caa a22 4500 606234055 CHVBK 20210128101235.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2254-5 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2254-5 Glial fibrillary acidic protein promoters direct adenovirus early 1A gene and human telomerase reverse transcriptase promoters direct sodium iodide symporter expression for malignant glioma radioiodine therapy [Elektronische Daten] [Wei Li, Jian Tan, Peng Wang, Ning Li, Chengxia Li] Malignant glioma can be treated with radioiodine following transfection with human sodium iodide symporter (hNIS) gene. Ad-Tp-E1A-Gp-NIS is engineered with human telomerase reverse transcriptase (hTERT) and glial fibrillary acidic protein (GFAP) promoters to express early region 1A (E1A) and hNIS genes, which may be useful in targeted gene therapy. The Ad-Tp-E1A-Gp-NIS was constructed and purified using the E1A and hNIS genes regulated by the hTERT and GFAP promoters, respectively. Glioma cells were infected by Ad-Tp-E1A-Gp-NIS. Selective replication ability of Ad-Tp-E1A-Gp-NIS was then evaluated by plaque forming assay, transgene expression by Western blot, 125I-iodide uptake and efflux, clonogenicity following 131I-iodide treatment in the tumor cells, and radioiodine therapy using nude mouse model. The Ad-Tp-E1A-Gp-NIS could selectively replicate; the hNIS gene was successfully expressed under the GFAP promoter. Western blot analyses using E1A- and hNIS-specific antibodies revealed two bands of approximately 40 and 70kDa. In addition, the cells showed about 93.4 and 107.1 times higher 125I uptake in U251 and U87 cells than in the control cells, respectively. Clonogenic assay indicated that >90% of cells transfected with Ad-Tp-E1A-Gp-NIS were killed. The Ad-Tp-E1A-Gp-NIS-transfected and 2mCi 131I-injected U87 xenograft nude mice survived the longest among the three groups. Ad-Tp-E1A-Gp-NIS has a good ability of selective replication and strong antitumor selectivity. An effective therapy of 131I was achieved activity in malignant glioma cells after induction of tumor-specific iodide uptake activity by GFAP promoter-directed hNIS gene expression in vitro and in vivo. Springer Science+Business Media New York, 2014 Human sodium iodide symporter gene nationallicence Human telomerase reverse transcriptase promoter nationallicence Glial fibrillary acidic protein promoter nationallicence Radioiodine therapy nationallicence Li Wei Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut Tan Jian Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut Wang Peng Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut Li Ning Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut Li Chengxia Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 279-289 0300-8177 399:1-2<279 2015 399 11010 https://doi.org/10.1007/s11010-014-2254-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2254-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Wei Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut NATIONALLICENCE 700 1- Tan Jian Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut NATIONALLICENCE 700 1- Wang Peng Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut NATIONALLICENCE 700 1- Li Ning Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut NATIONALLICENCE 700 1- Li Chengxia Department of Nuclear Medicine, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, 300052, Tianjin, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 399/1-2(2015-01-01), 279-289 0300-8177 399:1-2<279 2015 399 11010