RESUMO
Small ubiquitin-like modifier (SUMO) is a family of proteins structurally similar to ubiquitin that have been found to be covalently attached to certain lysine residues of specific target proteins. By contrast to ubiquitination, however, SUMO proteins do not promote protein degradation but, instead, modulate important functional properties, depending on the protein substrate. These properties include--albeit not limited to--subcellular localization, protein dimerization, DNA binding and/or transactivation of transcription factors, among them estrogen receptors. Moreover, it has been suggested that SUMO proteins might affect transcriptional co-factor complexes of the estrogen receptor signalling cascade. Tissue and/or state specificity seems to be one of their intriguing features. In this regard, elucidation of their contribution to estrogen receptor-mediated transcriptional activity during breast carcinogenesis will offer new insights into the molecular mechanisms governing sensitivity/resistance in currently applied endocrine treatment and/or chemoprevention, and provide novel routes to breast carcinoma therapeutics.
Assuntos
Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Animais , Moduladores de Receptor Estrogênico/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Biológicos , Processamento de Proteína Pós-Traducional , Estrutura Terciária de Proteína , Transcrição Gênica , Ativação TranscricionalRESUMO
Breast cancer is the most common cancer in women and the ErbB receptor family holds crucial role in its pathogenesis. Among them, epidermal growth factor receptor and HER-2 are the most studied members and their overexpression has been associated with aggressive clinical behaviour. These data were further strengthened by the clinical success of trastuzumab, a monoclonal antibody against HER-2 in breast cancer patients with HER-2 overexpression and/or amplification. However, trastuzumab failure in some patients may partly be attributed to co-expression of other ErbB receptors. Herein, we provide updated views regarding the role of HER-3 and HER-4 in breast cancer. Accumulated evidence implies that these receptors should be considered more than heterodimerisation partners. Their expression profile might be useful in predicting responsiveness to current treatment options, while new strategies targeting their ligands and downstream effectors are being developed.
Assuntos
Neoplasias da Mama/metabolismo , Receptores ErbB/metabolismo , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptores ErbB/fisiologia , Feminino , Humanos , Modelos Biológicos , Receptor ErbB-2/imunologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/fisiologia , Receptor ErbB-4 , TrastuzumabRESUMO
Malignant-appearing microcalcifications (MAMCs) represent one of the earliest mammographic findings of non-palpable breast carcinomas (NPBCs). In the present study, we have evaluated the expression of all EGFR family members in NPBCs and its possible association with MAMCs. Three hundred and fifty patients with non-palpable suspicious breast lesions detected during screening mammography were studied. EGFR family proteins' expression was found to be present since the preclinical phase of breast carcinomas and was strongly correlated (except HER-3) with MAMCs. The co-expression pattern of EGFR family members combined with other molecular prognostic factors and the mammographic appearance might predict the natural history of NPBCs.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Calcinose/diagnóstico por imagem , Calcinose/metabolismo , Receptores ErbB/metabolismo , Mamografia , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Calcinose/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Invasividade Neoplásica , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Receptor ErbB-4RESUMO
Pulmonary Langerhans' cell histiocytosis (LCH) represents an uncommon clinical disorder with unpredictable clinical presentation and outcome. Lung involvement may occur either in isolation or as part of a multiorgan disease. A 43-year-old woman was admitted to our hospital with acute left chest pain and shortness of breath. Spontaneous left pneumothorax was detected. All laboratory tests, including pulmonary function studies, were normal. Radiological findings posed high suspicion for LCH and lung biopsy confirmed this diagnosis. Further studies identified small cystic lesions in the scalp and liver. The diagnosis of multiple organ LCH involvement was made. Spontaneous pneumothorax might be the presenting clinical symptom of LCH. The present case emphasizes the capricious nature of LCH and the importance of an individualized therapeutic approach.
RESUMO
Screening mammography has greatly increased the number of non-palpable breast carcinomas diagnosed in asymptomatic women. Malignant-appearing microcalcifications represent one of the earliest mammographic findings of non-palpable breast carcinomas. Many studies have attempted to correlate radiological and histological features of malignant-appearing microcalcifications. In the present study, we evaluated the association between mammographically detected malignant-appearing microcalcifications and the expression profile of selected biological markers in non-palpable breast carcinomas. Two hundred and eighty patients with non-palpable suspicious breast lesions that were detected during screening mammography were studied. All patients underwent mammographically-guided needle localization-excision breast biopsy. Histological examination showed 74 (26.4%) carcinomas of various subtypes. Immunohistochemistry was carried out in 58/74 carcinomas by using a panel of monoclonal and polyclonal antibodies against estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, Bcl-2, Bax, Fas and DNA fragmentation factor (DFF). Malignant-appearing microcalcifications was the major mammographic finding in 45/58 (77%) patients. Nuclear ER positivity (65.5%) and PR positivity (46.5%) of non-palpable breast carcinomas were statistically correlated with malignant-appearing microcalcifications (p < 0.01 and p < 0.05, respectively). Statistically significant associations were also found between malignant-appearing microcalcifications and HER-2/neu positivity (p < 0.01), Bax positivity (p < 0.01), Fas positivity (p < 0.05) and DFF positivity (p < 0.01), whereas no statistical correlation was found with Bcl-2 positivity (p > 0.05). Malignant-appearing microcalcifications detected during screening mammography represent a diagnostic, prognostic and therapeutic challenge. The mammographic/biological associations and their potential implications in the management of women with non-palpable breast carcinomas are thoroughly discussed.
Assuntos
Doenças Mamárias/metabolismo , Neoplasias da Mama/metabolismo , Calcinose/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Mamografia , Adulto , Idoso , Proteínas Reguladoras de Apoptose , Biópsia , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Calcinose/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteínas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Proteína X Associada a bcl-2 , Receptor fas/metabolismoRESUMO
In this article, we describe a case of colonic ischemia masquerading as colonic carcinoma in a 75-yr-old female. Although this clinical diagnostic problem has been described before, it is rather unusual that the clinical, roentgenographical, endoscopic, and even histopathologic evaluation could not exclude carcinoma with certainty.