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

Etude des cellules inflammatoires au cours de la pathologie pulmonaire: contribution de l'immunohistochimie et de l'hybridation in sit

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 79335 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

L'amour, la violence et le pouvoir : la criminalité à Douai de 1496 à 1520

Fouret Claude, Deregnaucourt Jean-Pierre. L'amour, la violence et le pouvoir : la criminalité à Douai de 1496 à 1520. In: Revue du Nord, tome 66, n°263, Octobre-décembre 1984. pp. 1089-1096

L'amour, la violence et le pouvoir : la criminalité à Douai de 1496 à 1520

Fouret Claude, Deregnaucourt Jean-Pierre. L'amour, la violence et le pouvoir : la criminalité à Douai de 1496 à 1520. In: Revue du Nord, tome 66, n°263, Octobre-décembre 1984. pp. 1089-1096

Mechanisms of disease: signal transduction in lung carcinogenesis - a comparison of smokers and never-smokers

Although smoking has been established as the most important cause of lung cancer, approximately 10% of patients with this malignancy have no history of smoking. The pathogenesis of tobacco-related lung carcinogenesis is becoming well characterized, but the molecular mechanisms of neoplastic transformation in never-smokers have not yet been adequately elucidated. Nevertheless, numerous recent studies have revealed a distinct biological process of malignant transformation with unique epidemiological and clinicopathological characteristics in never-smokers. The molecular pathways involved in the differential pattern of lung oncogenesis according to smoking status, however, remain fairly obscure. Researchers have studied several molecular pathways implicated in lung carcinogenesis in smokers and never-smokers, examining these processes at the genomic, epigenetic and proteomic level. The differential protein expression according to smoking status in critical signal transduction pathways has attracted scientific interest because of the possibilities of therapeutic intervention. In this Review we describe the best-characterized signaling pathways implicated in the transduction of proliferative signals and discuss the activity of these pathways in smokers and never-smokers

Myocardial infarction in relation to colchicine poisoning: A precipitating cause of refractory toxic cardiogenic shock

International audienc

Compliance mismatch and compressive wall stresses drive anomalous remodelling of pulmonary trunks reinforced with Dacron grafts

Synthetic grafts are often satisfactory employed in cardiac and vascular surgery, including expanded poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene). However, accumulating evidences suggest the emergence of worrisome issues concerning the long-term fate of prosthetic grafts as large vessel replacement. Disadvantages related to the use of synthetic grafts can be traced in their inability of mimicking the elasto-mechanical characteristics of the native vascular tissue, local suture overstress leading to several prosthesis-related complications and retrograde deleterious effects on valve competence, cardiac function and perfusion. Motivated by this, in the present work it is analyzed – by means of both elemental biomechanical paradigms and more accurate in silico Finite Element simulations – the physical interaction among aorta, autograft and widely adopted synthetic (Dacron) prostheses utilized in transposition of pulmonary artery, highlighting the crucial role played by somehow unexpected stress fields kindled in the vessel walls and around suture regions, which could be traced as prodromal to the triggering of anomalous remodelling processes and alterations of needed surgical outcomes. Theoretical results are finally compared with histological and surgical data related to a significant experimental animal campaign conducted by performing pulmonary artery transpositions in 30 two-month old growing lambs, followed up during growth for six months. The in vivo observations demonstrate the effectiveness of the proposed biomechanical hypothesis and open the way for possible engineering-guided strategies to support and optimize surgical procedures