Gastric Cancer Open Access
Copyright ©The Author(s) 2002. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 2002; 8(6): 1009-1013
Published online Dec 15, 2002. doi: 10.3748/wjg.v8.i6.1009
Expression of gastric cancer-associated MG7 antigen in gastric cancer, precancerous lesions and H. pylori-associated gastric diseases
Dong-Li Guo, Ming Dong, Lan Wang, Li-Ping Sun, Yuan Yuan, Cancer Institute, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning Province, China
Author contributions: All authors contributed equally to the work.
Supported by The National Basic Research Program (973) of China, No.G1998051203
Correspondence to: Dr. Yuan Yuan, No.3 gastric cancer laboratory, Cancer Institute, First Affiliated Hospital, China Medical University, 155 Northern Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, China. yyuan@mail.cmu.edu.cn
Received: May 13, 2002
Revised: May 28, 2002
Accepted: June 3, 2002
Published online: December 15, 2002

Abstract

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. pylori infection 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. pylori infection 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 I and 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. pylori-positive 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. pylori positive 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 positive - H. pylori superficial 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.




INTRODUCTION

Gastric monoclonal antibody MG7 was first gotten by immunizing the BALB/C mice directly with poor-differentiated adenocarcinoma gastric cancer cell line MKN-46-9[1]. By immunohistochemistry method the MG7 antigen is distinguished limited in the gastric cancer tissue[2-5], which is specific and serves as a marker of gastric cancer. Helicobacter pylori (H. pylori) infection is established as a major cause of gastritis, peptic ulcer disease and gastric cancer[6-8]. The current study is to investigate the dynamic expression of MG7 antigen in different gastric mucosa, including the normal gastric tissue, H. pylori-associated gastric lesions as well as other precancerous conditions and gastric cancer, also to investigate the influence of H. pylori on MG7 antigen expression.

MATERIALS AND METHODS
Clinical data

The gastric cancer-associated antigen MG7 expression was studied in 383 gastric mucosal biopsied materials, including 26 normal gastric mucosa, 67 superficial gastritis, 21 gastric ulcer, 71 atrophic gastritis, 82 intestinal metaplasia, 59 dysplasia, and 57 gastric cancerous tissue, among which 29 were differentiated and 28 undifferentiated.

Reagents

The MoAb MG7 was gifted by Professor Fan Daiming in No. 4 China Military Medical University; The ABC kit was the product of American Vecter Company.

HID-ABpH2.5-PAS mucin histochemistry stain

82 IM were categorized into three types according to the morphology, degree of differentiation and mucin-protein secreted. These were stained with Alican blue pH 2.5/ periodic acid Schiff (AB/PAS) to visualize neutral mucin and some acidic mucins, and with high iron diamine/Alcian blue pH 2.5 (HID/AB) to identify sulphomucin and sialomucin[9]. Type I (complete) was characterized by mature absorptive and goblet cells, the latter secreted sialomucin. Paneth’s cells were often present. Type II(incomplete) showed few or no absorptive cells, but with ‘intermediate’ columnar cells in various differentiated stages, secreting neutral and sialomucins, while Paneth’s cells might not be present. In type III (incomplete), cell dedifferentiation was more obvious than that in type II, with ‘intermediate’ cells secreting predominantly sulphomucin and goblet cells containing sialo- and/or sulphomucin. Paneth’s cells were usually absent. A variable degree of disorganized architecture was often present in type III IM.

H. pylori examination

The H. pylori infection was detected by HE stain, PCR and ELISA. H. pylori was considered positive if two of the above three methods were positive. H. pylori could be found in the gastric epithelium or in the mucus by histological examination. Detection of H. pylori with H. pylori-DNA-PCR method followed the protocol of kit. The band in the same position as the positive control was defined as positive. When ELISA method was performed, the sample with OD value/ OD average value of negative controls ≥ 2.1 was defined as positive.

Immunohistochemistry stain (ABC method ) of gastric cancer-associated antigen MG7

4 μm thick sections were cut from paraffin wax blocks, mounted on acid cleaned glass slides, and heated at 55 °C for 60 min. The slides were dewaxed and dehydrated, then the endogenous peroxidase activity was inhibited by incubation with 3% H2O2 (20 min at room temperature). To reduce the non-specific background staining, the slides were incubated with 2% horse serum (20 minutes at room temperature), then were incubated with MG7 antibody in a moist chamber at 4 °C overnight. The avidin-biotin-peroxidase complex procedure was then performed as described by ABC immunohistochemistry kit. Peroxidase activity was detected with diaminobenzidine as substrate. Finally, the sections were weakly counterstained with Harris’s haematoxylin. Negative controls with PBS replacing specific primary antibodies were included in each run. Positive controls were cases of undifferentiated gastric cancer with MG7 expression. The sections were considered positively stained only when unequivocal cellular membrane and cytoplasm staining for MG7 were present. Diagnosis was made by brown coloration with varied intensities and the number of cells with brown coloration[10] . score 1: light brown; score 2: brown; score 3: deep brown. score 1: stained cells < 30%; score 2: stained cells 30%-70%; score 3: stained cells > 70%. According to the sum of the two index, as that comprehensive scores were made. Comprehensive score 0 was defined as negatively expressed, comprehensive scores 2-4 were defined positively expressed, the cases and that above 4 was defined as over-expressed.

Statistical analysis

The results were analyzed by χ2 test.

RESULTS
The expression of gastric cancer-associated MG7 antigen in different gastric mucosal tissues

The coloration in gastric cancerous tissue was often brown or deep brown, which was mainly located in the cellular membrane, cytoplasm and the glandular lumen, but not in the nucleus. The brown coloration was usually diffusely and non-polar distributed in the cytoplasm of cancer cells and might also be present in the luminal surface of the glands, sometimes it was located in some cancer cell nests or glands. The coloration in benign gastric lesions was often light brown, which was mainly located at the apex of the cytoplasm, the luminal surface membrane, none was seen in the cell nucleus. There were less positive cells in benign gastric lesions.

There was no expression of MG7 antigen in normal gastric mucosa. The positive rate of MG7 antigen expression in gastric cancer was 91.2%. The level of MG7 antigen expression in undifferentiated gastric cancer was higher than that of differentiated gastric cancer (89.7%, 92.3%, P > 0.05). From the viewpoint of histology, the positive rates of MG7 expression in normal gastric mucosa, metaplasia/dysplasia and gastric cancer increased gradually (P < 0.01), see Table 1. From clinical viewpoint the positive rates of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer also increased gradually (P < 0.01), see Table 2. The expression rates of MG7 antigen in the increasing order were normal gastric mucosa, superficial gastritis, intestinal metaplasia, atrophic gastritis, dysplasia and gastric cancer, there was significant difference between gastric cancer and other benign gastric lesion groups (P < 0.05), see Table 1 and Table 2.

Table 1 The expression of MG7 antigen in various gastric lessions.
Gastric lessionsnNo. of cases with MG7expression
Positive rate(%)Over-expression rate(%)
++++++
Normal26260000.0b0.0b
gastric mucosa
Intestinal8234434158.5bd6.1b
metaplasia
Dysplasia5930234249.2bd10.2b
Gastric cancer57523181191.2d50.9d
Table 2 The expression of MG7 antigen in different gastric diseases.
Gastric lessionsnNo. of cases withMG7expression
Positive rate(%)Over-expression rate(%)
++++++
Superficial gastritis675970111.9b1.5b
Atrophic gastritis7125397064.8bd9.9b
Gastric cancer57523181191.2d150.9d
The expression of gastric cancer-associated MG7 antigen in different types of intestinal metaplasia

According to different mucin secreted, the intestinal metaplasia of gastric mucosa could be categorized into three types. The positive rate of MG7 antigen expression in type III intestinal metaplasia of gastric mucosa was significantly different as compared with type I and type II intestinal metaplasia (P < 0.05), but was close to gastric cancer (P > 0.05). The over-expression rate of MG7 antigen in type I, type II, type III intestinal metaplasia and gastric cancer increased gradually, and there was significant difference between gastric cancer group and other groups respectively (P < 0.05), see Table 3.

