Abstract:
PURPOSE:This study determined whether adenovirus-mediated transfer of the murine interferon-beta (AdCMVIFN-beta) gene protects against liver metastases arising from intraocular melanomas in mice. METHODS:A replication-deficient adenovirus vector (AdCMVIFN-beta) was used for the in vivo transfer of the murine IFN-beta gene into intraocular melanoma-bearing mice. AdCMVIFN-beta was injected either intravenously or directly into the intraocular melanomas. The effect of gene transfer on liver metastases was ascertained by histopathologic analysis of the livers and by measuring serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are two enzymes associated with liver metastases in patients with uveal melanoma. RESULTS:Mice treated with two intratumoral injections of AdCMVIFN-beta had a 68% reduction in metastatic liver lesions (P = 0.016) and a 51% reduction in liver enzyme levels compared with control mice (P = 0.02). However, the antimetastatic effect of AdCMVIFN-beta was not directly attributable to the adenovirus vector or virus-mediated cytolysis of tumor cells. Intravenous treatment with AdCMVIFN-beta resulted in an 86% reduction in the number of metastatic foci in the liver (P = 0.014) and a 61% reduction of serum AST levels compared with mice treated with AdCMVLacZ (P = 0.015). AdCMVIFN-beta treatment produced a sharp increase in the NK cell activity that was demonstrable in vivo and in vivo. In vivo depletion of NK cells by anti-asialo GM1 antibody abrogated the antimetastatic effects of AdCMVIFN-beta. CONCLUSIONS:The results support the feasibility of activation of NK cell function through gene transfer as one possible therapeutic strategy for reducing hepatic metastases of uveal melanomas.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Alizadeh H,Howard K,Mellon J,Mayhew E,Rusciano D,Niederkorn JYdoi
10.1167/iovs.02-1147keywords:
subject
Has Abstractpub_date
2003-07-01 00:00:00pages
3042-51issue
7eissn
0146-0404issn
1552-5783journal_volume
44pub_type
杂志文章abstract:Purpose:To elucidate the molecular events in solute carrier family 4 member 11 (SLC4A11)-deficient corneal endothelium that lead to the endothelial dysfunction that characterizes the dystrophies associated with SLC4A11 mutations, congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy...
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abstract:Purpose:To determine whether mitochondrial DNA haplogroups or rare variants associate with primary open-angle glaucoma in subjects of European descent. Methods:A case-control comparison of age- and sex-matched cohorts of 90 primary open-angle glaucoma patients and 95 population controls. Full mitochondrial DNA sequenc...
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journal_title:Investigative ophthalmology & visual science
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abstract::Refractile inclusion bodies (approximately 0.80 micron in size) were found in the inner segments of cone photoreceptors in the aging human retina. They were easily resolved with the light microscope. They were never seen in rods, and occurred primarily in retinas from eye donors older than 40 years of age. The inciden...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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pub_type: 杂志文章
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更新日期:2012-01-17 00:00:00
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更新日期:2015-04-01 00:00:00
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更新日期:2011-09-27 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
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更新日期:2016-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1995-05-01 00:00:00
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更新日期:2011-06-08 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1994-11-01 00:00:00
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更新日期:2011-09-29 00:00:00
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更新日期:2011-05-17 00:00:00
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