Network of Mediators for Vascular Inflammation and Leakage Is Dysbalanced during Cytoreductive Surgery for Late-Stage Ovarian Cancer.
Journal
Mediators of inflammation
ISSN: 1466-1861
Titre abrégé: Mediators Inflamm
Pays: United States
ID NLM: 9209001
Informations de publication
Date de publication:
2019
2019
Historique:
received:
26
02
2019
revised:
07
06
2019
accepted:
24
06
2019
entrez:
10
8
2019
pubmed:
10
8
2019
medline:
14
1
2020
Statut:
epublish
Résumé
Cytoreductive surgery (CS) in late-stage ovarian cancer patients is often challenging due to extensive volume shifts, and high fluid intake may provoke postoperative complications. Expression of vasoactive mediators is altered in cancer patients, which may affect systemic vascular function. We sought to assess how serum levels of vasoactive markers and mediators change during CS in ovarian cancer. Following IRB approval and informed consent, pre- and postoperative serum samples were analyzed in 26 late-stage ovarian cancer patients using multiplex protein arrays and ELISA. The proinflammatory cytokines and chemokines IL-6, IL-8, and CCL2 were significantly elevated after 24 hrs compared to the baseline values, with IL-6 and IL-8 being most prominently increased. While ANGPT1 remained unchanged after surgery, its competitive antagonist ANGPT2 was significantly increased. In contrast, serum levels of the ANGPT receptor TIE2 were decreased to 0.6 of the baseline values. While VEGF-D, E-selectin, P-selectin, ICAM-1, and PECAM-1 remained unchanged, serum activity of both thrombomodulin and syndecan-1 was significantly increased following surgery. We identified a regulatory network of acute-phase reaction during CS in late-stage ovarian cancer. This suggests that IL-6 exerts positive regulation of other proinflammatory mediators and, by upregulating ANGPT2 and suppressing ANGPT1, induces a serum profile that promotes vascular leakage. This may contribute to the observed hemodynamic alterations during CS procedures.
Sections du résumé
BACKGROUND
BACKGROUND
Cytoreductive surgery (CS) in late-stage ovarian cancer patients is often challenging due to extensive volume shifts, and high fluid intake may provoke postoperative complications. Expression of vasoactive mediators is altered in cancer patients, which may affect systemic vascular function. We sought to assess how serum levels of vasoactive markers and mediators change during CS in ovarian cancer.
METHODS
METHODS
Following IRB approval and informed consent, pre- and postoperative serum samples were analyzed in 26 late-stage ovarian cancer patients using multiplex protein arrays and ELISA.
RESULTS
RESULTS
The proinflammatory cytokines and chemokines IL-6, IL-8, and CCL2 were significantly elevated after 24 hrs compared to the baseline values, with IL-6 and IL-8 being most prominently increased. While ANGPT1 remained unchanged after surgery, its competitive antagonist ANGPT2 was significantly increased. In contrast, serum levels of the ANGPT receptor TIE2 were decreased to 0.6 of the baseline values. While VEGF-D, E-selectin, P-selectin, ICAM-1, and PECAM-1 remained unchanged, serum activity of both thrombomodulin and syndecan-1 was significantly increased following surgery.
CONCLUSION
CONCLUSIONS
We identified a regulatory network of acute-phase reaction during CS in late-stage ovarian cancer. This suggests that IL-6 exerts positive regulation of other proinflammatory mediators and, by upregulating ANGPT2 and suppressing ANGPT1, induces a serum profile that promotes vascular leakage. This may contribute to the observed hemodynamic alterations during CS procedures.
