Pedeboscq S.,French Institute of Health and Medical Research |
Pedeboscq S.,Bordeaux University Hospital Center |
Rey C.,French Institute of Health and Medical Research |
Petit M.,Fluofarma |
And 4 more authors.
PLoS ONE | Year: 2012
The antioxidant properties of α-tocopherol have been proposed to play a beneficial chemopreventive role against cancer. However, emerging data also indicate that it may exert contrasting effects on the efficacy of chemotherapeutic treatments when given as dietary supplement, being in that case harmful for patients. This dual role of α-tocopherol and, in particular, its effects on the efficacy of anticancer drugs remains poorly documented. For this purpose, we studied here, using high throughput flow cytometry, the direct impact of α-tocopherol on apoptosis and cell cycle arrest induced by different cytotoxic agents on various models of cancer cell lines in vitro. Our results indicate that physiologically relevant concentrations of α-tocopherol strongly compromise the cytotoxic and cytostatic action of various protein kinase inhibitors (KI), while other classes of chemotherapeutic agents or apoptosis inducers are unaffected by this vitamin. Interestingly, these anti-chemotherapeutic effects of α-tocopherol appear to be unrelated to its antioxidant properties since a variety of other antioxidants were completely neutral toward KI-induced cell cycle arrest and cell death. In conclusion, our data suggest that dietary α-tocopherol could limit KI effects on tumour cells, and, by extent, that this could result in a reduction of the clinical efficacy of anti-cancer treatments based on KI molecules. © 2012 Pédeboscq et al. Source
Fluofarma | Date: 2009-12-15
Chemicals used in industry and science; chemicals products used in agriculture, horticulture and forestry, namely, chemical preparations used to identify environmentally hazardous products and toxic products. Pharmaceutical and veterinary preparations, namely, pharmaceutical preparations for the treatment of cancers, neurodegenerative pathologies,vascular accidents; sanitary preparations for medical applications for treating cancers, neurodegenerative pathologies, vascular accidents; dietary peptides for medical use; natural compounds, namely, powder of natural compounds for a medical or therapeutic application, namely, pharmaceutical preparations in the form of a powder for the treatment of cancers, neurodegenerative pathologies, vascular accidents, ageing, slimming or skin diseases; medicinal herbs; nutritional supplements in the form of medicinal roots, medicinal oils for medical use; small molecules adapted for medical application, namely, pharmaceutical preparations for treatment of cancers, neurodegenerative pathologies, vascular accidents, ageing and for skin care and slimming; chemical preparations for sanitary applications. Scientific, optical, measuring, monitoring and teaching apparatus and instruments, namely, high throughput screening laboratory robot, biological microscopes, laser measurement systems, fluorescence measurement systems and flow cytometer systems comprised of automated cell biology platform, namely, automated laboratory robot for cells seeding, cells culture and cells treatment, cytometers, optical readers, laser scanning cytometers, microscopes, fluorometers and computers for the analysis of fluorescence signal, all used for identifying compounds and evaluating toxicity, in research and development for the pharmaceutical, cosmetic, agrobusiness and environmental sectors. Surgical, medical and veterinary instruments and apparatus, namely, artificial skin for preclinical research purposes, blood testing apparatus, diagnostic apparatus for clinical diagnosis, probes for medical use, electrodes and needles for medical purposes, all for use in molecular screening. Engineering services, namely, evaluations, assessments and research in the fields of science and technology; scientific research for medical purposes; research and development of new products for third parties; technical project studies, namely, conducting feasibility studies. Medical and veterinary services for health, dental and pharmaceutical consulting; hygienic and beauty care for human beings or animals; agriculture, horticulture and forestry consulting in the field of assessing ecotoxicity, namely, measurement of cytotoxicity in unicellular algae as a marker for ecotoxicity.
Winckler P.,University of Bordeaux 1 |
Winckler P.,French National Center for Scientific Research |
Lartigue L.,French Institute of Health and Medical Research |
Giannone G.,Institut Universitaire de France |
And 9 more authors.
Scientific Reports | Year: 2013
Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the- Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial. Source
Rey C.,French Institute of Health and Medical Research |
Soubeyran I.,French Institute of Health and Medical Research |
Soubeyran I.,Institute Bergonie |
Mahouche I.,French Institute of Health and Medical Research |
And 6 more authors.
Cell Cycle | Year: 2013
HIPK1 (homeodomain interacting protein kinase 1) is a serine/threonine kinase that belongs to the CMGC superfamily. Emerging data point to the role of HIPK1 in cancer, but it is still not clear whether it acts as a tumor suppressor or promoter. Here we identified HIPK1 as a kinase that is significantly overexpressed in colorectal cancer (CRC) and whose expression is stage-dependent. Being abundantly expressed at the onset of the disease, the HIPK1 level gradually decreased as tumor stage progressed. To further uncover how this factor regulates tumorigenesis and establish whether it constitutes an early factor necessary for neoplastic transformation or for cellular defense, we studied the effect of its overexpression in vitro by investigating various cancer-related signaling cascades. We found that HIPK1 mostly regulates the p53 signaling pathway both in HCT116 and HeLa cells. By phosphorylating p53 on its serine-15, HIPK1 favored its transactivation potential, which led to a rise in p21 protein level and a decline in cell proliferation. Assuming that HIPK1 could impede CRC growth by turning on the p53/p21 pathway, we then checked p21 mRNA levels in patients. Interestingly, p21 transcripts were only increased in a subset of patients expressing high levels of HIPK1. Unlike the rest of the cohort, the majority of these patients hosted a native p53 protein, meaning that such a pro-survival pathway (HIPK1+ > p53 > p21) is active in patients, and that HIPK1 acts rather as a tumor suppressor. © 2013 Landes Bioscience. Source
Fluofarma | Date: 2012-04-16
Data processing system for generating representations and analyses of cytometric information for:loading one set of data including:one image of two wells on a plate each having one cell in a predetermined biological condition, each image being acquired with a microscope;features of each cell from each image;processing loaded data for obtaining representations and analyses of the data, from:Histogram in one dimension;Scattergram in two-dimensions;Density in two-dimensions;Plate layout management;Cell montage;Field;Plate heatmap;Dose response with regrouping of replicates;Statistics information percentage of cell in different gates;zFactor calculation with regrouping of replicates;List of well for selection and list of biological condition for selection;Statistics export capability;Ready to print layout capability on the selected well or biological condition or all wells and biological conditions.