Deleterious synergistic effects of distress and surgery on cancer metastasis: Abolishment through an integrated perioperative immune-stimulating stress-inflammatory-reducing intervention.
Animals
Cell Line, Tumor
Female
Laparotomy
/ adverse effects
Male
Mice
Mice, Inbred BALB C
Neoplasm Metastasis
/ immunology
Neoplasms
/ metabolism
Perioperative Period
/ methods
Rats
Rats, Inbred F344
Stress, Psychological
/ immunology
Surgical Procedures, Operative
/ adverse effects
Treatment Outcome
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
04
07
2018
revised:
26
02
2019
accepted:
05
03
2019
pubmed:
10
3
2019
medline:
2
6
2020
entrez:
10
3
2019
Statut:
ppublish
Résumé
The perioperative period holds disproportionate impact on long-term cancer outcomes. Nevertheless, perioperative interventions to improve long-term cancer outcomes are not clinical routines, including perioperative stress-reducing or immune-stimulating approaches. Here, mimicking the clinical setting of pre-operative distress, followed by surgery, we examined the separate and combined effects of these events on the efficacy of pre-operative immune stimulation in rats and mice, and on post-operative resistance to tumor metastasis of the syngeneic mammary adenocarcinoma MADB106 in F344 rats and the CT26 colon carcinoma in Balb/C mice. The novel immune stimulating agents, GLA-SE or CpG-C (TLR-4 and TLR-9 agonists, respectively), were employed pre-operatively. Sixteen hours of pre-operative behavioral stressors (i) lowered CpG-C induced plasma IL-12 levels, and reduced resistance to MADB106 and CT-26 experimental metastases, and (ii) worsened the deleterious effects of laparotomy on metastasis in both tumor models. In rats, these effects of pre-operative stress were further studied and successfully abolished by the glucocorticoid receptor antagonist RU-486. Additionally, in vitro studies indicated the dampening effect of corticosterone on immune stimulation. Last, we tested a perioperative integrated intervention in the context of pre-operative stress and laparotomy, based on (i) antagonizing the impact of glucocorticoids before surgery, (ii) activating anti-metastatic immunity perioperatively, and (iii) blocking excessive operative and post-operative adrenergic and prostanoid responses. This integrated intervention successfully and completely abolished the deleterious effects of stress and of surgery on post-operative resistance to experimental metastasis. Such and similar integrated approaches can be studied clinically in cancer patients.
Identifiants
pubmed: 30851377
pii: S0889-1591(18)30299-X
doi: 10.1016/j.bbi.2019.03.005
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-178Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.