隆起糜烂性胃炎脾胃湿热证与Hp感染及PCNA、p53表达的相关性研究
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摘要
目的:通过观察隆起糜烂性胃炎脾胃湿热证与Hp感染及增殖细胞核抗原(PCNA)、p53表达之间的关系,探讨中医证型与Hp感染及PCNA、p53的关系,以及不同证型在病理组织学和分子生物学水平上的异同,以期更好的协助指导中西医结合防治隆起糜烂性胃炎。
方法:选择隆起糜烂性胃炎中医辨证符合脾胃湿热证、脾胃气虚证的患者79例,脾胃湿热证54例,其中Hp阳性者36例,Hp阴性者18例,脾胃气虚组25例,其中Hp阳性者16例,Hp阴性者9例。并设正常对照组18例,所有受试者均行胃镜检查,取胃窦部活检标本行快速尿素酶试验及组织染色法检测Hp,并取活检标本用于病理组织学诊断及PCNA、p53的免疫组织化学检测。
结果:
1隆起糜烂性胃炎脾胃湿热证组的萎缩、肠化程度均高于脾胃气虚组,经统计学分析,均有显著性差异(p<0.05);脾胃湿热证组中Hp阳性组的萎缩、肠化均高于Hp阴性组,经统计学分析,均有显著性差异(p<0.05),而脾胃气虚组中Hp阳性组与Hp阴性组的萎缩、肠化程度比较,经统计学分析,均无显著性差异(p>0.05)。
2隆起糜烂性胃炎脾胃湿热证组与脾胃气虚证组的p53表达均较正常对照组增加,差异有显著性(p<0.01);脾胃湿热证组的p53表达高于脾胃气虚证组,经统计学分析,有显著性差异(p<0.01);脾胃湿热证组中的Hp阳性组的p53表达高于Hp阴性组,经统计学分析,有显著性差异(p<0.05),而脾胃气虚组中的的Hp阳性组与Hp阴性组的p53表达无显著性差异(p>0.05)。
3隆起糜烂性胃炎脾胃湿热证组与脾胃气虚证组PCNA的表达均较正常对照组增加,差异有显著性意义(p<0.01);脾胃湿热证组、脾胃气虚证组PCNA表达情况,经统计学分析,无显著性差异(p>0.05);脾胃湿热证组中的Hp阳性组与Hp阴性组、脾胃气虚证组中的Hp阳性组与Hp阴性组的PCNA表达,经统计学分析,均无显著性差异(p>0.05)。
结论:
1隆起糜烂性胃炎脾胃湿热证组萎缩、肠化程度均高于脾胃气虚证组且与Hp有关;
2隆起糜烂性胃炎脾胃湿热证患者胃黏膜存在p53过度表达与Hp有关。
3隆起糜烂性胃炎胃黏膜处于高增殖状态。
Objective:To study the relationship between the expression of PCNA,p53 and Helicobacter pylori infection and the Raised Erosive Gastritis with spleen-stomach dampness heat syndrome.To study the relationship between TCM syndrome and PCNA,p53, Helicobacter pylori;meanwhile observe the difference of pathological and molecular biology among different syndromes.In order to assistant the treatment of the Helicobacter Pylori Raised Erosive Gastritis with integrated traditional Chinese and Western Medicine.
Method:79 Raised Erosive Gastritis patients whoses syndromes meet with spleen stomach-dampness-heat(SSDH)and spleen stomach qi-deficiency(SSQD)accroding to TCM dialectics were selected as research subjects.There were 54 patients in spleen-stomach dampness-heat(SSDH) group,25 patients in spleen stomach qi-deficiency(SSQD)group.In SSDH group,there were 36 patients whoses HP is positive and 18 patients whoses Hp is negative.In SSQD group,there were 16 patients whoses Hp is positive and 9 patients whoses Hp is negative.There were 18 patients in control group.All subjects accepted gastroscopy examination.We got the samples from the gastric antrum,during the gastroscopy examination;and then the samples were used to do rapid urease test,detect the existence of Hp with histological stain method,do pathologic diagnosis and detect the expression of PCNA,p53 with immunohistochemistry.
Results:
1 The degree of atrophy,intestinal metaplasia in the SSDH group was much worse compared to it in the SSQD group(p＜0.05).In SSDH group,the result was the same when degree of atrophy,intestinal metaplasia in the Hp positive group and Hp negative group,but in the SSQD group,there were no difference between Hp positive group and Hp negative group about the degree of atrophy,intestinal metaplasia.
2 The expression of p53 in Raised Erosive Gastritis with SSDH was enhanced and obviously different with in the SSQD group and in the control group(p＜0.01),In SSDH group,the result was the same when the expression of p53 in the Hp positive group and Hp negative group(p＜0.05).but in the SSQD group,there were no difference between Hp positive group and Hp negative group about The expression of p53(p＞0.05).
3 The expression of PCNA in Raised Erosive Gastritis with SSDH group and SSQD group was enhanced and obviously different with in the control group(p＜0.01),.there were no difference between SSDH group and the SSQD group(p＞0.05).In SSDH group,the the result was the same when the expression of PCNA in the Hp positive group and Hp negative group on the expression of PCNA(p＞0.05).In SSQD group,the result was the same between the Hp positive group and Hp negative group(p＞0.05).
Conclusion:
1 The degree of atrophy,intestinal metaplasia in the SSDH group was much worse compared to it in the SSQD group and there was relationship between the difference and the existnace of Hp.
