L'aventure de la parole selon Jean-Louis Chrétien

L’oeuvre en cours de Jean-Louis Chrétien – une trentaine de volumes à ce jour – séduit par la beauté de son écriture et force l’admiration par la richesse de sa culture (philosophique, théologique et littéraire), mais il faut aussi la lire comme l’oeuvre d’un philosophe rigoureux. Dans L’Arche de la parole (1998) Chrétien se confronte au Heidegger d’Acheminement vers la parole en mobilisant des ressources à la fois poétiques, bibliques et phénoménologiques, notamment avec l’oeuvre très discrètement citée mais pour lui décisive d’Henri Maldiney. Comme Heidegger et Maldiney, sa phénoménologie de la parole est nourrie de poésie, l’horizon proprement chrétien est lui un apport original. The work in progress of Jean-Louis Chrétien –at this moment about thirty volumes– seduces by the beauty of its writing and forces the appraisal by the wealth of its culture (philosophical, theological and literary), but it is necessary to read it as the work of a rigorous philosopher. In L’Arche de la parole (1998) Chrétien confronts Heidegger’s Unterwegs zur Sprache mobilizing at the same time poetic, biblical and phenomenological resources, including the work of Henri Maldiney, which is most discreetly quoted by Chrétien, although it is decisive for him. As Heidegger and Maldiney, his phenomenology of the word is nurtured by poetry, whose properly Christian horizon is an original contribution

Mining for facts: PacRim Cayman LLC v. El Salvador

Responds to Perspective No. 23 by Gus Van Harten by briefly presenting Pacific Rim's case in Pacific Rim v. El Salvador and defends the international arbitration process by which this case is being adjudicated as fair, neutral and objective for both parties

STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

BACKGROUND: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. METHODS/DESIGN: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. DISCUSSION: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. TRIAL REGISTRATION: STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013. STRATEGIC-1 is registered at EudraCT-No.: 2013-001928-19, 25 April, 2013

STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer

International audienceBackground: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. Methods/Design: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies.Discussion: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. Trial registration: STRATEGIC-1 is registered a

Adjuvant therapies in advanced hepatocellular carcinoma: moving forward from the STORM

ABSTRACT: Like other previous treatments and approaches, sorafenib, an antiangiogenic drug, failed to show any benefit in the adjuvant setting for hepatocellular carcinoma in a large clinical trial. We discuss reasons and implications of these negative results and the implications for clinical practice and future research. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00692770. Registered 5 June 2008. This study has been completed

Targeting cancer cell metabolism in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided

Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection

There was no study funding. We are grateful to Tony Rafferty (Tailored Information for the People of Scotland, TIPs) for providing survival data.Peer reviewedPublisher PD

Turn indicator

This report presents a study of an instrument that can warn the pilot of the turning of his airplane. This instrument must satisfy three conditions: 1) It must give useful indication immediately from take-off; 2) The indications must be instantaneous and require no exertion by the pilot; 3) The indicator must be sensitive only to changes of orientation in the horizontal plane. Different solutions are presented such as a gyroscope driven by the suction of a Venturi tube

Disseminated and circulating tumor cells in gastrointestinal oncology.

International audienceCirculating (CTCs) and disseminated tumor cells (DTCs) are two different steps in the metastatic process. Several recent techniques have allowed detection of these cells in patients, and have generated many results using different isolation techniques in small cohorts. Herein, we review the detection results and their clinical consequence in esophageal, gastric, pancreatic, colorectal, and liver carcinomas, and discuss their possible applications as new biomarkers