Renversement des hétérogénéités spatiale et temporelle de la perfusion tumorale identifie la tumeur tonus vasculaire comme une variable ajustable pour améliorer la prestation de drogue

peer reviewedMaturation de la vascularisation tumorale implique le recrutement de péricytes qui protègent les tubes endothéliales provenant de diverses contraintes, y compris les médicaments anti-angiogéniques. Mural cells also provide mature tumor blood vessels with the ability to either relax or contract in response to substances present in the tumor microenvironment. cellules murale également fournir d'âge mûr vaisseaux sanguins des tumeurs avec la possibilité de détendre ou se contracter en réponse à des substances présentes dans le microenvironnement de la tumeur. The observed cyclic alterations in tumor blood flow and the associated deficit in chemotherapeutic drug delivery could in part arise from this vasomodulatory influence. To test this hypothesis, we focused on endothelin-1 (ET-1), which, besides its autocrine effects on tumor cell growth, is a powerful vasoconstrictor. Les cycliques altérations observées dans la circulation sanguine des tumeurs et le déficit lié à la livraison de médicaments chimiothérapeutiques pourrait en partie résulter de cette influence vasomodulatory. Pour tester cette hypothèse, nous nous sommes concentrés sur l'endothéline-1 (ET-1), qui, outre ses effets sur la tumeur autocrine la croissance cellulaire, est un puissant vasoconstricteur. We first document that an ET A receptor antagonist induced relaxation of microdissected tumor arterioles and selectively and quantitatively increased tumor blood flow in experimental tumor models. Nous premier document qu'un antagoniste des récepteurs ET A la relaxation induite par des artérioles tumeur microdisséquées et sélectivement et quantitativement l'augmentation du débit sanguin tumorale dans des modèles expérimentaux de tumeurs. We then combined dye staining of functional vessels, fluorescent microsphere-based mapping, and magnetic resonance imaging to identify heterogeneities in tumor blood flow and to examine the reversibility of such phenomena. Nous avons ensuite combiné de la coloration des vaisseaux fonctionnels, fluorescent à base de microsphères de cartographie et d'imagerie par résonance magnétique pour identifier les hétérogénéités du débit sanguin des tumeurs et d'examiner la réversibilité de ces phénomènes. Data from all these techniques concurred to show that administration of an ET A receptor antagonist could reduce the extent of underperfused tumor areas, proving the key role of vessel tone variations in tumor blood flow heterogeneity. Les données de toutes ces techniques d'accord pour montrer que l'administration d'un antagoniste des récepteurs ET A pourrait réduire l'étendue des zones tumorales underperfused, ce qui prouve le rôle clé du navire variations des flux de ton hétérogénéité sanguins des tumeurs. We also provide evidence that ET A antagonist administration could, despite an increase in tumor interstitial fluid pressure, improve access of cyclophosphamide to the tumor compartment and significantly influence tumor growth. Nous avons également fournir la preuve que l'administration antagoniste ET A pourrait, en dépit d'une augmentation de la tumeur interstitielle pression d'un fluide, d'améliorer l'accès de cyclophosphamide dans le compartiment des tumeurs et une influence significative sur la croissance tumorale. In conclusion, tumor endogenous ET-1 production participates largely in the temporal and spatial variations in tumor blood flow. En conclusion, une tumeur ET-1 endogène de production participe largement à l'espace et les variations temporelles du flux sanguin tumoral. ET A antagonist administration may wipe out such heterogeneities, thus representing an adjuvant strategy that could improve the delivery of conventional chemotherapy to tumors. ET Une administration antagoniste peut effacer ces hétérogénéités, ce qui représente une stratégie adjuvant qui pourraient améliorer la prestation de la chimiothérapie conventionnelle des tumeurs. [Mol Cancer Ther 2006;5(6):1620–7] [Cancer Mol Il 2006; 5 (6) :1620-7]Maturation of tumor vasculature involves the recruitment of pericytes that protect the endothelial tubes from a variety of stresses, including antiangiogenic drugs. Mural cells also provide mature tumor blood vessels with the ability to either relax or contract in response to substances present in the tumor microenvironment. The observed cyclic alterations in tumor blood flow and the associated deficit in chemotherapeutic drug delivery could in part arise from this vasomodulatory influence. To test this hypothesis, we focused on endothelin-1 (ET-1), which, besides its autocrine effects on tumor cell growth, is a powerful vasoconstrictor. We first document that an ETA receptor antagonist induced relaxation of microdissected tumor arterioles and selectively and quantitatively increased tumor blood flow in experimental tumor models. We then combined dye staining of functional vessels, fluorescent microsphere-based mapping, and magnetic resonance imaging to identify heterogeneities in tumor blood flow and to examine the reversibility of such phenomena. Data from all these techniques concurred to show that administration of an ETA receptor antagonist could reduce the extent of underperfused tumor areas, proving the key role of vessel tone variations in tumor blood flow heterogeneity. We also provide evidence that ETA antagonist administration could, despite an increase in tumor interstitial fluid pressure, improve access of cyclophosphamide to the tumor compartment and significantly influence tumor growth. In conclusion, tumor endogenous ET-1 production participates largely in the temporal and spatial variations in tumor blood flow. ETA antagonist administration may wipe out such heterogeneities, thus representing an adjuvant strategy that could improve the delivery of conventional chemotherapy to tumors. [Mol Cancer Ther 2006;5(6):1620–7

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Applied improvisation and transdisciplinary simulation: a necessity for any health curriculum ?

International audienceFrom practising a procedure, such as a lumbar puncture, to explaining the aim and method and listening to concerns, the practice of health professionals requires a range of skills, often classified into technical and non-technical skills. Just as gestures and procedures can be taught, so can empathy and communication skills. This article introduces an innovative approach that unites both necessary types of skills. The specific framework of improvisational theatre (“improv”) has widespread application, including the training of health professionals (health training improv). By sharing close contexts and skills, health training improv provides a valuable, safe, and effective learning environment that allows practitioners to practice exercises and situations that align with particular objectives. We created a transdisciplinary team to develop a programme of Health Professional Training Improv (HPTI), bringing together the fields of health, psychology, simulation, and arts. Since 2019, various health student groups (nurses, midwives, medical doctors, and speech therapists) have participated in a 16-h applied improv training workshop under the supervision of a professional improv facilitator. Additionally, drama students completed applied improv for health courses, which trained them to act as simulated patients, with a view to the implementation of transdisciplinary improv simulation sessions at SimUSanté (a multidisciplinary health simulation facility located in France). Students’ feedback emphasized their interest in HPTI, the realism of the simulation sessions, and the skills they felt had improved. This feedback needs to be supplemented with quantitative data from standardised assessments. The development of this rich pedagogical and research framework, based on a transdisciplinary approach, has brought different fields together to prepare students for real patient encounters. It is essential to continue this training and conduct research to evaluate the curricula developed

Pour prévoir l’imprévisible, il faut improviser en s’y préparant

International audienc

Evaluation of cost and length of stay, linked to complications associated with major surgical procedures

Introduction: A lot of studies have demonstrated the possibility of reducing the number of post-operative complications in the domain of major surgical procedures with the use of medical preventive techniques. However, complications following surgical procedures are unfortunately frequent and are a major problem, not only because of the impact for the patient, but also because of economic consequences that they provoke. The aim of the present study is to evaluate the extra length of stay and the extra cost, born by the hospital and the social security, linked to complications, incurring after major surgical procedures.Material and methods: Study based on the data from 13 Belgian hospitals for the year 2012. Complications were extracted through medical discharge summaries. The cost born by the social security was assessed on the basis of the billing data, hospital cost are taken from cost accounting studies.Results: The rate of complication for all the hospitals is 6.6%. About 30.3% of inpatient stays having a major or extreme severity of index had a complication during the stay, 1.8% of stays with a minor or moderate severity of index had a complication. The extra length of stay is 19.38 days when the stay has had a complication (p Discussion/conclusion: The present study has shown that the actual financing do not cover real hospital costs in the field of major surgical procedures having caused complications. Results should encourage Belgian authorities to propose and finance preventive measures in order to reduce these complications, which represent major economic impacts, not only for authorities but also for hospitals.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mechanism of reoxygenation after antiangiogenic therapy using SU5416 and its importance for guiding combined antitumor therapy

Emerging preclinical studies support the concept of a transient "normalization" of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated radiotherapy or chemotherapy. One key issue in this area of research is to determine whether this feature is common to all antiangiogenic drugs and whether the phenomenon occurs in all types of tumors. In the present study, we characterized the evolution of the tumor oxygenation (in transplantable liver tumor and FSAII tumor models) after administration of SU5416, an antagonist of the vascular endothelial growth factor receptor. SU5416 induced an early increase in tumor oxygenation [measured by electronic paramagnetic resonance (EPR)], which did not correlate with remodeling of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry) or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration (measured by EPR) was responsible for this early reoxygenation. Consistent with these unique findings in the tumor microenvironment, we found that SU5416 potentiated tumor response to radiotherapy but not to chemotherapy. In addition to the fact that the characterization of the tumor oxygenation is essential to enable correct application of combined therapies, our results show that the long-term inhibition of oxygen consumption is a potential novel target in this class of compounds