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1.
Int J Immunopathol Pharmacol ; 23(1): 307-16, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20378017

RESUMO

Thymomas are rare tumours that sustain T-lymphopoiesis and trigger a variety of autoimmune diseases and immunodeficiencies, including a fatal hypogammaglobulinemia, namely Goods Syndrome (GS). Due to its rarity, GS has been poorly investigated and immunological features, as well as pathogenetic mechanisms underlying this syndrome, are unclear. We studied 30 thymoma patients by performing an immunological assessment, including immunophenotype and analysis of T cell repertoire (TCR). Development of GS was characterized by a progressive decrease in B, CD4 T and NK lymphocytes. These alterations paired with accumulation of CD8+CD45RA+ T cells that showed a polyclonal repertoire without expansions of specific clonotypes. GS is defined as hypogammaglobulinemia with thymoma. Here, we show for the first time that this syndrome is characterized by a severe loss of CD4+, NK and B cells. Furthermore, the accumulation of CD8+CD45RA+ T lymphocytes parallels these changes; this accumulation may have a role in determining the disease and can be used to monitor clinical stages of immunodeficiency in thymoma.


Assuntos
Agamaglobulinemia/imunologia , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Matadoras Naturais/imunologia , Timoma/imunologia , Neoplasias do Timo/imunologia , Adulto , Idoso , Regiões Determinantes de Complementaridade , Feminino , Seguimentos , Humanos , Antígenos Comuns de Leucócito/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
2.
Oncogene ; 26(30): 4372-82, 2007 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-17237817

RESUMO

The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNA-damaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68(GSG) protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas de Ligação a DNA/fisiologia , Neoplasias da Próstata/patologia , Proteínas de Ligação a RNA/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética
3.
Cell Death Differ ; 11(11): 1179-91, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15257302

RESUMO

Deficiency of the apoptosome component Apaf1 leads to accumulation of supernumerary brain cells in mouse embryos. We observed that neural precursor cells (NPCs) in Apaf1(-/-) embryos escape programmed cell death, proliferate and retain their potential to differentiate. To evaluate the circumstances of Apaf1(-/-) NPC survival and investigate their fate under neurodegenerative conditions, we established cell lines of embryonic origin (ETNA). We found that Apaf1(-/-) NPCs resist common apoptotic stimuli and neurodegenerative inducers such as amyloid-beta peptide (typical of Alzheimer's disease) and mutant G93A superoxide dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results were obtained in Apaf1(-/-) primary cells. When death is prevented by Apaf1 deficiency, cytochrome c is released from mitochondria and rapidly degraded by the proteasome, but mitochondria remain intact. Under these conditions, neither activation by cleavage of initiator caspases nor release of alternative apoptotic inducers from mitochondria takes place. In addition, NPCs can still differentiate, as revealed by neurite outgrowth and expression of differentiation markers. Our findings imply that the mitochondrion/apoptosome pathway is the main route of proneural and neural cells to death and that its inhibition prevents them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell model is ideally suited for exploring the potential of novel cell therapies for the treatment of human neurodegenerations.


Assuntos
Apoptose , Degeneração Neural , Neurônios/patologia , Proteínas/fisiologia , Peptídeos beta-Amiloides/química , Animais , Fator Apoptótico 1 Ativador de Proteases , Western Blotting , Bromodesoxiuridina/farmacologia , Caspases/metabolismo , Morte Celular , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Imuno-Histoquímica , Imunoprecipitação , Potenciais da Membrana , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Neurodegenerativas , Fragmentos de Peptídeos/química , Plasmídeos/metabolismo , Fatores de Tempo , Transgenes
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