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1.
Clin Cancer Res ; 10(22): 7466-74, 2004 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-15569976

RESUMO

PURPOSE: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome. EXPERIMENTAL DESIGN: T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series. RESULTS: Infiltration by immature CD207/Langerin+ DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients. CONCLUSIONS: Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Células Dendríticas/citologia , Células Dendríticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Antígenos de Superfície/biossíntese , Complexo CD3/biossíntese , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Subunidade alfa de Receptor de Interleucina-3 , Lectinas Tipo C/biossíntese , Metástase Linfática , Lectinas de Ligação a Manose/biossíntese , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptores de Quimiocinas/biossíntese , Receptores de Interleucina-3/biossíntese , Recidiva , Linfócitos T/citologia , Fatores de Tempo , Resultado do Tratamento
2.
Eur J Immunol ; 33(9): 2619-29, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12938238

RESUMO

DC-LAMP, a member of the lysosomal-associated membrane protein (LAMP) family, is specifically expressed by human dendritic cells (DC) upon activation and therefore serves as marker of human DC maturation. DC-LAMP is detected first in activated human DC within MHC class II molecules-containing compartments just before the translocation of MHC class II-peptide complexes to the cell surface, suggesting a possible involvement in this process. The present study describes the cloning and characterization of mouse DC-LAMP, whose predicted protein sequence is over 50% identical to the human counterpart. The mouse DC-LAMP gene spans over 25 kb and shares syntenic chromosomal localization (16B2-B4 and 3q26) and conserved organization with the human DC-LAMP gene. Analysis of mouse DC-LAMP mRNA and protein revealed the expression in lung peripheral cells, but also its unexpected absence from mouse lymphoid organs and from mouse DC activated either in vitro or in vivo. In conclusion, mouse DC-LAMP is not a marker of mature mouse DC and this observation raises new questions regarding the role of human DC-LAMP in human DC.


Assuntos
Antígenos CD/genética , Clonagem Molecular , Células Dendríticas/metabolismo , Animais , Antígenos CD/metabolismo , Sequência de Bases , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Humanos , Pulmão/metabolismo , Proteínas de Membrana Lisossomal , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos/fisiologia , Filogenia , RNA Mensageiro/metabolismo , Alinhamento de Sequência
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