ABSTRACT
Helicobacter pylori (H. pylori) is responsible for causing chronic gastritis, which can cause peptic ulcer and premalignant lesions such as atrophic gastritis, intestinal metaplasia, and dysplasia, with the risk of developing gastric cancer. Recent data describe that H. pylori colonizes the gastric mucosa of more than 50% of the world's population; however, this bacterium has been described as infecting the human population since its prehistory. This review focuses on the populations and subpopulations of H. pylori, differentiated by the polymorphisms present in their constitutive and virulence genes. These genes have spread and associated with different human populations, showing variability depending on their geographical distribution, and have evolved together with the human being. The predominant genotypes worldwide, Latin America and Chile, are described to understand the genetic diversity and pathogenicity of H. pylori in different populations and geographic regions. The high similarity in the sequence of virulence genes between H. pylori strains present in Peruvian and Spanish natives in Latin America suggests a European influence. The presence of cagA-positive strains and vacA s1 m1 allelic variants is observed with greater prevalence in Chilean patients with more severe gastrointestinal diseases and is associated with its geographical distribution. These findings highlight the importance of understanding the genetic diversity of H. pylori in different regions of the world for a more accurate assessment of the risk of associated diseases and their potential impact on health.
Subject(s)
Gastritis, Atrophic , Gastritis , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Bacterial Proteins/genetics , Helicobacter pylori/genetics , Stomach Neoplasms/epidemiology , Stomach Neoplasms/microbiology , Latin America/epidemiology , Gastritis/pathology , Genotype , Risk Assessment , Helicobacter Infections/complications , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Antigens, Bacterial/geneticsABSTRACT
Our objective is to determine the gastric regenerative effect of Petroselinum sativum L. (parsley) consumption in rats with ethanolinduced gastritis. We developed an analytical, experimental, classical, cross-sectional, prospective study. We worked with 36 male Wistar rats (250 ± 30 g.p.c.) randomly distributed into 6 groups (n=6). Groups II-VI were subjected to a 24-hour fast to induce gastric ulcer by administering 10 mL/kg.p.c. of 70% ethanol via orogastric. After one hour, group II was sacrificed to observe the ulcerative damage in the stomach. Afterward, the aqueous extract of fresh parsley leaves (EAHP) was prepared, and the following treatment was administered to the other groups through the orogastric route for 3 days: group III, 10 mL/kg.p.c. 0.9% NaCl solution; and EAHP to groups IV-VI (150, 300, and 600 mg/Kg.p.c., respectively). The rats were then fasted for 24 hours before being sacrificed by breaking their necks. Subsequently, a laparotomy was performed to extract the stomach. The EAHP generated greater production of gastric mucus in the doses of 300 mg/kg.p.c. with 78.03% and 600 mg/kg.p.c. with 80.52% (p<0.05). This was consistent with what was observed histologically in the gastric mucosa, showing only signs of inflammation of the submucosa in the groups that consumed EAHP (IV-VI), compared with fibrinoid necrosis in the groups that did not consume it (II and III). In conclusion, the consumption of EAHP has a gastric regenerative effect in rats with ethanol-induced gastritis.
Subject(s)
Gastritis , Plant Extracts , Animals , Humans , Male , Rats , Anti-Ulcer Agents/therapeutic use , Cross-Sectional Studies , Ethanol/toxicity , Gastric Mucosa/pathology , Gastritis/chemically induced , Gastritis/pathology , Petroselinum , Plant Extracts/therapeutic use , Prospective Studies , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapyABSTRACT
BACKGROUND: Gastric non-Helicobacter pylori helicobacters (NHPH) naturally colonize the stomach of animals. In humans, infection with these bacteria is associated with chronic active gastritis, peptic ulceration and MALT-lymphoma. H. bizzozeronii belongs to these NHPH and its prevalence in children is unknown. CASE PRESENTATION: This case report describes for the first time a NHPH infection in a 20-month-old girl with severe gastric disorders in Mexico. The patient suffered from melena, epigastric pain, and bloating. Gastroscopy showed presence of a Hiatus Hill grade I, a hemorrhagic gastropathy in the fundus and gastric body, and a Forrest class III ulcer in the fundus. Histopathologic examination revealed a chronic active gastritis with presence of long, spiral-shaped bacilli in the glandular lumen. Biopsies from antrum, body and incisure were negative for presence of H. pylori by culture and PCR, while all biopsies were positive for presence of H. bizzozeronii by PCR. Most likely, infection occurred through intense contact with the family dog. The patient received a triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin for 14 days, completed with sucralfate for 6 weeks, resulting in the disappearance of her complaints. CONCLUSION: The eradication could not be confirmed, although it was suggested by clear improvement of symptoms. This case report further emphasizes the zoonotic importance of NHPH. It can be advised to routinely check for presence of both H. pylori and NHPH in human patients with gastric complains.
