幽门螺杆菌及其cagA因子对胃粘膜中原癌基因蛋白表达的影响

目的：探讨幽门螺杆菌（Ｈｐ）感染告别是其细胞毒素相关基因（ｃａｇＡ因子）与胃粘膜中ｂｃｌ－２、Ｂａｘ、ｐ２１－ＷＡＦ１、ｐ１６－ＭＴＳ１蛋白表达异常的关系。从而从分子水平初步探讨ｃａｇＡ是否为一致癌因子及其可能的一致癌的机理。方法：１、利用血抗Ｈｐ－ＩｇＧ、ＲＵＴ、ＰｃＲ－Ｈｐ－ＤＮＡ３种方法２７０例病人的ＨＰ感染情况及ｃａｇＡ＊Ｈｐ感染情况。２、利用免疫组化Ｓ－Ｐ法检测胃癌演化系列胃粘膜中ｂｃｌ     

宫颈腺癌c—erbB—2增殖细胞核抗原表达及其意义

探讨宫颈腺癌组织中ｃ－ｅｒｂＢ－２、增殖细胞核抗原（ＰＣＮＡ）表达的意义。方法采用免疫组化方法检测７４例宫颈腺癌组织ｃ－ｅｒｂＢ－２及ＰＣＮＡ的表达。结果ｃ－ｅｒｂＢ－２阳性表达率为４５．９％,阳性表达组盆腔淋巴结转移率（５７．１％）高于阴性组（２４．０％）,Ｐ＝０．０４１;５年生存率（３２．４％）低于阴性组（５８．９％）,Ｐ＝０．００８。全组ＰＣＮＡ平均标记指数为（４０．６±２０．１）％（０．１％～９１．４％）。淋巴结转移组平均ＰＣＮＡ标记指数（５６．４％）高于阴性组（３８．５％）,Ｐ＝０．０１６。ＰＣＮＡ指数＜４０％组预后较好,ｃ－ｅｒｂＢ－２阳性表达者ＰＣＮＡ标记指数值较高,为４４．７％,阴性表达者为３４．６％,Ｐ＝０．００３。结论ｃ－ｅｒｂＢ－２、ＰＣＮＡ表达状况与宫颈腺癌生物学行为有关,可作为判断预后的参考指标。     

Hp对胃癌,胃MALT淋巴瘤的致恶变作用研究进展

Ｈｐ对胃癌、胃ＭＡＬＴ淋巴瘤的致恶变作用研究进展吴云林幽门螺杆菌（Ｈｐ）不仅与胃、十二指肠球部溃疡和胃炎有关，而且与胃腺癌、胃粘膜相关性淋巴组织（ＭＡＬＴ）淋巴瘤的发生密切相关，并已发现经根除Ｈｐ治疗后，有关肿瘤生长受抑、患者生存期延长［１～４］。本...     

大肠肿瘤中bcl—2及PCNA表达及其意义

目的：研究ｂｃｌ－２及ＰＣＮＡ在大肠肿瘤肆生中的作用及其临床意义。方法：应用免疫组化Ｓ－Ｐ法分别检测大肠正常粘膜、腺瘤及腺癌中ｂｃ；－２及ＰＣＮＡ表达。结果：Ｂｃｌ－２在正常粘膜基底部上皮细胞表达，在腺瘤（７７．５％）和腺癌中（５６．３％）ｂｃｌ－２表达差异显（Ｐ〈０．０５）。高分化腺癌ｂｃｌ－２表达率（６８．４％）显高于差分化腺癌（４１．７％），ＰＣＮＡ表达在正常粘膜，腺瘤及腺癌中依次递增，     

