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In vivo fate and therapeutic efficacy of PF-4/CTF microspheres in an orthotopic human glioblastoma model

Cited 29 time in Web of Science Cited 33 time in Scopus
Authors
Benny, Ofra; Kim, Seung-Ki; Gvili, Koby; Radzishevsky, Inna S; Mor, Amram; Verduzco, Luis; Menon, Lata G; Black, Peter M; Machluf, Marcelle; Carroll, Rona S
Issue Date
2007-09-18
Publisher
Federation of American Society of Experimental Biology (FASEB)
Citation
FASEB J. 22(2), 488-499
Keywords
AnimalsCell Proliferation/drug effectsCells, CulturedDisease Models, AnimalGlioblastoma/*drug therapy/*pathologyHumansLactic AcidMagnetic Resonance ImagingMaleMiceMice, NudeMicroscopy, Electron, Scanning*MicrospheresParticle SizePeptide Fragments/*pharmacology/*therapeutic usePlatelet Factor 4/*pharmacology/*therapeutic usePolyglycolic AcidPolymersTime FactorsXenograft Model Antitumor Assays
Abstract
The correlation between glioma grade and angiogenesis suggests that antiangiogenic therapies are potentially therapeutically effective for these tumors. However, to achieve tumor suppression, antiangiogenic therapies need to be administered daily using high systemic quantities. We designed a biodegradable polymeric device that overcomes those barriers by providing sustained local delivery of a C-terminal fragment of platelet factor 4 (PF-4/CTF), an antiangiogenic agent. Fluorescent-labeled microspheres composed of poly lactic-coglycolic acid (PLGA) were loaded with rhodamine-labeled PF-4/CTF and formulated to release their contents over time. Fluorescent labeling enabled the correlation between the in vitro to the in vivo kinetic and release studies. PF-4/CTF microspheres were injected into established intracranial human glioma tumors in nude mice. Noninvasive magnetic resonance imaging (MRI) was used to assess the therapeutic response. Tumor size, microvessel density, proliferation, and apoptosis rate were measured by histological analysis. Intracranially, the microspheres were located throughout the tumor bed and continuously released PF-4/CTF during the entire experimental period. MRI and histological studies showed that a single injection of microspheres containing PF-4/CTF caused a 65.2% and 72% reduction in tumor volume, respectively, with a significant decrease in angiogenesis and an increase in apoptosis. Our data demonstrate that polymeric microspheres are an effective therapeutic approach for delivering antiangiogenic agents that result in the inhibition of glioma tumor growth.
ISSN
1530-6860 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17873103

http://www.fasebj.org/cgi/reprint/22/2/488.pdf

http://hdl.handle.net/10371/68353
DOI
https://doi.org/10.1096/fj.07-8801com
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College of Medicine/School of Medicine (의과대학/대학원)Neurosurgery (신경외과학전공)Journal Papers (저널논문_신경외과학전공)
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