A study on the effect of Helicobacter pylori infection on p53 expression in gastric cancer and gastritis tissues

Introduction: Helicobacter pylori cause damage to gastric epithelial cells and alterations in the p53 gene that lead to cancer development. This study aimed to determine the correlation of p53 expression with H. pylori using immunohistochemistry, RFLP-PCR, and histopathology. Methodology: Gastric biopsy samples from gastric cancer (GC) (n = 54) and gastritis (n = 31) patients were examined for histopathological changes and expression of p53 protein by immunohistochemistry. Results: Immunohistochemical analysis of p53 protein expression in H. pylori-positive GC sections showed an average of 44.3% positive cells in tumors and 6.9% in normal tissues, as compared to 16.4% and 4.4% in H. pylori-negative sections. P53 expression showed significant association with H. pylori (P = 0.005), invasion depth (P = 0.029) and inflammation reaction (P = 0.008). In gastritis sections, no difference in the average p53 staining in H. pylori-positive or -negative sections was seen. PCR-RFLP results also showed no difference in genotype frequencies of p53 in H. pylori-positive or -negative gastritis sections. Histopathology study of H. pylori-positive GC sections showed that 97.2% were the intestinal type and 2.8% the diffuse type, while in H. pylori-negative sections 35.2% were the intestinal type and 64.8% the diffuse type. Biopsy sections from H. pylori-positive gastritis patients revealed more severe inflammation than those of H. pylori-negative patients. Conclusion: Our results show that H. pylori infection affects p53 expression in GC. The average p53 expression was significantly higher in tumor than in normal tissues. In gastritis sections p53 expression was significantly associated with H. pylori.

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Helicobacter pylori and gastric cancer

Archive of oncology ◽

10.2298/aoo0304233o ◽

2003 ◽

Vol 11 (4) ◽

pp. 233-237 ◽

Cited By ~ 1

Author(s):

Marica Otasevic ◽

Aleksandar Nagorni ◽

Dobrila Stankovic-Djordjevic ◽

Marina Dinic ◽

Ljiljana Otasevic

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Treatment Group ◽

Intestinal Type ◽

Fisher Exact Test ◽

Diffuse Type ◽

Exact Test ◽

Significant Difference ◽

H Pylori ◽

Diffuse Type Gastric Cancer

BACKGROUND: Helicobacter pylori (H. pylori) is classified as a Group 1 carcinogen, because H. pylori infection considerably increases the risk of gastric cancer development. METHODS: The study involved a total of 191 patients divided into two groups. The first group comprised 117 patients who underwent endoscopy. A total of 203 biopsy specimens of the gastric mucosa were taken and analyzed using microbiological and histopathological methods. The second group comprised 74 patients with gastric cancer, who were examined for the gastric cancer type, the presence of H. pylori infection and the cancer localization. The presence of H. pylori infection in the tissue was con?firmed by staining pathohistological sections according to the method of Warthin-Starry. The microbilogical diagnosis involved the staining of direct tissue smears according to the method of Gram, as well as the cultivation of the specimens. To test the hypothesis for possible differences in H. pylori positive findings between the treatment groups, x2 test with Yates correction or Fisher exact test were used. RESULTS: The first treatment group comprised 117 patients with various clinical diagnoses. Gastric cancer was diagnosed in 8 patients, and of these 87.50% were found to have H. pylori. No statistically significant difference in H. pylori positive tests was detected between the patients with gastric ulcer and the patients with gastric cancer (Fisher exact test: p=1.00; p>0.05) nor was it established between the patients with duodenal ulcer and those with gastric cancer (Fisher exact test: p= 1.00; p>0.05). The second treatment group comprised 74 patients, of whom 52 (70.27%) had intestinal-type gastric cancer and 22 (29.72%) had diffuse-type gastric cancer. No statistically significant difference in the positive tests for H. pylori was registered between the patients with intestinal-type and those with diffuse-type gastric cancer (x2=0.07; p=0.798; p>0.05). The most frequent localization of the cancer was the antrum. CONCLUSION: The results are supportive of the hypothesis on a correlation between H. pylori infection and gastric adenocarcinoma development, but no differences between the intestinal and diffuse type of adenocarcinoma have been revealed with respect to the malignant process.

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KK-LC-1 may be an effective prognostic biomarker for gastric cancer

10.21203/rs.3.rs-50773/v3 ◽

2021 ◽

Author(s):

Jun Ji ◽

Jiahui Chen ◽

Anqiang Wang ◽

Wei Zhang ◽

Hongge Ju ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Cox Regression ◽

Staining Intensity ◽

Intestinal Type ◽

Clinicopathological Parameters ◽

Diffuse Type ◽

Clinical Prognosis ◽

Cox Regression Analysis ◽

Normal Tissues

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods : A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036); KK-LC-1 protein is more highly expressed in the intestinal type than the diffuse type, and it is statistically significant. The high expression of KK-LC-1 protein in the intestinal type is more than that in the diffuse type (P =0.008). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.

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Clinical Presentation, Histological Findings and Prevalence of Helicobacter pylori in Patients of Gastric Carcinoma

Faridpur Medical College Journal ◽

10.3329/fmcj.v6i2.9205 ◽

1970 ◽

Vol 6 (2) ◽

pp. 78-81 ◽

Cited By ~ 1

Author(s):

MA Kabir ◽

R Barua ◽

H Masud ◽

DS Ahmed ◽

MMSU Islam ◽

...

Keyword(s):

Helicobacter Pylori ◽

Blood Group ◽

Metastatic Lymph Node ◽

Abdominal Mass ◽

Study Data ◽

Intestinal Type ◽

Diffuse Type ◽

Poorly Differentiated ◽

H Pylori ◽

Carcinoma Stomach

Carcinoma stomach is the second leading cause of cancer death worldwide. This study was undertaken to determine the clinical and pathological profile of carcinoma stomach in Bangladesh and to find out the prevalence of H. pylori infection in carcinoma stomach subjects. Patients with carcinoma stomach confirmed on histopathology were included in the study. Data were recorded regarding demography, clinical features, blood group of the patients, location and macroscopic type of the cancer at endoscopy. Three to five biopsies from non-necrosed region and two paired biopsies from non-cancerous part of stomach were taken. One piece of each paired specimen was placed in the urea-agar media for CLO test and the other piece was used for histological examination. Out of 50 patients, 64% were male and 36% were female. The mean age was 51.05±14.98 years. Common presenting complains were dyspepsia/ abdominal pain, vomiting and dysphagia; abdominal mass, metastatic lymph node and ascites were predominant signs. About one third (34%) patients had blood group A. About 50% cancer was located in antrum followed by antrum and body (24%), then body (18%), fundus and body (4%) and fundus (4%). In 56% cases the lesion was ulcerative followed by polypoid (34%) and ulceroinfiltrative (10%). Histopathologically 52% was intestinal type, 28 % was diffuse type 20% was poorly differentiated adenocarcinoma. The prevalence of H. pylori in overall carcinoma stomach cases was 60% but individually in intestinal type 88%, in diffuse type 57% and in poorly differentiated type 50%. Key words: Carcinoma stomach; Helicobacter pylori. DOI: http://dx.doi.org/10.3329/fmcj.v6i2.9205 FMCJ 2011; 6(2): 78-81

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Prevalence of Helicobacter pylori infection in advanced gastric carcinoma

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032006000400009 ◽

2006 ◽

Vol 43 (4) ◽

pp. 288-292 ◽

Cited By ~ 7

Author(s):

Irami Araújo-Filho ◽

José Brandão-Neto ◽

Laíza Araújo Mohana Pinheiro ◽

Ítalo Medeiros Azevedo ◽

Flávio Henrique Miranda Araújo Freire ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Tumor Tissue ◽

Intestinal Type ◽

Gastric Carcinomas ◽

Tumor Tissues ◽

Lauren's Classification ◽

Lauren’S Classification ◽

H Pylori

BACKGROUD: There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS: A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS: Thirty-four tumors (60.7%) were intestinal-type and 22 (39.3%) diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6%) and atrophic mucosa in 36 patients (64.3%). All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was higher than that in diffuse carcinomas. In tumor tissues, 34 (60.7%) H. pylori-positive in gastric carcinomas were detected by Giemsa method. H. pylori was observed in 30 of 56 cases (53.5%) in tissues 4 cm adjacent to tumors. This difference was not significant. Eradication of H. pylori in non-tumor tissue of gastric remnant led to a complete negativity on the 12th postoperative month CONCLUSIONS: The data confirmed the hypothesis of a high prevalence of H. pylori in tumor tissue of gastric advanced carcinomas and in adjacent non-tumor mucosa of operated stomachs. The presence of H. pylori was predominant in the intestinal-type carcinoma.

