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Adenovirus vector-mediated gene transfer using degradable starch microspheres for hepatocellular carcinoma in rats
Authors:Shiba Hiroaki  Okamoto Tomoyoshi  Futagawa Yasuro  Misawa Takeyuki  Yanaga Katsuhiko  Ohashi Toya  Eto Yoshikatsu
Affiliation:Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. hs0817@ss.iij4u.or.jp
Abstract:
BACKGROUND: When gene therapy is performed for malignant tumors, gene transfer efficiency and selectivity are extremely important. The delivery of anticancer agents and embolic agents through tumor feeding artery is known as transarterial embolization. We speculated that genes might be efficiently and selectively transferred to hepatocellular carcinomas (HCCs) by degradable starch microspheres (DSM) as the embolic agent, which could be trapped within the tumor and release a gene vector. Therefore, we studied the use of DSM for adenovirus vector-mediated gene transfer to HCC in vivo. MATERIAL AND METHODS: HCC was induced in rats with diethylnitrosamine and phenobarbital, after which either AxCALacZ and DSM or AxCALacZ alone was injected through the hepatic artery. RESULTS: Histological examination revealed that beta-galactosidase expression was greater (P < 0.001), and more selective (P < 0.001) in tumors after injection of AxCALacZ and DSM, than after injection of the vector alone. CONCLUSION: Injection of DSM together with an adenovirus vector through the hepatic artery can result in efficient and cancer-selective transfer of genes to HCC.
Keywords:gene transfer   hepatocellular carcinoma   adenovirus vector   arterial injection   degradable starch microspheres   rat
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