| Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor. | |
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MedLine Citation:
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PMID: 10463618 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The goal of this investigation was to measure changes in vascular permeability, pore cutoff size, and number of transvascular transport pathways as a function of time and in response to vascular endothelial growth factor (VEGF), placenta growth factor (PIGF-1 and PIGF-2), or basic fibroblast growth factor (bFGF). Two human and two murine tumors were implanted in the dorsal skin chamber or cranial window. Vascular permeability to BSA (approximately 7 nm in diameter) and extravasation of polyethylene glycol-stabilized long-circulating liposomes (100-400 nm) and latex microspheres (approximately 800 nm) were determined by intravital microscopy. Vascular permeability was found to be temporally heterogeneous. VEGF superfusion (100 ng/ml) significantly increased vascular permeability to albumin in normal s.c. vessels, whereas a 30-fold higher dose of VEGF (3000 ng/ml) was required to increase permeability in pial vessels, suggesting that different tissues exhibit different dose thresholds for VEGF activity. Furthermore, VEGF superfusion (1000 ng/ml) increased vascular permeability to albumin in a hypopermeable human glioma xenograft in cranial window, whereas VEGF superfusion (10-1000 ng/ml) failed to increase permeability in a variety of hyperpermeable tumors grown in dorsal skin chamber. Interestingly, low-dose VEGF treatment (10 ng/ml) doubled the maximum pore size (from 400 to 800 nm) and significantly increased the frequency of large (400 nm) pores in human colon carcinoma xenografts. PIGF-1, PIGF-2, or bFGF did not show any significant effect on permeability or pore size in tumors. These findings suggest that exogenous VEGF may be useful for augmenting the transvascular delivery of larger antineoplastic agents such as gene targeting vectors and encapsulated drug carriers (typical range, 100-300 nm) into tumors. |
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Authors:
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W L Monsky; D Fukumura; T Gohongi; M Ancukiewcz; H A Weich; V P Torchilin; F Yuan; R K Jain |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 59 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1999 Aug |
Date Detail:
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Created Date: 1999-09-16 Completed Date: 1999-09-16 Revised Date: 2009-11-25 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4129-35 Citation Subset: IM |
Affiliation:
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Edwin L. Steele Laboratory, Massachusetts General Hospital, and Harvard Medical School, Boston 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Transport / drug effects Capillary Permeability / drug effects* Drug Delivery Systems Endothelial Growth Factors / pharmacology* Fibroblast Growth Factor 2 / pharmacology* Humans Liposomes Lymphokines / pharmacology* Macromolecular Substances Mice Microspheres Neoplasms, Experimental / blood supply* Neovascularization, Pathologic* Pregnancy Proteins / pharmacology* Time Factors Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| Grant Support | |
ID/Acronym/Agency:
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R35-CA56591/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Endothelial Growth Factors; 0/Liposomes; 0/Lymphokines; 0/Macromolecular Substances; 0/Pregnancy Proteins; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 103107-01-3/Fibroblast Growth Factor 2; 144589-93-5/placenta growth factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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