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1.
J Cancer Res Clin Oncol ; 147(4): 1077-1087, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33433655

RESUMO

PURPOSE: The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. METHODS: We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle-Ottawa-Scale. RESULTS: Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn's disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. CONCLUSIONS: IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.


Assuntos
Neoplasias Colorretais/etiologia , Doenças Inflamatórias Intestinais/complicações , Neoplasias Intestinais/etiologia , Intestino Delgado/patologia , Neoplasias Gástricas/etiologia , Neoplasias Colorretais/patologia , Humanos , Neoplasias Intestinais/patologia , Estudos Observacionais como Assunto , Prognóstico , Fatores de Risco , Neoplasias Gástricas/patologia
2.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440718

RESUMO

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 (PTGS2), ATP binding cassette subfamily C member 4 (ABCC4), hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), and solute carrier organic anion transporter family member 2A1 (SLCO2A1) PGE2 pathway-related genes with gastric cancer (GC) risk in a European Caucasian population. A hospital-based case-control study gathering 260 GC cases and 476 cancer-free controls was implemented. Using a tagSNP approach, 51 single nucleotide polymorphisms (SNPs) were genotyped through MassARRAY® iPLEX Gold Technology or allelic discrimination by real-time polymerase chain reaction (PCR). Homozygous carriers of the minor allele for both rs689466 and rs10935090 SNPs were associated with a 2.98 and 4.30-fold increased risk for GC, respectively (95% confidence interval (CI): 1.14-7.74, p = 0.027; 95% CI: 1.22-15.16, p = 0.026), with the latter also being associated with an anticipated diagnosis age. A multifactor dimensionality reduction analysis identified an overall three-factor best interactive model composed of age, rs689466, and rs1678374 that was associated with a 17.6-fold GC increased risk (95% CI: 11.67-26.48, p < 0.0001, (cross-validation) CV consistency of 8/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE2 pathway-related genes were identified as risk biomarkers for GC development. This approach may help to identify higher-risk individuals and may contribute to the tailoring screening of GC in intermediate-risk European countries.


Assuntos
Biomarcadores Tumorais , Dinoprostona/metabolismo , Suscetibilidade a Doenças , Variação Genética , Transdução de Sinais , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Europa (Continente) , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia
4.
PLoS One ; 15(9): e0237515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898138

RESUMO

BACKGROUND: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/etiologia , Estômago/patologia , Adolescente , Adulto , Idoso , Atrofia/etiologia , Atrofia/microbiologia , Atrofia/patologia , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estômago/microbiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Adulto Jovem
5.
Lancet ; 396(10251): 635-648, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32861308

RESUMO

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).


Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Terapia Combinada , Gastrectomia , Humanos , Excisão de Linfonodo , Neoplasias Gástricas/etiologia
6.
APMIS ; 128(2): 150-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32352605

RESUMO

Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.


Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/imunologia , Fatores de Virulência/imunologia , Virulência/imunologia , Carcinogênese/imunologia , Humanos , Prognóstico , Neoplasias Gástricas/microbiologia
7.
Oncogene ; 39(22): 4465-4474, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32350444

RESUMO

Helicobacter pylori infection is the main risk factor for the development of gastric cancer, the third leading cause of cancer death worldwide. H. pylori colonizes the human gastric mucosa and persists for decades. The inflammatory response is ineffective in clearing the infection, leading to disease progression that may result in gastric adenocarcinoma. We have shown that polyamines are regulators of the host response to H. pylori, and that spermine oxidase (SMOX), which metabolizes the polyamine spermine into spermidine plus H2O2, is associated with increased human gastric cancer risk. We now used a molecular approach to directly address the role of SMOX, and demonstrate that Smox-deficient mice exhibit significant reductions of gastric spermidine levels and H. pylori-induced inflammation. Proteomic analysis revealed that cancer was the most significantly altered functional pathway in Smox-/- gastric organoids. Moreover, there was also less DNA damage and ß-catenin activation in H. pylori-infected Smox-/- mice or gastric organoids, compared to infected wild-type animals or gastroids. The link between SMOX and ß-catenin activation was confirmed in human gastric organoids that were treated with a novel SMOX inhibitor. These findings indicate that SMOX promotes H. pylori-induced carcinogenesis by causing inflammation, DNA damage, and activation of ß-catenin signaling.


Assuntos
Adenocarcinoma/etiologia , Dano ao DNA , Gastrite/enzimologia , Infecções por Helicobacter/enzimologia , Helicobacter pylori/patogenicidade , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/fisiologia , Espermina/metabolismo , Neoplasias Gástricas/etiologia , Adenocarcinoma/microbiologia , Animais , Transformação Celular Neoplásica , Gastrite/genética , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Organoides , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/deficiência , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Proteoma , RNA Mensageiro/biossíntese , Transdução de Sinais , Espermidina/biossíntese , Neoplasias Gástricas/microbiologia , beta Catenina/fisiologia
8.
Cancer Sci ; 111(7): 2558-2569, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32412140

RESUMO

Dietary factors may affect the prognosis of digestive tract cancer, but evidence has been sparse. We investigated the association between pretreatment intake of 6 Japanese foods (including soy food, miso [soybean paste] soup and seaweed) and the risk of death among patients with histologically confirmed major digestive tract cancers (stomach, 1931; colon, 793; rectum, 510) diagnosed during 1997-2013 at a single institution in Japan. Pretreatment dietary intake was assessed using a food frequency questionnaire, and the patients were followed until December 2016. The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Among the patients with stomach cancer, frequent intake of soy food was inversely associated with the risk of all-cause (Ptrend for four frequency groups = 0.01; HR = 0.72, 95% CI: 0.50-1.04 for highest vs lowest group) and stomach cancer (Ptrend  = 0.03; HR = 0.63, 95% CI: 0.40-0.99) death. A similar inverse association was also found for intake of miso soup. In contrast, frequent seaweed intake was inversely associated with the risk of all-cause death among the patients with colon cancer (Ptrend  = 0.03). Rectal cancer patients who had frequently consumed seaweed tended to have a lower risk of rectal cancer death (Ptrend  = 0.02). These findings indicate that pretreatment intake of Japanese foods such as soybean products and seaweed may have favorable effects on patient survival of stomach and colorectal cancer, although this needs to be confirmed by further research.


Assuntos
Neoplasias Colorretais/epidemiologia , Dieta , Comportamento Alimentar , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Comorbidade , Suscetibilidade a Doenças , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
9.
Cancer Sci ; 111(9): 3195-3209, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32369664

RESUMO

Gastric cancer (GC) is one of the deadliest cancers worldwide, and the progression of gastric carcinogenesis (GCG) covers multiple complicated pathological stages. Molecular mechanisms of GCG are still unclear. Here, we undertook NMR-based metabolomic analysis of aqueous metabolites extracted from gastric tissues in an established rat model of GCG. We showed that the metabolic profiles were clearly distinguished among 5 histologically classified groups: control, gastritis, low-grade gastric dysplasia, high-grade gastric dysplasia (HGD), and GC. Furthermore, we carried out metabolic pathway analysis based on identified significant metabolites and revealed significantly disturbed metabolic pathways closely associated with the 4 pathological stages, including oxidation stress, choline phosphorylation, amino acid metabolism, Krebs cycle, and glycolysis. Three metabolic pathways were continually disturbed during the progression of GCG, including taurine and hypotaurine metabolism, glutamine and glutamate metabolism, alanine, aspartate, and glutamate metabolism. Both the Krebs cycle and glycine, serine, and threonine metabolism were profoundly impaired in both the HGD and GC stages, potentially due to abnormal energy supply for tumor cell proliferation and growth. Furthermore, valine, leucine, and isoleucine biosynthesis and glycolysis were significantly disturbed in the GC stage for higher energy requirement of the rapid growth of tumor cells. Additionally, we identified potential gastric tissue biomarkers for metabolically discriminating the 4 pathological stages, which also showed good discriminant capabilities for their serum counterparts. This work sheds light on the molecular mechanisms of GCG and is of benefit to the exploration of potential biomarkers for clinically diagnosing and monitoring the progression of GCG.


Assuntos
Transformação Celular Neoplásica/metabolismo , Espectroscopia de Ressonância Magnética , Metabolômica , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metabolismo Energético , Humanos , Espectroscopia de Ressonância Magnética/métodos , Redes e Vias Metabólicas , Metaboloma , Metabolômica/métodos , Ratos , Neoplasias Gástricas/diagnóstico , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(2): 148-153, 2020 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-32458603

RESUMO

OBJECTIVE: To examine the effect of schistosomiasis on the development of gastric cancer and colorectal cancer. METHODS: The clinical data of patients with gastric cancer and colorectal cancer with and without schistosomiasis japonica that were admitted to the Yijishan Hospital Affiliated to Wannan Medical College from January 2014 to December 2018 were collected. All cases were divided into schistosomal gastric cancer group and non - schistosomal gastric cancer group, schistosomal colorectal cancer group and non-schistosomal colorectal cancer group. The risk factors of gastric cancer and colorectal cancer were identified using univariate analysis and multivariate logistic regression analysis, and the effects of schistosomiasis on the development and progression of gastric cancer and colorectal cancer were evaluated. In addition, the survival of 32 patients with schistosomal colorectal cancer and 68 cases with non-schistosomal colorectal were estimated using telephone follow-up, and compared. RESULTS: There were 113 patients with schistosomal gastric cancer and 3 741 cases with non-schistosomal gastric cancer enrolled in this study, and there were significant differences between them in terms of sex ratio, age and prevalence of Helico-bacter pylori infection (all P values < 0.05). Logistic regression analysis revealed that age, H. pylori infection, and schistosomiasis were independent risk factors for gastric cancer (all P values < 0.05). There were 184 patients with schistosomal colorectal cancer and 2 205 cases with non-schistosomal colorectal cancer recruited in this study, and there were significant differences between them in terms of age, sex ratio, rate of history of alcohol consumption and rate of positive fecal occult blood test (all P values < 0.05). The phenotypes of both schistosomal and non-schistosomal colorectal cancer were predominantly ulcerative; however, the proportion of patients with invasive and protruded colorectal cancer was significantly greater than that of patients with non-schistosomal colorectal cancer (P = 0.003). Logistic regression analysis revealed that age (P = 0.003), gender (P = 0.002), phenotype (P = 0.005) and schistosomiasis (P = 0.029) were independent risk factors for colorectal cancer. The 5-year survival rate was significantly higher in patients with schistosomal colorectal cancer (68.90%) than in those with non-schistosomal colorectal cancer (46.40%), and the dead patients with schistosomal colorectal cancer had a significantly greater mean age than those with non-schistosomal colorectal cancer [ (66.33 ± 3.08) years vs. (56.29 ± 1.94), P < 0.05]. CONCLUSIONS: Schistosomiasis may alter the pathogenesis of colorectal cancer, resulting in the differences in the epidemiology, clinical characteristics and 5-year survival rate between patients with schistosomal and non-schistosomal colorectal cancer. Periodical gastrointestinal endoscopy and other examinations are recommended to exclude the likelihood of gastrointestinal cancers in men with anemia of unknown causes and at ages of 60 years living in schistosomiasis-endemic areas.


Assuntos
Neoplasias Colorretais , Esquistossomose Japônica , Neoplasias Gástricas , Idoso , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Esquistossomose Japônica/complicações , Esquistossomose Japônica/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
12.
Sci Rep ; 10(1): 6747, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317745

RESUMO

After endoscopic resection (ER) of gastric dysplasia, metachronous gastric neoplasm (MGN) appears to have an incidence rate similar to that detected after ER of early gastric cancer (EGC). We investigated whether the risk of MGN after ER for gastric dysplasia is different between patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Between March 2011 and December 2016, 198 patients with LGD (LGD group) and 46 patients with HGD (HGD group) who underwent ER were included in the study. During a median follow-up of 2.5 years, MGNs developed in 21 patients (10.6%) in the LGD group and in 6 patients (13.0%) in the HGD group. Hazard ratios (HRs) for MGNs (HR, 1.45; P = 0.425) and for metachronous HGD or gastric cancer (HR, 2.41; P = 0.214) in the HGD group were not different than those of the LGD group. However, considering patients without Helicobacter pylori infection, those in the HGD group had a significantly increased risk of metachronous HGD or gastric cancer compared to those in the LGD group (HR in HGD-group, 5.23; P = 0.044). These results indicate that meticulous surveillance endoscopy is needed to detect MGNs after ER of gastric dysplasia, especially in patients with HGD, including those without H. pylori infection.


