A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer

BACKGROUND: The detection of circulating tumour cells (CTCs) has been linked with poor prognosis in advanced breast cancer. Relatively few studies have been undertaken to study the clinical relevance of CTCs in early-stage breast cancer. METHODS: In a prospective study, we evaluated CTCs in the peripheral blood of 82 early-stage breast cancer patients. Control groups consisted of 16 advanced breast cancer patients and 45 healthy volunteers. The CTC detection was performed using ErbB2/EpCAM immunomagnetic tumour cell enrichment followed by multimarker quantitative PCR (QPCR). The CTC status and common clinicopathological factors were correlated to relapse-free, breast cancer-related and overall survival. RESULTS: Circulating tumour cells were detected in 16 of 82 (20%) patients with early-stage breast cancer and in 13 out of 16 (81%) with advanced breast cancer. The specificity was 100%. The median follow-up time was 51 months (range: 17 -60). The CTC positivity in early-stage breast cancer patients resulted in significantly poorer relapse-free survival (log rank test: P ¼ 0.003) and was an independent predictor of relapse-free survival (multivariate hazard ratio ¼ 5.13, P ¼ 0.006, 95% CI: 1.62 -16.31). CONCLUSION: The detection of CTCs in peripheral blood of early-stage breast cancer patients provided prognostic information for relapse-free survival

High Fill-Out, Extreme Mass Ratio Overcontact Binary Systems. X. The new discovered binary XY Leonis Minoris

The new discovered short-period close binary star, XY LMi, was monitored photometrically since 2006. It is shown that the light curves are typical EW-type and show complete eclipses with an eclipse duration of about 80 minutes. By analyzing the complete B, V, R, and I light curves with the 2003 version of the W-D code, photometric solutions were determined. It is discovered that XY LMi is a high fill-out, extreme mass ratio overcontact binary system with a mass ratio of q=0.148 and a fill-out factor of f=74.1%, suggesting that it is on the late evolutionary stage of late-type tidal-locked binary stars. As observed in other overcontact binary stars, evidence for the presence of two dark spots on both components are given. Based on our 19 epoches of eclipse times, it is found that the orbital period of the overcontact binary is decreasing continuously at a rate of dP/dt=-1.67\times10^{-7}\,days/year, which may be caused by the mass transfer from the primary to the secondary or/and angular momentum loss via magnetic stellar wind. The decrease of the orbital period may result in the increase of the fill-out, and finally, it will evolve into a single rapid-rotation star when the fluid surface reaching the outer critical Roche Lobe.Comment: 19 pages, 4 figures, 9 table

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral bloo

Alcohol intake and risk of breast cancer: the euramic study

To evaluate the association of alcohol intake with the risk of breast cancer in post-menopausal women, we analyzed the data from an international case-control study conducted in five European countries (FRG, Switzerland, Northern Ireland, the Netherlands and Spain). Information on alcohol intake was available in 315 cases and 364 controls. Medians for the tertiles of alcohol intake among current drinkers were 1.7, 6.0, and 20.0 g/day. Adjusted relative risks (and 95% confidence intervals) of breast cancer for each tertile of intake in current drinkers, compared to never drinkers, were 1.00 (0.60-1.67), 1.01 (0.60-1.73), and 1.18 (0.69-2.03). The adjusted relative risk for ex-drinkers was 1.73 (1.07-2.79). Among both current drinkers and ex-drinkers, the relative risk was higher for those with body mass index above the median compared to those with body mass index below the median. These results do not support a dose-response effect of alcohol on breast cancer risk, although consumption levels were too low to exclude increased risk with high regular intake. Further research is necessary to evaluate the risk of developing breast cancer among ex-drinkers and the potential interaction between body mass index and alcohol drinking.Thc EURAMIC Study was supported as an European Community Concerted Action by the Commission of the European Communities (con-tracts number MR4*/265/NL and MR4*/CT91/0369[SSMA]). The natio-nal studies were financed by grants from the Dutch Ministry of Health, the Spanish "Fondo de Invcstigacioncs Sanitarias" (91E0575), the German Fe-deral Health Office, the Cancer Research Switzerland (AKT76), the Swiss National Science Foundation (32-9257-87), the Yrjö Jahnsson Foundation, the Ulster Cancer Foundation and Milk Intervention Board (co-responsibi-lity Levy Disbursement Reg EEC 110/90 Contract 77.2).S

Predictive gene lists for breast cancer prognosis: A topographic visualisation study

<p>Abstract</p> <p>Background</p> <p>The controversy surrounding the non-uniqueness of predictive gene lists (PGL) of small selected subsets of genes from very large potential candidates as available in DNA microarray experiments is now widely acknowledged <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Many of these studies have focused on constructing discriminative semi-parametric models and as such are also subject to the issue of random correlations of sparse model selection in high dimensional spaces. In this work we outline a different approach based around an unsupervised patient-specific nonlinear topographic projection in predictive gene lists.</p> <p>Methods</p> <p>We construct nonlinear topographic projection maps based on inter-patient gene-list relative dissimilarities. The Neuroscale, the Stochastic Neighbor Embedding(SNE) and the Locally Linear Embedding(LLE) techniques have been used to construct two-dimensional projective visualisation plots of 70 dimensional PGLs per patient, classifiers are also constructed to identify the prognosis indicator of each patient using the resulting projections from those visualisation techniques and investigate whether <it>a-posteriori </it>two prognosis groups are separable on the evidence of the gene lists.</p> <p>A literature-proposed predictive gene list for breast cancer is benchmarked against a separate gene list using the above methods. Generalisation ability is investigated by using the mapping capability of Neuroscale to visualise the follow-up study, but based on the projections derived from the original dataset.</p> <p>Results</p> <p>The results indicate that small subsets of patient-specific PGLs have insufficient prognostic dissimilarity to permit a distinction between two prognosis patients. Uncertainty and diversity across multiple gene expressions prevents unambiguous or even confident patient grouping. Comparative projections across different PGLs provide similar results.</p> <p>Conclusion</p> <p>The random correlation effect to an arbitrary outcome induced by small subset selection from very high dimensional interrelated gene expression profiles leads to an outcome with associated uncertainty. This continuum and uncertainty precludes any attempts at constructing discriminative classifiers.</p> <p>However a patient's gene expression profile could possibly be used in treatment planning, based on knowledge of other patients' responses.</p> <p>We conclude that many of the patients involved in such medical studies are <it>intrinsically unclassifiable </it>on the basis of provided PGL evidence. This additional category of 'unclassifiable' should be accommodated within medical decision support systems if serious errors and unnecessary adjuvant therapy are to be avoided.</p

Nutri-RecQuest: a web-based search engine on current micronutrient recommendations

Background: The EURRECA (EURopean micronutrient RECommendations Aligned) Network of Excellence collated current micronutrient recommendations. A user-friendly tool, Nutri-RecQuest, was developed to allow access to the collated data and to create a database source for use in other nutritional software tools. Methods: Recommendations, that is, intakes of micronutrients sufficient to meet the requirements of the majority of healthy individuals of that population, from 37 European countries/organizations and eight key non-European countries/regions comprising 29 micronutrients were entered into a database. General information on the source of the recommendations, as well scientific background information, was added. Results: A user-friendly web-based interface was developed to provide efficient search, comparison, display, print and export functions. Conclusion: Easy access to existing recommendations through the web-based tool may be valuable for bodies responsible for setting recommendations, as well as for users of recommendations including scientists, policy makers, health professionals and industry. Adding related dietary reference values such as average nutrient requirements and upper limits may extend the utility of the tool. European Journal of Clinical Nutrition (2010) 64, S43-S47; doi:10.1038/ejcn.2010.6

EURRECA's General Framework to make the process of setting up micronutrient recommendations explicit and transparent

EURRECA is a Network of Excellence with the objective of addressing the problem of national variations in micronutrient recommendations and working towards a framework of advice to better inform policy-makers. It became apparent that the network needed a framework that puts the process of recommendation setting in the context of science, policy and society. Although variability in recommendations originates from the scientific evidence-base used and its interpretation (e.g. health outcomes, types and methods of evaluation of evidence, quantification of risk/benefit), the background information provided in the recommendation reports does not easily facilitate the disentangling of the relative contribution of these different aspects because of lack of transparency. The present report portrays the general framework (see Figure) that has been developed by and for EURRECA in order to make the process of setting up micronutrient recommendations explicit and transparent. In explaining the link from science to policy applications, the framework distinguishes four principal components or stages (see Figure). These stages are: a) Defining the nutrient requirements: A judgement about the (best) distribution(s) of the population requirement is necessary for estimating nutrient requirements. Many assumptions need to be made about the attributes of the population group. Furthermore, several factors (consumer behaviour as well as physiology) are to be included to characterize optimal health. b) Setting the nutrient recommendations: All available evidence is needed to formulate recommendations. Incorporating different endpoints provide the basis to formulate an optimal diet in terms of (non-)nutrients and food(group)s. c) Policy options: Policy options should be formulated on how the optimal diet can be achieved. They concern the advice of scientist and/or expert committees to the policy makers. Current policy options are setting up a task force, food based dietary guidelines, general health education, educational programme for specific group(s), voluntary or mandatory fortification, labelling, supplementation (general or for specific groups), inducing voluntary action in industry, legislation on micronutrient composition in food products, fiscal change, monitoring and evaluation of intake (via food consumption surveys) and/or nutritional status. d) Policy applications: Policies and planning, usually done by government, that lead to nutritional interventions or programmes. They usually require consideration of scientific, legal, regulatory, ethical and cultural issues, economic implications, and political and social priorities. This framework illustrates three dimensions of the process of setting (micro)nutrient requirements: 1) The logical sequence of scientific thinking from setting physiological requirements for nutritional health leading to evidence-based derivation of Nutrient Intake Values. 2) In the early stages nutritional and epidemiological science is the dominant source and in the later stages evidence from consumer and social sciences as well as stakeholder influences is used in deriving the options for changing the distribution of nutrient intakes. 3) The wider socio-political context: a feedback loop between health perception, actual health and food intake exists and is directly affected by the food industry and many other stakeholders. Moreover, from the viewpoint of policymakers, there are concerns for health promotion and disease prevention because of population health indices, costs of health care, and economic interests in the agro-food sector. In conclusion: A systematic approach for development and regular review of micronutrient requirements in Europe, transparently based on scientific evidence and best practices, enables national and international authorities/bodies to use the best available information obtained through evidence-based nutrition and accomplish well-considered food policy. Funded by an EU FP6 Network of Excellence (EURRECA, grant no. FP 6–036196-2). G. T. performed part of the work under a short-term contract for WHO Europe

Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is rather comparable across European populations

Purpose: We investigated whether group-level bias of a 24-h recall estimate of protein and potassium intake, as compared to biomarkers, varied across European centers and whether this was influenced by characteristics of individuals or centers. Methods: The combined data from EFCOVAL and EPIC studies included 14 centers from 9 countries (n = 1,841). Dietary data were collected using a computerized 24-h recall (EPIC-Soft). Nitrogen and potassium in 24-h urine collections were used as reference method. Multilevel linear regression analysis was performed, including individual-level (e.g., BMI) and center-level (e.g., food pattern index) variables. Results: For protein intake, no between-center variation in bias was observed in men while it was 5.7% in women. For potassium intake, the between-center variation in bias was 8.9% in men and null in women. BMI was an important factor influencing the biases across centers (p <0.01 in all analyses). In addition, mode of administration (p = 0.06 in women) and day of the week (p = 0.03 in men and p = 0.06 in women) may have influenced the bias in protein intake across centers. After inclusion of these individual variables, between-center variation in bias in protein intake disappeared for women, whereas for potassium, it increased slightly in men (to 9.5%). Center-level variables did not influence the results. Conclusion: The results suggest that group-level bias in protein and potassium (for women) collected with 24-h recalls does not vary across centers and to a certain extent varies for potassium in men. BMI and study design aspects, rather than center-level characteristics, affected the biases across center

Коло Марусі Чурай

In this article Marusya Churay*s (a character famous in story and song) life history is researched. On the basis of real events and historical facts the author tells about people who were related to the life of this personality