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Home › Dataset Library › Clinical, Molecular and Genetic Validation of a Murine Orthotopic Xenograft Model of Pancreatic Adenocarcinoma using Fresh Human Specimens

Dataset: Clinical, Molecular and Genetic Validation of a Murine Orthotopic Xenograft Model of Pancreatic Adenocarcinoma using Fresh Human Specimens

This project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that...

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This project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that recapitulates the critical components of human pancreatic adenocarcinoma. The authors discuss the proven and theoretical advantages of the model as well as future translational implications. Background: Relevant preclinical models that recapitulate the key features of human pancreatic ductal adenocarcinoma (PDAC) are needed in order to provide biologically tractable models to probe disease progression and therapeutic responses and ultimately improve patient outcomes for this disease. Here, we describe the establishment and clinical, pathological, molecular and genetic validation of a murine, orthotopic xenograft model of PDAC. Methods: Human PDACs were resected and orthotopically implanted and propagated in immunocompromised mice. Patient survival was correlated with xenograft growth and metastatic rate in mice. Human and mouse tumor pathology were compared. Tumors were analyzed for genetic mutations, gene expression, receptor tyrosine kinase (RTK) activation, and cytokine expression. Results: Fifteen human PDACs were propagated orthotopically in mice. Xenografts developed peritoneal and liver metastases. Time to growth and metastatic efficiency in mice each correlated with patient survival. Tumor architecture, nuclear grade and stromal content were similar in patient and xenografted tumors. Propagated tumors closely exhibited the genetic and molecular features known to characterize pancreatic cancer (e.g. high rate of KRAS, p53, SMAD4 mutation and EGFR activation). The correlation coefficient of gene expression between patient tumors and xenografts propagated through multiple generations was 93 to 99%. Analysis of gene expression demonstrated distinct differences between xenografts from fresh patient tumors versus commercially available PDAC cell lines. Conclusions: Our orthotopic xenograft model derived from fresh human PDACs closely recapitulates the clinical, pathologic, genetic and molecular aspects of human disease. This model has resulted in the identification of rational therapeutic strategies to be tested in clinical trials and will permit additional therapeutic approaches and identification of biomarkers of response to therapy. 47 Samples in total were generated for normal pancreatic tissue in patients, pancreatic tumors in patients, pancreatic tumors propagated in a mouse xenograft model, and pancreatic cancer cell lines in vitro. Clustering analysis was performed to evaluate the differences between patient tumors, xenograft tumors, established cancer cell lines, and cell lines derived from xenografts.

Species:
human

Samples:
47

Source:
E-GEOD-46385

Updated:
Dec.12, 2014

Registered:
Jul.11, 2014


Factors: (via ArrayExpress)
Sample TISSUE PRESERVE METHOD GENERATION IN XENOGRAFT MODEL ORGANISM PART MALIGNANCY PATIENT/LINE HOST ORGANISM CELL LINE
GSM1129598 n/a not specified not specified cancer PANC-1 in vitro PANC-1
GSM1129597 n/a not specified not specified cancer mPanc96 in vitro Panc96
GSM1129596 frozen not specified Tumor mPanc96 cancer mPanc96 Mus musculus Panc96
GSM1129595 n/a not specified not specified cancer L3.6p1 in vitro CL3.6p1
GSM1129594 n/a not specified not specified cancer BxPC-3 in vitro CBxPC-3
GSM1129593 Allprotect F1 Patient-derived tumor in mouse cancer UVA912 Mus musculus not specified
GSM1129592 RNAlater F5 Patient-derived tumor in mouse cancer UVA738 Mus musculus not specified
GSM112959 Allprotect F12 Patient-derived tumor in mouse cancer UVA738 Mus musculus not specified
GSM112959 Allprotect F12 Patient-derived tumor in mouse cancer UVA738 Mus musculus not specified
GSM112959 Allprotect F12 Patient-derived tumor in mouse cancer UVA738 Mus musculus not specified
GSM1129588 Allprotect F5 Patient-derived tumor in mouse cancer UVA738 Mus musculus not specified
GSM1129587 Allprotect F6 Patient-derived tumor in mouse cancer UVA738 Mus musculus not specified
GSM1129586 RNAlater not specified Patient pancreas tissue Non-cancer UVA67 Homo sapiens not specified
GSM1129585 Allprotect F1 Patient-derived tumor in mouse cancer UVA654 Mus musculus not specified
GSM1129584 Allprotect F1 Patient-derived tumor in mouse cancer UVA653 Mus musculus not specified
GSM1129583 Allprotect F1 Patient-derived tumor in mouse cancer UVA624 Mus musculus not specified
GSM1129582 frozen F2 Patient-derived tumor in mouse cancer UVA608 Mus musculus not specified
GSM112958 n/a not specified not specified cancer UVA608 Mus musculus UVA608
GSM1129580 Allprotect F10 Patient-derived tumor in mouse cancer UVA608 Mus musculus not specified
GSM1129580 Allprotect F10 Patient-derived tumor in mouse cancer UVA608 Mus musculus not specified
GSM1129578 Allprotect F11 Patient-derived tumor in mouse cancer UVA608 Mus musculus not specified
GSM1129577 n/a not specified Patient-derived tumor in mouse cancer UVA608 in vitro not specified
GSM1129582 frozen F2 Patient-derived tumor in mouse cancer UVA608 Mus musculus not specified
GSM1129575 Allprotect F1 Patient-derived tumor in mouse cancer UVA602 Mus musculus not specified
GSM1129574 Allprotect not specified Patient pancreas tissue Non-cancer UVA580 Homo sapiens not specified
GSM1129573 Allprotect F3 Patient-derived tumor in mouse cancer UVA530 Mus musculus not specified
GSM1129572 Allprotect F3 Patient-derived tumor in mouse cancer UVA450 Mus musculus not specified
GSM1129572 Allprotect F3 Patient-derived tumor in mouse cancer UVA450 Mus musculus not specified
GSM1129570 Allprotect not specified Patient pancreatic tumor cancer UVA450 Homo sapiens not specified
GSM1129569 Allprotect F1 Patient-derived tumor in mouse cancer UVA450 Mus musculus not specified
GSM1129568 frozen F1 Patient-derived tumor in mouse cancer UVA432 Mus musculus not specified
GSM1129567 frozen F1 Patient-derived tumor in mouse cancer UVA431 Mus musculus not specified
GSM1129567 frozen F1 Patient-derived tumor in mouse cancer UVA431 Mus musculus not specified
GSM1129565 cryopreservation not specified Patient pancreatic tumor cancer UVA431 Homo sapiens not specified
GSM1129564 frozen F1 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129563 Allprotect F8 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129563 Allprotect F8 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129563 Allprotect F8 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129560 frozen F5 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129560 frozen F5 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129560 frozen F5 Patient-derived tumor in mouse cancer UVA366 Mus musculus not specified
GSM1129557 n/a not specified not specified cancer UVA366 in vitro UVA366
GSM1129556 frozen F1 Patient-derived tumor in mouse cancer UVA232 Mus musculus not specified
GSM1129556 frozen F1 Patient-derived tumor in mouse cancer UVA232 Mus musculus not specified
GSM1129554 Allprotect F2 Patient-derived tumor in mouse cancer UVA215 Mus musculus not specified
GSM1129553 Allprotect not specified Patient pancreas tissue Non-cancer UVA190 Homo sapiens not specified
GSM1129552 Allprotect F2 Patient-derived tumor in mouse cancer UVA1049 Mus musculus not specified

Tags

  • adenocarcinoma
  • cancer
  • cell
  • cytokine
  • disease
  • ductal adenocarcinoma
  • liver
  • pancreatic adenocarcinoma
  • pancreatic cancer
  • pancreatic ductal adenocarcinoma
  • tyrosine

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