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      MDR1/P-glycoprotein and MRP-1 drug efflux pumps in pancreatic carcinoma.

      Anticancer research
      Adenocarcinoma, metabolism, Adult, Aged, Carcinoma, Neuroendocrine, Cholangiocarcinoma, Humans, Immunohistochemistry, Middle Aged, Multidrug Resistance-Associated Proteins, biosynthesis, P-Glycoprotein, Pancreatic Neoplasms

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          Abstract

          Pancreatic cancer is one of the most challenging solid organ malignancies. This is due to its aggressiveness, frequent late presentation as advanced disease and chemoresistance. A better understanding of the molecular basis of its drug resistance is needed. In this study, the first of its kind, the expression of both MDR1 P-gp and MRP-1 protein in pancreatic tumour specimens was examined by immunohistochemistry. Expression of these drug efflux pumps was examined using semi-quantitative immunohistochemistry according to the percentage of cells within the tumour, demonstrating another staining intencity. Overall, 93.3% of pancreatic carcinomas expressed MDR1 P-gp, approximately 31% co-expressed MRP-1 with MDR1 P-gp, while 6.7% expressed neither of these proteins. Our results show that drug efflux pumps, in particular that of MDR1 P-gp, are frequently expressed in pancreatic cancer. While a causative role for these efflux pumps in pancreatic cancer chemoresistance cannot necessarily be concluded, the information presented here should be considered when selecting chemotherapy/drug efflux pump inhibitors for future therapies.

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