scholarly journals cagA positive and negative Helicobacter pyloristrains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage

Gut ◽  
1998 ◽  
Vol 42 (6) ◽  
pp. 772-778 ◽  
Author(s):  
N Figura ◽  
C Vindigni ◽  
A Covacci ◽  
L Presenti ◽  
D Burroni ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intestinal Metaplasia ◽  
Normal Mucosa ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Glandular Cell ◽  
Increased Risk ◽  
Molecular Masses ◽  
Non Ulcer Dyspepsia ◽  
H Pylori

Background/Aims—Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with different cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation.Methods—Well separated H pyloricolonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined forcagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients’ sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically.Results—Of the 747 colonies examined, 45.3% werecagA+. All colonies from four patients werecagA+, and all colonies from two patients werecagA−. In 13 patients (68%) both cagA+ andcagA− colonies were found. CagA expression of isolates corresponded to their cagA status. H pyloristrains with different CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p< 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites.Conclusions—Most patients with non-ulcer dyspepsia are infected by both cagA+ and cagA−H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia.

scholarly journals Role of Activated Protein C in Helicobacter pylori-Associated Gastritis

2000 ◽  
Vol 68 (5) ◽  
pp. 2863-2869 ◽  
Author(s):  
Satoko Oka ◽  
Esteban Cesar Gabazza ◽  
Yukiko Taguchi ◽  
Michihiko Yamaguchi ◽  
Shigehito Nakashima ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Protein C ◽  
Activated Protein C ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Gastric Corpus ◽  
H Pylori

ABSTRACT The protein C (PC) pathway has recently been suggested to play a role in the regulation of the inflammatory response. To further extend the anti-inflammatory effect of activated PC (APC) in vivo, particularly its biological relevance to human disease, the activity of APC in the mucosa of patients with Helicobacter pylori-associated gastritis and the effect of vacuolating cytotoxin (VacA), cytotoxin-associated antigen (CagA), andH. pylori lipopolysaccharide (LPS) on PC activation were evaluated. This study comprised 35 patients with chronic gastritis. There were 20 patients with and 15 without H. pylori infection. The levels of PC and APC-PC inhibitor (PCI) complex were measured by immunoassays. The level of PC was significantly decreased and the level of APC-PCI complex was significantly increased in biopsy specimens from gastric corpus and antrum in patients with H. pylori-associated gastritis as compared to H. pylori-negative subjects. The concentrations of VacA, CagA, and LPS were significantly correlated with those of the APC-PCI complex in biopsy mucosal specimens from the gastric corpus and antrum. H. pylori LPS, VacA, and CagA induced a dose-dependent activation of PC on the surface of monocytic cells. APC inhibited the secretion of tumor necrosis factor alpha (TNF-α) induced by H. pylori LPS. Overall, these results suggest that H. pylori infection is associated with increased APC generation in the gastric mucosa. The inhibitory activity of APC on TNF-α secretion may serve to protect H. pylori-induced gastric mucosal damage.

scholarly journals Follow-up analysis and histopathological study of gastric mucosa in patients with Helicobacter pylori infection

2021 ◽  
Vol 49 (12) ◽  
pp. 030006052110553
Author(s):  
Guang Zhao ◽  
Zhishang Zhang ◽  
Baohui Li ◽  
Silin Huang ◽  
Wensi Li ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Intraepithelial Neoplasia ◽  
Mucosal Damage ◽  
Helicobacter Pylori Infection ◽  
Gastric Mucosal Damage ◽  
Histopathological Study ◽  
Significant Difference ◽  
H Pylori

Objective To investigate the histomorphological characteristics of the gastric mucosa and the prognosis in patients with Helicobacter pylori infection. Methods Progressive damage to the gastric mucosa was examined by immunohistochemistry in 2294 patients with H. pylori infection and follow-up information was analyzed. Results H. pylori initially colonized the mucus layer covered by the gastric mucosa epithelium, then selectively adhered to and destroyed the surface mucus cells causing intra-gastric and extra-gastric lesions. Gastric mucosal damage induced by H. pylori was divided into five stages according to the depth of H. pylori invasion and degree of lesion deterioration: mucilaginous, surface mucocellular, lamina propria lesion, mucosal atrophy, and intraepithelial neoplasia stages. Morphological follow-up analysis revealed no significant difference in 6-month curative effects between stage I and stage II, but significant differences were found between stages II and III, stages III and IV, and between stages IV and stage V, respectively. Conclusions This novel staging strategy may be a valuable tool for diagnosing and predicting the results of gastric mucosal damage induced by H. pylori infection.

