Protomic analysis of the receptor p75NTR in breast cancer

Le facteur de croissance neurotrophique NGF (Nerve Growth Factor) est un facteur mitogène et de survie pour les cellules de cancer du sein alors qu’il est sans effet sur la croissance des cellules épithéliales mammaires normales. Ce facteur de croissance agit sur ses cellules cibles par l’intermédiaire de deux récepteurs : TrkA, qui est un récepteur tyrosine kinase, et p75NTR, dépourvu d’activité catalytique intrinsèque. Le NGF stimule la survie des cellules cancéreuses mammaires via p75NTR en activant le facteur de transcription NF-ĸB. Au cours de mes travaux de thèse, je me suis tout d’abord appliqué à décrire les modifications du protéome induites par une surexpression de ce récepteur p75NTR. Pour cela, nous avons établi une lignée cellulaire MCF-7 surexprimant stablement le récepteur p75NTR. Par la suite, une étude par électrophorèse bidimensionnelle suivie par une analyse par spectrométrie de masse de type MALDI-TOF/TOF a été réalisée en comparant des cellules non stressées à des cellules induites en apoptose grâce à l’apoptogène TRAIL (TNF-related-apoptosis-inducing-ligand). Au cours de cette étude, nous avons pu mettre en évidence un certain nombre de protéines régulées par la présence de p75NTR en condition d’apoptose comme les cytokératines 8, 18 et 19, la protéine chaperonne HSP27 ou bien encore la protéine ribosomale RPLP0. Ces résultats suggèrent l’importance d’une réorganisation de ces protéines afin que p75NTR puisse effectuer son effet de survie. L’autre partie de mes travaux a consisté en une étude spécifique des partenaires de signalisation de p75NTR. Pour ce faire, nous avons décidé d’appliquer la stratégie TAP-Tag (Tandem Affinity Purification-Tag), une approche de protéomique fonctionnelle, au récepteur membranaire p75NTR. Une analyse différentielle de plusieurs conditions de culture par spectrométrie de masse de type nanoLC-MS/MS a abouti à l’obtention d’une liste de partenaires potentiels de signalisation de p75NTR dans un contexte de survie cellulaire. Cependant, l’implication fonctionnelle de ces protéines doit être confirmée. L’ensemble de ces travaux a permis d’ouvrir de nouvelles pistes de recherche pour comprendre à la fois les mécanismes cellulaires mis en œuvre lors de la survie des cellules cancéreuses mammaires, mais aussi les partenaires potentiels de signalisation du récepteur p75NTR.The growth factor NGF (nerve growth factor) is a mitogenic and survival factor for breast cancer cells but has no effect on normal epithelial mammary cell growth. This growth factor acts on breast cancer cells via two receptors : TrkA, a tyrosine kinase receptor, and p75NTR, which has no catalytic activity. NGF promotes breast cancer cells survival via p75NTR by activation of the transcriptional factor NF-κB. In the first time of my thesis work, I have described the proteome modification induced by an overexpression of p75NTR in apoptotic stress-induced breast cancer cells. We established a p75NTR overexpressing MCF-7 cell line. Thus, we investigated, by two dimensional electrophoresis followed by MALDI-TOF/TOF based mass spectrometry analysis, the proteome modification induced by the pro-apoptotic agent TRAIL (TNF-related-apoptosis-inducing-ligand). We describe some proteins regulated by p75NTR in an apoptosis condition like cytokeratin 8, 18 and 19, the HSP27 and the ribosomal protein RPLP0. These results show that the rearrangement of those proteins is associated to the survival effect of p75NTR in breast cancer cells. In a second part, we tried to identify the specific proteins partners of p75NTR for its survival pathway. For that, we applied the TAP-tag (tandem affinity purification tag) strategy, a functional proteomic approach, to the p75NTR receptor. A differential analysis by nanoLC-MS/MS mass spectrometry was conducted and we obtained a list of potentials proteins partners of the p75NTR activated survival pathway. The functional involvement of these proteins should be confirmed. Together, our work provides new data on the cellular mechanisms involved in the survival of breast cancer cells and also on the proteins partners implicated in p75NTR signaling

Hypocapnia measured by end-tidal carbon dioxide tension during anesthesia is associated with increased 30-day mortality rate

Study objective To evaluate the relationship between intraoperative end-tidal carbon dioxide (ETCO2) values and clinical outcomes with special attention on 30-day postoperative mortality and secondarily on hospital length of stay (LOS). Design Retrospective, observational study. Setting Surgical theaters of the University Hospital Center of Charleroi. Patients Five thousand three hundred seventeen patients ASA I-IV undergoing various surgical procedures (except pediatric and cardiac surgery) under general anesthesia. Interventions No intervention on the patients. Measurements The mean ETCO2 level measured during anesthesia was secondarily extracted from an electronic information management system. Patients were divided into 2 separate groups based on ETCO2 values less than or greater than or equal to 35 mm Hg. The primary end point was the in- and outhospital mortality in the 30-day period after surgery. The second was the LOS more than 6 days. Main results Hypocapnia occurred in 66% of the patients. Mortality rate at 30-day was 84 of 3554 (2.4%) in the low ETCO2 group vs 15 of 1763 (0.9%) in the other (odds ratio, 2.99 [1.69-5.28]; P < .001). In multivariate analysis, age and ASA scores had significant independent associations with mortality rate. Adjusting for these factors had an effect on the relative odds ratio of ETCO2 on mortality of 1.99 ([1.11-3.56]; P < .001). Patients with low ETCO2 experienced higher LOS (14.1 ± 9.4 vs 13.1 ± 8.9 days; P < .001). Thirty five percent of the patients in the low ETCO2 group were still hospitalized more than 6 days compared with 30% in the other (P < .001). Conclusion Low ETCO2 level during anesthesia is associated with an increase in postoperative mortality rate and LOS. These results emphasize the importance of preventing hypocapnia during anesthesia to improve surgical outcomes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Influence of malnutrition on childhood mortality in a rural hospital in Rwanda

info:eu-repo/semantics/publishe

Fetal limb growth: Part II

info:eu-repo/semantics/publishe

Improvements in nutritional management as a determinant of reduced mortality from community-acquired lower respiratory tract infection in hospitalized children from rural central Africa

info:eu-repo/semantics/publishe

Bactériémies chez les enfants admis à l’hôpital pédiatrique de Lwiro

info:eu-repo/semantics/nonPublishe

Amélioration de la gestion d'un programme de suivi de la croissance à base communautaire des enfants en milieu rural au Rwanda

Background: In order to improve the management of a community based nutrition program in the catchment area of Ruli District Hospital in Rwanda, we carried out a nutrition survey to determine the risk factors for childhood malnutrition in the area. Identifying the groups of children at risk of malnutrition and their risk factors allows the community nutrition workers to target the children who require close monitoring, and assists in the development of key messages for educational nutrition training. Methods: The prevalence of the three forms of malnutrition was estimated by using the Z-scores height for age, weight for age and weight for height with NCHS/OMS/2000 reference. Logistic regression was performed to identify the risk factors for malnutrition. Results: Our findings show that children from 12-35 months of age are at greatest risk of malnutrition. Risk factors for wasting include: low monthly income of the household, concurrent illness of the child and a household that does not practice breeding. Risk factors for underweight include: child being greater than 12 months of age, mother of the child being pregnant and history of malnutrition in the household. Finally, risk factors for stunting include the absence of a mosquito net in the household, an insufficient number of working adults in the household, the child being greater than 12 months of age and a household managed by a man alone or by an orphan. Conclusion: Community based growth monitoring must focus its attention on the children from nine to 35 months of age. Children less than nine months of age are generally followed by the health centers through the immunization program, and the older children are generally followed in the child minder schools that need to be promoted in all the cells. Community messages must focus on the identified risk factors of malnutrition, and a positive deviance approach must be introduced in the entire zone. © 2010 Elsevier Masson SAS.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Bacteremia in children admitted at the pediatric hospital in Lwiro, Zaïre

info:eu-repo/semantics/nonPublishe

Determinants of adherence to treatment for uncomplicated malaria in northeastern Democratic Republic of Congo

info:eu-repo/semantics/publishe

Biological risk factors for fatal protein energy malnutrition in hospitalized children in Zaire

SCOPUS: ar.jinfo:eu-repo/semantics/publishe