fig3

Figure 3. PDAC PDX models of acquired gemcitabine resistance harbored changes in expression of some gemcitabine transporters and metabolizing enzymes. Tumor tissue harvested on days 190, 120, and 179 for PA4.gemR, PA10.gemR and PA16.gemR, respectively, was immunostained for RRM1, RRM2, hCNT1, hENT1, CDA, and dCK. Tumor tissue harvested from control mice bearing gemcitabine-naïve PA4, PA10 or PA16 tumors served as controls for IHC staining experiments. Scale bar = 10 μm. Quantitation of IHC data in A is shown as expression indices below each photomicrograph (A); protein expression in gemR models that were developed by exposure to drug in vivo, compared to their respective parent tumor models. Each protein has been reported to be associated with gemcitabine resistance in models developed in vitro. ND: no difference between gemcitabine-naïve control and gemR tumors. Values in the Table were calculated by dividing the EI of each protein determined by IHC expressed by gemR/parent (control) tumors. A change of > 1.5-fold was interpreted as a real increase or decrease (B). PDAC: pancreatic ductal adenocarcinoma; PDX: patient-derived xenograft; gemR: gemcitabine resistance; IHC: immunohistochemistry