NDLI: Tissue slice grafts of human renal cell carcinoma: an authentic preclinical model with high engraftment rate and metastatic potential.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Thong, Alan E. Zhao, Hongjuan Ingels, Alexandre Valta, Maija P. Nolley, Rosalie Santos, Jennifer Young, Sarah R. Peehl, Donna M.
Description	Country affiliation: Canada Author Affiliation: Thong AE ( Department of Urology, Stanford University School of Medicine, Stanford, CA.); Zhao H ( Department of Urology, Stanford University School of Medicine, Stanford, CA.); Ingels A ( Department of Urology, Stanford University School of Medicine, Stanford, CA); Valta MP ( Department of Urology, Stanford University School of Medicine, Stanford, CA); Nolley R ( Department of Urology, Stanford University School of Medicine, Stanford, CA.); Santos J ( Department of Urology, Stanford University School of Medicine, Stanford, CA.); Young SR ( Department of Urology, Stanford University School of Medicine, Stanford, CA.); Peehl DM ( Department of Urology, Stanford University School of Medicine, Stanford, CA. Electronic address: dpeehl@stanford.edu.)
Abstract	OBJECTIVE: 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. MATERIALS AND METHODS: Cores of fresh RCC were precision-cut at 300 µm and implanted under the renal capsule of RAG2(-/-)Î³C(-/-) mice. Engraftment rate, histology, biomarker expression, genetic fidelity, and metastatic potential were evaluated. Magnetic resonance imaging (MRI) was tested as a noninvasive 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 noninvasively 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 von Hippel-Lindau (VHL) status between TSGs and parental tumors. Treatment of TSGs with sunitinib significantly decreased graft weight and mean vessel density compared with controls. CONCLUSION: 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 with other preclinical platforms.
File Format	HTM / HTML
ISSN	10781439
e-ISSN	18732496
DOI	10.1016/j.urolonc.2013.05.008
Journal	Urologic Oncology: Seminars and Original Investigations
Issue Number	1
Volume Number	32
Language	English
Publisher	Elsevier
Publisher Date	2014-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Urology Discipline Oncology Carcinoma, Renal Cell Drug Therapy Kidney Neoplasms Transplantation, Heterologous Xenograft Model Antitumor Assays Amino Acid Sequence Animals Antineoplastic Agents Pharmacology Tumor Markers, Biological Metabolism Genetics Gene Expression Profiling Graft Survival Drug Effects Indoles Mice Mice, Knockout Molecular Sequence Data Neoplasm Metastasis Pyrroles Sequence Homology, Amino Acid Von Hippel-lindau Tumor Suppressor Protein Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Urology Oncology

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Tissue slice grafts of human renal cell carcinoma: an authentic preclinical model with high engraftment rate and metastatic potential.