Noninvasive and real-time monitoring of the therapeutic response of tumors in vivo with an optimized hTERT promoter.
Cancer
; 118(7): 1884-93, 2012 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-22009660
ABSTRACT
BACKGROUND:
Telomerase is commonly recognized as an effective anticancer target. The human telomerase reverse transcriptase (hTERT), the rate-limiting component of telomerase, is expressed in most malignant tumors, but it is not found in most normal somatic cells. Here, we report a real-time and noninvasive method to monitor tumor response to a lentivirus-based hTERT-conditional suicidal gene therapy.METHODS:
In this study, we constructed a lentivirus system in which an optimized hTERT promoter was used to drive the expression of the cytosine deaminase (CD) gene, one of the suicide genes, and a green fluorescent protein (GFP) reporter gene (pLenti-CD/GFP). The lentivirus was used to infect telomerase-positive or telomerase-negative cell lines. In vitro and in vivo experiments were conducted to analyze the dynamic processes of exogenous gene expression noninvasively in cell culture and living animals in real time via optical imaging.RESULTS:
The lentivirus was able to express the CD gene and GFP in telomerase-positive tumor cells and significantly decrease cell proliferation after the use of prodrug 5-flucytosine. However, it could not express GFP and CD in telomerase-negative cell lines, nor could it induce any suicidal effect in those cells. The in vivo study showed that telomerase-positive tumors can be visualized after intratumor injection of the lentivirus in tumor-bearing nude mice via an optical imaging system. Significant tumor growth suppression was observed in telomerase-positive tumors.CONCLUSIONS:
Collectively, this technology provides a valuable, noninvasive method to evaluate the real-time therapeutic response of tumors in vivo.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Computer Systems
/
Genetic Therapy
/
Drug Monitoring
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Telomerase
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Cytosine Deaminase
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Neoplasms
Type of study:
Evaluation_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer
Year:
2012
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA