Pathological lesions in colonic biopsies during Parkinson's disease.

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Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

Les Nuées, dans Les Nuées d’Aristophane

Les Nuées furent représentées à Athènes une première fois en 423 avant J.-C., puis dans une seconde version entre 421 et 417. Comme chacun le sait, la verve comique d’Aristophane est dirigée dans cette pièce contre Socrate, qui s’y trouve présenté comme le grand maître des nouveaux savoirs de la sophistique, artificieux et trompeurs. La pièce met en scène l’Athénien Strépsiade, affolé par la passion ruineuse de son fils Phidippide, fou de chevaux. Strépsiade cherche le moyen de ne pas payer l..

Rousseau et Homère

Yves Touchefeu : Rousseau and Homer. The opposition, for J.-J. Rousseau, of the values of nature and the polity is well known, as is the fact the Discourse on the Origins of Inequality and the Essay on the Origin of Language celebrate the beginning of society which, at the dawn of history, allowed for a golden mean between the indolence of primitive life and the tension of civil life. This explains why Rousseau paid such passionate attention to Homer, for the world of Achilles and Ulysses led him to precisely those important moments at which emerging society was as if in tune with the natural order. The reference to Homer is particularly present in Emile. While this treatise on education begins by opposing categorically the education of the individual and that of the citizen, the Homeric imagery invites the reader to dream of a time when the two figures of "natural man" and "citizen" were not yet clearly separated into their contradictory relationship.Touchefeu Yves. Rousseau et Homère. In: Dix-huitième Siècle, n°27, 1995. L'Antiquité. pp. 179-190

L'Antiquité et le christianisme dans la pensée de Jean-Jacques Rousseau

La pensee de Jean-Jacques Rousseau continue d’appeler les lectures critiques les plus diverses et de susciter des interpretations parfois contradictoires. Jean-Jacques Rousseau défendit passionnément les valeurs de la communauté démocratique.Citoyen de la petite république de Genève il recueillit avec ferveur l’enseignement des Hommes illustres de Plutarque et les leçons de l’Antiquité républicaine. Mais Jean-Jacques est aussi le philosophe du XVIIIe siècle qui fit reconnaître avec le plus d’éclat son irréductible singularité. Quand il engagea sa grande entreprise autobiographique, il souligna surtout sa différence. Et dans cette quête personnelle, toute particulière, Jean-Jacques trouvait l’appui d’une conviction chrétienne protestante. Rousseau recueillait ainsi à sa manière la double tradition de la Reforme et de l’Antiquité républicaine. Mais alors que ces deux dimensions coexistaient dans la république calviniste de Genève, Rousseau fut conduit à les dissocier, dans un ‘triste et grand système’ qui opposait avec une douloureuse obstination les valeurs de l’Homme et celles du Citoyen. L’enquête conduite en ce livre explore les profondeurs de ce paradoxe qui fait la grandeur de Rousseau. Remerciements Abréviations et citations Introduction: ‘Le problème Jean-Jack Rousseau’ 1. Une enfance à Genève: les Romains et les romans 2. 1728-1749: une si longue attente 3. 1749-1756: ‘l’intrépidité de la vertu’ 4. Avril 1756-automne 1758: ermite, ‘berger’ ou citoyen? 5. 1758-1762: l’aboutissement du ‘système’. L’Emile et le Contrat social 6. 1762-1778: ‘Vitam impendere vero’ 7. L’individu et la communauté 8. Le statut du politique 9. Le clos et l’ouvert Conclusion Bibliographie Index <br/