胃黏膜病变中突变型p53、Mdm2和PCNA蛋白表达及与幽门螺杆菌感染的关系

目的探讨胃黏膜病变中突变型p53、Mdm2、增殖细胞核抗原（PCNA）蛋白的表达及其与幽门螺杆菌（Hp）感染的关系。方法应用免疫组化PV-9000法染色及Giemsa染色检测胃黏膜病变中突变型p53、Mdm2、PC-NA蛋白的表达和Hp感染情况。结果在慢性浅表性胃炎（csG）、慢性萎缩性胃炎伴肠上皮化生（CAG伴IM）、不典型增生（Bys）及胃癌（GC）中,突变型p53、Mdm2、PCNA阳性表达随病变发展而逐渐升高,突变型p53在CSG组高于GC组,GC组高于CAG伴IM组（P均〈0．05）。不同胃黏膜病变之间Mdm2比较均有统计学差异（P〈0．05）。在同一病变中Hp阳性者突变型p53、Mdm2、PCNA阳性表达一般高于Hp阴性者,突变型p53在CAG伴IM组Hp阳性与阴性者间有统计学差异（P〈0．05）,PCNA和Mdm2在Dys组Hp阳性与阴性者有统计学差异（P〈0．05）。GC组中突变型p53、Mdm2、PCNA蛋白表达无相关关系。结论突变型p53、Mdm2和PCNA蛋白的表达及Hp感染共同参与胃黏膜病变的发生、发展。     

残胃黏膜病变与幽门螺杆菌感染的关系

目的 研究幽门螺杆菌(Hp)感染与残胃黏膜病变的关系.方法 选取胃大部切除术后的残胃患者58例为残胃1组(良性消化性溃疡术后),83例为残胃2组(早期胃癌术后),分别进行胃镜、病理组织学及Hp检测.结果 残胃1组患者胃黏膜炎症(P＞0.05)、活动性(P＜0.05)和Hp感染发生率(P＜0.05)等均高于残胃2组.两组Hp感染者慢性萎缩性胃炎、癌前病变及活动性等均高于未感染者(P＜0.05),而未感染者在残胃2组中的慢性非萎缩性胃炎较感染者更多见(P＜0.05).残胃2组Hp检出率随着胃黏膜病变程度的加重而出现降低趋势(P＞0.05),且癌前病变与Hp感染有相关性(P＜0.05).结论 术后残胃黏膜病变与Hp感染密切相关.     

不同胃黏膜病变中幽门螺杆菌感染与环氧合酶表达相关性分析

幽门螺杆菌(Hp)感染与慢性胃炎、胃癌的发生有密切关系。动物实验已证实，Hp慢性感染易引起胃黏膜向恶性转化，但致癌机制未完全明了，环氧合酶(COX)是前列腺素(PG)合成的限速酶，COX至少有两种亚型，即COX-1和COX-2。国内外研究表明，COX-2与胃癌的发生密切相关。现已证明，Hp感染诱导胃黏膜COX-2表达，然而，Hp感染及其诱导的COX-2表达在胃黏膜病变转变过程中的相关性尚不清楚.     

幽门螺杆菌感染对血清胃蛋白酶原诊断价值的影响

背景:血清胃蛋白酶原(PG)能反映胃黏膜功能状态,可作为胃黏膜病变的血清学标记。幽门螺杆菌(Hp)感染可引起胃黏膜病理改变,有文献报道Hp感染可影响血清PG水平。目的:探讨Hp感染对血清PG对胃黏膜病变诊断价值的影响。方法:纳入2014年7月—2015年6月于嘉兴学院附属第一医院行胃镜和活检病理检查(包括Giemsa染色)以及血清PG检测的患者1 216例,根据病理诊断和Hp状态分组,分析各组间PG水平的差异。结果:不同胃黏膜病变组间,Hp阳性患者血清PGⅠ、PGⅡ水平、PGⅠ/Ⅱ比值(PGR)以及PG(+)(PGⅠ≤70μg/L且PGR3.0)者占比差异均无统计学意义(P0.05),Hp阴性患者PGⅠ、PGⅡ水平、PGR以及PGⅠ≤70μg/L者、PGR3.0者占比差异均有统计学意义(P0.05)。同一胃黏膜病变组内,Hp阳性患者PGⅠ水平和PGR低于Hp阴性患者,PGⅡ水平和PG(+)者占比高于Hp阴性患者,部分组间差异有统计学意义(P0.05)。结论:Hp感染可影响血清PG水平,缩小不同胃黏膜病变间PG水平的差异,加大与同种胃黏膜病变Hp阴性患者间PG水平的差异,降低PGR,提高PG(+)率。对于Hp阴性患者,可能需设定新的PG标准以提高其对胃黏膜病变的诊断敏感性。     

胃蛋白酶原水平与幽门螺旋杆菌感染及胃黏膜疾病分析

目的:探讨胃蛋白酶原(PG)水平与及幽门螺旋杆菌(Hp)感染及胃黏膜疾病的关系。方法:选取2016-09—2018-09有消化道症状且经胃镜诊断为慢性胃病的316例患者作为研究对象,根据患者病情分为浅表性胃炎76例,消化性溃疡98例,慢性萎缩性胃炎81例,胃癌61例。另选取同期健康体检者90例为健康组。采用化学发光法检测5组血清中胃蛋白酶原Ⅰ(PGⅠ)和胃蛋白酶原Ⅱ(PGⅡ)及两者比值(PGR),采用~(13)C尿素呼气试验和胶乳免疫法检测5组Hp感染状态;采用Spearman相关性分析PGⅠ、PGⅡ、PGR与Hp感染的相关性,分别采用ROC曲线评价PGⅠ、PGⅡ、PGR、Hp对胃黏膜病变的诊断价值,采用Logistic回归分析影响胃黏膜病变的独立危险因素。结果:随着胃黏膜病变的加重,PGⅠ和PGR水平下降,各组间差异有统计学意义(P0.05);Hp阴性患者的PGⅠ、PGⅡ和PGR显著高于Hp阳性患者,差异有统计学意义(P0.05);Spearman相关性分析表明,Hp感染与PGⅠ、PGⅡ、PGR呈负相关性,胃黏膜病变与PGⅠ、PGⅡ、PGR呈负相关性(P0.05);Logistic回归分析结果表明PGⅠ72、PGR3、Hp阳性是影响胃黏膜病变的独立危险因素;PGⅠ、PGⅡ、Hp、PGR的ROC曲线下面积(AUC)分别为0.545、0.726、0.738、0.806。结论:PGⅠ72、PGR3、Hp阳性有助于胃黏膜病变的病情诊断,Hp阴性胃黏膜病变患者PGⅠ、PGⅡ和PGR显著高于Hp阳性患者。     

幽门螺杆菌感染与人类免疫缺陷病毒感染者胃黏膜上皮细胞凋亡的关系

幽门螺旋杆菌(Hp)感染是胃黏膜病变过程中重要的致病或促进因素,长期感染可导致胃黏膜萎缩、肠上皮化生及异型增生,甚至癌变.普通人群中Hp感染可增加胃黏膜上皮细胞凋亡和Fas表达,但在人类免疫缺陷病毒(HIV)感染患者中的情况少见报道.本研究旨在对HIV患者胃黏膜上皮细胞凋亡和Fas表达进行检测,并与有消化道症状的人群比较,探讨Hp感染与HIV感染者胃黏膜上皮细胞凋亡的关系.     

老年2型糖尿病与幽门螺杆菌感染的相关性分析

目的探讨老年人2型糖尿病(T2DM)与幽门螺杆菌(Hp)感染的相关性。方法老年T2DM患者85例,其中有恶心、腹胀等上消化道症状的45例,无上消化道症状的40例;糖尿病病程在1年以内者38例,1年以上者47例。通过胃镜取组织活检和进行黏膜快速尿素酶试验来检测Hp感染的发生率。结果 T2DM患者Hp感染率为62.4%,有上消化道症状与无上消化道症状者Hp感染率、胃黏膜病变检出率比较均有统计学差异(P均<0.05);糖尿病病程>1年与1年内者Hp感染率比较有统计学差异(P<0.05)。结论 Hp感染导致的胃黏膜病变与糖尿病上消化道症状有密切关系,对有上消化道症状的糖尿病患者进行Hp检测和抗Hp治疗有重要的临床意义。     

胃癌组织中Hp感染与p16、c-erb-2的表达及临床意义

目的 探讨抑癌基因p16和c-erb-2癌基因蛋白在胃癌组织中的表达及幽门螺杆菌(Hp)感染在胃癌发生发展中的作用.方法 利用39例肠型胃癌,31例弥漫型胃癌和56例对照组胃癌组织及正常胃黏膜组织石蜡切片,Warthin-starry法检测Hp,胃癌组免疫酶组化S-P法检测p16、c-erb-2基因蛋白.结果 胃癌组Hp感染率高于对照组,肠型和弥漫型胃癌间Hp感染率差异无统计学意义.胃癌组中,Hp感染与c-erb-2及p16蛋白阳性表达有关.结论 Hp感染与p16和c-erb-2蛋白的联合表达可作为胃癌发生发展、判断预后的参考指标.     

幽门螺杆菌感染与胃癌及癌前病变中c-myc、p53、C-erbB-2及bcl-2蛋白表达关系的研究

目的 观察胃癌、癌前病变中幽门螺杆菌(Hp)感染情况及其与c-myc、p53、c-erbB-2、bcl-2在胃癌及癌前病变中的表达关系,探讨Hp在胃癌、癌前病变发生及发展中的作用以及探索从癌前病变到癌变过程中的基因变化规律.方法 放大内镜及超声内镜检查收集103例胃黏膜标本,用免疫组织化学染色方法检测Hp感染及不同组织间c-myc、p53、c-erbB-2、bcl-2的表达.结果 c-myc、p53、c-erbB-2和bcl-2阳性表达率在胃癌组及癌前病变组中呈过度表达,与正常对照组相比有显著性差异(P<0.05).此外,Hp感染组c-myc、p53、c-erbB-2及bcl-2同时表达者为5例(9.4%);与无Hp感染组相比有显著性差异(P<0.01).结论 胃癌及癌前病变中组织存在c-myc、p53、c-erbB-2、bel-2多个表达,与Hp感染密切相关.     

难治性幽门螺杆菌感染中西医协作治疗策略的探讨

幽门螺杆菌(Helicobacter pylori,Hp)感染是胃癌最重要的可控危险因素,作为一种感染性疾病,其根除治疗是临床医生最关注的问题之一。《第六次全国幽门螺杆菌感染处理共识报告》明确了连续规范的不同药物组合方案根除治疗≥2次仍未成功是为难治性Hp感染。Hp耐药为难治性Hp感染的重要原因,中医药在提高根除率、减少不良反应、减少抗生素使用、治疗耐药性Hp及改善胃黏膜病变等方面具有独特优势,因此中西医协作治疗是根除治疗的有效路径。标本兼治的分阶段综合疗法是目前根除难治性Hp感染比较成熟的中西医协作方案,可改善Hp感染导致的胃黏膜病变,实现对Hp感染胃炎的全程管理。     

胃癌和癌前病变中幽门螺杆菌及环氧化酶-2和p53的表达及相关性研究

[目的]检测慢性胃炎、胃癌前病变及胃癌（GGa）的胃黏膜组织中幽门螺杆菌（Hp）,环氧化酶-2（COX-2）和突变型p53的表达,探讨Hp感染在胃癌发生过程中与COX-2、p53动态表达的相关性.[方法]选择经胃镜检查及病理组织学证实为慢性浅表性胃炎（CSG）、慢性萎缩性胃炎（CAG）、肠上皮化生（IM）、不典型增生（Dys）及GCa患者各100例,快速尿素酶试验（HPUT法）和组织学改良Giemsa染色联合检测Hp,通过免疫组化检测Hp感染组和非感染组患者胃黏膜COX-2、p53.[结果]①Hp、COX-2阳性率随病变进展呈上升趋势,Hp阳性率在CAG、IM、Dys、GCa各组中显著高于CSG组（P＜0.05）;COX-2在IM、Dys、GCa各组中与慢性胃炎比较有统计学意义（P＜0.05）;②Hp感染阳性率和COX-2蛋白表达阳性率在胃癌前病变组织中存在相关性（P＜0.05）;③p53阳性率在GCa与CSG、CAG相比差异有统计学意义（P＜0.01）;④在GCa组中,Hp阳性组p53的阳性表达明显高于Hp阴性组（P＜0.05）.[结论]GCa的形成与Hp感染、突变型p53、COX-2等多种因素及其相互作用有关,可视为GCa发生的危险预警信号之一;在GCa高危人群的追踪观察和随访中,进行Hp、p53、COX-2的联合检测,对发现胃癌前病变和GCa有一定临床意义.     

Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions:H.pylori infection, histological types and staging

AIM:To investigate the expression of multiple genes and the behavior of cellular biology in gastric cancer (GC) and other gastric mucosal lesions and their relations to Helicobacter pylori (H. pylori) infection, tumor staging and histological subtypes.METHODS:Three hundred and twenty seven specimens of gastric mucosa obtained via endoscopy or surgical resection, and ABC immunohistochemical staining were used to detect the expression of p53, p16, Bcl-2 and COX-2 proteins.H. pylori was determined by rapid urea test combined with patholo-gical staining or 14 Curea breath test. Cellular image analysis was performed in 66 patients with intestinal metaplasia (IM) and/or dysplasia (Dys). In 30 of them, both cancer and the paracancerous tissues were obtained at the time of surgery. Histolo-gical pattern, tumor staging, lymph node metastasis, grading of differentiation and other clinical data were studied in the medical records.RESULTS:p16 expression of IM or Dys was significantly lower in positive H. pylori chronic atrophic gastritis (CAG) than those with negative H. pylori (CAG: 54.8% vs 88.0%, IM:34.4% vs 69.6%, Dys: 23.8% vs 53.6%, all P < 0.05), Bcl-2 or COX-2 expression of IM or Dys in positive H. pylori cases was signi-ficantly higher than that without H. pylori (Bcl-2: 68.8% vs 23.9%, 90.5% vs 60.7%; COX-2: 50.0% vs 10.8%, 61.8% vs 17.8%; all P <0.05). The mean number of most parame-ters of cellular image analysis in positive H. pylori group was significantly higher than that in negative H. pylori group (Ellipser: 53 plus minus 14, 40 plus minus 12&mgr;m, Area(1): 748 plus minus 572, 302 plus minus 202&mgr;m(2), Area(2): 3050 plus minus 1661, 1681 plus minus 1990&mgr;m(2), all P< 0.05; Ellipseb: 79 plus minus 23, 58 plus minus 15&mgr;m, Ratio-1: 22% plus minus5%,13% plus minus4%,Ratio-2:79% plus minus17%,53% plus minus20%,all P<0.01). There was significant correl-ation between Bcl-2 and histologic pattern of gastric carcinoma, and between COX-2 and tumor staging or lymph node metasta sis (Bcl-2: 75.0% vs16.7%; COX-2: 76.0% vs 20.0%, 79.2% vs 16.7%; all P< 0.05).CONCLUSION:p16, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infec-tion. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.     

Hp感染与胃癌和癌前病变中p53、ras、c-myc基因表达的关系

目的研究幽门螺杆菌（Hp）感染与胃癌（GC）和癌前病变中p53、ras、c-myc基因表达的关系,以探讨其致病机制。方法用美兰和W-S特殊染色方法确定Hp感染,免疫组化SP法检测p53、ras、c-myc基因的表达。结果慢性萎缩性胃炎（CAG）、肠化生（IM）、异型增生（DYS）、GC的Hp感染率均高于慢性浅表性胃炎（CSG）（P均〈0.05）;p53、ras、c-myc基因在GC、DYS中的表达均高于CAG（P均〈0.05）,p53、ras基因在IM中的表达均高于CAG（P〈0.05）;IM中Hp阳性者的p53阳性表达率高于Hp阴性者（P〈0.05）,DYS、GC中Hp阳性者p53、ras、c-myc的表达率高于Hp阴性者（P均〈0.05）。结论Hp感染可能通过调节p53、ras、c-myc基因的表达而促进GC的发生。     

Expression of COX-2 proteins in gastric mucosal lesions

AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions and to assess the relationship between COX-2 expression and type, pathologic stage, differentiation, or lymph node metastasis in gastric cancer and the relationship between COX-2 expression and H pylori infection in gastric mucosal lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical resection. Samples were taken from tumor site and paracancerous tissues, and ABC immunohistochemical staining was used to detect the expression of COX-2 proteins. H pylori was determined by rapid urea test combined with pathological stating/14C urea breath test. RESULTS: The positive rate and staining intensity of mutant COX-2 gene expression in gastric cancer were significantly higher than those in paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant correlation between COX-2 and pathologic stage or lymph node metastasis type of gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was found between COX-2 expression and type or grade of differentiation (P>0.05). COX-2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%, 60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large proportion of gastric cancer tissues compared with matched non-cancerous tissues and was significantly associated with advanced tumor stage and lymph node metastasis. Overexpression of COX-2 plays an important role in tumor progression of gastric cancer. COX-2 may also play a role in the early development/promotion of gastric carcinoma and is associated with H pylori infection.     

幽门螺杆菌感染患者胃癌及癌旁组织中p53,p16和bc1—2基因的表达

研究幽门螺杆菌（Ｈ．ｐｙｌｏｒｉ）感染胃癌得胃粘膜病变中抑癌基因ｐ５３、ｐ１６和关键性凋亡调节基因ｂｃ１－２蛋白的表达,进一步探讨Ｈ．ｐｙｌｏｒｉ在胃癌发生、发展过程中作用的分子机制。方法：胃镜检查及外科手术中取４０例胃癌患者的癌组织和癌旁２ ｃｍ处组织各２块,石蜡包埋,切片ＨＥ染色作病理诊断及免疫组化检查ｐ５３、ｐ１６及ｂｃ１－２蛋白的表达。Ｈ．ｐｙｌｏｒｉ阳性由快速尿素酶试验结合病理染色／＾１     

幽门螺杆菌感染和端粒酶活性以及c-myc、p16基因的表达在胃黏膜癌变中的相关性研究

幽门螺杆菌(H.pylori)是胃癌的主要致病因子,H.pylori、端粒酶和肿瘤相关基因的关系在胃黏膜癌变发生过程中研究很少。目的:观察H.pylori感染和端粒酶活性以及c-myc、p16基因在胃癌中的关系。方法:通过胃镜活检和外科手术获取171例胃组织标本,快速尿素酶试验和H.pylori培养确定有无H.pylori感染;酶联免疫法检测H.pylori感染患者的血清CagA-IgG水平;聚合酶链反应.酶联免疫吸附测定(PCR-ELISA)法检测端粒酶活性;免疫组化法检测c-myc、p16基因的表达。结果:胃癌(GC)组端粒酶表达率显著高于其他各组(P<0.01);慢性萎缩性胃炎(CAG)伴中、重度肠化(IM)组端粒酶和c-myc表达率显著高于CAG伴轻度IM组(P<0.05);而慢性浅表性胃炎(CSG)和CAG伴轻度IM组p16表达率显著高于CAG伴中、重度IM、异型增生(Dys)和GC组(P<0.05)。在CAG伴轻、中、重度IM组中,H.pylori阳性组端粒酶活性比阴性组高:无论有无H.pylori感染,胃癌组端粒酶活性都非常高。在CAG伴中、重度IM、Dys和GC组中,H.pylori阳性亚组c-myc表达显著高于阴性亚组(P<0.01),而在ECAG伴中、重度IM和Dys组中,H.pylori阳性亚组p16基因表达显著低于阴性亚组(P<0.01)。结论:H pylori感染很可能主要通过c-myc基因的激活和p16基因的失活以及其他基因的变化来诱导CAG伴中、重度     

Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis

AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach. METHODS: Gastric biopsies from 138 subjects (30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer) were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining. RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P<0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P<0.01). CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.     

幽门螺杆菌相关胃疾病组织中P53、iNOS的表达

目的通过检测慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生、胃癌组织幽门螺杆菌（Hp）和P53、一氧化氮合成酶（iNOS），探讨Hp感染与P53、iNOS表达的关系，以及Hp感染导致胃癌的可能分子机制。方法应用快速尿素酶试验和组织切片革兰氏染色和血清HpCagA抗体检测Hp，用免疫组化SP法检测上述组织的P53、iNOS。结果慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生、胃癌组织中Hp检出率分别为45．9％、68．4％、71．4％、75．O％、54．8％，病变各组中P53和iNOS表达阳性率与浅表性胃炎组比较均有显著性差异。除浅表性胃炎组、萎缩性胃炎Hp阳性组的P53表达阳性率外，各病变Hp阳性组的P53和iNOS表达阳性率与各组的Hp感染阳性率呈正相关，各病变组中Hp（＋）组的P53和iNOS表达阳性率显著高于Hp（-）组，均有显著性差异。结论Hp与P53和iNOS阳性表达有一定的相关性。     

Helicobacter pylori infection generated gastric cancer through p53-Rb tumor-suppressor system mutation and telomerase reactivation

AIM: To investigate the relationship between Helicobacterpylori (H. pylori) infection and the expressions of the p53,Rb, c-myc, bcl-2 and hTERT mRNA in a series of diseasesfrom chronic gastritis (CG), intestinal metaplasia type Ⅰ or Ⅱ(IMⅠ-Ⅱ), intestinal metaplasia type Ⅲ (IMⅢ), mild or modestdysplasia (DysⅠ-Ⅱ), severe dysplasia (DysⅢ) to gastric cancer(GC) and to elucidate the mechanism of gastriccarcinogenesis relating to H.pyloriinfection.METHODS: 272 cases between 1998 and 2001 wereavailable for the study including 42 cases of CG, 46 cases ofIMⅠ-Ⅱ, 25 cases of IMⅢ, 48 cases of DysⅠ-Ⅱ, 27 cases ofDysⅢ, 84 cases of GC.-H. pyloriinfection and the expressionsof p53, Rb, c-myc, bcl-2 were detected by means ofstreptavidin-peroxidase (SP) immunohistochemical method.HTERT mRNA was detected byin situ hybridization(ISH).RESULTS: The expressions of p53, Rb, c-myc, hTERT mRNAand bcl-2 were higher in the GC than in CG, IN, Dys. Theexpression of c-myc was higher in IMⅢ with-H.pyloriinfection(10/16) than that without infection (1/9) and the positive ratein DysⅠ-Ⅱ and DysⅢ with-H.pyloriinfection was 18/30 and 13/17, respectively, higher than that without infection (4/18 and3/10, respectively). In our experiment mutated p53 had noassociation with H.pyloriinfection, theexpression of Rb wasassociated with-H. pyloriinfection in GC, but the p53-Rb tumor-suppressor system abnormal in DysⅠ-Ⅱ cases, DysⅢⅡ and GCcases with H. pyloriinfection was 21/30, 15/17 and 48/48respecively, higher than non-infection groups (4/18, 3/10, 28/36). Furthermore the level of hTERT mRNA in GC with H. pyloriinfection (47/48) was higher than that without infection (30/36), however the relationship between bcl-2 and H. pyloriwasonly in IMⅢ. C-myc had a close association with hTERT mRNAin DysⅢ and GC (P＝0.0 253,0.0 305 respectively).CONCLUSION: In the gastric carcinogenesis, H. pylorimightcause the severe imbalance of proliferation and apoptosisin the precancerous lesions (IMⅢ and GysⅢ) first, leadingto p53-Rb tumor-suppressor system mutation and telomerasereactivation, and finally causes gastric cancer.     

胃幽门螺杆菌感染与抑癌基因失活的关系

目的探讨胃癌及癌前病变组织中幽门螺杆菌(H.pylori)感染与抑癌基因失活间的相互关系.方法运用DNA-PCR技术检测H.Pylori感染,采用PCR-RFLP,PCR-SSCP,RT-PCR及免疫组化技术分析182例胃癌及癌前病变及正常胃粘膜中抑癌基因APC,MCC,DCC,YNZ22及p53基因的杂合缺失、突变、mRNA及蛋白异常表达.结果胃癌及癌前病变组织中H.pylori的感染率(IM61.7%,Dys 63.3%,GC 42.3%)显著高于正常胃粘膜(17.5%,P＜0.05).但胃癌及癌前病变间H.pylori感染率无显著差别(P＞0.05),胃肠两型胃癌中H.pylori感染率分别为47.1%及42.2%,两者无显著差别(P＞0.05).胃癌及癌前病变组织中存在多种抑癌基因失活.H.pylori感染与癌前病变-肠化生中APC基因异常蛋白表达有关(Hp+43.2%vsHp-13.0%,P＜0.05).胃癌组织H.pylori感染阳性组中APC基因突变(50.0%)及蛋白表达(63.6%)、p53基因蛋白表达率(59.1%)显著高于阴性组(vs16.7%,P＜0.05;vs30.0%,P＜0.01;vs20.0%,P＜0.01).结论幽门螺杆菌感染及多种抑癌基因失活可能与胃癌的发生发展相关,H.pylori感染与APC,p53基因失活可能相关.