NARMER-1: a photon point-kernel code with build-up factors

International audienceThis paper presents an overview of NARMER-1, the new generation of photon point-kernel code developed by the Reactor Studies and Applied Mathematics Unit (SERMA) at CEA Saclay Center. After a short introduction giving some history points and the current context of development of the code, the paper exposes the principles implemented in the calculation, the physical quantities computed and surveys the generic features: programming language, computer platforms, geometry package, sources description, etc. Moreover, specific and recent features are also detailed: exclusion sphere, tetrahedral meshes, parallel operations. Then some points about verification and validation are presented. Finally we present some tools that can help the user for operations like visualization and pre-treatment

NARMER-1: a photon point-kernel code with build-up factors

This paper presents an overview of NARMER-1, the new generation of photon point-kernel code developed by the Reactor Studies and Applied Mathematics Unit (SERMA) at CEA Saclay Center. After a short introduction giving some history points and the current context of development of the code, the paper exposes the principles implemented in the calculation, the physical quantities computed and surveys the generic features: programming language, computer platforms, geometry package, sources description, etc. Moreover, specific and recent features are also detailed: exclusion sphere, tetrahedral meshes, parallel operations. Then some points about verification and validation are presented. Finally we present some tools that can help the user for operations like visualization and pre-treatment

Capacity of myeloid and plasmacytoid dendritic cells especially at mature stage to express and secrete HLA-G molecules

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research paper Expression of functional soluble human leucocyte antigen-G molecules in lymphoproliferative disorders

Membrane-bound and soluble human leucocyte antigen-G (sHLA-G) molecules display immunotolerant properties favouring tumour cell escape from immune surveillance. sHLA-G molecules have been detected in several tumour pathologies; this study aimed to evaluate sHLA-G expression in lymphoproliferative disorders. sHLA-G plasma level was significantly increased in 110 of 178 newly diagnosed lymphoid proliferations cases i.e. 59 % of chronic lymphocytic leukaemia, 65 % of B non-Hodgkin lymphomas (NHL) and 58 % of T-NHL. To assess the mechanisms involved in this secretion, the differential effect of cytokines was tested in in vitro cultures of NHL cells. A significant induction of sHLA-G level was shown in T-NHL in contrast with B-NHL and normal equivalent cells, after cytokine stimulation with (i) interferonc (IFNc), interleukin-2 (IL-2) and granulocytemacrophage colony-stimulating factor, (ii) IL-10 and (iii) transforming growth factor b. An impact of microenvironment on sHLA-G expression was found in B-NHL as shown by the in vitro effect of addition of normal monocytes. Finally, a functional effect of sHLA-G molecules purified from pathologic plasma was demonstrated by their strong capacity to inhibit T-cell proliferation at concentrations currently observed during these disorders. These results suggest that functional sHLA-G molecules are upregulated in lymphoproliferative disorders which can support their potential immunomodulatory role during this pathology

COX-2 independent effects of Celecoxib sensitize Lymphoma B cells to TRAIL-mediated apoptosis.

4 supplemental figures and supplemental methodsInternational audiencePURPOSE: Despite therapeutic advances, Non-Hodgkin lymphomas (NHL) remain incurable. They form a group of neoplasms strongly dependent on their inflammatory microenvironment, which plays an important supportive role in tumor B-cell survival and in the resistance to anti-tumor immune response. New therapies must consider both tumor cells and their surrounding microenvironment EXPERIMENTAL DESIGN: Stromal cells, derived from bone marrow or lymph nodes, and B cells from follicular lymphoma patients were co-cultured or cultured alone with Celecoxib treatment, a non-steroidal anti-inflammatory drug and/or TRAIL, a promising cytotoxic molecule for cancer therapy. RESULTS: In this study, we show that follicular lymphoma (FL) stromal cells produce large amounts of PGE2. This production is abrogated after Celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE2 synthesis. Furthermore, we demonstrate that Celecoxib increases apoptosis in NHL B-cell lines and in primary FL B-cells co-cultured with stromal cells, but independently of the PGE2/COX-2 axis. Finally, Celecoxib increases the apoptotic activity of TRAIL. We provide evidence that Celecoxib affects proliferation and sensitizes NHL B-cell lines to apoptosis through COX-2 independent effects by slowing down the cell cycle and decreasing the expression of survival proteins, such as Mcl-1. CONCLUSIONS: These data suggest new potent strategies for NHL therapy combining drugs targeting both tumour B cells and survival signals provided by the tumor microenvironment

Stromal cells regulate malignant B-cell spatial organization, survival, and drug response in a new 3D model mimicking lymphoma tumor niche

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. Until now, in vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B lymphomas remain scarce while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on the encapsulation of cells inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating extracellular matrix and/or stromal cells. Lymphoma B cells and stromal cells dynamically formed self-organized 3D spheroids, thus initiating a coevolution of these two cell types, reflecting their bidirectional crosstalk, and recapitulating the heterogeneity of B-NHL subtypes. In addition, this approach makes it suitable to assess in a relevant in vitro model the activity of new therapeutic agents in B-NHL