Food intake biomarkers for berries and grapes

Grapes and berries are two types of widely consumed fruits characterized by a high content in different phytochemicals. However, their accurate dietary assessment is particularly arduous, because of the already wide recognized bias associated with self-reporting methods, combined with the large range of species and cultivars and the fact that these fruits are popularly consumed not only in fresh and frozen forms but also as processed and derived products, including dried and canned fruits, beverages, jams, and jellies. Reporting precise type and/or quantity of grape and berries in FFQ or diaries can obviously be affected by errors. Recently, biomarkers of food intake (BFIs) rose as a promising tool to provide accurate information indicating consumption of certain food items. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs have been developed within the Food Biomarker Alliance (FoodBAll) Project. This paper aims to evaluate the putative BIFs for blueberries, strawberries, raspberries, blackberries, cranberries, blackcurrant, and grapes. Candidate BFIs for grapes were resveratrol metabolites and tartaric acid. The metabolites considered as putative BFI for berries consumption were mostly anthocyanins derivatives together with several metabolites of ellagitannins and some aroma compounds. However, identification of BFIs for single berry types encountered more difficulties. In the absence of highly specific metabolites reported to date, we suggested some multi-metabolite panels that may be further investigated as putative biomarkers for some berry fruits

Characteristics of platelet aggregation induced by the monoclonal antibody ALB6 (acute lymphoblastic leukemia antigen p 24) Inhibition of aggregation by ALB6Fab

AbstractThe leukemia-associated cell surface antigen p 24 is found on normal platelets as well as on Bernard Soulier syndrome and thrombasthenia type I platelets. ALB6 IgG (a monoclonal antibody against p 24) induces the aggregation of platelets from normal donors but not from thrombasthenia. In contrast, ALB6 Fab inhibits platelet aggregation induced by collagen, ADP, thrombin, ionophore A 23187 and ALB6 IgG. The results suggest that ALB6 interferes with a mechanism common to all aggregation pathways; the possible mechanisms are discussed

Rosuvastatin Counteracts Vessel Arterialisation and Sinusoid Capillarisation, Reduces Tumour Growth, and Prolongs Survival in Murine Hepatocellular Carcinoma

Background and Aims. An arterial blood supply and phenotypic changes of the sinusoids characterise the liver vasculature in human hepatocellular carcinoma (HCC). We investigated the effects of rosuvastatin on liver vessel anomalies, tumour growth and survival in HCC. Methods. We treated transgenic mice developing HCC, characterized by vessel anomalies similar to those of human HCC, with rosuvastatin. Results. In the rosuvastatin group, the survival time was longer (P < .001), and liver weight (P < .01) and nodule surface (P < .01) were reduced. Rosuvastatin decreased the number of smooth muscle actin-positive arteries (P < .05) and prevented the sinusoid anomalies, with decreased laminin expression (P < .001), activated hepatic stellate cells (P < .001), and active Notch4 expression. Furthermore, rosuvastatin inhibited endothelial cell but not tumour hepatocyte functions. Conclusions. Rosuvastatin reduced the vessel anomalies and tumour growth and prolonged survival in HCC. These results represent new mechanisms of the effects of statin on tumour angiogenesis and a potential target therapy in HCC

Down-Regulation of Vascular Endothelial Growth Factor by Tissue Inhibitor of Metalloproteinase-2: Effect on in Vivo Mammary Tumor Growth and Angiogenesis

The tissue inhibitor of metalloproteinases-2 (TIMP-2) has at least two independent functions, i.e., regulation of matrix metalloproteinases and growth promoting activity. We investigated the effects of TIMP-2 overexpression, induced by retroviral mediated gene transfer, on the in vivo development of mammary tumors in syngeneic mice inoculated with EF43.fgf-4 cells. The EF43.fgf-4 cells established by stably infecting the normal mouse mammary EF43 cells with a retroviral expression vector for the fgf-4 oncogene, are highly tumorigenic and overproduce vascular endothelial growth factor (VEGF). Despite a promotion of the in vitro growth rate of EF43.fgf-4 cells overexpressing timp-2, the in vivo tumor growth was delayed. At day 17 post-cell injection, the volume of tumor derived from TIMP-2-overexpressing cells was reduced by 80% as compared with that obtained with control cells. Overexpression of TIMP-2 was associated with a down-regulation of VEGF expression in vitro and in vivo, a reduction of vessel size, density, and blood supply in the induced tumors. In addition, TIMP-2 completely inhibited the angiogenic activity of EF43.fgf-4 cell-conditioned medium in vitro using a rat aortic ring model. Our findings suggest that overexpression of TIMP-2 delays growth and angiogenesis of mammary carcinoma in vivo and that down-regulation of VEGF expression may play an important role in this TIMP-2-mediated antitumoral and antiangiogenic effects. Finally the in vivo delivery of TIMP-2, as assessed by i.v. injection of recombinant adenoviruses vectors, significantly reduced the growth of the EF43.fgf-4-induced tumors. This effect of TIMP-2 was shown to be equally comparable with that of angiostatin, a known potent inhibitor of angiogenesis

