Linked Life Data

17315187

Source:http://linkedlifedata.com/resource/pubmed/id/17315187

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-4-30
pubmed:abstractText
Conditionally replicating oncolytic adenoviruses represent a promising developmental strategy for the treatment of cancer refractory to current treatments, such as hormone refractory metastatic breast cancer. In clinical cancer trials, adenoviral agents have been well tolerated, but gene transfer has been insufficient for clinical benefit. One of the main reasons may be the deficiency of the primary adenovirus receptor, and therefore viral capsid modifications have been employed. Another obstacle to systemic delivery is rapid clearance of virus by hepatic Kupffer cells and subsequent inadequate bioavailability. In this study, we compared several capsid-modified oncolytic adenoviruses for the treatment of breast cancer with and without Kupffer cell inactivation. Replication deficient capsid-modified viruses were analyzed for their gene transfer efficacy in vitro in breast cancer cell lines and clinical samples and in vivo in orthotopic models of breast cancer. The effect of Kupffer cell depleting agents on gene transfer efficacy in vivo was evaluated. An aggressive lung metastatic model was developed to study the effect of capsid-modified oncolytic adenoviruses on survival. Capsid-modified viruses displayed increased gene transfer and cancer cell killing in vitro and resulted in increased survival in an orthotopic model of lung metastatic breast cancer in mice. Biodistribution of viruses was favorable, tumor burden and treatment response could be monitored repeatedly. Kuppfer cell inactivation led to enhanced systemic gene delivery, but did not increase the survival of mice. These results facilitate clinical translation of oncolytic adenoviruses for the treatment of hormone refractory metastatic breast cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-74
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Systemic efficacy of oncolytic adenoviruses in imagable orthotopic models of hormone refractory metastatic breast cancer.
pubmed:affiliation
Cancer Gene Therapy Group, Molecular Cancer Biology Program, University of Helsinki, Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't