不同胃粘膜组织中幽门螺杆菌感染与端粒酶的关系

目的：探讨胃癌胃粘膜演变过程中各个不同阶段粘膜组织端粒酶表达规律及幽门螺杆菌（HP）感染的关系。方法：采用端粒酶TPCR－ELISA法检测19例慢性浅表性胃炎（CSG）、15例胃粘膜肠上皮化生（ICM）、15例胃粘膜轻度异型增生、14例胃粘膜重度异型增生、29例胃腺癌组织端粒酶活性，并对其中HP阳性与阴性病变组织的端粒酶阳性率进行对比研究。结果：端粒酶阳性率由CSG→ICM→胃粘膜轻度异型增生→重度异型增生→胃癌逐渐增高，分别为0、40．0％、40．0％、78．6％、79．3％、胃粘膜轻度异型增生66．7％、重度异型增生64．3％、胃癌44．8％。ICM及轻度异型增生组与CSG组比较差异显著(x^2＝5．85，P＜0．05）。各病变组织中HP阳性与阴性组间端粒酶阳性表达率无明显差异。结论：端粒酶激活是胃癌发生的早期事件。HP现行感染与端粒酶阳性表达无明显关系。     

原位逆转录PCR检测胃癌及癌前组织中端粒酶RNA及其临床意义

目的　研究胃癌及癌前病变胃粘膜端粒酶RNA的检测及其临床意义。方法　选取经病理组织学证实的胃粘膜活检标本 15 0例 ,包括慢性浅表性胃炎 3 2例、肠上皮化生 3 6例、不典型增生 3 4例、胃癌 48例 ,采用原位逆转录PCR、端粒重复序列扩增 (TRAP)法检测上述胃粘膜端粒酶RNA与端粒酶活性。结果　原位逆转录PCR技术检测胃粘膜活检标本端粒酶RNA阳性率为 5 5 .3 % (83 / 15 0 ) ,显著高于TRAP法检测端粒酶活性阳性率 (4 0 .0 % ,60 / 15 0 ) ,P <0 .0 5。端粒酶RNA在胃癌及癌前病变 (包括肠上皮化生与异型增生 )中检出率显著高于浅表性胃炎 (P <0 .0 5 ) ,胃癌中端粒酶RNA检出率亦显著高于肠上皮化生及不典型增生 (P <0 .0 5 ) ,但后两者比较差异无显著性 (P >0 .0 5 )。端粒酶RNA主要分布于胃粘膜癌细胞及癌前病变上皮细胞的胞核内。结论　端粒酶RNA与胃癌的发生密切相关。原位逆转录PCR技术检测胃粘膜端粒酶RNA对胃粘膜癌变的早期诊断和预测有重要价值 ,而且可能是较端粒酶活性更灵敏的生物学指标     

袁红霞教授用经方辨治慢性萎缩性胃炎癌前病变经验撷菁

正胃癌前病变是一个病理性概念,是指较易转变为胃癌组织的病理学变化,包括肠上皮化生(IM)和异型增生(Dys),是正常胃黏膜向胃癌转化过程中的一个重要阶段~[1]。慢性浅表性胃炎→慢性萎缩性胃炎→肠上皮化生→异型增生→胃癌的Correa级     

rasP^21、GST—π在胃癌及癌前病变组织表达的研究

目的;观察rasP^21、GST－π在胃癌及癌前病变组织中的表达,探讨复合表达在胃粘膜癌变过程中的意义。方法：应用免疫组化（S－P）法测定40例肠上皮化生（不全结肠型）,76例异型增生（轻度20例,中度34例,重度22例）和42全癌组织中rasP^21、GST－π的表达及复合表达情况,以10例萎缩性胃炎胃粘膜做对照。结果：（1）rasP^21、GST－π在萎缩性胃炎中无阳性表达,在肠上皮化生、异型增生及胃癌中表达率及表达强度逐渐增高（P＜0．05或0．01）;在轻、中重度异型增生中表达率及表达强度逐渐增高（P＜0．05或0．01）;在重度异型增生中表达率有表达强度与胃癌无显著性差异（P均＞0．05）。（2）rasP^21、GST－π在肠上皮化生、异型增生及胃癌中复合表达率逐渐增高（P＜0．01）;在轻、中、重度异型增生中复合表达率逐渐增高（P＜0．05）;在重度异型增生与胃癌的复合表达率无显著差异（P＞0．05）。结论：rasP^21、GST－π均与胃粘膜癌变过程有关,联合检测对胃癌的早期诊断有重要意义。     