Cell Proliferation and Inflammation on Biopsy Samples With Multifocal Atrophic Gastritis Before and 1 Year After Helicobacter pylori Eradication

2005 ◽  
Vol 129 (11) ◽  
pp. 1451-1456
Author(s):  
Jeannette Guarner ◽  
Jeanine Bartlett ◽  
Roslyn Seitz ◽  
Toni Whistler ◽  
Roberto Herrera-Goepfert ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Helicobacter Pylori ◽  
T Lymphocytes ◽  
Intestinal Metaplasia ◽  
Eradication Therapy ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Helicobacter Pylori Eradication ◽  
Biopsy Specimens ◽  
H Pylori

Abstract Context.—Results of clinical trials that have assessed whether gastric cancer is preventable with Helicobacter pylori eradication therapy remain inconclusive. These trials have used atrophy, intestinal metaplasia, and dysplasia as histopathologic end points that reflect possible preneoplastic lesions. Trial results would be more compelling if cell proliferation and inflammatory markers improved simultaneously with histopathologic lesions. Objective.—To study the presence of cell proliferation markers and type of inflammatory cells in biopsy specimens with gastritis, atrophy, and intestinal metaplasia before and 1 year after H pylori therapy and to determine if immunohistochemistry can be used to study these. Design.—We evaluated 12 subjects with gastritis and 16 with gastritis and multiple foci of atrophy and intestinal metaplasia by using immunohistochemical assays for tumor suppressor protein p53, proliferation marker Ki-67, cell cycle regulator cyclin D1, T and B lymphocytes, macrophages, and TUNEL (terminal deoxynucleotide transferase deoxyuridine triphosphate nick end labeling) assay for apoptosis. The biopsy specimens were selected from a randomized clinical trial that studied improvement of histopathologic gastric lesions after H pylori eradication. Results.—Groups of surface epithelial cells that expressed p53 and Ki-67 were observed more often in subjects with atrophy and intestinal metaplasia compared with those with gastritis alone. T lymphocytes in the lamina propria were frequently observed 1 year after treatment in subjects with atrophy and intestinal metaplasia. Conclusions.—Immunohistochemical assays for cell proliferation and inflammatory cell markers showed different distribution patterns in these gastric biopsy specimens. The presence of T lymphocytes and groups of cells that expressed proliferation markers in subjects with multiple foci of atrophy and intestinal metaplasia needs further study.

scholarly journals Combined Gastric and Colorectal Cancer Screening—A New Strategy

2018 ◽  
Vol 19 (12) ◽  
pp. 3854 ◽  
Author(s):  
Michael Selgrad ◽  
Jan Bornschein ◽  
Arne Kandulski ◽  
Jochen Weigt ◽  
Albert Roessner ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Intestinal Metaplasia ◽  
Incidence Rates ◽  
Screening Colonoscopy ◽  
Serum Pepsinogen ◽  
Serum Samples ◽  
Serological Screening ◽  
Increased Risk ◽  
H Pylori

