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| Status |
Public on Jan 01, 2016 |
| Title |
Tissue Slice Grafts of Human Renal Cell Carcinoma: an Authentic Preclinical Model with High Engraftment Rate and Metastatic Potential |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Purpose: Discovery of curative therapies for renal cell carcinoma (RCC) is hampered by lack of authentic preclinical models. Tumorgrafts, generated by direct implantation of patient-derived tissues into mice, have demonstrated superior ability to predict therapeutic response. We evaluated “tissue slice grafts” (TSGs) as an improved tumorgraft model of RCC. Experimental Design: Cores of fresh RCC were precision-cut at 300-μm and implanted under the renal capsule of RAG2-/-γC-/- mice. Engraftment rate, histology, biomarker expression, genetic fidelity and metastatic potential were evaluated. Magnetic resonance imaging (MRI) was tested as a non-invasive method to measure tumor volume, and response to a targeted therapy was determined. Results: All 13 cases of RCC engrafted and displayed characteristic histology and biomarkers. TSG volume quantified non-invasively by MRI highly correlated with graft weights, providing a unique tool for monitoring orthotopic growth. Moreover, in 2 cases, cancer cells from TSGs metastasized to clinically relevant sites, including bone. Microarray analysis and DNA sequencing demonstrated a high degree of correlation of global gene expression and VHL status between TSGs and parental tumors. Treatment of TSGs with sunitinib significantly decreased graft weight and mean vessel density compared to controls. Conclusions: The TSG model of RCC faithfully recapitulates tumor pathology, gene expression, genetic mutation and drug response. The high engraftment rate and metastatic potential of this authentic model, in conjunction with the ability to generate large first-generation animal cohorts and to quantitate tumor volume at the orthotopic site by MRI, proffer significant advantages compared to other preclinical platforms.
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| Overall design |
Three pairs of tissue slice graftes and parent tumors were included in the study. Tissue slice grafts and parent tumors were preserved in Allprotect tissue reagent (Qiagen, Valencia, CA) at -20°C prior to RNA extraction using an AllPrep DNA/RNA/Protein Mini Kit (Qiagen, Valencia, CA). The quality of RNA was determined using an Agilent 2100 Bioanalyzer (Agilent Biotechnologies, Santa Clara, CA). Microarray hybridization was performed using Illumina Human HT-12 v4 Beadchips (Illumina Inc., San Diego, CA) according to the manufacturer’s directions. Expression data was rank invariant normalized using BeadStudio software (Illumina Inc.).
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| Web link |
http://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/pubmed/23911681
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| Contributor(s) |
Thong AE, Zhao H, Ingels A, Valta MP, Nolley R, Santos J, Young SR, Peehl DM |
| Citation(s) |
23911681 |
| Submission date |
Feb 21, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Hongjuan Zhao |
| Organization name |
Stanford
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| Department |
Urology
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| Lab |
Donna Peehl
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| Street address |
300 Pasteur Dr
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
95014 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA190046 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44548_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE44548_non-normalized.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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