Berberine chloride suppresses pancreatic adenocarcinoma proliferation and growth by targeting inflammation-related genes: an in silico analysis with in vitro and vivo validation.

PURPOSE: Targeting inflammatory crosstalk between tumors and their microenvironment has emerged as a crucial method for suppressing pancreatic adenocarcinoma (PAAD) progression. Berberine (BBR) is a natural pentacyclic isoquinoline alkaloid known for its anti-inflammatory and antitumor pharmacological effects; however, the mechanism underlying PAAD suppression remains unclear. We aim to investigate the effects of BBR on PAAD progression and their underlying mechanisms. METHODS: The prognostic value of inflammation-related genes in PAAD was assessed using bioinformatics analyses, then the pharmacological effects and potential mechanisms of BBR on PAAD will be investigated in silico, in vitro, and in vivo. RESULTS: Fifty-eight prognostic inflammation-related genes were identified in PAAD, which were shown to have good sensitivity and specificity using a novel inflammation-related gene risk-prognosis prediction model. Among these, four candidate genes (CAPS3, PTGS2, ICAM1, and CXCR4) were predicted as targets of BBR in PAAD in silico. Molecular docking simulations showed that the four key targets docked well with BBR. Further BBR treatment suppressed cell proliferation, colony formation, and induced cell cycle arrest in vitro. Moreover, BBR exhibited a significant tumor-suppressive effect in murine subcutaneous xenografts without macroscopic hepatic and renal toxicities. In addition, BBR downregulated CAPS3, PTGS2, ICAM1, and CXCR4 protein expression. CONCLUSION: This study not only elucidated the prognostic value of inflammation-related genes in PAAD but also demonstrated the potential of BBR to inhibit PAAD by targeting these genes.

[Neuroendocrine tumors: analysis of 252 cases].

OBJECTIVE: To investigate the epidemiology, diagnosis, and treatment status of neuroendocrine tumors (NETs) in our hospital. METHODS: Medical records of 252 patients with neuroendocrine tumors diagnosed and treated in our hospital from January 1, 2004 to December 31, 2009 were collected and retrospectively reviewed in this study. The clinicopathological data including age of onset, initial symptoms, primary site, pathological conditions (Sny, CgA, Ki-67), disease stage at diagnosis, treatment, and follow up were analyzed. RESULTS: The gender ratio M/F of the 252 cases was 1.9:1, with mean age of 55.2 years, and the high incidence was in age of 60-69 years. The tumors were located in the gastrointestinal tract (117 cases, 46.4%), broncho-pulmonary system (74 cases, 29.4%), other sites (61 cases, 24.2%) and unknown primary site (2 cases, 0.8%). Their first clinical symptoms vary, depending on the primary site. The common symptoms of primary rectal NETs were changes in bowel habits (29.3%) and diarrhea or constipation (17.5%), and most gastric NETs presented epigastric discomfort (86.4%). Most patients (71.4%) were diagnosed with stage I, II, III disease. Among the 252 cases, there were 110 carcinoids (43.7%), 108 neuroendocrine carcinomas (42.9%), 23 atypical carcinoids (9.1%), five neuroendocrine tumors (2.0%), four Merkel cell tumors (1.6%), and two composite carcinoids (0.8%). 206 patients (81.7%) received surgery, 39 (15.5%) received chemotherapy, and 31 cases (12.3%) were treated by palliative radiotherapy. CONCLUSIONS: This single-center retrospective analysis of data demonstrated that males have a higher incidence rate than females. The most common primary sites of NETs are the digestive tract and lungs. The initial symptoms of NETs are different depending on their primary sites. Good prognosis can be achieved in the majority of patients after surgery, chemotherapy and palliative radiotherapy.