BACKGROUND: Helicobacter pylori (H. pylori) has been considered a definitive carcinogen in gastric cancer. Telomerase is activated in gastric cancer and some premalignant gastric lesions, including intestinal metaplasia (IM). In this study, we evaluated the relationships of both H. pylori infection and telomerase activity with endoscopic and histologic features in IM. The effects of H. pylori eradication on endoscopic, histologic and biochemical changes were evaluated. METHODS: Endoscopic biopsies were obtained from 43 patients with IM for rapid urease, histologic and telomerase tests. The endoscopic and histologic features, H. pylori infection and telomerase were assessed. After H. pylori eradication, 15 patients were re-evaluated and compared after 4 months. RESULTS: Thirty-four (79.1%) patients were infected with H. pylori. The incidence of H. pylori infection was borderline correlated to the severity of IM (p=0.076). Telomerase was elevated in eight (18.6%) patients. Telomerase tends to be high in subtype III and endoscopic grade III of IM. After H. pylori eradication, endoscopic extent (p=0.039) and histologic severity (p=0.074) showed improvements, and telomerase decreased significantly (p=0.0001). CONCLUSION: Our data suggest that telomerase is associated with the severity and extent of IM and that H. pylori eradication improves the endoscopic and histologic features in IM, and decreases telomerase activity. H. pylori eradication can be considered one of the methods to prevent gastric cancer in patients with H. pylori-infected IM. Further long-term and large-scaled study will be needed.
Female ; Helicobacter Infections/*enzymology ; *Helicobacter pylori ; Human ; Intestinal Mucosa/enzymology/microbiology/*pathology ; Male ; Metaplasia/enzymology/microbiology ; Middle Aged ; Precancerous Conditions/enzymology/microbiology ; Stomach Neoplasms/*enzymology/microbiology ; Telomerase/*metabolism

OBJECTIVETo investigate the protein expression of cyclooxygenase 2 (COX-2) and nuclear factor kappa B (NF-kappaB) in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its clinical significance.

METHODSProtein expression of COX-2 and NF-kappaB in gastric MALT lymphoma were examined by immunohistochemistry of Envision two-step method. The correlations of COX-2 and NF-kappaB expression with Helicobacter pylori (Hp) infection, clinical stage, depth of tumor invasion, tumor size, recurrent rate and treatment were analyzed by univariate, multivariate and Pearson analysis.

RESULTSThe positive expression of COX-2 and NF-kappaB in gastric MALT lymphoma were 48.9%(23/47) and 36.2% (17/47) respectively, and a positive correlation was found between these two factors(r=0.326,P<0.05). Moreover, COX-2 expression was positively correlated with Hp infection,clinical stage, depth of invasion and tumor size (P<0.05). Univariate analysis showed that the overall survival of gastric MALT lymphoma patients with positive COX-2 protein (59.9 months) was shorter than that of patients with negative COX-2 protein (77.8 months), but the difference was not significant (P>0.05). The survival was significantly shorter in gastric MALT lymphoma patients with positive NF-kappaB protein (26 months) than that of patients with negative NF-kappaB protein (123.2 months)(P<0.05). Multivariate Cox regression analysis revealed that clinicopathological stage was independent prognostic factor, and associated with short survival.

CONCLUSIONUp-regulated expression of COX-2 and activation of NF-kappaB are associated with Hp infection in gastric MALT lymphoma, and their protein expression is correlated with the development of tumor and prognosis.

Cyclooxygenase 2 ; metabolism ; Female ; Gastric Mucosa ; metabolism ; microbiology ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Humans ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; microbiology ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms ; metabolism ; microbiology ; pathology

BACKGROUND/AIMS: Peroxisome proliferator-activated receptorgamma (PPARgamma), a nuclear transcription factor, plays a critical role in the regulation of gene expression associated with inflammation and cancer. PPARgamma is expressed in human gastric cancer as well as in colon cancer. Activation of PPARgamma by ligand produces pro-apoptotic effect and ameliorate growing of cancer cells. Helicobacter pylori (H. pylori) is a main etiologic agent for gastric inflammation, and raises cell turnover in gastric epithelium. Longstanding infection with this organism is related with the development of non-cardiac gastric cancer. The aim of this study was to investigate the effect of H. pylori on the expression of PPARgamma protein and mRNA in chronic gastritis. METHODS: Gastric biopsy samples were taken from H. pylori infected (n=18) and non-infected (n=21) patients during endoscopic examination. PPARgamma expressions were assessed by real time polymerase chain reaction and immunohistochemistry. RESULTS: PPARgamma was localized to the nuclei of the foveolar epithelial cells in both infected and non-infected mucosa. PPARgamma protein expression was higher in H. pylori infected patients than in non-infected patients (3.8+/-0.4 vs. 2.6+/-1.0, H. pylori infected and non-infected, respectively; p<0.05). However, PPARgamma mRNA levels were not significantly different between the two groups (24+/-18 vs. 29+/-25, H. pylori infected and noninfected, respectively). CONCLUSIONS: PPARgamma expression is increased in the gastric mucosa of H. pylori infected chronic gastritis, which suggests a certain role of PPARgamma in the mucosal inflammatory reaction to H. pylori infection.
Adult ; Colonic Neoplasms/metabolism/microbiology/pathology ; Computer Systems ; Female ; Gastric Mucosa/*metabolism/microbiology/pathology ; Gastritis/*metabolism/microbiology/pathology ; Helicobacter Infections/*metabolism/microbiology ; *Helicobacter pylori ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; PPAR gamma/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms/metabolism/microbiology/pathology

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.
Aged ; Female ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Intestinal Diseases/*genetics/microbiology/pathology ; Male ; Metaplasia/pathology ; Middle Aged ; Polymerase Chain Reaction ; Precancerous Conditions/metabolism/pathology ; Stomach Neoplasms/etiology/*genetics/microbiology

Adult ; Aged ; Aged, 80 and over ; Female ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; classification ; pathogenicity ; Humans ; Lymphatic Metastasis ; Male ; Microvessels ; pathology ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; microbiology ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; microbiology ; Vascular Endothelial Growth Factors ; metabolism

OBJECTIVETo evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach.

METHODSH. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed.

RESULTSNo significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study.

CONCLUSIONSNo significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.

Adenocarcinoma ; microbiology ; pathology ; virology ; Aged ; Cardia ; China ; Epstein-Barr Virus Infections ; pathology ; Female ; Helicobacter Infections ; pathology ; Helicobacter pylori ; isolation & purification ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; microbiology ; pathology ; virology ; Viral Matrix Proteins ; metabolism

OBJECTIVETo investigate the correlation between infection with L-form of Helicobacter pylori (Hp-L) and the expressions of macrophage migration inhibition factor (MIF), matrix metalloproteinase 9 (MMP9), and vascular endothelial growth factor (VEGF) in gastric cancer.

METHODSHp-L was examined in 80 gastric carcinoma and 50 adjacent normal tissues by Gram staining and immunohistochemical staining, and the expressions of MIF, MMP9 and VEGF were detected by immunohistochemical staining; the expression of MIF mRNA was detected by RT-PCR and the expression of MIF, MMP9 and VEGF proteins were detected by Western blotting in 30 fresh gastric cancer tissues and the corresponding adjacent tissues.

RESULTSOf the 80 gastric carcinoma tissues, 57 (71.25%) showed Hp-L positivity detected by both Gram staining and immunohistochemical staining, as compared with a rate of only 14% in the adjacent normal tissues (P<0.05). The gastric carcinoma tissues showed higher expression levels of MIF, MMP9 and VEGF proteins than the corresponding adjacent normal mucosa; the positivity MIF, MMP-9 and VEGF proteins were significantly higher in Hp-L-positive gastric carcinoma than in Hp-L-negative cases (P<0.05). Positive correlations were found between Hp-L positivity and the expressions of MIF, MMP-9 and VEGF (r=0.598, 0.292, 0.341, respectively, P<0.05). The 30 fresh gastric cancer tissues showed also significantly higher MIF mRNA expression and MIF, MMP-9 and VEGF protein expressions than the adjacent tissues (t=3.729, P<0.01). The expressions of MIF and MMP-9 were also related to the clinicopathological factors including lymph node metastasis and depth of invasion (P<0.05).

CONCLUSIONInfection with L-form of Hp-L can be an important factor that contributes to the invasion and metastasis of gastric carcinoma, the mechanism of which involves up-regulated expressions of MIF, MMP-9 and VEGF.

Adult ; Aged ; Aged, 80 and over ; Female ; Helicobacter Infections ; metabolism ; pathology ; Helicobacter pylori ; Humans ; L Forms ; Lymphatic Metastasis ; Macrophage Migration-Inhibitory Factors ; metabolism ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Stomach Neoplasms ; metabolism ; microbiology ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study the expression of NFkappaB p65 and its target genes in intestinal metaplasia (IM), dysplasia (Dys), gastric cancer (GC) infected with Helicobacter pylori (Hp) and explore the mechanism of infection by cytotoxin-associated antigen A expressing Hp (CagA(+)Hp) in the development of gastric cancer.

METHODSCagA antibody in blood sample of 289 patients was determined by ELISA. Hp was detected by rapid urease test and Warthin starry staining. Expression of NFkappaB p65 and its target genes in IM, Dys and GC was examined by immunohistochemistry.

RESULTSIn IMI approximately II, IMIII, DysI, DysII approximately III and GC, the expression of NFkappaB p65 was significantly higher in patients with CagA(+)Hp infection than those without CagA Hp infection. In IMIII and DysII approximately III, the expression of NFkappaB p65, c-myc, CyclinD(1) and bcl-xl was significantly higher in patients with CagA Hp infection than those without CagA Hp infection. In gastric cancer infected with CagA(+)Hp, the expression of NFkappaB p65, c-myc, CyclinD(1) and bcl-xl was significantly higher in intestinal type than in diffuse type.

