Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes.
Transcatheter hepatic arterial chemoembolization using emulsions composed of anticancer agents and gelatin sponges (GS) has been an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed catheter-mediated left hepatic arterial embolization (CHAE) to increase transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion was prepared by mixing pieces of GSP and adenoviral vectors expressing recombinant beta-galactosidase (Ad.LacZ) or human hepatocyte growth factor (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ activity on day 7. The expression pattern of LacZ staining was either scarce or patchy around the central hilum of the hepatic artery, or was homogeneously distributed in whole lobes, depending on whether large or small pieces of GSP were used. Hematological and serum biochemical changes during CHAE exhibited only a few effects. The chronological measurement of serum HGF concentration showed that the duration of transgene expression was greater after CHAE with Ad.hHGF. A similar pattern of transgene expression was observed in a rat model after hepatic arterial embolization with differential doses of Ad.hHGF soaked in GSP. These results suggest that hepatic arterial embolization by transcatheter mediated infusion with a mixture of adenovirus-GSP could be used for human HCC.
Park
Byeong-Ho
BH
Department of Radiology, Medical College of Dong-A University, Busan 602-714, South Korea.
Lee
Jin-Hwa
JH
Jeong
Jin-Sook
JS
Rha
Seo-Hee
SH
Kim
Seung-Eun
SE
Kim
Jae-Seok
JS
Kim
Jeong-Man
JM
Hwang
Tae-Ho
TH
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004285:Dogs; D005781:Gelatin Sponge, Absorbable; D005822:Genetic Vectors / Q000008:administration & dosage*; D006499:Hepatic Artery; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D019076:Transgenes / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D017228:Hepatocyte Growth Factor; D001616:beta-Galactosidase; D000093542:Gemcitabine