As a result, effects of FGF19 on GB volumes may not be evident. In summary, we found normal activation of the bile salt-ileal FXR axis in patients with CC using the endogenous FXR ligand chenodeoxycholic acid. These findings provide a rationale to further explore clearly the potential therapeutic role of FXR agonists in this patient category. Supporting Information Table S1 qRT-PCR primer list. (DOC) Click here for additional data file.(33K, doc) Checklist S1 CONSORT Checklist. (DOC) Click here for additional data file.(222K, doc) Protocol S1 Trial Protocol. (DOC) Click here for additional data file.(390K, doc) Acknowledgments Chenodeoxycholic acid (CDCA) was a gift of Tramedico, Weesp, the Netherlands and Sigma-tau, Dusseldorf, Germany. We kindly thank Rebecca Stellato for her help with the statistical analyses.
Funding Statement FDMvS is supported by a grant from Abbott Laboratories, Abbott Park, Illinois, U.S.A. SWCvM is supported by the Netherlands Organization for Scientific Research (NWO) Project VIDI (917.11.365), a Utrecht University Support Grant and Wilhelmina Children’s Hospital Research Fund. Chenodeoxycholic acid (CDCA) was a gift of Tramedico, Weesp, the Netherlands and Sigma-tau, Dusseldorf, Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Colorectal cancer (CRC) is the third most common cancer type and the second leading cause of cancer related mortality in the Western countries [1].
It is thought to develop slowly via a progressive accumulation of genetic mutations, epigenetic and gene expression alterations; recurrence risk and overall mortality of CRC is closely related to the stage of disease at time of primary diagnosis [2]. Histological differentiation of high-grade dysplasia from well-differentiated carcinoma is often difficult, even in the case of correct sampling. A molecular test for CRC should be able to identify the disease at early stage with high specificity and sensitivity, thus enabling effective treatment from the onset before the disease progresses. Microarray analyses have already been applied to investigate gene expression changes in many cancer types including CRC [3]�C[14]. Gene expression marker sets GSK-3 can be identified by whole genomic expression profiling of colonic biopsy samples which would establish the basis of the molecular biological classification of colorectal diseases. Recent microarray studies determined mRNA expression patterns related to: �C colorectal carcinogenesis, progression and metastatic development [3]�C[8]. �C different subtypes of CRC with diverse clinicopathological parameters [4], [8]�C[10]. �C limited number of experiments focusing on molecular-based prognosis [11].