A victim of success? - Part 2.

[pjoshea13]

New paper. Odd that it would come so soon after the study that identified CXCL5 as an inflammatory promoter of cell growth, produced when there are a lot of dead cells waiting for clearance. See "A victim of success?" (3 days ago).

The natural antidote seems to be Resolvins.

"Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Thus, conventional cancer therapy is inherently a double-edged sword. In this study, we show that tumor cells killed by chemotherapy or targeted therapy (“tumor cell debris”) stimulate primary tumor growth when coinjected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure."

"Debris-stimulated tumors were inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin D1 (RvD1), RvD2, or RvE1."

"Resolvins counterregulate the release of cytokines/chemokines, including TNFα, IL-6, IL-8, CCL4, and CCL5, by human macrophages stimulated with cell debris."

Presumably "CCL5" is the same as the "CXCL5" mentioned in the first study.

...

Huang explained, "Dead-cell stimulated growth is naturally a part of the tissue regeneration cycle; debris is interpreted by the tissue as injury signal and stimulates wound healing and regeneration."

-Patrick

jem.rupress.org/content/ear...

Resolvins suppress tumor growth and enhance cancer therapy

Megan L. Sulciner, View ORCID ProfileCharles N. Serhan, View ORCID ProfileMolly M. Gilligan, Dayna K. Mudge, Jaimie Chang, Allison Gartung, Kristen A. Lehner, Diane R. Bielenberg, Birgitta Schmidt, Jesmond Dalli, Emily R. Greene, Yael Gus-Brautbar, Julia Piwowarski, Tadanori Mammoto, David Zurakowski, View ORCID ProfileMauro Perretti, Vikas P. Sukhatme, Arja Kaipainen, View ORCID ProfileMark W. Kieran, Sui Huang, Dipak Panigrahy

DOI: 10.1084/jem.20170681 | Published November 30, 2017

Abstract

Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Thus, conventional cancer therapy is inherently a double-edged sword. In this study, we show that tumor cells killed by chemotherapy or targeted therapy (“tumor cell debris”) stimulate primary tumor growth when coinjected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin D1 (RvD1), RvD2, or RvE1. These mediators specifically inhibit debris-stimulated cancer progression by enhancing clearance of debris via macrophage phagocytosis in multiple tumor types. Resolvins counterregulate the release of cytokines/chemokines, including TNFα, IL-6, IL-8, CCL4, and CCL5, by human macrophages stimulated with cell debris. These results demonstrate that enhancing endogenous clearance of tumor cell debris is a new therapeutic target that may complement cytotoxic cancer therapies.

Submitted: 12 April 2017

Revision received 15 September 2017

Accepted: 11 October 2017

[BigRich]

Patrick,

This sounds logical. What drugs or supplements generate Resolvins. In addition, to the effects generated above in the article, what other side effects could they have in the human body?

Rich

[pjoshea13 in reply to BigRich]

Rich,

My guess is that natural resolvins are harmless for most men, most of the time - but dangerous while under bacterial or viral attack that results in massive cell death.

Perhaps something to be used briefly, only while a CXCL5 test is positive. e.g. at the start of a new therapy, when cell death is high.

One wouldn't like to interfere with the regeneration of vital tissue.

-Patrick

[BigRich in reply to pjoshea13]

Is there an available blood test for CXCL5?

[pjoshea13 in reply to BigRich]

I don't know.

[SimonHL]

Hi Patrick

Two authors of the first paper have published a further paper which refers to the second paper you mentioned: Efferocytosis and prostate cancer skeletal metastasis: implications for intervention ncbi.nlm.nih.gov/pmc/articl....

Also, according to Wikipedia, CCL5 & CXCL5 are different:

Chemokine (C-C motif) ligand 5 (also CCL5) is a protein which in humans is encoded by the CCL5 gene.[5] It is also known as RANTES (regulated on activation, normal T cell expressed and secreted).

C-X-C motif chemokine 5 (CXCL5 or ENA78) is a protein that in humans is encoded by the CXCL5 gene