中医药治疗胃癌前期病变的研究进展

胃癌的癌前病变(Precancerous lesions of gastric cancer，PL-GC)一般是指在慢性萎缩性胃炎(Chronic atrophic gastritis，CAG)基础上伴发的肠上皮化生(Intestinal metaplasia，IM)和异型增生(Dysplasia，Dys)。资料表明，胃粘膜肠上皮化生癌变率为13．0％，发生癌变的平均间隔时间为3．5年，胃粘膜异型增生癌变率为18．1％，发生癌变的平均间隔时间为1．5年，其中轻度异型增生的癌变率为2．53％，中度为4％～8％，重度为10％～83％。     

端粒酶在胃粘膜活检组织中的表达及其与幽门螺杆菌关系的 …

目的：探讨幽门螺杆菌（ＨＰ）感染与端粒酶表达在胃癌发生发展中的意义。方法：采用ＴＲＡＰ－银染法对１００例胃粘膜活检标本进行端粒酶活性检测。结果：ＨＰ感染率在慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生及胃腺癌中逐渐升高,且ＨＰ阳性胃癌组端粒酶阳性率（９３．８％）明显高于ＨＰ阴性组（５０．０％）（Ｐ〈０．０１）。结论：ＨＰ感染在胃癌变中有非常重要的生物学意义,端粒酶有可能成为胃癌早期诊断的理想标记物。     

慢性萎缩性胃炎与胃癌

萎缩性胃炎是指胃的固有腺体数目减少甚至消失,常伴有广泛的肠上皮化生和异型增生,肠上皮化生及异型增生为胃癌的癌前病变。正常胃黏膜．浅表性胃炎一萎缩性胃炎一肠上皮化生一异型增生一胃癌是Correa提出的慢性胃炎向胃癌演变的规律模式,已得到相关学者的广泛认同。越来越多证据表明,慢性萎缩性胃炎作为一种癌前疾病与胃癌的发生及发展密切相关。     

胃粘膜活检标本端粒酶活性的检测

为探讨端粒酶活化在胃癌发生发展中的作用，本文采用ＴＲＡＰ法对７２例胃镜胃粘膜活检标本端粒酶活性进行检测，结果发现，胃癌端粒酶阳性率为８５．０％（１７／２０），萎缩性胃炎、肠上皮化生、异型增生及胃腺瘤性息肉端粒酶阳性率分别为２８．６％（１０／３５）、１６．７（１／６）、３３．３％（１／３）及１００％（２／２）。胃癌组织端粒酶阳性率与肿瘤部位、大体类型及组织学分类无明显相关。以上结果提示，胃粘膜活检标本端粒酶活性的检测对阐明胃癌的发生发展过程，胃粘膜癌变的预测及胃癌的早期诊断可能具有重要意义。     

老年胃癌及癌前病变中幽门螺杆菌感染情况的研究

采用ＰＣＲ方法检测老年胃癌及癌前病变组织中幽门螺杆菌（ＨＰ）感染情况。结果显示：正常组ＨＰ感染率为１５．０％，浅表性胃炎组为７０．０％，胃癌组为６３．３％；萎缩性胃炎组阳性率为８６．８％，不典型增生组为８４．０％，肠化生组为７５．０％。胃癌组中，高、中分化癌阳性率明显高于低分化组（Ｐ＜０．０１），肠型胃癌阳性率明显高于弥漫型（Ｐ＜０．０１）。萎缩性胃炎组及不典型增生组，中、重度者阳性率明显高于轻度者（Ｐ＜０．０５）。以上结果证明，ＨＰ与胃癌、癌前病变、胃炎均有密切相关性     

Cx32、Cx43在慢性浅表性胃炎、癌前病变及胃癌中的表达变化

目的观察Cx32、Cx43在慢性浅表性胃炎（CSG）和癌前病变（PL）和胃癌（GC）中的表达情况。方法采用免疫组织化学SABC法检测Cx32、Cx43在33例慢性浅表性胃炎、88例癌前病变及70例胃癌患者胃黏膜中表达规律。结果Cx32、Cx43阳性表达率在PL组及胃癌组均低于CSG组（P〈0、05）；肠上皮化生伴不典型增生组及不典型增生组阳性表达率均低于肠上皮化生组（P〈0．05）；低分化胃癌组阳性表达率低于中高分化胃癌组（P〈0．01）。讨论Cx32、Cx43阳性表达率从CSG、PL到GC逐渐下降，并与癌前病变类型及胃癌分化程度相关。     

c-Myc和端粒酶在幽门螺杆菌相关性胃病中协同表达

目的 通过检测幽门螺杆菌(Hp)相关性胃病[慢性浅表性胃炎(CSG)、慢性萎缩性胃炎(CAG)、异型增生及胃癌]中c—Myc和端粒酶的活性,分析c—Myc和端粒酶两者表达的关系,并探讨其与胃癌危险因子Hp之间的关系。方法 117例组织标本中c-Myc蛋白表达采用免疫组化法检测,端粒酶活性采用端粒酶PCR-ELISA法检测。结果 胃癌组中,端粒酶阳性率和c-Myc表达率(分别为87．7％和61．5％)高于非癌组;CAG伴有中、重度肠化组,端粒酶阳性率和c-Myc表达率(分别为52．4％和47．6％)显著高于CAG伴轻度肠化组(分别为13．3％和16．7％);有中、重度肠化的CAG组,伴有Hp感染者其端粒酶阳性率和c—Myc表达率(分别为67．9％和67．9％)显著高于无Hp感染者(分别为21．4％和7．1％);CSG组中无端粒酶阳性者。在胃癌及有中、重度肠化的CAG组,伴有Hp感染者其端粒酶阳性率和c—Myc表达率呈协同性增高(协同表达率分别为89．5％和100．0％)。结论 Hp感染可诱导慢性胃病、尤其是CAG中c-Myc和端粒酶的表达。在胃癌及CAG伴中、重度肠化的患者c-Myc和端粒酶协同表达。     

Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases

AIM: To detect the telomerase activity and c-Myc expression in gastric diseases and to examine the relation between these values and Helicobacter pylori (H pylori) as a risk factor for gastric cancer. METHODS: One hundred and seventy-one gastric samples were studied to detect telomerase activity using a telomerase polymerase chain reaction enzyme linked immunosorbent assay (PCR-ELISA), and c-Myc expression using immunohistochemistry. RESULTS: The telomerase activity and c-Myc expression were higher in cancers (87.69% and 61.54%) than in noncancerous tissues. They were higher in chronic atrophic gastritis with severe intestinal metaplasia (52.38% and 47.62%) than in chronic atrophic gastritis with mild intestinal metaplasia (13.33% and 16.67%). In chronic atrophic gastritis with severe intestinal metaplasia, the telomerase activity and c-Myc expression were higher in cases with H pylori infection (67.86% and 67.86%) than in those without infection (21.43% and 7.14%). c-Myc expression was higher in gastric cancer with H pylori infection (77.27%) than in that without infection (28.57%). The telomerase activity and c-Myc expression were coordinately up-regulated in H pylori infected gastric cancer and chronic atrophic gastritis with severe intestinal metaplasia. CONCLUSION: H pylori infection may influence both telomerase activity and c-Myc expression in gastric diseases, especially in chronic atrophic gastritis.     

