The Xenograft and Cell Line Core (Core B) will provide state of the art molecularly characterized human models representing childhood sarcoma histotypes to be studied in Projects 1-3. Patient derived xenografts (PDX) representing Ewing sarcoma (n=7). Osteosarcoma (n=10) and rhabdomyosarcoma (n=15) and cell lines (n=16) are available for study. Authenticity and validity of lines within the Core have been determined by periodic short tandem repeat (STR) analysis, and molecular profiling. The Core will provide subcutaneous, orthotopic and disseminated disease models as required for individual projects, as well as services listed: 1. Maintain and characterize human xenografts, and maintain frozen stocks of xenografts authenticated by short tandem repeat (STR) analysis. 2. Maintain and characterize cell lines by STR analysis for use in Projects 1-3. 3. To provide a facility for the propagation of xenografts of pediatric solid tumors, for use in all Projects. 4. Provide orthotopic and disseminated xenograft models for secondary testing. 5. Coordinate tumor transplantation and make available tumor-bearing mice for pharmacodynamic and pharmacokinetic studies as required. 6. Coordinate treatment and tissue collection. 7. Undertake drug evaluation studies using standardized protocols, and transfer data to the Biostatics Core. 8. Provide other services (e.g. blood and tissue collection, for PK/PD studies). 9. Assist in planning and experimental design in consultation with the biostatistics Core A. Although this is a new Core, the Core director has over 35 years experience developing and using human tumor xenograft models, and has published 50 papers reporting the evaluation of new agents using these models since 2007. The Core has provided services that have resulted in two publications since the AO submission.

Public Health Relevance

The Core will provide sarcoma cell lines and xenograft tissues, and undertake services that are essential for successful completion of studies proposed in each ofthe projects within the Program Project Grant.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-C)
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Nationwide Children's Hospital
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Bid, Hemant K; Roberts, Ryan D; Cam, Maren et al. (2014) ýýNp63 promotes pediatric neuroblastoma and osteosarcoma by regulating tumor angiogenesis. Cancer Res 74:320-9
Singh, Mamata; Leasure, Justin M; Chronowski, Christopher et al. (2014) FANCD2 is a potential therapeutic target and biomarker in alveolar rhabdomyosarcoma harboring the PAX3-FOXO1 fusion gene. Clin Cancer Res 20:3884-95
Bid, Hemant K; Roberts, Ryan D; Manchanda, Parmeet K et al. (2013) RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Mol Cancer Ther 12:1925-34