BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. MATERIALS AND METHODS: In this study, the first of its kind, the expression of both MDR1P-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. RESULTS: Overall, 93.3% of pancreatic carcinomas expressed MDR1P-gp, approximately 31% co-expressed MRP-1 with MDR1P-gp, while 6.7% expressed neither of these proteins. CONCLUSION: Our results show that drug efflux pumps, in particular that of MDR1P-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.
Authors: Iwao Ojima; Jin Chen; Liang Sun; Christopher P Borella; Tao Wang; Michael L Miller; Songnian Lin; Xudong Geng; Larisa Kuznetsova; Chuanxing Qu; David Gallager; Xianrui Zhao; Ilaria Zanardi; Shujun Xia; Susan B Horwitz; Jon Mallen-St Clair; Jennifer L Guerriero; Dafna Bar-Sagi; Jean M Veith; Paula Pera; Ralph J Bernacki Journal: J Med Chem Date: 2008-05-09 Impact factor: 7.446
Authors: Naomi Walsh; Annemarie Larkin; Susan Kennedy; Lisa Connolly; Jo Ballot; Wei Ooi; Giuseppe Gullo; John Crown; Martin Clynes; Lorraine O'Driscoll Journal: BMC Urol Date: 2009-06-24 Impact factor: 2.264