrosis. Lancet 1997;340:1447.
Tsai CC, Ma RH, Shieh TY. Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosis. J Oral Pathol Med 1999;28:59-63.
Tsuji MH, Yanagawa T, Iwasa S, Tabuchi K, Onizawa K, Bannai S, Toyooka H, Yoshida H. Heme oxygenase-1 expression in oral squamous cell carcinoma as involved in lymph node metastasis. Cancer Lett 1999;138:53-59.
Vachharajani TJ, Work J, Issekutz AC, Granger DN. Heme oxygenase modulates selectin expression in different regional vascular beds. Am J Physiol Heart Circ Physiol 2000;278:1613-1617.
Vayssier-Taussat M, Camilli T, Aron Y, Meplan C, Hainaut P, Polla BS, Weksler B. Effects of tobacco smoke and benzo[a]pyrene on human endothelial cell and monocyte stress responses. Am J Physiol Heat Circ Physiol 2001;280:1293-1300.
Vile G, Tyrrell R. Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. J Biol Chem 1993;268:4678-4681.
Wang GW, Zhou Z, Klein JB, Kang YJ. Inhibition of hypoxia/reoxygenation-induced apoptosis in metallothionein-overexpressing cardiomyocytes. Am J Physiol Heart Circ Physiol 2001;280:2292-2299.
Wargovich MJ, Chen CD, Harris C, Yang E, Velasco M. Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon. Int J Cancer 1995;60:515-519.
Wargovich MJ, Jimenez A, McKee K, Steele VE, Velasco M, Woods J, Price R, Gray K, Kelloff GJ. Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis 2000;21: 1149-1155.
Wary KK, Sharan RN. Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro. Int J Cancer 1991;47:396-400.
Weber CM, Eke BC, Maines MD. Corticosterone regulates heme oxygenase-2 and NO synthase transcription and protein expression in rat brain. J Neurochem 1994;63:953-962.
Weitberg AB, Weitzman SA, Destrempes M, Latt SA, Stossel TP. Stimulated human phagocytes produce cytogenetic changes in cultured mammalian cells. N Engl J Med 1983;308:26-30.
Wenke G, Hoffmann D. A study of betel quid carcinogenesis. 1. On the in vitro N-nitrosation of arecoline. Carcinogenesis 1983;4:169-172.
Wise C, Drabkin D. Degradation of haemoglobin and hemin to biliverdin by a new cell-free system obtained from the hemophagous organ of dog placenta. Fed Proc 1964;23:323.
Yanagawa T, Omura K, Harada H, Nakaso K, Iwasa S, Koyama Y, Onizawa K, Yusa H, Yoshida H. Heme oxygenase-1 expression predicts cervical lymph node metastasis of tongue squamous cell carcinomas. Oral Oncol 2004;40:21-27.
Ye B, Maret W, Vallee BL. Zinc metallothionein imported into liver mitochondria modulates respiration. Proc Natl Acad Sci USA 2001;98:2317-2322.
Yesilkaya A, Altinayak R, Korgun DK. The antioxidant effect of free bilirubin on cumene-hydroperoxide treated human leukocytes. Gen Pharmacol 2000;35:17-20.
Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 1999;103:129-135.
Zain RB. Cultural and dietary risk factors of oral cancer and precancer--a brief overview. Oral Oncol 2001;37:205-210.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top