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From 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.
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PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. EXPERIMENTAL DESIGN: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. RESULTS: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. CONCLUSIONS: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy.
Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/radioterapia , Animais , Antineoplásicos Alquilantes/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Técnicas In Vitro , Injeções Intralesionais , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/farmacologia , Oxigênio/metabolismo , Perfusão , Veia Safena/efeitos dos fármacos , Veia Safena/fisiopatologia , Veia Safena/efeitos da radiação , Resultado do Tratamento , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/efeitos da radiaçãoRESUMO
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 ET(A) 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 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. 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. In conclusion, tumor endogenous ET-1 production participates largely in the temporal and spatial variations in tumor blood flow. ET(A) antagonist administration may wipe out such heterogeneities, thus representing an adjuvant strategy that could improve the delivery of conventional chemotherapy to tumors.
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Sistemas de Liberação de Medicamentos , Antagonistas do Receptor de Endotelina A , Endotelina-1/farmacologia , Neoplasias/irrigação sanguínea , Neovascularização Patológica/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Ciclofosfamida/farmacologia , Marcação In Situ das Extremidades Cortadas , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Relaxamento Muscular/efeitos dos fármacos , Neoplasias/patologiaRESUMO
PURPOSE: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible "normalization" of the tumor vasculature that could be exploited to improve radiotherapy. EXPERIMENTAL DESIGN: Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO(2)) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrast-enhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a "wick-in-needle" technique. RESULTS: Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling. CONCLUSIONS: In summary, the microenvironmental changes induced by thalidomide were sufficient to radiosensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization.