Rosiglitazone Effect on Radioiodine Uptake in Thyroid Carcinoma Patients with High Thyroglobulin but Negative Total Body Scan: A Correlation with the Expression of Peroxisome Proliferator–Activated Receptor-Gamma

Thyroid ◽  
2008 ◽  
Vol 18 (7) ◽  
pp. 697-704 ◽  
Author(s):  
Supatporn Tepmongkol ◽  
Somboon Keelawat ◽  
Sittisak Honsawek ◽  
Preecha Ruangvejvorachai
2001 ◽  
Vol 86 (5) ◽  
pp. 2170-2177 ◽  
Author(s):  
Kazuyasu Ohta ◽  
Toyoshi Endo ◽  
Kazutaka Haraguchi ◽  
Jerome M. Hershman ◽  
Toshimasa Onaya

Ligands for peroxisome proliferator-activated receptor γ (PPARγ) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPARγ and the possibility that agonists for PPARγ also inhibit the growth of human thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP thyroid carcinoma cells, which originated from patients with papillary thyroid carcinoma. RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2–7, 7–13, 10–3, and 18–21 express PPARγ. More PPARγ was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPARγ-positive thyroid carcinoma cells were treated with agonists of PPARγ, troglitazone, BRL 49653, and 15-deoxy-Δ12,14-prostaglandin J2. Troglitazone (10μ mol/L), BRL 49653 (10 μmol/L), and 15-deoxy-Δ12,14-prostaglandin J2 (1 μg/mL) decreased[ 3H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPARγ. Under low serum conditions, ligands for PPARγ induced condensation of the nucleus and fragmentation of chromatin into nucleosome ladders. These findings indicate that the death of thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax, and c-myc. Troglitazone significantly increased the expression of c-myc messenger RNA but had no effect on the expression of bcl-2 and bax in thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human papillary thyroid carcinoma cells may be due to an increase of c-myc. Troglitazone (500 mg/kg·day) significantly inhibited tumor growth and prevented distant metastasis of BHP18–21 tumors in nude mice in vivo. Taken together, these results suggest that PPARγ agonist inhibit cell growth of some types of human thyroid cancer.


2009 ◽  
Vol 53 (7) ◽  
pp. 874-879 ◽  
Author(s):  
Maria Eduarda Mello ◽  
Rodrigo C. Flamini ◽  
Rossana Corbo ◽  
Marcelo Mamede

The radioactive iodine has been used with great value as a diagnostic and therapeutic method in patients with differentiated thyroid carcinoma previously submitted to total thyroidectomy. False-positive whole-body scans may occur due to misinterpretation of the physiologic distribution of the radioisotope or lack of knowledge on the existence of other pathologies that could eventually present radioiodine uptake. Thymic uptake is an uncommon cause of false-positive whole-body scan, and the mechanism through which it occurs is not completely understood. The present paper reports five cases of patients with differentiated thyroid cancer who presented a mediastinum uptake of radioiodine in a whole-body scan during follow-up. The patients had either histological or radiological confirmation of the presence of residual thymus gland. It is very important to know about the possibility of iodine uptake by the thymus in order to avoid unnecessary treatment, such as surgery or radioiodine therapy.


2010 ◽  
Vol 17 (3) ◽  
pp. 599-610 ◽  
Author(s):  
J Lado-Abeal ◽  
R Celestino ◽  
S B Bravo ◽  
M E R Garcia-Rendueles ◽  
J de la Calzada ◽  
...  

Our main objective was to search for mutations in candidate genes and for paired box gene 8–peroxisome proliferator-activated receptor gamma (PAX8–PPARγ) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's thyroid tumor, as well as ‘normal’ thyroid tissue, and from peripheral blood lymphocytes (PBLs) of the patient, her daughter, and two siblings. Nuclear isolation was extracted from the patient's tumor, ’normal’ thyroid tissue, PBLs, and uterine leiomyoma tissue. TSH receptor (TSHR), RAS, and BRAF genes were sequenced. We searched for PAX8–PPARγ in thyroid, PBL, and uterine leiomyoma samples from the patient and family members. Proliferative effects of detected mutants on non-transformed human thyrocytes cultures. An activating TSHR mutation, M453T, was detected in the tumor. PAX8 (exons 1–8+10)–PPARγ was found in all tested patient's tissues. A second rearrangement, PAX8 (exons 1–8)–PPARγ, was detected in the patient's normal thyroid tissue. Under deprived medium condition, co-transfection of PAX8–PPARγ and TSHR–M453T dramatically increased the number of thyrocytes, an effect that it was not observed with TSHR wild-type (WT); under complete medium conditions, co-transfection of PAX8–PPARγ with either TSHR–M453T or TSHR–WT inhibited cell proliferation. We report a patient with hyperthyroidism due to a FTC bearing an activating TSHR mutation and PAX8–PPARγ rearrangements. PAX8–PPARγ was present as a mosaicism affecting tissues from endodermal and mesodermal origin. PAX8–PPARγ and TSHR–M453T inhibited or promoted thyrocyte proliferation depending on medium conditions. The activating TSHR mutation could promote in vivo FTC development in PAX8–PPARγ-positive thyrocytes under poor blood supply with deprivation of growth factors but restraint the tumor growth when growth factors are supplied.


2005 ◽  
Vol 62 (3) ◽  
pp. 376-379 ◽  
Author(s):  
Anne Bachelot ◽  
Sophie Leboulleux ◽  
Eric Baudin ◽  
Dana M. Hartl ◽  
Bernard Caillou ◽  
...  

2008 ◽  
Vol 158 (3) ◽  
pp. 375-384 ◽  
Author(s):  
Ying Y Liu ◽  
Hans Morreau ◽  
Job Kievit ◽  
Johannes A Romijn ◽  
Nancy Carrasco ◽  
...  

ObjectivesThe microscopic distinction between benign and malignant thyroid lesions in clinical practice is still largely based on conventional histology. This study was performed to evaluate the diagnostic value of galectin-3 (Gal-3), Hector Battifora mesothelial-1 (HBME-1), cytokeratin (CK)-19, CBP P300-interacting transactivator with glutamic acid E- and aspartic acid D-rich C-terminal domain (CITED-1), fibronectin (FN)-1, peroxisome proliferator-activated receptor (PPAR)-γ, and intracellular sodium/iodide symporter (iNIS) immunostaining in a large panel of thyroid neoplasms. Our study differed from earlier ones with regard to the identification of optimal semiquantitative cut-off levels using receiver operator curve (ROC) analysis and hierarchical cluster analysis.MethodsWe used tissue arrays containing 177 thyroid tissues: 100 benign tissues (including normal thyroid, Graves disease, multinodular goiter, and follicular adenoma (FA)) and 77 thyroid carcinomas (including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)). Antibody staining was scored semiquantitatively based on the ROC analyses and with hierarchical cluster analysis.ResultsIn general, we found overexpression of FN-1, CITED-1, Gal-3, CK-19, HBME-1, and iNIS in malignant thyroid lesions. Gal-3, FN-1, and iNIS had the highest accuracy in the differential diagnosis of follicular lesions. A panel of Gal-3, FN-1, and iNIS, identified by hierarchical cluster analysis, had a 98% accuracy to differentiate between FA and malignant thyroid lesions. In addition, HBME-1 was found to be useful in the differentiation between FA and FVPTC (accuracy 88%).ConclusionWe conclude that identifying optimal antibody panels with cluster analysis increases the diagnostic value in the differential diagnosis of thyroid neoplasms, the combination of FN-1, Gal-3, and iNIS having the best accuracy (98%).


2002 ◽  
Vol 87 (10) ◽  
pp. 4728-4735 ◽  
Author(s):  
Maria Luisa Martelli ◽  
Rodolfo Iuliano ◽  
Ilaria Le Pera ◽  
Irene Sama’ ◽  
Carmen Monaco ◽  
...  

Epigenomics ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 1825-1843
Author(s):  
Eman A Toraih ◽  
Manal S Fawzy ◽  
Abdelrahman I Abushouk ◽  
Sameerah Shaheen ◽  
Yahya H Hobani ◽  
...  

The authors aimed to evaluate the prognostic value of miRNA-27a (miR-27a), peroxisome proliferator-activated receptor alpha/gamma ( PPARα/γ) and retinoid X receptor alpha (RXRα) tissue expression in patients with thyroid carcinoma. The expression levels were quantified in 174 archived thyroid specimens using real-time quantitative PCR. Downregulation of miR-27a was associated with lymph node stage and multifocality. PPARα expression was associated with histopathological type, tumor size and lymph node invasion. Moreover, RXRα expression was lower in patients who underwent total/subtotal thyroidectomy or received radioactive iodine treatment. Patients with upregulated miR-27a and downregulated RXRα showed a higher frequency of advanced lymph node stage and relapse by cluster analysis. Both miR-27a and PPARα/RXRα showed association with different poor prognostic indices in thyroid cancer patients.


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