Background: Our aim was to evaluate the feasibility of a serological assessment of gastric cancer risk in patients undergoing colonoscopy in countries with low-to-moderate incidence rates. Methods: Serum samples were prospectively collected from 453 patients (>50 years old) undergoing colonoscopies. Of these, 279 (61.6%) also underwent gastroscopy to correlate the results for serum pepsinogen I and II (sPG-I and sPG-II), sPG-I/II ratio, and anti-H. pylori antibodies with gastric histopathology findings (graded according to the updated Sydney classification and the Operative Link of Gastritis Assessment (OLGA) and the Operative Link for Gastric Intestinal Metaplasia assessment (OLGIM) systems). Results: H. pylori was found in 85 patients (30.5%). Chronic atrophic gastritis was diagnosed in 89 (31.9%) patients. High-risk OLGA (III–IV) stages were present in 24 patients, and high-risk OLGIM stages were present in 14 patients. There was an inverse correlation of sPG-I with the degree of atrophy and intestinal metaplasia (IM), as well as with the respective OLGA (r = −0.425; p < 0.001) and OLGIM (r = −0.303; p < 0.001) stages. A pathological sPG-I result was associated with a relative risk (RR) of 12.2 (95% confidence interval: 6.29–23.54; p < 0.001) for gastric preneoplastic changes. Conclusions: The assessment of serum pepsinogen allows the identification of patients at increased risk of gastric cancer. A prevention strategy of combining a screening colonoscopy with a serological screening for preneoplastic gastric changes should be considered in the general population.

scholarly journals Chronic gastritis and carcinogenesis issues

2019 ◽  
Vol 45 (4) ◽  
pp. 65-70
Author(s):  
M. M. Karimov ◽  
G. N. Sobirova ◽  
U. K. Abdullayeva
Keyword(s):  
Gastric Cancer ◽  
Intestinal Metaplasia ◽  
Chronic Atrophic Gastritis ◽  
Precancerous Conditions ◽  
Increased Risk ◽  
Operated Stomach ◽  
Increasing Risk ◽  
H Pylori ◽  
Definition Of

Risk factors contributing to the transformation of chronic atrophic gastritis into gastric cancer are analyzed. Detection and monitoring of patients with precancerous conditions/lesions (precancerous changes), proper screening of H. pylori make early diagnosis of gastric cancer real. Features of precancerous conditions are given in order of increasing risk of developing gastric cancer. Adenomatous polyps of the stomach take the first place. Subsequent precancerous conditions include: cancer of the operated stomach, Menetria disease (hypertrophic gastropathy), B12-deficient anemia, and gastric ulcer. A definition of intestinal metaplasia subtypes is proposed as a risk factor for gastric cancer, dividing into complete and incomplete one, taking into account reduction in the expression of gastric mucins MUC1, MUC5AC and MUC6. Currently, the development of gastric cancer (mainly of the “intestinal type”) is considered as a multistage process involving the sequence of mucosal change, such as chronic inflammation, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma. Role of the organism’s genetic susceptibility to H. pylori infection, factors of pathogenicity contributing to epithelial metaplasia, are analyzed. Role of Toll-like type 4 receptors (TLR4) involved in the recognition of H. pylori is clarified. It is with this type of receptors that the development of an excessive immune response of the host is associated, resulting in damage to the mucous membrane in H. pylori-infected individuals. In particular, carriers of TLR4+896A> G polymorphism have a more severe atrophy of the stomach and degree of inflammation, as well as an increased risk of non-cardiac gastric cancer.

scholarly journals Pathology and pathobiology of the gastric carcinoma

2011 ◽  
Vol 58 (1) ◽  
pp. 39-52 ◽  
Author(s):  
Marjan Micev ◽  
Milena Cosic-Micev
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Intestinal Metaplasia ◽  
Host Susceptibility ◽  
Diffuse Gastric Cancer ◽  
Type I ◽  
Increased Risk ◽  
Spasmolytic Polypeptide ◽  
H Pylori ◽  
Risk Of Cancer

