Drug development in oncology assisted by noninvasive optical imaging.

International audienceEarly and accurate detection of tumors, like the development of targeted treatments, is a major field of research in oncology. The generation of specific vectors, capable of transporting a drug or a contrast agent to the primary tumor site as well as to the remote (micro-) metastasis would be an asset for early diagnosis and cancer therapy. Our goal was to develop new treatments based on the use of tumor-targeted delivery of large biomolecules (DNA, siRNA, peptides, or nanoparticles), able to induce apoptosis while dodging the specific mechanisms developed by tumor cells to resist this programmed cell death. Nonetheless, the insufficient effectiveness of the vectorization systems is still a crucial issue. In this context, we generated new targeting vectors for drug and biomolecules delivery and developed several optical imaging systems for the follow-up and evaluation of these vectorization systems in live mice. Based on our recent work, we present a brief overview of how noninvasive optical imaging in small animals can accelerate the development of targeted therapeutics in oncology

In-situ Analysis of Laminated Composite Materials by X-ray Micro-Computed Tomography and Digital Volume Correlation

The complex mechanical behaviour of composite materials, due to internal heterogeneity and multi-layered composition impose deeper studies. This paper presents an experimental investigation technique to perform volume kinematic measurements in composite materials. The association of X-ray micro-computed tomography acquisitions and Digital Volume Correlation (DVC) technique allows the measurement of displacements and deformations in the whole volume of composite specimen. To elaborate the latter, composite fibres and epoxy resin are associated with metallic particles to create contrast during X-ray acquisition. A specific in situ loading device is presented for three-point bending tests, which enables the visualization of transverse shear effects in composite structures

Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy

Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is implicated in cell proliferation, differentiation, and apoptosis. Despite present advances, only the tip of the iceberg has so far been uncovered regarding the role of ECM compounds in influencing biotensegrity in pathological processes. Groups of cells, together with the surrounding ground substance, are subject to different and specific forces that certainly influence biological processes. In this paper, we review the current knowledge on the role of ECM elements in determining biotensegrity in malignant processes and describe their implication in therapeutic response, resistance to chemo- and radiotherapy, and subsequent tumor progression. Original data based on the study of neuroblastic tumors will be provided

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

International audienceAGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Is Crisis Management (only) a Management of exceptions?

International audienceThis paper revisits the concept of crisis within the field of crisis management and puts forward a series of avenues for building a theory of crisis that is in closer relation with the mainstream of organization theory. We suggest that if crisis management still limits itself to the analysis of exceptional situations, it might never go beyond the sphere of exception management and will for a long time remain an isolated discipline with little room for innovation and progress. As an alternative we analyze crises as a process of incubation that starts long before the triggering event. This proposition implies revisiting other related notions that have seldom been discussed by authors: first the status and place of the triggering event that should be viewed both as a fault line and a hinge between a degenerative organizational past evolution and a future of change; second, the temporality of a crisis so as to extract it from the urgency it is traditionally associated with; third and contrary to authors who see in the crisis a collapse of meaning and of sensemaking, we analyze it as a surge of meaning that fosters organizational change and transformations.<br/

Apprendre des crises. Entre le statu quo et la transformation

Learning from crises. Between status quo and transformation The article presents the results of research on the role of organizational learning in crisis management. Based on seven case studies of companies having managed crises, we expose a few mechanisms which limit the degree of organizational learning. Our results lead us to conclude the existence of a process of normalization in times of crisis. This process covers several dimensions in the management of a crisis. It indicates that organizations have a limited propensity to learn when they face a crisis and strive to retreat and to reduce the complexity of the event in order to make it psychologically and socially acceptable.Cet article présente les résultats d'une recherche sur les processus d'apprentissage organisationnel à l'œuvre dans la gestion des crises. En nous appuyant sur une recherche empirique auprès de sept entreprises ayant eu à gérer des crises, nous présentons quelques mécanismes propres à limiter leur apprentissage. Les principales conclusions convergent vers l'identification d'un processus de normalisation des crises qui atteste que les organisations ont une capacité limitée d'apprentissage lorsqu'elles sont confrontées à une crise et s'efforcent de retraiter les événements selon des normes préétablies afin de réduire et compresser la complexité de l'événement et les rendre psychologiquement et socialement acceptables.Aprender de las crisis. Entre statu quo y transformación Este articulo presenta los resultados de una investigación sobre los procesos de aprendizaje organizacional implementados en la gestión de las crisis. A partir de una investigación empirica ante siete empresas que se han enfrentado a crisis, presentamos unos mecanismos que permiten limitar su aprendizaje. Las principales conclusiones coinciden en la identificación de un proceso de normalización de las crisis. Muestra que las organizaciones tienen una capacidad limitada de aprendizaje cuando conocen una crisis y que intentan volver a tratar los eventos segun las normas para reducir la complejidad del acontecimiento y para que sean psicológicamente y socialmente aceptables.Roux-Dufort Christophe. Apprendre des crises. Entre le statu quo et la transformation. In: Sciences de la société, n°44, 1998. Urgence et décision. pp. 165-182

Gérer et décider en situation de crise

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The Devil lies in details! : How crises build up within organizations

International audienceIn this paper, we show that crises result from the combination of two parallel cumulative processes: first, an undercurrent accumulation of organizational imperfections that lay a favourable ground for crises to occur and second, the development of a growing ignorance that keeps managers blind to the presence of these imperfections. The central idea is to demonstrate that organizational imperfections are allowed to build up and grow into vulnerabilities because they are not noticed or taken into consideration. This managerial ignorance is described as a self-nourishing retreat from reality that decreases leaders’ ability to pay sufficient attention to the increasing process of accumulation of imperfections and vulnerabilities. A case study in a French chain of supermarket is used to illustrate this process of crisis.<br/