Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Castellani, C; Singer, G; Eibisberger, M; Obermüller, B; Warncke, G; Miekisch, W; Kolb-Lenz, D; Summer, G; Pauer, TM; ElHaddad, A; Kashofer, K; Till, H.
The effects of neuroblastoma and chemotherapy on metabolism, fecal microbiome, volatile organic compounds, and gut barrier function in a murine model.
Pediatr Res. 2019; 85(4):546-555
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Castellani Christoph
Eibisberger Margarita
Kashofer Karl
Kolb-Lenz Dagmar
Obermüller Beate
Singer Georg
Till Holger
Warncke Gert
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Abstract:
Following transplantation of human neuroblastoma (NB) cells into athymic mice, we investigated the effects of tumor growth and cyclophosphamide (CTX) treatment on systemic metabolism, gut inflammation and permeability, fecal microbiome and volatile organic compounds (VOCs). NB cells (MHH-NB11) were implanted into athymic mice (n=20); 20 healthy mice served as controls (sham).  CTX was given to 20 animals (10 NB and 10 sham) after 8 and 9 weeks. Metabolic changes were measured. Ileum samples were obtained for RT-PCR (claudins 2 and 4, occludin, tight junction protein 1) and apoptosis rate determination. Fecal microbiome and VOCs were analyzed. Values were compared to sham animals. NB caused reduction of adipose tissue, increases of IL-6 and TNF-α, and decreases of TGF-β1 and -β2. Serum FITC-dextrane levels were increased in NB and improved under CTX. Claudin 4 expression was higher in NB versus NB + CTX and sham animals. NB caused increased apoptosis of epithelial cells. NB but also CTX led to a reduction in the abundance of Lactobacillus. NB led to alterations of the fecal VOC profile. NB caused a catabolic pro-inflammatory state, increased gut permeability, altered fecal VOCs and reductions of Lactobacillus. Further investigations are required to determine if modifications of the intestinal microbiome may reverse some of the observed effects.

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