Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases

Panigrahy, Dipak; Gartung, Allison; Yang, Jun; Yang, Haixia; Gilligan, Molly M.; Sulciner, Megan L.; Bhasin, Swati S.; Bielenberg, Diane R.; Chang, Jaimie; Schmidt, Birgitta; 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.

doi:10.1172/jci127282

Cited by 103 publications

(109 citation statements)

References 100 publications

(142 reference statements)

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“…Preoperative administrations of the non-steroidal antiinflammatory drug ketorolac and/or resolvins induced T cell responses and eliminated micrometastases in multiple tumor-resection models. Ketorolac and resolvins exhibited synergistic antitumor activity (46). A similar observation was also found in leukemia.…”

Section: Tumor-derived Extracellular Vesicles Affect Bystander Cellssupporting

confidence: 53%

The Interplay Between the DNA Damage Response, RNA Processing and Extracellular Vesicles

2020

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RNA processing was recently found to affect DNA damage response. The RNA processing factors THRAP3 and BCLAF1 play critical role in keeping DNA genomic stability by regulating the transcription, mRNA splicing and export of DNA repair proteins BRCA2, PALB2, Rad51, FANCD2, and FANCL in response to DNA damage. RNA processing factors THRAP3 and BCLAF1 play critical roles in maintaining DNA genomic stability. These factors regulate transcription, mRNA splicing and nuclear RNA export of DNA repair proteins BRCA2, PALB2, Rad51, FANCD2, and FANCL in response to DNA damage. Splicing factors SRSF10 and Sam68 were found to control the DNA damage agent-induced mRNA splicing of transcripts including BCLAF1, BRCA1, BCL2L1, CASP8, CHK2, and RBBP8 to regulate apoptosis, cell-cycle transition and DNA repair. Splicing factors and RNA binding proteins (RBPs) were also found to play a critical role in DNA/RNA hybrids (R-loops) formed during transcription and RNA processing to prevent RNA-induced genome instability. At the same time, DNA repair proteins FANCI and FANCD2 were found to regulate the nuclear localization of splicing factors SF3B1 in the DNA damage response. In addition, tumor-derived extracellular vesicles (Evs) enhanced by chemotherapeutic agents in cancer were found to promote cancer metastasis and drug resistance. Inhibiting Evs from cancer cells significantly reduced cancer metastasis and drug resistance. Furthermore, cross-talk between the DNA damage response and the immune response was observed including the enhancement of the efficacy of immune checkpoint blockade by PARP inhibitors and the effect of PD-L1 on mRNA stability of various mRNAs involved in DNA damage response by acting as a novel RNA binding protein to increase drug resistance in cancer cells. This review will introduce recent progress on the interplay of the DNA damage response, the RNA processing and the extracellular vesicles mediated metastasis.

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Section: Tumor-derived Extracellular Vesicles Affect Bystander Cellssupporting

confidence: 53%

The Interplay Between the DNA Damage Response, RNA Processing and Extracellular Vesicles

2020

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“…The BLT1 receptor is expressed on human neutrophils, eosinophils, monocytes, macrophages, mast cells, dendritic cells, and T cells [ 48 ]. Both resolvins (RvE1, RvE2) are antagonists of the BLT1 receptor and have counterregulatory effects that lead to the inhibition of neutrophil chemotaxis, calcium mobilization, and NF-kB activation [ 55 , 56 ]. The types of resolvins and their roles are presented in Table 1 .…”

Section: Receptors For Resolvinsmentioning

confidence: 99%

The Role of Resolvins: EPA and DHA Derivatives Can Be Useful in the Prevention and Treatment of Ischemic Stroke

Tułowiecka

Kotlęga

Prowans

2020

IJMS

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Introduction: Most ischemic strokes develop as a result of atherosclerosis, in which inflammation plays a key role. The synthesis cascade of proinflammatory mediators participates in the process induced in the vascular endothelium and platelets. Resolvins are anti-inflammatory mediators originating from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which may improve the prognosis related to atherosclerosis by inhibiting the production of proinflammatory cytokines, limiting neutrophil migration, or positively influencing phagocytosis. Although clinical trials with resolvin in humans after stroke have not been realized, they may soon find application. Aim: The aim of the study was to review the available literature on the scope of the possibilities of the prevention and treatment of stroke with the use of resolvins, EPA and DHA derivatives. Materials and methods: The review features articles published until 31 January 2020. The search for adequate literature was conducted using the keywords: stroke and resolvins. Over 150 articles were found. Studies not written in English, letters to the editor, conference abstracts, and duplicate information were excluded. Results: In several studies using the animal model, the supplementation of resolvin D2 decreased brain damage caused by myocardial infarction, and it reversed the neurological dysfunction of the brain. A decrease in the concentration of proinflammatory cytokines, such as TNF-α, Il-6, and Il-1β, was also observed, as well as a decrease in the scope of brain damage. In the context of stroke in animals, the treatment with resolvin D2 (RvD2) (injection) has a better effect than supplementation with DHA. Conclusions: Resolvins are characterised by strong anti-inflammatory properties. Resolvins improve prognosis and decrease the risk of developing cardiovascular disease, consequently lowering the risk of stroke, and may find application in the treatment of stroke.

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“…Another very important paper by Panigrahy et al [84] reports in animal models that Ketorolac and resolvins exhibited synergistic antitumour activity and prevented surgery or chemotherapy-induced dormancy escape.…”

Section: Panigraphy Et Al (2019)mentioning

confidence: 99%

“…We propose that exploring the perioperative window will be a good place to start this process [80,81]. Other relevant papers have been published [82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99].…”

Section: The Black Swan Metaphormentioning

confidence: 99%

Breast cancer and the black swan

Retsky

Demicheli

Hrushesky

et al. 2020

ecancer

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Most current research in cancer is attempting to find ways of preventing patients from dying after metastatic relapse. Driven by data and analysis, this project is an approach to solve the problem upstream, i.e., to prevent relapse. This work aims, thus, to describe eventual mechanisms, and ways to test a solution addressing an unmet need. But first, we consider the context, including within an historical perspective, important to explain how and why a Kuhnian paradigm shift may be considered.

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Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases

Cited by 103 publications

References 100 publications

The Interplay Between the DNA Damage Response, RNA Processing and Extracellular Vesicles

The Interplay Between the DNA Damage Response, RNA Processing and Extracellular Vesicles

The Role of Resolvins: EPA and DHA Derivatives Can Be Useful in the Prevention and Treatment of Ischemic Stroke

Breast cancer and the black swan

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