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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Saraf, Amanda J; Fenger, Joelle M; Roberts, Ryan D (2018) Osteosarcoma: Accelerating Progress Makes for a Hopeful Future. Front Oncol 8:4
Bandyopadhyay, Abhik; Favours, Edward; Phelps, Doris A et al. (2018) Evaluation of patritumab with or without erlotinib in combination with standard cytotoxic agents against pediatric sarcoma xenograft models. Pediatr Blood Cancer 65:
Dowless, Michele; Lowery, Caitlin D; Shackleford, Terry et al. (2018) Abemaciclib Is Active in Preclinical Models of Ewing Sarcoma via Multipronged Regulation of Cell Cycle, DNA Methylation, and Interferon Pathway Signaling. Clin Cancer Res 24:6028-6039
Gross, Amy C; Cam, Hakan; Phelps, Doris A et al. (2018) IL-6 and CXCL8 mediate osteosarcoma-lung interactions critical to metastasis. JCI Insight 3:
Waters, Andrew M; Ozkan-Dagliyan, Irem; Vaseva, Angelina V et al. (2017) Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies. Sci Signal 10:
Zhou, Xinhui; Liu, Weijin; Hu, Xing et al. (2017) Regulation of CHK1 by mTOR contributes to the evasion of DNA damage barrier of cancer cells. Sci Rep 7:1535
Yu, Peter Y; Gardner, Heather L; Roberts, Ryan et al. (2017) Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. PLoS One 12:e0181885
Jayabal, Panneerselvam; Houghton, Peter J; Shiio, Yuzuru (2017) EWS-FLI-1 creates a cell surface microenvironment conducive to IGF signaling by inducing pappalysin-1. Genes Cancer 8:762-770
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
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

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