CYP24A1 Involvement in Inflammatory Factor Regulation Occurs via the Wnt Signaling Pathway.

OBJECTIVE: While the upregulation of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene expression has been reported in colon cancer, its role in tumorigenesis remains largely unknown. In this study, we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B (NF-κB) pathway. METHODS: The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6 (IL-6) as well as tumor necrosis factor alpha (TNF-α), with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). Furthermore, CYP24A1 expression was subjected to knockdown via the use of small interfering RNA (siRNA). Subsequently, NF-κB pathway activation was determined by an electrophoretic mobility shift assay, and the transcriptional activity of ß-catenin was determined by a dual-luciferase reporter assay. A mouse ulcerative colitis (UC)-associated carcinogenesis model was established, wherein TNF-α and the NF-κB pathway were blocked by anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides, respectively. Then the tumor size and protein level of CYP24A1 were determined. RESULTS: IL-6 and TNF-α upregulated CYP24A1 expression and activated the NF-κB pathway in colon cancer cells. PDTC significantly inhibited this increase in CYP24A1 expression. Additionally, knockdown of CYP24A1 expression by siRNA could partially antagonize Wnt pathway activation. Upregulated CYP24A1 expression was observed in the colonic epithelial cells of UC-associated carcinoma mouse models. Anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides decreased the tumor size and suppressed CYP24A1 expression. CONCLUSION: Taken together, this study suggests that inflammatory factors may increase CYP24A1 expression via NF-κB pathway activation, which in turn stimulates Wnt signaling.

Clinicopathological features of primary gastric neuroendocrine neoplasms: A single-center analysis.

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.