Src基因产物在贲门腺癌中表达的免疫组织化学观察

求实验用ｃ－ｓｒｃ基因表达产物ＰＰ６０（ｃ－ｓｒｃ）的特异性单克隆抗体ＭＡｂ３２７对５６例贲门腺癌、３６例癌旁组织及２０例淋巴结转移癌进行了免疫组织化学研究。结果发现癌旁正常上皮、增生上皮、腺癌及淋巴结转移癌ＰＰ６０（ｃ－ｓｒｃ）阳性率分别为２９．４％（１０／３４）、９４．４％（３４／３６）、７１．４％（４０／５６）、６０．０％（１２／２０）。腺癌及癌旁增生上皮ＰＰ６０（ｃ－ｓｒｃ）表达量显著高于癌旁正常上皮（Ｐ＜０．００５）。不同组织学类型贲门腺癌ＰＰ６０（ｃ－ｓｒｃ）阳性率分别为乳头状腺癌７５．０％（６／８）、管状腺癌８１．８％（１８／２２）、低分化腺癌５０．０％（１０／２０）粘液腺癌１００．０％（６／６），各组间有显著性差异（Ｐ＜０．０５）。且粘液腺癌、管状腺癌的表达量高于乳头状腺癌和低分化腺癌（Ｐ＜０．００５）。结果提示，ｃ—ｓｒｃ基因激活表达与贲门腺癌发生发展有关，在其癌变过程中ＰＰ６０（ｃ－ｓｒｃ）表达量升高，并与贲门腺癌的组织学类型、分化和转移有关。     

白介素-8在胃癌的表达及其与cag Ahp感染的相关性研究

幽门螺杆菌 (Ｈｐ)感染 ,特别是携带细胞毒素相关基因Ａ(ｃａｇＡ)的Ｈｐ感染与胃癌的发生密切相关。白介素 8(ＩＬ 8)在Ｈｐ感染所致的胃炎中起重要作用。我们采用流式细胞术对胃癌及相应的癌旁正常组织中ＩＬ 8蛋白的表达水平进行定量检测 ,并对ｃａｇＡＨｐ感染阳性及阴性的胃癌组织中ＩＬ 8的含量进行分析 ,以探讨ｃａｇＡＨｐ感染对ＩＬ 8表达的影响。一、资料与方法1 标本 :收集我院肿瘤科 2 7例胃癌术后标本 (包括癌组织、癌旁正常胃黏膜 )。男 17例 ,女 10例 ,年龄 4 6～ 73岁。均经组织学病理诊断。每例标本一分为二 ,分别进行Ｉ…     

Src基因产物在贲门腺癌中表达的免疫组织化学观察

本实验用ｃ－ｓｒｃ基因表达产物ＰＰ６０＾ｃ－ｓｒｃ的特异性单克隆抗体ＭＡｂ３２７对５６例贲门腺癌、３６例癌旁组织及２０例淋巴结转移癌进行了免疫组织化学研究，结果发现癌旁正常上皮、增生上皮、腺癌及淋巴结转移癌ＰＰ６０＾ｃ－ｓｒｃ阳性率分别为２９．４％（１０／３４）、９４．４％（３４／３６）．７１．４％（４０／５６）．６０．０＾（１２／２０）。腺癌及癌旁增生上皮ＰＰ６０＾ｃ－ｓｒｃ表达量显著高于癌旁正     

上消化道癌高低发区幽门螺旋杆菌感染与胃癌

目的：研究江苏上消化道癌高发区淮安市、低发区邳州市幽门螺旋杆菌（Ｈｐ）感染与胃癌发生的关系。方法：用酶联免疫法及乳胶凝集法检测７９例胃癌、７７例食管癌、１５６例患者亲属和１００名一般居民对照者血浆中Ｈｐ抗体,结果：低发区胃癌患者组Ｈｐ感染率（６６．６７％）显著高于发区（３８．６４％）,两地区其他组之间Ｈｐ感染率无显著差异,低发区ＨＰ感染者胃癌的危险性显著升高（ＯＲ３．６１,９５％ＣＩ１．０１－１２     

