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Publication year
2010Author(s)
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Cancer and Metastasis Reviews, 29, 2, (2010), pp. 317-329ISSN
Annotation
1 juni 2010
Publication type
Article / Letter to editor

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Organization
Internal Medicine
Journal title
Cancer and Metastasis Reviews
Volume
vol. 29
Issue
iss. 2
Page start
p. 317
Page end
p. 329
Subject
N4i 1: Pathogenesis and modulation of inflammationAbstract
The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1beta as an add-on therapy in human metastatic disease. In animal studies for over 20 years, IL-1 has been demonstrated to increase adherence of tumor cells to the endothelium in vitro, and administration of IL-1 to mice increases the number of metastatic colonies and tumor growth. Importantly, reducing endogenous IL-1 activity, particularly IL-1beta, with the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduces both metastasis as well as tumor burden. Inhibition of IL-1 activity prevents in vivo blood vessel formation induced by products released from hypoxic macrophages or vascular endothelial cell growth factor itself. Mice deficient in IL-1beta do not form blood vessels in matrigels embedded with vascular endothelial cell growth factor or containing products of macrophages. Recombinant IL-1Ra (anakinra) has been administered to over 1,000 patients with septic shock resulting in a consistent reduction in all-cause 28-day mortality. Approved for treatment of rheumatoid arthritis, anakinra has a remarkable safety record. Anakinra resulted in decreased blood vessels in the pannus of affected joints in patients with rheumatoid arthritis. Neutralizing monoclonal antibodies to IL-1beta and a soluble receptor to IL-1 are approved for treating chronic inflammatory diseases. Given the availability of three therapeutic agents for limiting IL-1 activity, the safety of blocking IL-1, and the clear benefit of blocking IL-1 activity in animal models of metastasis and angiogenesis, clinical trials of IL-1 blockade should be initiated, particularly as an add-on therapy of patients receiving antiangiogenesis-based therapies.
This item appears in the following Collection(s)
- Academic publications [204994]
- Electronic publications [103270]
- Faculty of Medical Sciences [81051]
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