Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV-p53 combined with CDDP to rat liver metastatic tumors.
Surgical resection is thought to be the best treatment for liver carcinoma, including hepatocellular carcinoma and metastatic liver carcinoma if there are a small number of tumors. Liver carcinoma is one of the main causes of death from cancer worldwide. The prognosis of liver carcinoma is still poor. Mutation of p53, which is well known as a tumor suppressor gene, is observed in many cases of advanced liver carcinoma. Cancer gene therapy using p53, which transduces the wild-type p53 gene in the tumor, is a promising new strategy for treating liver carcinoma. Selective and less invasive gene delivery to the liver tumor is necessary for clinical liver tumor gene therapy. The first purpose of the current study was to determine the best way to deliver the gene of interest to the liver tumor selectively. The second purpose was to study the tumor suppressive effect of intrahepatic arterial injection of an adenovirus vector with the p53 gene (AdCMV-p53), followed by administration of CDDP and noting its side effects. We injected AdCMV-LacZ via hepatic arteries of rats bearing RCN-9 colon cancer metastasis in the liver. Injection via the hepatic artery resulted in more successful gene transduction to the liver tumor in a tumor-selective manner than did injection via the portal vein. At 48 hrs after arterial injection of AdCMV-p53, CDDP (3 mg/kg) was administered in the peritoneal cavity of each rat. The use of CDDP with arterial injection of AdCMV-p53 resulted in more extensive apoptosis in the rat liver tumors without any deterioration in liver function. In conclusion, hepatic arterial injection of an adenovirus vector is better than portal vein injection for gene transduction efficiency, and causes no liver function disorder even when the injection is combined with CDDP.
Second Dept. of Surgery, Faculty of Medicine, Hiroshima University, Hiroshima, Japan. tatsuya@hiroshima-u.ac.jp
T
T
Okimoto
H
H
Yahata
H
H
Itou
K
K
Shinozaki
H
H
Tanji
T
T
Sakaguchi
T
T
Asahara
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology; D003587:Cytomegalovirus / Q000235:genetics; D018450:Disease Progression; D015316:Genetic Therapy / Q000379:methods*; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D008297:Male; D009362:Neoplasm Metastasis; D051381:Rats; D011916:Rats, Inbred F344; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53