2 Raised Erosive Gastritis patients whoses syndromes meet with spleen stomach-dampness-heat(SSDH) exist p53 over-expression and there was relationship between the difference and the existnace of Hp.
3 Raised Erosive Gastritis is in a highly proliferative condition
方法:选择隆起糜烂性胃炎中医辨证符合脾胃湿热证、脾胃气虚证的患者79例,脾胃湿热证54例,其中Hp阳性者36例,Hp阴性者18例,脾胃气虚组25例,其中Hp阳性者16例,Hp阴性者9例。并设正常对照组18例,所有受试者均行胃镜检查,取胃窦部活检标本行快速尿素酶试验及组织染色法检测Hp,并取活检标本用于病理组织学诊断及PCNA、p53的免疫组织化学检测。
结果:
1隆起糜烂性胃炎脾胃湿热证组的萎缩、肠化程度均高于脾胃气虚组,经统计学分析,均有显著性差异(p<0.05);脾胃湿热证组中Hp阳性组的萎缩、肠化均高于Hp阴性组,经统计学分析,均有显著性差异(p<0.05),而脾胃气虚组中Hp阳性组与Hp阴性组的萎缩、肠化程度比较,经统计学分析,均无显著性差异(p>0.05)。
2隆起糜烂性胃炎脾胃湿热证组与脾胃气虚证组的p53表达均较正常对照组增加,差异有显著性(p<0.01);脾胃湿热证组的p53表达高于脾胃气虚证组,经统计学分析,有显著性差异(p<0.01);脾胃湿热证组中的Hp阳性组的p53表达高于Hp阴性组,经统计学分析,有显著性差异(p<0.05),而脾胃气虚组中的的Hp阳性组与Hp阴性组的p53表达无显著性差异(p>0.05)。
3隆起糜烂性胃炎脾胃湿热证组与脾胃气虚证组PCNA的表达均较正常对照组增加,差异有显著性意义(p<0.01);脾胃湿热证组、脾胃气虚证组PCNA表达情况,经统计学分析,无显著性差异(p>0.05);脾胃湿热证组中的Hp阳性组与Hp阴性组、脾胃气虚证组中的Hp阳性组与Hp阴性组的PCNA表达,经统计学分析,均无显著性差异(p>0.05)。
结论:
1隆起糜烂性胃炎脾胃湿热证组萎缩、肠化程度均高于脾胃气虚证组且与Hp有关;
2隆起糜烂性胃炎脾胃湿热证患者胃黏膜存在p53过度表达与Hp有关。
3隆起糜烂性胃炎胃黏膜处于高增殖状态。
Objective:To study the relationship between the expression of PCNA,p53 and Helicobacter pylori infection and the Raised Erosive Gastritis with spleen-stomach dampness heat syndrome.To study the relationship between TCM syndrome and PCNA,p53, Helicobacter pylori;meanwhile observe the difference of pathological and molecular biology among different syndromes.In order to assistant the treatment of the Helicobacter Pylori Raised Erosive Gastritis with integrated traditional Chinese and Western Medicine.
Method:79 Raised Erosive Gastritis patients whoses syndromes meet with spleen stomach-dampness-heat(SSDH)and spleen stomach qi-deficiency(SSQD)accroding to TCM dialectics were selected as research subjects.There were 54 patients in spleen-stomach dampness-heat(SSDH) group,25 patients in spleen stomach qi-deficiency(SSQD)group.In SSDH group,there were 36 patients whoses HP is positive and 18 patients whoses Hp is negative.In SSQD group,there were 16 patients whoses Hp is positive and 9 patients whoses Hp is negative.There were 18 patients in control group.All subjects accepted gastroscopy examination.We got the samples from the gastric antrum,during the gastroscopy examination;and then the samples were used to do rapid urease test,detect the existence of Hp with histological stain method,do pathologic diagnosis and detect the expression of PCNA,p53 with immunohistochemistry.
Results:
1 The degree of atrophy,intestinal metaplasia in the SSDH group was much worse compared to it in the SSQD group(p＜0.05).In SSDH group,the result was the same when degree of atrophy,intestinal metaplasia in the Hp positive group and Hp negative group,but in the SSQD group,there were no difference between Hp positive group and Hp negative group about the degree of atrophy,intestinal metaplasia.
2 The expression of p53 in Raised Erosive Gastritis with SSDH was enhanced and obviously different with in the SSQD group and in the control group(p＜0.01),In SSDH group,the result was the same when the expression of p53 in the Hp positive group and Hp negative group(p＜0.05).but in the SSQD group,there were no difference between Hp positive group and Hp negative group about The expression of p53(p＞0.05).
3 The expression of PCNA in Raised Erosive Gastritis with SSDH group and SSQD group was enhanced and obviously different with in the control group(p＜0.01),.there were no difference between SSDH group and the SSQD group(p＞0.05).In SSDH group,the the result was the same when the expression of PCNA in the Hp positive group and Hp negative group on the expression of PCNA(p＞0.05).In SSQD group,the result was the same between the Hp positive group and Hp negative group(p＞0.05).
Conclusion:
1 The degree of atrophy,intestinal metaplasia in the SSDH group was much worse compared to it in the SSQD group and there was relationship between the difference and the existnace of Hp.
2 Raised Erosive Gastritis patients whoses syndromes meet with spleen stomach-dampness-heat(SSDH) exist p53 over-expression and there was relationship between the difference and the existnace of Hp.
3 Raised Erosive Gastritis is in a highly proliferative condition
引文
[1]Freise J,Hofmann R,Gebel M,et al.Follow-up study on chronic gastritis Erosi-ons[J].Endoscopy.1979,11:13-17.
[2]付唆林.国外医学.消化系疾病分册.隆起糜烂性胃炎的历史、现状与思考[M].2005,25(3):155-156.
[3]Munoz MC,Mendoza D,Palma E.An Fac Med Univ RepubMontev Urug[J].1960,45:72-77.
[4]郝志明,张玉厚,吴玉斌.隆起糜烂性胃炎198例临床、胃镜及病理分析[J].中国内镜杂志.1996,2(4):71.
[5]王杏妹,许文芳.隆起糜烂性胃炎胃镜普查的资料分析[J].中国实用医学研究杂志.2002,1(3):53.
[6]樊代明,陈强.第十届世界胃肠病大会[J].中华消化杂志.1995,15:33.
[7]柯晓.隆起糜烂性胃炎病理分类和中医临床证候学的研究[C].第二十次全国中西结合消化系统疾病学术会议论文汇编.2008年11月P73.
[8]Correa P.A human model of gastric carcinogenesis[J].Cancer Res.1998,48-3554.
[9]Hiwa H,Endo K,Wada R,et al.cellular proliferation and differenriation in ratatrophic gastric mucosa indred by N'-methyl-N'-hitro-N-nitrosoguanidine[J].J Clin Gastroenterol.1997,25(Suppl 1):116.
[10]EiDeiry WS,Tokino T,Velculescv VE,et al.WAF1,a potential Mediatorof p53 tumour supper-ssion[J].Cell.1993,75(19):817.
[11]Xia HH,Talley NJ.Apoptosis in gastric epithelium induced by helicobacterpylori infection implications in gastric carcoinogenesis[J].Am J Gastroenterol.2001,96(1):16.
[12]Hall PA.Assessment of cell proliferation in histological material[J].J Clin Pathol.1990,43:184.
[13]杨春波,黄可成,肖丽春,等.脾胃湿热证的临床研究—附400例资料分析[J].中医杂志.1994,35(7):425-427.
[14]杨春波.脾胃湿热证理论的应用与研究[J].中国中西医结合脾胃杂志.1998,6(3):129-131.
[15]杨春波,柯晓,傅肖岩,等.脾胃湿热证研究的初步揭示[J].中华中医药杂志.2003,(8):16-19.
[16]Rugge M,Shiao YH,Correa P,et al.Immunohistochemical evidence of p53 overexpression in gastric epithelial dysplasia[J].Cancer Epidemiol Biomarkers Prevention.1992,31(1):551.
[17]Moss SF,Calam J,Agarwal B,et al.Induction of gastric epithiliel apotosis by Holicobacter Pylori[J].Gut.1996,38(5):498-501.
[18]Mccoll KEL.Helicobacter pylori:chinical aspects[J].Jinfect.1997,34:7-13.
[19]赵立宇,褚惠民.慢性胃炎病理与中医证型的相关性研究[J].河北中医.2004,26(11):813-814.
[20]Harpper JW,A dami GR,Wei N,et al.The p21 cdk-enteracting protein cip;is a potene inhibitor of G1 cyclin-dependent kinases. Cell, 1993, 75:805-816.
[21] Linzer DI, Levine AJ. Characterization of a 54K dalton Cellular SV40 tumoran tigen presenting SV 402 transformed cell sand uninfecte dembryonal carcinoma cells[J]. Cell, 1979, 17(1):43252.
[22] Finlay CA, Hinds PW, Tan TH, et al. Activating mutations for transformation by p53 produce agene product that forms an hsc70-p53 complex with an altered half-life[J]. MolCelfbiol. 1988, 8: 531-539.
[23] HofsethLJ, UissainSP, Harris CC. p53: 25 years after its discovery[J]. Trends Pharmacol Sci.2004, 25(4): 177-181.
[24] Larongac C, Yang HY, Neal C, et al. Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulatescell cycle progression[J]. J Biol Chem. 2000, 275 (30): 23106-23112.
[25]SaceaP, CablleroF, BatlleA, et al. Cell cycle arrest and modulation of HO-1 expression induced by acetyl salicylic acid in hepatocarcinogenesis[J]. Int J Biochem Cell Biol. 2004, 36(10): 1945-1953.
[26] Lu X. p53: a heavily dictated dictator of life and death[J]. Curr Opin Genet Dev. 2005, 15(1): 27-33.
[27] Sigal A, Rotter V. Oncogenic mutations of the P53 tumor suppressor: the demons of the guardian of the genome[J]. CancerRes.2000, 60(24): 6788-6793.
[28] Frazier MW, He X, Wang J, et al. Activation of c-myc gene expression by tumor-derived p53 mutants requires a discrete C-terminal domain[J]. Mol Cell Biol. 1998, 18(7): 3735-3743.
[29] Yang X, Pater A, Tang SC. Cloning and characterization of the human BAG-1 gene promoter: upregulation by tumorderived p53 mutants[J]. Oncogene. 1999, 18(32): 4546-4553.
[30] Xu D, Wang Q, Gruber A, et al. Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells[J]. Oncogene. 2000, 19(45): 5123-5133.
[31] Sampath J, Sund, Kidd VJ, et al.Mutant p53 cooperates with FTS and selectively up-regulates human MDR1 not MRP1[J].J Biol Chem. 2001, 276(42): 39359-39367.
[32] Vikhanskay F, Lee MK, Mazzolftti M, et al. Cancer-derived p53 mutants suppress p53-target gene expression-potential mechanism for gain of function of mutant p53[J]. Nucleic Acids Res. 2007, 35(6): 2093-2104.
