诱导型一氧化氮合酶在人食管鳞癌中的表达
张林西, 金春亭, 李海军, 李玉珍, 河北北方学院病理学教研室 河北省张家口市 075029
齐凤英, 左连富, 刘江惠, 河北医科大学病理教研室 河北省石家庄市 050017
石卫东, 河北省人民医院病理科 河北省石家庄市 050051
河北省自然科学基金课题, No. 301351
通讯作者: 齐凤英, 050017, 河北省石家庄市中山东路361号, 河北医科大学病理学教研室. qifengying1945@yahoo.com.cn
电话: 0311-6265734
, 百拇医药
收稿日期: 2005-02-14 接受日期: 2005-03-03
摘要
目的:研究iNOS基因在我国食管鳞癌中的表达特点及iNOS基因表达与PCNA表达的关系，探讨iNOS基因在食管癌变中的可能作用.
方法:应用原位杂交、流式细胞术对81例食管鳞癌中iNOS及PCNA基因的表达进行检测，并应用图像分析技术对原位杂交结果进行定量分析.
结果:iNOS mRNA在正常食管鳞状上皮几乎无表达，在异型增生上皮近基底细胞有少量表达，而在鳞癌细胞中有明显阳性表达，癌细胞胞质呈棕黄色颗粒状.原位杂交定量分析及流式细胞术结果都显示:iNOS在正常食管上皮表达微量，在异型增生上皮明显增高，而在不同分化鳞癌中表达都较高，在低分化鳞癌中表达最高，组间差异非常显著(F= 14.001，P<0.01).PCNA表达也是随分化程度的降低而明显增高，组间差异显著(F= 20.393，P<0.01).且iNOS与PCNA表达呈显著正相关(r= 0.292，P= 0.009).
, http://www.100md.com
结论:在食管鳞癌中iNOS基因表达显著增高，iNOS基因表达异常与食管上皮癌变密切相关.
张林西, 金春亭, 齐凤英, 左连富, 刘江惠, 石卫东, 李海军, 李玉珍. 诱导型一氧化氮合酶在人食管鳞癌中的表达. 世界华人消化杂志 2005;13(8):1042-1044
王东旭, 李伟. 食管癌病因学进展. 世界华人消化杂志 2000;8:1029-1030
2 O'Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy.
Br J Cancer 2001;85:473-483
, http://www.100md.com 3 Chang CS, Chen WN, Lin HH, Wu CC, Wang CJ. Increased oxidative DNA damage, inducible nitric oxide synthase,nuclear factor kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac
gastric adenocarcinoma. World J Gastroenterol 2004;10:2232-2240
4 Li HL, Sun BZ, Ma FC. Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue
, 百拇医药
lymphoma. World J Gastroenterol 2004;10:1862-1866
5 Song ZY, Wen SQ, Peng JP, Huang X, Qian KD. Significance of vascular endothelial growth factor expression and its
correlation with inducible nitric oxide synthase in gastric cancer. World J Gastroenterol 2004;10:1250-1255
6 Kasper HU, Wolf H, Drebber U, Wolf HK, Kern MA. Expression of inducible nitric oxide synthase and cyclooxygenase-2
, http://www.100md.com
in pancreatic adenocarcinoma:correlation with microvessel density. World J Gastroenterol 2004;10:1918-1922
7 Puhakka A, Kinnula V, Napankangas U, Saily M, Koistinen P, Paakko P, Soini Y. High expression of nitric oxide synthases is
a favorable prognostic sign in non-small cell lung carcinoma. APMIS 2003;111:1137-1146
8 Niu XJ, Wang ZR, Wu SL, Geng ZM, Zhang YF, Qing XL. Relationship between inducible nitric oxide synthase expression
, 百拇医药
and angiogenesis in primary gallbladder carcinoma tissue. World J Gastroenterol 2004;10:725-728
9 齐凤英, 张林西, 韩彩丽, 左连富, 林培中, 郭建文. 食管上皮癌变过程中环氧化酶-2表达上调.
世界华人消化杂志 2003;11:508-511
10 Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology(Huntingt) 2002;16:217-226
11 Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-867
, 百拇医药
12 陈玺华, 李正中, 鲍民生, 郑绘霞. 一氧化氮在大鼠肝缺血再灌注损伤中的作用.
世界华人消化杂志 1999;7:295-297
13 黄颖秋, 王昕, 李骢, 刘丽. 糖尿病患者一氧化氮水平与食管内pH 值及食管动力变化的临床意义.
世界华人消化杂志 2000;8:374-376
14 郭津生, 古永亮, 王吉耀, 曹之宪. 结构型与诱生型一氧化氮合酶在大鼠胃溃疡模型中的表达和活性变化.
世界华人消化杂志 2001;9:288-292
15 Zhou JF, Cai D, Zhu YG, Yang JL, Peng CH, Yu YH. A study onrelationship of nitric oxide, oxidation, peroxidation,lipoperoxidation with chronicchole-cystitis. World J Gastroenterol 2000;6:501-507
, 百拇医药
16 王玉梅, 冯国和, 赵桂珍, 乔光彦. 肿瘤坏死因子-a及一氧化氮对暴发性肝衰竭肝损伤的作用.
世界华人消化杂志 2002;10:646-649
17 Kojima M, Morisaki T, Tsukahara Y, Uchiyama A, Matsunari Y, Mibu R, Tanake M. Nitric oxide synthase expression
and nitric oxide production in human colon carcinoma tissue. J Surg Oncol 1999;70:222-229
18 Lala PK, Chakraborty C. Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2001;2:149-156
, http://www.100md.com
19 Kawamori T, Takahashi M, Watanabe K, Ohta T, Nakatsugi S, Sugimura T, Wakabayashi K. Suppression of
azoxymethane-induced colonic aberrant crypt foci by a nitric oxide synthase inhibitor. Cancer Lett 2000;148:33-37
20 Marrogi A, Pass HI, Khan M, Metheny-Barlow LJ, Harris CC, Gerwin BI. Human mesothelioma samples overexpress
both cyclooxygenase-2(COX-2)and inducible nitric oxide synthase (NOS2):in vitro antiproliferative effects of a COX-2
, http://www.100md.com
inhibitor. Cancer Res 2000;60:3696-3700
21 Rajnakova A, Moochhala S, Goh PM, Ngoi S. Expression of nitric oxide synthase, cyclooxygenase, and p53 in different
stages of human gastric cancer. Cancer Lett 2001;172:177-185
22 Liu CY, Wang CH, Chen TC, Lin HC, Yu CT, Kuo HP. Increased level of exhaled nitric oxide and up-regulation of
inducible nitric oxide synthase in patients with primary lung cancer. Br J Cancer 1998;78:534-541
, 百拇医药
23 Son HJ, Kim YH, Park DI, Kim JJ. Interaction between cyclooxygenase-2 and inducible nitric oxide synthase in
gastric cancer. J Clin Gastroenterol 2001;33:383-388
24 Tanaka H, Kijima H, Tokunaga T, Tajima T, Himeno S, Kenmochi T, Oshiba G, Kise Y, Nishi T, Chino O, Shimada H,Machimura T, Tanaka M, Makuuchi H. Frequent expression of inducible nitric oxide synthase in esophageal squamous
, 百拇医药 cell carcinomas. Int J Oncol 1999;14:1069-1073
25 Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and
cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res 1998;58:2929-2934
26 Chen T, Stoner GD. Inducible nitric oxide synthase expression in N-nitrosomethylbenzylamine (NMBA)-induced rat
, 百拇医药
esophageal tumorigenesis. Mol Carcinog 2004;40:232-240
27 Brennan PA. The actions and interactions of nitric oxide in solid tumors. Eur J Surg Oncol 2000;26:434-437
28 Kagoura M, Matsui C, Toyoda M, Morohashi M. Immunohistochemical study of inducible nitric oxide synthase in skin
cancers. J Cutan Pathol 2001;28:476-481
29 Yu CC, Filipe MI. Update on proliferation-associated antibodies applicable to formalin fixed paraffin-embedded tissue
, 百拇医药
and their clinical applications. Histochem J 1993;25:843-853
30 Watanabe K, Kawamori T, Nakatsugi S, Wakabayashi K. COX-2 and iNOS, good targets for chemoprevention of colon
cancer. Biofactors 2000;12:129-133
31 Chen T, Nines RG, Peschke SM, Kresty LA, Stoner GD. Chemopreventive effects of a selective nitric oxide synthase
inhibitor on carcinogen-induced rat esophageal tumorigenesis. Cancer Res 2004;64:3714-3717
编辑 张海宁, http://www.100md.com( 张林西,金春亭, 齐凤英,左连富,刘江惠, 石卫东,李海军,李玉珍)
齐凤英, 左连富, 刘江惠, 河北医科大学病理教研室 河北省石家庄市 050017
石卫东, 河北省人民医院病理科 河北省石家庄市 050051
河北省自然科学基金课题, No. 301351
通讯作者: 齐凤英, 050017, 河北省石家庄市中山东路361号, 河北医科大学病理学教研室. qifengying1945@yahoo.com.cn
电话: 0311-6265734
, 百拇医药
收稿日期: 2005-02-14 接受日期: 2005-03-03
摘要
目的:研究iNOS基因在我国食管鳞癌中的表达特点及iNOS基因表达与PCNA表达的关系，探讨iNOS基因在食管癌变中的可能作用.
