The effects of aerobic exercise on the intestinal tumors and flora of the ApcMin/+ mouse.

INTRODUCTION: Intestinal tumor is one of the most common tumors that seriously threaten the health of residents all over the world. Studies suggest that the imbalance of intestinal flora is associated with tumorgenesis; meanwhile, long-term regular aerobic exercise can improve the occurrence and development of tumors. However, moderate aerobic exercise affecting the development of intestinal tumors and their related flora has not been explored. Thus, the purpose of our study is to explore the effects of aerobic exercise on intestinal tumor growth and flora changes in ApcMin/+ mice, and try to answer whether there is a correlation between them after exercise intervention. METHODS: In this study, 18 required ApcMin/+ mice were randomly divided into Model group (n = 6), Exercise group (n = 6), and Aspirin group (positive control, n = 6), while C57BL/6 J wild-type mice were used as the blank control group. Each group is given corresponding intervention. Weight monitoring, tumor counts, hematoxylin-eosin staining, TdT-mediated dUTP nick-end labeling (TUNEL) fluorescence assay, immunohistochemistry (IHC), fecal sampling and grouping, and bacterial 16S rDNA gene analysis were completed after 12 weeks' intervention for each group of mice. RESULTS: As a result, we were able to show significant improvements in mice' body weight changing rates (Exercise group 8.6% higher than Model control group), tumor numbers (Exercise group 4.33 ± 0.94 vs. Model control group 7.33 ± 2.49, Then put the slides into xylenewith tumor inhibition rate 40.93%), tumor pathological staging (Exercise group mainly low-grade tumorous adenomas vs. Model group mainly high-grade adenomas), and TUNEL staining (Exercise group 8.59% higher positive rate of apoptotic cells in tumors than Model group). The 16s rRNA sequencing analysis results showed that aerobic exercise could regulate the abundance of some genus (16/149, P < 0.01), and the number of intestinal tumors correlates with changes in the abundance of some bacteria in the intestinal flora (positive correlation with probiotics abundance and negative correlation with conditioned pathogens). DISCUSSION: Changes in flora abundance may be one of the reasons for aerobic exercise to reduce the number of intestinal tumors, probably mediated by cell apoptosis. Future studies should focus on the potential mechanism of aerobic exercise in preventing intestinal tumorgenesis, especially the molecular mechanism through intestinal flora. CONCLUSION: Aerobic exercise has a preventive effect on intestinal tumors in ApcMin/+ mice, and can regulate the abundance of intestinal flora.

Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer.

It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.

Association of COX2 gene hypomethylation with intestinal type gastric cancer in samples of patients from northern Brazil.

To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate their association with Helicobacter pylori in gastric adenocarcinomas. Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue. The presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analyses were performed using Fisher's exact test. The hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and 36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples, it was found in 13, 7, and 67 %. The presence of H. pylori was detected in 67 % of gastric cancer samples and 67 % in normal gastric samples. The methylation of THBS1 and GPX3 was not significantly different between the types of tumors, normal sample, the presence of H. pylori, or clinicopathological variables studied (P > 0.05). However, the methylation status of the gene COX2 is significantly different between normal tissue and intestinal type gastric cancer (P = 0.02). Therefore, our results suggest that the methylation status of the gene COX2 is associated with the intestinal type of gastric cancer.

Differential expression of MYC in H. pylori-related intestinal and diffuse gastric tumors.

Evidence suggests that the carcinogenic process guided by Helicobacter pylori is related to the expression of cell cycle and apoptosis proteins as BCL-2, BAX, and MYC. However, the literature is conflicting regarding the expression frequency in the histological subtypes and did not consider cagA gene presence. To investigate the expression of these proteins considering the histological subtypes of gastric cancer associated with H. pylori (cagA), a total of 89 cases were used. H. pylori infection and cagA status were determined by PCR. Immunodetection was performed for MYC, BCL-2, and BAX proteins. H. pylori was found in 95.5% of the patients, among them, 65.8% were cagA(+). Nuclear MYC was detected in 36.4%, BAX in 55.7%, while BCl-2 in just 5%. Nuclear MYC staining was significantly lower in the intestinal than diffuse subtype (p = 0.008) and was related with the presence of H. pylori cagA(+). Additionally, most of the few cases cytoplasmic MYC positive were in the intestinal subtype. In diffuse tumors, although most nuclear MYC positive cases were cagA(+), it was not significant. No difference was observed between BCL-2 or BAX expression considering the presence of cagA gene in the histological subtypes. It seems that MYC could be relevant for the diffuse tumorigenic pathway associated with H. pylori and possibly influenced by the presence of cagA gene, while in intestinal tumors, the tumorigenic pathway does not occur through the MYC expression.