Assuntos
Infecções por Helicobacter/diagnóstico , Segunda Neoplasia Primária/etiologia , Lesões Pré-Cancerosas/complicações , Neoplasias Gástricas/etiologia , Estômago/anormalidades , Idoso , Progressão da Doença , Ressecção Endoscópica de Mucosa/métodos , Feminino , Seguimentos , Gastroscopia/métodos , Infecções por Helicobacter/patologia , Infecções por Helicobacter/cirurgia , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Razão de Chances , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Estômago/cirurgia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo
13.
Cancer Sci ; 111(7): 2598-2607, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32338409

RESUMO

Cancer stem cells (CSCs) play a decisive role in the development and progression of cancer. To investigate CSCs in Epstein-Barr virus (EBV)-associated carcinoma (EBVaGC), we screened previously reported stem cell markers of gastric cancer in EBV-infected gastric cancer cell lines (TMK1 and NUGC3) and identified CD44v6v9 double positive cells as candidate CSCs. CD44v6/v9+/+ cells were sorted from EBVaGC cell line (SNU719) cells and EBV-infected TMK1 cells and these cell populations showed high spheroid-forming ability and tumor formation in SCID mice compared with the respective CD44v6/v9-/- cells. Sphere-forming ability was dependent on the nuclear factor-κB (NF-κB) signaling pathway, which was confirmed by decrease of sphere formation ability under BAY 11-7082. Small interfering RNA knockdown of latent membrane protein 2A (LMP2A), one of the latent gene products of EBV infection, decreased spheroid formation in SNU719 cells. Transfection of the LMP2A gene increased the sphere-forming ability of TMK1 cells, which was mediated through NF-κB signaling. Together, these results indicate that CD44v6v9+/+ cells are CSCs in EBVaGC that are maintained through the LMP2A/NF-κB pathway. Future studies should investigate CD44v6/v9+/+ cells in normal and neoplastic gastric epithelium to prevent and treat this specific subtype of gastric cancer infected with EBV.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Células-Tronco Neoplásicas/metabolismo , Neoplasias Gástricas/etiologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Imunofenotipagem , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
PLoS One ; 15(4): e0231531, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294114

RESUMO

Stomach cancer is a widespread health condition associated with environmental and genetic factors. Contribution of ionizing radiation to stomach cancer etiology is not sufficiently studied. This study was aimed to assess an association of the stomach cancer incidence risk with doses from occupational radiation exposure in a cohort of workers hired at main Mayak production association facilities in 1948-1982 taking into account non-radiation factors including digestive disorders. The study cohort comprised 22,377 individuals and by 31.12.2013 343 stomach cancer diagnoses had been reported among the cohort members. Occupational stomach absorbed doses were provided by the Mayak Worker Dosimetry System- 2008 (MWDS-2008) for external gamma ray exposure and by the Mayak Worker Dosimetry System- 2013 (MWDS-2013) for internal exposure to plutonium. Excess relative risks (ERR) per Gy for stomach cancer were estimated using the Poisson's regression. Analyses were run using the AMFIT module of the EPICURE software. The stomach cancer incidence risk in the study cohort was found to be significantly associated with the stomach absorbed dose of gamma rays: ERR/Gy = 0.19 (95% CI: 0.01, 0.44) with a 0 year lag, and ERR/Gy = 0.20 (95% CI: 0.01, 0.45) with a 5 year lag. To estimate the baseline risk, sex, attained age, smoking status and alcohol consumption, chronic diseases (peptic ulcer, gastritis and duodenitis) were taken into account. No modifications of the radiogenic risk by non-radiation factors were found in the study worker cohort. No association of the stomach cancer incidence risk with internal exposure to incorporated plutonium was observed.


Assuntos
Doenças Profissionais/epidemiologia , Exposição Ocupacional , Radiação Ionizante , Neoplasias Gástricas/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Plutônio/efeitos adversos , Estudos Retrospectivos , Risco , Federação Russa , Neoplasias Gástricas/etiologia
17.
J Gastroenterol Hepatol ; 35(9): 1495-1502, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32181516

RESUMO

Gastric cancer (GC) is the fifth most common cancer worldwide, and mortality rates are still high. Primary preventive strategies, aimed to reduce risk factors and promote protective ones, will lead to a decrease in GC incidence. Helicobacter pylori infection is a well-established carcinogen for GC, and its eradication is recommended as the best strategy for the primary prevention. However, the role of other factors such as lifestyle, diet, and drug use is still under debate in GC carcinogenesis. Unfortunately, most patients with GC are diagnosed at late stages when treatment is often ineffective. Neoplastic transformation of the gastric mucosa is a multistep process, and appropriate diagnosis and management of preneoplastic conditions can reduce GC-related mortality. Several screening strategies in relation to GC incidence have been proposed in order to detect neoplastic lesions at early stages. The efficacy of screening strategies in reducing GC mortality needs to be confirmed. This review provides an overview of current international guidelines and recent literature on primary and secondary prevention strategies for GC.


Assuntos
Prevenção Primária , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/prevenção & controle , Aciltransferases/efeitos adversos , Biomarcadores Tumorais , Dieta , Endoscopia , Exercício Físico , Gastrite/complicações , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter , Humanos , Estilo de Vida , Programas de Rastreamento , Segunda Neoplasia Primária/prevenção & controle , Lesões Pré-Cancerosas/diagnóstico , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Risco , Fumar/efeitos adversos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia
18.
PLoS One ; 15(3): e0230220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163505

RESUMO

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.


Assuntos
Proteínas de Bactérias/genética , Gastrite Atrófica/etiologia , Helicobacter pylori/genética , Glicoproteínas de Membrana/genética , Estômago/microbiologia , Estômago/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Técnicas de Cocultura/métodos , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia/métodos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Virulência/genética , Adulto Jovem
19.
Dig Dis Sci ; 65(7): 1917-1931, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32170476

RESUMO

As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.


Assuntos
Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Amoxicilina/uso terapêutico , Antígenos de Bactérias/análise , Biópsia , Bismuto/uso terapêutico , Testes Respiratórios , Claritromicina/uso terapêutico , Técnicas de Cultura , Doxiciclina/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Dispepsia/etiologia , Fezes/química , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Levofloxacino/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/etiologia , Metronidazol/uso terapêutico , Compostos Organometálicos/uso terapêutico , Úlcera Péptica/etiologia , Reação em Cadeia da Polimerase , Rifabutina/uso terapêutico , Salicilatos/uso terapêutico , Terapia de Salvação , Testes Sorológicos , Neoplasias Gástricas/etiologia , Tetraciclina/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Ureia/metabolismo
20.
J Gastroenterol Hepatol ; 35(9): 1532-1539, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32083327

RESUMO

BACKGROUND AND AIM: The aim of this study was to identify factors affecting persistent gastric regenerating atypia and determine the effect of Helicobacter pylori eradication on the course of this lesion. METHODS: In cross-sectional setting, comprehensive health check-up subjects who underwent both endoscopy and H. pylori test from 2001 to 2009 were included. The association between H. pylori and gastric regenerating atypia was evaluated. In cohort setting, patients with regenerating atypia who underwent H. pylori test from 2001 to 2013 were included. Factors affecting positive pathology (persistent regenerating atypia or new development of neoplasm) in patients with regenerating atypia at baseline were investigated. RESULTS: In cross-sectional setting, regenerating atypia was observed in 1.1% (241/22 133). H. pylori infection was associated with gastric regenerating atypia (adjusted odds ratio, 1.47; 95% confidence interval [CI], 1.12-1.91). In cohort setting, 310 patients with regenerating atypia were finally eligible. Positive pathology rate during follow up was 16.1% (15/93) in the persistent infection group, 2.8% (3/106) in successful eradication group, and 4.5% (5/111) in baseline H. pylori-negative group. Persistent H. pylori infection increased the risk of positive pathology (adjusted risk ratio [RR], 7.18; 95% CI, 1.95-26.48) compared to H. pylori eradication group. Persistent H. pylori infection increased the risk of regenerative atypia (adjusted RR, 5.70; 95% CI, 1.46-22.17) and new neoplasm (adjusted RR, 10.74; 95% CI, 1.10-105.17) compared to baseline negative H. pylori. CONCLUSIONS: H. pylori infection is an independent risk factor for gastric regenerating atypia. Eradication of H. pylori seems helpful for regression of regenerating atypia.


Assuntos
Mucosa Gástrica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Neoplasias Gástricas/etiologia , Úlcera Gástrica/etiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Úlcera Gástrica/patologia , Úlcera Gástrica/terapia
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