Management of undifferentiated thyroid cancer

Ain, Kenneth B.

doi:10.1053/beem.2000.0106

Cited by 51 publications

(30 citation statements)

References 59 publications

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“…The authors did not give information on the thyroid status of the patients. In addition, the interpretation of the findings of Dohan and colleagues 14 is obscured by the fact that tumors expected to be hNIS-negative such as anaplastic carcinomas corresponding to fully dedifferentiated tumors no longer expressing thyroid-specific genes 31,32 and medullary carcinomas that develop from C cells of neuronal crest origin, were also found highly hNIS-positive. Identification of the molecular species responsible for the immunolabeling of these tumors by Western blot would have been of a major interest to credit these findings.…”

Section: Discussionmentioning

confidence: 97%

Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Trouttet-Masson

Selmi-Ruby

Bernier-Valentin

et al. 2004

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 97%

Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Trouttet-Masson

Selmi-Ruby

Bernier-Valentin

et al. 2004

The American Journal of Pathology

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“…Unfortunately, around 10% of such cancers and most dedifferentiated thyroid cancers fail to concentrate radioiodine consequent to the loss of NIS expression (Robbins et al 1991, Ain 2000. For this reason, efforts to understand the mechanisms of this loss may lead to new treatments to restore NIS expression, permitting effective therapy with radioiodine.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, when hNIS expression is lost in dedifferentiated thyroid carcinomas, there are no effective systemic cytotoxic agents (Ain 2000). Restoration of hNIS expression in such tumors could restore the effectiveness of radioiodine treatment.…”

Section: Introductionmentioning

confidence: 99%

Human sodium–iodide symporter (hNIS) gene expression is inhibited by a trans-active transcriptional repressor, NIS-repressor, containing PARP-1 in thyroid cancer cells

Li¹,

Ain²

2010

Endocrine-Related Cancer

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Radioiodine remains the only tumoricidal therapy for disseminated thyroid carcinomas; however, dedifferentiated tumors lose the expression of human sodium-iodide symporter (hNIS) gene, and cannot respond to this treatment. Previous studies suggested that a trans-active protein factor (NIS-repressor) represses endogenous hNIS transcription, likely contributing to the loss of radioiodine uptake, and defined the NIS-repressor binding site (NRBS) in the proximal hNIS promoter. Using electrophoretic mobility shift assay (EMSA), we found evidence of NIS-repressor in the nuclear extract from KAK-1 cells, and confirmed this result using nuclear extracts prepared from multiple verified thyroid cell lines. Luciferase reporter assays of hNIS promoter constructs and EMSA were used to define two core sequences, NRBS-P and NRBS-D, in the hNIS promoter as the binding sites for NIS-repressor. Electrophoretic analysis of KAK-1 nuclear extract proteins cross-linked with NRBS-P suggests that NIS-repressor is a protein complex. Analysis of KAK-1 nuclear extract proteins bound to NRBS-P, via liquid chromatography coupled with tandem mass spectroscopy, demonstrated poly(ADP-ribose) polymerase-1 (PARP-1) as a NIS-repressor component. Pharmacological inhibition of PARP-1 enzymatic activity using PJ34 stimulated both the luciferase reporter activity driven by hNIS promoter and the endogenous hNIS mRNA level. Supershift studies suggest that thyroid transcription factor 2 (TTF-2) is also associated with the NIS-repressor complex. NIS-repressor, including its PARP-1 component, presents a potential therapeutic target to restore radioiodine uptake in dedifferentiated thyroid carcinomas.

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“…Although thyroid cancer is usually curable with conventional surgery and radioiodine ablation, it can be aggressive and incurable in some patients, particularly in those with extensive disease that has lost radioiodine avidity (11,29,30). The recently demonstrated importance of the MAPK pathway in tumorigenesis and progression of thyroid cancer suggests that this pathway may be a novel effective therapeutic target for thyroid cancer (14,31).…”

Section: Discussionmentioning

confidence: 99%

Potent Inhibition of Thyroid Cancer Cells by the MEK Inhibitor PD0325901 and Its Potentiation by Suppression of the PI3K and NF-κB Pathways

Liu

Xing

2008

Thyroid

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Background:We recently demonstrated inhibition of thyroid cancer cells by the MEK inhibitor CI-1040. The objective of this study was to use a potent new-generation MEK inhibitor PD0325901 to further investigate the therapeutic potential of specifically targeting MEK in the MAP kinase pathway for thyroid cancer. Methods: We examined the effects of PD0325901 on a variety of cellular and molecular activities of thyroid cancer cell lines with distinct genotypes. Results: PD0325901 remarkably inhibited MAP kinase pathway signaling in the thyroid cancer cells tested. It potently inhibited cell proliferation (IC 50 ¼ 0.059-0.783 mM) and arrested cell cycle at the G0=G1 phase of cells harboring BRAF or RAS mutations but not cells harboring wild-type alleles or the RET=PTC1 rearrangement. Synergistic inhibitory effects were observed when PD0325901 was combined with phosphatidylinositol 3-kinase (PI3K) or NF-kB pathway inhibitors in most cells, including the RET=PTC1-harboring cells. PD0325901 could inhibit invasion and anchorage-independent growth of thyroid cancer cells independently of the type of genetic alterations. This compound did not seem to have significant proapoptotic effects, however. Conclusions: The MEK inhibitor PD0325901 has a wide range of potent inhibitory effects on thyroid cancer cells, some of which seemed to be genotype-selective, consistent with the results previously observed with an earlygeneration MEK inhibitor, CI-1040. The data provide further evidence that targeted inhibition of MEK may be therapeutically effective for thyroid cancer, particularly if the PI3K and NF-kB pathways are concurrently inhibited.

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Management of undifferentiated thyroid cancer

Cited by 51 publications

References 59 publications

Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Evidence for Transcriptional and Posttranscriptional Alterations of the Sodium/Iodide Symporter Expression in Hypofunctioning Benign and Malignant Thyroid Tumors

Human sodium–iodide symporter (hNIS) gene expression is inhibited by a trans-active transcriptional repressor, NIS-repressor, containing PARP-1 in thyroid cancer cells

Potent Inhibition of Thyroid Cancer Cells by the MEK Inhibitor PD0325901 and Its Potentiation by Suppression of the PI3K and NF-κB Pathways

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