scholarly journals Molecular mechanisms of radioactive iodine refractoriness in differentiated thyroid cancer: Impaired sodium iodide symporter (NIS) expression owing to altered signaling pathway activity and intracellular localization of NIS

Theranostics ◽  
2021 ◽  
Vol 11 (13) ◽  
pp. 6251-6277
Author(s):  
Ji Min Oh ◽  
Byeong-Cheol Ahn
Keyword(s):  
Thyroid Cancer ◽  
Signaling Pathway ◽  
Differentiated Thyroid Cancer ◽  
Sodium Iodide ◽  
Molecular Mechanisms ◽  
Radioactive Iodine ◽  
Intracellular Localization ◽  
Sodium Iodide Symporter ◽  
Pathway Activity

Role of Radioactive Iodine for Adjuvant Therapy and Treatment of Metastases

2007 ◽  
Vol 5 (6) ◽  
pp. 631-640 ◽  
Author(s):  
Jacqueline Jonklaas
Keyword(s):  
Thyroid Cancer ◽  
Side Effects ◽  
Adjuvant Therapy ◽  
Cancer Cells ◽  
Differentiated Thyroid Cancer ◽  
Sodium Iodide ◽  
Radioactive Iodine ◽  
Radioiodine Therapy ◽  
Sodium Iodide Symporter ◽  
Thyroid Cancer Cells

Normal thyrocytes and thyroid cancer cells are characterized by possession of a sodium iodide symporter. Radioiodine administration is a unique and powerful means of treating differentiated thyroid cancer because of the ability of thyroid cancer cells to concentrate beta-emitting radiolabeled iodine. Several manipulations, such as iodine depletion and thyroid hormone-stimulating hormone elevation, are used to enhance uptake of radiolabeled iodine by tumor cells. Adjuvant radioiodine therapy, given to patients without evidence of residual disease, enhances the sensitivity of subsequent surveillance and may decrease recurrence rates and mortality. However, its exact role in the management of low-risk patients merits further investigation. In contrast, radioactive iodine therapy used in patients with residual or metastatic disease clearly improves outcomes. Several studies show decreased recurrence and mortality rates in patients treated with radioiodine compared with those not receiving radioactive iodine. Adverse events from radioiodine therapy include salivary gland dysfunction, bone marrow suppression, and reproductive disturbances. Side effects of radioiodine therapy are generally greater when higher activities of radioiodine are used and may be transient or permanent. Secondary malignancies also may occur after radioiodine therapy. These side effects must be weighed against potential benefits, especially when radioactive iodine is used as adjuvant therapy. Stimulation of the expression of the sodium iodide symporter, or its introduction de novo into nonthyroid cells, is promising in treating poorly differentiated thyroid cancer and nonthyroid malignancies, respectively.

Curcumin enhances the membrane trafficking of sodium iodide symporter and augments radioiodine uptake in dedifferentiated thyroid cancer cells via suppression of PI3K-AKT signaling pathway

2021 ◽  
Author(s):  
Li Zhang ◽  
Shichen Xu ◽  
Xian Cheng ◽  
Jing Wu ◽  
Xiaowen Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Membrane Trafficking ◽  
Differentiated Thyroid Cancer ◽  
Sodium Iodide ◽  
Radioactive Iodine ◽  
Distant Metastases ◽  
Sodium Iodide Symporter ◽  
Akt Signaling Pathway ◽  
Radioiodine Uptake ◽  
Thyroid Cancer Cells

Radioactive iodine (RAI) is commonly used to treat differentiated thyroid cancer (DTC). A major challenge is dedifferentiation of DTC with the loss of radioiodine uptake. Patients with distant metastases have...

scholarly journals Downregulation of miR-146b-3p Inhibits Proliferation and Migration and Modulates the Expression and Location of Sodium/Iodide Symporter in Dedifferentiated Thyroid Cancer by Potentially Targeting MUC20

2021 ◽  
Vol 10 ◽  
Author(s):  
Shasha Hou ◽  
Xiaorui Xie ◽  
Jing Zhao ◽  
Cailan Wu ◽  
Ning Li ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Sodium Iodide ◽  
Radioactive Iodine ◽  
Sodium Iodide Symporter ◽  
Whole Exome ◽  
And Migration ◽  
Thyroid Cancer Cells ◽  
Proliferation And Migration