方法:应用原位杂交、流式细胞术对81例食管鳞癌中iNOS及PCNA基因的表达进行检测，并应用图像分析技术对原位杂交结果进行定量分析.
结果:iNOS mRNA在正常食管鳞状上皮几乎无表达，在异型增生上皮近基底细胞有少量表达，而在鳞癌细胞中有明显阳性表达，癌细胞胞质呈棕黄色颗粒状.原位杂交定量分析及流式细胞术结果都显示:iNOS在正常食管上皮表达微量，在异型增生上皮明显增高，而在不同分化鳞癌中表达都较高，在低分化鳞癌中表达最高，组间差异非常显著(F= 14.001，P<0.01).PCNA表达也是随分化程度的降低而明显增高，组间差异显著(F= 20.393，P<0.01).且iNOS与PCNA表达呈显著正相关(r= 0.292，P= 0.009).
, http://www.100md.com
结论:在食管鳞癌中iNOS基因表达显著增高，iNOS基因表达异常与食管上皮癌变密切相关.
张林西, 金春亭, 齐凤英, 左连富, 刘江惠, 石卫东, 李海军, 李玉珍. 诱导型一氧化氮合酶在人食管鳞癌中的表达. 世界华人消化杂志 2005;13(8):1042-1044
王东旭, 李伟. 食管癌病因学进展. 世界华人消化杂志 2000;8:1029-1030
2 O'Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy.
Br J Cancer 2001;85:473-483
, http://www.100md.com 3 Chang CS, Chen WN, Lin HH, Wu CC, Wang CJ. Increased oxidative DNA damage, inducible nitric oxide synthase,nuclear factor kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac
gastric adenocarcinoma. World J Gastroenterol 2004;10:2232-2240
4 Li HL, Sun BZ, Ma FC. Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue
, 百拇医药
lymphoma. World J Gastroenterol 2004;10:1862-1866
5 Song ZY, Wen SQ, Peng JP, Huang X, Qian KD. Significance of vascular endothelial growth factor expression and its
correlation with inducible nitric oxide synthase in gastric cancer. World J Gastroenterol 2004;10:1250-1255
6 Kasper HU, Wolf H, Drebber U, Wolf HK, Kern MA. Expression of inducible nitric oxide synthase and cyclooxygenase-2
, http://www.100md.com
in pancreatic adenocarcinoma:correlation with microvessel density. World J Gastroenterol 2004;10:1918-1922
7 Puhakka A, Kinnula V, Napankangas U, Saily M, Koistinen P, Paakko P, Soini Y. High expression of nitric oxide synthases is
a favorable prognostic sign in non-small cell lung carcinoma. APMIS 2003;111:1137-1146
8 Niu XJ, Wang ZR, Wu SL, Geng ZM, Zhang YF, Qing XL. Relationship between inducible nitric oxide synthase expression
, 百拇医药
and angiogenesis in primary gallbladder carcinoma tissue. World J Gastroenterol 2004;10:725-728
9 齐凤英, 张林西, 韩彩丽, 左连富, 林培中, 郭建文. 食管上皮癌变过程中环氧化酶-2表达上调.
世界华人消化杂志 2003;11:508-511
10 Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology(Huntingt) 2002;16:217-226
11 Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-867
, 百拇医药
12 陈玺华, 李正中, 鲍民生, 郑绘霞. 一氧化氮在大鼠肝缺血再灌注损伤中的作用.
世界华人消化杂志 1999;7:295-297
13 黄颖秋, 王昕, 李骢, 刘丽. 糖尿病患者一氧化氮水平与食管内pH 值及食管动力变化的临床意义.
