A 50-gene signature is a novel scoring system for tumor-infiltrating immune cells with strong correlation with clinical outcome of stage I/II non-small cell lung cancer

Purpose: To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC). Methods/patients: Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed. Results: Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p < 0.0001) and CD20 (p < 0.05) were predictors for RFS, while CD79 and K-RAS mutations showed a tendency. Conclusions: Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies (AU)

No disponible

Significado pronóstico de la densidad microvascular en el cáncer de ovario: estudio de una serie de 74 casos / Prognostic value of microvascular density in ovarian cancer in a series of 74 patients

Introducción: La cuantificación de la angiogénesis, en teoría, podría ser un factor determinante del pronóstico de ciertos carcinomas, ya que determina la posibilidad de metastatizar por parte del tumor primario. Material y métodos: Se plantea un estudio retrospectivo sobre 74 pacientes con carcinoma de ovario en estadios I-IV (FIGO) y tratados en el Hospital Clínico San Carlos (Madrid) en el período 1985-1995. Se midió el índice angiogénico (determinación con anticuerpo monoclonal CD34, y cuantificación mediante un sistema digital de análisis de imagen Leika Q500IW con software propio), y se comparó el comportamiento de tumores con angiogénesis positiva y negativa en relación con los eventos de muerte y recidiva (estudio de regresión logística). El seguimiento mediano fue de 40,5 meses (rango, 3-105). Resultados: La angiogénesis es un parámetro cuantificable, y es un factor pronóstico independiente para el riesgo relativo de muerte y recidiva para todos los estadios de carcinoma de ovario (AU)

Effect of the growth conditions on the synthesis of a recombinant beta-1,4-endoglucanase in continuous and fed-batch culture.

Continuous culture and fed-batch fermentations were used to test the behavior of the system Bacillus subtilis DN1885(pCH7) that synthesizes a recombinant beta-1,4-endoglucanase. Continuous culture experiments were focused on the study of the instability aspects of the system as well as determination of the biomass growth rate range at which the recombinant enzyme synthesis was improved. Fed-batch fermentations were carried out to study the possibility of enhancing recombinant enzyme synthesis through the control of medium addition. It was found that, in continuous culture fermentations, the culture is less unstable at low dilution rates (dilution rate < 0.1 h(-)(1)). Also, low dilution rates give a higher specific recombinant enzyme concentration (10 times more than that obtained at high dilution rates). In fed-batch fermentation, the final recombinant enzyme concentration can be manipulated through the medium addition strategy. To increase the recombinant enzyme concentration, the carbon source has to be fed slowly, otherwise enzyme synthesis is impaired due to catabolite repression. Therefore, an increase in the biomass concentration does not necessarily imply an increase in the recombinant enzyme concentration. Higher recombinant enzyme concentrations were found in fed-batch fermentations compared to those obtained in continuous culture.