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Preventing tumor neovascularisation is one of the strategies recently developed to limit the dissemination of cancer cells and apparition of metastases. Although these approaches could improve the existing treatments, a number of unexpected negative effects have been reported, mainly linked to the hypoxic condition and the subsequent induction of the pro-oncogenic hypoxia inducible factor(s) resulting from cancer cells’ oxygen starvation. Here, we checked in vivo on colon cancer cells an alternative approach. It is based on treatment with myo-inositol trispyrophosphate (ITPP), a molecule that leads to increased oxygenation of tumors. We provide evidence that ITPP increases the survival of mice in a model of carcinomatosis of human colon cancer cells implanted into the peritoneal cavity. ITPP also reduced the growth of subcutaneous colon cancer cells xenografted in nu/nu mice. In the subcutaneous tumors, ITPP stimulated the expression of the homeobox gene Cdx2 that is crucial for intestinal differentiation and that also has an anti-tumoral function. On this basis, human colon cancer cells were cultured in vitro in hypoxic conditions. Hypoxia was shown to decrease the level of Cdx2 protein, mRNA and the activity of the Cdx2 promoter. This decline was unrelated to the activation of HIF1α and HIF2α by hypoxia. However, it resulted from the activation of a phosphatidylinositol 3-kinases-like mitogen-activated protein kinase pathway, as assessed by the fact that LY294002 and U0126 restored high Cdx2 expression in hypoxia. Corroborating these results, U0126 recapitulated the increase of Cdx2 triggered by ITPP in subcutaneous colon tumor xenografts. The present study provides evidence that a chemical compound that increases oxygen pressure can antagonize the hypoxic setting and reduce the growth of human colon tumors implanted in nu/nu mice.

Objectif et méthode : Le Plan obésité a permis la création en France de 37 centres spécialisés de l’Obésité (CSO) en 2012 pour assurer une double mission : la prise en charge pluridisciplinaire de l’obésité sévère ou complexe et l’organisation des filières de soins dans les régions. Ce rapport fait le bilan des trois premières années de fonctionnement des CSO, à partir des données recueillies par l’Observatoire national des CSO (oNCSO), mis en place par la direction générale de l’hospitalisation et de l’offre de soins. Résultats : Le bilan était globalement positif pour l’accès aux examens paracliniques, même si tous les CSO ne disposaient pas d’absorptiomètre biphotonique (DEXA) ni de calorimé- trie. Les CSO développaient d’emblée des liens avec les 12 secteurs de prise en charge étudiés par l’oNCSO, avec quelques points faibles, dont la psychiatrie. L’enquête ne permettait pas de faire le point sur les effectifs réels des CSO, au vu du nombre important de données aberrantes. Tous les CSO répondants déclaraient avoir des programmes d’éducation thérapeutique orientés vers les obèses pour les filières médicale, chirurgicale et pédiatrique. L’activité des CSO en médecine, chirurgie, gynécologie-obstétrique et pédiatrie était hétérogène. En 2014, environ 25 à 30 % de l’ensemble des interventions de chirurgie bariatrique en France étaient pratiquées dans les CSO. En moyenne, les CSO recevaient environ 2 500 patients adultes sévèrement obèses, en consultation ou en hospitalisation de jour pour la filière médicale. Les résultats suggéraient une certaine fragilité des filières de gynécologie-obstétrique et des filières pédiatriques. Conclusion : Cette enquête déclarative, malgré de nombreuses limites, montre cependant que les CSO ont pris d’ emblée une place importante dans le système de soins français. Objective and method: The French obesity plan enabled the creation of 37 specialized Obesity Centers (CSOs) in 2012 to ensure a dual mission, the multidisciplinary management of severe or complex obesity and the organization of care channels in the regions. This report takes stock of the first 3 years of operation of the CSOs, based on the data collected by the National Observatory of CSOs (oNCSO), set up by the General Directorate of Hospitalization and Care. Results: The overall results were positive for accessing para- clinical examinations, although all CSOs did not have a biphotonic absorptiometry (DEXA) or calorimetry. The CSOs were initially developing links with the 12 sectors of care studied by the oNCSO, with some weaknesses including psychiatry. However, the survey did not make it possible to take stock of the real numbers of the actual workforce of the CSOs, given the large number of outliers. All responding CSOs were reported having obese-oriented therapeutic education programs for the medical, surgical, and pediatric sectors. The activities of CSOs in medicine, surgery, gynecology, and obstetrics were heterogeneous. In 2014, about 25-30% of all bariatric surgery procedures were performed in the CSOs in France. On average, CSOs received about 2500 severely obese adult patients in day-care or in-patient care for the medical sector. The results suggested a certain fragility of the pathways of obstetric gynecology and the pediatric pathways. Conclusion: This declarative survey, despite many limitations, shows however that CSOs have taken an important place in the French care system.

Topoisomerase genes were analyzed at both DNA and RNA levels in 25 cases of newly diagnosed childhood acute lymphoblastic leukemia (ALL). The results of molecular analysis were compared to risk group classification of children in order to identify molecular characteristics associated with response to therapy. At diagnosis, allelic imbalance at topo-isomerase IIα ( TOP2A ) gene locus was found in 75% of informative cases whereas topoisomerase I and IIβ gene loci are altered in none or only one case, respectively. By semi-quantitative Polymerase chain reaction, we found a 2.5 to 8-fold TOP2A gene amplification in 72% of the children, which was correlated to gene overexpression in every case. These results show that TOP2A gene amplification is a frequent event in ALL at diagnosis. Interestingly, we also identified a small population of children that do not present TOP2A gene amplification or gene overexpression and who are significantly associated with very high risk classified patients showing glucocorticoid resistance. In conclusion, characterization of TOP2A gene status in childhood ALL at diagnosis provides useful complementary information for risk assessment.

Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin 1 chain (LM 1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LM 1, VEGFA expression triggered by the complex integrin 2 1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation. A gene signature comprising LAMA1, ITGB1, ITGA2, CXCR4 and VEGFA has negative predictive value in colon cancer. Together, this information opens novel opportunities for diagnosis and anti-cancer targeting.

Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumorstroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation. A gene signature comprising LAMA1, ITGB1, ITGA2, CXCR4 and VEGFA has negative predictive value in colon cancer. Together, this information opens novel opportunities for diagnosis and anti-cancer targeting.

The rise of human populations and the growth of cities contribute to the depletion of natural resources, increase their cost, and create potential climatic changes. To overcome difficulties in supplying populations and reducing the resource cost, a search for alternative pharmaceutical, nanotechnology, and energy sources has begun. Among the alternative sources, microalgae are the most promising because they use carbon dioxide (CO2) to produce biomass and/or valuable compounds. Once produced, the biomass is ordinarily harvested and processed (downstream program). Drying, grinding, and extraction steps are destructive to the microalgal biomass that then needs to be renewed. The extraction and purification processes generate organic wastes and require substantial energy inputs. Altogether, it is urgent to develop alternative downstream processes. Among the possibilities, milking invokes the concept that the extraction should not kill the algal cells. Therefore, it does not require growing the algae anew. In this review, we discuss research on milking of diatoms. The main themes are (a) development of alternative methods to extract and harvest high added value compounds; (b) design of photobioreactors; (c) biodiversity and (d) stress physiology, illustrated with original results dealing with oleaginous diatoms.