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3.
J Immunol ; 194(9): 4199-206, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25801430

RESUMO

Graves' disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients. We previously demonstrated that TSHR, the target of this autoimmune response, is also a key susceptibility gene for GD, probably acting through thymic-dependent central tolerance. We also showed that TSHR is, unexpectedly, expressed in thymocytes. In this report, we confirm the expression of TSHR in thymocytes by protein immunoblotting and quantitative PCR, and show that expression is confined to maturing thymocytes. Using functional assays, we show that thymic TSHR is functional and that TSAbs can stimulate thymocytes through this receptor. This new activity of TSAbs on thymocytes may: 1) explain GD-associated thymic enlargement (hyperplasia), and 2) suggest the provocative hypothesis that the continuous stimulation of thymocytes by TSAbs could lead to a vicious cycle of iterative improvement of the affinity and stimulating capability of initially low-affinity antibacterial (e.g., Yersinia) Abs cross-reactive with TSHR, eventually leading to TSAbs. This may help to fill one of the gaps in our present understanding of unusual characteristics of TSAbs.


Assuntos
Autoanticorpos/imunologia , Doença de Graves/imunologia , Ativação Linfocitária/imunologia , Receptores da Tireotropina/imunologia , Timócitos/imunologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Receptores da Tireotropina/genética , Timócitos/citologia
5.
Endocrinol. nutr. (Ed. impr.) ; 62(1): 24-28, ene. 2015. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-131636

RESUMO

Background Many reports have supported the relationship between high preoperative TSH levels and risk of thyroid cancer in nodular thyroid disease (NTD).Objectives We investigated whether TSH levels are related to the risk of differentiated thyroid carcinoma (DTC) in patients who have undergone total thyroidectomy for NTD. The relationship between TSH and size of malignant nodule was investigated. Finally, we assessed whether TSH levels are related to DTC and presence of additional benign nodules. Patients and methods A retrospective study of 980 patients was conducted. Variables included age at diagnosis, TSH level, nodule size, gender, final histology (benign versus DTC), and type of malignancy. Results Malignancy was present in 261 (26.6%) patients. These patients had higher median TSH levels as compared to those with no malignancy (1.61 mU/L (0.9–2.5) versus 0.9 mU/L (0.3–1.6); p-value < 0.001). TSH was higher in patients with DTC in whom the largest nodule was malignant than in patients in whom the largest nodule was benign (1.80 mU/L (1.1–2.6) versus 1.38 mU/L (0.7–2.1) respectively; p-value = 0.025). A significant correlation was seen between malignant nodule size and TSH level, but not between TSH levels and size of the largest benign nodule. Conclusions Our study supported an association between preoperative TSH levels (..) (AU)


Antecedentes Un gran número de artículos han confirmado la relación entre los niveles elevados de TSH preoperatoria y el riesgo de cáncer de tiroides en la enfermedad nodular tiroidea (ENT).Objetivos Analizamos si los valores de TSH preoperatoria se relacionan con el riesgo de cáncer diferenciado de tiroides (CDT) en pacientes tiroidectomizados por ENT. Además, investigamos la relación entre TSH y el tamaño del nódulo maligno. Finalmente, valoramos si la TSH se relaciona con la presencia de CDT y con la presencia de nódulos benignos adicionales. Pacientes y métodos Se estudiaron retrospectivamente 980 pacientes. Las variables consideradas fueron: edad al diagnóstico, sexo, valor de TSH, tamaño del nódulo, histología definitiva y tipo de CDT. Resultados En 261 (26,6%) casos el diagnóstico fue de CDT. Estos pacientes tenían niveles más elevados de TSH que los pacientes con histología benigna (mediana de 1,61 mU/l [0,9-2,5] versus 0,9 mU/l [0,3-1,6]; p < 0,001). La TSH fue más elevada en pacientes con CDT en los que el nódulo dominante fue maligno en relación con los que el nódulo dominante fue benigno (..) (AU)


Assuntos
Humanos , Tireotropina/sangue , Nódulo da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Hipertireoidismo/complicações , Período Pré-Operatório , Detecção Precoce de Câncer , Fatores de Risco , Testes de Função Tireóidea
6.
Endocrinol Nutr ; 62(1): 24-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25066642

RESUMO

BACKGROUND: Many reports have supported the relationship between high preoperative TSH levels and risk of thyroid cancer in nodular thyroid disease (NTD). OBJECTIVES: We investigated whether TSH levels are related to the risk of differentiated thyroid carcinoma (DTC) in patients who have undergone total thyroidectomy for NTD. The relationship between TSH and size of malignant nodule was investigated. Finally, we assessed whether TSH levels are related to DTC and presence of additional benign nodules. PATIENTS AND METHODS: A retrospective study of 980 patients was conducted. Variables included age at diagnosis, TSH level, nodule size, gender, final histology (benign versus DTC), and type of malignancy. RESULTS: Malignancy was present in 261 (26.6%) patients. These patients had higher median TSH levels as compared to those with no malignancy (1.61 mU/L (0.9-2.5) versus 0.9 mU/L (0.3-1.6); p-value<0.001). TSH was higher in patients with DTC in whom the largest nodule was malignant than in patients in whom the largest nodule was benign (1.80 mU/L (1.1-2.6) versus 1.38 mU/L (0.7-2.1) respectively; p-value=0.025). A significant correlation was seen between malignant nodule size and TSH level, but not between TSH levels and size of the largest benign nodule. CONCLUSIONS: Our study supported an association between preoperative TSH levels and risk of DTC in patients with NTD. There was also a direct relationship between malignant nodule size and TSH levels. By contrast, no relationship was found between the size of benign nodules and TSH levels.


Assuntos
Carcinoma/sangue , Carcinoma/patologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireotropina/sangue , Adulto , Idoso , Estudos de Coortes , Feminino , Bócio Nodular/patologia , Bócio Nodular/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Tireoidectomia
8.
Eur Thyroid J ; 3(3): 197-201, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25538902

RESUMO

BACKGROUND: Numerous studies have shown an increase in the incidence of thyroid cancer (TC) in recent years. OBJECTIVES: In this paper, we reviewed the incidence of TC in a series of patients undergoing thyroid surgery at a single institution over a 10-year period. PATIENTS AND METHODS: The cohorts were divided into two periods (2001-2005 and 2006-2010) with the purpose of comparing various clinicopathologic variables. RESULTS: A total of 1,263 patients were included. A significant increase in the number of malignancies was shown in the second period, namely 90 cases in 2001-2005 (15.2% of all interventions) compared to 163 cases in 2006-2010 (24.3%) (p < 0.001). These differences were attributed to an increase in papillary thyroid carcinoma (PTC), as there were 66 PTC cases in the first period (11.13% of thyroidectomies performed) compared to 129 cases in the second period (19.25%). There were no clinicohistological differences among PTC cases in these two periods. CONCLUSIONS: Over the last decade, there has been an increase in the incidence of TC in patients undergoing thyroid surgery. This increase is exclusively due to increases in PTC. Our study verifies the existence of this trend in our geographical area, similar to that noted in other parts of the world.

9.
Med. clín (Ed. impr.) ; 141(10): 442-446, nov. 2013. tab
Artigo em Espanhol | IBECS | ID: ibc-126210

RESUMO

Fundamento y objetivo: Hasta un 50% de los pacientes con acromegalia presentan alteraciones en el metabolismo hidrocarbonado (AMHC). La evolución natural de la enfermedad y las distintas alternativas terapéuticas impactan de forma diferente en esta predisposición. El objetivo de este trabajo fue valorar la prevalencia, las características de los pacientes y el efecto de los distintos tratamientos en la AMHC en los pacientes acromegálicos de nuestro centro. Pacientes y método: Se realizó un estudio transversal que incluyó a 55 pacientes con acromegalia. Se analizaron: edad, sexo, índice de masa corporal (IMC), factor de crecimiento insulínico tipo 1 (IGF-1), tamaño tumoral, tratamientos, y presencia de diabetes mellitus (DM) y grado de control metabólico inicial y tras las distintas alternativas terapéuticas. Resultados: De los 55 pacientes estudiados, el 54% eran varones, con una edad media (DE) de 50 (17) años y un IMC de 27,9 (3,8) kg/m2. Las AMHC estaban presentes en el 50,9% (n = 28) (DM en el 24% y glucosa basal alterada en el 27%). Los pacientes con DM no presentaban diferencias en el IMC, la edad ni el IGF-1 inicial respecto a los que no tenían DM. Sin embargo, presentaban más macroadenomas. En los pacientes diabéticos, la hemoglobina glucosilada (HbA1c) descendió después de la cirugía de 7,6 a 6,7% y después de los análogos de la somatostatina de 7,1 a 6,6%, pero solo con pegvisomant hemos observado una reducción significativa de HbA1c: del 9,8 al 5,6% (p < 0,05). Es más, solo pegvisomant ha permitido disminuir la intensidad del tratamiento hipoglucemiante. Conclusiones. La prevalencia de AMHC supera al 50% de los casos y se correlaciona con el tamaño tumoral. No hemos observado diferencias en el control glucémico en los pacientes tratados con las diferentes alternativas terapéuticas, excepto en el grupo que recibió pegvisomant, que logró una mejoría del mismo, junto con una reducción del tratamiento hipoglucemiante (AU)


Background and objective: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. Patients and method: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. Results: There were 30 men and 25 women. Mean age was 50 17 years and mean BMI was 27.9 3.8 Kg/ m2. Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. Conclusions: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment (AU)


Assuntos
Humanos , Erros Inatos do Metabolismo dos Carboidratos/epidemiologia , Acromegalia/epidemiologia , Diabetes Mellitus/epidemiologia , Somatostatina/análise , Estudos Retrospectivos , Adenoma/epidemiologia , Metabolismo Basal , Síndrome Metabólica/epidemiologia
10.
Med Clin (Barc) ; 141(10): 442-6, 2013 Nov 16.
Artigo em Espanhol | MEDLINE | ID: mdl-24012444

RESUMO

BACKGROUND AND OBJECTIVE: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. PATIENTS AND METHOD: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. RESULTS: There were 30 men and 25 women. Mean age was 50 ± 17 years and mean BMI was 27.9 ± 3.8 Kg/m(2). Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. CONCLUSIONS: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment.


Assuntos
Acromegalia/metabolismo , Hiperglicemia/etiologia , Acromegalia/tratamento farmacológico , Acromegalia/etiologia , Acromegalia/cirurgia , Adulto , Idoso , Glicemia/análise , Índice de Massa Corporal , Cabergolina , Terapia Combinada , Irradiação Craniana , Estudos Transversais , Ergolinas/uso terapêutico , Feminino , Glucose/metabolismo , Hemoglobina A Glicada/análise , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/radioterapia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hiperglicemia/sangue , Hipofisectomia , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Carga Tumoral
11.
Int Immunol ; 25(10): 563-74, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23929911

RESUMO

Reported alterations in T(reg) cells from type 1 diabetes (T1D) patients led us to a revision of their phenotypical features compared with controls. A fine cytometric analysis was designed for their characterization, using a panel of markers including FOXP3, CTLA4, glucocorticoid-induced TNFR family related (GITR) and CD127. The frequency of peripheral CD4(+)CD25(hi) T(reg) cells was similar between samples. However, the yield of sorted T(reg) cells was significantly lower in patients than in controls. When comparing the T(reg)-cell phenotype between samples, the only difference concerned the expression of GITR. A significant decrease of GITR(+) cells and GITR mean fluorescence intensity within the T(reg)-cell population, and to a lesser extent in the effector population, was observed in T1D compared with controls. Moreover, GITR expression was analyzed in several conditions of T-cell activation and differences were only observed in T1D T(reg) cells versus controls when responding to sub-optimal stimulation, that is, soluble anti-CD3 or medium alone but not in the presence of anti-CD3-/anti-CD28-coated beads. However, expanded T1D T(reg)-cell-mediated suppression was as efficient as that mediated by their control counterparts, showing no association between their regulatory capacity and the reduced GITR. Our results show a higher susceptibility to apoptosis in patients' versus controls' T(reg) cells, suggesting that GITR is a T(reg)-cell marker that would be primarily involved in T(reg)-cell survival rather than in their suppressor function.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Proteína Relacionada a TNFR Induzida por Glucocorticoide/metabolismo , Linfócitos T Reguladores/imunologia , Adulto , Antígenos CD4/metabolismo , Separação Celular , Sobrevivência Celular , Feminino , Citometria de Fluxo , Proteína Relacionada a TNFR Induzida por Glucocorticoide/genética , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Endocrine ; 43(1): 239-41, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22833431
13.
Anticancer Res ; 33(1): 337-40, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23267166

RESUMO

BACKGROUND AND AIM: There is an increased incidence of secondary primary cancer (SPC) in patients with papillary thyroid carcinoma (PTC). The risk is stronger in the first year after the first malignancy (synchronous tumours). The aim of this study was to assess the prevalence of SPC in patients with PTC, and to analyse whether the timing of tumour presentation influenced the clinicopathological characteristics of PTC. PATIENTS AND METHODS: A total of 184 patients with PTC were included in the study. RESULTS: There were 24 patients with SPC and nine with PTC and two other primary tumours (42 additional malignancies in total). Additional tumours were more prevalent in male and older patients. In 11 cases (33%), the two carcinomas were synchronous. PTCs from synchronous cases were significantly larger than those from non-synchronous cases. CONCLUSION: Patients with PTC were at elevated risk for SPC. In one third of patients, both neoplasms were diagnosed within the same year. Male and older patients were more likely to have SPC.


Assuntos
Fatores Etários , Carcinoma , Segunda Neoplasia Primária , Fatores Sexuais , Neoplasias da Glândula Tireoide , Idoso , Carcinoma/complicações , Carcinoma/patologia , Carcinoma Papilar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/complicações , Segunda Neoplasia Primária/patologia , Fatores de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia
14.
Endocr Relat Cancer ; 19(2): 209-16, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22285864

RESUMO

Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Piridinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Calcitonina/sangue , Antígeno Carcinoembrionário/sangue , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Metástase Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Estudos Retrospectivos , Sorafenibe , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia
15.
J Thyroid Res ; 2012: 530721, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21860806

RESUMO

We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08 ± 2.1 in cases with malignant lesions (P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level.

16.
Endocrinol Nutr ; 57(4): 165-9, 2010 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-20403734

RESUMO

INTRODUCTION AND OBJECTIVE: Regional lymph node metastases (LNM) are a common finding in papillary thyroid cancer (PTC). Approximately half of patients have LNM at diagnosis. The aim of this study was to analyze immunohistochemically the combined expression of different PTC-related molecules in order to identify cases with a tendency to show LNM. PATIENTS AND METHODS: Thirty-five patients were included in the study. The patients were distributed in two groups. Group I included 19 patients with no histological evidence of LNM at diagnosis. Group II included 16 patients with histological evidence of cervical LNM. Samples were stained for RET/PTC, EGFR, p16(INk4a), p21(cip1), p27(kip1), BCL2, and pAKT. RESULTS: Expression of p21(cip1), p27(kip1), p16(INk4a), Bcl-2, and pAKT showed no differences between the two groups. However, RET/PTC and EGFR expression showed significant differences: in both cases, staining was more frequent in patients with LNM. Simultaneous positivity of RET/PTC and EGFR was a discriminative marker in patients with LNM. Finally, the combination of RET/PTC negative, EGFR negative and p16(INk4a) negative was found in none of the patients with LNM but in nearly half of those in group I. CONCLUSIONS: Immunohistochemical analysis of several molecular markers could be useful in the phenotypic characterization of PTC. Application of these markers could enhance diagnosis and improve the management of patients with thyroid cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Papilar/secundário , Técnicas Imunoenzimáticas , Metástase Linfática/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Carcinoma Papilar/diagnóstico , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor de Quinase Dependente de Ciclina p21/análise , Inibidor de Quinase Dependente de Ciclina p27 , Receptores ErbB/análise , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Masculino , Pessoa de Meia-Idade , Pescoço , Proteínas de Neoplasias/análise , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-ret/análise , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
17.
Endocrinol. nutr. (Ed. impr.) ; 57(4): 165-169, abr. 2010. tab
Artigo em Espanhol | IBECS | ID: ibc-84004

