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

Microorganisms from aphid honeydew attract and enhance the efficacy of natural enemies

Aphids are one of the most serious pests of crops worldwide, causing major yield and economic losses. To control aphids, natural enemies could be an option but their efficacy is sometimes limited by their dispersal in natural environment. Here we report the first isolation of a bacterium from the pea aphid Acyrthosiphon pisum honeydew, Staphylococcus sciuri, which acts as a kairomone enhancing the efficiency of aphid natural enemies. Our findings represent the first case of a host-associated bacterium driving prey location and ovipositional preference for the natural enemy. We show that this bacterium has a key role in tritrophic interactions because it is the direct source of volatiles used to locate prey. Some specific semiochemicals produced by S. sciuri were also identified as significant attractants and ovipositional stimulants. The use of this host-associated bacterium could certainly provide a novel approach to control aphids in field and greenhouse systems

Les substances végétales non volatiles et leur effet phagostimulant sur les larves de cinquième stade de la teigne du poireau, Acrolepiopsis assectella (Lep.)

International audienc

Current status of combination therapy in other cardiovascular-diseases

As in hypertension, the addition of a second active drug is believed to enhance treatment efficacy; however, the extent to which a combination of two low-dose drugs outperforms conventional monotherapy remains uncertain. Established treatments of angina comprises nitrates compounds, beta-blockers and calcium antagonists, which are often given in combination. Beta-blockers are major players in this field as they inhibit the tachycardia induced by nitrates and calcium antagonists; there is therefore a pathophysiological justification for their use in combination therapy, supported by repeated confirmation of positive clinical effect. The most widely chosen calcium antagonists are dihydropyridines; verapamil may impair conduction. However, it is not clear whether combination enhances the effects of the individual antianginal substances. Diuretics are for most clinicians the keystone treatment of heart failure; diuretics are often combined with other drugs, e.g. amiloride and spironolactone. The latter also have a beneficial effect on myocardial structure (myocardium/collagen ratio). ACE-inhibitors are of proven clinical efficacy, and, in addition, have a beneficial effect on survival. They combine well with diuretics: because the diuretic stimulates renin release, the ACE-inhibitor can be given at a lower dose (enhancement of effect). There are, however, certain drawbacks (hypotension, hyperkalemia with antialdosterones). The results of combining ACE-inhibitors with calcium antagonists and beta-blockers await investigation. The ISIS studies demonstrated the advantages of combining beta-blockers, thrombolysis and aspirin in acute infarction. ACE-inhibitors have recently been added to the regimen with a positive effect (extended survival), especially in the presence of a decreased ejection fraction (SAVE, AIRE, GISSI 3 and ISIS 4 studies). However, as in angina, an enhancement effect has not yet been conclusively demonstrated. To prove this last point, studies are mandatory, but they will be difficult, costly and require a large number of patients