Assuntos
Fístula Pancreática/complicações , Fístula Pancreática/diagnóstico por imagem , Doenças Pleurais/complicações , Doenças Pleurais/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Fístula do Sistema Respiratório/complicações , Fístula do Sistema Respiratório/diagnóstico por imagem , Alcoolismo/complicações , Colangiopancreatografia Retrógrada Endoscópica , Drenagem , Humanos , Pessoa de Meia-Idade , Pancreatite Crônica/etiologia , Derrame Pleural/terapia , Radiografia Torácica , Índice de Gravidade de DoençaAssuntos
Carcinoma Papilar/patologia , Imunoglobulina G/química , Hormônio Luteinizante/sangue , Distúrbios Menstruais/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Carcinoma Papilar/sangue , Carcinoma Papilar/complicações , Feminino , Humanos , Hormônio Luteinizante/química , Distúrbios Menstruais/sangue , Distúrbios Menstruais/complicações , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/complicaçõesRESUMO
BACKGROUND: Several recent studies have reported on the overexpression of human epidermal growth factor receptor (HER)2 in extramammary Paget disease (EMPD). However, there are only a few cases in which both overexpression and gene amplification of HER2 have been examined. OBJECTIVES: To evaluate the overexpression and gene amplification of HER2 using a standardized method with a large number of cases of EMPD. METHODS: Immunohistochemically, the overexpression of the HER2 protein was examined in 104 cases of EMPD, including 31 intraepithelial cases and 73 invasive cases (35 superficially invasive and 38 deeply invasive). When the HER2 protein was overexpressed or potentially overexpressed, further analysis of amplification of the gene encoding HER2, ERBB2, was undertaken using fluorescence in situ hybridization. RESULTS: The HER2 protein was overexpressed in 16 cases (15%) in total, and in 13 of 73 cases (18%) of invasive EMPD. The ERBB2 gene was amplified in all cases with a HER2 score of 3+. A HER2 score of 3+ or 2+, and ERBB2 amplification were significantly more frequent in the cases of deeply invasive EMPD than in intraepithelial/superficially invasive EMPD (24% vs. 6%/3%, P=0·012) and were correlated with a larger number of lymph-node metastases (P=0·047). Log-rank tests for survival curves showed that lymph-node metastasis and ERBB2 amplification were significant prognostic factors (P=0·0001 and P=0·043, respectively). However, by a multivariate analysis, only lymph-node status was a significant indicator of Paget-disease-specific survival (P=0·0001). CONCLUSIONS: A subset of EMPD, both intraepithelial and invasive, showed HER2 overexpression and gene amplification. These HER2 alterations were correlated with biologically aggressive EMPDs, i.e. those with deep invasion and lymph-node metastasis. Clinical trials of HER2-targeted therapy are awaited for improvement of the prognosis of patients with aggressive EMPD.
Assuntos
Amplificação de Genes , Regulação da Expressão Gênica/fisiologia , Genes erbB-2/genética , Doença de Paget Extramamária/genética , Receptor ErbB-2/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Amplificação de Genes/genética , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença de Paget Extramamária/imunologia , Receptor ErbB-2/imunologia , Índice de Gravidade de Doença , Neoplasias Cutâneas/imunologiaAssuntos
Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Masculinos/diagnóstico , Doença de Paget Extramamária/diagnóstico , Biópsia de Linfonodo Sentinela/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Metástase Linfática/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoAssuntos
Nervo Facial/fisiopatologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Nervo Facial/cirurgia , Feminino , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/fisiopatologiaRESUMO
Heavy metal-dependent transcriptional activation of metallothionein (MT) genes is mediated by multiple enhancer sequences, metal responsive element (MRE), located in the upstream region of the genes. Previously, we have reported purification of a zinc-dependent MRE-binding protein, zinc regulatory factor (ZRF), from HeLa cells, and have pointed to the close relationship between ZRF and mouse MRE-binding transcription factor-1 (MTF-1) according to the analysis of partial amino acid sequences. By means of cDNA cloning and the product analyses, we show that ZRF is a variant of human MTF-1 (hMTF-1), which carries a single amino acid exchange in the zinc finger domain. Accordingly, ZRF is renamed hMTF-1b. Expression of hMTF-1b in HeLa cells is constitutive at both mRNA and protein levels, and is unaffected by treatment with cadmium (Cd). On the other hand, when cells were fractionated into nuclear extract and cytosol, a large part of the hMTF-1b was recovered in the cytosol fraction. A significant increase in the amount of nuclear hMTF-1b occurs when cells are treated with various heavy metals, including Cd, Zn, Cu and Ag, which is associated with concomitant decrease in the amount recovered in the cytosol fraction. Since immunocytochemical analysis revealed that intracellular distribution of hMTF-1b is restricted to the nucleus irrespective of the heavy metal treatment, such an increment in the nuclear extracts apparently results from promotion of nuclear retention of hMTF-1b by the heavy metal treatment. Analysis by native gel electrophoresis shows that the mobility of hMTF-1b significantly changes in association with Cd treatment, raising the possibility that a conformational change of hMTF-1b occurs in response to treatment with heavy metals in vivo.
Assuntos
Metais Pesados/farmacologia , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência de Bases , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Clonagem Molecular , DNA Complementar/análise , Proteínas de Ligação a DNA , Eletroforese em Gel Bidimensional , Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Conformação Proteica , Frações Subcelulares , Fatores de Transcrição/química , Fator MTF-1 de TranscriçãoRESUMO
From cultured human keratinocytes, seven glycolipid fractions were isolated by DEAE and silica-gel column chromatographies, and further by HPLC on a silica-gel column. By means of 1H-NMR spectroscopy, fast atom bombardment mass spectrometry and GLC-mass spectrometry, one fraction was determined to contain acylglucosylceramides, which consist of amide linked omega-hydroxy fatty acids (C30:0, C30:1, C32:1 and C34:1), fatty acids linked to the omega-hydroxy fatty acids through ester linkages (C14:1, C16:1, C18:1 and C18:2), a long-chain base (d18-sphingenine), and beta-glucose. Five of the other fractions contained glucosylceramides, and the seventh fraction contained a mixture of glucosylceramides and galactosylceramides. Glucosylceramides containing long-chain omega-hydroxy fatty acids, which are assumed to be immediate precursors of the acylglucosylceramides, were hardly detected in these glycolipid fractions. Six glucosylceramide fractions were separated due to differences in their fatty acids and sphingosines. On comparison with the results reported in our previous paper, the acylglucosylceramide content of the cultured human keratinocytes was about half that of human epidermis. Under the culture conditions used, the human keratinocytes did not differentiate into granular or horny cells. Taken together, the results suggest that the synthesis of acylglucosylceramides is not activated much in the cultured keratinocytes, but would be more activated in differentiated cells.
Assuntos
Glicoesfingolipídeos/química , Queratinócitos/química , Adulto , Diferenciação Celular , Células Cultivadas/química , Fracionamento Químico , Doença de Gaucher/metabolismo , Glicoesfingolipídeos/isolamento & purificação , Humanos , Masculino , Estrutura MolecularAssuntos
Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Couro Cabeludo , Neoplasias Cutâneas/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Biópsia , Docetaxel , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Hemangiossarcoma/secundário , Humanos , Linfonodos/patologia , Metástase Linfática , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
CASE HISTORY: A 30-year-old Japanese man who presented with recurrent ketoacidosis caused by IDDM was found to have increased secretion of growth hormone (GH). On initial cranial magnetic resonance imaging (MRI), no pituitary lesion was detected; however, a pituitary microadenoma was found 2 years later during a repeat MRI. In spite of the hypersecretion of GH, serum IGF-I was dramatically suppressed. Transsphenoidal surgery was performed to resect the pituitary tumor that was histologically an acidophilic pituitary adenoma. Although the GH excess rapidly improved postoperatively, the IGF-I level remained low. Subsequent insulin therapy initiated 1 year after the operation elevated the serum IGF-I level to within the normal range. DISCUSSION: The first case of coexistent IDDM and a GH-producing pituitary adenoma suggests that patients with uncontrolled IDDM may develop GH hypersecretion. Furthermore, the low IGF-I levels may be closely associated with the GH excess and with the development or progression of GH-secreting pituitary adenomas.
Assuntos
Adenoma/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Neoplasias Hipofisárias/diagnóstico , Adenoma/metabolismo , Adenoma/cirurgia , Adulto , Diabetes Mellitus Tipo 1/sangue , Hormônio do Crescimento Humano/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Japão , Imageamento por Ressonância Magnética , Masculino , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgiaRESUMO
Clinical evidence of malignant epithelial tumors developing on the lesions of porokeratosis has accumulated. To determine the cytologic basis for the malignant change of porokeratosis, the nuclear DNA content of epidermal cells from porokeratosis lesions was measured using microfluorometry. A total of 42% of 33 porokeratosis skin lesions in eight of the 16 patients showed DNA polyploidization in the epidermis. Most of the porokeratosis skin lesions, with or without DNA polyploidization, increased cell proportions in the S and G2/M phase range. These findings suggest that porokeratosis is undergoing the neoplastic process, and is the precursor skin manifestation of malignant tumors.