幽门螺杆菌感染和环氧合酶-2表达在胃癌发生中的作用

目的探讨幽门螺杆菌 (Hp) 感染和环氧合酶-2(COX-2)表达在胃癌发生中的作用.方法 138例胃镜活检标本包括慢性非萎缩性胃炎30例,慢性萎缩性胃炎85例(其中伴有中度以上肠化生45例,中、重度异型增生12例),和胃癌23例.快速尿素酶试验和组织学改良Giemsa染色联合检测Hp,免疫组化检查COX-1和COX-2表达.结果胃癌的Hp阳性率为69.6%,显著高于慢性非萎缩性胃炎的36.7%(P<0.05).慢性非萎缩性胃炎、慢性萎缩性胃炎、肠化生、异型增生和胃癌的COX-2表达率分别为10.0%、37.6%、37.8%、41.7%和69.6%,而不同胃黏膜病变中COX-1表达无明显差异.慢性萎缩性胃炎、肠化生和异型增生中Hp阳性病例的COX-2表达显著高于Hp阴性病例(P<0.01).结论 Hp感染及其诱导的COX-2表达可能是胃癌发生的早期事件之一.     

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。     

幽门螺杆菌感染与胃癌前病变及胃癌的相关性研究

 目的　从病理形态学方面探讨幽门螺杆菌 ( Helicobacter pylori,Hp)感染与胃粘膜癌前病变和胃癌的关系。方法　采用 HE、Warthin- Starry及 HID- AB( p H2 .5) - PAS染色法 ,对 1 51例胃镜活检及手术切除胃标本中慢性萎缩性胃炎 ( CAG)、胃上皮不典型增生 ( gastric epithelialdysplasia,GED)、肠上皮化生 ( intestinal metaplasia,IM)及胃癌 ( Ca)组织中 Hp的感染状况进行观察 ,并对 Hp的感染与各病变间的关系进行对比研究。结果　本组病例胃粘膜 Hp检出率为 66.2 %( 1 0 0 /1 51 )。 Hp的感染主要见于胃贲门以外部位 ,尤其胃窦部多见 ,但 Hp感染与 CAG、IMI、 型及弥漫型胃癌的发生无明显关系 ( ( P>0 .0 5) ,与 GED(尤其 GED 、 级 )、IM 型和肠型胃癌的发生显著相关 ( P<0 .0 5)。结论　Hp感染是导致胃粘膜 型肠上皮化生、中度和重度不典型增生及肠型胃癌的重要致病因素 ,应引起高度重视.     

胃癌及癌前病变中p53蛋白表达与HP感染的关系

目的 观察幽门螺旋杆菌(HP)感染后胃癌、胃粘膜异型增生和胃粘膜肠化生中p53蛋白表达的特点,探讨HP在胃癌发生发展过程中的作用.方法 应用免疫组化SP法及美兰染色,对胃癌79例,胃粘膜异型增生23例,胃粘膜肠化生21例进行p53蛋白表达及HP检测并与56例慢性胃炎对比分析.结果 胃癌组、胃粘膜异型增生组及胃粘膜肠化生组的HP感染率及p53蛋白阳性表达率均明显高于慢性胃炎组(P＜0.05);122例HP阳性者p53蛋白表达80例,阳性率65.6%,58例HP阴性者p53蛋白表达5例,阳性率8.6%,两者比较,差异显著(P＜0.05).结论 在慢性胃炎、胃粘膜肠化生、胃粘膜异型增生、胃癌的进展过程中,p53蛋白的表达水平在增高.HP感染在胃癌发生、发展过程中起一定作用.p53蛋白的表达可能是HP致癌的作用机制之一.     

Hp感染与p16基因甲基化在胃癌发生中的作用

目的 探讨幽门螺杆菌（Hp）感染与p16基因甲基化在胃癌发生发展中的作用及其作用机制。方法 应用MSP技术检测75例不同胃黏膜组织中p16基因甲基化状态,应用硼酸美蓝法检测Hp感染情况。结果 75例标本中19例测得p16基因甲基化（25.3%）,其中在萎缩性胃炎、重度异型增生和胃癌组中分别测得2例（11.1%）、4例（23.5%）和13例（43.3%）,而在慢性浅表性胃炎和轻 中度异型增生组中未检测到p16基因甲基化。异型增生组和胃癌组中p16基因甲基化率显著高于浅表性胃炎（P<0.05）;75例标本中Hp感染阳性率为56%（42/75）,其中在慢性浅表性胃炎、萎缩性胃炎、异型增生和胃癌组中分别测得2例（20%）、12例（66.7%）、12例（70.6%）和16例（53.3%）。萎缩性胃炎和异型增生组中Hp感染阳性率显著高于浅表性胃炎（P<0.05）。42例Hp感染阳性的标本中测得16例发生p16基因甲基化（38.1%）,33例Hp感染阴性的标本中只测得3例p16基因发生甲基化,Hp感染与p16基因甲基化呈正相关（P<0.05）。结论 Hp感染、p16基因甲基化可能是胃癌的发生发展过程中的重要因素,Hp感染可能与p16基因启动子甲基化率增高有关。     

