Abstract | BACKGROUND: Hydrodynamic injection of naked plasmid DNA (pDNA) via the tail vein is a safe and effective method of gene transfer to the liver. However, successful gene transfer has yet to be shown for hepatocellular carcinoma (HCC); therefore, we investigated the feasibility and efficacy of hydrodynamic injection via the tail vein and hepatic artery in a diethylnitrosamine (DEN)-induced HCC model in rats. METHODS: HCC was induced in Sprague-Dawley rats by 100 ppm DEN in drinking water. pCMV-SPORT- beta-galactosidase (beta-gal, 400 microg) was injected (i) via the tail vein in a volume of 0.1 ml/g in 30 s or (ii) via the hepatic artery in a volume of 5 or 10 ml at 1 ml/s, either with or without temporary occlusion of the inferior vena cava (IVC) and portal vein (PV). The liver was harvested 24 h after administration, and beta-gal expression was evaluated with X-gal staining and measurement of enzymatic activity in tissue homogenates. RESULTS: Hydrodynamic injection via the tail vein achieved transgene expression only in non-cancerous tissue ( tumor: 0.16 +/- 0.04%, non- tumor: 5.07 +/- 1.66%). Hydrodynamic injection via the hepatic artery was tolerated, but failed to produce efficient transgene expression in tumor and non- tumor cells. On the other hand, concomitant use of temporary IVC/PV occlusion with hydrodynamic injection via the hepatic artery dramatically increased transgene expression in cancer cells, but tumor-selective gene transfer was not achieved with this procedure ( tumor: 7.38 +/- 3.66%, non- tumor: 7.77 +/- 1.06%). CONCLUSIONS: High-volume hydrodynamic injection of a pDNA solution via the hepatic artery with IVC/PV occlusion achieved a high level of gene expression in a HCC rat model. This gene transfer technique may have potential in clinical gene therapy for HCC.
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Authors | Masaharu Tada, Etsuro Hatano, Kojiro Taura, Takashi Nitta, Naoki Koizumi, Iwao Ikai, Yasuyuki Shimahara |
Journal | The journal of gene medicine
(J Gene Med)
Vol. 8
Issue 8
Pg. 1018-26
(Aug 2006)
ISSN: 1099-498X [Print] England |
PMID | 16779866
(Publication Type: Comparative Study, Journal Article)
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Copyright | 2006 John Wiley & Sons, Ltd. |
Chemical References |
- Alkylating Agents
- Carcinogens
- Diethylnitrosamine
- DNA
- beta-Galactosidase
- Indocyanine Green
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Topics |
- Alkylating Agents
- Animals
- Carcinogens
- Carcinoma, Hepatocellular
(metabolism, pathology, therapy)
- Cytomegalovirus
(genetics)
- DNA
(administration & dosage, genetics)
- Diethylnitrosamine
- Disease Models, Animal
- Gene Expression
- Gene Transfer Techniques
- Genetic Therapy
(methods)
- Genetic Vectors
(chemistry, genetics)
- Hepatic Artery
(metabolism)
- Indocyanine Green
(metabolism)
- Injections, Intravenous
- Liver Neoplasms
(metabolism, pathology, therapy)
- Male
- Plasmids
(administration & dosage, genetics)
- Rats
- Rats, Sprague-Dawley
- Transgenes
- beta-Galactosidase
(genetics)
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