RESUMO

Introducción y objetivo En el carcinoma papilar de tiroides, la detección de metástasis linfáticas (ML) en la región cervical es frecuente, observándose en cerca de la mitad de los casos en el momento del diagnóstico. El objetivo del estudio es analizar mediante técnica inmunohistoquímica la expresión combinada de diversas moléculas con el fin de establecer las características de aquellos casos con mayor tendencia a desarrollar ML. Pacientes y métodos Treinta y cinco pacientes con carcinoma papilar de tiroides fueron distribuidos en 2 grupos. El grupo i incluyó 19 pacientes que no presentaron ML al diagnóstico. En el grupo ii se incluyeron 16 pacientes en los cuales se había demostrado la presencia de ML. En todos los casos se practicó tinción inmunohistoquímica para RET/PTC, receptor del factor de crecimiento epidérmico (EGFR), p16INk4a, p21cip1, p27kip1, BCL2 y pAKT. Resultados No se apreciaron diferencias en ambos grupos en relación a p21cip1, p27kip1, p16INk4a, Bcl-2 y pAKT. No obstante, se observaron diferencias de expresión para RET/PTC y para EGFR, siendo ambas más frecuentes en los pacientes con ML. Asimismo se vio que la doble positividad de RET/PTC y el EGFR discriminaba de manera significativa los casos con ML. Finalmente, la triple combinación: RET/PTC negativo, EGFR negativo y p16INk4a negativo no se daba en ningún paciente del grupo ii y en casi la mitad del grupo i. Conclusiones El estudio de la expresión de diversas moléculas de manera combinada puede resultar eficaz en la caracterización fenotípica del carcinoma papilar de tiroides. Con ello se podría mejorar el manejo de los pacientes con cáncer de tiroides (AU)


Introduction and objective Regional lymph node metastases (LNM) are a common finding in papillary thyroid cancer (PTC). Approximately half of patients have LNM at diagnosis. The aim of this study was to analyze immunohistochemically the combined expression of different PTC-related molecules in order to identify cases with a tendency to show LNM. Patients and methods Thirty-five patients were included in the study. The patients were distributed in two groups. Group I included 19 patients with no histological evidence of LNM at diagnosis. Group II included 16 patients with histological evidence of cervical LNM. Samples were stained for RET/PTC, EGFR, p16INk4a, p21cip1, p27kip1, BCL2, and pAKT. Results Expression of p21cip1, p27kip1, p16INk4a, Bcl-2, and pAKT showed no differences between the two groups. However, RET/PTC and EGFR expression showed significant differences: in both cases, staining was more frequent in patients with LNM. Simultaneous positivity of RET/PTC and EGFR was a discriminative marker in patients with LNM. Finally, the combination of RET/PTC negative, EGFR negative and p16INk4a negative was found in none of the patients with LNM but in nearly half of those in group I. ConclusionsI mmunohistochemical analysis of several molecular markers could be useful in the phenotypic characterization of PTC. Application of these markers could enhance diagnosis and improve the management of patients with thyroid cancer (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma Papilar/secundário , Técnicas Imunoenzimáticas , Metástase Linfática/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Biomarcadores Tumorais/análise , Carcinoma Papilar/diagnóstico , Inibidor de Quinase Dependente de Ciclina p21/análise , /análise , Pescoço , Proteínas de Neoplasias/análise , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-ret/análise , Receptores ErbB/análise , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
18.
J Thyroid Res ; 2011: 639156, 2010 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-21209704

RESUMO

Papillary thyroid carcinomas (PTCs) with a diameter ≤1 cm are referred to as papillary microcarcinomas (PTMCs). The prognostic factors for PTMCs have not been defined. Different clinical and histopathologic variables were studied in 152 PTCs, including 74 PTMCs and 78 PTCs of larger size. We found that PTMCs are associated with less multifocality (P = .046) and bilaterality (P = .003), fewer lymphadenectomies (P < .001), and a higher rate of incidental tumours (P < .001). Moreover, patients with a low aggressive profile were significantly older than the remaining patients (54 ± 13.7 years versus 45.8 ± 13.1 years; P = .001). In conclusion PTMCs show significant differences compared to PTCs of larger size in the form of presentation. Furthermore, it is possible that the classic risk factors, which are well validated in PTCs, such as age, must be cautiously interpreted in the current increasing subgroup of PTMCs.

19.
Target Oncol ; 4(4): 275-85, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19904500

RESUMO

Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations that characterize tumor growth has provided novel targets in cancer therapy. Several proteins have been implicated as having a crucial role in the carcinogenesis of differentiated thyroid cancer, such as those involved in RET/PTC-RAS-RAF-MAPK pathway. Moreover, vascular aberrations and angiogenesis equilibrium have also been related to tumor growth. The development of new, targeted therapies and their encouraging initial results have opened a hopeful opportunity of treatment for these orphan therapy tumor patients.


Assuntos
Carcinoma Papilar/genética , Sistemas de Liberação de Medicamentos/métodos , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Animais , Carcinoma Papilar/tratamento farmacológico , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Modelos Animais de Doenças , Desenho de Drogas , Genes ras/genética , Genes ras/fisiologia , Humanos , Camundongos , Camundongos Nus , Recidiva Local de Neoplasia , Transplante de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas c-ret/metabolismo , Ratos , Neoplasias da Glândula Tireoide/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Endocrinol Nutr ; 56(4): 176-86, 2009 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-19627734

RESUMO

In recent years, significant progress has been made in elucidating the genetic bases promoting tumorigenesis in various human neoplasms. Constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway is a major event in the carcinogenesis of papillary thyroid carcinoma (PTC), the most prevalent endocrine malignancy. Affected elements include RET/PTC rearrangements and point mutations of the Ras and BRAF genes. Mutations in these genes are found in over 70% of PTC. Chromosomal RET rearrangements, called RET/PTC, result in constitutive ligand-independent activation of RET kinase, which was the first genetic anomaly detected in PTC and is found in 5-70% of tumoral samples. Although less frequent, the activation of other tyrosine kinase receptors, such as NTRK1, c-Met or EGFR, has also been reported in PTC. The BRAF mutation represents the most common genetic alteration found in PTC. More than 90% of BRAF mutations lead to a change of a valine to a glutamic acid at position 600 (V600E). Finally, Ras is the least affected molecule in the pathway. A relationship between clinical behavior and these genetic alterations has been proposed. Thus, the BRAF mutation is associated with a more aggressive PTC phenotype and is correlated with poorer outcomes. However, no clear association has been found between RET/PTC and clinical features. The discovery of these alterations opens the way to new therapeutic strategies, especially to treat those patients in whom conventional therapy is not effective. Several new drugs are being tested, such as small molecule tyrosine kinase inhibitors. Some of these recently developed agents have begun to be used with promising results.


Assuntos
Adenocarcinoma Papilar/enzimologia , Sistema de Sinalização das MAP Quinases , Proteínas de Neoplasias/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Glândula Tireoide/enzimologia , Adenocarcinoma Papilar/tratamento farmacológico , Adenocarcinoma Papilar/genética , Antineoplásicos/uso terapêutico , Transformação Celular Neoplásica , Ensaios Clínicos como Assunto , Genes ras , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Mutação , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/fisiologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/fisiologia , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/fisiologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/fisiologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética
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