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1.
J Med Microbiol ; 69(2): 218-227, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32011229

RESUMO

Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.Aim. To genotype the vacA s, m and i and cag pathogenicity island (cagPAI) genes in H. pylori from Alaskans and investigate associations with gastropathy.Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI, the cagA, cagE, cagT and virD4 genes and to genotype the vacA s, m and i regions.Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI; those were associated with a more severe gastropathy (P≤0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy (P≤0.03 for all comparisons).Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.


Assuntos
Proteínas de Bactérias/genética , Ilhas Genômicas , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alaska , Nativos do Alasca/estatística & dados numéricos , Proteínas de Bactérias/metabolismo , Feminino , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/microbiologia , Neoplasias Gástricas/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Adulto Jovem
2.
Arq Gastroenterol ; 56(4): 419-424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800739

RESUMO

BACKGROUND: Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. OBJECTIVE: To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. METHODS: A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. RESULTS: Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. CONCLUSION: The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.


Assuntos
Infecções por Helicobacter/patologia , Helicobacter pylori , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Atrofia/microbiologia , Biópsia , Doença Crônica , Feminino , Gastroscopia , Humanos , Masculino , Metaplasia/microbiologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(11): 1166-1169, 2019 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-31683407

RESUMO

The fungal microbiota from self-retained soil and tongue coating of 18 patients with precancerous lesions of upper gastrointestinal (PLUG) were sequenced. The diversity of α, ß in and the structure of the microbial community were analyzed, and the association of them was quantified by using the Spearman rank correlation method. The richness index (1.67±2.79) and the diversity index (0.25±0.10) of the fungal microbiota from tongue coating of PLUG patients were significantly lower than those from soil (4.00±4.69; 0.99±0.18) (all P values<0.001). The relative abundance of 11 taxa from tongue coating of these PLUG patients was positively associated with that from soil (all P values<0.05).


Assuntos
Neoplasias Esofágicas/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Neoplasias Gastrointestinais/microbiologia , Trato Gastrointestinal/microbiologia , Microbiota , Lesões Pré-Cancerosas/microbiologia , Microbiologia do Solo , Língua/microbiologia , Fungos/genética , Microbioma Gastrointestinal/genética , Humanos , Neoplasias Gástricas/microbiologia
4.
Arq Gastroenterol ; 56(3): 264-269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633723

RESUMO

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.


Assuntos
Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter/complicações , Neoplasias Gástricas/microbiologia , Urease/análise , Adulto , Fatores Etários , Biópsia , Brasil/epidemiologia , Estudos Transversais , Endoscopia do Sistema Digestório , Feminino , Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/enzimologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Mucosa Intestinal/enzimologia , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Fatores Sexuais , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia
5.
New Microbiol ; 42(4): 210-220, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31524946

RESUMO

Helicobacter pylori (H. pylori) is involved in the etiology of gastric cancer (GC). miRNAs are short RNAs that regulate gene expression by marking mRNAs for degradation. miRNAs are involved in tumorigenesis, metastasis, and cell proliferation. We aimed to investigate the miRNA expression profiles of tissues from H. pylori (+) and (-) GC patients. Forty GC patients, 20 H. pylori (+) and 20 H. pylori (-), and a healthy control group were included. The miRNA expression levels were investigated by microarrays and quantitative RT-PCR. We detected 9 upregulated and 4 downregulated miRNAs by microarray. We selected 5 upregulated and 5 downregulated miRNAs for the quantitative RT-PCR assay. The relative fold changes of miRNAs in the cancerous tissue and non-tumor mucosa specimens of H. pylori (+) GC patients for hsa-miR-194 were 4.24- and 3.83-fold higher, respectively, whereas the hsa-miR-145 expression levels were downregulated 0.33-fold and 0.43-fold, respectively, in the same group. The presence of H. pylori significantly upregulated hsa-miR-194 and downregulated hsa-miR-145 expression levels in H. pylori (+) GC cases, compared to H. pylori (-) GC cases. Regional differences in the virulence of H. pylori strains may also be involved in the up- or downregulation of miRNA expression levels.


Assuntos
Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter , Helicobacter pylori , MicroRNAs , Neoplasias Gástricas , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Humanos , MicroRNAs/metabolismo , Estudos Prospectivos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Turquia
6.
World J Gastroenterol ; 25(35): 5220-5232, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558869

RESUMO

Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which cause gastrointestinal diseases. Connexins function in gap junctional homeostasis, and their downregulation is closely related to gastric carcinogenesis. Investigations into H. pylori infection and the fine-tuning of connexins in cells or tissues have been reported in previous studies. Therefore, in this review, the potential mechanisms of H. pylori-induced gastric cancer through connexins are summarized in detail.


