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Inhibition of carcinoma cell-derived VEGF reduces inflammatory characteristics in xenograft carcinoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2006 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, no 12, 2795-2802 p.Article in journal (Refereed) Published
Abstract [en]

The stroma of carcinomas shares several characteristics with inflamed tissues including a distorted vasculature, active angiogenesis and macrophage infiltration. In addition, the tumor interstitial fluid pressure (P-IF) of the stroma is pathologically elevated. We show here that bevacizumab [rhuMab vascular endothelial growth factor (VEGF), Avastin], a monoclonal antibody to VEGF, at a dose of 5 mg/kg modulated inflammation in KAT-4 xenograft human anaplastic thyroid carcinoma tissue. At this dose, bevacizumab reduced the density of macrophages, MHC class II antigen expression by macrophages and II-1 beta mRNA expression. Furthermore, bevacizumab lowered tumor extracellular fluid volume, plasma protein leakage from tumor vessels, the number of CD31positive structures and tumor P-IF. The tumor plasma volume and the number of alpha-smooth muscle actin-positive vessels, however, remained unchanged. Our data suggest that carcinoma cellderived VEGF either directly or indirectly participates in maintaining an inflammatory microenvironment in experimental KAT4 carcinoma. Furthermore, our data indicate that the reduction of inflammation resulting in reduced vascular permeability and decrease in the tumor extracellular fluid volume by bevacizurnab contributes to reduced tumor P-IF.

Place, publisher, year, edition, pages
2006. Vol. 119, no 12, 2795-2802 p.
Keyword [en]
angiogenesis, anaplastic thyroid carcinoma, growth factors, interstitial fluid pressure, vasculature
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-22404DOI: 10.1002/ijc.22217ISI: 000242307800010PubMedID: 17019708OAI: oai:DiVA.org:uu-22404DiVA: diva2:50177
Available from: 2007-07-10 Created: 2007-07-10 Last updated: 2011-05-06Bibliographically approved

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Heldin, Nils-ErikReed, Rolf K.Rubin, Kristofer
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