Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

International audienceBiocharacterization of circulating tumor cells (CTCs) in the peripheral blood of advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were separated and stained using the CellSearch System. HER2 status was assessed by immunofluorescence and, when technically feasible, by fluorescence in situ hybridization. Blood samples were obtained from 66 ABC patients. Forty patients had a positive CTC sample (61%) and of these, 15 (37%) had HER2 + CTCs. We found non-concordant results in 32% of cases: 29% (8/28) of HER2-negative primary tumors had HER2-positive CTCs and 42% (5/12) of HER2-positive primary tumors had HER2-negative CTCs ( = 0.278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression

Ambulatory blood pressure monitoring during pregnancy: an Italian experience

Objective: To describe the impact of a collaborative Italian diagnostic pathway offering ambulatory blood pressure (BP) monitoring (ABPM) in High Risk Antenatal Clinic (HRAC) pregnant women. The study included 395 pregnant women evaluated at HRAC between 2012 and 2016, while analyzing demographic, clinical characteristics, and prescription of ABPM. Pregnant women were firstly seen when gestational age was 19.6 +/- 9.6 weeks. In at least one-third of cases, ABPM was followed by medical intervention aiming to modify the preexisting therapeutic treatment. Hypertension and overweight were the main reasons for performing ABPM. WCH: white-coat hypertension

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Statistical quality assessment and outlier detection for liquid chromatography-mass spectrometry experiments

<p>Abstract</p> <p>Background</p> <p>Quality assessment methods, that are common place in engineering and industrial production, are not widely spread in large-scale proteomics experiments. But modern technologies such as Multi-Dimensional Liquid Chromatography coupled to Mass Spectrometry (LC-MS) produce large quantities of proteomic data. These data are prone to measurement errors and reproducibility problems such that an automatic quality assessment and control become increasingly important.</p> <p>Results</p> <p>We propose a methodology to assess the quality and reproducibility of data generated in quantitative LC-MS experiments. We introduce quality descriptors that capture different aspects of the quality and reproducibility of LC-MS data sets. Our method is based on the Mahalanobis distance and a robust Principal Component Analysis.</p> <p>Conclusion</p> <p>We evaluate our approach on several data sets of different complexities and show that we are able to precisely detect LC-MS runs of poor signal quality in large-scale studies.</p

Multimodal Atlas of the Murine Inner Ear: From Embryo to Adult

The inner ear is a complex organ housed within the petrous bone of the skull. Its intimate relationship with the brain enables the transmission of auditory and vestibular signals via cranial nerves. Development of this structure from neural crest begins in utero and continues into early adulthood. However, the anatomy of the murine inner ear has only been well-characterized from early embryogenesis to post-natal day 6. Inner ear and skull base development continue into the post-natal period in mice and early adulthood in humans. Traditional methods used to evaluate the inner ear in animal models, such as histologic sectioning or paint-fill and corrosion, cannot visualize this complex anatomy in situ. Further, as the petrous bone ossifies in the postnatal period, these traditional techniques become increasingly difficult. Advances in modern imaging, including high resolution Micro-CT and MRI, now allow for 3D visualization of the in situ anatomy of organs such as the inner ear. Here, we present a longitudinal atlas of the murine inner ear using high resolution ex vivo Micro-CT and MRI

Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2) was used for both the experiments and simulations. Our computational model was composed of three parts: (1) media flow equations, (2) mass transport equations and (3) cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS) from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that should prove advantageous for biologicals or drug delivery investigations