Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters.
Gene therapy for cancer requires efficient, selective gene transfer to cancer cells. In gene therapy for hepatocellular carcinoma (HCC), gene transfer is efficient for small tumors, but not for large tumors. The delivery of anticancer agents and of iodized oil esters as embolic agents through tumor-feeding arteries is known as transarterial embolization. We speculate that genes may be efficiently and selectively transferred for HCC using iodized oil esters because these esters may remain together with a genetic vector within HCC selectively. Hence, we have studied the effect of iodized oil esters on adenovirus vector-mediated gene transfer for HCC in vivo. A rat model of HCC induced with diethylnitrosamine and phenobarbital was injected with either AxCALacZ, which expresses the beta-galactosidase of Escherichia coli, or AxCALacZ and iodized oil esters into the hepatic artery. Histological comparisons revealed that the beta-galactosidase expression in the rats with HCC injected with AxCALacZ and iodized oil esters was greater (P<.0001) in small tumors (P=.0046) and large tumors (P=.0023), and more selective (P=.0229) than in only AxCALacZ-injected rats. These results suggest that iodized oil esters are injected into hepatic artery together with adenovirus vector, and that genes may be efficiently and cancer-selectively transferred to HCC.
Shiba
H
H
Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. hs0817@ss.iij4u.or.jp
Okamoto
T
T
Futagawa
Y
Y
Ohashi
T
T
Eto
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000477:Alkylating Agents; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000628:therapy*; D004052:Diethylnitrosamine; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007269:Injections, Intra-Arterial; D007459:Iodized Oil / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000628:therapy*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D001616:beta-Galactosidase / Q000378:metabolism
D000477:Alkylating Agents; D000927:Anticonvulsants; D004052:Diethylnitrosamine; D007459:Iodized Oil; D001616:beta-Galactosidase; D010634:Phenobarbital