dc.contributor.author
Knitter, Sebastian
dc.contributor.author
Duwe, Gregor
dc.contributor.author
Beierle, Anika Sophie
dc.contributor.author
Pesthy, Sina
dc.contributor.author
Ritschl, Paul Viktor
dc.contributor.author
Hillebrandt, Karl Herbert
dc.contributor.author
Arnold, Alexander
dc.contributor.author
Malinka, Thomas
dc.contributor.author
Modest, Dominik Paul
dc.contributor.author
Bahra, Marcus
dc.contributor.author
Pratschke, Johann
dc.contributor.author
Sauer, Igor Maximilian
dc.contributor.author
Schmelzle, Moritz
dc.contributor.author
Andreou, Andreas
dc.date.accessioned
2023-03-29T14:51:12Z
dc.date.available
2023-03-29T14:51:12Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/38675
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-38391
dc.description.abstract
Simple Summary: For patients undergoing multimodal treatment for colorectal liver metastases (CLM), the development of sinusoidal obstruction syndrome (SOS) as a side effect of oxaliplatin-based chemotherapy may endanger the prospects after liver resection. In this study, we aimed to investigate possible protective effects of an additional preoperative inhibition of vascular endothelial growth factor (VEGF) on the occurrence of SOS and its implications on liver function and regeneration after liver resection. After successful establishment of a novel murine model of SOS, we were able to show a reduced incidence of SOS after additive treatment with a VEGF inhibitor. Changes in the VEGF pathway, namely in the expression of VEGF receptor-2 (VEGF-R2), may be responsible for these findings. By preventing the incidence of SOS, the inhibition of VEGF may help to reduce morbidity after liver resection for patients with CLM. Further clinical studies are needed to corroborate our results.
Abstract:
(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model.
(2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma.
(3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition.
(4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
colorectal liver metastases
en
dc.subject
sinusoidal obstruction syndrome
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Inhibition of Vascular Endothelial Growth Factor Protects against the Development of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome in Wild-Type but Not in CD39-Null Mice
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
5992
dcterms.bibliographicCitation.doi
10.3390/cancers14235992
dcterms.bibliographicCitation.journaltitle
Cancers
dcterms.bibliographicCitation.number
23
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
14
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
36497474
dcterms.isPartOf.eissn
2072-6694