A comparative study of adhesion of melanoma and breast cancer cells to blood and lymphatic endothelium

Background: Lymphovascular invasion (LVI) is an important step in the metastatic cascade; tumor cell migration and adhesion to blood and lymphatic vessels is followed by invasion through the vessel wall and subsequent systemic spread. Although primary breast cancers and melanomas have rich blood vascular networks, LVI is predominately lymphatic in nature. Whilst the adhesion of tumor cells to blood endothelium has been extensively investigated, there is a paucity of information on tumor cell adhesion to lymphatic endothelium. Methods and Results: Breast cancer (MDA-MB-231 and MCF7) and melanoma (MeWo and SKMEL-30) cell adhesion to lymphatic (hTERT-LEC and HMVEC dLy Neo) and blood (HUVEC and hMEC-1) endothelial cells were assessed using static adhesion assays. The effect of inflammatory conditions, tumor necrosis factor-a (TNF-a) stimulation of endothelial and tumor cells, on the adhesive process was also examined. In addition, the effects of TNF-a stimulation on tumor cell migration was investigated using haplotaxis (scratch wound) assays. Breast cancer and melanoma cells exhibited higher levels of adhesion to blood compared to lymphatic endothelial cells ( p < 0.001). TNF-a stimulation of endothelial cells, or of tumor cells alone, did not significantly alter tumor–endothelial cell adhesion or patterns.When both tumor and endothelial cells were stimulated with TNF-a, a significant increase in adhesion was observed ( p < 0.01), which was notably higher in the lymphatic cell models ( p < 0.001). TNF-a-stimulation of all tumor cell lines significantly increased their migration rate ( p < 0.01). Conclusions: Results suggest that metastasis resultant from lymphatic vessel-tumor cell adhesion may be modulated by cytokine stimulation, which could represent an important therapeutic target in breast cancer and melanoma

Salience-based selection: attentional capture by distractors less salient than the target

Current accounts of attentional capture predict the most salient stimulus to be invariably selected first. However, existing salience and visual search models assume noise in the map computation or selection process. Consequently, they predict the first selection to be stochastically dependent on salience, implying that attention could even be captured first by the second most salient (instead of the most salient) stimulus in the field. Yet, capture by less salient distractors has not been reported and salience-based selection accounts claim that the distractor has to be more salient in order to capture attention. We tested this prediction using an empirical and modeling approach of the visual search distractor paradigm. For the empirical part, we manipulated salience of target and distractor parametrically and measured reaction time interference when a distractor was present compared to absent. Reaction time interference was strongly correlated with distractor salience relative to the target. Moreover, even distractors less salient than the target captured attention, as measured by reaction time interference and oculomotor capture. In the modeling part, we simulated first selection in the distractor paradigm using behavioral measures of salience and considering the time course of selection including noise. We were able to replicate the result pattern we obtained in the empirical part. We conclude that each salience value follows a specific selection time distribution and attentional capture occurs when the selection time distributions of target and distractor overlap. Hence, selection is stochastic in nature and attentional capture occurs with a certain probability depending on relative salience

A New Measurement of the Radiative Ke3 Branching Ratio and Photon Spectrum

We present a preliminary report on a new measurement of the radiative neutral Ke3 branching ratio and the first study of the photon spectrum in this decay. We find BR(Ke3g, E*_g>30 GeV, Th*_eg>20 deg)/BR(Ke3) = 0.911+-0.009(stat)+0.021-0.010(syst)%. Our measurement of the spectrum is consistent with inner bremsstrahlung only as the source of photons at the 2 sigma level.Comment: 5 pages, 4 figures, proceedings paper from Meson 2000, Cracow, Poland, May 200

Project 8: Precision electron specroscopy to measure the mass of the neutrino

The Project 8 Collaboration is exploring a new technique for the spectroscopy of medium-energy electrons (∼ 1 - 100 keV) with the ultimate goal of measuring the effective mass of the electron antineutrino by the tritium endpoint method. Our method is based on the detection of microwave-frequency cyclotron radiation emitted by magnetically trapped electrons. The immediate goal of Project 8 is to demonstrate the utility of this technique for a tritium endpoint experiment through a high-precision measurement of the conversion electron spectrum of ^(83)mKr . We present concepts for detecting this cyclotron radiation, focusing on a guided wave design currently being implemented in a prototype apparatus at the University of Washington

Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis

Introduction HIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets). Methods and analysis Service evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses. Ethics and dissemination The chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners