PMID: 9544428Apr 17, 1998Paper

Role of nitric oxide in IL-2 therapy-induced capillary leak syndrome

Cancer Metastasis Reviews
A Orucevic, P K Lala

Abstract

Nitric oxide (NO) is a potent short-lived and short range bioactive molecule, which plays a key role in physiological and pathological processes including inflammation and cancer. Detrimental effects of excessive NO production during septic shock have been well recognized. We tested the hypothesis that 'capillary leak syndrome' following systemic interleukin-2 (IL-2) therapy resulted from a cascade of events leading to the induction of NO which, directly or indirectly, injured capillaries and caused fluid leakage. Our results provided the first direct evidence that the induction of active NO synthase (NOS) leading to the overproduction of NO is instrumental in IL-2-induced capillary leakage in mice and that successful blocking of this overproduction with chronic oral administration of NOS inhibitors can mitigate this leakage without interfering with the beneficial antitumor effects of IL-2 therapy. NO blocking agents can, in fact, improve IL-2-induced antitumor effector cell activation, as well as tumor regression. In our studies, NO blocking agents alone reduced the growth and metastasis of a murine mammary carcinoma, at least in part, by mitigating the invasion and angiogenesis-stimulating role of tumor-derived NO. Thus, NOS ...Continue Reading

Citations

Apr 16, 2008·BJU International·Rituraj KonwarHemant Kumar Bid
Mar 13, 2010·Bulletin of Mathematical Biology·Raluca EftimieDavid J D Earn
Aug 9, 2003·Critical Care Medicine·Rhonda S FishelAdrian Barbul
May 22, 2003·Journal of the National Cancer Institute·Alan L EpsteinLeslie A Khawli
Apr 9, 2008·Journal of Immunotherapy·Muralidhar KondapaneniWolfram E Samlowski
Jun 3, 2008·Blood·Karolien CastermansArjan W Griffioen
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Jun 22, 2006·Expert Opinion on Investigational Drugs·Lynn Feun, Niramol Savaraj
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Jun 9, 2021·La Revue de médecine interne·A BichonJ Carvelli

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