Table 3 The expression of MG7 in different types of intestinal metaplasia and gastric cancer.
Types of intestinalmetaplasianNo. of cases with MG7expression
Positive rate(%)Over-expression rate(%)
++++++
Type I and II intestinal metaplasia5328241047.2bb1.9b
Type III intestinal metaplasia296193179.3dd13.8b
gastric cancer57523181191.2dd50.9d
The expression of MG7 antigen in H. pylori-associated gastric diseases

On examination, H. pylori infection was detected in 291 specimens of different gastric mucosa tissues including 66 superficial gastritis, 20 gastric ulcer, 70 atrophic gastritis, 80 intestinal metaplasia and 55 dysplasia. The MG7 antigen expression was also examined in H. pylori-positive and H. pylori-negative groups of different gastric diseases. It was found that the positive rates of MG7 antigen expression in H. pylori-positive and H. pylori-negative cases of superficial gastritis, gastric ulcer, atrophic gastritis, intestinal metaplasia and dysplasia were 20.5%/0, 25%/12.5%, 62.5%/65.8%, 52%/66.7%, 30.3%/54.5%, respectively. The positive rate of MG7 expression in H. pylori-positive superficial gastritis (20.5%) was significantly higher than that in H. pylori-negative superficial gastritis ones (0), (P < 0.05). There was no significant differences between H. pylori-negative and H. pylori-positive atrophic gastritis, intestinal metaplasia and dysplasia of gastric epithelium in positive rates of MG7 antigen expression, see Table 4. In the MG7 antigen expression positive ones, positive-H. pylori in superficial gastritis, intestinal metaplasia, atrophic gastritis and dysplasia of gastric epithelium was counted as 8/ 8, 26/46, 20/45, 10/22 respectively. Among the 8 superficial gastritis with MG7 expression, the rate of H. pylori infection was 100%.

Table 4 The expression of MG7 antigen in H. pylori-associated gastric lesions.
Gastric lesionsH. pylori-positive
H. pylori-negative
nMG7 expression
nMG7 expression
No. of casesrate (%)No.of casesrate (%)
superficial gastritis39820.5270a
gastric ulcer123258112.5
atrophic gastritis322062.5382565.8
intestinal metaplasia502652.0302066.7
dysplasia331030.3221254.5
The follow-up of cases with H. pylori-associated gastric diseases

34 cases were followed up for 2 years, among which 3 cases without H. pylori infection and 31 cases with H.pylori infection. There were 19 with negative MG7 antigen expression (-); 13 with weakly positive MG7 antigen expression (+); (++) and (+++) each. One year later, among the 3 without H. pylori infection, 1 case was found newly H. pylori infected accompanied by increased MG7 expression. Among 31 cases of H. pylori-positive diseases, early gastric cancer was detected in 3 with MG7 antigen expression, of which one with weakly positive MG7 antigen expression (+) was atrophic gastritis, one with MG7 antigen expression (++) was also atrophic gastritis but one case with MG7 antigen expression (+++) was superficial gastritis, see Table 5. After surgical operation and drug treatment, the reduced MG7 expression with H. pylori eradication was found in a case of superficial gastritis.

Table 5 The follow-up results of 34 cases with H. pylori-associ-ated gastric diseases.
Change of H. pylori statusNo.of casesMG7 antigen expression
mitigatedunchangedaggravatedmalignant change
H. pylori infection unchanged1941311
H. pylori eradicated144712
H. pylori newly infected10010
DISCUSSION

Gastric cancer is still a major health problem and the leading cause of cancer mortality despite a worldwide decline in incidence. Early detection and early diagnosis are important in prevention and treatment of gastric cancer. The antigen recognized by gastric monoclonal antibody MG7[1] is different from other gastrointestinal tumor markers as reported[11,12]. It has been taken as a promising index in gastric cancer screening because of its specificity[1-4,13,14]. In this study, we found that the expression of MG7 antigen in different gastric tissue was different. The positive rate of MG7 antigen expression in gastric cancer is 91.2%.The positive rate of MG7 expression in normal gastric mucosa, metaplasia/dysplasia and gastric cancer increased in ascending order (P < 0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer increased in succession (P < 0.01). The expression rate of MG7 antigen in undifferentiated gastric cancer was higher than that of differentiated gastric cancer (P > 0.05), cases with positive expression cells are more above 70% in undifferentiated gastric cancer than that in differentiated gastric cancer (P < 0.05), showing the presence of somewhat tendency of certain histopathologic type. The dynamic changes in expression of MG7 antigen in normal gastric mucosa, precancerous lesions and gastric cancer implicated that in the gastric precancerous conditions, MG7 antigen increased gradually with the development and progression of gastric cancer and its sensitivity was higher in gastric cancer, and could be used as a marker for screening.

This study showed that among the benign gastric lesions the positive rate of MG7 expression in atrophic gastritis and dysplasia were significantly higher than that in superficial gastritis but significantly lower than that in gastric cancer, implicating there were more gastric cancer-associated antigens in the cell membrane and cytoplasm of atrophic gastritis and dysplasia which was in access to gastric cancer. Intestinal metaplasia is taken as gastric precancerous lesion[16,17]. It was found that type III(incomplete) intestinal metaplasia had cancerous potential, our study demonstrated the positive rate of MG7 antigen expression in type III intestinal metaplasia of gastric mucosa was significantly different compared with typeIand typeII intestinal metaplasia (P < 0.05), and was analogous, even more closed to gastric cancer (P < 0.05). Since the dynamic changes in of MG7 antigen expression was closely related with the development and progression of gastric cancer, cases with atrophic gastritis, dysplasia and type III intestinal metaplasia should be closely followed up for the early detection of gastric cancer.

The development of gastric cancer is a multistep process that is multifactorial. Several factors may act in stages of development of cancer[9]. Epidemiology data show the close relationship between H. pylori and gastric cancer[18,19]. H. pylori has been assigned as a class I carcinogen by WHO, and acts as the initiating agent. It virulence factors can damage gastric epithelial cells[20-22], break the balance between proliferation and apoptosis[23-33]. but it is still unclear weather H. pylori plays a role after development of atrophic gastritis and intestinal metaplasia[34,35].

Our study found that the positive rate of MG7 expression in H. pylori-positive superficial gastritis was higher than that in H. pylori-negative cases (P < 0.05). There were 8 cases of positive H. pylori superficial gastritis with MG7 antigen expression, which suggested that H. pylori infection was directly stated to MG7 antigen expression. But there was no significant difference between H. pylori-negative and H. pylori-positive atrophic gastritis, intestinal metaplasia and dysplasia in the positive rate of MG7 antigen expression. This might be due to the change of the environment in atrophic gastritis, intestinal metaplasia and dysplasia, which was unsuitable for the growth of H. pylori.

By following up of the 34 cases of H. pylori-associated disease, we detected early gastric cancer in 3 H. pylori-positive cases with MG7 antigen expression, (2 cases of atrophic gastritis, one case of superficial gastritis). After surgical operation and drug treatment with H. pylori eradication reduced MG7 expression was found in the case of superficial gastritis. Among the 3 cases without H. pylori infections, 1 case had newly emerged H. pylori infection accompanied by increased MG7 expression. These implicated the close relationship between the H. pylori infection and the expression of MG7 antigen in gastric mucosa, although some H. pylori-positive gastric lesions with MG7 antigen expression showed benign morphology, there is still the potential risk of developing into gastric cancer, hence follow up study is essential; more attention should be paidto those with increased MG7 antigen expression.

Footnotes

Edited by Wu XN

References
1.  Fan DM, Zheng XY, Chen XT, Mu ZX, Hu JL, Qiao TD, Chen BJ, Wang JY, Zhang ZQ, Gao ZQ. Preparation of anti-undifferenti-ated gastric cancer cell line MKN-46-9 monocolonal antibody and immunohistochemical identification. Jiefangjun Yixue Zaizhi. 1988;13:12-13.  [PubMed]  [DOI]  [Cited in This Article: ]
2.  Jin N. [Distribution of monoclonal antibodies MG7 and MGd-1 against gastric carcinoma in stomach cancer]. Zhonghua Zhongliu Zazhi. 1990;12:193-195.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Hu JL. [A study on the expression of MG7 corresponding antigen in gastric mucosa with dysplasia and its significance in detection of early gastric cancer]. Zhonghua Yixue Zazhi. 1988;68:363-35, 26.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Ren Q, Zhang XY, Chen XT, Liu J. The immunoelectromicroscopic studies on the distribution of MG7, MG9, MGd1 antigens with monoclonal antibodies against gastric cancers. Aizheng. 1990;9:100-102.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Qiao TD, Zhang XY, Hu JL, Fan DM, Chen BJ, Chen XT, Zhou SJ, Mu ZX. Expression of the tumor-associated antigen (MG7-Ag) in 1000 cases of atypical dysplasia of the gastric mucosa. Jiefangjun Yixue Zazhi. 1993;18:121-123.  [PubMed]  [DOI]  [Cited in This Article: ]
6.  Kang SP, Chang QL, He HM, Li SP, Zhang KQ, Kang P, Liu YS. Epidemiologic investigation of upper gastroinestonal diseases in Liulin county Shanxi Province. Shijie Huaren Xiaohua Zazhi. 1998;6:210-211.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Guo CQ, Wang YP, Liu GY, Ma SW, Ding GY, Li JC. Study on Helicobacter pylori infection and -p53, c-erbB-2 gene expression in carcinogenesis of gastric mucosa. Shijie Huaren Xiaohua Zazhi. 1999;7:313-315.  [PubMed]  [DOI]  [Cited in This Article: ]
8.  Lu SY, Pan XZ, Peng XW, Shi ZL. Effect of Hp infection on gas-tric epithelial cell kinetics in stomach diseases. Shijie Huaren Xiaohua Zazhi. 1999;7:760-762.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735-6740.  [PubMed]  [DOI]  [Cited in This Article: ]
10.  Filipe MI, Potet F, Bogomoletz WV, Dawson PA, Fabiani B, Chauveinc P, Fenzy A, Gazzard B, Goldfain D, Zeegen R. Incomplete sulphomucin-secreting intestinal metaplasia for gastric cancer. Preliminary data from a prospective study from three centres. Gut. 1985;26:1319-1326.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 138]  [Cited by in F6Publishing: 149]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
11.  Fang DC, Liu WW. The expression of 8 kinds of tumor-associ-ated antigen in gastric lesions. Neijing. 1994;11:259-262.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Zhang JR, Zhang XY, Chen XT, Fan DM. The purification and analysis of new gastric cancer-associated antigen MG5-Ag, MG7-Ag and MG9-Ag. Disi Junyi Daxue Xuebao. 1988;9:282.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Ren J, Chen Z, Juan SJ, Yong XY, Pan BR, Fan DM. Detection of circulating gastric carcinoma-associated antigen MG7-Ag in human sera using an established single determinant immuno-polymerase chain reaction technique. Cancer. 2000;88:280-285.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 3]  [Reference Citation Analysis (0)]
14.  Chen SZ. [The expression of MG7 corresponding antigen in gastrointestinal polyps and its relation with cancer]. Zhonghua Waike Zazhi. 1992;30:716-78, 716-78.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Fang DC, Liu WW. Subtypes of intestinal metaplasia and gastric carcinoma. A clinicoendoscopic follow-up of 112 cases. Chin Med J (Engl). 1991;104:467-471.  [PubMed]  [DOI]  [Cited in This Article: ]
16.  Wu MS, Shun CT, Lee WC, Chen CJ, Wang HP, Lee WJ, Lin JT. Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of intestinal metaplasia. Br J Cancer. 1998;78:125-128.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 38]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
17.  Filipe MI, Muñoz N, Matko I, Kato I, Pompe-Kirn V, Jutersek A, Teuchmann S, Benz M, Prijon T. Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer. 1994;57:324-329.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 298]  [Cited by in F6Publishing: 285]  [Article Influence: 9.5]  [Reference Citation Analysis (0)]
18.  Chang WK, Kim HY, Kim DJ, Lee J, Park CK, Yoo JY, Kim HJ, Kim MK, Choi BY, Choi HS. Association between Helicobacter pylori infection and the risk of gastric cancer in the Korean population: prospective case-controlled study. J Gastroenterol. 2001;36:816-822.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 23]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