Assuntos
Carcinogênese/patologia , Conexinas/metabolismo , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/patologia , Regulação para Baixo , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Ilhas Genômicas , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Neoplasias Gástricas/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
7.
J Immunol Res ; 2019: 1394191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485458

RESUMO

Recent research on cancer-associated microbial communities led to the accumulation of data on the interplay between bacteria, immune and tumor cells, the pathways of bacterial induction of carcinogenesis, and its meaningfulness for medicine. Microbial communities that have any kind of impact on tumor progression and microorganisms associated with tumors have been defined as oncobiome. Over the last decades, a number of studies were dedicated to Helicobacter pylori and its role in the progression of stomach tumors, so this correlation can be regarded as proven. Involvement of bacteria in the induction of lung cancer has been largely ignored for a long time, though some correlations between this type of cancer and lung microbiome were established. Despite the fact that in the present the microbial impact on lung cancer progression has many confirmations, the underlying mechanisms are poorly understood. Microorganisms can contribute to tumor initiation and progression through production of bacteriotoxins and other proinflammatory factors. The purpose of this review is to organize the available data on lung cancer microbiome and its role in malignant tumor progression.


Assuntos
Neoplasias Pulmonares/microbiologia , Pulmão/microbiologia , Microbiota , Carcinogênese/imunologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/patologia , Progressão da Doença , Microbioma Gastrointestinal , Infecções por Helicobacter/microbiologia , Helicobacter pylori/metabolismo , Humanos , Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Gástricas/microbiologia
8.
Artif Cells Nanomed Biotechnol ; 47(1): 3862-3872, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556767

RESUMO

Zinc finger and BTB domain containing 20 (ZBTB20), a sequence-specific transcriptional repressor, has been found to be involved in tumorigenesis. However, its role(s) in gastric cancer and the molecular mechanisms involved are poorly investigated. Here, our data demonstrated that ZBTB20 expression was markedly upregulated in gastric cancer cell lines infected with Helicobacter pylori (H. pylori) and in gastric cancer tumor samples. Loss- and gain-of-function studies showed that ZBTB20 promoted cell proliferation, invasion and migration of gastric cancer cell lines. Mechanistically, the phosphorylation of NF-κBp65 and expression and activity of MMP-2 and MMP-9 were increased, while IκBα expression was decreased by ZBTB20 in gastric cancer cells. We further revealed that IκBα overexpression significantly inhibited NF-κB signaling as well as cell migration, invasion and proliferation in gastric cancer cell lines induced by ZBTB20 overexpression. Therefore, our findings emphasize an important role for ZBTB20 in controlling gastric cancer development, which is helpful to identify potential therapeutic targets for its treatment.


Assuntos
Movimento Celular , Inibidor de NF-kappaB alfa/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Helicobacter pylori/fisiologia , Humanos , Invasividade Neoplásica , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
9.
J Korean Med Sci ; 34(35): e231, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31496141

RESUMO

Detection of early-stage gastric cancer improves the prognosis of patients. Endoscopic submucosal dissection (ESD) is a curative and stomach-preserving treatment for early gastric cancer (EGC) associated with a low risk of lymph node metastasis. However, several studies have reported missed diagnosis of gastric cancer. Therefore, endoscopists are required to learn accurate diagnostic skills to eliminate endoscopic blind spots. A systematic screening protocol to map the entire stomach without blind spots reduces the risk of missed lesions. Knowledge of the features of EGC or dysplasia is essential to identify suspicious lesion. Information of the common sites of occurrence of EGC can also enable a detailed endoscopic examination to improve detection rates. Previous reports investigating the location of gastric cancers resected by ESD or surgery showed that the antrum and lesser curvature of stomach were predominantly affected. Helicobacter pylori-induced atrophic changes advance from the antrum to the corpus along the lesser curvature, predominantly affecting these areas. Gastric cancers in the antrum and the lower corpus are also commonly missed during screening examination. Therefore, a careful examination of the lower third stomach is warranted to avoid missing synchronous and metachronous gastric lesions. Knowledge of the location of EGC enables accurate endoscopic examination and detection of EGC in early stage.


Assuntos
Neoplasias Gástricas/patologia , Detecção Precoce de Câncer , Ressecção Endoscópica de Mucosa , Mucosa Gástrica/patologia , Gastroscopia , Helicobacter pylori/patogenicidade , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiologia
10.
Biochim Biophys Acta Rev Cancer ; 1872(2): 188309, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31394110

RESUMO

While Helicobacter pylori is a fundamental risk factor, gastric cancer (GC) aetiology involves combined effects of microbial (both H. pylori and non-H. pylori), host and environmental factors. Significant differences exist between the gastric microbiome of those with gastritis, intestinal metaplasia and GC, suggesting that dysbiosis in the stomach is dynamic and correlates with progression to GC. Most notably, a consistent increase in abundance of lactic acid bacteria (LAB) has been observed in GC patients including Streptococcus, Lactobacillus, Bifidobacterium and Lactococcus. This review summarises how LAB can influence GC by a number of mechanisms that include supply of exogenous lactate -a fuel source for cancer cells that promotes inflammation, angiogenesis, metastasis, epithelial-mesenchymal transition and immune evasion-, production of reactive oxygen species and N-nitroso compounds, as well as anti-H. pylori properties that enable colonization by other non-H. pylori carcinogenic pathobionts.


Assuntos
Disbiose/metabolismo , Lactobacillales/patogenicidade , Neoplasias Gástricas/microbiologia , Progressão da Doença , Disbiose/complicações , Transição Epitelial-Mesenquimal , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/metabolismo , Evasão Tumoral , Microambiente Tumoral
11.
Medicine (Baltimore) ; 98(35): e16626, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464899

RESUMO

Gastric cancer (GC) is one of the common malignant tumors in China, with a high morbidity and mortality. With the development and application of high-throughput sequencing technologies and metagenomics, a great quantity of studies have shown that gastrointestinal microbiota is closely related to digestive system diseases. Although some studies have reported the effect of long-term follow-up after subtotal gastrectomy on intestinal flora changes in patients with GC. However, the features of gut microbiota and their shifts in patients with GC in perioperative period remain unclear.This study was designed to characterize fecal microbiota shifts of the patients with GC before and after the radical distal gastrectomy (RDG) during their hospital staying periods. Furthermore, fecal microbiota was also compared between the GC patients and healthy individuals.Patients who were diagnosed with advanced gastric adenocarcinoma at distal stomach were enrolled in the study. The bacterial burden within fecal samples was determined using quantitative polymerase chain reaction. To analyze the diversity and composition of gut microbiota from fecal DNA of 20 GC patients and 22 healthy controls, amplicons of the 16S rRNA gene from all subjects were pyrosequenced. To study gut microbiota shifts, the fecal microbiota from 6 GC patients before and after RDG was detected and subsequently analyzed. Short-chain fatty acids were also detected by chromatography spectrometer in these 6 GC patients.RDG had a moderate effect on bacterial richness and evenness, but had pronounced effects on the composition of postoperative gut microbiota compared with preoperative group. The relative abundances of genera Akkermansia, Esherichia/Shigella, Lactobacillus, and Dialister were significant changed in perioperative period. Remarkably, higher abundances of Escherichia/Shigella, Veillonella, and Clostridium XVIII and lower abundances of Bacteroides were observed in gut microbiota of overall GC patients compared to healthy controls.This study is the first study to characterize the altered gut microbiota within fecal samples from GC patients during perioperative period, and provide a new insights on such microbial perturbations as a potential effector of perioperative period phenotype. Further research must validate these discoveries and may evaluate targeted microbiota shifts to improve outcomes in GC patients.


Assuntos
Bactérias/classificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Neoplasias Gástricas/cirurgia , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , China , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Gastrectomia , Microbioma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Filogenia , Neoplasias Gástricas/microbiologia
12.
Z Gastroenterol ; 57(7): 883-888, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-31288284

RESUMO

Viruses and bacteria play central roles in gastrointestinal tumor development. This includes well-characterized contributions of Helicobacter pylori to gastric carcinoma and MALT lymphoma and of Hepatitis B and C virus infections to hepatocellular cancer. However, recent studies have demonstrated a much broader role of the microbiota in the regulation of cancer development. As such, it was shown that barrier defects and alterations in microbial community structure contribute to colorectal and hepatocellular cancer. Moreover, intriguing studies have highlighted the microbiota as a central regulator of the efficacy of systemic anti-tumor therapies. Here, we provide an overview of recent observations on the role of the microbiota in tumor development and the regulation of therapeutic anti-tumor responses and discuss the implications of these findings for clinical diagnostics and treatment.


