[Exavir: Implementation and evaluation of experimental pharmacology skills acquisition by pharmacy students]. / Exavir : mise en place et évaluation de l'acquisition de compétences en pharmacologie expérimentale par des étudiants en pharmacie.

With the evolution of European and French regulations on animal experimentation in higher education, taking greater account of animal welfare, the University of Angers has developed a virtual animal experimentation software named Exavir. Used for practical work (PW) in physiology, pharmacology and toxicology in the Health, Sciences, and engineering curricula, Exavir can be used to simulate various experiments for teaching purposes, in vivo or ex vivo. Thanks to an original approach integrating serious games with different scenarios, students gain autonomy and become directly involved in their learning. In addition, Exavir's collaborative and participative development approach fosters inter-university partnerships and the emergence of innovative teaching methods. A hybrid pilot study carried out on a sample of 22 students in the Pharmacy Department of the Faculty of Health showed that Exavir improved students' acquisition of teaching skills in both physiology and pharmacology, compared with practical work only based on animal organs. These encouraging results demonstrate for the first time the pedagogical advantages of Exavir and confirm the interest in developing such a platform. In this context, it appears that Exavir also opens up the possibility of adapting the practical work offered within universities, and thus responding to the changing ethical issues of the coming decades.

Caliper, contrast enhanced-ultrasound or laser speckle contrast imaging: Techniques to follow mice melanoma growth.

Due to morphological characteristics, metastatic melanoma is a cancer for which vascularization is not a diagnostic criterion. Laser speckle contrast imaging (LSCI) and contrast enhanced ultrasound (CEUS) are two imaging techniques that will be explored in this study, which aims to confirm these two techniques for monitoring tumor vascularization. B16F10 cells were xenografted to C57BL/6 mice treated with anti-PD1 or 0.9% NaCl. Tumor volume was measured daily while CEUS and LSCI were performed weekly. LSCI and CEUS analyses showed a decrease in tumor perfusion in both groups of mice. Although both CEUS and LSCI are useful for measuring tumor volume, LSCI appears to be more robust and effective for monitoring tumor microcirculation. Non-invasive investigations are needed to better predict tumor vascularization: CEUS and LSCI have a good applicability in a mice model.

Therapeutic strategies for non-small cell lung cancer: Experimental models and emerging biomarkers to monitor drug efficacies.

While new targeted therapies have considerably changed the treatment and prognosis of non-small cell lung cancer (NSCLC), they are frequently unsuccessful due to primary or acquired resistances. Chemoresistance is a complex process that combines cancer cell intrinsic mechanisms including molecular and genetic abnormalities, aberrant interactions within the tumor microenvironment, and the pharmacokinetic characteristics of each molecule. From a pharmacological point of view, two levers could improve the response to treatment: (i) developing tools to predict the response to chemo- and targeted therapies and (ii) gaining a better understanding of the influence of the tumor microenvironment. Both personalized medicine approaches require the identification of relevant experimental models and biomarkers to understand and fight against chemoresistance mechanisms. After describing the main therapies in NSCLC, the scope of this review will be to identify and to discuss relevant in vitro and ex vivo experimental models that are able to mimic tumors. In addition, the interests of these models in the predictive responses to proposed therapies will be discussed. Finally, this review will evaluate the involvement of novel secreted biomarkers such as tumor DNA or micro RNA in predicting responses to anti-tumor therapies.

NOX1 and NOX2: Two enzymes that promote endothelial-to-mesenchymal transition induced by melanoma conditioned media.

Tumor microenvironment plays an important role in melanoma progression. Recent studies reported endothelial cells (EC) are involved in endothelial-to-mesenchymal transition (EndMT). During this phenotypic switch, EC progressively lose their endothelial markers and acquire mesenchymal properties. Depending on their concentration, reactive oxygen species (ROS) can control tumor growth. In EC, ROS are mainly produced by NAPDH oxidases (NOX) such as NOX1 and NOX2. The aim of the present study was to determine the role of these enzymes in EndMT induced by conditioned media (CM) from SK-MEL 28 melanoma cells. The capacity of CM to induce EndMT in HUVEC after 24 h, 48 h or 72 h has been evaluated by following endothelial HUVECs proliferation, migration and their capacity to form capillary on ECMgel®. Furthermore, EndMT was confirmed by western blot and flow cytometry. To determine the role of NOX in EndMT, specific NOX1 and/or NOX2 inhibitors has been tested. TGF-ß2 + /- IL-1ß was used as positive control. ROS production was determined through DCFDA assay. An altered endothelial phenotype was found in CM-treated HUVECs. This phenotypic modification was correlated with a decrease in both capillary formation on ECMgel® and cell proliferation and an increase in cell migration. Exposure to CM for 48 h significantly enhanced intracellular HUVECs ROS production and this increase was prevented by the dual pharmacological inhibition of NOX1 and NOX2. Furthermore, inhibition of NOX1/2 also leads to a partial reversion of CM-induced EndMT. These data confirmed the role of NOX1 and NOX2 in EndMT induced by melanoma cancer cell secretome.

p722 ferrocifen loaded lipid nanocapsules improve survival of murine xenografted-melanoma via a potentiation of apoptosis and an activation of CD8+ T lymphocytes.

Metastatic melanoma is a malignant tumor with a poor prognosis. Recent new therapeutics improved the survival of patients at a metastatic stage. However, the low response rate to immunotherapy, explained in part by resistance to apoptosis, needs to develop new strategies. The ferrocifen family represents promising bioorganometallic molecules for melanoma treatment since they show potent anticancer properties. The aim of this study is (i) to evaluate the benefits of a strategy involving encapsulated p722 in lipid nanocapsules (LNC) in B16F10 melanoma mice models and (ii) to compare the beneficial effects with an existing therapy such as anti-CTLA4 mAb. Interestingly, LNC-p722 induces a significant decrease of melanoma cell viability. In vivo data shows a significant improvement in the survival rate and a slower tumor growth with p722-loaded LNC in comparison with anti-CTLA4 mAb. Western blots confirm that LNC-p722 potentiates intrinsic apoptotic pathway. Treatment with LNC-p722 significantly activates CD8+ T lymphocytes compared to treatment with anti-CTLA4 mAb. This study uncovers a new therapeutic strategy with encapsulated p722 to prevent B16F10 melanoma growth and to improve survival of treated mice.