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J Surg Res ; 182(1): 85-93, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22998776

RESUMO

BACKGROUND: The BRAF(V600E) mutation is present in 62% of radioactive iodine-resistant thyroid tumors and is associated with downregulation of the sodium-iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHr). We sought to evaluate the combined effect of BRAF inhibition and TSH supplementation on (131)I uptake of BRAF(V600E)-mutant human thyroid cancer cells. MATERIALS AND METHODS: WRO cells (a BRAF(V600E)-mutant follicular-derived papillary thyroid carcinoma cell line) were transfected with small interfering RNA targeting BRAF for 72 h in a physiological TSH environment. NIS and TSHr expression were then evaluated at three levels: gene expression, protein levels, and (131)I uptake. These three main outcomes were then reassessed in TSH-depleted media and media supplemented with supratherapeutic concentrations of TSH. RESULTS: NIS gene expression increased 5.5-fold 36 h after transfection (P = 0.01), and TSHr gene expression increased 2.8-fold at 24 h (P = 0.02). NIS and TSHr protein levels were similarly increased 48 and 24 h after transfection, respectively. Seventy-two hours after BRAF inhibition, (131)I uptake was unchanged in TSH-depleted media, increased by 7.5-fold (P < 0.01) in physiological TSH media, and increased by 9.1-fold (P < 0.01) in supratherapeutic TSH media. CONCLUSIONS: The combined strategy of BRAF inhibition and TSH supplementation results in greater (131)I uptake than when either technique is used alone. This represents a simple and feasible approach that may improve outcomes in patients with radioactive iodine-resistant thyroid carcinomas for which current treatment algorithms are ineffective.


Assuntos
Adenocarcinoma Folicular/metabolismo , Inativação Gênica , Iodo/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/metabolismo , Tireotropina/farmacologia , Adenocarcinoma Folicular/patologia , Linhagem Celular Tumoral , Inativação Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Radioisótopos do Iodo , Mutação/genética , RNA Interferente Pequeno/farmacologia , Receptores da Tireotropina/metabolismo , Simportadores/metabolismo , Neoplasias da Glândula Tireoide/patologia , Transfecção
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