syndecan-1在胃黏膜癌变不同阶段组织中的表达及意义

目的探讨黏附分子syndecan-1在胃癌癌变各阶段的表达及其在胃癌发生和转移中的意义。方法选取56例慢性浅表性胃炎、50例慢性萎缩性胃炎、59例肠化生、61例中重度异型增生、55例无淋巴结转移胃癌、57例有淋巴结转移胃癌的病理组织蜡块,采用免疫组化ABC法检测syndecan-1在胃黏膜癌变各阶段组织中的表达。结果慢性浅表性胃炎组、慢性萎缩性胃炎组、肠化生组、中重度异型增生组、无淋巴结转移胃癌组、有淋巴结转移胃癌组syndecan-1阳性表达率分别为96.43%、98.00%、100.00%、91.80%、45.45%和24.56%。慢性浅表性胃炎组、慢性萎缩性胃炎组、肠化生组3组间差异无统计学意义(P>0.05);肠化生组与中重度异型增生组、中重度异型增生组与无淋巴结转移胃癌组、无淋巴结转移胃癌组与有淋巴结转移胃癌组之间差异均有统计学意义(P均< 0.05)。低分化胃癌组syndecan-1阳性表达率为24.62%,明显低于中、高分化胃癌组(42.55%)。结论黏附分子syndecan-1表达下调与胃癌的发生有关,并可能进一步促进胃癌转移。     

胃癌单克隆抗体MG_7对胃癌高危人群检查的临床意义

目前多数学者认为胃癌癌前疾病(或状态)包括慢性萎缩性胃炎(CAG),冒息肉,肥厚性胃炎,残胃,恶性贫血,胃溃疡;胃癌癌前病变包括胃粘膜异型增生,肠化生。胃癌高危人群即指患有上述疾病或病变的人群。现国内外经验认为在高危人群中进行普查与随访是发现早期胃癌的最有效方法。为了进一步在高危人群中寻找癌变规律,缩小随访范围,我们选其中常见的CAG,残胃,胃息肉,胃溃疡(GU),及伴异型增生和肠化生病变的活检胃粘膜组织,应用胃癌单克隆抗体MG_7,进行ABC免疫酶标组化染色,观察MG_7的相应抗原     

CREB1和CREB3在胃癌及癌前病变组织中的表达及其临床意义

目的 探究环磷腺苷反应元件结合蛋白1(CREB1)和环磷腺苷反应元件结合蛋白3(CREB3)在胃癌及癌前病变组织中的表达及临床意义。方法 收集慢性浅表性胃炎40例,慢性萎缩性胃炎伴肠化生40例,异型增生40例,胃癌50例,采用免疫组化法检测CREB1和CREB3在四种组织中的表达,并分析其与临床病理参数的关系。另收集同期新鲜组织慢性浅表性胃炎、慢性萎缩性胃炎伴肠化生、胃癌共30例,应用蛋白印迹法(Western blot)检测CREB1和CREB3在不同胃组织中的表达。利用Kaplan-Meier plotter分析CREB1和CREB3的表达与胃癌患者总生存时间(OS)和无进展生存时间(FP)的相关性。利用STRING数据库分析CREB1和CREB3在信号通路中的位置以及与之相关的上下游基因。结果 免疫组化显示：胃癌组、异型增生组、萎缩性胃炎伴肠化生组CREB1、CREB3阳性表达率明显高于慢性浅表性胃炎组(P<0.05);并且CREB1、CREB3在胃癌组的阳性表达率明显高于慢性萎缩性胃炎伴肠化生组(P<0.05),但与异型增生组无统计学差异(P>0.05)。临床...     

胃粘膜肠化生细胞增值状态分型的研究

应用免疫组织化学方法检测230例胃粘膜病变中增殖细胞核抗原（PCNA）的表达情况，计算细胞增殖指数（PI）、探讨胄粘膜肠化生的增殖状态分型以及肠化生细胞增殖分型与肿瘤相关基因蛋白产物的关系。结果显示正常或慢性浅表性胃炎、伴肠化生慢性萎缩性胃炎、伴异型增生萎缩性胃炎以及胃腺癌的PI逐渐增高，差异非常明显（P＜0．0）。根据胃粘膜肠化生细胞的PI分布，进行畅化生细胞的增殖状态分型：高增殖状态型为PI≥40，中增殖状态型为20≤P＜40，低增殖状态型为PI＜20。此分型与各类胃粘膜病变显示较好的相关性，低增殖状态型为正常或基本正常胃粘膜，中增殖状态型为胃粘膜良性病变，高增殖状态型为胃粘膜癌前病变。高增殖状态型肠化生中肿瘤相关基因蛋白产物rasp21、EGFR、h-met的表达以及叵型肠化生的检出率显著高于中、低增殖状态型肠化生（P＜0．05）。提示高增殖状态型肠化生细胞基因表达的异常率增高，且细胞分化不良，更具胃癌前病变的特征。     

胃粘膜肠化生细胞增殖状态分型的研究

应用免疫组织化学方法检测２３０例胃粘膜病变中增殖细胞核抗原的表达情况，计算细胞增殖指数，探讨胃粘膜肠化生的增殖状态分型以及肠化生细胞增分型与肿瘤相关基因蛋白产物的关系。结果显示正常或慢性浅表性胃炎，伴肠化生慢性萎缩性胃炎，伴异型增生萎缩性胃炎以及胃腺癌的ＰＩ逐渐增高；差异非常明显。     

幽门螺旋杆菌感染胃黏膜COX-2和P-gp表达与胃癌发生

背景与目的通过检测幽门螺旋杆菌(Helicobacter Pylori,H.pylori)感染胃粘膜组织环氧合酶-2(Cyclooxygenase-2,COX-2)和多药耐药-1(Multidrug resistance-1,MDR-1)基因表达产物P糖蛋白(P-glycoprotein,P-gp)表达,探讨幽门螺旋杆菌相关胃癌的发生机制,以及P-gp高表达的机制。材料与方法慢性胃炎155例(30例慢性浅表性、40例慢性萎缩性、45例肠化、40例非典型增生)及胃癌80例(肠型40例,弥漫型40例),COX-2和P-gp表达检测选择免疫组化S-P法,H.pylori感染检测采用快速脲素酶及改良Giemsa染色方法。结果H.pylori阳性感染率、COX-2和P-gp的阳性表达率,肠型胃癌均明显高于弥漫型胃癌(P<0.01)。慢性萎缩性胃炎、肠化、非典型增生及肠型胃癌中H.pylori感染与COX-2的表达呈正相关(P<0.01)。H.pylori感染的慢性浅表性胃炎、慢性萎缩性胃炎、肠化、非典型增生及肠型胃癌中COX-2的表达与P-gp的表达也均呈正相关(P<0.01)。结论H.pylori依赖的COX-2表达与P-gp表达有关,可能有助于胃癌形成以及胃癌对化疗抵制。     

胃癌组织中Sonic Hedgehog表达及其与NF-kappaB的关系研究

目的探讨Hedgehog在胃癌及其癌前病变中的表达及与NF-kappaB的关系。方法选择50例萎缩性胃炎、46例肠化生和57例胃癌患者的胃黏膜内镜活检样本,同时选择30例正常人作为对照;分为萎缩性胃炎组、肠化生组、胃癌组和正常黏膜组。通过病理学检测患者Hpylori感染状况。免疫组化法检测Hedgehog和NF-kappaB在不同阶段胃癌组织中的表达差异。流式细胞仪分析各组胃黏膜细胞的周期分布和凋亡率。Western blot检测Hedgehog表达。结果在胃癌的发展过程中,胃黏膜组织中Hedgehog表达水平先降低后升高。NF-kappaB表达水平在正常胃组织、萎缩性胃炎和肠化生组织中无明显变化,但在胃癌组织中表达显著增强。与正常胃黏膜组织比较,萎缩性胃炎、肠化生和胃癌组织中的S期细胞比例更高。细胞凋亡率萎缩性胃炎组和肠化生组较高,而胃癌组较低。抑制NF-kappaB后,Hedgehog蛋白在胃癌组织中的表达降低。结论在胃癌的发展过程中,Hedgehog蛋白表达水平先降低后升高。H pylori感染可能通过激活NF-kappaB,继而增强Hedgehog表达,同时赋予胃癌细胞凋亡抵抗。     