细胞周期蛋白、细胞增殖核抗原在胸腺瘤中的表达及意义

目的：研究细胞周期蛋白（ｃｙｃｌｉｎＤ１）、细胞增殖核抗原（ＰＣＮＡ）在胸腺瘤中表达及意义。方法：用免疫组织化学方法（Ｓ－Ｐ）法,检测１８例良性胸腺瘤、２０例侵袭性胸腺瘤和１６例胸腺癌标本ｃｙｃｌｉｎＤ１、ＰＣＮＡ。结果：在３组胸腺肿瘤中ｃｙｃｌｉｎＤ１阳性表达分别为５／１８（２７．７８％）、１３／２０（６５．００％）、１４／１６（８７．５０％）（Ｐ〈０．０５）;ＰＣＮＡⅢ－Ⅳ指数分别为：５／１８     

胃的肝样腺癌的临床病理分析

目的 研究胃的肝样腺癌（ｈｅｐａｔｏｉｄ ａｄｅｎｏｃａｒｃｉｎｏｍａ ｏｆ ｔｈｅ ｓｔｏｍａｃｈ，ＨＡＳ）和病理形态和临床特点。方法 采用常规ＨＥ染色和免疫组织化学方法对３例胃的肝样腺癌进行研究。结果 ３例ＨＡＳ细胞胞质内均有甲胎蛋白（ＡＦＰ），α－抗胰糜蛋白酶（ＡＣＴ）和α－抗胰蛋白酶（ＡＡＴ）表达。肿瘤的发病部位以胃窦部多见，３例均有局部胃壁脉管浸润和局部淋巴结转移，其中２例有肝转移，分别     

Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation

Helicobacter pylori has been assigned as a class I carcinogen because of its relation to gastric adenocarcinoma. Chronic H. pylori infection may lead to severe gastritis, glandular atrophy (AT), and intestinal metaplasia (IM). Strains secreting the vacuolating toxin VacA and producing the cytotoxin-associated antigen CagA (type 1 strains), as well as the blood group antigen binding adhesin (BabA) targeting Lewis(b) antigens, have been associated previously with distal gastric adenocarcinoma (M. Gerhard et al., Proc. Natl. Acad. Sci. USA, 96: 12778-12783, 1999) and may therefore also be related to lesions preceding gastric cancer. Antral and corpus biopsies were collected from 451 patients; 151 were H. pylori positive, as determined by PCR. Gastric biopsies were histologically evaluated for activity of gastritis (G0-G3, granulocyte infiltration), chronicity of gastritis (L1-L3, lymphocyte infiltration), and the presence of IM and/or AT according to the Sydney classification. Simultaneously, the presence of bacterial genes encoding virulence and adherence factors (racAs1/s2, cagA, and babA2) was determined by PCR. The presence of cagA+ and vacAs1 (alone or combined) both correlated with activity and chronicity of gastritis (P < 0.05); however, the overall prevalence of these genes was 60 or 72%, respectively, and was thus relatively frequent. The babA2 gene, encoding the adhesin BabA, was detected in 38% of infected patients and was correlated with the activity of gastritis in antrum and corpus (P < 0.005). cagA+/vacAs1+ strains (suggesting the presence of type 1 strains) that were also babA2 positive were detected more frequently in patients with severe histological alterations (such as G3, IM, or AT) compared with subjects without these changes (P < 0.01). cagA+/vacAs1+ strains that were babA2 negative, however, lacked a significant correlation with severe histological changes, activity, or chronicity of gastritis in antrum and corpus. Adherence of H. pylori via BabA appears to be of importance for efficient delivery of VacA and CagA and may play a special role in the pathogenesis of severe histological changes.     

胃癌及癌前病变与幽门螺杆菌感染相关性的临床分析

目的:测定幽门螺杆菌在萎缩肠化生胃炎,异型增生及胃癌中感染情况,探讨Hp与它们的相关性。方法:萎缩肠化生胃炎(A组)患者342例,异型增生(B组)229例,胃癌患者(C组)298例,采用Hp抗体ELISA法检测血清抗Hp-IgG抗体。结果:肠化生患者较非肠化生胃黏膜中的Hp感染多见。异型增生和胃癌的Hp感染率均高于萎缩性胃炎组(P<0.05),异型增生和胃癌两者间的Hp感染率亦存在差异(P<0.05)。幽门螺杆菌感染的萎缩肠化生胃炎及异性增生较非幽门螺杆菌感染者发生癌变的差异性显著,P<0.05;幽门螺杆菌感染的胃癌5年生存期显著短于非感染者,P<0.05。结论:Hp感染与萎缩肠化生胃炎,异型增生及胃癌有密切相关性,并缩短萎缩肠化生胃炎,异型增生癌变时间,缩短胃癌5年生存时间。     

Patients younger than 40 years with gastric carcinoma: Helicobacter pylori genotype and associated gastritis phenotype.

BACKGROUND: In the general population, Helicobacter pylori (H. pylori), particularly the cagA positive strain, has been associated with intestinal-type gastric carcinoma. Gastric carcinomas are rarely observed in patients age < or = 40 years. Host-related factors have been thought to be more important than environmental agents in these early-onset cancers. The aim of this study was to ascertain the possible role of H. pylori infection and that of cagA positive strains in the development of gastric carcinoma in these young patients. METHODS: In this case-control study, 105 gastric carcinoma patients (male-to-female ratio = 1.1; mean age, 34.4 years; range, 16-40 years) and an equal number of controls (matched for gender and age) were retrospectively selected from the same geographic area. The phenotypes of gastritis and H. pylori were histologically assessed, and the presence of the ureC gene, which is indicative of H. pylori infection, and the cagA genotype were determined by polymerase chain reaction. Gastric carcinoma risk was calculated by both univariate and multivariate statistical methods, taking into account the cancer phenotype, the gastritis phenotype detected in both patients and controls, and the H. pylori genotype. RESULTS: For 74 diffuse and 31 intestinal gastric carcinomas, multivariate logistic regression analysis produced results consistent with those of univariate statistical tests, showing a significant association between gastric carcinoma and both H. pylori infection (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.52-5.11) and cagA positive status (OR = 2.94; 95% CI = 1.56-5.52). CONCLUSIONS: In young Italian patients with gastric carcinoma, the significant association with cagA positive H. pylori infection suggests that the bacterium has an etiologic role in both diffuse-type and intestinal-type gastric carcinoma.     

Regulation of gastric carcinogenesis by Helicobacter pylori virulence factors

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes. We previously reported that an in vivo adapted H. pylori strain, 7.13, induces gastric adenocarcinoma in rodent models of gastritis. In the current study, we used carcinogenic strain 7.13 as a prototype to define the role of virulence constituents in H. pylori-mediated carcinogenesis. Mongolian gerbils were infected with wild-type strain 7.13 or cagA(-), vacA(-), or oipA(-) mutants for 12 to 52 weeks. All infected gerbils developed gastritis; however, inflammation was significantly attenuated in animals infected with the cagA(-) but not the vacA(-) or oipA(-) strains. Gastric dysplasia and cancer developed in >50% of gerbils infected with either the wild-type or vacA(-) strain but in none of the animals infected with the cagA(-) strain. Inactivation of oipA decreased beta-catenin nuclear localization in vitro and reduced the incidence of cancer in gerbils. OipA expression was detected significantly more frequently among H. pylori strains isolated from human subjects with gastric cancer precursor lesions versus persons with gastritis alone. These results indicate that loss of CagA prevents the development of cancer in this model. Inactivation of oipA attenuates beta-catenin nuclear translocation and also decreases the incidence of carcinoma. In addition to defining factors that mediate H. pylori-induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states.     

