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Preoperativestimulation ofresolution andinflammation blockadeeradicatesmicrometastases Dipak PanigrahyAllison GartungJun Yang2019 год

Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases
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Аннотация: 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.
Год издания: 2019
Авторы: Dipak Panigrahy, Allison Gartung, Jun Yang, Haixia Yang, Molly M. Gilligan, Megan L. Sulciner, Swati S. Bhasin, Diane R. Bielenberg, Jaimie Chang, Birgitta Schmidt, Julia Piwowarski, Anna Fishbein, Dulce Soler-Ferran, Matthew A. Sparks, Steven J. Staffa, Vidula Sukhatme, Bruce D. Hammock, Mark W. Kieran, Sui Huang, Manoj Bhasin, Charles N. Serhan, Vikas P. Sukhatme
Издательство: American Society for Clinical Investigation
Источник: Journal of Clinical Investigation
Ключевые слова: Cancer, Stress, Anesthesia, and Immune Response, Inflammatory mediators and NSAID effects, Eicosanoids and Hypertension Pharmacology
Другие ссылки: Journal of Clinical Investigation (PDF)
Journal of Clinical Investigation (HTML)
eScholarship (California Digital Library) (PDF)
eScholarship (California Digital Library) (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
eScholarship (California Digital Library) (HTML)
PubMed Central (HTML)
PubMed (HTML)