A Novel Therapeutic Strategy for Medullary Thyroid Cancer Based on Radioiodine Therapy following Tissue-Specific Sodium Iodide Symporter Gene Expression

Cengic, Neziha; Baker, Claire; Schütz, Martin; Göke, Burkhard; Morris, John C.; Spitzweg, Christine

doi:10.1210/jc.2004-2140

Cited by 58 publications

(36 citation statements)

References 47 publications

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“…Differentiated thyroid carcinoma with hNIS expression responds to 131 I therapy; however, most ATCs respond poorly to this therapy because of their inability to accumulate iodine (26). Several investigators have suggested the use of radioiodine therapy after exogenous hNIS gene expression in anaplastic thyroid carcinoma or other nonthyroid cancers that lack hNIS expression (19)(20)(21)27,28). These results suggest that hNIS gene transfer may be used for cancer therapy by restoring or inducing radioiodine uptake in various cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Combined RNA Interference of Hexokinase II and ¹³¹I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

et al. 2011

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The purpose of this study was to investigate the enhanced therapeutic effect of the combined use of shRNA (small hairpin RNA) therapy for the hexokinase II (HKII) gene and 131 I human sodium iodide symporter (hNIS) as a gene therapy for in vitro and in vivo treatment of anaplastic thyroid carcinoma cells (ARO) in an animal model. Methods: A recombinant lentivirus containing a plasmid with the hNIS gene driven by phosphoglycerate kinase promoter and green fluorescent protein (GFP) linked with an internal ribosome entry site sequence was produced. ARO cells were transfected with the virus and sorted by fluorescent activated cell sorting using GFP (ARO-NG). The messenger RNA expression of hNIS and GFP were evaluated with reverse-transcriptase polymerase chain reaction, and the function of hNIS was verified by 125 I uptake. The lentiviral vector expressing shRNA against HKII (Lenti-HKII shRNA) was constructed and used to infect ARO-NG cells. The effect of Lenti-HKII shRNA was evaluated by reverse-transcriptase polymerase chain reaction, 18 F-FDG uptake, and HK activity. An in vitro clonogenic assay was performed after Lenti-HKII shRNA therapy, 131 I therapy, and a combined therapy. The therapies were also applied in vivo to an animal model with an ARO-NG xenograft, and the effects were assessed with caliper measurements and 18 F-FDG PET. Results: ARO-NG cells showed an 125 I uptake 76-fold higher than the parent ARO cells. Compared with the uninfected ARO-NG cells, ARO-NG cells infected with Lenti-HKII shRNA had lower HKII messenger RNA expression, lower 18 F-FDG uptake, and HK activity. The proliferation of ARO-NG cells was inhibited by 131 I and Lenti-HKII shRNA therapies and further inhibited by the combined 131 I and Lenti-HKII shRNA therapy. Both the Lenti-HKII shRNA therapy and the 131 I therapy inhibited in vivo tumor growth in the tumor xenograft model. The combined Lenti-HKII shRNA and 131 I therapy resulted in a further decrease of tumor growth. Conclusion: Our results suggest that the combined HKII shRNA and 131 I therapy has a stronger antitumor effect than either the 131 I therapy or the HKII shRNA alone. Therefore, this combined therapy could be used as a powerful strategy for treating anaplastic thyroid carcinoma.

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Section: Discussionmentioning

confidence: 99%

Combined RNA Interference of Hexokinase II and ¹³¹I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

et al. 2011

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“…Clonogenic survival was reduced in the NIS-expressing QGP and Bon1 cells by 99.8 and 98.8%, respectively, after incubation with 100 µCi/ml of 131 I [144]. Cengic et al (2005) assessed the feasibility of radioiodide therapy of medullary thyroid cancer (MTC) after NIS gene transfer using the tissue-specific calcitonin promoter to target hNIS gene expression to MTC cells. MTC cells were stably transfected with an expression vector, in which hNIS cDNA was coupled to the calcitonin promoter.…”

Section: Preclinical Studies Of Nis Gene Transfer By Replication-defementioning

confidence: 99%

“…The stably transfected HCT116 cells concentrated 125 I about 10-fold in vitro without evidence of iodide organification. Furthermore, 95% of stably transfected HCT116 cells were killed by exposure to 131 I, while only about 5% of NIS-negative control cells were killed [146]. reported on a study of in vivo NIS gene transfer followed by radioiodide imaging and treatment in a breast cancer model.…”

Section: Preclinical Studies Of Nis Gene Transfer By Replication-defementioning

confidence: 99%

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

Hingorani¹

2010

CCDT

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The sodium iodide symporter (NIS) is responsible for thyroidal, salivary, gastric, intestinal and mammary iodide uptake. It was first cloned from the rat in 1996 and shortly thereafter from human and mouse tissue. In the intervening years, we have learned a great deal about the biology of NIS. Detailed knowledge of its genomic structure, transcriptional and post-transcriptional regulation and pharmacological modulation has underpinned the selection of NIS as an exciting approach for targeted gene delivery. A number of in vitro and in vivo studies have demonstrated the potential of using NIS gene therapy as a means of delivering highly conformal radiation doses selectively to tumours. This strategy is particularly attractive because it can be used with both diagnostic ( 99m Tc, 125 I, 124 I) and therapeutic ( 131 I, 186 Re, 188 Re, 211 At) radioisotopes and it lends itself to incorporation with standard treatment modalities, such as radiotherapy or chemoradiotherapy. In this article, we review the biology of NIS and discuss its development for gene therapy.

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“…These findings indicate that NIS gene delivery can lead to sufficient NIS activity for radioiodide therapeutic use and also that iodide organification is not a fundamental step for radioiodine effectiveness to occur. hNIS gene transfer has also been tested using the calcitonin-promoter to target NIS gene expression to medullary thyroid cancer cells (97). After NIS-gene transfer, these cells were able express functional NIS and to significantly uptake iodide.…”

Section: Nis Gene Transfer For Cancer Managementmentioning

confidence: 99%

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Carvalho

Ferreira

2007

Arq Bras Endocrinol Metab

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The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124 I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors. A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o cotransportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124 I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.

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A Novel Therapeutic Strategy for Medullary Thyroid Cancer Based on Radioiodine Therapy following Tissue-Specific Sodium Iodide Symporter Gene Expression

Cited by 58 publications

References 47 publications

Combined RNA Interference of Hexokinase II and ¹³¹I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

Combined RNA Interference of Hexokinase II and ¹³¹I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

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A Novel Therapeutic Strategy for Medullary Thyroid Cancer Based on Radioiodine Therapy following Tissue-Specific Sodium Iodide Symporter Gene Expression

Cited by 58 publications

References 47 publications

Combined RNA Interference of Hexokinase II and 131I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

Combined RNA Interference of Hexokinase II and 131I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

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Product

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About

Combined RNA Interference of Hexokinase II and ¹³¹I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

Combined RNA Interference of Hexokinase II and ¹³¹I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma