Christoph Castellani1, Georg Singer2, Margarita Eibisberger1, Beate Obermüller3, Gert Warncke1, Wolfram Miekisch4, Dagmar Kolb-Lenz5, Gregor Summer1, Theresa M Pauer1, Ahmed ElHaddad1, Karl Kashofer6, Holger Till1. 1. Department of Paediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria. 2. Department of Paediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria. georg.singer@medunigraz.at. 3. Department of Biomedical Research, Medical University of Graz, Graz, Austria. 4. Experimental Research Center, Department of Anaesthesiology and Intensive Care, University of Rostock, Rostock, Germany. 5. Core Facility Ultra-Structure Analysis, Medical University of Graz, Graz, Austria. 6. Institute of Pathology, Medical University of Graz, Graz, Austria.
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Ulrike Erben; Christoph Loddenkemper; Katja Doerfel; Simone Spieckermann; Dirk Haller; Markus M Heimesaat; Martin Zeitz; Britta Siegmund; Anja A Kühl Journal: Int J Clin Exp Pathol Date: 2014-07-15
Authors: Andreas Sponring; Wojciech Filipiak; Tomas Mikoviny; Clemens Ager; Jochen Schubert; Wolfram Miekisch; Anton Amann; Jakob Troppmair Journal: Anticancer Res Date: 2009-01 Impact factor: 2.480