Intratumoural expression of TNF-R1 and EMAP-II in relation to response of patients treated with TNF-based isolated limb perfusion

International Journal of Cancer. Journal International Du Cancer
Remco van HorssenAlexander M M Eggermont

Abstract

Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating polypeptide-II (EMAP-II) before and after ILP and evaluated this against clinical response. Tumour biopsies were taken before and after ILP of patients (n = 27) with advanced sarcoma or metastatic melanoma. Biopsies were randomly analysed by western blotting for proEMAP/EMAP-II and TNF-R1 expression. Appropriate melanoma biopsies were stained for EMAP-II, TNF-R1, CD31 and CD68. For melanomas we found that an up-regulation of EMAP-II, in contrast to proEMAP or TNF-R1, directly after ILP significantly correlated with a complete tumour response. No correlation was found for sarcoma patients. In a comparative analysis we found that the overall proEMAP and EMAP-II expression was higher in melanoma as compared to sarcoma cases and measurements in cell lines revealed high proEMAP expression by melanoma cells. We report high EMAP-II expression by endothelial cells and association with macrophages. In addition, macrophages are r...Continue Reading

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Citations

Oct 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·Remco van HorssenTimo L M ten Hagen
May 10, 2011·Current Problems in Surgery·Amira SankiJohn F Thompson
Mar 28, 2008·Immunological Reviews·Timo L M ten HagenAlexander M M Eggermont
Sep 2, 2006·Cytokine & Growth Factor Reviews·Remco van HorssenTimo L M ten Hagen
Jun 3, 2016·American Journal of Respiratory Cell and Molecular Biology·Daniel D LeeMargaret A Schwarz

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