Hp感染与胃癌组织中Bcl-2、Bax表达的相关性研究

目的 揭示Bcl-2,Bax在胃癌组织的表达与Hp感染的相关性.方法 采用快速尿素酶试验及组织学改良Giemsa染色法联合检测130例胃癌组织与70例慢性胃炎组织中Hp感染情况,免疫组织化学PV9000法,检测130例胃癌组织与70例慢性胃炎组织中Bcl-2,Bax蛋白的阳性表达情况.结果 Hp(+)组Bcl-2蛋白的阳性表达率明显高于Hp(-)组(P<0.01);胃癌组织中Hp感染与Bcl-2蛋白表达之间存在正相关关系(P<0.01,r=0.288);Hp(+)组Bax蛋白的阳性表达率明显低于Hp(-)组(P<0.01);胃癌组织中Hp感染与Bax蛋白表达之间存在负相关关系(P<0.01,r=-0.536).结论 Hp感染与Bcl-2蛋白表达存在正相关性,与Bax蛋白表达存在负相关性,提示Hp感染与细胞凋亡,二者可能共同参与胃癌的发生发展过程.     

Virulence Genes of Helicobacter pylori in Gastritis,Peptic Ulcer and Gastric Cancer in Laos

Background: Helicobacter pylori (H. pylori) infection is an established cause of peptic ulcers and gastric cancer.The aim of this study was to identify H. pylori genotypes and to examine their associations with geographicalregions and gastritis, peptic ulcers and gastric cancer in Laos. Materials and Methods: A total of 329 Lao dyspepticpatients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010 - March 2012were enrolled. Two biopsy specimens (one each from the antrum and corpus) were obtained for CLO testing andonly CLO test-positive gastric tissue were used to extract DNA. PCR and sequencing were identified for variantsof the cagA and vacA genotypes. Results: Some 119 Laos patients (36.2%) were found to be infected with H. pyloriincluding 83 with gastritis, 13 with gastric ulcers (GU), 20 with duodenal ulcers (DU) and 3 with gastric cancer.cagA was detected in 99.2%. East-Asian-type cagA (62%) and vacA s1c (64.7%) were predominant genotypes inLaos. vacA s1c-m1b was significantly higher in GU than gastritis (53.8% vs. 24.1%; P-value=0.04) whereas vacAs1a-m2 was significantly higher in DU than gastritis (40.0% vs. 16.9%; P-value=0.03). East-Asian-type cagA andvacA s1c were significantly higher in highland than lowland Lao (100% vs. 55.8%; P-value=0.001 and 88.2% vs.61.5%, P-value=0.03 respectively). Conclusions: H. pylori is a common infection in Laos, as in other countriesin Southeast Asia. The cagA gene was demonstrated in nearly all Laos patients, cagA and vacA genotypes beingpossible important factors in explaining H. pylori infection and disease outcomes in Laos.     

SOD在Hp感染阳性的胃癌、胃粘膜不典型增生及慢性胃炎中表达的研究

目的　观察 SOD在 Hp感染与胃癌、胃粘膜不典型增生及慢性胃炎之间所起的作用。方法　采用免疫组织化学方法观察 SOD在 Hp感染阳性胃癌、胃粘膜不典型增生及慢性胃炎组织中的表达。结果　 Hp感染的阳性胃癌、胃粘膜不典型增生及慢性胃炎组织中的 SOD表达无变化。而在胃癌、胃粘膜不典型增生及慢性胃炎三者之间 SOD的表达有差异。结论　胃癌、胃粘膜不典型增生及慢性胃炎组织中 SOD的表达不受 Hp感染的影响。监测胃粘膜中 SOD的变化 ,可为早期诊断胃癌提供帮助     

Reversibility of Heterotopic Proliferative Glands in Glandular Stomach of Helicobacter pylori-infected Mongolian Gerbils on Eradication

