Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

Salmonella Strains Isolated from Galápagos Iguanas Show Spatial Structuring of Serovar and Genomic Diversity

It is thought that dispersal limitation primarily structures host-associated bacterial populations because host distributions inherently limit transmission opportunities. However, enteric bacteria may disperse great distances during food-borne outbreaks. It is unclear if such rapid long-distance dispersal events happen regularly in natural systems or if these events represent an anthropogenic exception. We characterized Salmonella enterica isolates from the feces of free-living Galápagos land and marine iguanas from five sites on four islands using serotyping and genomic fingerprinting. Each site hosted unique and nearly exclusive serovar assemblages. Genomic fingerprint analysis offered a more complex model of S. enterica biogeography, with evidence of both unique strain pools and of spatial population structuring along a geographic gradient. These findings suggest that even relatively generalist enteric bacteria may be strongly dispersal limited in a natural system with strong barriers, such as oceanic divides. Yet, these differing results seen on two typing methods also suggests that genomic variation is less dispersal limited, allowing for different ecological processes to shape biogeographical patterns of the core and flexible portions of this bacterial species' genome

The Airway Microbiota in Cystic Fibrosis: A Complex Fungal and Bacterial Community—Implications for Therapeutic Management

International audienceBackground Given the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways. Methodology and Principal Findings Fungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients. Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values). Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus

Biogeography of bacterial communities exposed to progressive long-term environmental change

12 pages, 5 figuresThe response of microbial communities to long-term environmental change is poorly understood. Here, we study bacterioplankton communities in a unique system of coastal Antarctic lakes that were exposed to progressive long-term environmental change, using 454 pyrosequencing of the 16S rDNA gene (V3-V4 regions). At the time of formation, most of the studied lakes harbored marine-coastal microbial communities, as they were connected to the sea. During the past 20 000 years, most lakes isolated from the sea, and subsequently they experienced a gradual, but strong, salinity change that eventually developed into a gradient ranging from freshwater (salinity 0) to hypersaline (salinity 100). Our results indicated that present bacterioplankton community composition was strongly correlated with salinity and weakly correlated with geographical distance between lakes. A few abundant taxa were shared between some lakes and coastal marine communities. Nevertheless, lakes contained a large number of taxa that were not detected in the adjacent sea. Abundant and rare taxa within saline communities presented similar biogeography, suggesting that these groups have comparable environmental sensitivity. Habitat specialists and generalists were detected among abundant and rare taxa, with specialists being relatively more abundant at the extremes of the salinity gradient. Altogether, progressive long-term salinity change appears to have promoted the diversification of bacterioplankton communities by modifying the composition of ancestral communities and by allowing the establishment of new taxa.© 2013 International Society for Microbial Ecology All rights reservedFinancial support for this work was provided by the Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning (FORMAS) via Uppsala Microbiomics Centre (UMC) (granted to SB and LT), the Swedish Research Council (granted individually to SB, ESL and KR), the Marie Curie Intra-European Fellowship (PIEFGA-2009-235365, EU) and Juan de la Cierva fellowship (JCI- 2010-06594, Ministry of Science and Innovation, Spain) (granted to RL), the Australian Antarctic Research Assessment Committee (granted to JL-P and KR), FORMAS (granted to SL) and the Olsson-Borghs and Helge Ax:son Johnsons Foundation (granted to JBL)Peer Reviewe

The Potential Energy of a Pair of Polystyrene Spheres in Alternating Electric Fields

The drastic change in the viscosity of electrorheological (ER) fluids when an external electric field is applied has intrigued scientists from many different fields including engineering, chemistry, and physics for over half a century. It has been generally understood that the microscopic attractive forces between induced dipole moments of the suspended particles have important effects on macroscopic fluid properties. Great effort has been given recently to maximizing the strength of the attractive forces between the particles in ER fluids to achieve practical fluids, and important progress has been made. In the preliminary work presented here, we focus on trying to understand the strength of the microscopic interactions between colloidal particles in alternating electric fields. The system used is a model system of aqueous suspensions of monodisperse polystyrene spheres. By using digital microscopy techniques to measure the inter-particle separations between two spheres at thousands of different times and at several different field strengths, we have been able to determine the probability density function P(r) for the separation distance r between the two particle centers. We begin this paper with a theoretical discussion in which the contributions of electrostatic repulsion, electric-field-induced dipole interaction, and van der Waals attraction to the pair potential are first considered. A probability density function for the distance between a pair of particles is then obtained from the pair potential using equilibrium statistical mechanics. The theoretical discussion is followed by a detailed description of the experimental apparatus - one that allows us to isolate pairs of polystyrene spheres in an essentially two-dimensional geometry by restricting the particles to a narrow gap between parallel glass plates. Finally, we examine the results of our experiments and compare our findings with theoretical predictions