RESUMO
BACKGROUND: To analyze the difference of serum gastrin-17 (G17) level in healthy people with different sex, age, and body mass index (BMI), to explore the correlation between G17 and pepsinogen, and to study the influences of Helicobacter pylori (H. pylori) infection and various inflammatory factors on G17 secretion level. METHODS: A total of 531 subjects who received physical examination in our center from April 2019 to December 2019 were enrolled in the study. All subjects were tested for G17, pepsinogen I (PGI), pepsinogen II (PGII), PGI/PGII ratio (PGR), H. pylori, serum amyloid A (SAA), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The difference of G17 secretion in different subjects and its correlation with PG were analyzed to investigate H. pylori infection and expound the effects of inflammatory indicators on G17. RESULTS: There was no significant difference in G17 secretion level in people with different sex, age and BMI (p > .05). G17 positively correlated with PGI and PGII, but negatively correlated with PGR. The G17 level of H. pylori-positive subjects was 10.16 ± 12.84, and prominently higher than that of H. pylori-negative subjects (3.27 ± 6.65). SAA and H. pylori infection were the greater risk factors for G17 abnormality among various indicators. CRP and ESR had no effect on G17 abnormality. CONCLUSIONS: G17 secretion is closely related to PG and H. pylori. Combined screening contributes to early screening of gastrointestinal diseases in normal people or groups at high risk for gastric cancer, but the influence of inflammatory indicators on G17 should be excluded to improve the reliability of the results.
Assuntos
Mucosa Gástrica , Gastrinas , Humanos , Mucosa Gástrica/metabolismo , Reprodutibilidade dos Testes , Gastrinas/metabolismo , Pepsinogênio A/metabolismo , Pepsinogênio C/metabolismo , Exame FísicoRESUMO
BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.
Assuntos
Refluxo Gastroesofágico , Refluxo Laringofaríngeo , Humanos , Pepsina A/análise , Pepsinogênio A/análise , Pepsinogênio A/metabolismo , Cromatografia Líquida , Saliva , Espectrometria de Massas em Tandem , Refluxo Gastroesofágico/diagnósticoRESUMO
EDUCATIONAL OBJECTIVE: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. OBJECTIVE: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H+ /K+ ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H+ /K+ ATPase proton pumps. STUDY DESIGN: In vitro translational. METHODS: BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing. RESULTS: Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. CONCLUSIONS: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. LEVEL OF EVIDENCE: NA Laryngoscope, 133:59-69, 2023.
Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Bombas de Próton , Pepsinogênio A/metabolismo , Inibidores da Bomba de Prótons , Esôfago de Barrett/complicações , Neoplasias Esofágicas/patologia , Pepsina A/metabolismo , Carcinogênese , Adenosina Trifosfatases/metabolismo , Microambiente TumoralRESUMO
Gastric adenocarcinoma of the fundic gland type (GAFG) has been recently classified by the World Health Organization (WHO), however, clinicopathologic features of pepsinogen I- or H+/K+-ATPase-positive gastric tumors remain unclear. Therefore, this study evaluates the frequency and clinicopathologic features of those tumors, using a tissue microarray block to identify pepsinogen I- or H+/K+-ATPase-positive tumors from 810 endoscopically resected, early gastric epithelial tumors. The frequency of pepsinogen I-positive lesions was 2.1%, and that of H+/K+-ATPase-positive lesions was 2.0%. Pepsinogen I- or H+/K+-ATPase positivity was not observed in undifferentiated-type tumors, while gastric tumors with morphologic similarity to fundic glands were positive for pepsinogen I- or H+/K+-ATPase. We divided pepsinogen I- or H+/K+-ATPase-positive gastric tumors into group A, with fundic gland-like structure, or group B, without fundic gland-like structure. The frequency of group A was 1.6%: 46.2% were positive only for pepsinogen I and 53.8% for H+/K+-ATPase and pepsinogen I. The frequency of group B was 1.5%: 25% were positive only for pepsinogen I, 8.3% for H+/K+-ATPase and pepsinogen I, and 66.7% only for H+/K+-ATPase. The 2 tumor groups differed in location and endoscopic features. Hematoxylin and eosin staining showed that group B had more exposed tumors to the surface, larger nuclei, and more background atrophy than group A. Immunostaining showed significantly higher positivity rates for MUC5AC, CD10, CDX2, and p53 expression, and a higher Ki-67 labeling score. Our results provide novel insights into the pathology of early gastric tumors with histologic or immunohistochemical evidence of fundic gland differentiation.
Assuntos
Adenocarcinoma , ATPase Trocadora de Hidrogênio-Potássio , Neoplasias Gástricas , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Humanos , Pepsinogênio A/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
We examined the development of gastric cancer risk screening, from rat pepsinogen studies in an experimental rat gastric carcinogenesis model induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and human pepsinogen studies in the 1970s and 1980s to the recent "ABC method" for human gastric cancer risk screening. First, decreased expression or absence of a major pepsinogen isozyme, PG1, was observed in the rat gastric mucosa from the early stages of gastric carcinogenesis to adenocarcinomas following treatment with MNNG. In the 1980s, decreases in PGI in the human gastric mucosa and serum were identified as markers of atrophic gastritis. In the 1990s, other researchers revealed that chronic infection with Helicobacter pylori (Hp) causes atrophic gastritis and later gastric cancer. In the 2000s, a gastric cancer risk screening method combining assays to detect serum anti-Hp IgG antibody and serum PGI and PGII levels, the "ABC method", was established. Eradication of Hp and endoscopic follow-up examination after the ABC method are recommended to prevent gastric cancer.
Assuntos
Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Animais , Carcinogênese , Detecção Precoce de Câncer , Humanos , Metilnitronitrosoguanidina , Pepsinogênio A/metabolismo , Infecção Persistente , Ratos , Neoplasias Gástricas/diagnósticoRESUMO
Based on the antibody typing classification, Helicobacter pylori infection can be divided into type I H. pylori infection and type II H. pylori infection. To observe the effects of different H. pylori infection types on the distribution of histopathological characteristics and the levels of three items of serum gastric function (PG I, PG II, G-17). 1175 cases from October 2018 to February 2020 were collected with ratio 1:2. All patients were performed with 14C-Urea breath test (14C-UBT), H. pylori antibody typing classification, three items of serum gastric function detection, painless gastroscopy, pathological examination, etc. According to H. pylori antibody typing classification, patients were divided into three groups: type I H. pylori infection group, type II H. pylori infection group and control group. Significant difference existed among type I H. pylori infection group, type II H. pylori infection group and control group in inflammation and activity (χ2 = 165.43, 354.88, P all < 0.01). The proportion of three groups in OLGA staging had statistic difference (χ2 = 67.99, P all < 0.01); Compared with type II H. pylori infection group and control group, the level of pepsinogen I, pepsinogen II, gastrin17 in type I H. pylori infection group increased, and PG I/PG II ratio (PG I/PG II ratio, PGR) decreased, which was statistically significant (χ2 = 35.08, 166.24, 134.21, 141.19; P all < 0.01). Type I H. pylori infection worsened the severity of gastric mucosal inflammation and activity. H. pylori infection was prone to induce atrophy of gastric mucosa, while type I H. pylori infection played a key role in promoting the progress of atrophic gastritis and affected the level of serum gastric function. The study indicated that the eradication of H. pylori should be treated individually.
Assuntos
Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Aceleração , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/metabolismo , Atrofia/metabolismo , Atrofia/microbiologia , Atrofia/patologia , Testes Respiratórios/métodos , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/metabolismo , Gastroscopia/métodos , Infecções por Helicobacter/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/metabolismo , Pepsinogênio C/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.
Assuntos
Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter , Helicobacter pylori , Medição de Risco/métodos , Neoplasias Gástricas/etiologia , Biomarcadores/metabolismo , Metilação de DNA , Reações Falso-Negativas , Feminino , Mucosa Gástrica/metabolismo , Gastrite/diagnóstico , Gastrite/genética , Humanos , Masculino , MicroRNAs/metabolismo , Pepsinogênio A/metabolismo , Risco , Fatores de Risco , Testes Sorológicos , Índice de Gravidade de DoençaRESUMO
1Department of General Surgery, The No.1 Hospital of Shijiazhuang, Shijiazhuang, China.