La protéine RhoA et ses voies de signalisation (Perspectives d'une nouvelle stratégie thérapeutique dans le traitement des cancers du sein agressifs)

Nous avons montré que les inhibiteurs de l'HMG-CoA réductase (statines) utilisés classiquement en clinique comme hypocholestérolémiant préviennent la formation de géranylgéranylpyrophosphate (GGPP) et réduisent la fixation membranaire (=activation) de RhoA ce qui conduit in vitro et in vivo à l'inhibition de prolifération et d'invasion des cellules agressives de cancer du sein. D'autres mécanismes impliqués dans l'activité anti-cancéreuse des statines (action sur les CDKi, les protéases et Wnt-5a) ont été identifiés au niveau moléculaire en utilisant des micro-puces à ADN. Enfin, nous avons montré que les bisphosphonates, qui ont une bio-disponibilité supérieure à celle des statines, préviennent également la fixation membranaire de RhoA ce qui conduit à une diminution de l'invasion et du chémotactisme des cellules cancéreuses. En conclusion, l'inhibition des voies de signalisation dirigées par RhoA semble être une bonne stratégie pour lutter contre les cancers agressifs.We have shown that HMG-CoA reductase inhibitors (statins) currently used in the treatment of hypercholesterolemia prevent the formation of geranylgeranylpyrophosphate (GGPP) and reduce the membrane localisation (=activation) of RhoA leading to the inhibition of cell proliferation and invasion of aggressive breast cancer cells in vitro and in vivo. Other mechanisms involved in the anticancer activity of statins (action on CDKi, proteases, Wnt-5a) were identified at molecular level using microarray. Finally, we have shown that bisphosphonates, which have a biodisponibility higher than statin, prevent also the membrane localisation of RhoA leading to the reduction of both cell invasion and chemotactic effect of cancer cells. To conclude, the inhibition of RhoA cell signalling pathways seems to be a good strategy to fight aggressive cancers.ROUEN-BU Sciences (764512102) / SudocSudocFranceF

La protéine Z (nouveau facteur de risque d'athérothrombose ?)

La protéine Z, facteur vitamine K-dépendant, est un modulateur dfe la cascade de la coagulation par inhibition du facteur Xa, en formant un complexe avec une protéase, l'inhibiteur dépendant de la protéine Z (ZPI). Les premières études chez l'homme semblent indiquer que le déficit en protéine Z pourrait être un facteur de risque de survenue d'accidents vasculaires cérébraux ischémiques, mais de nombreuses études qui ont suivi se sont révélées contradictoires. Des travaux additionnels ont montré qu'un déficit en protéine Z pourrait être impliqué aussi dans le syndrome coronarien aigu et les fausses-couchess d'étiologie inconnue. ainsi, nous avons étudié la relation entre le taux protéine Z et la survenue d'accidents ischémiques chez les patients atteints de la maladie de Seddon et chez de jeunes patients atteints d'un syndrome coronarien aigu. Les résultats de notre expérienc confirment la tendance qu'un déficit en protéine Z semble associée à un risque de thrombose artérielle.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Place des statines dans le risque cardiovasculaire et le risque osseux

Les statines, mise à part leur action hypocholestérolémiante, semblent avoir des effets sur divers constituants participant à la formation et fragilisation de la plaque d'athérome : les cellules endothéliales, les macrophages ou les monocytes, les CML, le cellules NK, les plaquettes, des facteurs impliqués dans la coagulation. Ce sont les effets pléiotropes qui seraient liés à la baisse du LDL-cholestérol et/ou à l'inhibition de l'isoprénylation de protéines régulatrices, Ras et Rho en particulier. Effectivement, en inhibant l'HMG-CoA réductase, les statines induisent une diminution de FPP et de GGPP. De plus, les essais cliniques évoquent une diminution de la mortalité cardiovasculaire et de la mortalité totale. Plus récemment, il a été démontré que les statines pourraient trouver une place dans le traitement de l'ostéoporose : en augmentant la synthèse de BMP-2, elles stimuleraient la formation osseuse. Le MVA empêche ce phénomène.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF