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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA165995-02
Application #
8745058
Study Section
Special Emphasis Panel (ZCA1-RPRB-C)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$234,949
Indirect Cost
$33,208
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Cam, Maren; Gardner, Heather L; Roberts, Ryan D et al. (2016) ΔNp63 mediates cellular survival and metastasis in canine osteosarcoma. Oncotarget :
Bid, Hemant K; Phelps, Doris A; Xaio, Linlin et al. (2016) The Bromodomain BET Inhibitor JQ1 Suppresses Tumor Angiogenesis in Models of Childhood Sarcoma. Mol Cancer Ther 15:1018-28
Murphy, Brendan; Yin, Han; Maris, John M et al. (2016) Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis. Cancer Res 76:5798-5809
Wu, Xiaojuan; Xiao, Hui; Wang, Ruoning et al. (2016) Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells. Curr Cancer Drug Targets 16:631-8
Forest, Amelie; Amatulli, Michael; Ludwig, Dale L et al. (2015) Intrinsic Resistance to Cixutumumab Is Conferred by Distinct Isoforms of the Insulin Receptor. Mol Cancer Res 13:1615-26
Studebaker, Adam; Bondra, Kathryn; Seum, Star et al. (2015) Inhibition of MEK confers hypersensitivity to X-radiation in the context of BRAF mutation in a model of childhood astrocytoma. Pediatr Blood Cancer 62:1768-74
Phelps, Doris; Bondra, Kathryn; Seum, Star et al. (2015) Inhibition of MDM2 by RG7388 confers hypersensitivity to X-radiation in xenograft models of childhood sarcoma. Pediatr Blood Cancer 62:1345-52
Adamson, Peter C; Houghton, Peter J; Perilongo, Giorgio et al. (2014) Drug discovery in paediatric oncology: roadblocks to progress. Nat Rev Clin Oncol 11:732-9
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; Cam, Maren et al. (2014) ýýNp63 promotes pediatric neuroblastoma and osteosarcoma by regulating tumor angiogenesis. Cancer Res 74:320-9

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