Recent epidemiological studies in Serbia revealed that gastric carcinoma is the third and the fifth main cause of cancer morbidity in men and women, respectively. Despite the declining incidence of gastric cancer, it remains the second most common cause of cancer-related deaths as it is worldwide. A well-defined carcinogenic inflammation-metaplasia-dysplasia-cancer sequence typically precedes the development of most gastric adenocarcinomas. Alterations such as gastric mucosal atrophy and intestinal metaplasia are merely markers of increased risk, while gastric epithelial dysplasia (GED) represent a direct precursor of cancer. DNA damage and increased mucosal proliferation secondary to H pylori infection, combined with a suitable host susceptibility phenotype (eg, genetic polymorphisms in interleukin IL-1B, IL-1RN, and tumor necrosis factor a TNF-a genes), are important factors in this progression pathway. However, only a small minority of patients infected with H. pylori eventually develops gastric cancer, and eradication of H pylori in these patients does not seem to eliminate the risk of cancer completely. It has been shown that atrophy may be a better indicator of risk of cancer than intestinal metaplasia, and remains to be validated in routine clinical practice according to recent proposal for new quantitative methods. It is often associated with pseudopyloric gland metaplasia in the gastric corpus mucosa, which expresses a type of trefoil peptide, the spasmolytic polypeptide (termed spasmolytic polypeptide-expressing metaplasia or SPEM) and has been shown to be linked more closely to gastric cancer than intestinal metaplasia. Better histological characterization of adenomatous (or type I), hyperplastic (foveolar or type II) and tubule-neck (mucocellular or type III) GED, two-tiered grading system (low and high grade dysplasia) as well as the introduction of Padova and Vienna international classificatons of dysplasia seem to be more helpful in GED survillance and comparative studies. A combination of histopathological features, serum markers such as pepsinogen I, and molecular tests that analyze host susceptibility polymorphisms and bacterial virulence factors, may allow development of strategies for early detection of cancer in the future. At present, pathobiology of gastric cancerogenesis is far from known, despite the progressive knowlegde on predisposing environmental conditions and genetic and epigenetic abnormalities, including tumour supressor genes, oncogenes, microsatellite instability and hypermethylation or the significance of E-cadherin mutational status association with hereditary diffuse gastric cancer syndrome. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as resection margin status and lymph node metastases and their implications have also been discussed. We aim to review these aspects, with special relevance to gastric cancer specimen reporting.

scholarly journals Association of interleukin 12B rs3212227 polymorphism with gastric cancer, intestinal metaplasia, and helicobacter pylori infection

Genetika ◽  
2020 ◽  
Vol 52 (1) ◽  
pp. 115-126
Author(s):  
Seda Orenay-Boyacioglu ◽  
Elmas Kasap ◽  
Hakan Yuceyar ◽  
Mehmet Korkmaz
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Intestinal Metaplasia ◽  
Clinical Features ◽  
Statistical Significance ◽  
Study Groups ◽  
Interleukin 12 ◽  
Allelic Frequencies ◽  
Increased Risk ◽  
H Pylori

Interleukin 12 (IL-12) has a key function in promoting Th1 immune response in the gastrointestinal mucosa. Although cytokine gene polymorphisms are associated with increased risk of gastric cancer (GC), studies on different geographic regions and ethnic groups are not able to draw a consistent result. The current case-control study aims to find out an association between a functional IL-12B rs3212227 polymorphism and the susceptibility and clinical features of the study groups, which are GC, Helicobacter pylori-infected and H. pylori-uninfected intestinal metaplasia (IM). In this study, IL-12B rs3212227 polymorphism was genotyped in 35 GC cases, 25 H. pylori-infected IM patients, 25 H. pylori-uninfected IM patients, and 25 control subjects. PCR-RFLP analysis was performed to find out and compare the polymorphism profiles of case biopsies. There was statistical significance in genotype distributions and allelic frequencies in GC patients with proximal arrest in stomach (p=0.042). The rs3212227 genotypes and allelic frequencies were not correlated with any of the study groups (p>0.05). Other clinical features examined in the GC patients were also not correlated with the rs3212227 genotypes and allelic frequencies (p>0.05). Current findings suggest that IL-12B rs3212227 polymorphism may play a role in GC development.

scholarly journals Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Adenielson Vilar e Silva ◽  
Mario Ribeiro da Silva Junior ◽  
Ruth Maria Dias Ferreira Vinagre ◽  
Kemper Nunes Santos ◽  
Renata Aparecida Andrade da Costa ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Intestinal Metaplasia ◽  
Gastric Adenocarcinoma ◽  
Brazilian Amazon ◽  
Caga Gene ◽  
Neutrophil Activity ◽  
Increased Risk ◽  
Brazilian Amazon Region ◽  
H Pylori ◽  
Epiya Motifs

The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92–7.46, and P=0.002). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation.