Assuntos
Gastrinas/metabolismo , Gastrite Atrófica/sangue , Microbioma Gastrointestinal/fisiologia , Pepsinogênio A/metabolismo , Neoplasias Gástricas/sangue , Adulto , Idoso , Feminino , Gastrite Atrófica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologiaRESUMO
AIM: Develop a program to identify, treat, and prevent severe atrophic gastritis to reduce gastric cancer incidence and mortality. MATERIALS AND METHODS: In total, 2,847 people aged > 40 years old underwent serological noninvasive screening for atrophic gastritis by identifying postprandial gastrin-17 and pepsinogen-1 in the fasting state. Anti-H pylori IgG was found in 2,134 patients. Seven years later, 2,220 patientswho had undergone serological noninvasive screening were asked to fill out a questionnaire survey (were interviewed). We could not find any information on 627 of 2,847 patients. Next, 75 patients with multifocal atrophic gastritis who underwent gastroscopy and biopsies (the Updated Sydney System (USS)) were selected. To study gastrin-17 production, morpho-functional correlation was studies in 75 patients with multifocal atrophic gastritis. RESULTS: During seven years, no reported case of gastric cancer was done among 2,220 persons who underwent serological screening and treatment. In the same population, 4.3 persons who did not receive screening during the same period, developed gastric cancer and died of it. In this study, we can say that 4.3 lives were saved out of 2,220 tested persons. The cost for screening this number of people amounted to 23,750. A comparison of the prevalence rate of the four stages of multifocal atrophic gastritis based on the data of the histopathology tests and noninvasive serologic screening in accordance with OLGA classification showed a strong correlation (the correlation coefficient is 0.812). This finding suggested that using this classification not only for histopathology tests for atrophic gastritis but also for serologic markers of antral mucosa and corpus ventriculi atrophy: gastrin-17 and pepsinogen-1. CONCLUSION: Complex pathogenetic treatment of atrophic gastritis significantly reduced gastric cancer risk and incidence for such patients.
.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/metabolismo , Mucosa Gástrica/patologia , Gastrite Atrófica/patologia , Programas de Rastreamento/métodos , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrinas/metabolismo , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/metabolismo , Gastroscopia , Infecções por Helicobacter/virologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pepsinogênio A/metabolismo , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/metabolismo , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismoRESUMO
BACKGROUND: The characteristics of Helicobacter pylori (HP) infection-negative gastric cancer (HPINGC) have not been well documented because of the rareness. The aim of this study was to classify HPINGC endoscopically and clinicopathologically. METHODS: This retrospective study included 1,741 early gastric cancer lesions and evaluated their HP infection status. Expression levels of MUC5AC, MUC6, MUC2, CD10, p53, MIB-1, pepsinogen-I, H+/K+ ATPase, chromogranin A, E-cadherin, and gastrin were evaluated in tumors by immunohistochemistry (IHC). RESULTS: Among the analyzed lesions, 19 (1.1%) were diagnosed as HPINGC and classified into 6 types: undifferentiated (5 lesions), fundic gland (2 lesions), cardiac gland (1 lesion), pyloric gland (3 lesions), foveolar (5 lesions), and mixed (3 lesions) types. Undifferentiated lesions were of pale color, with unclear demarcation and decreased E-cadherin expression. Fundic-type lesions were tan to reddish in color, with submucosal tumor-like protrusions, and positive for pepsinogen-I and H+/K+ ATPase. The cardiac gland type was located in the gastroesophageal junction and was positive for MUC6 and pepsinogen-I. Pyloric gland-type lesions were of the same color as normal mucosa, with mild elevation and unclear demarcation, likely positive for CD10 and chromogranin A. Foveolar epithelial-type lesions were white and elevated, with defined demarcation, and contained MUC5AC-positive cells. Mixed-type lesions, showing various staining patterns in IHC, had both elevated and depressed shape and reddish color. CONCLUSION: Endoscopic observation and IHC were useful for classifying the characteristics of HPINGC, which may preserve the characteristics of its region of origin.
Assuntos
Endoscopia , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Diferenciação Celular , Feminino , Mucosa Gástrica/patologia , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pepsinogênio A/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Although the high-throughput sequencing technique is useful for evaluating gastric microbiome, it is difficult to use clinically. We aimed to develop a predictive model for gastric microbiome based on serologic testing. METHODS: This study was designed to analyze sequencing data obtained from the Hanyang University Gastric Microbiome Cohort, which was established initially to investigate gastric microbial composition according to the intragastric environment. We evaluated the relationship between the relative abundance of potential gastric cancer-associated bacteria (nitrosating/nitrate-reducing bacteria or type IV secretion system [T4SS] protein gene-contributing bacteria) and serologic markers (IgG anti-Helicobacter pylori [HP] antibody or pepsinogen [PG] levels). RESULTS: We included 57 and 26 participants without and with HP infection, respectively. The relative abundance of nitrosating/nitrate-reducing bacteria was 4.9% and 3.6% in the HP-negative and HP-positive groups, respectively, while that of T4SS protein gene-contributing bacteria was 20.5% and 6.5% in the HP-negative and HP-positive groups, respectively. The relative abundance of both nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria increased exponentially as PG levels decreased. Advanced age (only for nitrosating/nitrate-reducing bacteria), a negative result of IgG anti-HP antibody, low PG levels, and high Charlson comorbidity index were associated with a high relative abundance of nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria. The adjusted coefficient of determination (R2) was 53.7% and 70.0% in the model for nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria, respectively. CONCLUSION: Not only the negative results of IgG anti-HP antibody but also low PG levels were associated with a high abundance of nitrosating/nitrate-reducing bacteria and T4SS protein gene-contributing bacteria.
