La nutrition parentérale chez les patients en phase palliative de cancer : de "l'oralité bouche" à "l'oralité cutanée".

The practice of prescribing parenteral nutrition in the palliative phase of cancer leads to different reactions in patients. In this work, we will take a psychological approach to the experience of body image in this phase of cancer. Interviewing patients who accept or refuse this parenteral nutrition, we will focus on certain functions of the “Moi-peau” concept defined by Didier Anzieu. Indeed, creating an artificial area of the body for nutrition purposes disturbs body image in the field of orality. How will the “me” of the subject invest in this new body economically ?La pratique de la prescription de la nutrition parentérale en phase palliative d’un cancer soulève différentes réactions chez le malade. Dans ce travail, nous proposons d’orienter notre réflexion vers une approche psychologique de l’image inconsciente du corps. En interrogeant des patients qui acceptent ou refusent ce nouveau type d’alimentation, nous viendrons questionner le rôle de certaines fonctions du « Moi-peau » définit par Didier Anzieu. Effectivement, la création d’une zone artificielle de nutrition vient perturber l’image du corps dans le registre pulsionnel de l’oralité. Comment le Moi du sujet peut-il économiquement investir ou non cette nouvelle zone du corps

Systematic transcriptional profiling of responses to STAT1- and STAT3- activating cytokines in different cancer types

Cytokines orchestrate responses to pathogens and in inflammatory processes but they also play an important role in cancer by shaping the expression levels of cytokine response genes. Here, we conducted a large profiling study comparing miRNome and mRNA transcriptome data generated following different cytokine stimulations. Transcriptomic responses to STAT1- (IFN, IL-27) and STAT3-activating cytokines (IL6, OSM) were systematically compared in nine cancerous and nonneoplastic cell lines of different tissue origins (skin, liver and colon). The largest variation in our datasets was seen between cell lines of the three different tissues rather than stimuli. Notably, the variability in miRNome datasets was a lot more pronounced than in mRNA data. Our data also revealed that cells of skin, liver and colon tissues respond very differently to cytokines and that the cell signaling networks activated or silenced in response to STAT1- or STAT3- activating cytokines are specific to the tissue and the type of cytokine. However, globally, STAT1-activating cytokines had stronger effects than STAT3-inducing cytokines with most significant responses in liver cells, showing more genes up-regulated and with higher fold change. A more detailed analysis of gene regulations upon cytokine stimulation in these cells provided insights into STAT1- versus STAT3-driven processes in hepatocarcinogenesis. Finally, independent component analysis revealed interconnected transcriptional networks distinct between cancer cells and their healthy counterparts

DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations

The PD-L1- and IL6-mediated dampening of the IL27/STAT1 anticancer responses are prevented by a-PD-L1 or a-IL6 antibodies

Interleukin-27 (IL27) is a type-I cytokine of the IL6/IL12 family and is predominantly secreted by activated macrophages and dendritic cells.We show that IL27 induces STAT factor phosphorylation in cancerous cell lines of different tissue origin. IL27 leads to STAT1 phosphorylation and recapitulates an IFN- -like response in the microarray analyses, with up-regulation of genes involved in antiviral defense, antigen presentation, and immune suppression. Like IFN- , IL27 leads to an up-regulation of TAP2 and MHC-I proteins, which mediate increased tumor immune clearance. However, both cytokines also upregulate proteins such as PD-L1 (CD274) and IDO-1, which are associatedwith immune escape of cancer. Interestingly, differential expression of these geneswas observed within the different cell lines and when comparing IL27 to IFN- . In coculture experiments of hepatocellular carcinoma (HCC) cells with peripheral blood mononuclear cells, pre-treatment of the HCC cells with IL27 resulted in lowered IL2 production by anti-CD3/-CD28 activated T-lymphocytes. Addition of anti-PD-L1 antibody, however, restored IL2 secretion. The levels of other TH1 cytokines were also enhanced or restored upon administration of anti-PD-L1. In addition, we show that the suppression of IL27 signaling by IL6-type cytokine prestimulation— mimicking a situation occurring, for example, in IL6-secreting tumors or in tumor inflammation–induced cachexia—can be antagonized by antibodies against IL6-type cytokines or their receptors. Therapeutically, the antitumor effects of IL27 (mediated, e.g., by increased antigen presentation) might thus be increased by combining IL27with blocking antibodies against PD-L1 or/and IL6-type cytokines

Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients.: Effectiveness of triple therapy in cirrhotic patients

International audienceTriple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P = 0.5), but there was a significant difference in the 50% effective concentrations (EC50) (P = 0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively, P = 0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day(-1)) and was higher in patients who subsequently eradicated HCV (P = 0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients

Parenteral nutrition in the palliative phase of cancer in patients : orality to orality through the skin

La pratique de la prescription de la nutrition parentérale en phase palliative d’un cancer soulève différentes réactions chez le malade. Dans ce travail, nous proposons d’orienter notre réflexion vers une approche psychologique de l’image inconsciente du corps. En interrogeant des patients qui acceptent ou refusent ce nouveau type d’alimentation, nous viendrons questionner le rôle de certaines fonctions du « Moi-peau » définit par Didier Anzieu. Effectivement, la création d’une zone artificielle de nutrition vient perturber l’image du corps dans le registre pulsionnel de l’oralité. Comment le Moi du sujet peut-il économiquement investir ou non cette nouvelle zone du corps ?The practice of prescribing parenteral nutrition in the palliative phase of cancer leads to different reactions in patients. In this work, we will take a psychological approach to the experience of body image in this phase of cancer. Interviewing patients who accept or refuse this parenteral nutrition, we will focus on certain functions of the “Moi-peau” concept defined by Didier Anzieu. Indeed, creating an artificial area of the body for nutrition purposes disturbs body image in the field of orality. How will the “me” of the subject invest in this new body economically

Variabilité génétique du virus de l'hépatite C et persistance virale

TOULOUSE3-BU Sciences (315552104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF