RESUMEN
AIM: To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium (AOM/DSS) induced mice model. METHODS: C57BL/6 mice were administered AOM/DSS to develop the ulcerative colitis (UC) carcinogenesis model. Mice were treated with 5-ASA (75 mg/kg/d), VSL#3 (1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months (five days/week). The tumor load was compared in each group, and tumor necrosis factor (TNF-α) and interleukin (IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16s rDNA sequencing method. RESULTS: VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Alloprevotella in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION: VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.
Asunto(s)
Colitis Ulcerosa/complicaciones , Microbioma Gastrointestinal , Neoplasias Intestinales/prevención & control , Probióticos/uso terapéutico , Animales , Bifidobacterium , Carcinogénesis , Colitis Ulcerosa/metabolismo , Colon/metabolismo , Daño del ADN , Modelos Animales de Enfermedad , Interleucina-6/metabolismo , Neoplasias Intestinales/complicaciones , Lactobacillus , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16S/aislamiento & purificación , Ruminococcus , Análisis de Secuencia de ADN , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To assess the clinical characteristics, diagnosis and therapeutic modalities for gastric neuroendocrine neoplasms (GNENs) among the Chinese population in a single institution. METHODS: A total of 57 patients with histologically confirmed GNENs, who were diagnosed between 1995 and 2015 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinical, imaging and histopathologic characteristics as well as the treatments of GNENs were collected and analyzed. RESULTS: Patients with GNENs mostly presented with non-specific symptoms. Gastric body was the most common site of involvement. The choice of imaging modality, such as endoscopy and computed tomography depended on the tumor subtype. Chromogranin A (CgA) and synaptophysin were indispensable immunohistochemical markers for diagnosis. Significant inter-group differences in the positivity rate of CD56 were observed among the three grades (G1, G2 and G3). Therapeutic modalities included endoscopic intervention, surgical resection and pharmacotherapy, which were largely guided by the tumor subtype and the presence or absence of distant metastasis or tumor recurrence. CONCLUSIONS: Routine endoscopic examination is recommended for the early diagnosis of GNENs. Histopathological examination can make the definite diagnosis of GNENs and clarify the nature of gastric polyps. A multidisciplinary approach is important in the management of patients with GNENs.