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     

Expression of gastric cancer—associated MG7 antigen in gastric cancer,precancerous lesions and H.pylori—associated gastric diseases

AIM: To investigate the relationship between the antigen MG7 antigen expression and gastric cancer as well as precancerous condition; to study the relationship between the MG7 antigen expression and H. pyloriinfection in benign gastric lesions in order to find out the effect of H. pylori infection on the process of gastric cancer development.METHODS: The level of MG7 antigen expression was determined by immunohistochemical method in 383 gastric biopsied materials. The intestinal metaplasia was determined by histochemistry method. The H. pyloriinfection was determined by HE stain, PCR and ELISA in 291 specimens, among which only 34 cases of H. pylori-associated gastric lesions were followed up.RESULTS: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric cancer increased gradually in ascending order (P＜0.01). The positive rate of MG7 antigen expression in type Ⅲ intestinal metaplasia of gastric mucosa was higher than that of type Ⅰand Ⅱ intestinal metaplasia, being highly significant (P＜0.05).The positive rate of MG7 antigen expression in superficial gastritis, atrophic gastritis and gastric cancer increased gradually (11.9 %, 64.8 %, 91.2 %, P＜0.01). There was no significant difference between H.pylori-negative and H. pyloripositive intestinal metaplasia, atrophic gastritis and dysplasia of gastric epithelium in the positive rate of MG7 antigen expression. There was no expression of MG7 antigen in H. pylori-negative superficial gastritis. The positive rate of MG7 expression in H. pylori-positive superficial gastritis was 20.5 %, and the difference between them was significant (P＜0.05). During following up, one of the three H. pylori negative cases turned positive again, and its MG7 antigen expression turned to be stronger correspondingly. 3 of 31 H. pyloripositive cases were detected as early gastric cancer, among which one with "+++" MG7 antigen expression was diminished after H. pylori eradication.CONCLUSION: MG7 antigen expression is highly specific in gastric cancer and can be used as a good marker for screening of gastric cancer; type Ⅲ intestinal metaplasia, atrophic gastritis and dysplasia should be followed up and MG7 antigen expression has high clinical value in the dynamic follow-up study; although the positive -MG7 in positiveH. pylorisuperficial gastritis show benign morphology in features, there is still the potential risk of developing into gastric cancer, hence special attention should be paid to those showing increasing MG7 antigen expression.     

HSP60和CD44 V6在胃腺癌中的表达及其意义

目的研究热休克蛋白60(HSP60)、CD44V6在人胃癌组织中的表达.方法对60例非癌胃粘膜病变及50例胃腺癌组织手术及内镜活检石蜡标本,应用抗人HSP60,CD44V6单克隆抗体,以免疫组织化学检测方法检测HSP60,CD44V6的表达.结果 HSP60在慢性浅表性胃炎、肠上皮化生、不典型增生、胃腺癌的阳性率为30%,65%,70%,76%,过表达率为10%,25%,35%,58%.CD44V6在慢性浅表性胃炎、肠上皮化生、不典型增生、胃腺癌的阳性率为5%,25%,30%,78%,HSP60,CD44V6在肠上皮化生、不典型增生及胃腺癌中的阳性率和过表达率均明显高于慢性浅表性胃炎(P＜0.05);HSP60在胃腺癌组织的过表达率高于肠上皮化生和不典型增生(P＜0.05).HSP60在高、中、低分化胃腺癌中的阳性表达率为64.7%,77.7%,75.0%.HSP60在不同分化程度胃腺癌中表达无明显差异(P＞0.05),而CD44V6在高、中、低分化胃腺癌中的阳性表达率为64.7%,66.2%,91.7%,CD44V6在低分化胃腺癌的表达明显高于高、中度分化胃腺癌(P＜0.05).结论 HSP60,CD44V6在人胃癌及癌前情况或病变中过度表达,可能与胃腺癌的发生、发展有关,还可能有助于预测胃腺癌的分化程度.     

