Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases.

Authors: Panigrahy, Dipak; Gartung, Allison; Yang, Jun; Yang, Haixia; Gilligan, Molly M; Sulciner, Megan L; Bhasin, Swati S; Bielenberg, Diane R; Chang, Jaimie; Schmidt, Birgitta A; Piwowarski, Julia; Fishbein, Anna; Soler-Ferran, Dulce; Sparks, Matthew A; Staffa, Steven J; Sukhatme, Vidula; Hammock, Bruce D; Kieran, Mark W; Huang, Sui; Bhasin, Manoj; Serhan, Charles N; Sukhatme, Vikas P

Published In J Clin Invest, (2019 06 17)

Abstract: Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 (TXA2) pathway. Preoperative stimulation of inflammation resolution via resolvins (RvD2, RvD3, and RvD4) inhibited metastases and induced T cell responses. Ketorolac and resolvins exhibited synergistic antitumor activity and prevented surgery- or chemotherapy-induced dormancy escape. Thus, simultaneously blocking the ensuing proinflammatory response and activating endogenous resolution programs before surgery may eliminate micrometastases and reduce tumor recurrence.

PubMed ID: 31205032 Exiting the NIEHS site

MeSH Terms: Animals; Docosahexaenoic Acids/pharmacology*; Immunity, Cellular/drug effects*; Ketorolac/pharmacology*; Male; Mice; Mice, Knockout; Neoplasm Metastasis; Neoplasm Recurrence, Local/metabolism; Neoplasm Recurrence, Local/pathology; Neoplasm Recurrence, Local/prevention & control*; Neoplasms, Experimental*/metabolism; Neoplasms, Experimental*/pathology; Neoplasms, Experimental*/therapy; Preoperative Care*; T-Lymphocytes/metabolism*; T-Lymphocytes/pathology

Back
to Top