Efficacy of suicide gene therapy in hypoxic rat 9L glioma cells.
J Neurooncol
; 90(1): 19-24, 2008 Oct.
Article
in En
| MEDLINE
| ID: mdl-18594766
ABSTRACT
Viral vector mediated suicide gene therapy (SGT) involving thymidine kinase (TK) or cytosine deaminase (CD) have considerable promise in the treatment of malignant brain tumors. An unresolved issue is to what extent tumor hypoxia influences the outcome of SGT since brain tumors characterized by regions of hypoxia have potentially reduced cellular metabolism and SGT's cytotoxicity is manifest through cellular metabolism. We studied in vitro and in vivo, the effect of hypoxia on the cytotoxicity of SGT in rat 9L glioma cells. Neither acute nor chronic hypoxia affected the cell killing of SGT by TK or CD. In vivo confirmation that SGT efficacy was not adversely affected by tumor hypoxia using the hypoxic cell marker pimonidazole was shown by the absence of a change in tumor hypoxia by SGT. These studies support the use of SGT utilizing either TK or CD gene strategies even when tumors are characterized by a hypoxic microenvironment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Genetic Therapy
/
Cell Hypoxia
/
Genes, Transgenic, Suicide
/
Glioma
Limits:
Animals
Language:
En
Journal:
J Neurooncol
Year:
2008
Document type:
Article
Affiliation country:
Estados Unidos