Assuntos
Microbioma Gastrointestinal , Neoplasias Gastrointestinais/microbiologia , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B/microbiologia , Microbiota , Neoplasias Gástricas/microbiologia , Estômago/microbiologia , Infecções por Helicobacter , Humanos
13.
World J Gastroenterol ; 25(25): 3183-3195, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333310

RESUMO

Helicobacter pylori (H. pylori) is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of the world's population, in Africa its prevalence reach as high as 80% as the infection is acquired during childhood. Risk factors for H. pylori acquisition have been reported to be mainly due to overcrowding, to have infected siblings or parent and to unsafe water sources. Despite this high H. pylori prevalence there still does not exist an African guideline, equivalent to the Maastricht V/Florence Consensus Report of the European Helicobacter and Microbiota Study Group for the management of this infection. In this continent, although there is a paucity of epidemiologic data, a contrast between the high prevalence of H. pylori infection and the low incidence of GC has been reported. This phenomenon is the so-called "African Enigma" and it has been hypothesized that it could be explained by environmental, dietary and genetic factors. A heterogeneity of data both on diagnosis and on therapy have been published. In this context, it is evident that in several African countries the increasing rate of bacterial resistance, mainly to metronidazole and clarithromycin, requires continental guidelines to recommend the appropriate management of H. pylori. The aim of this manuscript is to review current literature on H. pylori infection in Africa, in terms of prevalence, risk factors, impact on human health, treatment and challenges encountered so as to proffer possible solutions to reduce H. pylori transmission in this continent.


Assuntos
Antibacterianos/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/epidemiologia , África/epidemiologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Gastroenterologia/normas , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Guias de Prática Clínica como Assunto , Prevalência , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/prevenção & controle
14.
Phytomedicine ; 63: 152968, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31280140

RESUMO

BACKGROUND: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.


Assuntos
Anticarcinógenos/farmacologia , Artemisininas/farmacologia , Infecções por Helicobacter/complicações , Helicobacter pylori/efeitos dos fármacos , Neoplasias Gástricas/prevenção & controle , Animais , Artesunato/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Helicobacter pylori/patogenicidade , Humanos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
15.
Oncogene ; 38(37): 6461-6477, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332288

RESUMO

Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.


Assuntos
Gastrite , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Infiltração de Neutrófilos , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Animais , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/patologia , Células Cultivadas , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/genética , Gastrite/imunologia , Gastrite/microbiologia , Gastrite/patologia , Células HL-60 , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estômago/imunologia , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia
16.
Gut ; 68(9): 1545-1575, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31278206

RESUMO

Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer-in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.


Assuntos
Adenocarcinoma/diagnóstico , Detecção Precoce de Câncer/métodos , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/microbiologia , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/sangue , Gerenciamento Clínico , Progressão da Doença , Medicina Baseada em Evidências/métodos , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/microbiologia , Gastrite Atrófica/cirurgia , Gastroscopia/métodos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/cirurgia , Medição de Risco/métodos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/cirurgia
17.
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
18.
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
19.
Eur J Clin Microbiol Infect Dis ; 38(9): 1591-1597, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31114971

RESUMO

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.


Assuntos
Carcinogênese , Disbiose , Gastrite/microbiologia , Microbioma Gastrointestinal , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/microbiologia , Gastrite Atrófica/microbiologia , Humanos , Estômago/microbiologia , Microambiente Tumoral
20.
Int J Oncol ; 54(6): 2200-2210, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081048

RESUMO

Helicobacter pylori (HP) is a pathogenic bacterium associated with chronic gastritis, gastric ulcer and gastric cancer. In the present study, the primary carcinogenesis process of normal gastric epithelial cells (GES­1) infected with HP was investigated. It was determined that infected gastric mucosal epithelial GES­1 cells secreted increased interleukin­8 (IL­8) and IL­23, and exhibited enhanced expression of inducible nitric oxide synthase and cyclooxygenase­2, inducing inflammatory reactions and resulting in apoptosis. The bacterial infection significantly increased the expression of carcinogenesis­associated genes, including p16, c­Myc, p53 and p21, as well as the expression of cell surface signaling molecules cluster of differentiation 44 (CD44) and CD54 in GES­1 cells or tissues of patients with gastritis and gastric cancer in vitro or in vivo. Simultaneously, the migration and invasion abilities of normal gastric epithelial GES­1 cells were increased following HP infection. These observations demonstrated that the inflammatory response of HP infection could cause normal gastric epithelial cells to undergo significant cancerous reactions, indicating that HP is a risk factor for gastric cancer.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Neoplasias Gástricas/microbiologia , Estômago/citologia , Linhagem Celular , Movimento Celular , Células Epiteliais/citologia , Células Epiteliais/microbiologia , Infecções por Helicobacter/imunologia , Humanos , Interleucina-23/metabolismo , Interleucina-8/metabolismo , Invasividade Neoplásica , Óxido Nítrico Sintase Tipo II/metabolismo , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/imunologia
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