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1.
Anticancer Res ; 39(10): 5715-5720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570472

RESUMO

BACKGROUND/AIM: The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS: PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS: Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION: PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.


Assuntos
Expressão Gênica/genética , Isoenzimas/genética , Proteína Quinase C/genética , Neoplasias Gástricas/genética , Gastrectomia/métodos , Mucosa Gástrica/patologia , Humanos , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/patologia
2.
Cancer Invest ; 37(9): 417-426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483161

RESUMO

To investigate the molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication, expression of miR-124a, miR-34b, and miR-34c was examined in nonneoplastic gastric specimens after successful H. pylori eradication. The magnifying narrow-band imaging (NBI) endoscopic features of gastric mucosa were also examined. The atrophic type, an informative endoscopic feature for histological intestinal metaplasia, showed lower expression of miR-124a. Lower expression of miR-124a correlated with hypermethylation of the miR-124a3 locus. The atrophic type represents gastric microarchitectures associated with irreversibility with H. pylori eradication and downregulation of miR-124a.


Assuntos
Regulação para Baixo , Mucosa Gástrica/diagnóstico por imagem , Infecções por Helicobacter/prevenção & controle , MicroRNAs/genética , Imagem de Banda Estreita/métodos , Neoplasias Gástricas/genética , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Erradicação de Doenças , Epigênese Genética , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico por imagem
3.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
4.
Z Gastroenterol ; 57(8): 952-959, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31398766

RESUMO

AIMS: The aim of this study was to evaluate the short-term complications of submucosal tunneling endoscopic resection (STER) for large submucosal tumors (SMTs) originating from the muscularis propria (MP) layer in the esophagus and gastric cardia. METHODS: We performed 286 cases of STER from September 2012 to December 2017. The clinical data of patients with SMTs originating from the MP layer of 3.0-7.0 cm, who underwent STER procedure at the endoscopy center of Tianjin Medical University General Hospital, were collected retrospectively. Epidemiological data, tumor location, tumor size, procedure-related parameters, complications, and follow-up were included. RESULTS: A total of 27 (9.4 % [27/286]) patients were large-size SMTs, with a mean age of 51.9 ±â€Š9.4 years. The male/female ratio was 19:8. Of the 27 SMTs, 23 were located in the esophagus and 4 in the gastric cardia. The mean tumor size was 4.0 ± 1.1 cm. The en bloc resection rate was 85.2 % (23/27), and the complete resection rate was 100 % (27/27). Intra-operative perforation occurred in 2 patients (7.4 %) and post-operative perforation occurred in 2 patients (7.4 %). No other complications were observed. The average cost of the procedure was $3357.99 ± $1171.60 per inpatient stay (including both the procedure and an additional inpatient stay). The mean follow-up time was 15 ±â€Š10.1 months. No recurrence and metastasis occurred during the follow-up period. CONCLUSIONS: There is low risk of STER for the large-sized SMTs in the esophagus and gastric cardia, and the most common complication occurred during or after the procedure is perforation.


Assuntos
Cárdia/patologia , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/cirurgia , Gastrectomia/métodos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Neoplasias Esofágicas/patologia , Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(32): e16578, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393357

RESUMO

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been well-established methods of treating upper gastrointestinal neoplasia. The aim of this study was to identify the safety and effectiveness of endoscopic treatment for gastric neoplasia within a 2-day hospital stay.Between 2004 and 2015, a total of 914 patients with gastric neoplasia were treated with EMR or ESD within 2 days of hospitalization. The neoplasia sites, en bloc resection rates, pathology, local residual neoplasia rates, and major complications were evaluated retrospectively.The mean age was 63.4 years old, and 636 (69.6%) patients were male. Adenoma was the most common final diagnosis (60.9%), followed by adenocarcinoma (28.9%). The first follow-up endoscopy was performed 4.9 ±â€Š1.1 months after the procedure, and an average of 4.4 endoscopic examinations were performed for 7.16 years (range, 2.1 to 10.2 years). Additional surgery was performed in 11 (1.2%) cases based on post-procedure pathology results. On follow-up endoscopy, a mean of 5.9 months after the procedure, there were 18 residual neoplasia cases (EMR = 13, ESD = 5). Only 4 (0.4%) patients returned to the emergency unit with delayed bleeding, but all 4 cases were successfully controlled with endoscopic treatment. There were no other complications such as delayed perforation or aspiration pneumonia during the 2 days in hospital.EMR and ESD within only 2 days in hospital showed safe and effective outcomes in terms of managing early gastric neoplasia with low complication and local residual rates.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/estatística & dados numéricos , Mucosa Gástrica/cirurgia , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Mucosa Gástrica/patologia , Gastroscopia/métodos , Gastroscopia/estatística & dados numéricos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Estudos Retrospectivos , Neoplasias Gástricas/patologia
6.
Toxicol Lett ; 313: 150-158, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276768

