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Interferon\u2010\u03b2 (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2) has been used to treat several cancer indications; however, little is known about the efficacy of<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2, each conjugated with a polyethylene glycol molecule (<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">hIFN<\/jats:styled-content>\u2010\u03b2 and<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">mIFN<\/jats:styled-content>\u2010\u03b2, respectively). We provide evidence that these<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 molecules retain anti\u2010viral potency comparable to unmodified<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2<jats:italic>in vitro<\/jats:italic>and manifested improved pharmacokinetics<jats:italic>in vivo<\/jats:italic>. Interestingly,<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">mIFN<\/jats:styled-content>\u2010\u03b2 significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">hIFN<\/jats:styled-content>\u2010\u03b2 directly suppresses<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content><jats:sub>165<\/jats:sub>\u2010induced hyperpermeability in a monolayer of human vascular endothelial cells and that<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">mIFN<\/jats:styled-content>\u2010\u03b2 enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b2 in maintaining vascular integrity, and provide proof\u2010of\u2010mechanism for a novel and long\u2010acting pegylated<jats:styled-content style=\"fixed-case\">hIFN<\/jats:styled-content>\u2010\u03b2 for the therapeutic treatment of malignant ascites.<\/jats:p>","DOI":"10.1111\/cas.13176","type":"journal-article","created":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T19:37:03Z","timestamp":1485545823000},"page":"581-589","source":"Crossref","is-referenced-by-count":9,"title":["Novel pegylated interferon\u2010\u03b2 as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer"],"prefix":"10.1111","volume":"108","author":[{"given":"Tomokatsu","family":"Iwamura","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Laboratory Toray Industries Kamakura Kanagawa 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