Evidence map›Paper›PMID 20860424›Full record

ArticleThyroid : official journal of the American Thyroid Association2010

Thyroid cancer resistance to vitamin D receptor activation is associated with 24-hydroxylase levels but not the ff FokI polymorphism.

Vibha Sharma, Deborah Fretwell, Zachary Crees, Anna Kerege, Joshua P Klopper

Open access · greenAbstract read
In one paragraph

Article in Thyroid : official journal of the American Thyroid Association, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Vitamin D-Related Genes and Thyroid Cancer-A Systematic Review.International journal of molecular sciences · 2022
    Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Endocrine connections · 2017
    Article
  7. Article
  8. Review
  9. Review
  10. Very important pharmacogene summary for VDR.Pharmacogenetics and genomics · 2012
    Review
  11. Article
  12. Altered expression of key players in vitamin D metabolism and signaling in malignant and benign thyroid tumors.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2012
    Article
  13. Article
  14. Review
  15. Article
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 2 institutions in 1 country.

Vibha SharmaDivision of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado School of Medicine, 12801 E. 17th Ave., Aurora, CO 80045, USA.
Deborah Fretwell
Zachary Crees
Anna Kerege
Joshua P Klopper
University of Colorado Denver · USUniversity of Colorado Cancer Center · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
MBRS-IMSD Program at the University of Colorado at Denver and Health Sciences CenR25GM083333 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI FLORES, SONIA CASTRO · 2008 to 2012
$1.5M
NCI NIH HHS P30 CA046934NIGMS NIH HHS R25 GM083333
6 · The paper itself

Abstract

backgroundThe vitamin D receptor (VDR) has been studied as a novel target for cancer therapy in many tissue types as VDR ligands decrease cell proliferation in vitro and decrease tumor growth in vivo in sensitive cells. The objective of this study was to analyze the response to VDR agonist therapy in a panel of validated thyroid cancer cells and assess genetic markers predicting sensitivity and resistance to calcitriol and the noncalcemic analog DP006.

methodsThyroid cancer cell lines were analyzed for VDR and RXR protein by Western blot. Cell growth after VDR agonist treatment (calcitriol or DP006) was assessed after 6 days of treatment by viable cell assay. To investigate calcitriol/DP006 resistance in VDR-expressing cells, the VDR was sequenced and 1-α and 24-hydroxylase mRNA expression was assessed.

resultsVDR protein was variably expressed in the thyroid cancer cell lines and its presence was not sufficient for decreased viable cell count in response to calcitriol or DP006. The most sensitive cells (TPC1) have an ff FokI VDR polymorphism and the most resistant cells (HTh7 and 8505C) have an FF FokI VDR. This is a unique finding given that the balance of the literature of VDR polymorphisms describes an association of the ff FokI polymorphism with cancer risk and/or decreased VDR transactivation. 1-α and 24-hydroxylase mRNA expression before and after VDR agonist therapy was examined. 1-α-Hydroxylase levels did not change after calcitriol treatment. However, we found that higher baseline 24-hydroxylase levels and/or lower stimulation of 24-hydroxylase levels after calcitriol treatment were associated with relative resistance to calcitriol/DP006.

conclusionsThe VDR represents a novel therapeutic target in poorly differentiated thyroid cancer; however, the efficacy of VDR agonist therapy to decrease viable thyroid cancer cell count cannot be predicted solely on the presence of the VDR. The FF FokI VDR genotype and high baseline 24-hydroxylase levels were associated with relative resistance to calcitriol and DP006. Therefore, identifiable markers of sensitivity or resistance to VDR agonist therapy may allow for a personalized use of these agents in poorly differentiated thyroid cancer.

Indexed as

25-Hydroxyvitamin D3 1-alpha-HydroxylaseBase SequenceCalcitriolCell Line, TumorCell SurvivalDeoxyribonucleases, Type II Site-SpecificDrug Resistance, NeoplasmHumansPolymorphism, GeneticReceptors, CalcitriolRetinoid X ReceptorsSteroid HydroxylasesThyroid NeoplasmsVitamin DVitamin D3 24-Hydroxylase25-Hydroxyvitamin D3 1-alpha-HydroxylaseCalcitriolDeoxyribonucleases, Type II Site-Specificendodeoxyribonuclease FokIReceptors, CalcitriolRetinoid X ReceptorsSteroid HydroxylasesVitamin DVitamin D3 24-Hydroxylase

Identifiers

PMID20860424
PMCPMC2958447
OpenAlexW2033076908

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.