RESUMO

Ochratoxin A (OTA), one of the most abundant food-contaminating mycotoxins, is a possible carcinogen to humans. We previously demonstrated that long-term (40 weeks) OTA exposure induces the malignant transformation of human gastric epithelium cells (GES-1) in vitro. However, the specific mechanism underlying OTA-induced gastric carcinogenesis is complex. In the present study, we used 2-DE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF MS) combined with bioinformatics and immunoblotting to investigate the differentially expressed proteins between GES-1 and OTA-malignant transformed GES-1 cells (OTA-GES-1T cells) in vitro. We found that four differentially expressed proteins were identified after malignant transformation, including actin, cytoplasmic 1 (ACTB), F-actin-capping protein subunit alpha-1 (CAPZA1), Annexin A3 (ANXA3), thioredoxin peroxidase B from red blood cells (TPx-B) and Fibrinogen beta B (Fibrinogen ß). Among the differentially expressed proteins, the effect of Annexin A3 was analyzed by MTT assay, western blot, cell cycle analysis, wound healing assay, Transwell assay, and colony formation assay in OTA-GES-1T cells. The results showed that inhibition of Annexin A3 by siRNA effectively prevented the proliferation, migration, and invasion abilities of OTA-GES-1T cells. Collectively, the results of this study will guide future research on OTA carcinogenicity.


Assuntos
Anexina A3/metabolismo , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Ocratoxinas/toxicidade , Neoplasias Gástricas/induzido quimicamente , Anexina A3/genética , Western Blotting , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Biologia Computacional , Eletroforese em Gel Bidimensional , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Invasividade Neoplásica , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(7): 634-638, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31302960

RESUMO

Objective: To evaluate the clinical value of dual channel dual curved endoscope in the endoscopic submucosal dissection (ESD) for gastric angle mucosal lesions. Methods: A descriptive cohort study was carried out. Clinicopathological data of 20 cases with gastric angle mucosal lesions undergoing ESD by dual channel dual curved endoscope in our center from October 2016 to August 2018 were collected and analyzed retrospectively. Inclusion criteria: (1) the lesion was located in the gastric angle confirmed by gastroscopy before ESD. (2) CT examination showed no distant metastasis. (3) pathological biopsy confirmed precancerous lesion or early cancerous lesion without submucosal invasion. (4) the whole operation was performed by the same endoscopist with ESD experience of about 2000 cases. Patients with previous ESD history of gastric angle and other serious diseases were excluded. The dual channel dual curved endoscopy (Olympus, GIF-2TQ260M) and other conventional endoscopic surgical instruments were used in all the cases. Complete tumor resection rate, pathological results, intraoperative and postoperative complications, operation time and hospitalization time were observed. Follow - up parameters included residual tumor, local recurrence and heterogeneous lesion. Results: Of 20 patients, 14 were male and 6 were female with an average of 55.6 years (range, 37 to 75). All the tumors located in gastric angle. Specimen size ranged from 1.2 to 5.5 (average 2.9) cm. Operation time ranged from 50 to 120 (average 85.8) minutes. Hospital stay ranged from 3 to 7 (average 5.1) days. The en bloc excision was performed successfully in all 20 cases. There was no perforation or bleeding during or after operation. Pathological results showed curative or nearly curative resection stage in all the cases. No tumor residual or recurrence was found during follow-up for 8 to 30 (average 18.5) months. Conclusion: Dual channel dual curved endoscope can provide good vision and easy control in removing the lesion completely and avoiding complications during the ESD procedure in gastric angle mucosal lesions with good long-term efficacy.


Assuntos
Ressecção Endoscópica de Mucosa/instrumentação , Mucosa Gástrica/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Biópsia , Estudos de Coortes , Endoscópios Gastrointestinais , Feminino , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia
8.
Mol Carcinog ; 58(8): 1427-1437, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31162747

RESUMO

The Helicobacter pylori (H. pylori) cytotoxin-associated gene A (CagA) and Krüppel-like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA-mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori-positive GC cells compared with the H. pylori-negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR-155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR-155 in GES-1 promoted epithelial-mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR-155/KLF4 signaling pathway provided a new insight into the development and treatment of GC.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Transformação Celular Neoplásica/patologia , Mucosa Gástrica/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Gástricas/patologia , Adulto , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/genética , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Mucosa Gástrica/citologia , Células HEK293 , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , MicroRNAs/metabolismo , Transplante de Neoplasias , Transdução de Sinais , Estômago/patologia , Neoplasias Gástricas/genética , Transplante Heterólogo
9.
Nat Commun ; 10(1): 2735, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227713

RESUMO

The contribution of mast cells in the microenvironment of solid malignancies remains controversial. Here we functionally assess the impact of tumor-adjacent, submucosal mast cell accumulation in murine and human intestinal-type gastric cancer. We find that genetic ablation or therapeutic inactivation of mast cells suppresses accumulation of tumor-associated macrophages, reduces tumor cell proliferation and angiogenesis, and diminishes tumor burden. Mast cells are activated by interleukin (IL)-33, an alarmin produced by the tumor epithelium in response to the inflammatory cytokine IL-11, which is required for the growth of gastric cancers in mice. Accordingly, ablation of the cognate IL-33 receptor St2 limits tumor growth, and reduces mast cell-dependent production and release of the macrophage-attracting factors Csf2, Ccl3, and Il6. Conversely, genetic or therapeutic macrophage depletion reduces tumor burden without affecting mast cell abundance. Therefore, tumor-derived IL-33 sustains a mast cell and macrophage-dependent signaling cascade that is amenable for the treatment of gastric cancer.


Assuntos
Interleucina-33/imunologia , Macrófagos/imunologia , Mastócitos/imunologia , Neoplasias Gástricas/imunologia , Aminopiridinas/administração & dosagem , Animais , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Cromolina Sódica/administração & dosagem , Modelos Animais de Doenças , Epitélio/imunologia , Epitélio/patologia , Feminino , Mucosa Gástrica/citologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Pirróis/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise Serial de Tecidos , Microambiente Tumoral/imunologia
10.
Food Chem Toxicol ; 131: 110539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158404

RESUMO

The chemical characterization and protective role against ethanol-induced gastric ulcerated rats of a polysaccharide fraction from Bletilla striata (BSP) collected by ultrafiltration membrane approach were evaluated. This BSP faction was consisted of mannose and glucose at a molar ratio of 2.4:1 approximately, with a molecular weight of 146 KDa. FT-IR, NMR and XRD spectra indicated that BSP faction contained α-Man and ß-Glc residues with low overall crystallinity. The polysaccharide exhibited significant scavenging activities of ABTS and FRAP, as well as non-toxicity against human gastric epithelial GES-1 cells. Oral administration with 100 mg/kg of BSP for 3 days continuously could significantly prevent the formation of ethanol-induced gastric mucosal lesion. It could also reduce the levels of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IL-18, and MPO activity in gastric tissue. Additionally, the BSP faction exhibited antioxidant activity, increased the content of PEG2 as a defensive factor, and suppressed MAPK/NF-κB signaling pathway in gastric tissue. These results indicated that the gastroprotective activity of BSP faction could be attributed to the reduction of pro-inflammatory cytokines and oxidative stress and the inhibition of MAPK/NF-κB pathways. Our results provided substantial evidence that BSP could be a promising phytomedicine for gastric ulcer prevention.


Assuntos
Fármacos Gastrointestinais/farmacologia , Orchidaceae/química , Polissacarídeos/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Linhagem Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Etanol , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Ratos , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
11.
Ann Hematol ; 98(8): 1981-1987, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177299

RESUMO

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidade , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Carcinogênese/patologia , Estudos de Casos e Controles , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Humanos , Japão , Modelos Logísticos , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/microbiologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/microbiologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pepsinogênio A/sangue , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
12.
BMC Public Health ; 19(1): 730, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185961

RESUMO

BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.


Assuntos
Efeitos Psicossociais da Doença , Gastrite/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Regiões Árticas/epidemiologia , Biópsia , Testes Respiratórios , Canadá/epidemiologia , Criança , Pré-Escolar , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastroscopia/estatística & dados numéricos , Infecções por Helicobacter/microbiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Metaplasia , Pessoa de Meia-Idade , Prevalência , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Adulto Jovem
13.
Curr Top Microbiol Immunol ; 421: 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123883

RESUMO

It has been over 30 years since a link was established between H. pylori infection of the gastric mucosa and the development of chronic gastric diseases. Research in rodent models supported by data from human tissue demonstrated that the host immune response to H. pylori is limited by host regulatory T cells. Immunization has been shown to induce a potent Th1- and Th17-mediated immune response capable of eradicating or at least significantly reducing the bacterial load of H. pylori in the stomach in small animal models. These results have not translated well to humans. Clinical trials employing many of the strategies used in rodents for oral immunization including the use of a mucosal adjuvant such as Escherichia coli LT or delivery by attenuated enteric bacteria have failed to limit H. pylori infection and have highlighted the potential toxicity of exotoxin-based mucosal adjuvants. A recent study, however, utilizing a recombinant fusion protein of H. pylori urease and the subunit B of E. coli LT, was performed on over 4000 children. Efficacy of over 70% was demonstrated against naturally acquired infection compared to control volunteers one year post-immunization. Efficacy was reduced, but still above 50% at three years. This study provided new insight into the strategies for developing an improved vaccine for widespread use in countries with high infection rates and where gastric cancer (GC) remains one of the most common causes of death due to cancer.


Assuntos
Vacinas Bacterianas/imunologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/química , Escherichia coli/imunologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/prevenção & controle , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia
14.
Curr Top Microbiol Immunol ; 421: 107-137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123887

RESUMO

Over the last years, intensive investigations in molecular biology and cell physiology extended tremendously the knowledge about the association of inflammation and cancer. In frame of this paradigm, the human pathogen Helicobacter pylori triggers gastritis and gastric ulcer disease, and contributes to the development of gastric cancer. Mechanisms, by which the bacteria-induced inflammation in gastric mucosa leads to intestinal metaplasia and carcinoma, are represented in this review. An altered cell-signaling response and increased production of free radicals by epithelial and immune cells account for the accumulation of DNA damage in gastric mucosa, if infection stays untreated. Host genetics and environmental factors, especially diet, can accelerate the process, which offers the opportunity of intervention based on a balanced nutrition. It is supposed that inflammation might influence stem- or progenitor cells in gastric tissue predisposing for metaplasia or tumor relapse. Herein, DNA is strongly mutated and labile, which restricts therapy options. Thus, the understanding of the mechanisms that underlie gastric carcinogenesis will be of preeminent importance for the development of strategies for screening and early detection. As most gastric cancer patients face late-stage disease with a poor overall survival, the development of multi-targeted therapeutic intervention strategies is a major challenge for the future.


Assuntos
Carcinogênese , Dano ao DNA , Mucosa Gástrica/patologia , Inflamação/patologia , Neoplasias Gástricas/patologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Inflamação/genética , Inflamação/microbiologia , Recidiva Local de Neoplasia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia
15.
Curr Top Microbiol Immunol ; 421: 319-359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123895

RESUMO

The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in etiopathogenesis and ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer (GC) cases. As we increase our understanding of how chronic inflammation develops in the stomach and contributes to carcinogenesis, there is increasing interest in targeting cancer-promoting inflammation as a strategy to treat GC. Moreover, once cancer develops and anti-cancer immune responses are suppressed, there is evidence of a substantial shift in the microenvironment and new targets for immune therapy emerge. In this chapter, we provide insight into inflammation-related factors, including T lymphocytes, macrophages, pro-inflammatory chemokines, and cytokines, which promote H. pylori-associated GC initiation and growth. While intervening with chronic inflammation is not a new practice in rheumatology or gastroenterology, this approach has not been fully explored for its potential to prevent carcinogenesis or to contribute to the treatment of GC. This review highlights current and possible strategies for therapeutic intervention including (i) targeting pro-inflammatory mediators, (ii) targeting growth factors and pathways involved in angiogenesis in the gastric tumor microenvironment, and (iii) enhancing anti-tumor immunity. In addition, we highlight a significant number of clinical trials and discuss the importance of individual tumor characterization toward offering personalized immune-related therapy.