CONCLUSIONThere are different mechanisms in intestinal type and diffuse type in the development of gastric cancer. The occurrence of intestinal type gastric cancer is associated with CagA(+)Hp infection which by NFkappaB p65 upregulating the expression of c-myc, CyclinD(1),bcl-xl in patients with IMIII, DysII approximately III. It may be an effective method to prevent gastric cancer by inhibiting NFkappaB p65.

Adult ; Aged ; Antigens, Bacterial ; analysis ; Bacterial Proteins ; analysis ; Cyclin D1 ; metabolism ; Female ; Helicobacter Infections ; complications ; metabolism ; microbiology ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Precancerous Conditions ; metabolism ; microbiology ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Stomach Neoplasms ; metabolism ; microbiology ; pathology ; Transcription Factor RelA ; genetics ; metabolism ; bcl-X Protein ; metabolism

OBJECTIVETo investigate the expression feature of heterogeneous nuclear ribonucleoprotein K in gastric carcinoma and its clinical significance, and to explore the relationship between hnRNPK expression and Helicobacter pylori L-form infection.

METHODSThe expression of hnRNPK protein was examined in 100 cases of gastric carcinoma, 50 paracancerous gastric tissues and 30 matched normal gastric mucosa by Elivision immunohistochemistry and hnRNPK-mRNA by in situ hybridization. Hp-L was detected with Gram staining and immunohistochemical staining.

RESULTSThe positive rates of hnRNPK protein and mRNA in gastric carcinoma were 82.0% and 86.0%, respectively, significantly higher than those in the paracancerous gastric tissues and normal controls (P < 0.05). The expression of hnRNPK protein was significantly correlated with histological differentiation, TNM stage and lymph node metastasis (P < 0.05). The positive rates of Hp-L in the three groups were 67.0%, 58.0% and 23.3%, respectively. The positive rate of Hp-L in gastric carcinoma had no significant correlation with it in the paracancerous gastric tissues, but was significantly higher than it in the normal controls (P < 0.05). In gastric carcinoma, the expression of hnRNPK protein was higher in cases of Hp-L positive patients than those of Hp-L negative cases (P < 0.05). Positive correlation existed between the expression of hnRNPK protein and Hp-L infection (r = 0.391, P < 0.01).

CONCLUSIONSThere is a higher expression of hnRNPK in gastric carcinoma. Hp-L infection may be associated with the up-regulated hnRNPK expression. The two factors may play a synergetic role in gastric carcinogenesis.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastric Mucosa ; metabolism ; Helicobacter Infections ; metabolism ; microbiology ; Helicobacter pylori ; Heterogeneous-Nuclear Ribonucleoprotein K ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Precancerous Conditions ; metabolism ; microbiology ; pathology ; RNA, Messenger ; metabolism ; Ribonucleoproteins ; genetics ; metabolism ; Stomach Neoplasms ; metabolism ; microbiology ; pathology

OBJECTIVETo investigate the regulatory effect of jianpi jiedu Recipe (JJR) on the microvessel density (MVD) and cyclooxygenase-2 (COX-2) in long-term infection of Helicobacter pylori induced gastric cancer of C57BL/6 mice, thus providing experimental bases for its treatment of the H. pylori correlated gastropathy.

METHODSC57BL/6 mouse gastric cancer model induced by H. pylori infection was established by gastrogavage of H. pylori standard strain SS1. Mice were divided into the control group, the model group, low dose JJR group, and the high dose JJR group, 40 in each group. Mice were sacrificed after 72-week medication. Changes of the gastric mucosa MVD of mice in each group were detected by immunohistochemical method. Expressions of COX-2 mRNA and protein were detected by Real-time fluorescent quantitative polymerase chain reaction and immunohistochemical method.

RESULTSThe occurrence rate of gastric cancer in the control group, the model group, the low dose JJR group, and the high dose JJR group was 0, 22.2%, 11.1%, and 10.0%, respectively. The gastric mucosa MVD (number/cm2) of mice in each group was 2.50 +/- 1.54, 18.56 +/- 2.62, 14.61 +/- 3.60, and 7.39 +/- 1.75, respectively. The gastric mucosa MVD in the model group increased more obviously than that in the control group (P < 0.01). The gastric mucosa MVD significantly decreased in the low dose JJR group and the high dose JJR group (P < 0.01). Expressions of COX-2 mRNA and protein in the model group increased more obviously than those in the control group (P < 0.01). Low dose JJR and high dose JJR could decrease their expressions in a dose dependent manner.

CONCLUSIONSH. pylori infection could increase the gastric mucosa MVD of C57BL/6 mice and promote COX-2 expressions, which might play a promoting effect in the incidence of H. pylori induced gastric cancer. JJR could decrease the gastric mucosa MVD and inhibit COX-2 expressions, which might be one of its important mechanisms of preventing and treating gastric cancer.

Animals ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gastric Mucosa ; blood supply ; drug effects ; metabolism ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; microbiology