Expression of BCRP in Icteric Patients
The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Bile acids are also substrates of the drug efflux transporter breast cancer resistance protein (BCRP) that is highly expressed in the human intestine. Therefore we intend to analyze whether intestinal BCRP expression could be altered during cholestasis.
|Study Design:||Observational Model: Defined Population
Observational Model: Natural History
Time Perspective: Cross-Sectional
Time Perspective: Prospective
|Official Title:||Influence of Cholestasis on Intestinal BCRP Expression|
|Study Start Date:||June 2003|
|Estimated Study Completion Date:||August 2004|
BCRP is capable of transport bile acids and may indicate that this transporter is involved in bile acid homeostasis. As an efflux pump, it could protect the enterocytes from potential toxic bile acid concentrations. During cholestasis, where the enterohepatic circulation is disrupted, there occurs an adaptive regulation of transporters for bile acids, bilirubin and cholesterol. These changes take place in liver, kidney, as well as in the intestine.
Using real-time RT-PCR analysis we determine BCRP mRNA expression levels in duodenal tissue of healthy subjects and cholestatic patients. BCRP protein levels will be determined by immunohistochemistry.
Healthy subjects and cholestatic patients are enrolled in the study after giving informed consent. Control subjects with an indication for a gastrointestinal tract endoscopy within a cancer-screening program and patients with obstructive cholestasis with an interventional endoscopic retrograde cholangiopancreatography (ERCP) are included in this study. During endoscopy four biopsy specimens are obtained from the distal part of the duodenum. Biopsies are immediately stored at –70°C until further processing.
|University Basel, Department of Research|
|Basel, Basel- Stadt, Switzerland, 4031|
|Principal Investigator:||Jürgen Drewe, MD, MSc||Department of Clinical Pharmacology, University Basel|