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

ezc3d: An easy C3D file I/O cross-platform solution for C++, Python and MATLAB

<p>EZC3D is an easy to use reader, modifier and writer for C3D format files. It is written en C++ with proper binders for Python and MATLAB scripting langages.</p> <p>C3D (<a href="http://c3d.org">http://c3d.org</a>) is a format specifically designed to store biomechanics data. Hence many biomechanics softwares can produce C3D files in order to share data. However, there is a lack in the biomechanics community of an easy to use, free and open source library to read, modify and write them as needed when it gets to the data analysis. EZC3D addresses these issues. It offers a comprehensive and light API to read and write C3D files. The source code is written in C++ allowing to be compiled and used by higher level langages.</p&gt

Modulation du phénotype de multichimiorésistance des cancers (identification de cibles potentielles et développement de nouveaux outils génothérapeutiques)

La chimiorésistance des cancers est une cause majeure d échec des chimiothérapies et résulte du phénotype de multichimiorésistance (MDR). Il est dû notamment à la surexpression du gène MDR1 produisant la glycoprotéine-P (P-gp) qui expulse les médicaments hors de la cellule. Nous avons montré l existence d une forme dimérique de la P-gp, abondante dans les régions membranaires riches en cholestérol, dont la formation dépend de la glycosylation de la P-gp. Nous avons pu moduler in vitro le phénotype MDR en diminuant la production de transporteurs ABC (P-gp, MRP1, BCRP) et des protéines MVP et LRP130 par interférence par ARN. Cet outil a été adapté aux lignées MDR difficilement transfectables grâce à des vecteurs lentiviraux, et a suggéré un rôle nouveau de la LRP130 dans l apoptose des cellules MDR, complémentaire de son activité trans-activatrice de MDR1. Ces travaux ouvrent de nouvelles perspectives d étude et proposent des solutions originales dans la chimiothérapie des cancers MDR.The chemoresistance of cancers is a major cause of failure of chemotherapy. It results from the multidrug resistance phenotype (MDR), due in particular to the overexpression of the MDR1 gene. MDR1 produces P-glycoprotein (P-gp) that ejects drugs out of the cell. We showed the existence of P-gp dimers, particularly in cholesterol-enriched membranes, the formation of which depends on P-gp glycosylation. We could modulate the MDR phenotype in vitro by decreasing the production of ABC transporters (P-gp, MRP1, BCRP) and other proteins (MVP and LRP130) by using RNA interference. Lentiviral vectors carrying modulator siRNAs allowed us to transfect MDR cell lines that were hardly transfectable by other means. With this tool we could evidence a new role of LRP130 in the apoptosis of MDR cells that is complementary of its MDR1 trans-activating activity. This work opens new prospects and proposes original solutions in the chemotherapy of MDR cancersLYON1-BU.Sciences (692662101) / SudocSudocFranceF