ABSTRACT
BACKGROUND: Bile acid diarrhoea or BAD is a common but little recognised cause of chronic diarrhoea. Few of these patients in China have been diagnosed due to a lack of diagnostic options. AIMS: To clarify the diagnostic value of serum fibroblast growth factor19 (FGF19) in BAD patients. METHODS: We reported on 60 chronic diarrhoea patients and 80 healthy volunteers (HV). Based on the 90th percentile levels of serum 7a-hydroxy-4-cholesten-3-one (C4) of HV, these patients were divided into BAD group (C4 ≥ 90th) and non-bile acid diarrhoea group (NBAD, C4 < 90th). Serum FGF19 in the two clinical groups and HV group were compared, as was distal ileum FGF19 in clinical groups. The diagnostic value of serum FGF19 for BAD was evaluated. RESULTS: The 90th percentile of serum C4 in HV group was 65.87 ng/ml. Serum FGF19 concentrations in BAD group (Median 69.28 pg/ml; n = 23) were significantly lower than those in HV (Median 122.18 pg/ml; n = 80) and NBAD (Median 129.57 pg/ml; n = 29) groups. FGF19 mRNA of the distal ileum in BAD group, was lower than that in NBAD group, P = 0.002. The rate of FGF19 protein low expression of distal ileum in BAD and NBAD group were 78.3% and 48.3%, P = 0.027. Using an ROC curve, statistical analysis yielded a threshold FGF19 concentration of 117.3 pg/ml (AUC, 0.906; 91.3% sensitivity, 79.3% specificity) for a clinical diagnosis of BAD. CONCLUSIONS: Serum and distal ileum expression of FGF19 significantly decreased in BAD patients. The suggested clinical ranges for serum FGF19 < 117.3 pg/ml has high sensitivity and specificity for BAD patients with a normal structural and histological ileum.
Subject(s)
Bile Acids and Salts , Fibroblast Growth Factors , Diarrhea/etiology , Down-Regulation , Fibroblast Growth Factors/metabolism , Fibroblasts/metabolism , Humans , Ileum/metabolismABSTRACT
Colon cancer is one of the most common malignant tumors in the digestive system. Although oxaliplatin, a chemotherapy drug, has been clinically used to treat colon cancer, its therapeutic effect is unsatisfactory. It has been proved that indoleamine dioxygenase 2,3 (IDO) is a tumor immunosuppressive factor for the immune response. Herein, an IDO inhibitor, D-MT (indoximod, 1-Methyl-D-tryptophan), was combined with oxaliplatin to treat colon cancer in mice. T cell infiltration in tumor tissues, the ratios of immune cells in the spleens, and the tumor growth and survival of the mice were detected and recorded. The results showed that the combination of oxaliplatin and D-MT significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. More importantly, the combination treatment increased the ratios of CD4+ T, CD8+ T and NK cells from the spleen in tumor-bearing mice, and prompted T cell infiltration in tumor tissues. This study provided a new therapeutic strategy for colon cancer treatment in the clinic, especially for patients with oxaliplatin resistance.