[33] Blagoskonny MV, Trostel S, Kayastha G, et al. Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors[J]. Cancer Res. 2005, 65(16): 7386-7392.
[34] Bossi G, Lapie E, Strano S, et al. Mutant p53 gain of function: reduction of tumor malignancy of human cancer cell lines through abrogation of mutant p53 epression[J]. Oncogene. 2006, 25(2): 304-309.
[35] GregorioCD , Morandip , Fantek , etal. Gastricdys-plasia. afollow-upstudy [J]. AnJ Gastroenterol.1993,88(10):1714.
[36]刘月萍,丁顺德,温玉梅.胃粘膜良恶性病变中P53和bcl-2的表达的研究[J].中国微创外科杂志.2001,1(3):165-168.
[37]孟华,刘丽娜,盂晓光.胃癌及癌前病变中PCNA、p53表达及其与H pylori感染的关系[J].世界华消化杂志.2005,13(10):1253-1255.
[38]陆宇平,王长洪.脾胃湿热证胃病患者胃黏膜细胞凋亡基因相关蛋白的表达[J].中国中西医结合消化杂志.2007,15(3):174-176.
[39]TakasakiY,Kaneda K,Takeuchi K,et al.Analysis of the Structure of Proteasome Proliferating Cell Nuclear Antigen(PCNA)Multiprotein Complex and Its Autoimmune Response in Lupus Patients[J].Ann N Y A cad Sci,2003,987:316-318.
[40]陈松妹,应梅雪.幽门螺杆菌感染与胃癌、慢性胃炎、溃疡病、异型增生的关系及PCNA表达[J].实用肿瘤杂志.2003,18(5):399-400.
[41]朱冲林.胃粘膜病变中p16、p53、CyelinD1和PCNA的表达[J].江西医学检验.2002,20(5):265-266.
[42]杨兰泽,高静.胃癌及癌前病变组织中幽门螺杆菌感染与p53、p21WAF1、PCNA、cyclinA蛋白表达的相关性研究[J].实用癌症杂志.2007,22(2):129-132.
[43]李生强,葛振华,周凡,等.幽门螺杆菌对PCNA及HSP60在慢性胃炎中的表达的影响[J].中国组织化学与细胞学杂志.2006,15(4):422-425.
[44]刘海峰,刘为纹,房殿春,等.幽门螺杆菌诱导胃黏膜上皮细胞凋亡和增殖与P53基因表达[J].世界华人消化杂志.2001,9(11):1265-1268.
[45]黄梅芳,朱尤庆,张春香,等.Hp感染对胃黏膜增殖、DNA含量及癌基因表达的影响[J].世界华人消化杂志.2000,8(9):1057-1059.
[1] Lauren P. The two histo]ogic types of gastric carcinoma: difuse and so-called intestinal type carcinoma. An attempt at histocmicale classification. Acta Pathol Microbial Seand. 1965, 64: 31-49.
[2] Cornea P.Human gastric carcinogenesis:a multistep and multifactorial process-first American cancer Society Award Lecture on Cancer Epidemiology and prevention[J]. Cancer Res. 1992, 52: 6735-6740.
[3] lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells[J]. Nature. 1979, 278: 261-263.
[4] Linzer D1, levine AJ. Characterization of a 54K dalton cellular.SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells[J]. cell. 1979, 17: 43-52.
[5] Chao C, Saito S, Anderson CW, et al. Phosphorylation of murine p53 at ser-18 regulates the p53 responses to DNA damage[J]. Proc Natl Acad Sci USA. 2000, 97: 11936-11941.
[6] Venot C, Maratrat M, Dureuil C, et al. The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific P1G3 gene transactivation and with transcriptional repression[J]. EMBO J. 1998, 17: 4668-4679.
[7] Prives C, Hall PA. The p53 pathway[J].J Pathol. 1999, 187: 112-126.
[8] Zhan Q, Antinore MJ, Wang XW, et al. Association with Cdc2 and inhibition of Cdc2 / Cyclin B1 kinase activity by the p53-regulated protein Gadd45[J]. Oncogene. 1999, 18: 2892-2900.
[9] OdaE, Ohki R, Murasawa H, et al. Noxa, a BH3-only member of the Bc1-2 family and candidate mediator of p53-induced apoptosis[J]. Science. 2000, 288: 1053-1058.
[10] Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53[J].Mol Cell. 2001, 7: 683-694.
[11] Gu Z, Flemington C, Chittenden T, et al.ei24,a p53 response gene involved in growth suppression and apoptosis[J]. Mol Ceff biol 2000, 20: 233-241.
[12] Baudino TA, Cleveland JL. The Max network gone mad[J]. Mol Ceff Biol. 2001, 21: 691-702.
[13] Rambhatla L, Bohn SA, Stadler PB, et al. Cellular Senescence Ex Vivo p53 Dependent Asymmetric Cell Kinetics[J]. Biomed Biotechnol. 2001, 1: 28-37.
[14] Esposito V, Baldi A, De Luca A, et al. Prognostic role ofthe cyclin-dependcnt kinase inhibitor p27 in non-small cell lung cancer[J]. Cancer Res.1997, 57(16): 3381-3385.
[15] CorreaP, A human model ofgastric carcinogenesis. Cancer Res, 1998 48: 3554
[16] Hollsltein M, Sidransky D, Vogelstein B, et al. P53 mutation human cancer[J]. Science, 1991, 253: 4953.
[17] RanzaniGN, f uinetti D, Padovan LS, et al.p53 gene mutations and protein nuclear accumulation are early events in intestinal type gastric cancer but late events its difuse type[J].Cancer Epiderrsiol ornarkersPrey.1995,4(3):223-231.
[18]王 波,杨志宏,阮水良,等.胃癌及胃癌前病变p53蛋白PCNA表达及其临床意义的研究[J].实用肿瘤学杂志.2005,19(1):7-9.
[19]吴丽华,韩莹,张忠.胃癌及癌前病变组织中p53蛋白表达的研究[J].沈阳医学院学报.2004,6(2):80-81.
[20]Moss SF,Calam J,Agrwal B,et al.Induction of gastric epithelial apoptosis by helieobacter pylori[J].Gut.1996,38(4):498-501.
[21]Nguyen T,13runson D,Crespi CL,at al.DNA damage and mutalion in human cells exposed to nitric oxide in vitro[J].Fmc Natl Acad Sci USA.1992,89(7):3030-3034.
[22]Marx J.How p53 suppresses cel growth[J].Science.1993,262(5140):1644-1645.
[23]Zhang Z,Yuan Y,Gao H,et al.Apoptasis,proliferation and p53 gene expression of H pylori associated gastric epithelial lesions[J].W J Gasttoenterology.2001,7(6):779-782.
[24]Schistosomes,liver flukes and Helicobacter pylori.IRAC Working Group on the Evaluation of Carcinogenic Risks to Humans.Lyon,7-14 June 1994.IARC Monogr Eval Carcinog Risks Hum.1994,61:1-241.
[25]Parkin DM.The global health burden of infection-associated cancers in the year 2002[J].Int J Cancer.2006,118:3030-3044.
[26]崔轶霞,于海军,惠起源.胃癌高危人群胃粘膜组织中突变型P53蛋白、Runx3蛋白的表达及HP 感染的研究[J].陕西医学杂志.2008,37:291-293.
[27]郭晓林,姜雅秋,王丹.幽门螺杆菌感染与c-myc基因和P53基因表达与胃癌的相关性研究[J].中国老年学杂志.2007,27:56-58.
[28]赵松,付英梅,赵柏,等.慢性萎缩性胃炎黏膜上皮中P53和C-erbB-2表达的临床意义[J].世界华人消化杂志.2006,14:2943-2947.
[29]Li JH,Shi XZ,Lv S,et al.Effect of Helicobacter pylori infection on p53 expression of gastric mucosa and adenocarcinoma with microsatellite instability[J].World J Gastroenterol.2005,11:4363-4366.
[30]Kodama M,Fujioka T,Murakami K,et al.Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa[J].J Gastroenterol Hepatol.2005,20:941-946.
[31]郜恒骏,白剑峰,彭延申,等.幽门螺杆菌感染胃黏膜病变基因表达和细胞生物学行为[J].中华消化杂志.2001,21:18-20.
[32]Zhou BP,Hung MC.Novel targets of Akt,p21(Cip1/WAF1),and MDM2[J].Semin Oncol.2002:29:62-70.
[33]Jones SN,Roe AE,Donehower LA,et al.Rescue of embryonic lethality in Mdm2-deficlent mice by absence of p53[J].Nature.1995,378:206-208.
[34]Buschmann T,Fuchs SY,Lee CG,et al.SINO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53[J].Cell.2000,101:753-762.
[35]Lev Bar-Or R,Maya R,Segel LA,et al.Generation of oscillations by the p53-Mdm 2 feedback loop:a theoretical and experimental study[J].Proc Natl Acad Sci U S A.2000,97:11250-11255.
[36]Moss SF,Calam J,Agarwal B,et al.Induction of gastric epithelial apoptosis hy Helicobacter pylori[J].Gut.1996,38:498-501.
[37]Nguyen T,Brunson D,Crespi CL,et,al.DNA damage and mutation in human cells exposed to nitric oxide in vitro[J].Proc Natl Acad Sci U S A.1992,89:3030-3034.
[38]Marx J.How p53 suppresses cell growth[J].Science.1993,261:1644-1645.
[39]陈艺丹,杨玉珍,宋娟.Cyclin G1、Mdm2和P53在胃癌组织中的表达及相关性研究[J].胃肠病学利肝病学杂志.2007,16:127-129.
[40]Haupt Y,Maya R,Kazaz A,et al.Mdra2 promotes the rapid degradation of p53[J].Nature.1997,387:296-299.
[41]Liang H,Atkins H,Abdel-Fattah R,et al.Genomic Orgnisation of the human MDM2 oncogene and refationship to its alternatively spliced mRNAs[J].Gene.2004,338:217-223.
[42]Sengupta S,Wasylyk B.Physiological and pathological consequences of the interactions of the p53 tumor suppressor with the glucocorticoid,androgen,and estrogen receptors[J].Ann N Y Acad Sci.2004,1024:54-71.
[43]Xie HL,Su Q,He XS,et al.Expression of p21(WAF1)and p53 and po]ymorphism or p21(WAF1)gene in gastric Carcinoma[J].World J Gastroenterol.2004,10:1125-1131.
[44]曹大中,刘顺英,孙为豪,等.叶酸对胃癌前病变bcl-2 bax及p53基因的影响[J].临床内科杂志.2004,21(3):189-191.
[45]涂水平,江石湖,谭继宏,等.羟基喜树碱诱导胃癌细胞凋亡的作用机制初步研究[J].中华消化杂志.2001,21(5):274-277.
[46]施俊,许玲,何金,等.胃癌中医证型p53与nm23基因蛋白表达性别差异分析[J].世界华人消化杂志.2005,13(8):940-944.