19.  Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784-789.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3126]  [Cited by in F6Publishing: 3019]  [Article Influence: 131.3]  [Reference Citation Analysis (0)]
20.  Kohda K, Tanaka K, Aiba Y, Yasuda M, Miwa T, Koga Y. Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer. Gut. 1999;44:456-462.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 60]  [Cited by in F6Publishing: 66]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
21.  Peng H, Pan GZ, Lu CM. Relationship between gastric H. pylori infection and cell apoptosis. Zhonghua Xiaohua Zazhi. 1999;19:154-155.  [PubMed]  [DOI]  [Cited in This Article: ]
22.  Suganuma M, Kurusu M, Okabe S, Sueoka N, Yoshida M, Wakatsuki Y, Fujiki H. Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter pylori. Cancer Res. 2001;61:6356-6359.  [PubMed]  [DOI]  [Cited in This Article: ]
23.  Moss SF, Sordillo EM, Abdalla AM, Makarov V, Hanzely Z, Perez-Perez GI, Blaser MJ, Holt PR. Increased gastric epithelial cell apoptosis associated with colonization with cagA + Helicobacter pylori strains. Cancer Res. 2001;61:1406-1411.  [PubMed]  [DOI]  [Cited in This Article: ]
24.  Szaleczky E, Prónai L, Molnár B, Berczi L, Fehér J, Tulassay Z. Increased cell proliferation in chronic Helicobacter pylori positive gastritis and gastric carcinoma--correlation between immuno-histochemistry and Tv image cytometry. Anal Cell Pathol. 2000;20:131-139.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 14]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
25.  Moss SF, Calam J, Agarwal B, Wang S, Holt PR. Induction of gastric epithelial apoptosis by Helicobacter pylori. Gut. 1996;38:498-501.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 290]  [Cited by in F6Publishing: 331]  [Article Influence: 11.8]  [Reference Citation Analysis (0)]
26.  Nardone G, Staibano S, Rocco A, Mezza E, D'armiento FP, Insabato L, Coppola A, Salvatore G, Lucariello A, Figura N. Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis. Gut. 1999;44:789-799.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 93]  [Cited by in F6Publishing: 108]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
27.  Dong Q, Liu W, Zheng X. [Effect of Helicobacter pylori on gastric epithelial apoptosis]. Zhonghua Neike Zazhi. 1997;36:751-753.  [PubMed]  [DOI]  [Cited in This Article: ]
28.  Li ZJ, Lin QX, Nie YQ, Chen YF, Wang QY. Apoptosis and pro-liferation in gastric epithelial cells is induced by Helicobacter py-lori and accompanied by increased expression of p53. Linchuang Xiahuabing Zazhi. 1999;11:102-104.  [PubMed]  [DOI]  [Cited in This Article: ]
29.  Zhang Z, Yuan Y, Gao H, Dong M, Wang L, Gong YH. Apoptosis, proliferation and p53 gene expression of H. pylori associated gastric epithelial lesions. World J Gastroenterol. 2001;7:779-782.  [PubMed]  [DOI]  [Cited in This Article: ]
30.  Gao H, Yuan Y, Wu YQ, Wang L, Dong M, Zhang Z. Effect of the eradiation of Helicobacter pylori on PCNA, p53 protein and p16 protein expression. Zhonghua Yufang Yixue Zazhi. 1999;33:14-17.  [PubMed]  [DOI]  [Cited in This Article: ]
31.  Konturek PC, Konturek SJ, Pierzchalski P, Bielański W, Duda A, Marlicz K, Starzyńska T, Hahn EG. Cancerogenesis in Helicobacter pylori infected stomach--role of growth factors, apoptosis and cyclooxygenases. Med Sci Monit. 2001;7:1092-1107.  [PubMed]  [DOI]  [Cited in This Article: ]
32.  Lu XL, Qian KD, Tang XQ, Zhu YL, Du Q. Detection of H.pylori DNA in gastric epithelial cells by in situ hybridization. World J Gastroenterol. 2002;8:305-307.  [PubMed]  [DOI]  [Cited in This Article: ]
33.  Yao YL, Xu B, Song YG, Zhang WD. Overexpression of cyclin E in Mongolian gerbil with Helicobacter pylori-induced gastric precancerosis. World J Gastroenterol. 2002;8:60-63.  [PubMed]  [DOI]  [Cited in This Article: ]
34.  Asaka M, Kimura T, Kato M, Kudo M, Miki K, Ogoshi K, Kato T, Tatsuta M, Graham DY. Possible role of Helicobacter pylori infection in early gastric cancer development. Cancer. 1994;73:2691-2694.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 5]  [Reference Citation Analysis (0)]
35.  Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, Sitas F. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ. 1991;302:1302-1305.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 941]  [Cited by in F6Publishing: 905]  [Article Influence: 27.4]  [Reference Citation Analysis (0)]