世界华人消化杂志 2000;8:374-376
14 郭津生, 古永亮, 王吉耀, 曹之宪. 结构型与诱生型一氧化氮合酶在大鼠胃溃疡模型中的表达和活性变化.
世界华人消化杂志 2001;9:288-292
15 Zhou JF, Cai D, Zhu YG, Yang JL, Peng CH, Yu YH. A study onrelationship of nitric oxide, oxidation, peroxidation,lipoperoxidation with chronicchole-cystitis. World J Gastroenterol 2000;6:501-507
, 百拇医药
16 王玉梅, 冯国和, 赵桂珍, 乔光彦. 肿瘤坏死因子-a及一氧化氮对暴发性肝衰竭肝损伤的作用.
世界华人消化杂志 2002;10:646-649
17 Kojima M, Morisaki T, Tsukahara Y, Uchiyama A, Matsunari Y, Mibu R, Tanake M. Nitric oxide synthase expression
and nitric oxide production in human colon carcinoma tissue. J Surg Oncol 1999;70:222-229
18 Lala PK, Chakraborty C. Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2001;2:149-156
, http://www.100md.com
19 Kawamori T, Takahashi M, Watanabe K, Ohta T, Nakatsugi S, Sugimura T, Wakabayashi K. Suppression of
azoxymethane-induced colonic aberrant crypt foci by a nitric oxide synthase inhibitor. Cancer Lett 2000;148:33-37
20 Marrogi A, Pass HI, Khan M, Metheny-Barlow LJ, Harris CC, Gerwin BI. Human mesothelioma samples overexpress
both cyclooxygenase-2(COX-2)and inducible nitric oxide synthase (NOS2):in vitro antiproliferative effects of a COX-2
, http://www.100md.com
inhibitor. Cancer Res 2000;60:3696-3700
21 Rajnakova A, Moochhala S, Goh PM, Ngoi S. Expression of nitric oxide synthase, cyclooxygenase, and p53 in different
stages of human gastric cancer. Cancer Lett 2001;172:177-185
22 Liu CY, Wang CH, Chen TC, Lin HC, Yu CT, Kuo HP. Increased level of exhaled nitric oxide and up-regulation of
inducible nitric oxide synthase in patients with primary lung cancer. Br J Cancer 1998;78:534-541
, 百拇医药
23 Son HJ, Kim YH, Park DI, Kim JJ. Interaction between cyclooxygenase-2 and inducible nitric oxide synthase in
gastric cancer. J Clin Gastroenterol 2001;33:383-388
24 Tanaka H, Kijima H, Tokunaga T, Tajima T, Himeno S, Kenmochi T, Oshiba G, Kise Y, Nishi T, Chino O, Shimada H,Machimura T, Tanaka M, Makuuchi H. Frequent expression of inducible nitric oxide synthase in esophageal squamous
, 百拇医药 cell carcinomas. Int J Oncol 1999;14:1069-1073
25 Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and
cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res 1998;58:2929-2934
26 Chen T, Stoner GD. Inducible nitric oxide synthase expression in N-nitrosomethylbenzylamine (NMBA)-induced rat
, 百拇医药
esophageal tumorigenesis. Mol Carcinog 2004;40:232-240
27 Brennan PA. The actions and interactions of nitric oxide in solid tumors. Eur J Surg Oncol 2000;26:434-437
28 Kagoura M, Matsui C, Toyoda M, Morohashi M. Immunohistochemical study of inducible nitric oxide synthase in skin
cancers. J Cutan Pathol 2001;28:476-481
29 Yu CC, Filipe MI. Update on proliferation-associated antibodies applicable to formalin fixed paraffin-embedded tissue
, 百拇医药
and their clinical applications. Histochem J 1993;25:843-853
30 Watanabe K, Kawamori T, Nakatsugi S, Wakabayashi K. COX-2 and iNOS, good targets for chemoprevention of colon
cancer. Biofactors 2000;12:129-133
31 Chen T, Nines RG, Peschke SM, Kresty LA, Stoner GD. Chemopreventive effects of a selective nitric oxide synthase
inhibitor on carcinogen-induced rat esophageal tumorigenesis. Cancer Res 2004;64:3714-3717
编辑 张海宁, http://www.100md.com( 张林西,金春亭, 齐凤英,左连富,刘江惠, 石卫东,李海军,李玉珍)
