Alimentary TractHigh multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy☆,☆☆
Section snippets
Patients
From an IBD database that compiled the clinical records of more than 500 patients with IBD who attended our hospital, we identified 3 patient groups: (1) outpatients with UC who had required a proctocolectomy with an ileoanal pouch (PIAP) in the past for either failed medical therapy or colonic dysplasia; (2) outpatients with CD who had required at least 1 bowel resection in the past for either failed medical therapy or bowel obstruction; and (3) IBD patients who had never required bowel
PBL MDR expression in patients with UC requiring proctocolectomy
The characteristics of the patient with IBD and control population are summarized in Tables 1 and 2.
Empty Cell Prior surgery (n = 41) No prior surgery (n = 40) Empty Cell Empty Cell Failed treatment Dysplasia Inactive Active Controls (n = 50) n 28 13 21 19 50 Age (yr) and sex Mean ± SD 43.3 ± 15.1 48.6 ± 17.3 43.7 ± 18.6 46.3 ± 16.2 40.3 ± 12.3 Range 20–72 20–75 20–73 17–72 21–62 Female (%) 43% 46% 43% 53% 58% Duration of disease (yr) Mean ± SD 3.4 ± 5.1 10.9 ± 8.1b 6.8 ± 6.0 6.9 ± 6.1 — Range 0.1–30 3–26 1.2–23 0.1–31 — Duration
Discussion
The major findings in this study were (1) significantly elevated PBL MDR expression in IBD patients who required surgery several years earlier for failed medical therapy; (2) stable PBL MDR expression among patients with IBD and controls regardless of disease activity or glucocorticoid therapy; and (3) a significant correlation between PBL and colonic mucosal MDR expression among patients with IBD and controls that appeared to be independent of mucosal disease activity.
Some overlap in PBL MDR
Acknowledgements
The authors thank Dr. Alan Kelly, Medical Statistics, Department of Community Health, Trinity College Dublin, for his assistance with the manuscript.
References (38)
Indications for surgery in inflammatory bowel disease: a gastroenterologist's opinion
- et al.
Clinical patterns, natural history, and progression of ulcerative colitis. A long-term follow-up of 1116 patients
Dig Dis Sci
(1993) - et al.
Clinical pattern of corticosteroid dependent Crohn's disease
Eur J Gastroenterol Hepatol
(1998) - et al.
Frequency of glucocorticoid resistance and dependency in Crohn's disease
Gut
(1994) - et al.
An overview of membrane, cytosolic and nuclear proteins associated with expression of resistance to multiple drugs in vitro
Biochem Biophys Acta
(1992) - et al.
The biochemistry of P-glycoprotein mediated multidrug resistance
Annu Rev Biochem
(1989) - et al.
MDR activity in human lymphocytes
Hum Immunol
(1991) - et al.
Classical and novel forms of multidrug resistance and the physiological functions of P-glycoproteins in mammals
Pharmacol Ther
(1993) - et al.
Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone
J Biol Chem
(1992) - et al.
Expression of MDR-1 is associated with a new form of resistance to dexamethasone-induced apoptosis
Mol Endocrinol
(1993)
Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes
Blood
Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate
Int J Cancer
A rapid and sensitive flow cytometric method for the detection of multidrug-resistant cells
Cytometry
Use of rhodamine 123 dyes in fluorescent assay of P-glycoprotein function
Biochem Biophys Acta
The effect of ion channel blockers, immunosuppressive agents and other drugs on the activity of the multi-drug transporter
Int J Cancer
Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy
J Clin Oncol
P-glycoprotein (Pgp-170) inhibition reduces cortisol and cyclosporin efflux from human intestinal epithelial (Caco-2) cells
Gastroenterology
Biochemistry of multidrug resistance mediated by the multidrug transporter
Ann Rev Biochem
Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes
Blood
Cited by (0)
- ☆
Address requests for reprints to: Richard J. Farrell, M. D., Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Dana 501, 330 Brookline Avenue, Boston, Massachusetts 02215. e-mail: [email protected]; fax: (617) 667-2767.
- ☆☆
Drs. Farrell and Donnelly were recipients of Health Research Board research fellowships, Aideen Long was a recipient of a Wellcome Trust Career Development Award, and for part of the period of the study Dr. Dermot Kelleher was a Wellcome Senior Fellow in Clinical Science.