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Open Access 01-12-2015 | Research

Decreased functional activity of multidrug resistance protein in primary colorectal cancer

Authors: Tamás Micsik, András Lőrincz, Tamás Mersich, Zsolt Baranyai, István Besznyák Jr, Kristóf Dede, Attila Zaránd, Ferenc Jakab, László Krecsák Szöllösi, György Kéri, Richard Schwab, István Peták

Published in: Diagnostic Pathology | Issue 1/2015

Abstract

Background

The ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies.

Methods

100 colorectal cancer and 28 adjacent healthy mucosa samples were obtained by intraoperative surgical sampling. Activity of MDR1 and MRP1 of viable epithelial and cancer cells were determined separately with the modified calcein-assay for multidrug resistance activity and sufficient data of 73 cancer and 11 healthy mucosa was analyzed statistically.

Results

Significantly decreased mean MDR1 activity was found in primary colorectal cancer samples compared to normal mucosa, while mean MRP1 activity showed no significant change. Functional activity was not affected by gender, age, stage or grade and localization of the tumor.

Conclusion

We found lower MDR activity in cancer cells versus adjacent, apparently, healthy control tissue, thus, contrary to general belief, MDR activity seems not to play a major role in primary drug resistance, but might rather explain preferential/selective activity of Irinotecan and/or Oxaliplatin. Still, this picture might be more complex since chemotherapy by itself might alter MDR activity, and furthermore, today limited data is available about MDR activity of cancer stem cells in colorectal cancers.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1675739129145824

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Title: Decreased functional activity of multidrug resistance protein in primary colorectal cancer
Authors: Tamás Micsik
András Lőrincz
Tamás Mersich
Zsolt Baranyai
István Besznyák Jr
Kristóf Dede
Attila Zaránd
Ferenc Jakab
László Krecsák Szöllösi
György Kéri
Richard Schwab
István Peták
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-015-0264-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Decreased functional activity of multidrug resistance protein in primary colorectal cancer

Abstract

Background

Methods

Results

Conclusion

Virtual slides

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Virtual slides

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