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.
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.
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|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|
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