RESUMEN
Objective: A network model of ulcerative colitis-associated colon cancer (UCRCC) and NF-κB signaling pathway was established, in order to predict the key inflammatory targets of UCRCC and identify the effect of GQD and composition of index components on these targets. Methods: HPLC method was used, the mobile phase was acetonitrile-0.2% phosphoric acid aqueous solution, and the gradient elution was carried out. The 10 indicators were determined. The literature of databases such as Pubmed and ScienceDirect were searched, the terms of the upstream and downstream proteins of UCRCC disease and NF-κB pathway were examined. The Cytoscape software was used to predict the key inflammatory targets of UCRCC. The UCRCC model was established by AOM/DSS method, and the effect of GQD and composition of index components on key inflammatory targets were identified by immunohistochemistry and ELISA. Results: The contents of puerarin, daidzin, glycyrrhizin, jatrorrhizine, baicalin, palmatine, berberine, baicalein, glycyrrhizic acid and wogonin in GQD were 1.677, 0.154, 0.159, 0.045, 0.448, 0.035, 0.095, 0.013, 0.111 and 0.006 μg/g, respectively. The top eight inflammatory factors of the key protein in the interaction network were NF-κBp65, iNOS, COX-2, Bcl-2, TNF-α, IL-1β, ICAM-1 and VCAM-1. Compared with the model group, the high-, medium- and low-dose groups of GQD, the composition of index components group and the 5-ASA group were able to down-regulate the relative expression levels of NF-κBp65, iNOS, Bcl-2, COX-2 in colonic tissues of UCRCC mice (P < 0.01), and down-regulate the expression levels of TNF-α, IL-1β, ICAM-1, VCAM-1 in serum of UCRCC mice (P < 0.05, 0.01). Conclusion: GQD and composition of index components can improve the pathological condition of colon tissue in UCRCC mice, down-regulate the expression of inflammatory factors in colon tissue of UCRCC mice, and have a certain intervention effect on UCRCC, which laid the foundation for determining the quality marker (Q-marker) of GQD.
RESUMEN
BACKGROUND/AIMS: The number of patients with ulcerative colitis has steadily increased since the mid-1980s. As the risk of colon cancer increases with duration and extents, colitic cancers are expected to increase in number in Korea. We surveyed the current status of colitic cancers and provided the perspectives in Korea. METHODS: Korean Association for the Study of Intestinal Diseases (KASID) collected and descriptively analyzed a total of eleven cases of colitic cancers occurred between 1993 and 2003. RESULTS: The mean age at the diagnosis of colitic cancer was 49.3 years, and the mean duration of ulcerative colitis was 12.5 years. Of the diagnosed cases, 91% was associated with pancolitis, 28% had right colon cancers and 18.2% had multiple tumors. Colitic cancers diagnosed at Dukes' stage D were 36.3%. Stages at diagnosis were lower in patients with good compliance. Up to 2003, cumulative incidence ratio of colitic cancer to ulcerative colitis was estimated to be 0.5%, which was much less than the overall prevalence of 3.7% in the Western countries. This incidence was also less than the expected cumulative incidence ratio of 0.9%, which was estimated by adopting the average results of meta-analysis in the Western world. CONCLUSIONS: As the incidence of ulcerative colitis has not reached a plateau, and as the diagnosis of colitic caners are delayed in Korea, the cumulative incidence of colitic cancers might have appeared to be low. Geographic and racial factors, and the effect of preventive measures might have contributed to the lower incidence which remains to be proven. Since colitic cancers are expected to increase steeply in the near future in Korea, the importance of surveillance and prevention cannot be over-emphasized.