Identifiants
pubmed: 31396019
doi: 10.1155/2019/5263717
pmc: PMC6664492
doi:
Substances chimiques
Chemokine CCL2
0
Interleukin-6
0
Interleukin-8
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5263717Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
Références
Eur J Cancer. 2001 Dec;37(18):2392-7
pubmed: 11720833
Blood. 2002 Mar 1;99(5):1646-50
pubmed: 11861279
Clin Chim Acta. 2002 Jul;321(1-2):11-6
pubmed: 12031586
J Am Soc Nephrol. 2002 Jun;13(6):1534-47
pubmed: 12039983
Am J Pathol. 2003 May;162(5):1463-73
pubmed: 12707029
Nature. 2005 Oct 13;437(7061):1032-7
pubmed: 16136080
J Cereb Blood Flow Metab. 2006 Jun;26(6):797-810
pubmed: 16192992
Surgery. 1992 Feb;111(2):201-9
pubmed: 1736391
Ann N Y Acad Sci. 2007 Jan;1095:129-33
pubmed: 17404025
J Biol Chem. 2008 Jul 18;283(29):19895-903
pubmed: 18499671
J Biol Chem. 2009 Dec 4;284(49):34342-54
pubmed: 19833726
Int Arch Allergy Immunol. 2010;152(2):140-50
pubmed: 20016196
Anesth Analg. 2010 Aug;111(2):464-7
pubmed: 20418537
Int J Gynecol Cancer. 2010 Dec;20(9):1498-505
pubmed: 21119365
Clin Sci (Lond). 1990 Aug;79(2):161-5
pubmed: 2167805
Semin Immunopathol. 2012 Jan;34(1):107-25
pubmed: 21805323
Am J Physiol Heart Circ Physiol. 2012 Feb 15;302(4):H1003-12
pubmed: 22180648
Cardiovasc Res. 2012 Jun 1;94(3):510-8
pubmed: 22505659
Rheumatology (Oxford). 2012 Sep;51(9):1571-9
pubmed: 22596210
Ann Rheum Dis. 2012 Aug;71(8):1402-10
pubmed: 22730375
Eur J Intern Med. 2013 Mar;24(2):132-8
pubmed: 23352000
Intensive Care Med. 2013 Jul;39(7):1262-71
pubmed: 23563632
Virulence. 2013 Aug 15;4(6):517-24
pubmed: 23652985
Coll Antropol. 2013 Mar;37(1):195-201
pubmed: 23697273
Int J Biol Sci. 2013 Sep 23;9(9):966-79
pubmed: 24155670
Pharmacol Res. 2014 Feb;80:43-51
pubmed: 24407281
Inhal Toxicol. 2014 Feb;26(3):185-92
pubmed: 24517841
Ann Surg Oncol. 2015 Apr;22(4):1332-40
pubmed: 25234021
Cytokine Growth Factor Rev. 2015 Jun;26(3):281-91
pubmed: 25466648
J BUON. 2015 May-Jun;20(3):870-8
pubmed: 26214642
Rev Esp Anestesiol Reanim. 2016 Mar;63(3):149-58
pubmed: 26318757
Cancer Res. 2015 Nov 15;75(22):4742-52
pubmed: 26471360
Mediators Inflamm. 2015;2015:418290
pubmed: 26770016
Mucosal Immunol. 2016 Sep;9(5):1125-36
pubmed: 26813342
Crit Care. 2016 Mar 06;20:51
pubmed: 26951111
J Med Case Rep. 2016 May 24;10:125
pubmed: 27386947
Gynecol Oncol. 2016 Oct 28;:null
pubmed: 28029449
Chest. 2017 Jul;152(1):22-31
pubmed: 28109962
Cardiovasc Res. 2017 May 1;113(6):671-680
pubmed: 28453727
Immunol Invest. 2017 Oct;46(7):677-688
pubmed: 28872976
J Trauma Acute Care Surg. 2018 Jan;84(1):81-88
pubmed: 28885470
Ann Oncol. 2017 Nov 1;28(suppl_8):viii25-viii29
pubmed: 29232471
Front Immunol. 2018 Apr 05;9:663
pubmed: 29675023
PLoS One. 2018 Jun 21;13(6):e0193657
pubmed: 29927924
Crit Care Med. 1993 Feb;21(2 Suppl):S55-68
pubmed: 8428499
J Biol Chem. 1996 Jan 12;271(2):736-41
pubmed: 8557680
Surgery. 1997 Jul;122(1):60-8
pubmed: 9225916