Role of the Transcriptional Corepressor Bcor in Embryonic Stem Cell Differentiation and Early Embryonic Development

Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG) proteins, Skp-Cullin-F-box (SCF) ubiquitin ligase components and a Jumonji C (Jmjc) domain containing histone demethylase. To model OFCD in mice and dissect the role of Bcor in development we have characterized two loss of function Bcor alleles. We find that Bcor loss of function results in a strong parent-of-origin effect, most likely indicating a requirement for Bcor in extraembryonic development. Using Bcor loss of function embryonic stem (ES) cells and in vitro differentiation assays, we demonstrate that Bcor plays a role in the regulation of gene expression very early in the differentiation of ES cells into ectoderm, mesoderm and downstream hematopoietic lineages. Normal expression of affected genes (Oct3/4, Nanog, Fgf5, Bmp4, Brachyury and Flk1) is restored upon re-expression of Bcor. Consistent with these ES cell results, chimeric animals generated with the same loss of function Bcor alleles show a low contribution to B and T cells and erythrocytes and have kinked and shortened tails, consistent with reduced Brachyury expression. Together these results suggest that Bcor plays a role in differentiation of multiple tissue lineages during early embryonic development

Screening for lung cancer

The large clinical studies of lung cancer screening carried out more than 20 years ago were interpreted as evidence against screening. Those studies have been recently reassessed in the light of methodologic flaws in the randomization of subjects at risk for lung cancer. There is no evidence to support the former conclusion that screening is ineffective and the consequent official recommendation not to screen for lung cancer. The hypothesis of overdiagnosis of lung cancers diagnosed by screening is false. Clinical evidence supports the concept that the current dogma against screening for lung cancer is untrue. Indeed, the 5-year survival rate of patients with NSCLC detected in stage I and radically resected ranges from 60% to 80%. This rate is in sharp contrast to the 10% survival rate of stage I NSCLC not resected. About 90% of lung cancer cases are detected among smokers and former smokers; these well-known at-risk subjects should be offered a screening test with the goal of detecting the disease when it is in stage I. It is expected that the techniques for early detection of lung cancer will be refined and become more sensitive in the near future, so that it will be possible to detect an increasingly large proportion of lung cancers when they are truly in stage I (i.e., nonmetastatic) and curable by radical surgical resection. Low-dose helical CT scan is currently believed to represent a very useful technique for screening for lung cancer, with a higher sensitivity than chest radiograph screening. Chest radiography for lung cancer screening, however, is cheaper and ubiquitously available, and it should still be recommended if CT scan is locally unavailable. As underscored in a recent commentary in The Lancet, the existing public health policy discouraging the screening for lung cancer is in urgent need of reconsideration

The nutritional risk in oncology: a study of 1,453 cancer outpatients

There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists. We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1-3 points, respectively). A score a parts per thousand yen3 indicates "nutritional risk". The association of the nutritional scores with some patient/tumour/therapy-related variables was investigated through univariable and multivariable linear regression models. Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk. The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support