对幽门螺杆菌相关性胃癌前病变的监测及中西医结合干预治疗
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摘要
目的(1)探讨胃癌前病变、胃癌患者之间血清与胃组织HP、CEA表达的差异，为胃癌前病变的监测和治疗提供依据，为早期发现、诊断和治疗胃癌提供参考指标；(2)观察以黄芩为主的中药组方联合传统的三联疗法与三联疗法治疗胃癌前病变患者的疗效差异，了解黄芩组方对胃癌前病变患者HP感染的协同抑菌作用和胃黏膜保护作用，为根除胃癌前病变患者HP感染探索新的思路。
方法(1)采用免疫层析一步法、蛋白芯片法测定血清HP、CEA，免疫组化S-P法测定胃组织HP、CEA；(2)将83例胃癌前病变患者随机分为三联疗法组和中药+三联疗法组。三联组胃溃疡患者予以奥美拉唑+阿莫西林+甲硝唑，萎缩性胃炎予以枸橼酸铋钾+阿莫西林+甲硝唑连用7天。联合治疗组在此基础上加用黄芩组方煎服，每日一利，连用3周。观察治疗前后临床症状的改善和胃组HP、CEA的改变。
结果(1)癌前病变的各阶段及胃癌患者的血清及胃组织中均可检测到HP，血清及胃组织中HP的检出率以胃癌前病变组最高，胃癌组次之，浅表性胃炎中检出率较低。三组之间比较差异均有统计学意义(P＜0.05)，各组与正常组之间差异也均有统计学意义(P＜0.05)。胃组织HP检出率明显高于血清。(2)血清及胃组织CEA检测显示，胃癌组最高，其次为癌前病变组，浅表性胃炎中CEA的检出率较低，正常胃黏膜中未检出。胃癌组分别与癌前病变组及对照组比较差异有统计学意义(P＜0.01)。(3)对CEA阳性患者的阳性程度分析时发现，胃癌组++—+++的阳性率明显高于癌前病变组及浅表性胃炎组。此外，癌前病变组+—+++的阳性率均明显高于浅表性胃炎组。(4)中药+三联疗法组在症状的改善、根除HP感染和减低胃组织CEA等方面优于三联疗法组
结论(1)HP参与了胃癌前病变和胃癌的发病过程，可把血清及胃组织Hp检测作为对癌前病变的初步监测及治疗观察指标之一。(2)血清及组织CEA检测可协助胃癌的诊断，并对慢性萎缩性胃炎、胃黏膜肠上皮化生、胃溃疡等癌前病变患者的监测有较为重要的价值。胃组织CEA检测明显优于血液中CEA的检测。血清与胃组织CEA协同检测可提高临床诊断率。(3)对Hp阳性的癌前病变患者动态检测血清及组织CEA更有助于对胃癌的早期发现、早期诊断和早期治疗。(4)以黄芩为主的中药组方联合三联疗法在治疗胃癌前病变可提高疗效。
Objective (1) (?)o p(?)o(?)ide the basis for early de(?)eec(?)ion and treatment of preeanceous lesions of gastric carcinom. and reference for early discovery. diagnosis and treatment of gastric cancer. by examining the differences of expression of the CEA and Hp between precancerous lesions of gastric carcinoma patients and gastric cancer patients. (2)To understand synergism of fungistasis and protection of gastric mucosa on precancerous lesions patients, who were treated by the prescription mianly of Chinese traditional baical skullcap root, by observing the therapeutic effect of precancerous lesions of gastric carcinoma patients, who were treated by triple therapy or jointing traditional chinese medicine. Through this study we wanted to explore new ideas.
Methods (1)Detected the expression of helicobacter pylori and carcinoembryonic antigen in blood serum by immunochromatographic method and Protein Chip System. Useing immunohistochemistray to detect the expression of helicobacter pylori and carcino-embryonic antigen in gastric mucosa. (2) 83 patients with precancerous lesions were classified triple therapy group and jointing traditional chinese medicine group. The modern medicine group was treated with omeprazole, amoxicillin and colloidal bismuth subcitrate for 7 days. The jointing traditional chinese medicine group on the basis of triple therapy group was treated with the prescription mianly of Chinese tr-aditional baical skullcap root for 21days. After treatment. observed the change on clinical symptoms, Hp and CEA.
Results (1) The expression of Hp was deteced on every stages of precancerous lesions and gastric cancer. compared by the detection rate of Hp. precancerous lesions group was higher than gastric cancer group and superficial gastritis group, superficial gastritis group was the lolowest. The differences of the three groups were significant (P＜0.05). The detection rate of Hp in gastric mucosa was obviously higher than in blood serum. (2) Compared by the expression of CEA, the highest group was gastric cancer group. the lowest was superficial gastritis group, both in blood serum and gastric mucosa. The expression of CEA was not detected in nemal stomach mucosa.(3) Through analysis of the positive patients of CEA.found that the positive degree of gastriic cancer group was highest.and the preeancerous lesions group is obviously higher than superficial gastritis group.(4) Jointing traditional chinese medicine group was better than triple therapy group in the improvement of symptoms, the eradication of Hp,and reduction of the expression of Hp andCEA.
Conclusion: (1)Hp participate the process of the precancerous lesions and gastric cancer.The expression of Hp could be one of the index ,which monitor the process and curative effect of the precancerous lesions. (2) The expression of CEA could help diagnosis of gastric cancer.It is important to moniitor the precancerous lesions. The expression of CEA in gastric mucosawas better than in blood serum.Detected CEA both in gastric mucosa and blood serum,which could raise the rate of clinical diagnosis.(3)Observering CEA of Hp positive patients was benefit for early discovery, diagnosis and treatment of stomach cancer.(4)jointing traditional chinese medicine could elevate curative effect ofprecancerous lesion.
方法(1)采用免疫层析一步法、蛋白芯片法测定血清HP、CEA，免疫组化S-P法测定胃组织HP、CEA；(2)将83例胃癌前病变患者随机分为三联疗法组和中药+三联疗法组。三联组胃溃疡患者予以奥美拉唑+阿莫西林+甲硝唑，萎缩性胃炎予以枸橼酸铋钾+阿莫西林+甲硝唑连用7天。联合治疗组在此基础上加用黄芩组方煎服，每日一利，连用3周。观察治疗前后临床症状的改善和胃组HP、CEA的改变。
结果(1)癌前病变的各阶段及胃癌患者的血清及胃组织中均可检测到HP，血清及胃组织中HP的检出率以胃癌前病变组最高，胃癌组次之，浅表性胃炎中检出率较低。三组之间比较差异均有统计学意义(P＜0.05)，各组与正常组之间差异也均有统计学意义(P＜0.05)。胃组织HP检出率明显高于血清。(2)血清及胃组织CEA检测显示，胃癌组最高，其次为癌前病变组，浅表性胃炎中CEA的检出率较低，正常胃黏膜中未检出。胃癌组分别与癌前病变组及对照组比较差异有统计学意义(P＜0.01)。(3)对CEA阳性患者的阳性程度分析时发现，胃癌组++—+++的阳性率明显高于癌前病变组及浅表性胃炎组。此外，癌前病变组+—+++的阳性率均明显高于浅表性胃炎组。(4)中药+三联疗法组在症状的改善、根除HP感染和减低胃组织CEA等方面优于三联疗法组
结论(1)HP参与了胃癌前病变和胃癌的发病过程，可把血清及胃组织Hp检测作为对癌前病变的初步监测及治疗观察指标之一。(2)血清及组织CEA检测可协助胃癌的诊断，并对慢性萎缩性胃炎、胃黏膜肠上皮化生、胃溃疡等癌前病变患者的监测有较为重要的价值。胃组织CEA检测明显优于血液中CEA的检测。血清与胃组织CEA协同检测可提高临床诊断率。(3)对Hp阳性的癌前病变患者动态检测血清及组织CEA更有助于对胃癌的早期发现、早期诊断和早期治疗。(4)以黄芩为主的中药组方联合三联疗法在治疗胃癌前病变可提高疗效。
Objective (1) (?)o p(?)o(?)ide the basis for early de(?)eec(?)ion and treatment of preeanceous lesions of gastric carcinom. and reference for early discovery. diagnosis and treatment of gastric cancer. by examining the differences of expression of the CEA and Hp between precancerous lesions of gastric carcinoma patients and gastric cancer patients. (2)To understand synergism of fungistasis and protection of gastric mucosa on precancerous lesions patients, who were treated by the prescription mianly of Chinese traditional baical skullcap root, by observing the therapeutic effect of precancerous lesions of gastric carcinoma patients, who were treated by triple therapy or jointing traditional chinese medicine. Through this study we wanted to explore new ideas.
Methods (1)Detected the expression of helicobacter pylori and carcinoembryonic antigen in blood serum by immunochromatographic method and Protein Chip System. Useing immunohistochemistray to detect the expression of helicobacter pylori and carcino-embryonic antigen in gastric mucosa. (2) 83 patients with precancerous lesions were classified triple therapy group and jointing traditional chinese medicine group. The modern medicine group was treated with omeprazole, amoxicillin and colloidal bismuth subcitrate for 7 days. The jointing traditional chinese medicine group on the basis of triple therapy group was treated with the prescription mianly of Chinese tr-aditional baical skullcap root for 21days. After treatment. observed the change on clinical symptoms, Hp and CEA.
Results (1) The expression of Hp was deteced on every stages of precancerous lesions and gastric cancer. compared by the detection rate of Hp. precancerous lesions group was higher than gastric cancer group and superficial gastritis group, superficial gastritis group was the lolowest. The differences of the three groups were significant (P＜0.05). The detection rate of Hp in gastric mucosa was obviously higher than in blood serum. (2) Compared by the expression of CEA, the highest group was gastric cancer group. the lowest was superficial gastritis group, both in blood serum and gastric mucosa. The expression of CEA was not detected in nemal stomach mucosa.(3) Through analysis of the positive patients of CEA.found that the positive degree of gastriic cancer group was highest.and the preeancerous lesions group is obviously higher than superficial gastritis group.(4) Jointing traditional chinese medicine group was better than triple therapy group in the improvement of symptoms, the eradication of Hp,and reduction of the expression of Hp andCEA.
Conclusion: (1)Hp participate the process of the precancerous lesions and gastric cancer.The expression of Hp could be one of the index ,which monitor the process and curative effect of the precancerous lesions. (2) The expression of CEA could help diagnosis of gastric cancer.It is important to moniitor the precancerous lesions. The expression of CEA in gastric mucosawas better than in blood serum.Detected CEA both in gastric mucosa and blood serum,which could raise the rate of clinical diagnosis.(3)Observering CEA of Hp positive patients was benefit for early discovery, diagnosis and treatment of stomach cancer.(4)jointing traditional chinese medicine could elevate curative effect ofprecancerous lesion.
引文
[1] 张学斌．胃癌的病理学[J]．新消化病学，1994，4(2)：96．
[2] 邹建湘，陈玉龙，王立东．胃癌发病机制的研究[J]．新消化病学，1997，5(3)：180．
[3] CorreaP.A human model of gastric carcinogenesis.Cancer Res,1998;48: 3554.
[4] ROZEN P. Cancer of the gastroitestinal tract: early detection or early prevention[J] Eur J Cancer Prey. 2004, 13: 71.
[5] CORREA P. The biological model of gastric careinoge nesis[J]. IARC Sci Publ.2004, 157: 301.
[6] TESTINO G. Gastric preneoplastic changes[J]. Recemti Prog Med, 2004. 95: 239.
[7] 刘改芳，林三仁．幽门螺杆菌感染与胃癌关系的研究进展[J]．中国实用内科杂志，2003，23(9)：573．
[8] Matsukura N, Onda M, Yamashita K. Helieobacter pylori in peptic ulcer and gastric cancer[J]. Gan-To-Kagaku-Ryoho, 1995, 22(2): 169—178
[9] 余菲菲．幽门螺杆菌的球形变异及其特征和意义[J]．中国微生态学杂志，2001，13：299—300．
[10] 于东红，承泽农，贾继辉，等．食管癌幽门螺杆菌Ⅰ型感染与其血管形成的关系[J]．中华肿瘤杂志，2003，25(1)：51-54．
[11] 郑鹏远，唐芙爱，华杰松，等．幽门螺杆菌二种形态的研究[J]．中华消化杂志，1999，19：230-232．
[12] Asaka M, Kndo M. Kndo M. et al. Relationship between ltelicobacter pylori infection, atrophic gastritis and gastric carci-noma in a Japanese population [J]. Eur-J-Gastroenterol-@(hepatol). 1995. suppl 1: 7-10.
[13] Christian D et,al. Carcinoembryortic antlgenl plasthe level determination in the management Of gastric cancer patients. Cancer Detect Prev, 1985. 8: 181
[14] 任毅，周德俊，王鹏志．胃癌与胃溃疡病人血液及胃液中癌胚抗原(CEA)的定量研究．中国肿瘤临床．1994，21(2)：108-109]．
[15] LAUWERS GY. Defining the pathologic diagnosis of metaplasia, atrophy, dysplasia, and gastric adenocarcinoma[J]. J Cin Gastroenterol, 2003, 36(5 Suppl): 37.
[16] ANNIBAIE B, Di Giulio E, CARUANA P, et al. The long-term offects of cure of helicobacter bylori infection On patients with atrophic body gastritis[J]. Aliment Pharmacol Ther, 2002, 16: 1723.
[17] 石雪迎，赵凤志，由江峰，等．三中中药有效成分对转化的人胃粘膜上皮细胞的抑制作用．中国中医基础医学杂志，2004，10(12)：894～898
[18] 王绪林，缴稳铃，吕宗舜，等．抑制幽门螺杆菌中药的初步筛选[J]．中国中西医结合杂志，1994，14(9)：534～536．
[19] 朱生梁，叶洁星，何玉辉，等．中医药治疗慢性胃炎伴幽门螺杆菌感染的实验研究与临床观察[]]．上海中医药杂志，1995，29(12)：33．
[20] 蒋鹏程，倪鸿昌，李琦恒．奥美拉唑对胃癌前病变细胞凋亡的影响．中国医院药学杂志，2006，26(4)：405～407．
[1] 王垂杰．胃癌前病变与脾虚胃热气滞血瘀的关系．辽宁中医杂志，1997(12)：542．
[2] 李乾构，周学文，单兆伟．实用中医消化病学．第1版．北京：人民卫生出版社，2001：121．
[3] 危北海．中医脾胃学说应用研究．第1版．北京：北京出版社，1993：194．
[4] 王永炎，李明富，戴锡孟等．中医内科学．第1版．上海：上海科学技术出版社，1999：169．
[5] 王绪林，缴稳铃，吕宗舜，等．抑制幽门螺杆菌中药的初步筛选[J]．中国中西医结合杂志，1994，14(9)：534～536．
[6] 张琳，杨连文，杨李君，等．幽门螺杆菌与慢性萎缩性胃炎发病的关系及防治研究[J]．中国中西医结合杂志，1992，12(9)：521～523．
[7] 沈映君．中药药理学[M]．第1版．北京：人民卫生出版社，2000：656～661．
[8] 翁维良，王汀华，王怡，等．20种活血化瘀药对实验性微循环障碍的影响[J]．辽宁中医杂志，1984，4(9)：555～557
[9] 蔡永敏，任玉让，王黎．中药药理与临床应用[M]．第2版．北京：华夏出版社，1999：54，80，314．
[10] 陈士军，徐纯超．中西医结合治疗胃癌前病变158例．广东医学，2006，27(4)：596～597．
[11] 张继攻，等．活血化瘀治疗胃癌前病变90例疗效分析．中医中西医结合杂志，1992(8)：492．
[12] 李琦，沈俊．慢性萎缩性胃炎伴肠上皮化生108例辨证治疗．上海中医药杂志，1997，(11)：27．
[13] 董建华．虚痞(慢性萎缩性胃炎癌前病变)中药治疗观察．中国医药学报，1981，12(6)：12～15．
[14] 王长洪，王艳红，周莹，等．益胃解毒汤治疗胃粘膜异型增生．辽宁中医杂志，1993，(2)：28．
[15] 徐千里．柴平汤加味治疗萎缩性胃炎伴肠化临床研究．实用中西医结合杂志，1993，(10)：607．
[16] 刘承伟．柴胡疏肝散加减治疗HP阳性56例．吉林中医药，2001，(3)：7．
[17] 王巍．舒肝散加味治疗胃粘膜异型增生．陕西中医，1995，16(3)：31．
[18] 王文仲，陈大权，赵俊宏，等．软坚散结法治疗慢性萎缩性胃炎伴胃粘膜异型增生的对比观察．中医杂志，1994，35(8)：477．
[19] 唐存雄．血府逐淤汤加减治疗萎缩性胃炎463例．陕西中医，1999，(4)：160．
[20] 金萍．萎炎康治疗慢性萎缩性胃炎疗效分析．浙江中医学院学报，2001，25(5)：29．
[21] 曹巍鲲．香砂参术汤治疗萎缩性胃炎113例．陕西中医，2000，(6)：243．
[22] 张建文．胃肠病诊治大全．第1版．北京：中国医药科技出版社，2000：271．
[23] Bethi P, etal.Gastroenology,1993,(104):1057.
[24] 阳凡．幽门螺杆菌感染与胃癌前病变的关系．中医杂志，1999，5(2)：46．
[25] 许岸高，李韶光，刘集鸿，等．胃癌癌前病变演化与细胞凋亡和增殖的关系．中华医学杂志，1999，79(3)：185．
[26] 吴小翎．表皮生长因子受体在胃癌中表达及意义．重庆医科大学学报，1999，24(2)：136．
[27] RatnasingheD, TangreajA, RothMj, etal. Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus ON colRep, 1999, 6(5): 965-968.
[28] WilliamsCS, Smalley W, DuboisRN. Aspirin use and potential menchanisms for colorectal cancer prevention[J].J Clin Tnvest, 1997, 100: 1325-1329.
[29] 高华，袁媛，王兰，等．幽门螺杆菌相关性胃疾病抑癌基因P16表达的研究．中华消化杂志，1997，17：242．
[30] 孙春兰．人胃癌和胃癌前病变组织中P53蛋白的表达及亚细胞定位．延边医学院学报，1994，17(3)：157．
[31] 刘天卿，赵鲁茄，邢广莹，等．PCNA、P53、EGFR在胃粘膜上皮异型增生和癌变中的表达．医师进修杂志，1996，19(5)：16．
[32] 刘勇．胃粘膜肠化细胞增殖状态分型的研究．江西医药，1997(4)：198．
[2] 邹建湘，陈玉龙，王立东．胃癌发病机制的研究[J]．新消化病学，1997，5(3)：180．
[3] CorreaP.A human model of gastric carcinogenesis.Cancer Res,1998;48: 3554.
