Primary esophageal (E) and gastro-esophageal junction (GEJ) cancer xenografts have the potential to become useful pre-clinical models of disease. In this study, we determined that p16 negative tumors that have not been exposed to neo-adjuvant chemo-radiation have higher engraftment chances. Morphological features and expression of certain molecular markers (p53, p16, Ki-67, EGFR, Her-2/neu) suggest that no major changes occur between primary tumors and xenografts or between early passage and late passage xenografts. Global gene expression data supported these results but revealed that approximately 2000 genes differed significantly between passage one xenografts and human tumors. Most of these genes, however, might coincide with stromal signals present in patient tumors but absent in xenografts. Primary E/GEJ cancer xenografts also showed a wide range of chemosensitivities to cisplatin-paclitaxel treatment, confirming the usefulness of these models in drug testing. These models also revealed potential ways to interrogate tumor initiating cell (TIC) dynamics after chemotherapy.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65431 |
| Date | 18 June 2014 |
| Creators | Dodbiba, Lorin |
| Contributors | Liu, Geoffrey, Ailles, Laurie |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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