ABSTRACT
PURPOSE: Liver-directed gene therapy is being actively pursued and developed as a method of treating various liver diseases. A number of aspects, including gene intervention, an efficient gene delivery system, and stable transgene expression are key to the success of the chosen strategy, and to overcome problems in these areas, several tactics can be used. In this study, we assess the utility of transarterial embolization using gelfoam particles soaked in an adenovirus vector as a gene-delivery method. MATERIALS AND METHODS: Using the angiographic approach, three dogs each weighing 9.5-11 kg were superselectively catheterized at the left hepatic artery using a 3-F microcatheter and the coaxial method. Two of the dogs were embolized at the left hepatic artery using 3x2x2-mm and 2x1x1-mm gelfoam particles soaked in 2x1011 particles/kg of recombinant adv.CMV.LacZ (LacZ-adv). The left hepatic artery of the remaining animal, used as a control, was infused with the same dose of lacZ-adv in the same way as before but without embolization of the left hepatic artery. Three days after embolization or the infusion of LacZ-adv, the dogs were sacrificed prior to harvest of the entire liver for the evaluation of gene transduction. RESULTS: X-gal staining of the liver tissue obtained was positive for hepatocytes, but the pattern and degree of gene transduction differed according to gelfoam particle size. Where this was 3x2x2 mm, gene transduction along the liver hilum varied, but where 2x1x1-mm particles were used, transduction was more even. No pathologic hepatic tissue injury or inflammation was apparent, and control liver tissue was not stained by Xgal. Serum SGOT and SGPT levels were slightly higher one day after the procedure, but had normalized by day 3. CONCLUSION: Intrahepatic transarterial embolization using gelfoam particles soaked in LacZ-adv appears to be a good method for effective liver-targed gene therapy.
Subject(s)
Animals , Dogs , Adenoviridae , Alanine Transaminase , Aspartate Aminotransferases , Catheters , Gelatin Sponge, Absorbable , Gene Transfer Techniques , Genetic Therapy , Hepatic Artery , Hepatocytes , Inflammation , Liver , Liver Diseases , Particle Size , TransgenesABSTRACT
Objective To evaluate the clinical value of the preoperative intra-arterial embolization of the nasopharyngeal angiofibromas. Methods The treatment group of 7 male patients with the nasopharyngeal angiofibromas were undergone angiographic evaluation and embolization of tumor-feeding vessels before surgery. All patients were embolized with gelfoam particles and PVA. The control group of 7 patients received surgical treatment without preoperative embolization. We compared the volumes of intraoperative bleeding and the blood transfusions during oprations between the two groups. Results All patients achieved symptomatic remission,with no complications. Comparing with the control group,the amount of intraoperative bleeding and the blood transfusions during operations were much less in the treatment group submitted to endovascular embolirzation.Marked edema in the peripheral region of tumor of the treatment group made the tumor easy to be dissociated. Conclusion The intraoperative bleeding can be reduced significantly by preoperative embolization of supplying arteries to the nasopharyngeal angiofibromas,therefore it should be used routinely as an adjunct to surgery. (J Intervent Radiol,2006,15: 345-347)