Network of Mediators for Vascular Inflammation and Leakage Is Dysbalanced during Cytoreductive Surgery for Late-Stage Ovarian Cancer.

Sven Klaschik,Tobias Hilbert,Mignon-Denise Keyver-Paik,Stilla Frede,Claudia Neumann,Markus Velten,Martin Soehle,Jennifer Gehlen,Andreas Hoeft

doi:10.1155/2019/5263717

Sven Klaschik, Tobias Hilbert + Show 7 more

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https://doi.org/10.1155/2019/5263717

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Journal: Mediators of Inflammation	Publication Date: Jul 17, 2019
Citations: 14	License type: CC BY 4.0

Affiliation: University Hospital Bonn

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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 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 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 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.

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In recent years, improved outcome and prolonged survival has been demonstrated for cytoreductive surgery (CS) in ovarian cancer (OC) patients even in advanced disease stages [1]
The proinflammatory cytokines and chemokines IL-6, IL-8, and CC chemokine ligand 2 (CCL2) were significantly elevated after 24 hrs compared to the baseline values, with IL6 and IL-8 being most prominently increased
We identified a regulatory network of acute-phase reaction during Cytoreductive surgery (CS) in late-stage ovarian cancer

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In recent years, improved outcome and prolonged survival has been demonstrated for cytoreductive surgery (CS) in ovarian cancer (OC) patients even in advanced disease stages [1]. Cancer tissues express a number of peptides that indicate and promote tumor progression, such as proteases, growth factors, or proinflammatory cytokines [4, 5] Since these soluble proteins can be detected in peripheral blood, their altered expression levels relative to healthy individuals can be used to estimate tumor load and patients’ prognosis. 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

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