Assuntos
Anticorpos Antibacterianos/imunologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Microbiota , Pepsinogênio A/metabolismo , Adulto , Carga Bacteriana , Comorbidade , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Pessoa de Meia-Idade , Prognóstico , Testes Sorológicos , Neoplasias Gástricas/etiologiaRESUMO
Background/Aims: In the ABC classification system, group A consists of seronegative subjects without gastric corpus atrophy. This study aimed to determine the prevalence and characteristics of pseudo group A subjects. Methods: Group A subjects were identified among consecutive Korean adults who underwent a serum anti-Helicobacter pylori immunoglobulin G (IgG) test and pepsinogen (PG) assay on the day of endoscopy. Past infection was defined as the presence of either eradication history or endoscopic findings suggesting past infection (i.e., gastric xanthoma, metaplastic gastritis, or advanced atrophy >closed-type 1). Results: Among 2,620 group A subjects, 448 (17.1%) had eradication history, and 133 (5.1%) showed endoscopic findings suggesting past infection. Older age (odds ratio [OR], 1.148; 95% confidence interval [CI], 1.067 to 1.236) and earlier year of birth (OR, 1.086; 95% CI, 1.009 to 1.168) were independent risk factors for classification into pseudo group A, with cutoff points at 50.5 years and birth year of 1959.5, respectively. Positive H. pylori test findings were found in 22 subjects (3.1%) among the 715 subjects who underwent the urea breath test or Giemsa staining on the same day. Current infection was positively correlated with PG I and PG II levels (p<0.001) but not with age, anti-H. pylori IgG titer, or classification into pseudo group A. Conclusions: Among the group A subjects, 22.2% had past infection. The risk was higher in subjects older than 50 years, especially those born before 1960. Furthermore, current infection was found in 3.1% of the subjects and was correlated with increased gastric secretory ability.
Assuntos
Gastrite Atrófica/complicações , Infecções por Helicobacter/complicações , Neoplasias Gástricas/diagnóstico , Idoso , Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Feminino , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/etnologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/etnologia , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/metabolismo , Estudos Prospectivos , Recidiva , República da Coreia/etnologia , Estudos Retrospectivos , Neoplasias Gástricas/etnologiaRESUMO
BACKGROUND: Helicobacter pylori (HP) infection and chronic atrophic gastritis (CAG) have shown strong associations with the development of gastric cancer. This study aimed to examine whether both risk factors are associated with accelerated epigenetic ageing, as determined by the 'DNA methylation age', in a population-based study of older adults (n=1477). METHODS: Serological measurements of HP antibodies and pepsinogen I and II for CAG definition were obtained by ELISA kits. Whole blood DNA methylation profiles were measured by Illumina Human Methylation450K Beadchip. DNA methylation ages were calculated by two algorithms proposed by Horvath and Hannum et al. RESULTS: After adjusting for potential covariates in linear regression models, we found that HP infection, infection with virulent HP strains (CagA+) and severe CAG were significantly associated with an increase in DNA methylation age by â¼0.4, 0.6 and 1 year (all P-values <0.05), respectively. CONCLUSIONS: Our study indicates that both CagA+ HP infection and CAG go along with accelerated epigenetic ageing.
Assuntos
Envelhecimento/genética , Senescência Celular/genética , Metilação de DNA , Epigênese Genética/genética , Gastrite Atrófica/genética , Infecções por Helicobacter/genética , Idoso , Anticorpos Antibacterianos/imunologia , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Gastrite Atrófica/complicações , Gastrite Atrófica/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/metabolismo , Helicobacter pylori/imunologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/metabolismo , Pepsinogênio C/metabolismo , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors. MATERIALS AND METHODS: Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO) 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands. RESULTS: As for patient characteristics, there were 76 men (75.2%) and 25 women (24.8%), with a median age of 65 years (range, 34 to 84). The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1%) and gastric-type tumors (12 lesions, 10.9%). Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7%) and tubulovillous-type tumors (7 lesions, 6.4%). Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7%) and pyloric gland-type (PG) tumors (9 lesions, 8.2%). The grade of atypia was significantly higher in gastric-type tumors (p<0.01). PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands. CONCLUSIONS: About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.
Assuntos
Neoplasias Duodenais/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adenoma/metabolismo , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/metabolismo , Carcinoma/patologia , Neoplasias Duodenais/classificação , Neoplasias Duodenais/metabolismo , Feminino , Mucinas Gástricas/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
Endoscopic findings of the background gastric mucosa are important in the Helicobacter pylori-seroprevalent population. It is strongly correlated not only with the risk of gastric cancer, but also with the excretion ability of gastric mucosa cells. In noninfected subjects, common endoscopic findings are regular arrangement of collecting venules, chronic superficial gastritis, and erosive gastritis. In cases of active H. pylori infection, nodularity on the antrum, hemorrhagic spots on the fundus, and thickened gastric folds are common endoscopic findings. The secreting ability of the gastric mucosa cells is usually intact in both noninfected and actively infected stomachs, and the intragastric condition becomes hyperacidic upon inflammation. Increased serum pepsinogen II concentration correlates well with active H. pylori infection, and also indicates an increased risk of diffuse-type gastric cancer. In chronic inactive H. pylori infection, metaplastic gastritis and atrophic gastritis extending from the antrum (closed-type chronic atrophic gastritis) toward the corpus (open-type chronic atrophic gastritis) are common endoscopic findings. The intragastric environment is hypoacidic and the risk of intestinal-type gastric cancer is increased in such conditions. Furthermore, there is a decrease in serum pepsinogen I concentration when the secreting ability of the gastric mucosa cells is damaged. Serologic and endoscopic changes that occur upon H. pylori infection are important findings for estimating the secreting ability of the gastric mucosa cells, and could be applied for the secondary prevention of gastric cancer.
Assuntos
Gastrite/diagnóstico por imagem , Infecções por Helicobacter/diagnóstico por imagem , Helicobacter pylori , Mucosa Gástrica/metabolismo , Gastrite/sangue , Gastrite/complicações , Gastroscopia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/complicações , Humanos , Pepsinogênio A/sangue , Pepsinogênio A/metabolismo , Fatores de Risco , Neoplasias Gástricas/etiologiaRESUMO
OBJECTIVE: To analyze the role and significance of pepsin and pepsinogen in the pathogenesis of OME in children. METHOD: Pediatric patients with otitis media aged 2-8 years who enrolled in our department of the hospital from May of 2012 to December of 2012 were set as experimental group (38 cases, 48 ears) which should be underwent tympanic membrane puncture/tube insertion. Meanwhile, pediatric patients waiting for cochlear implant without otitis media (10 ears), were set as control group. Middle ear lavage fluid and plasma samples from the two groups were collected and detected using enzyme-linked immune method for pepsin and pepsinogen. RESULT: The concentrations of pepsin and pepsinogen in the middle ear lavage fluid of OME group [(48.8 ± 415.99) ng/ml and 676.32 ± 336.71)ng/ml] were significantly higher than those in the control group [(8.20 ± 4.59)ng/ml and (77.27 ± 50.33) ng/ml] (P < 0.01). Meanwhile, the concentration of pepsinogen in the middle ear lavage of OME patients was significantly higher than that of plasma (P < 0.01). The concentration of pepsin in the middle ear lavage fluid from the dry ear subgroup was lower than those in the serum ear and mucous ear subgroups (P < 0.01), but there was no significant difference about concentrations of pepsinogen among the dry ear, serum ear and mucous ear subgroups (P > 0.05). CONCLUSION: Pepsin and pepsinogen in the middle ear cavity of OME patients maybe originated from laryngopharyngeal reflux (LPR), indicating that LPR is associated with the pathogenesis of OME in children.
Assuntos
Otite Média com Derrame/metabolismo , Pepsina A/metabolismo , Pepsinogênio A/metabolismo , Criança , Pré-Escolar , Orelha Média/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Refluxo Laringofaríngeo/fisiopatologia , Membrana Timpânica/cirurgiaRESUMO
The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84-95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.