[4] ROZEN P. Cancer of the gastroitestinal tract: early detection or early prevention[J] Eur J Cancer Prey. 2004, 13: 71.
[5] CORREA P. The biological model of gastric careinoge nesis[J]. IARC Sci Publ.2004, 157: 301.
[6] TESTINO G. Gastric preneoplastic changes[J]. Recemti Prog Med, 2004. 95: 239.
[7] 刘改芳，林三仁．幽门螺杆菌感染与胃癌关系的研究进展[J]．中国实用内科杂志，2003，23(9)：573．
[8] Matsukura N, Onda M, Yamashita K. Helieobacter pylori in peptic ulcer and gastric cancer[J]. Gan-To-Kagaku-Ryoho, 1995, 22(2): 169—178
[9] 余菲菲．幽门螺杆菌的球形变异及其特征和意义[J]．中国微生态学杂志，2001，13：299—300．
[10] 于东红，承泽农，贾继辉，等．食管癌幽门螺杆菌Ⅰ型感染与其血管形成的关系[J]．中华肿瘤杂志，2003，25(1)：51-54．
[11] 郑鹏远，唐芙爱，华杰松，等．幽门螺杆菌二种形态的研究[J]．中华消化杂志，1999，19：230-232．
[12] Asaka M, Kndo M. Kndo M. et al. Relationship between ltelicobacter pylori infection, atrophic gastritis and gastric carci-noma in a Japanese population [J]. Eur-J-Gastroenterol-@(hepatol). 1995. suppl 1: 7-10.
[13] Christian D et,al. Carcinoembryortic antlgenl plasthe level determination in the management Of gastric cancer patients. Cancer Detect Prev, 1985. 8: 181
[14] 任毅，周德俊，王鹏志．胃癌与胃溃疡病人血液及胃液中癌胚抗原(CEA)的定量研究．中国肿瘤临床．1994，21(2)：108-109]．
[15] LAUWERS GY. Defining the pathologic diagnosis of metaplasia, atrophy, dysplasia, and gastric adenocarcinoma[J]. J Cin Gastroenterol, 2003, 36(5 Suppl): 37.
[16] ANNIBAIE B, Di Giulio E, CARUANA P, et al. The long-term offects of cure of helicobacter bylori infection On patients with atrophic body gastritis[J]. Aliment Pharmacol Ther, 2002, 16: 1723.
[17] 石雪迎，赵凤志，由江峰，等．三中中药有效成分对转化的人胃粘膜上皮细胞的抑制作用．中国中医基础医学杂志，2004，10(12)：894～898
[18] 王绪林，缴稳铃，吕宗舜，等．抑制幽门螺杆菌中药的初步筛选[J]．中国中西医结合杂志，1994，14(9)：534～536．
[19] 朱生梁，叶洁星，何玉辉，等．中医药治疗慢性胃炎伴幽门螺杆菌感染的实验研究与临床观察[]]．上海中医药杂志，1995，29(12)：33．
[20] 蒋鹏程，倪鸿昌，李琦恒．奥美拉唑对胃癌前病变细胞凋亡的影响．中国医院药学杂志，2006，26(4)：405～407．
[1] 王垂杰．胃癌前病变与脾虚胃热气滞血瘀的关系．辽宁中医杂志，1997(12)：542．
[2] 李乾构，周学文，单兆伟．实用中医消化病学．第1版．北京：人民卫生出版社，2001：121．
