Severe Intestinal Inflammation in the Small Intestine of Mice Induced by Controllable Deletion of Claudin-7.

BACKGROUND: As a potential tumor suppressor gene, Claudin-7 (Cldn7), which is a component of tight junctions, may play an important role in colorectal cancer occurrence and development. AIMS: To generate a knockout mouse model of inducible conditional Cldn7 in the intestine and analyze the phenotype of the mice after induction with tamoxifen. METHODS: We constructed Cldn7-flox transgenic mice and crossed them with Villin-CreERT2 mice. The Cldn7 inducible conditional knockout mice appeared normal and were well developed at birth. We induced Cldn7 gene deletion by injecting different dosages of tamoxifen into the mice and then conducted a further phenotypic analysis. RESULTS: After induction for 5 days in succession at a dose of 200 µl tamoxifen in sunflower oil at 10 mg/ml per mouse every time, the mice appeared dehydrated, had a lower temperature, and displayed inactivity or death. The results of hematoxylin-eosin staining showed that the intestines of the Cldn7 inducible conditional knockout mice had severe intestinal defects that included epithelial cell sloughing, necrosis, inflammation and hyperplasia. Owing to the death of ICKO mice, we adjusted the dose of tamoxifen to a dose of 100 µl in sunflower oil at 10 mg/ml per mouse (aged more than 8 weeks old) every 4 days. And we could induce atypical hyperplasia and adenoma in the intestine. Immunofluorescent staining indicated that the intestinal epithelial structure was destroyed. Electron microscopy experimental analysis indicated that the intercellular gap along the basolateral membrane of Cldn7 inducible conditional knockout mice in the intestine was increased and that contact between the cells and matrix was loosened. CONCLUSIONS: We generated a model of intestinal Cldn7 inducible conditional knockout mice. Intestinal Cldn7 deletion induced by tamoxifen initiated inflammation and hyperplasia in mice.

Prognostic factors for overall survival in patients with primary duodenal adenocarcinoma.

BACKGROUND: The complete resection of primary duodenal adenocarcinoma (PDA) offers a chance for a cure, but the clinical and pathological characteristics of survivors have not been well studied. METHODS: Patients with stage I-III PDA who underwent surgical resection between 2013 and 2018 were identified retrospectively and followed until December 2019. All patients are from the Cancer Hospital Chinese Academy of Medical Sciences. The clinical and pathological information of the patients, such as age, gender, tumor location, operative procedure, pathologic features, TNM stage, common presenting symptoms, lymph node dissection status, serum tumor markers, etc., was collected in detail. The KaplanMeier method and a Cox proportional hazards model were used for the survival analysis. RESULTS: In total, 85 patients with PDA were eligible for this study. Among these patients, 48 were male (56.5%), 37 were female (43.5%), the median age was 59 (range, 22-79) years, 44 (51.8%) patients were aged <60 years, and 41 (48.2%) patients were aged ≥60 years. The 1-, 3-, and 5-year survival rates were 93.7%, 79.4%, and 64.9%, respectively. The median overall survival (OS) was 27 months (range, 2-82 months), and the median follow-up was 27 months (range, 3-82 months). The patients with stage III disease had the worst prognosis (P=0.001). The univariate analysis showed that lymph node positivity (P=0.000), the N stage (P=0.000), the TNM stage (P=0.001) and carbohydrate antigen 19-9 (CA19-9) positivity (P=0.038) were related to OS. However, the total number of lymph nodes (LN) retrieved (P=0.723), tumor differentiation (P=0.136), carcinoembryonic antigen (CEA) (P=0.812), gender (P=0.477), operation type (P=0.860), tumor size (P=0.869), tumor site (P=0.120), age (P=0.733), intraoperative blood loss (P=0.660), and intraoperative blood transfusion (P=0.748) were not correlated with OS. The multivariate analysis suggested that the lymph node status was an independent prognostic risk factor for OS. CONCLUSIONS: In our study the median OS was 27 months (range, 2-82 months), and the 5-year survival rates was 64.9%. The lymph node status was the only prognostic factor for OS in PDA.