Previously, our group examined 10 primary patient tumour samples and nine matched normal adjacent specimens and 10 matched F1 and F2 generation PDX tumours using high-resolution mass spectrometry. MS identification allowed for the isolation of the human only protein, representing the tumour cells, and these were tracked from patient tumour, to F1 and F2 generation PDX tumours. Between patient primary and F1 tumour 32 proteins were upregulated and 113 downregulated. In comparison, between F1 and F2 generation of PDX tumour, only eight human-specific proteins were differentially expressed when analysed by quantitative label-free differential analysis. This demonstrates the fidelity of tumour phenotype once engrafted [30]. This is in line with previously published data the shows, once established, xenografts tend to be robust with stable gene expression profile between early and late passage PDX tumours [31]. This bank of pancreatic PDX tumours models the subset of pancreatic cancer patients who are eligible for surgical resection. Mutational analyses by Sequenom MassArray MALDI-TOF showed 80% of samples examined possessed a KRAS mutation. This is in line with previously reported clinical KRAS mutation rates [32]. These PDX samples are a truer representation of human pancreatic cancer than pancreatic cancer cell lines or cell-line derived xenograft models, which often fail to recapitulate the stroma and desmoplasia of pancreatic cancer. In recent years, given the unmet need of pancreatic cancer patients, banks of patient-derived xenograft tumours have been established. The bank established in this study displays a higher engraftment rate for PDAC tumours than many others previously reported. Two recent reports showed similar engraftment rates (72% and 71%), although this was observed in more immune compromised NSG and NSG nude mice [33,34].
High Line Nudes Kevin McDermott
Download File: https://jinyurl.com/2vE7xI
2ff7e9595c
Comments