The dedifferentiation of differentiated thyroid cancer (DTC) is a challenging problem for radioactive iodine (131I) treatment, also known as radioiodine refractory differentiated thyroid cancer (RAIR-DTC). The purpose of this study was to further explore the mechanism of the redifferentiation of dedifferentiated thyroid cancer. Ineffective and effective groups of 131I therapy were analyzed and compared in both our clinical and TCGA samples. Whole-exome sequencing, mutation analysis, transcriptome analysis, and in vitro functional experiments were conducted. FLG, FRG1, MUC6, MUC20, and PRUNE2 were overlapping mutation genes between our clinical cases, and the TCGA cases only appeared in the ineffective group. The expression of miR-146b-3p target MUC20 was explored. The expression levels of miR-146b-3p and MUC20 were significantly increased, and the inhibition of miR-146b-3p expression significantly inhibited proliferation and migration, promoted apoptosis, regulated the expression and location of thyroid differentiation-related genes, and sodium/iodide symporter (NIS) in dedifferentiated thyroid cancer cells (WRO). Thus, miR-146b-3p potentially targets MUC20 participation in the formation of DTC dedifferentiation, resulting in resistance to 131I and the loss of the iodine uptake ability of DTC cancer foci, promoting refractory differentiated thyroid cancer. miR-146b-3p may be a potentially therapeutic target for the reapplication of 131I therapy in dedifferentiated thyroid cancer patients.

Expression of the sodium iodide symporter in differentiated thyroid cancer

2005 ◽  
Vol 44 (03) ◽  
pp. 86-96 ◽  
Author(s):  
G. Schmitz ◽  
L. Füzesi ◽  
J. Struck ◽  
U. Siefker ◽  
A. Hamann ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Sodium Iodide ◽  
Primary Tumour ◽  
Sodium Iodide Symporter ◽  
Radioiodine Uptake ◽  
Imaging Results ◽  
Group 2 ◽  
Radionuclide Uptake ◽  
Group 1

Summary Aim: Molecular analysis of the expression of the sodium iodide symporter (NIS) in 32 patients with differentiated thyroid cancer (DTC) and correlation with scintigraphic findings (131I,123I) in 19 (59.4%) of them. Patients, methods: NIS expression of 27 primary tumours, 13 lymphnodes and 18 distant metastases was determined by immunostaining using a murine monoclonal anti-NIS-antibody. NIS expression and radionuclide uptake of metastases were analysed by a semiquantitative visual score. Patients were divided into two subgroups: Group 1 (n = 8 patients): indirect correlation of radioiodine uptake (RIU) of subsequent metastases with NIS expression of 7 primary tumours and 3 metastases; Group 2 (n=11 patients): direct correlation of radionuclide uptake with NIS expression of 19 metastases which were excised after imaging. Results: 49 of 58 specimens (84.5%) were NIS-positive. A preserved NIS-expression was found in 12 primary tumours and 8 of 10 (80%) synchrone and 6 of 7 (85.7%) metachrone metastases. Group 1 revealed a 100% positive predictive value (PPV) of a preserved NIS expression in the primary tumour regarding radioiodine uptake in metastases while a lack of NIS expression in the primary tumor did not reliable predict a loss of the metastases’ ability to concentrate radioiodine. In group 2, only 11 of 19 (57.9%) specimens showed a concordant NIS expression and RIU whereas in the remaining 8 cases without visible RIU NIS expression was still present. Conclusions: NIS expression of the primary tumour and metastases in DTC is usually well preserved. We found a positive correlation between NIS expression of the primary and metastatic tissue but could not identify such well correspondence between NIS expression and the RIU of subsequent metastases.

APOPTOSIS ROLE IN FORMING RADIOIODINE RESISTANCE IN DIFFERENTIATED THYROID CANCER

2020 ◽  
pp. 301-310
Author(s):  
K.A. GARIPOV ◽  
◽  
Z.A. AFANASIEVA ◽  
A.D. GAFIULLINA ◽  
◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Radioactive Iodine ◽  
Tumour Regression ◽  
Therapeutic Effects ◽  
Multikinase Inhibitors ◽  
Complete Tumour ◽  
Apoptosis Proteins

According to studies, 25-66% of patients with metastatic highly differentiated thyroid cancer (DTC) develop partial or complete resistance of metastases to therapy with radioactive iodine. The review discusses the molecular mechanisms for the involvement of various apoptosis proteins in the formation of radioiodine resistance in patients with DTC, as well as the molecular mechanisms of the action of multikinase inhibitors, with a range of therapeutic effects from complete tumour regression to stabilization, on apoptosis. Considering the literature on the ambiguous role of apoptosis in the formation of radioiodine resistance in DTC, required further examination of its molecular mechanisms, its relationship with such a process as autophagy, the effect of multikinase inhibitors on its molecular basis and on overcoming iodine resistance. Studying the mechanism of apoptosis regulations gives a chance to find new targeted aims exposure in its individual stages in order to regulate or correct them.

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