Experimental targeted radioiodide therapy following transfection of the sodium iodide symporter gene: effect on clonogenicity in both two-and three-dimensional models
Autor: | S. H. Cunningham, Sean Carlin, Anthony G. McCluskey, Robert J. Mairs, Marie Boyd |
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Rok vydání: | 2001 |
Předmět: |
Cancer Research
Thyroid Gland Gene Expression Sodium Iodide Adenocarcinoma In Vitro Techniques Transfection Iodine Radioisotopes chemistry.chemical_compound Neuroblastoma Glioma Neoplasms medicine Bystander effect Tumor Cells Cultured Cytotoxic T cell Humans Molecular Biology health care economics and organizations Tumor Stem Cell Assay Ovarian Neoplasms Symporters Membrane Proteins medicine.disease Disease Models Animal chemistry Sodium iodide Symporter Cancer research Molecular Medicine Female Carrier Proteins |
Zdroj: | Cancer gene therapy. 7(12) |
ISSN: | 0929-1903 |
Popis: | To evaluate the potential of the expression of the sodium/iodide symporter (NIS) as a means of targeting radioiodine to tumor cells, we have employed plasmid-mediated transfection of the NIS gene into a range of mammalian cell hosts. We observed perchlorate-inhibitable iodide uptake up to 41-fold over control in all NIS-transfected cells. We assessed the effect of NIS expression followed by exposure to 131I- on the clonogenic survival of UVW glioma cells. After exposure of two-dimensional monolayer cultures of UVW-NIS cells to 131I- at a radioactive concentration of 4 MBq/mL, clonogenic survival was reduced to 21%. Similar treatment of UVW-NIS cells in three-dimensional spheroid cultures resulted in a reduction of clonogenic survival to 2.5%. This increase in sensitivity to 131I- exposure is likely to be due to a radiological bystander effect. These results are very encouraging for the development of a novel cytotoxic gene-therapy strategy in which a radiological bystander effect plays a significant role in tumor cell sterilization. |
Databáze: | OpenAIRE |
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