Assuntos
Inflamação/imunologia , Inflamação/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Citocinas/imunologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/terapia , Helicobacter pylori/patogenicidade , Humanos , Inflamação/microbiologia , Inflamação/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia , Microambiente Tumoral
16.
Gastroenterology ; 157(2): 349-364.e1, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31082367

RESUMO

In patients with Barrett's esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin, including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophagogastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.


Assuntos
Esôfago de Barrett/patologia , Células Epiteliais/patologia , Mucosa Esofágica/patologia , Adenocarcinoma/patologia , Adenocarcinoma/prevenção & controle , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Cárdia/citologia , Cárdia/patologia , Transdiferenciação Celular , Progressão da Doença , Mucosa Esofágica/citologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/prevenção & controle , Junção Esofagogástrica/citologia , Junção Esofagogástrica/patologia , Mucosa Gástrica/citologia , Mucosa Gástrica/patologia , Humanos , Metaplasia/patologia , Estados Unidos , Cicatrização/fisiologia
17.
Nat Commun ; 10(1): 2273, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118420

RESUMO

The human pathogen Helicobacter pylori displays extensive genetic diversity. While H. pylori is known to evolve during infection, population dynamics inside the gastric environment have not been extensively investigated. Here we obtained gastric biopsies from multiple stomach regions of 16 H. pylori-infected adults, and analyze the genomes of 10 H. pylori isolates from each biopsy. Phylogenetic analyses suggest location-specific evolution and bacterial migration between gastric regions. Migration is significantly more frequent between the corpus and the fundus than with the antrum, suggesting that physiological differences between antral and oxyntic mucosa contribute to spatial partitioning of H. pylori populations. Associations between H. pylori gene polymorphisms and stomach niches suggest that chemotaxis, regulatory functions and outer membrane proteins contribute to specific adaptation to the antral and oxyntic mucosa. Moreover, we show that antibiotics can induce severe population bottlenecks and likely play a role in shaping the population structure of H. pylori.


Assuntos
Adaptação Biológica/genética , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Taxa de Mutação , Adulto , Idoso , Biópsia , Quimiotaxia/genética , Mucosa Gástrica/patologia , Genoma Bacteriano/genética , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Pessoa de Meia-Idade , Filogenia , Polimorfismo Genético
18.
Medicine (Baltimore) ; 98(20): e15710, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096520

RESUMO

BACKGROUND: To systematically evaluate efficacy of traditional Chinese medicine (TCM) in treating chronic gastritis (CG). METHODS: Data sources from PubMed, Embase, Springer Link, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Biomedicine Database, and Wan-fang database were searched up to July 5, 2018. Review Manager software version 5.3, the Cochrane Collaboration's risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation profiler software were conducted for this meta-analysis. RESULTS: Sixteen studies involving 1673 participants (906 vs 767) were included in this study. Pooled data showed significant statistical differences between TCM groups and current routine pharmacotherapy (RP) groups in overall clinical efficacy (odds ratio [OR] 4.65; 95% confidence interval [CI] 3.29, 6.56; P < .00001), efficacy under endoscopy (OR 2.46; 95% CI 1.12, 5.43; P = .03), stomach distension (mean difference [MD] -0.37; 95% CI -0.56, -0.19; P < .0001), stomachache (standardized MD [SMD] -0.80; 95% CI -1.45, -0.14; P = .02), and belching (SMD -2.00; 95% CI -3.80, -0.20; P = .03). However, acid regurgitation (SMD -0.71; 95% CI -1.69, 0.28; P = .16) and anorexia (SMD -0.75; 95% CI -2.30, 0.80; P = .35) showed no significant statistical differences between 2 groups. In addition, incidence of adverse reactions of TCM groups was lower than that of RP groups. CONCLUSION: Evidence from this meta-analysis suggests that TCM could be more efficacious than current RP in treating CG. But further standardized research of rigorous design should be needed to further validate its efficacy.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Doença Crônica , Endoscopia do Sistema Digestório/métodos , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Gastrite/diagnóstico por imagem , Gastrite/patologia , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
19.
Isr Med Assoc J ; 5(21): 339-344, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31140227

RESUMO

BACKGROUND: The prevalence of Helicobacter pylori varies geographically by age, race, and socioeconomic status (SES). However, the impact of ethnicity on endoscopic outcomes in infected individuals is not well known. OBJECTIVES: To assess the impact of ethnicity among Israelis with biopsy-proven H. pylori infection. METHODS: A retrospective study, including patients who underwent gastroscopy and were diagnosed histologically with H. pylori infection, was conducted. Information on demographics, SES, medications, and co-morbidities were extracted from medical records. Univariate (Student's t-test, chi-square test) and multivariate (multinomial and logistic) regression analysis were conducted to examine the predictors of the clinical outcome. RESULTS: The study included 100 Israeli Jews and 100 Israeli Arabs diagnosed with biopsy-proven H. pylori infection. At univariate analysis, the number of households was higher among Arabs (P < 0.001), whose family income and parental education were lower than among Jews (P < 0.001 for both variables). The response to amoxicillin and clarithromycin differed between the two groups, being higher among Jews (P < 0.001).In clinical outcomes (gastritis severity, gastric and duodenal ulcer, intestinal metaplasia, atrophic gastritis, and MALT), no statistically significant differences could be detected between Jews and Arabs. Concerning intestinal metaplasia, lack of consumption of nonsteroidal anti-inflammatory drugs resulted a statistically significant protective factor (odds ratio 0.128, 95% confidence interval 0.024-0.685, P = 0.016). CONCLUSIONS: Although in the literature ethnicity seems to be a risk factor for H. pylori colonization, no statistical significance was detected in various endoscopic and histological findings related to H. Pylori infection between Israeli Arabs and Jews.


Assuntos
Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Mucosa Gástrica , Gastrite , Gastroscopia , Infecções por Helicobacter , Helicobacter pylori/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Árabes/estatística & dados numéricos , Biópsia/métodos , Biópsia/estatística & dados numéricos , Demografia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/etnologia , Gastrite/patologia , Gastrite/fisiopatologia , Gastroscopia/métodos , Gastroscopia/estatística & dados numéricos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/etnologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/fisiopatologia , Humanos , Israel/epidemiologia , Judeus/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos
20.
Medicine (Baltimore) ; 98(22): e15686, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145282

RESUMO

RATIONALE: Severe mucosal atrophy or intestinal metaplasia is a risk factor for synchronous and metachronous intestinal gastric cancer. Magnifying endoscopy with narrow-band imaging was useful for assessing differentiated early gastric cancer (EGC). PATIENT CONCERNS: A 62-year-old Chinese female was diagnosed with 5 multiple EGCs or high-grade dysplasia (HGD) with endoscopic surveillance for 7 years. DIAGNOSES: Synchronous and metachronous multiple EGCs. INTERVENTIONS: Endoscopic submucosal dissection (ESD) with en bloc resection was performed for all 5 multiple lesions. The ESD specimens were pathologically diagnosed with adenocarcinoma confined to the mucosa or HGD. OUTCOMES: After endoscopy resection, no residual, recurrent, or synchronous lesions were detected by endoscopic surveillance after ESD. LESSONS: Long-term, meticulous endoscopic surveillance is needed to monitor risk factors associated with multiple EGCs in patients with severe mucosal atrophy or intestinal metaplasia despite successful Helicobacter pylori eradication.


Assuntos
Adenocarcinoma/patologia , Mucosa Gástrica/patologia , Lesões Pré-Cancerosas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Conduta Expectante/métodos , Adenocarcinoma/diagnóstico por imagem , Ressecção Endoscópica de Mucosa , Feminino , Gastroscopia , Humanos , Metaplasia , Pessoa de Meia-Idade , Imagem de Banda Estreita , Fatores de Risco , Neoplasias Gástricas/diagnóstico por imagem , Fatores de Tempo
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