La reprise, Kant, Marx

Le concept de reprise est à ce point décisif chez Eric Weil que sans lui il ne pourrait y avoir de logique de la philosophie. En effet, c’est grâce à la négation que la reprise entre dans le langage et la logique philosophique n’est rien d’autre qu’une analyse du langage. Cette proposition est ici explicitée sur deux exemples de grande importance : Kant et Marx. Chez l’un, la reprise permet de comprendre enfin clairement le sens du renversement eff ectué par la Critique de la faculté de juger et révèle que la Logique de la philosophie est un aboutis­sement de la révolution copernicienne initiée par Kant. Chez l’autre, ce concept donne un éclairage nouveau à la compréhension de la pensée de Marx, appréciée ici dans son rapport à la catégorie de l’Action, laquelle reprend celle de la Condition. Cet éclairage ainsi dirigé permet de re-poser la question du statut de l’œuvre intitulée Le Capital et de l’entendre comme un mode d’effectuation de la philosophie en tant que Science (Wissenschaft).O conceito de retomada é de tal forma decisivo para Eric Weil que sem ele não poderia haver lógica da filosofia. Com efeito, é graças à negação que a retomada entra na linguagem e a lógica filosófica não é nada mais que uma análise da linguagem. Esta afirmação é expli­cada neste artigo através de dois exemplos extremamente importantes: Kant e Marx. Em relação ao primeiro, a retomada permite compreender de forma clara o sentido da inversão operada pela Crítica da Faculdade de Julgar e mostra que a Lógica da Filosofia é um ponto de chegada da revolução coperniciana iniciada por Kant. No que respeita a Marx, a retomada permite uma nova compreensão do seu pensamento, considerado através da sua relação com a categoria da Ação a qual retoma a categoria da Condição. Essa nova compreensão permite assim relançar a questão do estatuto da obra O Capital e de a ler como um modo de efetuação da filosofia como Ciência (Wissenschaft)

Philosophie et politiqueHeidegger, nazisme et la pensée française

La philosophie de Heidegger a exercé une influence considérable sur une certaine pensée française et la question de son engagement politique occupe périodiquement le devant de la scène. Tel est le double constat d’où part cette étude. Elle s’efforce de montrer que cet engagement interpelle la philosophie entière et lui révèle une dimension jusque là inconnue de son être. Elle examine le problème en articulant le nazisme et l’heideggérianisme, compris comme le double aboutissement, politique et philosophique, de la même réalité, celle de l’histoire allemande.Tout comme le nazisme est l’aboutissement de toute une évolution dont le point de départ est la Réforme, l’heideggérianisme est l’achèvement logique, porté à sa perfection, d’une dimension permanente de la mentalité allemande. Heidegger est ainsi compris comme le pendant de Hegel : chacun parachève le courant dont il est l’héritier et ils donnent ensemble le tout de la pensée.Comment penser après cette double fin ? Telle est la question posée à notre fin de siècle, à laquelle a tenté de répondre Eric Weil.Heideggers Philosophie hat einen bedeutenden Einfluss ausgeübt auf gewisse französische Denker, und das Problem seines politischen Engagements wird immer wieder aufgeworfen. Dies sind die beiden Feststellungen, von denen der vorliegende Aufsatz ausgeht. Es wird versucht zu zeigen, dass dieses Engagement die Philosophie in ihrer Gesamtheit anspricht und ihr eine bisher unbekannte Dimension ihrer selbst eröffnet. Dieses Problem wird anhand einer Doppelbetrachtung des Nationalsozialismus und der Philosophie Heideggers erörtert, die als die beiden Realitäten aufgefasst werden, die politische und die philosophische, in welche die deutsche Geschichte einmündet.Ebenso wie der Nationalsozialismus das Ergebnis einer langen Entwicklung ist, deren Anfang bei der Reformation liegt, ist Heideggers Philosophie der logische Endaspekt, dargestellt in seiner Vollkommenheit, einer permanenten Dimension der deutschen Geistesverfassung. Heidegger erscheint also als der Gegenspieler von Hegel: jeder von beiden bringt die Denkrichtung, deren Erbe er ist, auf ein Endstadium, und zusammen bildet ihr Gedankengut ein Ganzes. Wie soll aber danach das Denken weitergehen ? Dies ist die Frage, die sich unserem ausgehenden Jahrhundert stellt, und auf welche Eric Weil versucht hat, eine Antwort zu geben

Avant-propos

La tension entre deux orientations opposées de l’esprit humain constitue, semble-t-il, un trait caractéristique essentiel de la pensée allemande. Son histoire est faite d’un équilibre instable entre l’affirmation du pouvoir de la raison et l’exaltation des forces irrationnelles, la recherche d’un humanisme centré sur l’idée de Bildung et la revendication impétueuse du sentiment. Notre siècle a connu la rupture tragique de cet équilibre. Le nazisme a offert au monde la figure de la violence pu..

Overview of Cellular Immunotherapy for Patients with Glioblastoma

High grade gliomas (HGG) including glioblastomas (GBM) are the most common and devastating primary brain tumours. Despite important progresses in GBM treatment that currently includes surgery combined to radio- and chemotherapy, GBM patients' prognosis remains very poor. Immunotherapy is one of the new promising therapeutic approaches that can specifically target tumour cells. Such an approach could also maintain long term antitumour responses without inducing neurologic defects. Since the past 25 years, adoptive and active immunotherapies using lymphokine-activated killer cells, cytotoxic T cells, tumour-infiltrating lymphocytes, autologous tumour cells, and dendritic cells have been tested in phase I/II clinical trials with HGG patients. This paper inventories these cellular immunotherapeutic strategies and discusses their efficacy, limits, and future perspectives for optimizing the treatment to achieve clinical benefits for GBM patients

Differential analysis of glioblastoma multiforme proteome by a 2D-DIGE approach

<p>Abstract</p> <p>Background</p> <p>Genomics, transcriptomics and proteomics of glioblastoma multiforme (GBM) have recently emerged as possible tools to discover therapeutic targets and biomarkers for new therapies including immunotherapy. It is well known that macroscopically complete surgical excision, radiotherapy and chemotherapy have therapeutic limitations to improve survival in these patients. In this study, we used a differential proteomic-based technique (2D-Difference Gel Electrophoresis) coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify proteins that may serve as brain tumor antigens in new therapeutic assays. Five samples of patients presenting a GBM and five samples of microscopically normal brain tissues derived from brain epileptic surgery specimen were labeled and run in 2D-PAGE (Two-Dimensional Polyacrylamide Gel Electrophoresis) with an internal pool sample on each gel. Five gels were matched and compared with DIA (Difference In-gel Analysis) software. Differential spots were picked, in-gel digested and peptide mass fingerprints were obtained.</p> <p>Results</p> <p>From 51 protein-spots significantly up-regulated in GBM samples, mass spectrometry (MS) identified twenty-two proteins. The differential expression of a selected protein set was first validated by western-blotting, then tested on large cohorts of GBM specimens and non-tumor tissues, using immunohistochemistry and real-time RT-PCR.</p> <p>Conclusions</p> <p>Our results confirmed the importance of previously described proteins in glioma pathology and their potential usefulness as biological markers but also revealed some new interesting targets for future therapies.</p

DGKI Methylation Status Modulates the Prognostic Value of MGMT in Glioblastoma Patients Treated with Combined Radio-Chemotherapy with Temozolomide

International audienceBackgroundConsistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status.Methods399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2.ResultsThe nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram.ConclusionsOur results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future

Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients

Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategie

DNA methylation in glioblastoma: impact on gene expression and clinical outcome

International audienceBACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key biological pathways have been reported in glioblastoma. Genome-wide assessments of DNA methylation levels are now required to decipher the epigenetic events involved in the aggressive phenotype of glioblastoma, and to guide new treatment strategies. RESULTS: We performed a whole-genome integrative analysis of methylation and gene expression profiles in 40 newly diagnosed glioblastoma patients. We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter of which was differentially expressed in a concordant way. Thirteen of the genes with concordant CpG sites displayed an inverse correlation between promoter methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival analysis identified six CpG sites associated with overall survival. SOX10 promoter methylation status (two CpG sites) stratified patients similarly to MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters identified patients with MGMT-methylated tumors that did not respond to STUPP treatment (p-value < 1e-04). CONCLUSIONS: This study provides the first genome-wide integrative analysis of DNA methylation and gene expression profiles obtained from the same GBM cohort. We also present a methylome-based survival analysis for one of the largest uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We have identified genes whose expression may be tightly regulated by epigenetic mechanisms and markers that may guide treatment decisions

L’image de Wilhelm von Humboldt dans la postérité

Notre but n’est pas de donner une présentation érudite, visant à l’exhaustivité, ni de dénombrer, sur le mode vain de la litanie, tous ceux qui, d’une manière ou d’une autre, ont porté un jugement sur Humboldt, mais de cerner les contours de ce que, pour l’essentiel, la postérité a retenu de l’œuvre, C’est pourquoi il nous suffira de constater que telle thèse, par exemple que la langue est energeia, est constamment citée, sans juger nécessaire de faire le recensement des auteurs qui la rappor..