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

Tags

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

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