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2.
Histopathology ; 57(5): 716-24, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21083601

RESUMO

AIMS: Chromatin assembly factor-1 (CAF-1), whose function is critical for maintaining chromatin stability during DNA replication and repair, has been identified as a proliferation marker in breast cancer. The aim was to investigate CAF-1 as a proliferation marker in a wide variety of solid tumours, and to assess its potential value in predicting clinical outcome. METHODS AND RESULTS: Using immunocytochemistry on paraffin-embedded tissue sections, the CAF-1 labelling index was compared with known proliferation markers Ki-67 and minichromosome maintenance (MCM), and its association with clinicopathological data and patients' outcome analysed. CAF-1 expression showed a strong positive correlation with Ki-67, used routinely to detect proliferating cells, while it generally displayed weaker correlations with MCM markers, known to label cells with replicative potential. CAF-1 expression was associated significantly with histological grade in breast, cervical, endometrial and renal cell carcinomas, and with disease stage in endometrial and renal carcinomas. Furthermore, high expression of CAF-1 was an independent predictor of adverse clinical outcome in renal, endometrial and cervical carcinomas. CONCLUSIONS: CAF-1 is a proliferation marker in various malignant tumours with prognostic value in renal, endometrial and cervical carcinomas, which supports the value of CAF-1 as a clinical marker of cancer progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Fator 1 de Modelagem da Cromatina/metabolismo , Idoso , Proliferação de Células , Fator 1 de Modelagem da Cromatina/genética , Replicação do DNA , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína 1 de Manutenção de Minicromossomo/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico
3.
J Allergy Clin Immunol ; 126(3): 602-10.e1-11, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20673987

RESUMO

BACKGROUND: Hematopoietic stem cell transplantation remains the only treatment for most patients with severe combined immunodeficiencies (SCIDs) or other primary immunodeficiencies (non-SCID PIDs). OBJECTIVE: To analyze the long-term outcome of patients with SCID and non-SCID PID from European centers treated between 1968 and 2005. METHODS: The product-limit method estimated cumulative survival; the log-rank test compared survival between groups. A Cox proportional-hazard model evaluated the impact of independent predictors on patient survival. RESULTS: In patients with SCID, survival with genoidentical donors (n = 25) from 2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005). Transplantation after year 1995, a younger age, B(+) phenotype, genoidentical and phenoidentical donors, absence of respiratory impairment, or viral infection before transplantation were associated with better prognosis on multivariate analysis. For non-SCID PID, in contrast with patients with SCID, we confirm that, in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival was 76% in phenoidentical transplants (n = 23) and worse in mismatched related donor transplants (n = 47; 46%; P = .016). CONCLUSION: This is the largest cohort study of such patients with the longest follow-up. Specific issues arise for different patient groups. Patients with B-SCID have worse survival than other patients with SCID, despite improvements in each group. For non-SCID PID, survival is worse than SCID, although more conditions are now treated. Individual disease categories now need to be analyzed so that disease-specific prognosis may be better understood and the best treatments planned.


Assuntos
Transplante de Células-Tronco Hematopoéticas/normas , Imunodeficiência Combinada Severa/terapia , Criança , Pré-Escolar , Europa (Continente) , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , História do Século XX , História do Século XXI , Humanos , Análise Multivariada , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
4.
J Immunol ; 184(9): 4907-17, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20368277

RESUMO

Progressive restriction to a differentiation pathway results from both activation and silencing of particular gene expression programs. To identify the coexpression and the expression levels of regulatory genes during hematopoietic stem cell (HSC) differentiation toward the T cell branch, we applied a new single-cell RT-PCR technique to analyze the simultaneous expression of 13 genes in 9 functionally purified populations from the bone marrow and the thymus. We report in this paper that Lin(-)Sca1(+)ckit(+) HSCs display, at the single-cell level, a homogeneous and high transcriptional activity as do early thymic progenitors. Moreover, the coexpression of lymphoid and myeloid genes is an early event detected in approximately 30% of short-term HSC and most multipotent progenitors, suggesting novel sources for the generation of early thymic progenitors, common lymphoid progenitors (CLPs), and common myeloid progenitors. Loss of multipotency in Lin(-)Sca1(+)ckit(+) cells directed to the lymphoid branch is characterized by Lmo2 and Gata2 gene expression downregulation. Indeed, highest levels of Gata2 expression are detected only in long-term and short-term HSC populations. Complete shutdown of Pu1 gene expression in all triple-negative (TN)3 stage thymic pre-T cells is indicative of total T cell commitment. Interestingly, this is also observed in 30% of TN2 cells and 25% of CLP in the bone marrow, suggesting a possible initiation of T cell engagement in TN2 and CLP. Also, our strategy highlights similar gene patterns among HSCs and intrathymic progenitors, proposing, therefore, that identical activation signals are maintained until further maturation and generation of CD4 and CD8 coreceptors bearing thymocytes.