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Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication

Journal of Gastroenterology ◽

10.1007/s00535-019-01639-w ◽

2019 ◽

Vol 55 (3) ◽

pp. 281-288 ◽

Cited By ~ 10

Author(s):

Susumu Take ◽

Motowo Mizuno ◽

Kuniharu Ishiki ◽

Chiaki Kusumoto ◽

Takayuki Imada ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Incidence Rate Ratio ◽

Gastric Atrophy ◽

Diffuse Type ◽

Gastric Cancer Risk ◽

Helicobacter Pylori Eradication ◽

H Pylori ◽

Diffuse Type Gastric Cancer

Abstract Background and aims Eradication of Helicobacter pylori reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of H. pylori. Methods We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of H. pylori infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade. Results During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk. Conclusions The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of H. pylori irrespective of the severity of gastric atrophy.

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NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

Biological Research ◽

10.1186/s40659-021-00336-4 ◽

2021 ◽

Vol 54 (1) ◽

Author(s):

Patricio Gonzalez-Hormazabal ◽

Diana Pelaez ◽

Maher Musleh ◽

Marco Bustamante ◽

Juan Stambuk ◽

...

Keyword(s):

Gastric Cancer ◽

Intestinal Type ◽

Diffuse Type ◽

Pathogen Recognition Receptors ◽

H Pylori ◽

Gastric Cancer Patients ◽

Diffuse Type Gastric Cancer ◽

Allele Model ◽

Control Study ◽

Oligomerization Domain

Abstract Background Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori. Results A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41–5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63–2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80–3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40–21.33, p = 4.1 × 10− 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13–0.10, p = 0.03). Conclusions NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.

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Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

International Journal of Veterinary Science ◽

10.37422/ijvs/20.043 ◽

2020 ◽

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Helicobacter Pylori ◽

Cancer Stem Cells ◽

Histopathological Examination ◽

Physiological Saline ◽

Rrna Gene ◽

Peptic Ulcers ◽

Gastric Cancer Stem Cells ◽

H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

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The correlation between lncRNAs and Helicobacter pylori in gastric cancer

Pathogens and Disease ◽

10.1093/femspd/ftaa004 ◽

2019 ◽

Vol 77 (9) ◽

Author(s):

Narges Dastmalchi ◽

Seyed Mahdi Banan Khojasteh ◽

Mirsaed Miri Nargesi ◽

Reza Safaralizadeh

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Molecular Mechanisms ◽

Gastrointestinal Diseases ◽

Mechanisms Of Action ◽

Molecular Pathways ◽

Gastric Diseases ◽

Non Coding Rnas ◽

H Pylori ◽

The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

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Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

International Journal of Molecular Sciences ◽

10.3390/ijms22094823 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4823

Author(s):

María Fernanda González ◽

Paula Díaz ◽

Alejandra Sandoval-Bórquez ◽

Daniela Herrera ◽

Andrew F. G. Quest

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Outer Membrane ◽

Extracellular Vesicles ◽

Membrane Vesicles ◽

Outer Membrane Vesicles ◽

Host Cells ◽

Gastric Epithelium ◽

Infected Cells ◽

H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

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Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Toxins ◽

10.3390/toxins13030181 ◽

2021 ◽

Vol 13 (3) ◽

pp. 181

Author(s):

Masami Suganuma ◽

Tatsuro Watanabe ◽

Eisaburo Sueoka ◽

In Kyoung Lim ◽

Hirota Fujiki

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cell Surface Receptor ◽

Tumor Promoter ◽

Cancer Development ◽

Human Gastric Cancer ◽

Tnf Α ◽

Surface Receptor ◽

H Pylori ◽

Factor Α

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

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