Prognostic impact of vitamin B6 metabolism in lung cancer

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.publishedVersio

Vitamin K antagonists and emergencies

International audienc

Self-Assembling of Redox-Active Atrazine Poly(ethylenimine) Conjugates – Interfacial Electrochemical and Spectroscopic Characterization

International audienceThin films of polymers tethered with both atrazine haptens and ferrocenyl (Fc) probes were formed on polycrystalline gold electrodes by taking advantage of the facile formation of self-assembled monolayers (SAMs) of thiolates. These films were characterized by polarization modulation Fourier transform infrared reflection – absorption spectrometry (PM-IRRAS), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry. The combination of these techniques gave a full insight into the structure and the binding mode of the polymers and provided useful quantitative information about both Fc entity and atrazine hapten surface density. This may open the way to a new type of immunosensor for atrazine monitoring

An immunosurveillance mechanism controls cancer cell ploidy

Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers

An immunosurveillance mechanism controls cancer cell ploidy

Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers

Etude de la qualité sanitaire des fromages artisanaux dans la région d'Antsirabé

L'étude a été menée dans la région d'Antsirabe à Madagascar d'avril à août 2004. Initiée dans le cadre du projet FSP-FORMA en collaboration avec la DSAPS, elle avait pour objet la qualité sanitaire des fromages artisanaux. La réussite d'un fromage dépend en effet du contrôle de la technologie de fabrication, de la maîtrise de la qualité du lait et du respect des conditions de l'hygiène. Ce travail a comporté deux étapes. Dans un premier temps, il s'agissait d'identifier tous les producteurs de fromages artisanaux de la région d'Antsirabe et de caractériser leur production. Dans un second temps les risques microbiologiques liés à la consommation des différents types de fromages ont été évalués. Il ressort de notre travail, que plus de 85% des fromages artisanaux produits dans la région d'Antsirabe ne présente pas de risques bactériologiques majeurs pour le consommateur. Seuls trois échantillons de fromages étaient contaminés par des germes pathogènes comme S. aureus et E. coli. Certaines améliorations au niveau de l'hygiène de travail et du processus de transformation fromagère pourraient être cependant apportées afin d'accroître la sécurité alimentaire: appliquer un traitement thermique du lait (la pasteurisation), favoriser une étape de maturation (acidification), prolonger la période d'affinage des pâtes pressées non cuites à 15 jours. (Résumé d'auteur