Evidence map›Paper›PMID 26751190›Full record

ArticleThe Journal of clinical endocrinology and metabolism2016

Robust Thyroid Gene Expression and Radioiodine Uptake Induced by Simultaneous Suppression of BRAF V600E and Histone Deacetylase in Thyroid Cancer Cells.

Weiwei Cheng, Rengyun Liu, Guangwu Zhu, Hui Wang, Mingzhao Xing

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Predictive analysis ofOncology letters · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Combined Vorinostat and Chloroquine Inhibit Sodium-Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  12. Review
  13. Review
  14. Article
  15. Redox Homeostasis in Thyroid Cancer: Implications in NaInternational journal of molecular sciences · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Weiwei ChengLaboratory for Cellular and Molecular Thyroid Research (W.C., R.L., G.Z., M.X.), Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Nuclear Medicine (H.W.), Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Rengyun LiuLaboratory for Cellular and Molecular Thyroid Research (W.C., R.L., G.Z., M.X.), Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Nuclear Medicine (H.W.), Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Guangwu ZhuLaboratory for Cellular and Molecular Thyroid Research (W.C., R.L., G.Z., M.X.), Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Nuclear Medicine (H.W.), Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Hui WangLaboratory for Cellular and Molecular Thyroid Research (W.C., R.L., G.Z., M.X.), Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Nuclear Medicine (H.W.), Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Mingzhao XingLaboratory for Cellular and Molecular Thyroid Research (W.C., R.L., G.Z., M.X.), Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Nuclear Medicine (H.W.), Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Johns Hopkins University · USJohns Hopkins Medicine · USShanghai Jiao Tong University · CN

Funding

Genetic & Epigenetic Events in Papillary Thyroid CancerR01CA113507 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2006 to 2015
$2.2M
TERT Promoter Mutations in Thyroid CancerR01CA189224 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2015 to 2019
$1.8M
NCI NIH HHS R01 CA113507NCI NIH HHS R01CA113507NCI NIH HHS R01 CA189224NCI NIH HHS R01CA189224
6 · The paper itself

Abstract

contextUse of BRAF V600E inhibitors to restore thyroid iodide-handling gene expression and radioactive iodine (RAI) avidity is an attractive therapeutic strategy for RAI-refractory thyroid cancer, but recent initial clinical responses were modest. Given histone deacetylation at the sodium/iodide symporter promoter by histone deacetylase (HDAC) as a mechanism, simultaneously targeting BRAF V600E and HDAC could be a more effective strategy.

objectivesThe objective of the study was to test whether suppressing both BRAF V600E and HDAC could more effectively induce thyroid gene expression and RAI uptake in thyroid cancer cells. RESEARCH

designWe tested the BRAF V600E inhibitor PLX4032 (vemurafenib) and the HDAC inhibitor SAHA (vorinostat), two major anticancer drugs currently approved for clinical use, in inducing thyroid gene expression and RAI uptake in thyroid cancer cells.

resultsPLX4032 alone induced a modest expression of thyroid genes and RAI uptake preferentially in thyroid cancer cells harboring BRAF V600E. SAHA showed an effect in a genetic-independent manner in all the cells. A robust synergistic effect on thyroid gene expression and RAI uptake was observed in BRAF V600E-positive thyroid cancer cells when the two inhibitors were simultaneously used. This was dramatically enhanced further by TSH; triple combination of PLX4032, SAHA, and TSH showed the most robust effect on thyroid gene expression and RAI uptake in cells harboring BRAF V600E. Abundant sodium/iodide symporter protein expression in thyroid cancer cells under these conditions was confirmed by immunofluorescent microscopy.

conclusionsSimultaneously suppressing BRAF V600E and HDAC, particularly when cotreated with TSH, induced a far more robust expression of thyroid genes and RAI uptake in thyroid cancer cells than suppressing BRAF V600E alone. Triple combination of PLX4032, SAHA, and TSH is a specific robust regimen to restore RAI avidity in RAI-refractory BRAF V600E-positive thyroid cancer, which warrants clinical trials to confirm.

Indexed as

Antineoplastic AgentsCell Line, TumorGene ExpressionHistone Deacetylase InhibitorsHistone DeacetylasesHumansIndolesIodine RadioisotopesProto-Oncogene Proteins B-rafSodium-Iodide SymportersSulfonamidesSymportersThyroid GlandThyroid NeoplasmsThyrotropinVemurafenibAntineoplastic AgentsBRAF protein, humanHistone Deacetylase InhibitorsHistone DeacetylasesIndolesIodine RadioisotopesProto-Oncogene Proteins B-rafSodium-Iodide SymportersSulfonamidesSymportersThyrotropinVemurafenib

Identifiers

PMID26751190
PMCPMC4803151
OpenAlexW2235303687

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.