Development and characterization of immuno-nanocarriers targeting the cancer stem cell marker AC133

In the context of targeted therapy, we addressed the possibility of developing a drug delivery nanocarrier capable to specifically reach cancer cells that express the most prominent marker associated with cancer stem cell (CSC) phenotype, AC133. For this purpose, 100 nm lipid nanocapsules (LNCs) were functionalized with a monoclonal antibody (mAb) directed against AC133 according to two distinct methods: firstly, post-insertion within 100 nm LNCs of a lipid poly(ethylene glycol) functionalized with reactive-sulfhydryl maleimide groups (DSPE-PEG2000-maleimide) followed by thiolated mAb coupling, and, secondly, creation of a thiolated lipo-immunoglobulin between DSPE-PEG2000-maleimide and AC133, then post-inserted within LNCs. Due to the reduced number of purification steps, lower amounts of DSPE-PEG2000-maleimide that were necessary as well as lower number of free maleimide functions present onto the surface of immuno-LNC, the second method was found to be more appropriate. Thus, 126 nm AC133-LNC with a zeta potential of −22 mV while keeping a narrow distribution were developed. Use of the IgG1κ isotype control-immunoglobulins produced similar control IgG1-LNCs. Micro-Bradford colorimetric assay indicated a fixation of about 40 immunoglobulins per LNC. Use of human Caco-2 cells that constitutively express AC133 (Caco-2-AC133high) allowed addressing the behavior of the newly functionalized immuno-LNCs. siRNA knockown strategy permitted to obtain Caco-2-AC133low for comparison. Immunofluorescence-combined flow cytometry analysis demonstrated that the epitope-recognition function of AC133 antibody was preserved when present on immuno-LNCs. Although grafting of immunoglobulins onto the surface of LNCs repressed their internalization within Caco-2 cells as evaluated by flow cytometry, AC133-specific cellular binding was obtained with AC133-LNC as assessed by computer-assisted fluorescence microscopy. In conclusion, interest of AC133-LNCs as niche carriers is discussed toward the development of CSC targeted chemo- or radio-nanomedicines

In vitro expansion of human glioblastoma cells at non-physiological oxygen tension irreversibly alters subsequent in vivo aggresiveness and AC 133 expression

Among markers of glioblastoma initiating cells, AC133 has been shown to be associated with glioblastoma resistance and malignancy. Recently, it was demonstrated that increasing oxygen tension (pO(2)) down-regulated AC133 expression in glioblastoma cells in vitro. In order to better understand extrinsic factor regulation of AC133, this work aimed to investigate the relationship between cell culture pO(2), AC133 expression, and tumor development and phenotype. Using treatments with CoCl(2) and HIF-1α shRNA knockdowns on non-sorted human primary glioblastoma cells cultured at low (3%) versus high (21%) oxygen tension, we established a responsibility for low pO(2) in the maintenance of high levels of AC133 expression, with a major but non-exclusive role for HIF-1α. We also demonstrated that human glioblastoma cells previously cultured under high oxygen tension can lose part of their aggressiveness when orthotopically engrafted in SCID mice or lead to tumors with distinct phenotypes and no re-expression of AC133. These observations showed that the specific pO(2) microenvironment irreversibly impacts glioblastoma cell phenotypes, highlighting the pertinence of culture conditions when extrapolating data from xenogenic models to human cells in their source environment. They also raised AC133 as a marker of non-exposure to oxygenated areas rather than a marker of aggressiveness or low pO(2) niches

Recent developments of marine ingredients for food and nutraceutical applications: a review.

Remerciements à l'éditeur pour son accord de diffusion. L'article original est aussi accessible sur le site de l'éditeur à l'adresse : http://www.halieutique.org/23201b.htmlInternational audienceIn a global context of marine biological resource overexploitation, a better upgrading of fish and shellfish biomass is a challenge for the 21st century. One of the main and promising issues will be the production of marine bio-ingredients using enzymatic hydrolysis. This paper presents the key steps in the production of enzymatic hydrolysates, such as (i) enzymatic treatment for the bioconversion of solid discards, and more particularly, use of proteases, (ii) quantification of the proteolysis extend and procedures of quality-control and (iii) identification of biological activity, using in vitro and in vivo methods. In the last part, examples of marine, commercially available functional foods or nutraceutical ingredients carrying bioactive properties are presented in order to demonstrate the interest of biotechnological exploitation of marine resources

Séance spécialisée : géodynamique des bassins océaniques et des marges continentales

Une morphologie de fonds sous-marins bathyaux comportant des indurations liées à des dépôts ferro-manganésifères inclus dans des sédiments hémipélagiques peu ou pas cimentés a été découverte sur une ride volcanique tertiaire au large de la Nouvelle-Calédonie (SW Pacifique). Elle semble être en relation avec des circulations hydrothermales au travers de la couverture sédimentaire pendant l'activité volcanique miocène de la ride des Loyauté. (Résumé d'auteur

Fishman, Sarah, La bataille de l’enfance. Délinquance juvénile et justice des mineurs en France pendant la Seconde Guerre mondiale

Il faut se féliciter de la publication par les Presses Universitaires de Rennes de la traduction française du livre de Sarah Fishman, The Battle for Children, paru en 2002 à Harvard University Press. En effet,cet ouvrage marque un jalon en matière d’historiographie de la jeunesse de la Seconde Guerre mondiale, ou plus précisément d’« une » jeunesse dans la Seconde Guerre mondiale : la jeunesse délinquante. La réflexion brillamment menée par Sarah Fishman dans ce livre part d’un constat : perc..

Pragmatisch redeneren in modelgebaseerde diagnose

Model-gebaseerde diagnose bepaalt de defecte componenten in een technisch systeem door middel van een gerichte reeks testen en metingen. Meetadvies wordt gegeven op basis van verkregen diagnostische hypothesen. De huidige model-gebaseerde diagnostische methoden2 hebben een hoge berekeningscomplexiteit (in 0(2")) waarbij n het aantal componenten in het model is). De Pragmatic Diagnostic Engine (POE) is een model-gebaseerde redeneermethode die een polynomiale berekeningscomplexiteit heeft (in 0(n2)). Door een beperking van het diagnostisch redeneren tot de belangrijkste diagnostische hypothesen, kan in korte tijd een goed meetadvies gegeven worden. In een aantal experimenten werd bevestigd dat PDE's meetadvies nagenoeg hetzelfde is als dat van de standaardmethode GDE

Concentration of aroma compounds from an industrial solution of soluble coffee by pervaporation process

AbstractPervaporation experiments with PDMS membrane have been performed in a plate and frame module to investigate its ability to concentrate volatile compounds identified in an industrial soluble coffee solution. Eight compounds were chosen to depict key aroma of soluble coffee. The effect of feed flow rate, temperature and permeate pressure on the pervaporation performance has been analyzed. Concentration polarization phenomena was not identified in the feed flow rate studied. The temperature effect showed a good agreement with the nonlinear Arrhenius equation. The permeate pressure followed the solution–diffusion model behavior. Results showed that pervaporation is a promising alternative to concentrate aroma compounds from soluble coffee

Membrane fitration for the recovery of lipids from microalgae extracts

International audienc