Rituximab for the treatment of acute exacerbation of interstitial lung disease associated with connective tissue disease.

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) is a severe complication with a poor prognosis. No clinical trials have supported the use of rituximab in AE-ILD associated with connective tissue disease. METHODS: We present a series of four cases in which administration of rituximab was associated with appropriate clinical, radiological and functional progress. RESULTS: The four patients were alive 30 days after discharge following their exacerbation. CONCLUSIONS: Given the speed of action, safety and efficacy profile observed for rituximab, we believe that this agent should be further investigated in clinical trials so that it could be included in the daily clinical management of this severe condition.

Assessment of Topoisomerase II α status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization.

Anthracyclines are frequently used for the treatment of breast cancer and topoisomerase II alpha (TOP2A) is considered to be the molecular target. Numerous studies have evaluated the predictive value of TOP2A using different methodological approaches and inconsistent results have been reported. Indeed, the correlation between techniques for the assessment of TOP2A status has not been well evaluated. In this study, we determined TOP2A status in 61 breast tumor samples by real-time PCR, DNA microarrays, immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH), and then evaluated these results with clinical-pathological features and breast cancer intrinsic subtypes. First, we observed a statistical significant correlation of TOP2A gene expression between real-time PCR and microarrays (Pearson coefficient, 0.816; P < 0.001), and both predicted TOP2A IHC results fairly well (area under the curve > 0.74). In contrast, poor agreement between FISH and IHC data was observed (k: 0.134). Secondly, TOP2A expression was found significantly associated with cell proliferation, and with the highly proliferative Luminal B, Her2-enriched and Basal-like intrinsic subtypes. In conclusion, TOP2A expression in breast cancer was associated with high proliferation and aggressive tumor subtypes and appears to be independent of its amplification status. All of these features should be taken into consideration when assessing the predictive value of TOP2A for anthracycline-based chemotherapy.

Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.

BACKGROUND: Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS: After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS: Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS: Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

Utilidad del PSA-Complex en el diagnóstico del carcinoma de próstata / Utility of complexed PSA in the diagnosis of carcinoma of the prostate

OBJETIVOS: Desde el hallazgo del antígeno prostático específico (PSA), como marcador del cáncer de próstata, han sido muchos los intentos de mejorar su eficacia diagnóstica. Uno de ellos ha sido el estudio del comportamiento de las diferentes formas plasmáticas de PSA en su unión a distintas antiproteasas, entre las que destaca la 1-antiquimiotripsina, con la que forma el PSA complex (PSA-c). El objetivo es estudiar la validez del PSA-c para aumentar la especificidad sin variar la sensibilidad, frente al uso del PSA total (PSA-t).MÉTODOS: Entre septiembre de 1998 y marzo de 1999 se tomaron muestras de sangre a 96 pacientes que fueron sometidos a biopsia prostática por sospecha de cáncer de próstata. En estos pacientes se determinó el PSA-c, PSAt (ambos realizados por el Sistema Technicon Immuno 1 de Bayer) y se calculó el PSA-c/PSA-t. RESULTADOS: Se calcularon las curvas ROC y se hallaron los puntos de corte óptimos, para los cuales, ante un valor de sensibilidad semejante (90 por ciento), la especifici dad resultó mayor en el PSA-c (44,6 por ciento [IC 95 por ciento, 32-57]) frente al PSA-t (35,4 por ciento [IC 95 por ciento, 25-49]), y la ratio PSAc/PSA-t (38,5 por ciento[IC 95 por ciento, 27-51]). Para otros valores de sensibilidad el comportamiento del PSA-c fue análogo. CONCLUSIÓN: el PSA-c mejora la especificidad frente al PSA-t y el PSA-c/PSA-t, por lo cual sería posible con su uso una reducción de biopsias innecesarias sin dejar de detectar el mismo número de cánceres de próstata (igual sensibilidad) (AU)