Adenovirus vector-mediated gene transfer using degradable starch microspheres for hepatocellular carcinoma in rats.
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.


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.


CONCLUSIONS
Injection of DSM together with an adenovirus vector through the hepatic artery can result in efficient and cancer-selective transfer of genes to HCC.
Shiba
Hiroaki
H
Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. hs0817@ss.iij4u.or.jp
Okamoto
Tomoyoshi
T
Futagawa
Yasuro
Y
Misawa
Takeyuki
T
Yanaga
Katsuhiko
K
Ohashi
Toya
T
Eto
Yoshikatsu
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004621:Embolization, Therapeutic / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008863:Microspheres; D051381:Rats; D017208:Rats, Wistar; D013213:Starch
D013213:Starch