慢性胃病伴肠上皮化生、胃癌与幽门螺旋杆菌感染的关系

目的探讨慢性胃病伴肠上皮化生、胃癌与幽门螺旋杆菌（helicobacter pylore,HP）感染的关系。方法采用warthin—strarry银染色方法,对380例慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织进行HP检测．应用（alcianblue—PH2．5-periodic—schiff,AB—PAS）、（high-iron—diamine-alcianblue—PH2．5,HID-AB）黏液组织化学方法,区别慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织伴有肠上皮化生的类型。结果总例数380例。HP阳性率为69．74％。慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织伴肠上皮化生的HP感染率分别为77．78％、85．71％、100．00％、80．95％。慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡及胃癌的癌旁组织伴肠上皮化生AB—PAS染色阳性率分别为86．84％、91．43％、93．33％、100．00％;HID—AB染色阳性率分别为34．21％、42．86％、53．33％、85．71％。癌旁组织的肠上皮化生中,78．57％为不完全大肠型,慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡伴肠上皮化生中,不完全小肠型比例分别为52．63％、54．28％、53．33％;不完全大肠型比例分别为28．95％、31．43％、20．00％。结论HP感染与慢性胃病伴肠上皮化生及胃癌的发生密切相关。癌旁组织的不完全大肠型肠上皮化生与胃癌的发生密切相关;慢性胃病组织当中的小灶状不完全大肠型上皮化生具有潜在发生癌变的可能性。     

老年患者的幽门螺杆菌（HP）感染与胃癌及癌前病变中C-myc、p16、p53、K-ras和C-erbB-2基因表达

目的探讨老年患者幽门螺杆菌（HP）感染与胃癌及癌前病变中C-myc、p16、p53、K-ras和C．erbB-2基因表达及其临床意义。方法分析老年患者的胃镜检查活检标本116例,HE染色观察胃黏膜的炎症和异型增生变化,特染法检测胃黏膜的肠上皮化生,应用Warthin-stary银染色法检测HP,应用ELISA法检测血清学HPIgG,14C尿素呼气试验（14C-UBT）检测HP,应用免疫组化sP法检测C-myc、p16、p53、K-ras和C-erbB-2基因的表达。结果老年患者在不同胃组织中C-myc、p16、p53基因的表达均有显著差异,而K-ras和C-erbB-2基因表达未见显著性差异。HP感染率以胃癌为最高,其次为胃溃疡。结论本实验通过老年患者的HP检测和观察胃黏膜的炎症和异型增生变化,再结合癌基因和抑癌基因的表达异常,提示萎缩性胃炎异型增生、肠上皮化生和胃癌的HP感染率均高于非萎缩性胃炎。再次表明胃癌与HP感染有一定相关性。     

Helicobacter pylori Infection Promotes Gastric Premalignancies and Malignancies Lesions and Demotes Hyperplastic Polyps: A 5 Year Multicentric Study among Cameroonian Dyspeptic Patients

Background: Helicobacter pylori infection is the most well-known risk factor for gastric mucosa abnormalities. However, some geographic regions with persistent high H. pylori infection rates do not suffer from high gastric mucosa lesions incidence. The aim of the study was to establish the relationship between H. pylori infection and gastric pathological features in Cameroon. Methods: We performed a retrospective study, collecting data from the University Teaching Hospital and the Cameroon Pasteur institute on 1290 patients (mean age 46.31 ± 16.45 years, sex ratio 1.19:1) for whom histological features of the gastric mucosa and H. pylori infection were investigated from 2014 to 2019. Data were extracted from the medical records; hospital computerized databases; or clinical charts of these patients and reviewed according to gender and age of participants. The study was approved by the Ethical Committee of Medical Sciences. Result: Approximately 3% (2.56%) of the sample population were with normal gastric mucosa whereas chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, carcinoma, hyperplastic polyps and MALT lymphoma was found in 75.35, 8.2, 7.7, 2.8, 9.3, 1.55 and 0.8% of cases respectively. Unlike hyperplasia (OR= 0.3838), infected participants were in a high risk to develop gastric lesions with an odds ratio of 1.1775, 1.4866, 1.4415, 1.2088, 0.9408 and 0.9075 for gastritis, atrophic gastric, dysplasia, carcinoma, intestinal metaplasia and MALT lymphoma respectively. Conclusion: our finding showed that chronic gastritis, gastric premalignancies and malignancies are positively link to Helicobacter pylori infection and that hyperplastic polyp is inversely associated with H. pylori infection in our milieu.     

Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study

To investigate the relationship between p16 methylation and Helicobacter pylori infection in precancerous gastric lesions, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer in China. Methylation status of p16 was evaluated by methylation-specific polymerase chain reaction in 920 subjects with precancerous gastric lesions. H. pylori status was determined by 13C-urea breath test and the density of H. pylori in biopsy specimens used for detecting methylation status was assessed by the modified Giemsa stain. The frequency of p16 methylation was significantly higher in subjects with H. pylori positive than those with H. pylori negative in each category of gastric lesion (p<0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs) of p16 methylation were markedly elevated in subjects with H. pylori positive for superficial gastritis (OR, 9.45; 95% confidence interval [CI]: 2.94-30.41), chronic atrophic gastritis (OR, 15.92; 95%CI: 7.60-33.36), intestinal metaplasia (OR, 4.46; 95%CI: 2.44-8.13), indefinite dysplasia (OR, 3.67; 95%CI: 1.90-7.10), and dysplasia (OR, 2.48; 95%CI: 1.02-5.99). Moreover, the frequencies of p16 methylation increased steadily with the severity of H. pylori density in gastric mucosa. Compared with H. pylori negative, the OR of p16 methylation was 1.02-16.13 times higher in subjects with mild H. pylori infection, and 2.69-38.73 times higher in those with moderate/severe infection, respectively. Our findings indicate that p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island.     

Ectopic expression of guanylyl cyclase C and endogenous ligand guanylin correlates significantly with Helicobacter pylori infection in gastric carcinogenesis

The molecular mechanisms leading to gastric carcinogenesis still remain unclear. Recently, several studies demonstrated that over-expression of guanylyl cyclase C (GCC) has been detected in intestinal-type gastric cancer (GC) and precursor lesions. Our objective was to explore the expression levels of GCC and endogenous ligands guanylin (GN) and uroguanylin (UGN) and the correlation between Helicobacter pylori (H. pylori) and GCC, GN, and UGN expressions in patients at different stages from normal mucosa to superficial gastritis, atrophic gastritis, intestinal metaplasia (IM), dysplasia, and finally adenocarcinoma. The expression of GCC and GN was absent in the distal normal gastric tissues and superficial gastritis in all cases, whereas they were measured in IM, dysplasia, and GC. The expression of GCC and GN was closely related to intestinal-type GC. From superficial gastritis to gastric carcinomas, the H. pylori positive rate was 19.7, 33.3, 69.6, 80.0, and 82.1%, respectively. The positive correlation was found between GCC and GN in IM, dysplasia, and GC. Also, the positive correlation was found between GCC, GN, and H. pylori infection in them. These results demonstrate that the detection of GCC and GN will be beneficial to diagnosis human gastric carcinoma and precancerous lesions. Ectopic expression of GCC and GN in human gastric mucosa and H. pylori infection may play an important role in the carcinogenesis of the intestinal-type GC.     

Does treatment of Helicobacter Pylori Infection Reduce Gastric Precancerous Lesions?

Background: Treatment of Helicobacter pylori (H. pylori) decreases the prevalence of gastric cancer, andmay inhibit gastric precancerous lesions progression into gastric cancer. The aim of this study was to determinethe effect of treatment on subsequent gastric precancerous lesion development. Materials and Methods: Weprospectively studied 27 patients who had low grade dysplasia at the time of enrollment, in addition to dysplasiaatrophic gastritis and intestinal metaplasia observed in all patients. All were prescribed quadruple therapy totreat H. Pylori infection for 10 days. Patients underwent endoscopy with biopsy at enrollment and then at followup two years later. Biopsy samples included five biopsies from the antrum of lesser curvature, antrum of greatercurvature, angularis, body of stomach and fundus. Results of these biopsies were compared before and aftertreatment. Results: Overall, the successful eradication rate after two years was 15/27 (55.6%). After antibiotictherapy, the number of patients with low grade dysplasia decreased significantly (p=0.03), also with reductionof the atrophic lesions (p=0.01), but not metaplasia. Conclusions: Treatment of H. pylori likely is an effectivetherapy in preventing the development of subsequent gastric premalignant lesions.