[2]付唆林.国外医学.消化系疾病分册.隆起糜烂性胃炎的历史、现状与思考[M].2005,25(3):155-156.
[3]Munoz MC,Mendoza D,Palma E.An Fac Med Univ RepubMontev Urug[J].1960,45:72-77.
[4]郝志明,张玉厚,吴玉斌.隆起糜烂性胃炎198例临床、胃镜及病理分析[J].中国内镜杂志.1996,2(4):71.
[5]王杏妹,许文芳.隆起糜烂性胃炎胃镜普查的资料分析[J].中国实用医学研究杂志.2002,1(3):53.
[6]樊代明,陈强.第十届世界胃肠病大会[J].中华消化杂志.1995,15:33.
[7]柯晓.隆起糜烂性胃炎病理分类和中医临床证候学的研究[C].第二十次全国中西结合消化系统疾病学术会议论文汇编.2008年11月P73.
[8]Correa P.A human model of gastric carcinogenesis[J].Cancer Res.1998,48-3554.
[9]Hiwa H,Endo K,Wada R,et al.cellular proliferation and differenriation in ratatrophic gastric mucosa indred by N'-methyl-N'-hitro-N-nitrosoguanidine[J].J Clin Gastroenterol.1997,25(Suppl 1):116.
[10]EiDeiry WS,Tokino T,Velculescv VE,et al.WAF1,a potential Mediatorof p53 tumour supper-ssion[J].Cell.1993,75(19):817.
[11]Xia HH,Talley NJ.Apoptosis in gastric epithelium induced by helicobacterpylori infection implications in gastric carcoinogenesis[J].Am J Gastroenterol.2001,96(1):16.
[12]Hall PA.Assessment of cell proliferation in histological material[J].J Clin Pathol.1990,43:184.
[13]杨春波,黄可成,肖丽春,等.脾胃湿热证的临床研究—附400例资料分析[J].中医杂志.1994,35(7):425-427.
[14]杨春波.脾胃湿热证理论的应用与研究[J].中国中西医结合脾胃杂志.1998,6(3):129-131.
[15]杨春波,柯晓,傅肖岩,等.脾胃湿热证研究的初步揭示[J].中华中医药杂志.2003,(8):16-19.
[16]Rugge M,Shiao YH,Correa P,et al.Immunohistochemical evidence of p53 overexpression in gastric epithelial dysplasia[J].Cancer Epidemiol Biomarkers Prevention.1992,31(1):551.
[17]Moss SF,Calam J,Agarwal B,et al.Induction of gastric epithiliel apotosis by Holicobacter Pylori[J].Gut.1996,38(5):498-501.
[18]Mccoll KEL.Helicobacter pylori:chinical aspects[J].Jinfect.1997,34:7-13.
[19]赵立宇,褚惠民.慢性胃炎病理与中医证型的相关性研究[J].河北中医.2004,26(11):813-814.
[20]Harpper JW,A dami GR,Wei N,et al.The p21 cdk-enteracting protein cip;is a potene inhibitor of G1 cyclin-dependent kinases. Cell, 1993, 75:805-816.
[21] Linzer DI, Levine AJ. Characterization of a 54K dalton Cellular SV40 tumoran tigen presenting SV 402 transformed cell sand uninfecte dembryonal carcinoma cells[J]. Cell, 1979, 17(1):43252.
[22] Finlay CA, Hinds PW, Tan TH, et al. Activating mutations for transformation by p53 produce agene product that forms an hsc70-p53 complex with an altered half-life[J]. MolCelfbiol. 1988, 8: 531-539.
[23] HofsethLJ, UissainSP, Harris CC. p53: 25 years after its discovery[J]. Trends Pharmacol Sci.2004, 25(4): 177-181.
[24] Larongac C, Yang HY, Neal C, et al. Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulatescell cycle progression[J]. J Biol Chem. 2000, 275 (30): 23106-23112.
[25]SaceaP, CablleroF, BatlleA, et al. Cell cycle arrest and modulation of HO-1 expression induced by acetyl salicylic acid in hepatocarcinogenesis[J]. Int J Biochem Cell Biol. 2004, 36(10): 1945-1953.
[26] Lu X. p53: a heavily dictated dictator of life and death[J]. Curr Opin Genet Dev. 2005, 15(1): 27-33.
[27] Sigal A, Rotter V. Oncogenic mutations of the P53 tumor suppressor: the demons of the guardian of the genome[J]. CancerRes.2000, 60(24): 6788-6793.
[28] Frazier MW, He X, Wang J, et al. Activation of c-myc gene expression by tumor-derived p53 mutants requires a discrete C-terminal domain[J]. Mol Cell Biol. 1998, 18(7): 3735-3743.
[29] Yang X, Pater A, Tang SC. Cloning and characterization of the human BAG-1 gene promoter: upregulation by tumorderived p53 mutants[J]. Oncogene. 1999, 18(32): 4546-4553.
[30] Xu D, Wang Q, Gruber A, et al. Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells[J]. Oncogene. 2000, 19(45): 5123-5133.
[31] Sampath J, Sund, Kidd VJ, et al.Mutant p53 cooperates with FTS and selectively up-regulates human MDR1 not MRP1[J].J Biol Chem. 2001, 276(42): 39359-39367.
[32] Vikhanskay F, Lee MK, Mazzolftti M, et al. Cancer-derived p53 mutants suppress p53-target gene expression-potential mechanism for gain of function of mutant p53[J]. Nucleic Acids Res. 2007, 35(6): 2093-2104.
[33] Blagoskonny MV, Trostel S, Kayastha G, et al. Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors[J]. Cancer Res. 2005, 65(16): 7386-7392.
[34] Bossi G, Lapie E, Strano S, et al. Mutant p53 gain of function: reduction of tumor malignancy of human cancer cell lines through abrogation of mutant p53 epression[J]. Oncogene. 2006, 25(2): 304-309.
[35] GregorioCD , Morandip , Fantek , etal. Gastricdys-plasia. afollow-upstudy [J]. AnJ Gastroenterol.1993,88(10):1714.
[36]刘月萍,丁顺德,温玉梅.胃粘膜良恶性病变中P53和bcl-2的表达的研究[J].中国微创外科杂志.2001,1(3):165-168.
[37]孟华,刘丽娜,盂晓光.胃癌及癌前病变中PCNA、p53表达及其与H pylori感染的关系[J].世界华消化杂志.2005,13(10):1253-1255.
[38]陆宇平,王长洪.脾胃湿热证胃病患者胃黏膜细胞凋亡基因相关蛋白的表达[J].中国中西医结合消化杂志.2007,15(3):174-176.
[39]TakasakiY,Kaneda K,Takeuchi K,et al.Analysis of the Structure of Proteasome Proliferating Cell Nuclear Antigen(PCNA)Multiprotein Complex and Its Autoimmune Response in Lupus Patients[J].Ann N Y A cad Sci,2003,987:316-318.
[40]陈松妹,应梅雪.幽门螺杆菌感染与胃癌、慢性胃炎、溃疡病、异型增生的关系及PCNA表达[J].实用肿瘤杂志.2003,18(5):399-400.
[41]朱冲林.胃粘膜病变中p16、p53、CyelinD1和PCNA的表达[J].江西医学检验.2002,20(5):265-266.
[42]杨兰泽,高静.胃癌及癌前病变组织中幽门螺杆菌感染与p53、p21WAF1、PCNA、cyclinA蛋白表达的相关性研究[J].实用癌症杂志.2007,22(2):129-132.
[43]李生强,葛振华,周凡,等.幽门螺杆菌对PCNA及HSP60在慢性胃炎中的表达的影响[J].中国组织化学与细胞学杂志.2006,15(4):422-425.
[44]刘海峰,刘为纹,房殿春,等.幽门螺杆菌诱导胃黏膜上皮细胞凋亡和增殖与P53基因表达[J].世界华人消化杂志.2001,9(11):1265-1268.
[45]黄梅芳,朱尤庆,张春香,等.Hp感染对胃黏膜增殖、DNA含量及癌基因表达的影响[J].世界华人消化杂志.2000,8(9):1057-1059.
[1] Lauren P. The two histo]ogic types of gastric carcinoma: difuse and so-called intestinal type carcinoma. An attempt at histocmicale classification. Acta Pathol Microbial Seand. 1965, 64: 31-49.
[2] Cornea P.Human gastric carcinogenesis:a multistep and multifactorial process-first American cancer Society Award Lecture on Cancer Epidemiology and prevention[J]. Cancer Res. 1992, 52: 6735-6740.
[3] lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells[J]. Nature. 1979, 278: 261-263.
[4] Linzer D1, levine AJ. Characterization of a 54K dalton cellular.SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells[J]. cell. 1979, 17: 43-52.
[5] Chao C, Saito S, Anderson CW, et al. Phosphorylation of murine p53 at ser-18 regulates the p53 responses to DNA damage[J]. Proc Natl Acad Sci USA. 2000, 97: 11936-11941.
[6] Venot C, Maratrat M, Dureuil C, et al. The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific P1G3 gene transactivation and with transcriptional repression[J]. EMBO J. 1998, 17: 4668-4679.
[7] Prives C, Hall PA. The p53 pathway[J].J Pathol. 1999, 187: 112-126.
[8] Zhan Q, Antinore MJ, Wang XW, et al. Association with Cdc2 and inhibition of Cdc2 / Cyclin B1 kinase activity by the p53-regulated protein Gadd45[J]. Oncogene. 1999, 18: 2892-2900.
[9] OdaE, Ohki R, Murasawa H, et al. Noxa, a BH3-only member of the Bc1-2 family and candidate mediator of p53-induced apoptosis[J]. Science. 2000, 288: 1053-1058.
[10] Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53[J].Mol Cell. 2001, 7: 683-694.
[11] Gu Z, Flemington C, Chittenden T, et al.ei24,a p53 response gene involved in growth suppression and apoptosis[J]. Mol Ceff biol 2000, 20: 233-241.
[12] Baudino TA, Cleveland JL. The Max network gone mad[J]. Mol Ceff Biol. 2001, 21: 691-702.
[13] Rambhatla L, Bohn SA, Stadler PB, et al. Cellular Senescence Ex Vivo p53 Dependent Asymmetric Cell Kinetics[J]. Biomed Biotechnol. 2001, 1: 28-37.
[14] Esposito V, Baldi A, De Luca A, et al. Prognostic role ofthe cyclin-dependcnt kinase inhibitor p27 in non-small cell lung cancer[J]. Cancer Res.1997, 57(16): 3381-3385.
[15] CorreaP, A human model ofgastric carcinogenesis. Cancer Res, 1998 48: 3554
[16] Hollsltein M, Sidransky D, Vogelstein B, et al. P53 mutation human cancer[J]. Science, 1991, 253: 4953.
[17] RanzaniGN, f uinetti D, Padovan LS, et al.p53 gene mutations and protein nuclear accumulation are early events in intestinal type gastric cancer but late events its difuse type[J].Cancer Epiderrsiol ornarkersPrey.1995,4(3):223-231.
[18]王 波,杨志宏,阮水良,等.胃癌及胃癌前病变p53蛋白PCNA表达及其临床意义的研究[J].实用肿瘤学杂志.2005,19(1):7-9.
[19]吴丽华,韩莹,张忠.胃癌及癌前病变组织中p53蛋白表达的研究[J].沈阳医学院学报.2004,6(2):80-81.
[20]Moss SF,Calam J,Agrwal B,et al.Induction of gastric epithelial apoptosis by helieobacter pylori[J].Gut.1996,38(4):498-501.
[21]Nguyen T,13runson D,Crespi CL,at al.DNA damage and mutalion in human cells exposed to nitric oxide in vitro[J].Fmc Natl Acad Sci USA.1992,89(7):3030-3034.
[22]Marx J.How p53 suppresses cel growth[J].Science.1993,262(5140):1644-1645.
[23]Zhang Z,Yuan Y,Gao H,et al.Apoptasis,proliferation and p53 gene expression of H pylori associated gastric epithelial lesions[J].W J Gasttoenterology.2001,7(6):779-782.
[24]Schistosomes,liver flukes and Helicobacter pylori.IRAC Working Group on the Evaluation of Carcinogenic Risks to Humans.Lyon,7-14 June 1994.IARC Monogr Eval Carcinog Risks Hum.1994,61:1-241.
[25]Parkin DM.The global health burden of infection-associated cancers in the year 2002[J].Int J Cancer.2006,118:3030-3044.
[26]崔轶霞,于海军,惠起源.胃癌高危人群胃粘膜组织中突变型P53蛋白、Runx3蛋白的表达及HP 感染的研究[J].陕西医学杂志.2008,37:291-293.
[27]郭晓林,姜雅秋,王丹.幽门螺杆菌感染与c-myc基因和P53基因表达与胃癌的相关性研究[J].中国老年学杂志.2007,27:56-58.
[28]赵松,付英梅,赵柏,等.慢性萎缩性胃炎黏膜上皮中P53和C-erbB-2表达的临床意义[J].世界华人消化杂志.2006,14:2943-2947.
[29]Li JH,Shi XZ,Lv S,et al.Effect of Helicobacter pylori infection on p53 expression of gastric mucosa and adenocarcinoma with microsatellite instability[J].World J Gastroenterol.2005,11:4363-4366.
[30]Kodama M,Fujioka T,Murakami K,et al.Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa[J].J Gastroenterol Hepatol.2005,20:941-946.
[31]郜恒骏,白剑峰,彭延申,等.幽门螺杆菌感染胃黏膜病变基因表达和细胞生物学行为[J].中华消化杂志.2001,21:18-20.
[32]Zhou BP,Hung MC.Novel targets of Akt,p21(Cip1/WAF1),and MDM2[J].Semin Oncol.2002:29:62-70.
[33]Jones SN,Roe AE,Donehower LA,et al.Rescue of embryonic lethality in Mdm2-deficlent mice by absence of p53[J].Nature.1995,378:206-208.
[34]Buschmann T,Fuchs SY,Lee CG,et al.SINO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53[J].Cell.2000,101:753-762.
[35]Lev Bar-Or R,Maya R,Segel LA,et al.Generation of oscillations by the p53-Mdm 2 feedback loop:a theoretical and experimental study[J].Proc Natl Acad Sci U S A.2000,97:11250-11255.
[36]Moss SF,Calam J,Agarwal B,et al.Induction of gastric epithelial apoptosis hy Helicobacter pylori[J].Gut.1996,38:498-501.
[37]Nguyen T,Brunson D,Crespi CL,et,al.DNA damage and mutation in human cells exposed to nitric oxide in vitro[J].Proc Natl Acad Sci U S A.1992,89:3030-3034.
[38]Marx J.How p53 suppresses cell growth[J].Science.1993,261:1644-1645.
[39]陈艺丹,杨玉珍,宋娟.Cyclin G1、Mdm2和P53在胃癌组织中的表达及相关性研究[J].胃肠病学利肝病学杂志.2007,16:127-129.
[40]Haupt Y,Maya R,Kazaz A,et al.Mdra2 promotes the rapid degradation of p53[J].Nature.1997,387:296-299.
[41]Liang H,Atkins H,Abdel-Fattah R,et al.Genomic Orgnisation of the human MDM2 oncogene and refationship to its alternatively spliced mRNAs[J].Gene.2004,338:217-223.
[42]Sengupta S,Wasylyk B.Physiological and pathological consequences of the interactions of the p53 tumor suppressor with the glucocorticoid,androgen,and estrogen receptors[J].Ann N Y Acad Sci.2004,1024:54-71.
[43]Xie HL,Su Q,He XS,et al.Expression of p21(WAF1)and p53 and po]ymorphism or p21(WAF1)gene in gastric Carcinoma[J].World J Gastroenterol.2004,10:1125-1131.
[44]曹大中,刘顺英,孙为豪,等.叶酸对胃癌前病变bcl-2 bax及p53基因的影响[J].临床内科杂志.2004,21(3):189-191.
[45]涂水平,江石湖,谭继宏,等.羟基喜树碱诱导胃癌细胞凋亡的作用机制初步研究[J].中华消化杂志.2001,21(5):274-277.
[46]施俊,许玲,何金,等.胃癌中医证型p53与nm23基因蛋白表达性别差异分析[J].世界华人消化杂志.2005,13(8):940-944.