Silencing of the hPOT1 gene by RNA inference promotes apoptosis and inhibits proliferation and aggressive phenotype of gastric cancer cells, likely through up-regulating PinX1 expression

2011 ◽  
Vol 64 (12) ◽  
pp. 1051-1057 ◽  
Author(s):  
Shun-Mei Wan ◽  
Jun Tie ◽  
Ya-Fei Zhang ◽  
Jun Guo ◽  
Liu-Qin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Intestinal Metaplasia ◽  
Cancer Cells ◽  
Protein A ◽  
Normal Mucosa ◽  
Gastric Cancer Cells ◽  
Down Regulation ◽  
Proliferation And Invasion

BackgroundThe human protection of telomeres 1 (hPOT1) protein, a single-strand telomeric DNA binding protein, plays an important role in telomere protection and telomere length regulation. However, its effect on invasion of gastric cancer remains unclear.AimsTo explore the role of hPOT1 in the proliferation and invasion of gastric cancer cells.MethodsThe gastric expression of hPOT1 was examined in normal gastric mucosa (n=25), intestinal metaplasia (n=20), gastric dysplasia (n=20) and gastric cancer (n=150) by immunohistochemistry. The mean optical density (MOD) of the immunostaining was determined by semi-quantitative image analysis. The role of hPOT1 in the cell proliferation, apoptosis and invasion of gastric cancer 7901 cells was determined by means of the RNA interference (RNAi) of hPOT1 mRNA. The effects of hPOT1 RNAi on the expression of hPinX1 and hTERT were detected with western blotting.ResultsThe hPOT1 MOD was progressively increased from the normal mucosa to intestinal metaplasia, dysplasia, and gastric cancer. An increased hPOT1 expression significantly correlated with tumour serosal invasion, node metastasis and advanced stage. Transfection of hPOT1 siRNA into SGC-7901 cells led to a decrease in cell proliferation, colony formation and invasion, and also an increase of apoptosis. An up-regulation of hPinX1 and down-regulation of hTERT were found in gastric cancer cells with hPOT1 siRNA.ConclusionsIncreased hPOT1 expression is associated with an advanced tumour stage. hPOT1 RNAi inhibits proliferation and invasion, and induces apoptosis of gastric cancer cells. The effects of hPOT1 RNAi seem to be functionally linked to up-regulation of PinX1 and down-regulation of hTERT.

scholarly journals Helicobacter pylorias an oncogenic pathogen, revisited

2017 ◽  
Vol 19 ◽  
Author(s):  
Muhammad Miftahussurur ◽  
Yoshio Yamaoka ◽  
David Y. Graham
Keyword(s):  
Gastric Cancer ◽  
Cytidine Deaminase ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
Mucosal Inflammation ◽  
Current Evidence ◽  
Dna Mismatch ◽  
Micro Rnas ◽  
The Difference ◽  
H Pylori

Gastric cancer is an inflammation-associated malignancy aetiologically related to infection with the bacterium,Helicobacter pylori, which is considered a necessary but insufficient cause. Unless treated,H. pyloricauses life-long acute and chronic gastric inflammation resulting in progressive gastric mucosal damage that may result in gastric cancer. The rate of progression from superficial gastritis, to an atrophic metaplastic mucosa, and ultimately to cancer relates to the virulence of the infectingH. pylorias well as host and environmental factors.H. pylorivirulence is a reflection of its propensity to cause severe gastric inflammation. Both mucosal inflammation andH. pylorican cause host genomic instability, including dysregulation of DNA mismatch repair, stimulation of expression of activation-induced cytidine deaminase, abnormal DNA methylation and dysregulation of  micro RNAs, which may result in an accumulation of mutations and loss of normal regulation of cell growth. The difference in cancer risk between the most and least virulentH. pyloristrain is only approximately 2-fold. Overall, none of the putative virulence factors identified to date have proved to be disease-specific. The presence, severity, extent and duration of inflammation appear to be the most important factors and current evidence suggests that any host, environmental or bacterial factor that reliably enhances the inflammatory response to theH. pyloriinfection increases the risk of gastric cancer.

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