Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1. © 2001 Cancer Research Campaign http://www.bjcancer.co

Cross-cultural adaptation, reliability, internal consistency and validation of the Trinity Amputation and Prosthetic Experience Scales-Revised (TAPES-R) for French speaking patients with lower limb amputation

AimThe aim of this study was the French cross-cultural adaptation and validation of The Trinity Amputation and Prosthetic Experience Scales-Revised (TAPES-R-F), in a lower limb amputation population. This self-reported multidimensional amputee-specific questionnaire [1] evaluates with 33 items psychosocial adjustment (3 subscales), activity restriction (1 subscale) and satisfaction with prosthesis (2 subscales).Patients and methodsOne hundred and twenty-nine patients with a mean age of 62 years and with lower limb amputations for at least 1 year were recruited in 5 clinical centers. Translation and cross-cultural adaptation were made according to international guidelines. Internal consistency of each subscale was measured with Cronbach's alpha. Test-retest reliability was assessed by intraclass correlation in a sub- group of 24 subjects who completed the TAPES-R twice with an interval of 7 days. Construct validity was estimated through correlations with 2 main components of SF-36 (MCS, PCS). Correlations were also calculated with 3 scales of the Brief Pain Inventory (BPI).ResultsCronbach's alpha was high, ranging from 0.85 to 0.95. Reliability was acceptable to high (ICC=0.72 to 0.91) for all subscales with the exception of the Social adjustment (ICC=0.67) and Adjustment to limitation (ICC=0.42) subscales. The 2 component of SF-36 was significantly correlated with all subscales (PCS: r=0.24 to 0.66); MCS: r=0.30 to 0.58), except with aesthetic satisfaction and adjustment to limitation. Regarding the BPI, significant correlations were found for all subscales (r=–0.20 to –0.68) with the exception of adjustment to limitation. Ceiling or floor effects (>15%) were found for all but Activity Restriction and Functional Satisfaction Scales.DiscussionThe TAPES-R-F has acceptable psychometric properties for most of its subscales. Our results may suggest that the French version is more useful in a population research perspective than in an individual perspective. Other studies are necessary to clarify the role and the psychometric properties of this measurement

Assessment of an automatic prosthetic elbow control strategy using residual limb motion for transhumeral amputated individuals with socket or osseointegrated prostheses

International audienceMost transhumeral amputated individuals deplore the lack of functionality of their prosthesis due to control-related limitations. Commercialized prosthetic elbows are controlled via myoelectric signals, yielding complex control schemes when users have to control an entire prosthetic limb. Limited control yields the development of compensatory strategies. An alternative control strategy associates residual limb motions to automatize the prosthetic elbow motion using a model of physiological shoulder/elbow synergies. Preliminary studies have shown that elbow motion could be predicted from residual limb kinematic measurements, but results with transhumeral amputated individuals were lacking. This study focuses on the experimental assessment of automatic prosthetic elbow control during a reaching task, compared to conventional myoelectric control, with six transhumeral amputated individuals, among whom, three had an osseointegrated device. Part of the recruited participants had an osseointegrated prosthetic device. The task was achieved within physiological precision errors with both control modes. Automatic elbow control reduced trunk compensations, and restored a physiologically-like shoulder/elbow movement synchronization. However, the kinematic assessment showed that amputation and prosthesis wear modifies the shoulder movements in comparison with physiological shoulder kinematics. Overall, participants described the automatic elbow control strategy as intuitive, and this work highlights the interest of automatized prosthetic elbow motion

Crowd-sourced amputee gait data : a feasibility study using YouTube videos of unilateral trans-femoral gait

Collecting large datasets of amputee gait data is notoriously difficult. Additionally, collecting data on less prevalent amputations or on gait activities other than level walking and running on hard surfaces is rarely attempted. However, with the wealth of user-generated content on the Internet, the scope for collecting amputee gait data from alternative sources other than traditional gait labs is intriguing. Here we investigate the potential of YouTube videos to provide gait data on amputee walking. We use an example dataset of trans-femoral amputees level walking at self-selected speeds to collect temporal gait parameters and calculate gait asymmetry. We compare our YouTube data with typical literature values, and show that our methodology produces results that are highly comparable to data collected in a traditional manner. The similarity between the results of our novel methodology and literature values lends confidence to our technique. Nevertheless, clear challenges with the collection and interpretation of crowd-sourced gait data remain, including long term access to datasets, and a lack of validity and reliability studies in this area

Gene Expression Patterns in Peripheral Blood Correlate with the Extent of Coronary Artery Disease

Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall