scholarly journals 131I therapy mediated by sodium/iodide symporter combined with kringle 5 has a synergistic therapeutic effect on glioma

2015 ◽  
Vol 35 (2) ◽  
pp. 691-698 ◽  
Author(s):  
SHUO SHI ◽  
MIN ZHANG ◽  
RUI GUO ◽  
MIAO ZHANG ◽  
JIAJIA HU ◽  
...  
2011 ◽  
Vol 96 (9) ◽  
pp. E1435-E1443 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Antonio De la Vieja ◽  
Irene Rodríguez ◽  
Soledad Miranda ◽  
Pilar Martín-Duque ◽  
...  

Abstract Context: Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging. Objective: The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines. Design and Methods: Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide. Results: Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter. Conclusions: These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.


2007 ◽  
Vol 92 (11) ◽  
pp. 4451-4458 ◽  
Author(s):  
Michael J. Willhauck ◽  
Bibi-Rana Sharif Samani ◽  
Franz-Josef Gildehaus ◽  
Ingo Wolf ◽  
Reingard Senekowitsch-Schmidtke ◽  
...  

Abstract Context: We reported recently the induction of iodide accumulation in prostate cancer cells (LNCaP) by prostate-specific antigen promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131iodine (131I). These data demonstrated the potential of the NIS gene as a novel therapeutic gene, although in some extrathyroidal tumors, therapeutic efficacy may be limited by rapid iodide efflux due to a lack of iodide organification. Objective: In the current study, we therefore studied the potential of 188rhenium (188Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy β-particles than 131I. Results: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of 188Re as compared with 16% of 125I, which was sufficient for a therapeutic effect in an in vitro clonogenic assay. γ-Camera imaging of NP-1 cell xenografts in nude mice revealed accumulation of 8–16% injected dose (ID)/g 188Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for 188Re as compared with 131I. After application of 55.5 MBq 131I or 188Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after 131I treatment to 85% after application of 188Re. Conclusion: Although in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after prostate-specific antigen promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for 188Re in larger tumors.


2010 ◽  
Vol 18 (9) ◽  
pp. 1599-1605 ◽  
Author(s):  
Mohan Hingorani ◽  
Christine L White ◽  
Shane Zaidi ◽  
Hardev S Pandha ◽  
Alan A Melcher ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 54795-54810 ◽  
Author(s):  
Andrea M. Müller ◽  
Kathrin A. Schmohl ◽  
Kerstin Knoop ◽  
Christina Schug ◽  
Sarah Urnauer ◽  
...  

2019 ◽  
Vol 25 (19) ◽  
pp. 5997-6008 ◽  
Author(s):  
Christina Schug ◽  
Carolin Kitzberger ◽  
Wolfgang Sievert ◽  
Rebekka Spellerberg ◽  
Mariella Tutter ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e92326 ◽  
Author(s):  
Min Zhang ◽  
Rui Guo ◽  
Shuo Shi ◽  
Yin Miao ◽  
Yifan Zhang ◽  
...  

2016 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Bhavika Modasia ◽  
Waraporn Imruetaicharoenchoke ◽  
Rebecca Thompson ◽  
...  

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