Ingénierie tumorale au sein d'un hydrogel d'acide hyaluronique : un modèle d'étude des propriétés des cellules malignes

ROUEN-BU Sciences (764512102) / SudocSudocFranceF

Three Dimensional Tumor Engineering by Co-Culture of Breast Tumor and Endothelial Cells Using a Hyaluronic Acid Hydrogel Model

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Artificial intelligence in diagnostic: How does the use of artificial intelligence affect the trust of kidney cancer patients in relation to the diagnostic process?

Dette projekt dykker ned i spørgsmålet om patienters tillid til kunstig intelligens-drevet nyrekræftdiagnostik i sundhedsvæsenet. Vi vil fokusere på, hvordan kunstig intelligens påvirker patienter i forhold til faktorer som følelser og tillid. Gennem et ekspertinterview med Henning Christiansen og interviews med vores målgruppe sigter vi mod at udfolde grundlaget for patienttillid. Denne rapport er inspireret af forskning udført af Pedersen (et al. 2020), "Efficient and Precise Classification of CT Scans of Renal Tumors Using Convolutional Neural Networks" (2020). Udover denne tekst har vi brugt andre relevante teorier og tekster om kunstig intelligens, tillid og samfund. Vi har udviklet et interaktivt webbaseret supportværktøj til læger og patienter som vores designløsning. Denne designløsning præsenterer et simuleret diagnostisk værktøj til nyrekræft baseret på CT-scanningsbilleder. Denne rapport konkluderer, at for patienter at stole på kunstig intelligens, er det afgørende at bygge et stærkt fundament, der vil hjælpe patienter med at blive mere komfortable med hensyn til dette problem. Det er vigtigt at gøre opmærksom på, at dette kun vil blive brugt i en sammenhæng, hvor læger arbejder sammen med kunstig intelligens i diagnosticering af nyrekræft.This project delves into the issue of patient trust in artificial intelligence-driven kidney cancer diagnostics in healthcare. We will focus on how artificial intelligence impacts patients in relation to factors such as emotions and trust. Through an expert interview with Henning Christiansen and interviews with our target group, we aim to unfold the base of patient trust. This report was inspired by the research of Pedersen (et al. 2020), “Efficient and Precise Classification of CT Scans of Renal Tumors Using Convolutional Neural Networks” (2020). Besides this text we have used other relevant theories and texts about artificial intelligence, trust and society. We have developed an interactive web-based support tool for doctors and patients as our design solution. This design solution presents a simulated diagnostic tool for kidney cancer based on CT scan images. This report concludes that for patients to trust artificial intelligence, it is crucial to build a strong foundation that will help patients become more comfortable in regard to this issue. It is important to address that this will only be used in a context where doctors work together with artificial intelligence in diagnosis of kidney cancer

Direct Effect of Bevacizumab on Glioblastoma Cell Lines In Vitro

International audienceBevacizumab is a humanized monoclonal antibody directed against the pro-angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Investigation of how bevacizumab interacts with glioblastoma cells and the resulting downstream signaling pathways will help targeting populations of resistant glioblastoma cells

Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry

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Biomimetic Three Dimensional Cell Culturing: Colorectal Cancer Micro-Tissue Engineering

International audienceBackground: Spheroid cultures are known to mimic closely the properties of tumor tissue than monolayer cultures with regard to growth kinetics and metabolic rates. The aim of this paper is to confirm that tumor micro-tissue in a 3D biocompatible microenvironment maintain the cells natural behavior when compared to 2D monolayer culturing.Method: In order to validate our 3D culture system, we compared the 3D culture within a cross-linked hydrogel of hyaluronic acid, one of the major components of the extracellular matrix and the conventional 2D culture system.Results: Interestingly within our culture system, cells could be analyzed either after retrieval from the scaffold or even without being extracted in the 3D form rendering the HA hydrogel an ideal tool for biological applications. We observed the difference in the cell cycle, cell proliferation and behavior in both culture systems. Additionally drug testing was carried out using a chemotherapeutic agent (cis-platinium) that is already in clinical use to unequivocally prove the clinical predictive significance of the test strategy as compared with less complex assay systems and more complex in vivo models. We observed the presence of cell cycle heterogeneity very similar to the situation in vivo human tumors. Moreover, we have confirmed that resistance to chemotherapeutic reagents within this 3D culture system is much higher than those used in 2D cultures, since the tight assembly of cells in 3D culture systems render them more resistant requiring chemotherapeutic doses that recapitulate the drug sensitivity of tumor cells in vivo. Additionally we have observed the difference of apoptotic protein expression between 2D and 3D cell culture

Gas6 promotes inflammatory (CCR2hiCX3CR1lo) monocyte recruitment in venous thrombosis

Objective - Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. Approach and Results - Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl and flow reduction in the inferior vena cava. Total monocyte depletion was achieved by injection of clodronate before deep venous thrombosis. Inflammatory monocytes were depleted using an anti-C-C chemokine receptor type 2 (CCR2) antibody. Similarly, injection of an anti-chemokine ligand 2 (CCL2) antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6 was associated with a reduction of monocyte recruitment in both deep venous thrombosis models. Global monocyte depletion by clodronate leads to smaller thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6 mice contain less inflammatory (CCR2CXCR1) monocytes, consistent with a Gas6-dependent recruitment of this monocyte subset. Correspondingly, selective depletion of CCR2CXCR1 monocytes reduced the formation of venous thrombi in wild-type mice demonstrating a predominant role of the inflammatory monocytes in thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in monocytes and endothelial cells, respectively, impacting monocyte migration. Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase). Conclusions - This study demonstrates that Gas6 specifically promotes the recruitment of inflammatory CCR2CXCR1 monocytes through the regulation of both CCR2 and CCL2 during deep venous thrombosis