胃黏膜病变演化过程中抗氧化蛋白Peroxiredoxin6的表达及其与幽门螺杆菌感染的关系

目的探讨胃黏膜病变演化过程中抗氧化蛋白Peroxiredoxin 6(Prx6)表达水平变化及其与幽门螺杆菌(H.pylori)感染的关系。方法根据组织形态学将104例临床内镜检查活检标本分为慢性浅表性胃炎(33例)、慢性萎缩性胃炎(25例)、肠上皮化生(32例)及异型增生(14例)4组。用免疫组织化学方法检测组织标本中Prx6的表达水平。用快速尿素酶试验及Warthin-Starry银染检测H.pylori感染。结果 Prx6在慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、异型增生组的阳性表达率分别为39.4%(13/33)、80.0%(20/25)、93.8%(30/32)、92.9%(13/14),过表达率分别为15.2%(5/33)、44.0%(11/25)、81.3%(26/32)、85.7%(12/14)。慢性浅表性胃炎、慢性萎缩性胃炎组H.pylori阳性者Prx6阳性表达率显著高于H.pylori阴性者(P<0.05),肠上皮化生组Prx6的表达在H.pylori阳性者和阴性者无显著差异(P>0.05)。结论在胃黏膜病变演化过程中,Prx6的表达随着胃黏膜病变的进展而增加,H.pylori在胃黏膜病变演化的早期阶段促进了Prx6的表达。     

Alterations of telomerase activity and terminal restriction fragment in gastric cancer and its premalignant lesions

AIMS: In order to explore the role of alterations of telomerase activity and terminal restriction fragment (TRF) length in the development and progression of gastric cancer. METHODS: Telomerase activity was detected in 176 specimens of gastric mucosa obtained through an operation or endoscopical biopsy by using the telomeric repeat amplification protocol (TRAP) assay. Meanwhile, the mean length of TRF was measured with the use of a Southern blot in part of those samples. RESULTS: Telomerase activity was detected in 14 of 57 (24.6%) chronic atrophy gastritis patients, six of 18 (33.3%) intestinal metaplasia patients, three of eight (37.5%) dysplasia patients and 60 of 65 (92.3%) gastric cancer patients, respectively. Normal gastric mucosa revealed no telomerase activity. No association was found between telomerase activity and any clinicopathological parameters. The mean TRF length was decreased gradually with age in normal mucosa and in gastric cancer tissue. Regression analysis demonstrated that the reduction rate in these tissues was 41 +/- 12 base pairs/year. Among 35 gastric cancers, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 cases (34.3%) and elongated in three cases (7.6%), compared to the corresponding adjacent tissues. The mean TRF length tended to decrease as the mucosa underwent chronic atrophy gastritis, intestinal metaplasia, dysplasia and into gastric cancer. The mean TRF length in gastric cancer was not statistically correlated with clinicopathological parameters and telomerase activity. CONCLUSIONS: Our results suggest that telomerase is expressed during the early stage of gastric carcinogenesis, and that the clinical significance of TRF length appears to be limited in gastric cancer.     

Atypical regenerative changes, dysplasia, and carcinoma in situ in chronic gastritis associated with Helicobacter pylori

In the present work we study the association between chronic active gastritis (CAG), atypical regeneration and dysplasia and gastric Helicobacter pylori (HP) infection. We study two groups of endoscopic biopsies. Regenerative changes and dysplasia were evaluated according to Gandur-Maymneh et al. classification which was simplified in typical and atypical regeneration, and mild and severe dysplasia. The group I included 94 patients with CAG, 9 with chronic non active gastritis (CNAG) and 2 with normal gastric mucosa. CAG was graded according to activity in; severe 28 patients; moderate 54 patients and; mild 12 patients. HP association in these cases was 100%, 77% and 25%. In cases of CNAG HP was present in 22%, there were not HP in normal gastric mucosa. There were atypical regeneration in 25% of moderate CAG and in 42% of severe CAG. Mild dysplasia was present in 7.5 and 25% in cases of moderate and severe CAG. Two biopsies showed severe dysplasia. In addition, intestinal metaplasia was found in 15% of CAG, the metaplasia was present in 25% of cases with CAG and atypical regeneration; in 54% of cases with mild dysplasia and; in 100% on cases with severe dysplasia. The group II included 9 cases of gastric cancer of intestinal type, 7 cases of diffuse type, and 4 cases of mixed type. In all these cases there was viewed CAG associated to HP infection in non-neoplastic mucosa. In 75% of cases there were showed atypical regeneration and 60% presented some type of dysplasia. There was transition between atypical regeneration and dysplasia in 6 cases of intestinal gastric cancer and in 3 cases of mixed type. We found relationship between the intensity of CAG and HP colonization, and the association with atypical regeneration and dysplasia.