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Radioiodine gene therapy of hepatocellular carcinoma targeted human alpha fetoprotein
Cited 7 time in
Web of Science
Cited 7 time in Scopus
- Authors
- Issue Date
- 2008-11-07
- Publisher
- Mary Ann Liebert
- Citation
- Cancer Biother Radiopharm. 2008;23(5):551-560
- Keywords
- Animals ; Carcinoma, Hepatocellular/*radiotherapy/*therapy ; Cell Line, Tumor ; Enhancer Elements, Genetic ; Gene Therapy/*methods ; Humans ; Iodine Radioisotopes/*pharmacology ; Liver Neoplasms/*radiotherapy/*therapy ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Promoter Regions, Genetic ; Rats ; Technetium/metabolism ; alpha-Fetoproteins/*biosynthesis
- Abstract
- INTRODUCTION: We conducted a molecular imaging and gene therapy method in alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) by tumor-specific expression of the human sodium/iodide symporter (hNIS) using an AFP promoter. METHODS: The tumor-specific expression of hNIS gene by the AFP enhancer/promoter was constructed as pcDNA3-AFP/hNIS. The pcDNA3-AFP/hNIS was stably transfected to human HCC (Huh-7/AN) and rat glioma cells (C6/AN). Functional hNIS expression was confirmed by radioiodine uptake. The mRNA and protein-expression level of hNIS were measured. Biodistribution of 131I was evaluated, and scintigraphic images of 99mTc were obtained in xenografted mice. A clonogenic assay was performed by 131I. And, the in vivo therapeutic effect of 131I was evaluated in xenografted mice. RESULTS: In Huh-7/AN cells, iodine was highly accumulated and completely blocked by perchlorate. The protein and mRNA expression levels were correlated with iodine uptake. Radioiodine uptake in Huh-7/AN tumors was higher than those of control tumors and clearly visualized. The survival rate was significantly decreased in Huh-7/AN cells by 131I. Moreover, a growth of Huh-7/AN tumors was inhibited by 131I in mice. CONCLUSIONS: AFP-producing hepatoma can be targeted and treated with radionuclides and hNIS, using AFP enhancer/promoter. This targeted hNIS gene therapy and molecular imaging have the potential to be used in the management of AFP-producing HCC.
- ISSN
- 1557-8852 (Electronic)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18986218
https://hdl.handle.net/10371/67758
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