scholarly journals Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach

2011 ◽  
Vol 96 (9) ◽  
pp. E1435-E1443 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Antonio De la Vieja ◽  
Irene Rodríguez ◽  
Soledad Miranda ◽  
Pilar Martín-Duque ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Cell Lines ◽  
Sodium Iodide ◽  
Human Cancer ◽  
131I Therapy ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Tumor Xenografts ◽  
Human Cancer Cell Lines

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.

scholarly journals Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

2005 ◽  
Vol 184 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Andrea C F Ferreira ◽  
Lívia P Lima ◽  
Renata L Araújo ◽  
Glaucia Müller ◽  
Renata P Rocha ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Iodine Content ◽  
Concomitant Administration ◽  
High Serum ◽  
Sodium Iodide Symporter ◽  
Physiological Control ◽  
Iodide Uptake ◽  
Thyroid Hormone Biosynthesis ◽  
Serum Tsh

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium–iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

Single-Agent Inhibition of Chk1 Is Antiproliferative in Human Cancer Cell Lines In Vitro and Inhibits Tumor Xenograft Growth In Vivo

2011 ◽  
Vol 19 (7) ◽  
pp. 349-363 ◽  
Author(s):  
Kurtis D. Davies ◽  
Michael J. Humphries ◽  
Francis X. Sullivan ◽  
Ira von Carlowitz ◽  
Yvan Le Huerou ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Single Agent ◽  
Tumor Xenograft ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Xenograft Growth ◽  
Tumor Xenograft Growth

Reestablishment of In Vitro and In Vivo Iodide Uptake by Transfection of the Human Sodium Iodide Symporter (hNIS) in a hNIS Defective Human Thyroid Carcinoma Cell Line

Thyroid ◽  
2000 ◽  
Vol 10 (11) ◽  
pp. 939-943 ◽  
Author(s):  
Jan W.A. Smit ◽  
Janny P. Schröder-van der Elst ◽  
Marcel Karperien ◽  
Ivo Que ◽  
Gabri van der Pluijm ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Line ◽  
Sodium Iodide ◽  
Carcinoma Cell ◽  
Human Thyroid ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Carcinoma Cell

scholarly journals A newfangled coordinated ruthenium phloretin complex reprogramming breast cancer microenvironment interceded by modulation of PI3K/Akt/mTOR/VEGF pathway and modifying the antioxidant status correlated with intensified apoptotic events.

2020 ◽  
Author(s):  
Chenyang He ◽  
Guo Yu ◽  
Anil Kumar Mondru ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Human Cancer ◽  
In Vivo Model ◽  
Human Cancer Cell Lines ◽  
Vegf Pathway ◽  
Breast Carcinoma Cell Lines ◽  
Mcf 7

Abstract Background: Our recent investigation directed to synthesize and characterize a novel ruthenium– phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, and to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo approach.Methods: Ruthenium–phloretin complex was synthesized and characterized using various spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human cancer cell lines and finally in an in vivo model of DMBA induced mammary carcinogenesis in ratsResults: Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Additionally, ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the intrinsic apoptotic trail facilitated by the Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways.Conclusions: Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the antiangiogenic pathway, hence fulfilling the role of a prospective candidate in cancer chemotherapeutics in the in the near future.

scholarly journals A Newfangled Coordinated Ruthenium Phloretin Complex Reprogramming Breast Cancer Microenvironment Interceded by Modulation of PI3K/Akt/Mtor/VEGF Pathway and Modifying The Antioxidant Status Correlated With Intensified Apoptotic Events.

2020 ◽  
Author(s):  
Chenyang He ◽  
Junli Wang ◽  
Tania Chakraborty ◽  
Souvik Roy
Keyword(s):  
Breast Carcinoma ◽  
Cell Lines ◽  
Human Cancer ◽  
In Vivo Model ◽  
Human Cancer Cell Lines ◽  
Vegf Pathway ◽  
Breast Carcinoma Cell Lines ◽  
Mcf 7

Abstract Background: Our recent investigation directed to synthesize and characterize a novel ruthenium– phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, and to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo approach.Methods: Ruthenium–phloretin complex was synthesized and characterized using various spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human cancer cell lines and finally in an in vivo model of DMBA induced mammary carcinogenesis in ratsResults: Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Additionally, ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the intrinsic apoptotic trail facilitated by the Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways.Conclusions: Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the antiangiogenic pathway, hence fulfilling the role of a prospective candidate in cancer chemotherapeutics in the in the near future.

scholarly journals The Design, Synthesis, and Evaluation of Hypoxia-Activated Prodrugs of the KDAC Inhibitor Panobinostat

2020 ◽  
Author(s):  
Ewen Calder ◽  
Anna Skwarska ◽  
Deborah Sneddon ◽  
Lisa Folkes ◽  
Ishna N. Mistry ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Parent Drug ◽  
Human Cancer Cell ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Design And Synthesis ◽  
Initial Validation

The design and synthesis of four hypoxia-activated prodrugs of the KDAC inhibitor panobinostat is described. Initial validation of these compounds using isolated enzymes, and in two human cancer cell lines, reveals that the nitroimidazole-based prodrug (NI-Pano, CH-03) undergoes efficient bioreduction and fragmentation to release the parent drug, panobinostat. NI-Pano was identified as the optimum compound for use in further studies in cells, spheroid tumor models, and <i>in vivo</i>.

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