Summary of Study ST002354

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001511. The data can be accessed directly via it's Project DOI: 10.21228/M8CQ6T This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002354
Study TitleCombination of TP-252 and Naproxen elicit tumor protective Eicosanoid changes.
Study SummaryColorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Patients with the genetic disorder Familial Adenomatous Polyposis (FAP) develop hundreds to thousands of polyps that unless removed by prophylactic colectomy will progress to CRC at an early age. Non-steroidal anti-inflammatory drugs (NSAIDs) and -3 marine polyunsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA), have been evaluated for their chemopreventive potential in delaying the onset of CRC in high-risk patients. In this study, we determined whether the NSAID, naproxen, alone or in combination with a chemically-stable form of EPA (TP-252), affects tumor formation in the ApcPirc rat model. When compared to control diet, animals fed naproxen or HD TP-252 had 66%, and 82% fewer tumors respectively. However, when fed a combination of naproxen and HD TP-252, animals exhibited a 95% reduction in tumor formation and a 98% reduction in tumor volume, respectively. To elucidate potential mechanisms of tumor protection, a comprehensive, targeted lipidomic analysis was performed on colonic mucosa to determine changes in eicosanoid metabolism. Animals receiving TP-252 alone or in combination with naproxen had significantly reduced mucosal levels of pro-inflammatory -6 eicosanoids (PGE2, 5-HETE, and 14,15-DiHETrE), along with a simultaneous increase in anti-inflammatory EPA-derived -3 eicosanoids. Our colonic mucosal lipidomic analysis also uncovered several potential pharmacodynamic (PD) lipid biomarkers, including resolvin E2, 9-HEPE, 12-HEPE and 18-HEPE, that were increased in both the tissue and plasma of rats receiving TP-252 and were significantly correlated with tumor protection. Further studies with this drug combination should be focused on dose optimization and the role of EPA-derived lipid mediators in CRC initiation and progression.
UConn Health
Last NameBeach
First NameRyan
Address263 Farmington Avenue, Farmington CT 06030
Submit Date2022-11-21
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2022-12-22
Release Version1
Ryan Beach Ryan Beach application/zip

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Collection ID:CO002436
Collection Summary:Animals were sacrificed by CO2 narcosis, and large intestines were excised, washed with ice-cold PBS, and laid flat on filter paper. Tumor-adjacent full-thickness colon segments were flash-frozen in liquid Nitrogen and stored at -80C until analysis. Blood was collected via cardiac puncture and put in lithium heparin tubes on ice. Samples were centrifuged at 2,000 g for 20 minutes, and supernatant (plasma) was collected and stored at -80C until analysis.
Sample Type:Blood (Plasma) and Large Intestine