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John C Morris - One of the best experts on this subject based on the ideXlab platform.

Christine Spitzweg - One of the best experts on this subject based on the ideXlab platform.

  • Sodium Iodide Symporter (NIS)-mediated radiovirotherapy of hepatocellular cancer using a conditionally replicating adenovirus.
    Gene therapy, 2012
    Co-Authors: G K Grünwald, K Klutz, Michael J. Willhauck, Nathalie Schwenk, Reingard Senekowitsch-schmidtke, M Schwaiger, C. Zach, Burkhard Göke, Per Sonne Holm, Christine Spitzweg
    Abstract:

    Sodium Iodide Symporter (NIS)-mediated radiovirotherapy of hepatocellular cancer using a conditionally replicating adenovirus

  • functional Sodium Iodide Symporter expression in breast cancer xenografts in vivo after systemic treatment with retinoic acid and dexamethasone
    Breast Cancer Research and Treatment, 2008
    Co-Authors: Michael J. Willhauck, John C Morris, Burkhard Göke, Bibi Sharifsamani, Reingard Senekowitschschmidtke, Nathalie Wunderlich, Christine Spitzweg
    Abstract:

    Context The Sodium Iodide Symporter (NIS) mediates Iodide uptake in the thyroid gland as well as in lactating breast, and is also expressed in the majority of breast cancers. Recently, we have reported stimulation of all-trans retinoic acid (atRA)-induced NIS expression in the human breast cancer cell line MCF-7 by dexamethasone (Dex), resulting in an enhanced therapeutic effect of 131I in vitro.

  • The practical relevance of the Sodium Iodide Symporter
    Zeitschrift fur arztliche Fortbildung und Qualitatssicherung, 2004
    Co-Authors: Christine Spitzweg
    Abstract:

    The Sodium Iodide Symporter (NIS) is an intrinsic plasma membrane protein mediating the active transport of Iodide in the thyroid gland and a number of extrathyroidal tissues, in particular in the lactating mammary gland. Because of its crucial role for the ability of thyroid follicular cells to trap Iodide, cloning of NIS opened up an exciting and extensive new field of thyroid-related research. Cloning and molecular characterisation of NIS allows investigation of its expression and regulation in thyroidal and non-thyroidal tissues and its potential pathophysiological and therapeutic implications in benign and malignant thyroid disease. In addition to its key function in thyroid physiology, NIS-mediated Iodide accumulation allows both diagnostic thyroid scintigraphy and the effective therapeutic application of radioiodine in benign and malignant thyroid disease. Characterisation and application of NIS as a novel therapeutic gene for cytoreductive gene therapy of extra-thyroidal tumours and the presence of high endogenous NIS expression in the majority of breast cancers further suggest a promising role of NIS in the diagnosis and treatment of cancer outside the thyroid gland.

  • The Sodium Iodide Symporter: its pathophysiological and therapeutic implications
    Clinical endocrinology, 2002
    Co-Authors: Christine Spitzweg, John C Morris
    Abstract:

    Summary The Sodium Iodide Symporter (NIS) is an intrinsic plasma membrane protein that mediates the active transport of Iodide in the thyroid gland and a number of extrathyroidal tissues, in particular lactating mammary gland. Because of its crucial role in the ability of thyroid follicular cells to trap Iodide, cloning of NIS opened an exciting and extensive new field of thyroid-related research. Cloning and molecular characterization of NIS allowed investigation of its expression and regulation in thyroidal and nonthyroidal tissues, and its potential pathophysiological and therapeutic implications in benign and malignant thyroid disease. In addition to its key function in thyroid physiology, NIS-mediated Iodide accumulation allows diagnostic thyroid scintigraphy as well as effective therapeutic application of radioiodine in benign and malignant thyroid disease. Characterization and application of NIS as a novel therapeutic gene and the presence of high native NIS expression in the majority of breast cancers further suggest a promising role of NIS in diagnosis and therapy of cancer outside the thyroid gland.

  • Approaches to gene therapy with Sodium/Iodide Symporter
    Experimental and clinical endocrinology & diabetes : official journal German Society of Endocrinology [and] German Diabetes Association, 2001
    Co-Authors: Christine Spitzweg, John C Morris
    Abstract:

    Since cloning and characterization of the Sodium Iodide Symporter (NIS) gene, several investigators explored the possibility of a novel cytoreductive gene therapy strategy based on NIS gene transfer into non-thyroidal tumor cells followed by radioiodine therapy. NIS gene transfer has been shown to be capable of inducing radioiodine accumulation in vitro and in vivo in several non-thyroidal cancer cell lines. Following PSA promoter-mediated NIS gene delivery we were able to demonstrate prostate-specific Iodide accumulation in prostate cancer cells that was high enough to elicit a therapeutic response of 131-I in vitro and in vivo. This study clearly demonstrates the potential of NIS as a novel therapeutic gene for non-thyroidal cancers, in particular prostate cancer.

June-key Chung - One of the best experts on this subject based on the ideXlab platform.

  • Sodium Iodide Symporter (NIS) in the Management of Patients with Thyroid Carcinoma
    Nuclear Medicine and Molecular Imaging, 2018
    Co-Authors: June-key Chung, Haewon Youn, Gi Jeong Cheon
    Abstract:

    Although radioiodine has been applied in thyroid diseases including carcinoma for over 70 years, it was only in 1996 that the basic molecular mechanism of iodine uptake was identified. Iodide is actively transported into the thyroid via a membrane glycoprotein known as Sodium Iodide Symporter (NIS). NIS mediates radioiodine uptake into thyroid normal and cancer cells. The knowledge on NIS expression has provided scientific background to the empirical management of thyroid carcinoma. Based on recent studies of the NIS gene, this paper provides current clinical applications and future studies.

  • In Vitro Radionuclide Therapy and In Vivo Scintigraphic Imaging of Alpha-Fetoprotein-Producing Hepatocellular Carcinoma by Targeted Sodium Iodide Symporter Gene Expression
    Nuclear medicine and molecular imaging, 2012
    Co-Authors: Kwang Il Kim, June-key Chung, Gi Jeong Cheon, Yong Jin Lee, Tae Sup Lee, In Ho Song, Sang Moo Lim, Joo Hyun Kang
    Abstract:

    Purpose This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human Sodium/Iodide Symporter (hNIS) gene driven by an AFP enhancer/promoter.

  • The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells.
    Nuclear medicine and molecular imaging, 2012
    Co-Authors: Hyewon Youn, Myung Geun Song, Dong Soo Lee, June-key Chung
    Abstract:

    Purpose The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as Sodium Iodide Symporter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes.

  • Sodium Iodide Symporter in Thyroid Carcinoma
    Therapeutic Nuclear Medicine, 2012
    Co-Authors: June-key Chung
    Abstract:

    Thyroid Iodide uptake is essential for the clinical application of radioiodine in patients with well-differentiated thyroid carcinoma. Iodide uptake occurs across the plasma membranes of thyroid follicular cells and cancer cells via an active transporter process mediated by Sodium Iodide Symporter (NIS). The cloning of the NIS gene enabled the molecular mechanisms underlying Iodide transport to be better characterized, and thus, opened the way to the expansion of its role in thyroid carcinoma. Thyroid-stimulating hormone (TSH) is the principal regulator of Iodide uptake, although many other factors, including insulin, insulin-like growth factor I, epidermal growth factor, and Iodide itself, also influence Iodide uptake by the thyroid gland. Human NIS expression may be increased, decreased, or absent in well-differentiated thyroid cancer. However, the reason for reduced Iodide uptake in well-differentiated thyroid carcinoma is not solely due to lower NIS expression, and probably depends on a complex combination of regulatory changes that ultimately affect NIS expression, targeting, or activation. Nevertheless, reduced functional levels of NIS on cell membranes do account for the reduced Iodide uptake observed in thyroid carcinoma. Furthermore, thyroid cancer tissues expressing NIS take up more I-131 than those not expressing NIS, and these tumors subsequently show a higher rate of response to radioiodine therapy. Accordingly, NIS appears to have the potential to expand the role of nuclear medicine in the management of thyroid carcinoma.

  • Sodium Iodide Symporter and the Radioiodine Treatment of Thyroid Carcinoma
    Nuclear Medicine and Molecular Imaging, 2010
    Co-Authors: June-key Chung, Joo Hyun Kang, Hyewon Youn, Ho Young Lee, Keon Wook Kang
    Abstract:

    Since the specific accumulation of Iodide in thyroid was found in 1915, radioiodine has been widely applied to diagnose and treat thyroid cancer. Iodide uptake occurs across the membrane of the thyroid follicular cells and cancer cells through an active transporter process mediated by the Sodium Iodide Symporter (NIS). The NIS coding genes were cloned and identified from rat and human in 1996. Evaluation of the NIS gene and protein expression is critical in the management of thyroid cancer, and several approaches have been tried to increase NIS levels. Identification of the NIS gene has provided a means of expanding its role in the radionuclide gene therapy of nonthyroidal cancers as well as thyroid cancer. In this article, we explain the relationship between NIS expression and the treatment of thyroid carcinoma with I-131, and we include a review of the results of our experimental and clinical trials.

Sissy M. Jhiang - One of the best experts on this subject based on the ideXlab platform.

  • Modulation of Sodium Iodide Symporter in Thyroid Cancer
    Hormones and Cancer, 2014
    Co-Authors: Aparna Lakshmanan, Daniel H. Shen, Daniel Scarberry, Sissy M. Jhiang
    Abstract:

    Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium Iodide Symporter (NIS) mediates Iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future.

  • modulation of Sodium Iodide Symporter expression in the salivary gland
    Thyroid, 2013
    Co-Authors: Krista M. D. La Perle, Dong Chul Kim, Nathan Hall, Adam Bobbey, Daniel H. Shen, Rebecca Nagy, Paul E. Wakely, Amy Lehman, David Jarjoura, Sissy M. Jhiang
    Abstract:

    Background: Physiologic Iodide-uptake, mediated by the Sodium/Iodide Symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine–induced damage following 131I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland. Methods: NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative 123I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after 123I administration in 50 thyroid cancer patients. Results: N...

  • Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland
    Thyroid : official journal of the American Thyroid Association, 2013
    Co-Authors: Krista M. D. La Perle, Dong Chul Kim, Nathan Hall, Adam Bobbey, Daniel H. Shen, Rebecca Nagy, Paul E. Wakely, Amy Lehman, David Jarjoura, Sissy M. Jhiang
    Abstract:

    Background: Physiologic Iodide-uptake, mediated by the Sodium/Iodide Symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine–induced damage following 131I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland. Methods: NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative 123I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after 123I administration in 50 thyroid cancer patients. Results: N...

  • PI3K activation is associated with intracellular Sodium/Iodide Symporter protein expression in breast cancer
    BMC cancer, 2007
    Co-Authors: Katherine A.b. Knostman, Charles C. Capen, James A. Mccubrey, Carl Morrison, Zhaoxia Zhang, Sissy M. Jhiang
    Abstract:

    Background The Sodium/Iodide Symporter (NIS) is a membrane glycoprotein mediating active Iodide uptake in the thyroid gland and is the molecular basis for radioIodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident Iodide uptake ability. We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer.

  • Effect of exogenous human Sodium Iodide Symporter expression on growth of MATLyLu cells.
    Thyroid : official journal of the American Thyroid Association, 2003
    Co-Authors: Krista M. D. La Perle, Eric A.g. Blomme, Charles C. Capen, Sissy M. Jhiang
    Abstract:

    The Sodium Iodide Symporter (NIS) mediates Iodide uptake in thyroid cells and enables the effective radioIodide treatment of thyroid cancers. There is much interest in facilitating radioIodide ther...

Takahiko Kogai - One of the best experts on this subject based on the ideXlab platform.

  • Sodium Iodide Symporter in the fight against thyroid cancer
    Future oncology (London England), 2013
    Co-Authors: Takahiko Kogai
    Abstract:

    n radioIodide n signal transduction inhibitor n Sodium Iodide Symporter n thyroid cancer More than 60 years of experience of radioIodide therapy has indicated its usefulness for the treatment of differentiated thyroid cancer. This therapy utilizes the differentiated function of thyroid cells, namely Iodide uptake for thyroid hormone synthesis. The Sodium Iodide Symporter (NIS) efficiently mediates the Iodide uptake in thyroid cells. If functional NIS expression is preserved in metastatic tumors, b-emitting radioIodide-131 (I) is administered after total thyroidectomy, and tumors will concentrate I sufficiently for selective ablation. A total of 30–40% of metastatic diseases, however, do not respond to I therapy [1], mainly due to loss of functional NIS expression [2]. In addition, moderate side effects are still common (10–60%) in NIS-expressing nonthyroidal tissues [3], including sialadenitis and conjunctivitis. Since greater NIS expression in thyroid cancer is associated with more robust I uptake and a better prognosis, enhancement of the native NIS expression has been widely attempted in basic and preclinical research [4]. Attenuation of oncogenic signaling pathways has become a promising approach for expanding the indications and usage of radioIodide therapy to treat resistant tumors.

  • Ectopic expression of the thyroperoxidase gene augments radioIodide uptake and retention mediated by the Sodium Iodide Symporter in non-small cell lung cancer.
    Cancer Gene Therapy, 2001
    Co-Authors: Min Huang, Raj K. Batra, Takahiko Kogai, Ying Q. Lin, Alan Lichtenstein, Jerome M. Hershman, Sherven Sharma, Li X. Zhu, Gregory A. Brent, Steven M. Dubinett
    Abstract:

    Ectopic expression of the thyroperoxidase gene augments radioIodide uptake and retention mediated by the Sodium Iodide Symporter in non–small cell lung cancer

  • Differential Regulation of the Human Sodium/Iodide Symporter Gene Promoter in Papillary Thyroid Carcinoma Cell Lines and Normal Thyroid Cells
    Endocrinology, 2001
    Co-Authors: Takahiko Kogai, Jerome M. Hershman, Katsuaki Motomura, Toyoshi Endo, Toshimasa Onaya, Gregory A. Brent
    Abstract:

    The absence of TSH-stimulated radioIodide uptake in differentiated thyroid cancer is associated with a high recurrence rate and reduced survival. We studied regulation of the Sodium/Iodide Symporter gene in human papillary thyroid cancer cell lines (BHP) and primary human thyroid cells. BHP cells expressed very low levels of Sodium/Iodide Symporter mRNA and did not concentrate Iodide, but Iodide uptake was restored to levels seen in FRTL-5 rat thyroid cells by stable transfection of a Sodium/Iodide Symporter cDNA. Sodium/Iodide Symporter gene expression, therefore, was necessary and sufficient for Iodide uptake in BHP cells. We cloned the human Sodium/Iodide Symporter gene 5′-flanking region and analyzed progressive 5′-deletions in transient transfections. We identified a region, −596 to −268, essential to confer full promoter activity in primary normal human thyroid cells. Sodium/Iodide Symporter promoter activity in four BHP cell lines, however, was markedly reduced, consistent with down-regulation of t...