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PURPOSE: The aim of this study was to investigate the usefulness of (18)F-FDG PET/CT with neck ultrasonography (neck US) in patients with recurrent, papillary thyroid cancer. MATERIAL AND METHODS: This retrospective study (December 2006 to April 2008) enrolled sixty-one patients (ninety-one lesions) who underwent high-dose (131)I-ablation therapy after total thyroidectomy, and evaluated recurred papillary thyroid cancer. All lesions were confirmed by histopathology and compared histopathologic findings to PET, PET/CT, and neck US findings. RESULTS: In sixty-one patients (57 women, 4 men; age range, 24-81 years, mean 49 years; 61 papillary carcinomas), the sensitivity, specificity, accuracy of (18)F-FDG PET/CT was 87.2%, 64.0%, 78.1% on a patient basis and 92.3%, 66.7%, 80.9% on a lesion basis, respectively. The sensitivity, specificity, accuracy of (18)F-FDG PET was 71.8% (p=0.03), 59.0% (p=1.00), 67.2% (p=0.03) on a patient basis and 78.8% (p<0.01), 64.1% (p=1.00), 72.5% (p=0.02) on a lesion basis, respectively. The sensitivity, specificity, accuracy of neck US was 71.1% (p=0.07), 52.2% (p=0.75), 63.9% (p=0.05) on a patient basis and 71.2% (p<0.01), 61.5% (p=1.00), 67.0% (p=0.06) on a lesion basis, respectively. Combined (18)F-FDG PET/CT with neck US improved the sensitivity, specificity, accuracy to 94.7% (p=0.50), 82.6% (p=0.13), 90.2% (p=0.03) on a patient basis and 96.2% (p=0.50), 89.7% (p<0.01), 93.4% (p<0.01) on a lesion basis, respectively. CONCLUSION: (18)F-FDG PET/CT demonstrated significantly higher sensitivity than neck US for the detection of recurred papillary thyroid cancer lesions. Furthermore, combined (18)F-FDG PET/CT with neck US showed more improved sensitivity, specificity, accuracy for diagnosis of recurrent papillary thyroid cancer.
Assuntos
Feminino , Humanos , Pescoço , Recidiva , Estudos Retrospectivos , Sensibilidade e Especificidade , Tireoglobulina , Glândula Tireoide , Neoplasias da Glândula Tireoide , TireoidectomiaRESUMO
No abstract available.
Assuntos
Pesquisa em Genética , Glândula Tireoide , Neoplasias da Glândula TireoideRESUMO
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, are widely used for primary and secondary prevention of coronary artery atherosclerosis. Pathogenesis of atherosclerosis is multistep processes where transendothelial migration of various leukocytes including monocytes is a crucial step. Interferon-gamma(IFN-gamma) contributes in this process by activating macrophages and T-lymphocytes, and by inducing adhesion molecules in vascular endothelial and smooth muscle cells. In this study we investigated the expression of intercellular cell adhesion molecule- 1 (ICAM-1) in transformed endothelial cell line ECV304 cells as influenced by lovastatin, tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma. Results show that lovastatin suppresses expression of ICAM-1 by inhibiting the IFN-gamma-induced extracellular signal-regulated kinase (ERK) p44/p42-STAT1 signaling pathway. In cells treated with lovastatin and IFN-gamma.ICAM-1 was expressed at a lower level than in cells treated with IFN-gamma alone. However, lovastatin does not reduce TNF-alpha induced expression of ICAM-1. A similar result was observed in cells treated with the MEKK inhibitor PD98059 and IFN-gamma. Cis-acting DNA sequence elements were identified in the 5'-flanking region of the ICAM-1 promoter that mediate inhibition by lovastatin; these sequences map to the IFN-gamma activated site which also binds the STAT1 homodimer. However, lovastatin did not inhibit IFN-gamma-mediated induction of the Y701 phosphorylated form of STAT1. But lovastatin does inhibit the IFN-gamma-mediated phosphorylation of ERK1/ERK2 (T202/Y204) and S727 phosphorylation of STAT1. TNF-alpha does not induce phosphorylation of ERK1/ERK2 and S727 in ECV304 and smooth muscle cells. The results provide the evidences that statins may have beneficial effects by inhibiting IFN-gamma action in atherosclerotic process
Assuntos
Animais , Ratos , Linhagem Celular , Proteínas de Ligação a DNA/metabolismo , Endotélio Vascular/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/genética , Interferon gama/antagonistas & inibidores , Lovastatina/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos de Músculo Liso/citologia , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Proteínas Recombinantes , Transativadores/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Peroxiredoxins (Prx) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. One mechanism for this action involves modulation of hydrogen peroxide (H2O2)-mediated cellular responses. This report examines the expression of Prx I and Prx II in thyroid cells and their roles in eliminating H2O2 produced in response to TSH. METHODS: The expression of Prx-I and Prx-II were quantiated in FRTL-5 after stimulation with Thyroid stimulating hormone (TSH), Forskolin (FSK), Methimazole (MMI) and hydrogen peroxide (H2O2). Transient transfections were carried out with FRTL-5 cells at 80% confluency and 20microgram of pCRprx I and pCRprx II or equivalent molar amounts of the pCR3.1TM basic vector. Transient transfection used an electroporation technique. Intracellular H2O2 was assayed in FRTL-5 cells with a fluorescent dye, 2', 7'-dichlorofluoresceindiacetate (DCFH-DA). Apoptosis of cells were evaluated by using an detection kit (Promega, Inc., Madison, WI). RESULTS: Prx I and Prx II are constitutively expressed in FRTL-5 thyroid cells. Prx I expression, but not Prx II expression, is stimulated by exposure to TSH and H2O2. In addition, methimazole (MMI) induces a high level of Prx I mRNA and protein in these cells. Overexpression of Prx I and Prx II enhance the elimination of H2O2 produced by TSH in FRTL-5 cells. Treatment with 500microM H2O2 causes apoptosis in FRTL-5 cells as evidenced by standard assays of apoptosis (i.e., terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end-labeling (TUNEL), BAX expression and PARP cleavage. Overexpression of Prx I and Prx II reduces the amount of H2O2-induced apoptosis measured by these assays. CONCLUSION: These results suggest that Prx I and Prx II are involved in the removal of H2O2 in thyroid cells, and can protect these cells from undergoing apoptosis. These proteins are likely to be involved in the normal physiological response to TSH-induced production of H2O2 in thyroid cells.
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Apoptose , Colforsina , Desoxiuridina , DNA Nucleotidilexotransferase , Eletroporação , Peróxido de Hidrogênio , Hidrogênio , Marcação In Situ das Extremidades Cortadas , Metimazol , Dente Molar , Peroxirredoxinas , RNA Mensageiro , Glândula Tireoide , Tireotropina , TransfecçãoRESUMO
No abstract available.
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Íntrons , Mutação Puntual , Proteínas Tirosina Quinases , TirosinaRESUMO
Our previous works have shown that human thyroid follicular cells from Graves' disease and FRTL-5 rat thyroid cells express the intercellular adhesion molecule-1 (ICAM-1) molecule and its expression is upregulated by several cytokines, interferon-gamma, tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6. We used FRTL-5 cells which show hormonal dependence of growth and function for the study of hormonal regulation of ICAM-1 gene, We studied ICAM-1 mRNA expression and promoter regulation after cloning of rat ICAM-1 promoter. We found very interesting findings that thyroid stimulating hormone (TSH) and forskolin downregulates steady state MHC class land ICAM-1 mRNA levels in FRTL-5 cells; furthermore, TSH/cAMP inhibit cytokines (interferon-gamma,tumor necrosis factor-alpha)-mediated maximal ICAM-1 mRNA expression, In addition, hydrocortisone and insulin differentially regulate the ICAM-1 mRNA levels; hydrocortisone markedly suppresses the mRNA level but insulin partially recovers hydrocortisone mediated ICAM-1 suppression, The interferon-gamma and tumor necrosis factor-alpha increases full ICAM-1 promoter (pCAM-1822) activity and this cytokine mediated increase of the promoter activity is also inhibited by TSH and forskolin, Thus TSH/cAMP pathways play roles as a antagonistic action for maximal expression of ICAM-1 gene by these cytokines. We propose this TSH action is one of physiologic mechanisms to preserve self tolerance in face of abnormal cytokine challenges in systemic inflammatory condition or acute phase response.
Assuntos
Animais , Humanos , Ratos , Células Clonais , Clonagem de Organismos , Colforsina , Citocinas , Expressão Gênica , Doença de Graves , Hidrocortisona , Insulina , Molécula 1 de Adesão Intercelular , Interferon gama , Interleucina-1beta , Interleucina-6 , Necrose , RNA Mensageiro , Tolerância a Antígenos Próprios , Glândula Tireoide , Tireotropina , Fator de Necrose Tumoral alfaRESUMO
Intercellular Adhesion Molecule-1(ICAM-1) plays an important role in a variety of inflammatory and immune-mediated mechanisms, including lymphocyte recruitment and targeting, antigen presentation and recognition, and lymphocyte cytotoxicity.In order to study the changes of soluble ICAM-1 and relationship to the immune mechanism of Graves' disease, we performed the measurement of a soluble form of ICAM-1 in sera from patients with Graves' disease before and after treatment with antithyroid drugs using a highly sensitive ELISA method.Our results were as followed.1) The serum levels of soluble ICAM-1 in patients with Graves' disease before treatment were significantly elevated than normal controls(p0.2).4) The serum levels of soluble ICAM-1 showed no significant correlation with serum titers of anti-thyroperoxidase antibody and anti-thyroglobulin antibody, serum T_3, T_4, TSH and goiter size in patients with Graves' disease.In conclusion, the soluble ICAM-1 levels reflect the activity of autoimmune reaction and might be used as a index of efficacy of antithyroid drug treatment of Graves' disease.
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Humanos , Apresentação de Antígeno , Antitireóideos , Ensaio de Imunoadsorção Enzimática , Bócio , Doença de Graves , Molécula 1 de Adesão Intercelular , LinfócitosRESUMO
No abstract available.
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No abstract available.
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Hipotireoidismo , Imunoglobulina G , Receptores da Tireotropina , TireotropinaRESUMO
It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)