Subject(s)
Gastritis , Helicobacter Infections , Helicobacter pylori , Helicobacter , Stomach Diseases , Child , Female , Humans , Animals , Dogs , Infant , Mexico , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Gastritis/diagnosis , Gastritis/microbiology , Gastritis/pathologyABSTRACT
Along with Helicobacter pylori infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencingâ¯approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres (n = 10, H. pylori-positive = 7) and low-risk town of Tumaco (n = 10, H. pylori-positive = 6). Kraken2/Bracken was used for taxonomic classification and abundance. Functional gene profiles were inferred by InterProScan and KEGG analysis of assembled contigs and gene annotation. The most abundant taxa represented bacteria, non-human eukaryota, and viral genera found in skin, oral, food, and plant/soil environments including Staphylococus, Streptococcus, Bacillus, Aspergillus, and Siphoviridae. H. pylori was the predominant taxa present in H. pylori-positive samples. Beta diversity was significantly different based on H. pylori-status, risk group, and sex. WMS detected more bacterial taxa than 16S rRNA sequencing and aerobic, anaerobic, and microaerobic culture performed on the same gastric biopsy samples. WMS identified significant differences in functional profiles found between H. pylori-status, but not risk or sex groups. H. pylori-positive samples were significantly enriched for H. pylori-specific genes including virulence factors such as vacA, cagA, and urease, while carbohydrate and amino acid metabolism genes were enriched in H. pylori-negative samples. This study shows WMS has the potential to characterize the taxonomy and function of the gastric microbiome as risk factors for H. pylori-associated gastric disease. Future studies will be needed to compare and validate WMS versus traditional culture and 16S rRNA sequencing approaches for characterization of the gastric microbiome.
Subject(s)
Gastritis , Gastrointestinal Microbiome , Helicobacter Infections , Helicobacter pylori , Microbiota , Stomach Neoplasms , Humans , Stomach Neoplasms/microbiology , Colombia , RNA, Ribosomal, 16S/genetics , Helicobacter Infections/microbiology , Gastritis/pathology , Helicobacter pylori/genetics , Biopsy , Risk Factors , South AmericaABSTRACT
BACKGROUND: There is much debate over the occurrence of biliary reflux to the gastric pouch after one anastomosis gastric bypass (OAGB) and its potential risks. OBJECTIVE: To assess endoscopic and histopathological findings following a standardized protocol of biopsy collection two years after OAGB. METHODS: A historical cohort study was conducted, based on a prospectively collected database, which involved 39 participants who underwent OAGB. Participants underwent clinical evaluation and esophagogastroduodenoscopy at the time of surgery and 24 months afterward. Post-operatively, biopsy specimens in esophagogastric junction, pouch, and anastomosis were systematically collected. RESULTS: 92.3% of the participants were female and the mean age was 37 ± 8.5 years. The mean body mass index (BMI) significantly decreased from 37.6 ± 5.7 kg/m2 to 27 ± 4.1 kg/m2 after 2 years (p < 0.001). The mean %TWL was 27.2 ± 10.5%. The prevalence of non-erosive gastritis significantly increased from 25.6 to 51.3% (p = 0.02). Erosive gastritis significantly decreased from 28.2 to 10.3% (p = 0.04). Four cases of marginal ulcers were identified (10.3%). The commonest histopathological finding was mild inflammation in 74.3% (esophagogastric junction), 58.9% (pouch), and 71.8% (anastomosis). There was one case of focal intestinal metaplasia in each site of interest and no cases of dysplasia or severe inflammation. CONCLUSIONS: Using a standardized protocol of post-operative biopsy collection, low rates of severe endoscopic and histopathological abnormalities were observed two years after OAGB. Nevertheless, as most patients have histologically proven inflammation, bile in the gastric pouch, and endoscopic gastritis, long-term surveillance is essential because of the uncertain risk of these abnormalities.
Subject(s)
Gastric Bypass , Gastritis , Laparoscopy , Obesity, Morbid , Stomach Ulcer , Humans , Female , Adult , Middle Aged , Male , Gastric Bypass/adverse effects , Gastric Bypass/methods , Obesity, Morbid/surgery , Follow-Up Studies , Cohort Studies , Gastritis/epidemiology , Gastritis/etiology , Gastritis/pathology , Laparoscopy/methods , Metaplasia , Esophagogastric Junction/surgery , Esophagogastric Junction/pathology , Inflammation , Stomach Ulcer/surgery , Retrospective StudiesABSTRACT
In Argentina, despite the important studies conducted on the prevalence of infection and the antibiotic resistance of Helicobacter pylori, there are no reports simultaneously analyzing a profile of virulence factors of the bacterium and polymorphisms in cytokine genes in patients with different alterations in the gastric mucosa (including intestinal metaplasia, IM). Our aim was to evaluate H. pylori genotypes in 132 adult patients with chronic gastritis presenting three different histological findings (inactive chronic gastritis, active chronic gastritis IM- and active chronic gastritis IM+) along with SNP-174 G>C in the IL-6 gene. cagA, vacA and babA2 genes were analyzed by multiplex PCR. The -174 G>C SNP IL-6 gene was analyzed by PCR-RFLP. Patients with active chronic gastritis IM+ showed the highest proportion of the cagA(+)/IL-6GG, cagA(+)/vacAm1s1/IL-6GG and cagA(+)/vacAm1s1/babA2(+)/IL-6GG combinations (p<0.05). There was 4-5 times greater probability of finding patients presenting the GG genotype for SNP-174 G>C IL-6, which in turn were infected with the most virulent H. pylori genotypes -cagA(+), cagA(+)/vacAm1s1 and cagA(+)/vacAm1s1/babA2- in the ACGIM+ group in comparison to the ICG group. Our results provide regional data to the idea that the transition towards severe alterations in the gastric mucosa would be the result of a balance between specific factors of H. pylori and inherent host factors. This fact can be useful to identify patients at greater risk and to select those individuals requiring appropriate eradication treatment to prevent progression to gastric cancer.
Subject(s)
Gastritis , Helicobacter Infections , Helicobacter pylori , Adult , Humans , Bacterial Proteins/genetics , Antigens, Bacterial/genetics , Helicobacter pylori/genetics , Helicobacter Infections/microbiology , Interleukin-6/genetics , Gastritis/epidemiology , Gastritis/microbiology , Gastritis/pathology , GenotypeABSTRACT
Emerging deep learning-based applications in precision medicine include computational histopathological analysis. However, there is a lack of the required training image datasets to generate classification and detection models. This phenomenon occurs mainly due to human factors that make it difficult to obtain well-annotated data. The present study provides a curated public collection of histopathological images (DeepHP) and a convolutional neural network model for diagnosing gastritis. Images from gastric biopsy histopathological exams were used to investigate the performance of the proposed model in detecting gastric mucosa with Helicobacter pylori infection. The DeepHP database comprises 394,926 histopathological images, of which 111 K were labeled as Helicobacter pylori positive and 283 K were Helicobacter pylori negative. We investigated the classification performance of three Convolutional Neural Network architectures. The models were tested and validated with two distinct image sets of 15% (59K patches) chosen randomly. The VGG16 architecture showed the best results with an Area Under the Curve of 0.998%. The results showed that CNN could be used to classify histopathological images from gastric mucosa with marked precision. Our model evidenced high potential and application in the computational pathology field.
Subject(s)
Gastritis , Helicobacter Infections , Helicobacter pylori , Humans , Helicobacter Infections/diagnosis , Helicobacter Infections/pathology , Gastric Mucosa/pathology , Gastritis/diagnosis , Gastritis/pathology , Gastroscopy/methodsABSTRACT
Helicobacter pylori (H. pylori) infection involves multiple factors internal and external to the host. Among the internal factors, the immune response plays a fundamental role in the process of antigen presentation, lymphocytic response and cytokine-mediated regulatory response that are directly as sociated with disease progression and prognosis. OBJECTIVE: To compare the immune response in gas tric mucosa of H. pylori infected patients in two regions comparing the risk of developing gastric can cer. PATIENTS AND METHOD: 71 participants with symptoms of dyspepsia were included. The samples for biopsies were collected from different regions of the gastric mucosa; the identification of H. pylori was carried out by culture and polymerase chain reaction (PCR) of the ureA gene. For the characteri zation of the histopathological alterations and the immunophenotyping of lymphocytes, anti-human mouse monoclonal antibodies specific for each antigen were used: T lymphocytes: CD3 and CD8; B lymphocytes: CD20; Natural Killer Cells: CD56; Macrophages: CD68. RESULTS: The prevalence of H. pylori was 83.1%, the predominant types of gastritis were chronic gastritis and multifocal atrophic gastritis with intestinal metaplasia (63.4% and 22.5%, respectively). The cellular response was charac terized mainly by polymorphonuclear lymphocytes and positive anti-CD8 reactivity both in stroma and epithelium. CONCLUSIONS: Multifocal atrophic gastritis was more prevalent in the high-risk region for gastric cancer (GC) while non-atrophic gastritis and the expression of CD3 and CD8 antigens in the foveolar epithelium was higher in the low-risk region.
Subject(s)
Gastritis, Atrophic , Gastritis , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Animals , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Gastritis/metabolism , Gastritis/pathology , Gastritis, Atrophic/metabolism , Gastritis, Atrophic/pathology , Helicobacter Infections/complications , Helicobacter Infections/metabolism , Helicobacter Infections/pathology , Humans , Immunophenotyping , Mice , Stomach Neoplasms/etiology , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , T-Lymphocytes/metabolism , T-Lymphocytes/pathologyABSTRACT
Abstract Autoimmune gastritis is an underdiagnosed disease in the pediatric population due to the absence of specific signs and symptoms and late clinical manifestations. Iron deficiency anemia has recently been identified as an early hematological manifestation, allowing an early diagnostic approach. We present the case of a Colombian teenager, with no history of autoimmunity, with refractory iron deficiency. He underwent extension studies; biopsies and serology compatible with autoimmune gastritis were documented, requiring parenteral iron in its evolution. This pathology is underdiagnosed in our context since early diagnosis requires a high index of suspicion to prevent associated complications.
Resumen La gastritis autoinmune es una enfermedad subdiagnosticada en la población pediátrica. Lo anterior se debe a la ausencia de signos y síntomas específicos y manifestaciones clínicas tardías. Recientemente se ha identificado la anemia ferropénica como una manifestación hematológica precoz, lo que permite un enfoque diagnóstico temprano. Se presenta el caso de un adolescente colombiano, sin antecedentes de autoinmunidad, con ferropenia refractaria, en el que se realizaron estudios de extensión y se documentaron biopsias y serología compatible con gastritis autoinmune, con requerimiento de hierro parenteral en su evolución. Esta patología es subdiagnosticada en nuestro medio, ya que el diagnóstico temprano requiere un alto índice de sospecha, lo que permite la prevención de las complicaciones asociadas.
Subject(s)
Humans , Male , Adolescent , Autoimmune Diseases/diagnosis , Anemia, Iron-Deficiency/diagnosis , Gastritis/diagnosis , Autoimmune Diseases/pathology , Biopsy , Endoscopy, Digestive System , Early Diagnosis , Gastric Mucosa/pathology , Gastritis/pathologyABSTRACT
BACKGROUND: Recent experimental studies have suggested a potential link between cathepsin S (CTTS) and gastric adenocarcinoma progression. Herein, we aimed to evaluate the expression of CTTS in gastric adenocarcinoma in patients who underwent curative-intent surgical resection. METHODS: This was a cross-sectional study that included two groups: gastric adenocarcinoma (n = 42) and gastritis (n = 50). The gastritis group was then subdivided into H. pylori-positive (n = 25) and H. pylori-negative (n = 25) groups. Gastric tissue samples were analysed to determine CTTS expression through immunohistochemistry. Samples were obtained by oesophagogastroduodenoscopy or surgical specimens. RESULTS: In patients with gastritis, the age ranged from 18 to 78 years. Among them, 34% were male, and 66% were female. In patients with gastric adenocarcinoma, the age ranged from 37 to 85 years. Among them, 50% were male. When comparing the expression of CTTS between the two groups, only 16% of the gastritis samples had an expression higher than 25%. Alternatively, among patients with gastric adenocarcinoma, 19% had expression between 25-50%, 14.3% between 51-75%, and 26.2% had expression higher than 75% (p < 0.001). In the gastritis group, CTTS expression was significantly higher in patients with a positive test for H. pylori than negative test for H. pylori: 87.5% and 38.5%, respectively (p<0.001). There was no statistically significant association between CTTS positivity and clinicopathological variables, including tumour staging, histological type, angiolymphatic invasion, recurrence, current status and death. CONCLUSION: CTTS expression is higher in gastric adenocarcinoma samples. Patients with gastritis due to H. pylori also show a higher expression of CTTS than patients with negative results for this bacterium.
Subject(s)
Adenocarcinoma , Gastritis , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Adenocarcinoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Cathepsins , Cross-Sectional Studies , Female , Gastric Mucosa/pathology , Gastritis/pathology , Helicobacter Infections/complications , Helicobacter Infections/pathology , Humans , Male , Middle Aged , Stomach Neoplasms/pathology , Young AdultABSTRACT
PURPOSE: Analyze the expression of caspase-9, Smac/DIABLO, XIAP, let-7a, and let-7b in patients with normal gastric tissue, chronic gastritis, and gastric adenocarcinoma. METHODS: The expression of caspase-9, Smac/DIABLO, XIAP, let-7a, and let-7b by qRT-PCR was analyzed in 158 samples from 53 patients with normal gastric mucosa, 86 with chronic gastritis, and 19 with gastric cancer. RESULTS: The comparison between the gastric cancer and the control group revealed a decreased expression of caspase-9 in gastric cancer tissues; considering the Helicobacter pylor presence, comparable results were revealed. Smac/DIABLO was increased in gastric cancer cells, while XIAP demonstrated no significant difference in the gene expression. The microRNA analysis revealed a decreased expression of let-7a and let-7b in samples positive to H. pylori infection and in gastric cancer group, regardless of the presence of the bacterium. CONCLUSION: Our study provided some evidence of low activity of the intrinsic apoptosis pathway, as well as the influence of H. pylori on let-7a and let-7b expression.
Subject(s)
Adenocarcinoma/genetics , Apoptosis/genetics , Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Adult , Aged , Apoptosis Regulatory Proteins/genetics , Biopsy , Caspase 9/genetics , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/genetics , Gastritis/microbiology , Gastritis/pathology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Helicobacter Infections/genetics , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Humans , Male , MicroRNAs/genetics , Middle Aged , Mitochondrial Proteins/genetics , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , X-Linked Inhibitor of Apoptosis Protein/geneticsABSTRACT
PURPOSE: The aim of this study was to evaluate the expression of miR-125a-5p in patients with dyspeptic symptoms and gastric cancer, correlating them with the development of this cancer and H. pylori. METHODS: Patients were divided in groups according to histopathological analysis (control, gastritis, and cancer groups). Polymerase chain reaction was performed to detect H. pylori and real-time quantitative PCR to determine miR-125a-5p expression. RESULTS: H. pylori was detected in 44% of the patients, with prevalence in the gastritis and cancer groups. A statistically significant decrease of miR-125a-5p expression was found in the control positive (p = 0.0183*), gastritis positive (p = 0.0380*), and cancer positive (p = 0.0288*) groups when compared with the control negative group. CONCLUSION: We suggest that decreased expression of the miRNA-125a-5p associated with the presence of the H. pylori is an important mechanism in gastric diseases and could be a possible marker for early diagnosis of gastric cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Gastritis/genetics , Helicobacter Infections/genetics , MicroRNAs/metabolism , Stomach Neoplasms/genetics , Adult , Aged , Biomarkers, Tumor/analysis , Brazil/epidemiology , Cell Line, Tumor , Cell Proliferation , Early Detection of Cancer/methods , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/microbiology , Gastritis/pathology , Gene Expression Profiling , Genetic Predisposition to Disease , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Humans , Male , MicroRNAs/analysis , Middle Aged , Prevalence , Stomach Neoplasms/diagnosis , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: Though a few studies in animal models suggest that intestinal helminths (IH) favorably affect evolution of gastritis associated with Helicobacter pylori (H. pylori) the studies supporting this concept in humans are only a few and are based on serological data. METHODS: To evaluate the possible influence of IH on the human gastric mucosa, three groups of Venezuelan adults with gastropathy (endoscopically diagnosed) were studied: H. pylori-/IH- (n = 17), H. pylori+/IH- (n = 18), and H. pylori+/IH+ (n = 11). Histological analysis (hematoxylin-eosin) and immunohistochemical staining (peroxidase) for cytokines interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin 4 (IL-4) were undertaken in gastric antral biopsies. RESULTS: Expression of the four cytokines was detected in all individuals in varying degrees, but proinflammatory cytokines were expressed in a higher degree in the H. pylori+/IH- group, mainly IL-1ß (Th1-dominant immune response), associated with a higher degree of both histological inflammation and gastric cancer risk index (GCRI), as compared to the H. pylori-/IH- group. In contrast, an increased expression of IL-4 and a reduced expression of proinflammatory cytokines (Th2-dominant response), plus the tendency to a lower degree of mononuclear infiltration, mucosal atrophy in gastric corpus, and GCRI, were evidenced in the coinfected group. CONCLUSIONS: The findings of the present study is perhaps the first histological evidence of a possible modulatory effect of IH on the gastric mucosal inflammatory response due to H. pylori infection in humans.
Subject(s)
Coinfection/metabolism , Coinfection/pathology , Cytokines/metabolism , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections , Helicobacter pylori , Inflammation Mediators/metabolism , Intestinal Diseases, Parasitic/metabolism , Intestinal Diseases, Parasitic/pathology , Adolescent , Adult , Atrophy , Coinfection/immunology , Female , Gastric Mucosa/immunology , Gastritis/immunology , Gastritis/metabolism , Humans , Immunohistochemistry , Intestinal Diseases, Parasitic/immunology , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Young AdultABSTRACT
Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.
Subject(s)
Gastric Mucosa/pathology , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Precancerous Conditions/microbiology , Stomach Neoplasms/epidemiology , Adult , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Biopsy , Colombia/epidemiology , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Female , Gastric Mucosa/microbiology , Gastritis/microbiology , Gastritis/pathology , Genetic Markers , Genome, Bacterial/genetics , Genomic Islands , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Helicobacter pylori/pathogenicity , Humans , Male , Metaplasia/microbiology , Metaplasia/pathology , Mexico/epidemiology , Middle Aged , Polymorphism, Genetic , Precancerous Conditions/pathology , Risk Assessment/methods , Risk Factors , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology , Whole Genome SequencingABSTRACT
Helicobacter pylori (H. pylori) is one of the main causes of gastric gancer. TNF-related apoptosis-inducing ligand (TRAIL) is a protein able to promote apoptosis in cancer cells, however not in gastric cancer, which presents resistance to apoptosis via TRAIL. It is believed that MicroRNA-106b-5p might be involved in this resistance, although its role in Gastric Cancer is unclear. We aimed to determine the expression of microRNA-106b-5p and TRAIL in patients with gastric diseases, infected by H. pylori, and understand the relationship between these genes and their role in apoptosis and the gastric cancer pathways. H. pylori was detected by PCR, gene expression analysis was performed by real-time-qPCR, and bioinformatics analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape software. A total of 244 patients were divided into groups (Control, Gastritis, and Cancer); H. pylori was detected in 42.2% of the samples. The cancer group had a poor expression of TRAIL (p < 0.0001) and overexpression of microRNA-106b-5p (p=0.0005), however, our results confirmed that these genes are not directly related to each other although both are apoptosis-related regulators. Our results also indicated that H. pylori decreases microRNA-106b-5p expression and that this is a carcinogenic bacterium responsible for gastric diseases.
Subject(s)
Helicobacter Infections/genetics , MicroRNAs/genetics , Stomach Neoplasms/genetics , TNF-Related Apoptosis-Inducing Ligand/genetics , Apoptosis/genetics , Female , Gastritis/genetics , Gastritis/microbiology , Gastritis/pathology , Gene Expression Regulation, Neoplastic/genetics , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Humans , Male , Middle Aged , Signal Transduction/genetics , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathologyABSTRACT
In women, serum levels of CTSB, GKN2, LIPF, LIPFG, AZGP1, TOP2A and PGA4 are proposed as predictive markers of gastric cancer. It is unknown whether GKN1 expression varies with the sex of patients with chronic gastritis or gastric cancer. We studied 36 patients with histopathological diagnosis of chronic gastritis from the state of Guerrero, Mexico. PCR was performed for H. pylori detection and GKN1 expression was determined by RT-qPCR and western blot. GKN1 mRNA expression was significantly lower in patients with chronic follicular gastritis than in those with chronic chemical gastritis (p = 0.00071). The mRNA and protein level of expression of GKN1 were significantly lower in women with chronic follicular gastritis than in men with the same condition (p = 0.0279 and p = 0.0014, respectively); the lowest levels of GKN1 were detected in women with H. pylori-positive follicular gastritis (p = 0.0175 and p = 0.0111, respectively). Through a bioinformatic analysis, estrogen response elements were identified in the GKN1 promoter.
Subject(s)
Biomarkers/analysis , Gastritis/pathology , Helicobacter Infections/complications , Helicobacter pylori/isolation & purification , Peptide Hormones/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Chronic Disease , Female , Follow-Up Studies , Gastritis/epidemiology , Gastritis/metabolism , Gastritis/microbiology , Helicobacter Infections/microbiology , Humans , Mexico/epidemiology , Middle Aged , Peptide Hormones/genetics , Prognosis , Young AdultABSTRACT
BACKGROUND AND AIMS: Nodular gastropathy (NG) is an inflammatory condition of the gastric mucosa characterized by the endoscopic detection of multiple millimeter protrusions. A strong association between NG and Helicobacter pylori and a possible role of NG as a risk factor for undifferentiated gastric cancer have been described. The aim of this study was to characterize the pathogenic and inflammatory profile of patients with NG. METHODS: Adult patients referred for upper gastrointestinal endoscopy were prospectively enrolled in this study. H. pylori infection status was determined by rapid urease test. Biopsies were stained with hematoxylin-eosin. Sydney and OLGA scores were used to assess gastritis characteristics and gastric cancer risk. PCR analysis was performed to determine bacterial load and virulence factors CagA (and its EPIYA motifs) and VacA alleles. Finally, gastric mucosa cytokine gene expression (IL-8, IL-1ß, and TNF-α) was determined by real-time RT-PCR. RESULTS: Forty-eight patients, mean age of 36 years, were recruited. All NG patients were infected by H. pylori. OLGA score was similar in both groups (NG patients and non-NG patients). NG patients had higher bacterial load in the gastric corpus (p = 0.01) and significantly less pro-inflammatory cytokine levels than non-NG infected patients (p = 0.01). CONCLUSIONS: In our study, NG is not associated with preneoplastic lesions. An increase in bacterial load without a concomitant increase in mucosal inflammatory cytokine responses in H. pylori-infected subjects with NG may represent a general dampening of immune responses or an additional mechanism of H. pylori active immune evasion.
Subject(s)
Bacterial Load , Cytokines/genetics , Gastric Mucosa/microbiology , Gastritis/microbiology , Helicobacter Infections/microbiology , Adult , Antigens, Bacterial , Bacterial Proteins , Case-Control Studies , Cytokines/metabolism , Endoscopy, Digestive System , Endosonography , Female , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Gastritis/genetics , Gastritis/metabolism , Gastritis/pathology , Helicobacter Infections/genetics , Helicobacter Infections/metabolism , Helicobacter Infections/pathology , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Male , Middle Aged , Narrow Band Imaging , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Young AdultABSTRACT
BACKGROUND: It is widely assumed that gender, age, gastritis and Helicobacter pylori , all have some degree of correlation and, therefore, can synergistically lead to the development of gastric cancer. OBJECTIVE: In this cross-sectional study, we expected to observe the above mentioned correlation in the analysis of medical records of 67 patients of both sexes (female, n=44), mean age ± standard deviation: 41±12 years old, all from Belém (capital of Pará State, Brazilian Amazon), a city historically known as one with the highest gastric cancer prevalence in this country. METHODS: All patients were submitted to upper gastrointestinal endoscopy for gastric biopsy histopathological analysis and rapid urease test. All diagnoses of gastritis were recorded considering its topography, category and the degree of inflammatory activity, being associated or not associated with H. pylori infection. RESULTS: The results show that no statistically relevant associations were found among the prevalences of the observed variables. CONCLUSION: The authors hypothesize that observed risk factors associated to gastric cancer might be lesser synergistic than is usually expected.
Subject(s)
Gastric Mucosa/microbiology , Gastritis/microbiology , Helicobacter Infections/complications , Stomach Neoplasms/microbiology , Urease/analysis , Adult , Age Factors , Biopsy , Brazil/epidemiology , Cross-Sectional Studies , Endoscopy, Digestive System , Female , Gastric Mucosa/pathology , Gastritis/pathology , Helicobacter Infections/enzymology , Helicobacter Infections/epidemiology , Helicobacter pylori , Humans , Intestinal Mucosa/enzymology , Male , Middle Aged , Prevalence , Sex Distribution , Sex Factors , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathologyABSTRACT
ABSTRACT BACKGROUND: It is widely assumed that gender, age, gastritis and Helicobacter pylori , all have some degree of correlation and, therefore, can synergistically lead to the development of gastric cancer. OBJECTIVE: In this cross-sectional study, we expected to observe the above mentioned correlation in the analysis of medical records of 67 patients of both sexes (female, n=44), mean age ± standard deviation: 41±12 years old, all from Belém (capital of Pará State, Brazilian Amazon), a city historically known as one with the highest gastric cancer prevalence in this country. METHODS: All patients were submitted to upper gastrointestinal endoscopy for gastric biopsy histopathological analysis and rapid urease test. All diagnoses of gastritis were recorded considering its topography, category and the degree of inflammatory activity, being associated or not associated with H. pylori infection. RESULTS: The results show that no statistically relevant associations were found among the prevalences of the observed variables. CONCLUSION: The authors hypothesize that observed risk factors associated to gastric cancer might be lesser synergistic than is usually expected.
RESUMO CONTEXTO: É amplamente assumido que gênero, idade, gastrite e Helicobacter pylori , todos têm algum grau de correlação e, portanto, podem sinergicamente levar ao desenvolvimento de câncer gástrico. OBJETIVO: Neste estudo transversal, esperamos observar a correlação acima mencionada na análise de prontuários de 67 pacientes de ambos os sexos (sexo feminino, n=44), média de idade ± desvio padrão: 41±12 anos, todos de Belém (capital do Estado do Pará, Amazônia Brasileira), uma cidade historicamente conhecida como sendo uma das que apresenta maior prevalência de câncer gástrico no país. MÉTODOS: Todos os pacientes foram submetidos à endoscopia digestiva alta para análise histopatológica da biópsia gástrica e teste rápido da urease. Todos os diagnósticos de gastrite foram registrados considerando sua topografia, categoria e grau de atividade inflamatória, sendo associada ou não associada à infecção por H. pylori . RESULTADOS: Os resultados mostram que não foram encontradas associações estatisticamente relevantes entre as prevalências das variáveis observadas. CONCLUSÃO: Os autores levantam a hipótese de que os fatores de risco associados ao câncer gástrico podem ser menos sinérgicos do que o esperado.