[3] 危北海．中医脾胃学说应用研究．第1版．北京：北京出版社，1993：194．
[4] 王永炎，李明富，戴锡孟等．中医内科学．第1版．上海：上海科学技术出版社，1999：169．
[5] 王绪林，缴稳铃，吕宗舜，等．抑制幽门螺杆菌中药的初步筛选[J]．中国中西医结合杂志，1994，14(9)：534～536．
[6] 张琳，杨连文，杨李君，等．幽门螺杆菌与慢性萎缩性胃炎发病的关系及防治研究[J]．中国中西医结合杂志，1992，12(9)：521～523．
[7] 沈映君．中药药理学[M]．第1版．北京：人民卫生出版社，2000：656～661．
[8] 翁维良，王汀华，王怡，等．20种活血化瘀药对实验性微循环障碍的影响[J]．辽宁中医杂志，1984，4(9)：555～557
[9] 蔡永敏，任玉让，王黎．中药药理与临床应用[M]．第2版．北京：华夏出版社，1999：54，80，314．
[10] 陈士军，徐纯超．中西医结合治疗胃癌前病变158例．广东医学，2006，27(4)：596～597．
[11] 张继攻，等．活血化瘀治疗胃癌前病变90例疗效分析．中医中西医结合杂志，1992(8)：492．
[12] 李琦，沈俊．慢性萎缩性胃炎伴肠上皮化生108例辨证治疗．上海中医药杂志，1997，(11)：27．
[13] 董建华．虚痞(慢性萎缩性胃炎癌前病变)中药治疗观察．中国医药学报，1981，12(6)：12～15．
[14] 王长洪，王艳红，周莹，等．益胃解毒汤治疗胃粘膜异型增生．辽宁中医杂志，1993，(2)：28．
[15] 徐千里．柴平汤加味治疗萎缩性胃炎伴肠化临床研究．实用中西医结合杂志，1993，(10)：607．
[16] 刘承伟．柴胡疏肝散加减治疗HP阳性56例．吉林中医药，2001，(3)：7．
[17] 王巍．舒肝散加味治疗胃粘膜异型增生．陕西中医，1995，16(3)：31．
[18] 王文仲，陈大权，赵俊宏，等．软坚散结法治疗慢性萎缩性胃炎伴胃粘膜异型增生的对比观察．中医杂志，1994，35(8)：477．
[19] 唐存雄．血府逐淤汤加减治疗萎缩性胃炎463例．陕西中医，1999，(4)：160．
[20] 金萍．萎炎康治疗慢性萎缩性胃炎疗效分析．浙江中医学院学报，2001，25(5)：29．
[21] 曹巍鲲．香砂参术汤治疗萎缩性胃炎113例．陕西中医，2000，(6)：243．
[22] 张建文．胃肠病诊治大全．第1版．北京：中国医药科技出版社，2000：271．
[23] Bethi P, etal.Gastroenology,1993,(104):1057.
[24] 阳凡．幽门螺杆菌感染与胃癌前病变的关系．中医杂志，1999，5(2)：46．
[25] 许岸高，李韶光，刘集鸿，等．胃癌癌前病变演化与细胞凋亡和增殖的关系．中华医学杂志，1999，79(3)：185．
[26] 吴小翎．表皮生长因子受体在胃癌中表达及意义．重庆医科大学学报，1999，24(2)：136．
[27] RatnasingheD, TangreajA, RothMj, etal. Expression of cyclooxygenase-2 in human adenocarcinomas of the gastric cardia and corpus ON colRep, 1999, 6(5): 965-968.
[28] WilliamsCS, Smalley W, DuboisRN. Aspirin use and potential menchanisms for colorectal cancer prevention[J].J Clin Tnvest, 1997, 100: 1325-1329.
[29] 高华，袁媛，王兰，等．幽门螺杆菌相关性胃疾病抑癌基因P16表达的研究．中华消化杂志，1997，17：242．
[30] 孙春兰．人胃癌和胃癌前病变组织中P53蛋白的表达及亚细胞定位．延边医学院学报，1994，17(3)：157．
[31] 刘天卿，赵鲁茄，邢广莹，等．PCNA、P53、EGFR在胃粘膜上皮异型增生和癌变中的表达．医师进修杂志，1996，19(5)：16．
[32] 刘勇．胃粘膜肠化细胞增殖状态分型的研究．江西医药，1997(4)：198．