Pathological disorders of the gastric mucosa surrounding carcinomas and primary lymphomas.

OBJECTIVE: Gastritis, intestinal metaplasia, atrophy, and dysplasia are disorders that frequently precede the full development of gastric adenocarcinoma. On the other hand, primary gastric lymphomas seem to arise from mucosa-associated lymphoid tissue. It is well accepted that these histological changes are caused by Helicobacter pylori infection. The objective of this study is to determine the frequency and characteristics of epithelial and lymphoid tissue disorders of the gastric mucosa surrounding primary carcinomas and lymphomas. METHODS: We studied 111 gastrectomies from patients harboring primary adenocarcinomas (30 intestinal and 30 diffuse type) and 51 gastric lymphomas. For comparative purposes, we analized 86 stomachs from patients who died of diseases other than gastric malignancies. Histopathological disorders of the gastric mucosa adjacent to primary neoplasms such as atrophy, intestinal metaplasia, and dysplasia were recorded. Lymphoid follicles were classified in two groups, with or without expansion. Expansion was characterized by increased size, irregular borders, enlarged marginal zone, and expanded germinal centers. Differences were statistically evaluated with chi2 and Fisher exact tests, odds ratio, and relative risk, with 95% CI. p values <0.05 were considered statistically significant. RESULTS: Most intestinal-type adenocarcinomas showed atrophy (76.6%) and intestinal metaplasia (86.6%) and less frequently, dysplasia (23.3%), in the surrounding gastric mucosa. Expansive lymphoid follicles were more frequent among lymphomas than in adenocarcinomas (56.8% vs 25%); however, a high percentage of lymphomas were also associated with atrophy (50.9%), intestinal metaplasia (62.7%), and rarely dysplasia (11.8%). On the contrary, diffuse-type adenocarcinoma displayed less frequently atrophy (33%), intestinal metaplasia (50%), and dysplasia (3%). Gastric mucosa from patients without any gastric neoplasia was almost normal (84%), whereas the remaining 16% showed, both or alone, atrophy and intestinal metaplasia. CONCLUSION: Histopathological disorders of the gastric mucosa are not specific for any neoplasm, but intestinal-type adenocarcinomas frequently showed atrophy, intestinal metaplasia, and not uncommonly, dysplasia of the surrounding non-neoplastic gastric mucosa. Diffuse-type adenocarcinomas did not frequently show such lesions. Primary lymphomas displayed expansive lymphoid follicles and also a high percentage of atrophy and intestinal metaplasia of the surrounding gastric mucosa. The presence of intestinal metaplasia, atrophy, and lymphoid follicles with expansion in endoscopic biopsies could suggest a higher suceptibility for the development of gastric intestinal-type adenocarcinoma or gastric lymphoma. Patients harboring such histopathological changes must receive eradication therapy against H. pylori and probably closer follow-up.

Primary intestinal non-Hodgkin's lymphoma and Epstein-Barr virus: high frequency of EBV-infection in T-cell lymphomas of Mexican origin.

Epstein-Barr virus is universally associated with endemic Burkitt's lymphoma (BL) and undifferentiated nasopharyngeal carcinoma and can be detected in a significant proportion of cases of Hodgkin's disease (HD) and peripheral T-cell lymphoma, but only rarely in sporadic B-NHL. The frequency of EBV-positivity in certain neoplasms shows important geographic variations. Both HD and sporadic BL from Latin America have shown higher rates of EBV-association than cases from Western countries. In T-NHL, the frequency of EBV-positivity is influenced by the site of the primary tumor and the phenotype of the neoplastic cells. Nasal and nasal-type T-NHL, which show a T/NK-cell phenotype with expression of CD56 are virtually always EBV-associated, whereas only a proportion of nodal, gastrointestinal and pulmonary T-NHL are EBV-infected. A recent investigation of primary intestinal lymphomas of Mexican origin demonstrated EBV-positivity in all examined cases of T-NHL and BL and a proportion of other B-NHLs. The presence of EBV was independent of the presence or absence of enteropathy. Two of 6 cases studied showed CD56 expression. The high rate of EBV-positivity independent of histologic subtype is in contrast to the low to intermediate rates of EBV-positivity found in cases of intestinal T-NHL from Western countries and indicates that geographic differences in the frequency of EBV-association of lymphoid neoplasms might also extend to a fraction of peripheral T-cell lymphomas.