Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 111(1): 367-72, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24344271

RESUMO

Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.


Assuntos
Regulação da Expressão Gênica , Interleucina-17/metabolismo , Interleucinas/metabolismo , Linfócitos/citologia , Fibrose Pulmonar/metabolismo , Idoso , Animais , Moléculas de Adesão Celular/metabolismo , Colágeno/química , Colágeno/metabolismo , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Imunidade Inata , Inflamação , Interleucina-13/metabolismo , Fígado/parasitologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fibrose Pulmonar/patologia , Schistosoma mansoni
2.
Endocr Relat Cancer ; 17(1): 255-64, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20032008

RESUMO

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.


Assuntos
Adenocarcinoma Folicular/etiologia , Receptor alfa de Estrogênio/fisiologia , Receptor ErbB-2/fisiologia , Neoplasias da Glândula Tireoide/etiologia , Fatores de Transcrição/fisiologia , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/etiologia , Carcinoma/metabolismo , Carcinoma/mortalidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteínas Correpressoras/metabolismo , Proteínas Correpressoras/fisiologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/fisiologia , Receptor ErbB-2/metabolismo , Análise de Sobrevida , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/mortalidade , Transativadores/metabolismo , Transativadores/fisiologia , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Adulto Jovem
3.
Clin Cancer Res ; 15(6): 2098-106, 2009 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-19276281

RESUMO

PURPOSE: This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments. EXPERIMENTAL DESIGN: The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients. RESULTS: Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with human epidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively). CONCLUSIONS: SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/fisiologia , Histona Acetiltransferases/fisiologia , Recidiva Local de Neoplasia/etiologia , Proteínas Nucleares/fisiologia , Proteínas de Transporte Nucleocitoplasmático/fisiologia , Tamoxifeno/uso terapêutico , Fatores de Transcrição/fisiologia , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Receptor alfa de Estrogênio/análise , Feminino , Histona Acetiltransferases/análise , Humanos , Proteínas Nucleares/análise , Coativador 1 de Receptor Nuclear , Coativador 3 de Receptor Nuclear , Proteínas de Transporte Nucleocitoplasmático/análise , Prognóstico , Proteínas de Ligação a RNA , Análise Serial de Tecidos , Transativadores/análise , Transativadores/fisiologia , Fatores de Transcrição/análise
4.
Endocr Relat Cancer ; 15(3): 745-53, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18469157

RESUMO

Cyclooxygenase-2 (COX-2) is associated with breast tumour progression. Clinical and molecular studies implicate human epidermal growth factor receptor 2 (HER2) in the regulation of COX-2 expression. Recent reports raise the possibility that HER2 could mediate these effects through direct transcriptional mechanisms. The relationship between HER2 and COX-2 was investigated in a cohort of breast cancer patients with or without endocrine treatment. A tissue microarray comprising tumours from 560 patients with 10-year follow-up was analysed for HER2, ERK1/2, polyoma enhancer activator 3 (PEA3) and COX-2 expression. Subcellular localisation of HER2 was assessed by immunofluorescence and confocal microscopy. Expression of markers examined was analysed in relation to classic clinicopathological parameters and disease-free survival in the presence and absence of tamoxifen. COX-2 expression associated with both membranous and nuclear expression of HER2 (P=0.0033 and P<0.00001 respectively). No association was detected between COX-2 and either ERK1/2 or PEA3 (P=0.7 and P=0.3 respectively). None of the markers were found to be independently prognostic. Membrane HER2, nuclear HER2 and COX-2, however, were all found to predict poor disease-free survival in patients on endocrine treatment (P=0.0017, P=0.0003 and P=0.0202 respectively). Moreover, patients who were positive for COX-2 predicted adverse effects of tamoxifen (P=0.0427). These clinical ex vivo data are consistent with molecular observations that HER2 can regulate COX-2 expression through direct transcriptional mechanisms. COX-2 expression correlates with disease progression on endocrine treatment. This study supports a role for COX-2 as a predictor of adverse effects of tamoxifen in breast cancer patients.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Núcleo Celular/metabolismo , Ciclo-Oxigenase 2/fisiologia , Receptor ErbB-2/fisiologia , Tamoxifeno/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma/tratamento farmacológico , Carcinoma/metabolismo , Carcinoma/mortalidade , Núcleo Celular/efeitos dos fármacos , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Distribuição Tecidual , Fatores de Transcrição/metabolismo , Resultado do Tratamento
5.
Urology ; 70(4): 812.e3-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17991576

RESUMO

We report the case of a 71-year-old male who presented with squamous cell carcinoma of the renal pelvis in a solitary functioning kidney, 34 years after orchidectomy and adjuvant retroperitoneal radiotherapy for stage II seminoma. This rare second malignancy occurred in the radiation treatment field. Second malignancies are an uncommon but serious sequela of radiotherapy, with potential for significant health problems in patients with complete remission of primary disease. To our knowledge, this is the first report of squamous cell carcinoma of the renal pelvis occurring after radiation treatment.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Renais/etiologia , Neoplasias Induzidas por Radiação , Segunda Neoplasia Primária/etiologia , Seminoma/radioterapia , Neoplasias Testiculares/radioterapia , Idoso , Humanos , Pelve Renal , Masculino
6.
BMC Cancer ; 6: 164, 2006 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-16796740

RESUMO

BACKGROUND: The association of nipple discharge with breast carcinoma has resulted in numerous women undergoing exploratory surgery to exclude malignancy. The aim of this study was to determine whether pre-operative factors can identify those patients that are most at risk of carcinoma. METHODS: All patients over a 14-year period (1991-2005) who had a microdochectomy or subareolar exploration for the evaluation of nipple discharge were assessed. Patient characteristics, pre-operative imaging and pathological findings were analysed. RESULTS: Of the 211 patients included in this study, 116 patients had pathological (unilateral, uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with pathological discharge and 2.4% (n = 2) of patients with non-pathological discharge were diagnosed with carcinoma. Overall, major duct excision resulted in the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in 39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 111) of patients. In the patients determined to have malignancy, 44% (n = 4) were premenopausal. No patient with a non-bloody discharge in the total population analysed (28%; n = 59/211), or in the population with a pathological discharge (21%; n = 24/116) was found to have carcinoma upon excision. CONCLUSION: Microdochectomy or major duct excision performed for nipple discharge resulted in a low rate of malignancy on excision. Conservative management of non-bloody nipple discharge can be considered in patients with no other clinical or radiological signs of malignancy.


Assuntos
Doenças Mamárias/cirurgia , Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Exsudatos e Transudatos , Hemorragia/cirurgia , Glândulas Mamárias Humanas/cirurgia , Mamilos/cirurgia , Adulto , Idoso , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/etiologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/epidemiologia , Calcinose/patologia , Calcinose/cirurgia , Carcinoma/diagnóstico por imagem , Carcinoma/epidemiologia , Carcinoma/patologia , Carcinoma/cirurgia , Dilatação Patológica/diagnóstico , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/epidemiologia , Dilatação Patológica/patologia , Dilatação Patológica/cirurgia , Reações Falso-Negativas , Feminino , Fibroadenoma/diagnóstico , Fibroadenoma/diagnóstico por imagem , Fibroadenoma/epidemiologia , Fibroadenoma/patologia , Fibroadenoma/cirurgia , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Mamografia , Pessoa de Meia-Idade , Palpação , Papiloma/diagnóstico , Papiloma/diagnóstico por imagem , Papiloma/epidemiologia , Papiloma/patologia , Papiloma/cirurgia , Pré-Menopausa , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
7.
J Cyst Fibros ; 5(1): 59-61, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16290154

RESUMO

As the life expectancy of patients with cystic fibrosis increases, unusual complications including amyloidosis are increasingly recognised. We report three cases of amyloidosis including a unique case presenting with a hemorrhagic and thrombotic diatheisis. This complication of amyloidosis has never been reported in cystic fibrosis.


Assuntos
Amiloidose/etiologia , Fibrose Cística/complicações , Cardiopatias/etiologia , Nefropatias/etiologia , Adulto , Amiloidose/diagnóstico , Biópsia , Diagnóstico Diferencial , Ecocardiografia , Evolução Fatal , Feminino , Cardiopatias/diagnóstico , Humanos , Nefropatias/diagnóstico , Masculino
8.
Curr Diab Rep ; 3(1): 56-9, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12643147

RESUMO

Sclerosing lymphocytic lobulitis or "diabetic mastopathy" is strongly associated with type 1 diabetes but may occur occasionally in its absence. It is characterized by keloid-type fibrosis, lymphocytic lobulitis, and perivasculitis and epithelioid cells. Infiltrating cells are predominantly B lymphocytes. It may be associated with retinopathy and neuropathy, but more research is needed to verify this association. The etiopathogenesis is unknown and the disorder does not seem to predispose to breast carcinoma or lymphoma.


Assuntos
Complicações do Diabetes , Linfócitos/patologia , Mastite/etiologia , Adulto , Linfócitos B/patologia , Biópsia , Mama/patologia , Diabetes Mellitus Tipo 1/complicações , Neuropatias Diabéticas/complicações , Retinopatia Diabética/complicações , Feminino , Doença da Mama Fibrocística , Fibrose , Humanos , Mastite/patologia , Esclerose , Tireoidite Autoimune/complicações
9.
Diabetes Care ; 25(1): 121-6, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11772912

RESUMO

OBJECTIVE: To demonstrate the strong association of diabetic mastopathy or sclerosing lymphocytic lobulitis with type 1 diabetes mellitus by studying appropriate control groups and to describe risk factors and natural history of the disorder. RESEARCH DESIGN AND METHODS: This was a retrospective cross-sectional study of four groups of patients conducted at a setting tertiary care medical center. We examined benign breast biopsies (investigator masked to identity) from age-matched patients with types 1 and 2 diabetes, autoimmune thyroid disease, or none of the above disorders for sclerosing lymphocytic lobulitis. Several risk factors proposed for the disorder (age at diagnosis of benign breast disease, duration of diabetes, age at onset of diabetes, prevalence of retinopathy, neuropathy, nephropathy and cheiroarthropathy, glycemic control, parity, oral contraceptive use, menopausal status, or number of breast biopsies) were evaluated, and patients were contacted to describe the natural history of the disorder. RESULTS: Sclerosing lymphocytic lobulitis was identified in 69.7% of the subjects with type 1 diabetes and 1.8% of those with autoimmune thyroid disease diagnosed with benign breast disease at surgery. It did not occur in patients with type 2 diabetes with or without insulin treatment or in control subjects. Only retinopathy and peripheral neuropathy were associated with sclerosing lymphocytic lobulitis. Breast carcinoma or lymphoma did not occur subsequently in any type 1 diabetes patient with or without sclerosing lymphocytic lobulitis. CONCLUSIONS: Sclerosing lymphocytic lobulitis is strongly associated with type 1 diabetes. Retinopathy and neuropathy are associated with the disorder. The risk of malignancy is not increased.


Assuntos
Doenças Mamárias/complicações , Diabetes Mellitus Tipo 1/complicações , Adulto , Idade de Início , Linfócitos B/patologia , Doenças Mamárias/sangue , Doenças Mamárias/patologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/análise , Humanos , Linfócitos/patologia , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Fatores de Risco , Tireoidite Autoimune/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...