TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model.

TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (P<0.01) and size of metastases (P<0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer

How to define the hemodynamic significance of an equivocal iliofemoral artery stenosis: Review of literature and outcomes of an international questionnaire

Purpose: The goal of the study was to review current literature regarding the diagnosis of equivocal (50–70%) iliofemoral artery stenosis and compare these findings with the daily practice of an international panel of endovascular experts. Methods: The Medline Database was searched for relevant publications, and an electronic survey was sent to experts in the field covering the following topics: definition of an equivocal iliofemoral artery stenosis, angiographic visualization and investigation protocols of an equivocal stenosis, intra-arterial pressure measurements, and definition of hemodynamic significance of an equivocal iliofemoral artery stenosis using a physiologic measure. Results: Of the 37 invited endovascular experts, 21 (53.8%) agreed to participate in the survey. Analysis of existing literature shows that the level of evidence for diagnosing equivocal iliofemoral artery stenosis is mediocre and is not being implemented by experts in the field. Conclusion: Studies have shown that a stenosis of between 50% and 70% iliofemoral lumen diameter reduction shows a wide range of trans-stenotic pressure gradients. Equivocal iliofemoral artery stenosis can best be identified using three-dimensional quantitative vascular analysis software. Although evidence for a clear hemodynamic cutoff point is weak, performing trans-lesion intra-arterial pressure measurements at rest and during maximal hyperemia is preferred. Diagnosing iliofemoral artery stenosis solely on lumen diameter reduction is inadequate