BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer

Groener, Jan B.; Gelen, Debora; Mogler, Carolin; Herpel, Esther; Tóth, Csaba; Κender, Ζoltan; Peichl, Marco; Haufe, Sabine; Haberkorn, Uwe; Sulaj, Alba; Zemva, Johanna; Kopf, Stefan; Nawroth, Peter P.; Brune, Maik; Rudofsky, Gottfried

doi:10.1055/a-0765-9078

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…Retinoic acid is the bioactive metabolite of Vitamin A, which is a compound that potentially prevents or treats malignancy and which participates in multiple biological processes [29,30]. Retinoic acid can suppress the growth of cancer cells in vitro and induces cell death in breast cancer, neuroblastoma, gastric carcinoma, prostate cancer, pancreatic cancer, and acute promyelocytic leukemia cells [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor

et al. 2020

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The funding was mainly used for data analysis and interpretation, and the costs incurred during the manuscript preparation Background:Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. Material/Methods:Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. Results:From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. Conclusions:RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

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Section: Discussionmentioning

confidence: 99%

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor

et al. 2020

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“…At the clinical levels, the results of studies assessing the impact of vitamin A supplementation on human subjects with thyroid disorders have been controversial yet mostly promising. Recently, the use of vitamin A derivatives as a potential therapeutic option in thyroid cancer has gained the interest of researchers like never before (38,183,184). At this moment, we might have effective techniques to tackle some problems in this area.…”

Section: Recent Clinical Studiesmentioning

confidence: 99%

Is beta-carotene consumption associated with thyroid hormone levels?

et al. 2023

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The thyroid hormones play a pivotal role in various physiological processes, including growth, metabolism regulation, and reproduction. While non-modifiable factors are known to impact thyroid function, such as genetics and age, nutritional factors are also important. Diets rich in selenium and iodine are conventionally acknowledged to be beneficial for the production and release of thyroid hormones. Recent studies have suggested a potential link between beta-carotene, a precursor to vitamin A (retinol), and thyroid function. Beta-carotene is known for its antioxidant properties and has been shown to play a role in the prevention of various clinical conditions such as cancer and cardiovascular and neurological diseases. However, its impact on thyroid function is still unclear. Some studies have suggested a positive association between beta-carotene levels and thyroid function, while others have found no significant effect. Conversely, the hormone produced by the thyroid gland, thyroxine, enhances the conversion of beta-carotene to retinol. Furthermore, vitamin A derivatives are being explored as potential therapeutic options for thyroid malignancies. In this review, we highlight the mechanisms through which beta-carotene/retinol and thyroid hormones interact and review the findings of clinical studies examining the association between beta-carotene consumption and thyroid hormone levels. Our review underscores the need for further research to clarify the relationship between beta-carotene and thyroid function.

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“…These authors also suggested that adequate vitamin A intake might be able to prevent extra-thyroidal extension and lymph node metastasis ( 52 ). Notably, one small group of patients with radioiodine-refractory thyroid cancer was treated with 13-cis-retinoic acid followed by iodine-131 treatment; after this “re-differentiation therapy,” 2 out of 3 patients whose cancers featured the BRAF V600E mutation showed a response expressed in terms of tumor size, serum Tg levels, and iodine uptake ( 53 ). Unfortunately, despite the interesting scientific basis, no studies have shown a definitive usefulness of vitamin A in thyroid cancer.…”

Section: Vitamin a And Thyroid Cancermentioning

confidence: 99%

The relationship between thyroid disorders and vitamin A.: A narrative minireview

et al. 2022

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The terms “vitamin A” and “retinoids” encompass a group of fat-soluble compounds essential for human nutrition. Some of them (retinol, retinal, 9-cis-retinoic acid, tretinoin, and 13-cis-retinoic acid) are fully natural, while others are synthetic compounds used mostly for therapeutic purposes. Some evidence indicates that the nutritional status of these retinoids (i.e., the presence or absence of deficiency) is able to modulate thyroid gland metabolism. Vitamin A deficiency is tightly correlated with structural and functional impairment of the thyroid gland and is often associated with iodine deficiency. Furthermore, retinoids are involved in different immune functions, as well as in the process of activation, proliferation, and differentiation of regulatory T cells (Treg). This is particularly significant given the high prevalence of thyroid autoimmune disorders, whose pathogenesis seems to be related to the altered homeostasis of regulatory T cells. Retinoids are also involved in the modulation of gene expression via their interaction with nuclear receptors, and they also act as cofactors in cell growth and differentiation. The ability of retinoic acid to increase iodine uptake and sodium-iodine symporter activity in human thyroid cancer cell lines suggests that some retinoids and their derivatives may be of use in the treatment of different thyroid tumors. This minireview summarizes the current knowledge on the link between nutritional intake of vitamin A and various thyroid disorders.

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BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer

Cited by 10 publications

References 40 publications

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor

Is beta-carotene consumption associated with thyroid hormone levels?

The relationship between thyroid disorders and vitamin A.: A narrative minireview

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