Assuntos
Canais de Cloreto/genética , Digestão/fisiologia , Ácido Gástrico/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/biossíntese , Células Parietais Gástricas/metabolismo , Animais , Transporte Biológico , Canais de Cloro CLC-2 , Contagem de Células , Vesículas Citoplasmáticas/metabolismo , Digestão/genética , Imunofluorescência , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Camundongos , Camundongos Knockout , Microscopia Eletrônica , Células Parietais Gástricas/ultraestrutura , Pepsinogênio A/metabolismoRESUMO
Isolated porcine pepsinogen A was used for the preparation of polyclonal rabbit and polyclonal chicken anti-pepsinogen A antibodies. Immunochemical properties of both immunoglobulin fractions were compared. The rabbit anti-serum was further purified using immobilized porcine pepsinogen A on magnetic cellulose beads and the resulting anti-pepsinogen A fraction proved to be applicable for the separation and the determination of porcine pepsinogen A. In contrary, antibodies prepared from chicken eggs by the same way have been found not suitable for the evaluation of the pepsinogen A level. Unexpectedly, the pre-immune fraction of chicken antibodies showed reactivity against porcine pepsinogen A and the affinity separation of specific polyclonal chicken anti-pepsinogen A antibodies on immobilized porcine pepsinogen A did not result in an enrichment of anti-pepsinogen A antibodies.
Assuntos
Anticorpos/imunologia , Mucosa Gástrica/imunologia , Pepsinogênio A/imunologia , Animais , Bovinos , Galinhas , Ensaio de Imunoadsorção Enzimática , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Imuno-Histoquímica , Pepsinogênio A/metabolismo , Coelhos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , SuínosRESUMO
UNLABELLED: Gastric cancer remains a significant medical and social problem. Familial, hereditary, social, and demographic factors increase the susceptibility of subjects to cancer development, especially those infected with Helicobacter pylori (H. pylori). Apart from genetic studies, there are ongoing biochemical studies of possible practical value in assessment of the risk of gastric cancer development. The GastroPanelBiohit test, that include determination of the levels of gastrin (G-17), pepsinogen I (PGI), pepsinogen II (PGII) and antibodies IgG/IgA against H. pylori in serum, allowed us to determine whether there are any abnormal changes in the gastric mucosa. The aim of the study was to determine whether GastroPanel parameters, identified in patients with dyspeptic symptoms (with or without history of gastric cancer in first degree relatives) before and after successful eradication of H. pylori, have any clinical value, especially in gastric cancer development. MATERIAL AND METHODS: The study comprised 61 patients aged 18-56 years with symptoms of dyspepsia. In all patients, the preliminary urea breath test (UBT) for the presence of H. pylori was performed and the positive result qualified for further study. For final analysis, 42 patients were approved, who were divided into two groups: group I (a control group) - 22 patients with negative family history of gastric cancer among the relatives of first degree, group II - 20 patients with positive history of gastric cancer among the relatives of first degree. All the patients had the gastroscopy with the biopsy of gastric mucosa for the histopathological evaluation. Additionally, the GastroPanel test was performed. RESULTS: In the blood serum of the patients with H. pylori infection, the concentrations of gastrin (G-17), pepsinogen I (PGI) and pepsinogen II (PGII) did not depend on family history of gastric cancer (p > 0.05). Successful eradication of H. pylori decreases the levels of G-17, PGI and PGII (statistical significance p < 0.05), and this correlates with the histopathological changes of gastric mucosa. The patients with positive family history of gastric cancer had more intense H. pylori colonization of gastric mucosa (IV degree of insensitivity of infection in UBT; group I - 22% vs group II - 69%) as compared to the control group. After effective eradication of H. pylori, statistically significant decreases of IgG H. pylori antibodies and of the level of gastrin (p < 0.05) in blood serum were seen (in a 3 months follow up) only in the control group. CONCLUSIONS: Independently of the history of familial gastric cancer, the GastroPanelBiohit test provides important clinical data useful for diagnosis, for assessment of effectiveness of H. pylori eradication therapy and in evaluation of the degree of the inflammatory changes in gastric mucosa.
Assuntos
Dispepsia/complicações , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/genética , Adolescente , Adulto , Biópsia , Testes Respiratórios , Feminino , Mucosa Gástrica/patologia , Gastrinas/metabolismo , Gastroscopia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Anamnese , Pessoa de Meia-Idade , Pepsinogênio A/metabolismo , Pepsinogênio C/metabolismo , Ureia/análise , Adulto JovemRESUMO
BACKGROUND/AIMS: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5ß1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5ß1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5ß1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis. METHODS: The expressions of integrin α5 and ß1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5ß1 expression were compared among the 172 H. pylori-infected patients with different cancer risks. RESULTS: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin ß1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5ß1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5ß1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05). CONCLUSIONS: H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication.