The overall goal ofthe comparative animal core is to support the development and use ofthe animal models employed within this Program Project Grant. The guiding principals for the comparative animal core are efficient planning and utilization of tissue and tumor samples, standardization of processing and diagnoses, and continued development of the canine spontaneous tumor animal model. This Core is housed and coordinated in the Department of Veterinary Biosciences in the College of Veterinary Medicine at OSU and includes individuals with expertise in comparative pathology, tissue banking, and clinical trial development and execution. Dr. Cheryl London, the proposed Core Director, is a Board Certified Veterinary Medical Oncologist with extensive expertise in cancer drug development including validating novel targets, identifying appropriate small molecules for target inhibition, and testing these compounds in relevant canine cancers with the goal of providing critical information that can assist in the human drug development process. Drs. Krista La Perie and Brad Bolon, Co-Investigators, are Board Certified in Veterinary Anatomic Pathology and are experts in the field of comparative pathology, particularly with respect to mouse models of cancer and evaluation of novel therapeutics in these models. The primary objective of this Core is to assist investigators in determining both the toxicities and activity associated with novel therapeutic approaches in mouse models of sarcoma, to identify candidate drugs/treatments that are likely to have success in the clinical setting, and to evaluate these treatments in dogs with spontaneous sarcomas as a prelude to future human clinical trials. As such, the specific aims of this Core are to: 1) Provide a standardized histopathologic evaluation of sarcomas generated in mouse models of disease following treatment with various targeted therapeutics;2) Identify adverse effects associated with treatment of mice with novel therapeutics. 3) Provide high quality normal and tumor tissue samples from dogs with spontaneous sarcomas;and 4) Assess the adverse event profile and biologic activity of a novel STATS inhibitor (LY5) in normal dogs and dogs with spontaneous osteosarcoma.

Public Health Relevance

The proposed Core is relevant as it assists in the integration of drug development efforts in mice with those in dogs and provides a platform to help rapidly move findings generated in vitro and mouse sarcoma models into the clinical setting. Given the challenges with respect to clinical trials in pediatric patients, the proposed Core will facilitate identifying therapeutic strategies most likely to be successful in this patient population.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-C)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Nationwide Children's Hospital
United States
Zip Code
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:
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:
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
Cam, Maren; Gardner, Heather L; Roberts, Ryan D et al. (2016) ?Np63 mediates cellular survival and metastasis in canine osteosarcoma. Oncotarget 7:48533-48546
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

Showing the most recent 10 out of 22 publications