Linked Life Data

18006807

Source:http://linkedlifedata.com/resource/pubmed/id/18006807

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2007-11-16
pubmed:abstractText
Oncolytic viral vectors show enormous potential for the treatment of many solid tumors. However, these vectors often suffer from insufficient delivery within tumors, which limits their efficacy in both preclinical and clinical settings. We have previously shown that tumor collagen can significantly hinder diffusion, and that its degradation can enhance the distribution and efficacy of an oncolytic herpes simplex virus (HSV) vector. Here, we identify two members of the matrix metalloproteinase (MMP) family of enzymes, MMP-1 and MMP-8, which can modulate the tumor matrix and enhance HSV delivery and efficacy. We show that overexpression of MMP-1 and MMP-8 in the human soft tissue sarcoma HSTS26T leads to a significant depletion of tumor-sulfated glycosaminoglycans. This increases the hydraulic conductivity of these tumors and enhances the flow of virus during injection. In control tumors, injected virus accumulates primarily in the periphery of the tumor. In contrast, we observed a more widespread distribution of virus around the injection site in MMP-1- and MMP-8-expressing tumors. Due to this enhanced vector delivery, MMP-expressing tumors respond significantly better to oncolytic HSV treatment than control tumors. Thus, these findings introduce a new approach to improve the delivery and efficacy of oncolytic viral vectors: modulation of tumor glycosaminoglycans to enhance convection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10664-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Matrix metalloproteinases-1 and -8 improve the distribution and efficacy of an oncolytic virus.
pubmed:affiliation
Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural