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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-11-26
pubmed:abstractText
Previous studies showed promise of coupling genetically engineered neural stem cells (NSCs) with blood-brain barrier permeable prodrugs as an effective anti-brain tumor therapy. Here, we further advance those findings by testing the suicide gene therapeutic system in syngenic glioblastoma immunocompetent mice. After intracranial injection of HB1.F3.CD, an immortalized human NSC cell line engineered to constitutively produce cytosine deaminase (CD), the prodrug 5-fluorocytosine (5-FC) was administered for five days, q.d., via intraperitoneal injection. The HB1. F3.CD hNSCs migrated specifically to the brain tumor site via the corpus callosum and significantly reduced the tumor volume (67%) by converting 5-FC into the cytotoxic 5-fluorouracil. A corresponding increase in F4/80-positive population was observed in the treatment group, although CD3-positive population remained unchanged compared to control. No toxic effects or morphological changes were observed in the spleen and the lymph nodes. The data suggest that the NSC-enzyme/prodrug treatment is an effective anti-tumor therapeutic strategy that specifically targets only the tumor site with little or no systemic side effects. In addition, the treatment modeled here successfully elicited a macrophagic immune response which seemed to have a synergistic role in reducing tumor volume, thus showing promise for treatment-mediated enhancement of inherent immune responses against brain tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1791-2431
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
63-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Combined treatment of tumor-tropic human neural stem cells containing the CD suicide gene effectively targets brain tumors provoking a mild immune response.
pubmed:affiliation
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't