title: Gene therapy for hepatocellular carcinoma using sonoporation enhanced by contrast agents.
abstract: We examined whether sonoporation enhanced by a contrast agent (BR14) was effective in gene therapy for hepatocelluar carcinoma (HCC). Human hepatic cancer cells (SK-Hep1) and plasmid cDNAs expressing green fluorescent protein (GFP), interferonbeta (IFNbeta), and LacZ were used. In vitro, SK-Hep1 cell suspensions with DNA and BR14 were sonoporated. Expressions of every plasmid cDNA and the antitumor effect of IFNbeta were analyzed. In vivo, GFP and IFNbeta genes with BR14 were directly injected into subcutaneous tumors using SK-Hep1 in nude mice, and transcutaneous sonoporation of the tumors was performed. GFP gene transfections and tumor diameters after IFNbeta gene transfection were examined. In vitro, no SK-Hep1 cells were transfected without sonication, whereas transfections were successful after sonication with BR14. Antitumor effect of IFNbeta gene transfection by ultrasound (US) and with BR14 was revealed. In vivo, the SK-Hep1 cells expressed GFP, and the IFNbeta gene transfection by US with BR14 reduced tumor size significantly. In conclusion, gene therapy with sonoporation enhanced by a contrast agent may become a new treatment option for HCC.
authors.affiliation: Department of Surgery II, Nagoya University School of Medicine, Nagoya 466-8550, Japan. sakakima@med.nagoya-u.ac.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sakakima
authors.forename: Shuji
authors.initials: S
authors.lastname: Hayashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yagi
authors.forename: Akemi
authors.initials: A
authors.lastname: Hayakawa
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D018076:DNA, Complementary / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005466:Fluorocarbons; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D016899:Interferon-beta / Q000032:analysis; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010743:Phospholipids; D010957:Plasmids; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured; D014465:Ultrasonics
chemical_list: C471302:BR14 contrast agent; D018076:DNA, Complementary; D005466:Fluorocarbons; D010743:Phospholipids; D049452:Green Fluorescent Proteins; D016899:Interferon-beta