Assuntos
Diferenciação Celular/genética , Diferenciação Celular/imunologia , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Células-Tronco Hematopoéticas/imunologia , Subpopulações de Linfócitos/imunologia , Células-Tronco Multipotentes/imunologia , Células Mieloides/imunologia , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Feminino , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Subpopulações de Linfócitos/citologia , Subpopulações de Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Células Mieloides/citologia , Células Mieloides/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Timo/citologia , Timo/imunologia , Timo/metabolismo
5.
Anticancer Res ; 29(5): 1475-82, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19443353

RESUMO

UNLABELLED: This retrospective analysis was designed to confirm the predictive role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type I (PAI-1) in the outcome of early stage, node-negative breast cancer patients. PATIENTS AND METHODS: Node-negative patients having not received adjuvant chemotherapy, and for whom frozen samples were available, were selected. RESULTS: Among the 169 patients included, 56.8% presented with uPA >3 ng/mg of proteins and/or PAI-1 >14 ng/mg of proteins. The median follow-up was 73 months. Significant correlations were found between uPA and disease-free survival (p [univariate]=0.003; p [multivariate]=0.01), and between uPA, PAI-1, and uPA plus PAI-1 and distant relapses (p=0.002). No significant correlation was found between uPA/PAI-1 and the risk of locoregional recurrence. CONCLUSION: This study demonstrated that uPA and PAI-1 are useful predictors of distant metastases in a subset of early stage, node-negative breast cancer patients.


Assuntos
Neoplasias da Mama/metabolismo , Metástase Neoplásica , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
6.
Pediatr Nephrol ; 23(4): 575-80, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18204939

RESUMO

Many children with steroid-dependent nephrotic syndrome (NS) have significant sequelae despite steroid-sparing therapies. Levamisole may reduce short-term relapse frequency (RF) with minimal side effects. Little data exist, however, as to its long-term effect. To assess both short- and long-term efficacy in NS, RF and cumulative annual steroid burden were quantified in ten consecutive children with steroid-dependent NS treated with levamisole. Data were analyzed for three time periods: 1 year prior to levamisole therapy (Pre-Lev), during 1 year of levamisole therapy (During-Lev), and the year after cessation of all levamisole therapy (Off-Lev). Median RF fell from 6.0 (4.0-9.0) relapses/patient per year Pre-Lev to 0.0 (0.0-4.0) During-Lev (p = 0.002) with 6/10 patients having no relapse and 0.5 (0.0-8.0) Off-Lev (p = 0.01) with 5/10 patients without relapse. Concurrently, cumulative annual steroid burden fell from 6,067 (1,660-8,691) mg/m(2) per year Pre-Lev to 2,920 (782-5,271) During-Lev (p = 0.002) and 716 (0-3,637) Off-Lev (p = 0.002). In 4/5 hypertensive children, blood pressure normalized During-Lev. Somatic indices also improved: height Z scores, which fell from 0.8 (-2.4 to 3.6) at diagnosis to -0.6 (-2.7 to 0.4) Pre-Lev (p = 0.004), remained stable at -0.6 (-3.0 to 0.6) after 1 year of therapy and -0.5 (-2.6 to 0.2) Off-Lev. Height velocity improved from 3.0 (0.3-6.0) cm/year Pre-Lev to 3.7 (0.0-8.0) cm/year During-Lev and 5.4 (0.0-9.1) Off-Lev. We conclude that levamisole is an effective short- and long-term steroid-sparing agent in pediatric NS.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Levamisol/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Síndrome Nefrótica/sangue , Indução de Remissão , Estudos Retrospectivos , Prevenção Secundária , Resultado do Tratamento
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