Helicobacter pylori ( Hp ) infection is an important factor in human gastric disorders. Mongolian gerbils can be easily infected with Hp and represent excellent experimental models to clarify the role of Hp in chronic active gastritis, peptic ulcers, intestinal metaplasia, and gastric carcinoma. We have proved the enhancing effects of Hp infection on all histological types of gastric cancers in Mongolian gerbils exposed to chemical carcinogens. Heterotopic proliferative glands (HPGs) also frequently develop with Hp infection in the glandular stomach of infected gerbils, with a slightly dysplastic change of constituent cells. Distinguishing reversible inflammatory lesions from true neoplasms upon eradication is necessary for further biological or histochemical investigations using this model. We employed an experimental model of long-term Hp infection and eradication in gerbils. HPGs finally developed with a phenotypic shift of intestinalization with Paneth cells. After eradication, HPGs were obviously reduced, and gastric lesions in mucosa also improved with few remnants of the former injury. This shows that reversible HPGs are frequently induced solely by Hp infection in this annual species, and are related to severe gastritis, rather than being malignant in character. Thus, distinguishing reversible lesions from true neoplasms is necessary to investigate the relationship of Hp infection and gastric carcinogenesis in this animal model.     

Reversibility of heterotopic proliferative glands in glandular stomach of Helicobacter pylori-infected Mongolian gerbils on eradication.

Helicobacter pylori (Hp) infection is an important factor in human gastric disorders. Mongolian gerbils can be easily infected with Hp and represent excellent experimental models to clarify the role of Hp in chronic active gastritis, peptic ulcers, intestinal metaplasia, and gastric carcinoma. We have proved the enhancing effects of Hp infection on all histological types of gastric cancers in Mongolian gerbils exposed to chemical carcinogens. Heterotopic proliferative glands (HPGs) also frequently develop with Hp infection in the glandular stomach of infected gerbils, with a slightly dysplastic change of constituent cells. Distinguishing reversible inflammatory lesions from true neoplasms upon eradication is necessary for further biological or histochemical investigations using this model. We employed an experimental model of long-term Hp infection and eradication in gerbils. HPGs finally developed with a phenotypic shift of intestinalization with Paneth cells. After eradication, HPGs were obviously reduced, and gastric lesions in mucosa also improved with few remnants of the former injury. This shows that reversible HPGs are frequently induced solely by Hp infection in this animal species, and are related to severe gastritis, rather than being malignant in character. Thus, distinguishing reversible lesions from true neoplasms is necessary to investigate the relationship of Hp infection and gastric carcinogenesis in this animal model.     

胃蛋白酶原C基因插入-缺失多态和幽门螺杆菌感染的交互作用与胃癌发病风险

目的 探讨胃癌发生发展过程中,胃蛋白酶原C(PGC)基因插入-缺失多态与幽门螺杆菌(Hp)及其不同基因亚型菌株感染的交互作用.方法 1:1频数配伍,选择基本正常(NOR)、胃糜烂溃疡(GU)、萎缩性胃炎(AG)和胃癌(Gc)各141例,分析PGE基因多态和Hp感染的交互作用.同时选择177例Hp感染阳性者,分析PGC基因多态与不同基因亚型Hp感染的交互作用.以聚合酶链反应(MR)检测PGC基因多态型及Hp基因亚型.以酶联免疫吸附实验(ELISA)检测血清Hp-IgG抗体.结果 PGG基因多态与Hp感染两因素交互作用,PGC等位基因1纯合型、Hp-IgG阳性者罹患GU、AG和GC的OR值分别为8.69、11.16和10.61(P值分别为0.049、0.02和0.03),交互作用指数分别为5.40、6.48和4.34,归因比分别为0.721、0.770和0.697.P02基因多态与不同基因亚型Hp感染对于AG和GC患病均无交互作用.结论 GC发生发展过程中,PGC基因多态与Hp感染存在正交互作用,而与不同基因亚型Hp菌株感染无交互作用.