20 research outputs found
Improved antitumor response to isolated limb perfusion with tumor necrosis factor after upregulation of endothelial monocyte-activating polypeptide II in soft tissue sarcoma
BACKGROUND: Experiments with tumor necrosis factor alpha (TNF) in rodents
have shown that a high dose can lead to hemorrhagic necrosis in tumors.
Endothelial monocyte-activating polypeptide II (EMAP-II) is a novel
tumor-derived cytokine, and its expression increases the TNF-1 receptor on
tumor endothelium, enhances the induction of tissue factor on tumor
endothelial cells, and has an antiangiogenic effect. It has recently been
shown that in vivo sensitivity of tumor vasculature to TNF is determined
by tumor production of EMAP-II. METHODS: We measured the level of EMAP-II
in a TNF-resistant soft tissue sarcoma. We subsequently
stabile-transfected this cell line with a retroviral construct containing
the EMAP gene. In an extremity perfusion model in tumor-bearing rats, we
measured response rates to TNF therapy. RESULTS: Functional EMAP-II
production was increased after this transfection. Immunostaining of
paraffin-embedded tumor tissue sections in rats showed an overexpression
of human EMAP-II. Results of the TNF perfusions in rats suggest that this
tumor is more sensitive to TNF therapy. CONCLUSIONS: EMAP-II is produced
in various levels. One can increase the sensitivity of tumor for TNF
therapy in vivo by upregulating the EMAP-II production. This result leaves
an opportunity for enhanced TNF response of tumors in future settings