BCL2L10 is a predictive factor for resistance to Azacitidine in MDS and AML patients

Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment. These patients have a drastically reduced life expectancy as compared to sensitive patients. Therefore identifying predictive factors for AZA resistance is of great interest to propose alternative therapeutic strategies for non-responsive patients. We generated AZA-resistant myeloid cell line (SKM1-R) that exhibited increased expression of BCL2L10 an anti-apoptotic Bcl-2 family member. Importantly, BCL2L10 knockdown sensitized SKM1-R cells to AZA effect suggesting that increased BCL2L10 expression is linked to AZA resistance in SKM1-R. We next established in 77 MDS patients that resistance to AZA is significantly correlated with the percentage of MDS or AML cells expressing BCL2L10. In addition, we showed that the proportion of BCL2L10 positive bone marrow cells can predict overall survival in MDS or AML patients. We propose a convenient assay in which the percentage of BCL2L10 expressing cells as assessed by flow cytometry is predictive of whether or not a patient will become resistant to AZA. Therefore, systematic determination of BCL2L10 expression could be of great interest in newly diagnosed and AZA-treated MDS patients

Dissolved organic matter dynamics in the pristine Krka River estuary (Croatia)

The karstic Krka River is characterized by having lower dissolved organic carbon (DOC) concentrations (~30 μM) than coastal seawater (~60 μM). This peculiarity, together with the pristine nature of this area, makes the Krka River estuary a natural laboratory where it is possible to discriminate among the different dissolved organic matter (DOM) sources (riverine, marine and produced in-situ) and to study the main processes of DOM production and removal. The hypothesis behind this work is that in winter, due to the high discharge of the river, most of the DOM has a terrestrial signature, whereas in summer autochthonous DOM compose the main fraction of the DOM pool because of the reduced discharge, the high temperature and primary production. Our data shows that DOM in the river mainly consists of terrestrial molecules, as suggested by the high chromophoric content and low spectral slope (S275–295) values, as well by the predominance of humic-like substances. DOM in the seawater features the concentration and optical properties of the “typical” marine DOM from open sea waters. In summer, low riverine discharge and high temperature promote the intense biological activity, with an increase in DOC concentrations of up to 148 μM, resulting in a non-conservative behavior of DOM in the estuary. The high stratification combined with a decoupling between production and removal processes can explain the observed DOM accumulation. In the bottom layer DOM was released and quickly removed when oxygen was available, whereas in hypoxic waters the production of DOC, chromophoric DOM (CDOM) and fluorescent DOM (FDOM) was linearly related to oxygen consumption. Our work highlights the need of further studies combining chemical and biological information in order to gain new insights into the main processes responsible for DOM dynamics in this system

Long‐term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials

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Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation

PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2

Teaching of English in French-Canada

Thesis (Ed.M.)--Boston University, 1935. This item was digitized by the Internet Archive

A Reply to My Critics: The Critical Spirit of Bourdieusian Language

Drawing on my article “Bourdieusian reflections on language: Unavoidable conditions of the real speech situation”, this paper provides a detailed response to the above commentaries by Lisa Adkins, Bridget Fowler, Michael Grenfell, David Inglis, Hans-Herbert Kögler, Steph Lawler, William Outhwaite, Derek Robbins and Bryan S. Turner. The main purpose of this “Reply to my critics” is to reflect upon the most important issues raised by these commentators and thereby contribute to a more nuanced understanding of key questions arising from Bourdieu’s analysis of language

Lymphomes de mauvais pronostic (impact de la tomographie par émission de positons couplée à la tomodensitométrie avant et après l'autogreffe de cellules souches périphériques)

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Association des lymphomes T périphériques, sans autre spécificité au virus EBV (analyse d'une série de 110 patients)

Les lymphomes T périphériques forment un groupe hétérogène de tumeurs dont le type histologique le plus fréquent est celui des " lymphomes T périphériques, sans autre spécificité ". L'association de certains cas au virus d'Epstein-Barr (EBV) a été rapportée, et des études antérieures ont suggéré une influence pronostique péjorative d'une telle association. Nous avons recherché une association au virus EBV par la technique d'hybridation in situ EBER dans une série de 110 patients porteurs de lymphomes T périphériques, sans autre spécificité. L'analyse de cette série a permis de confirmes, sur un grand nombre de patients, les données cliniques rapportées dans ce type de tumeurs. Une association à EBV a été retrouvée dans 41% des cas. Nous avons confirmé la valeur pronostique péjorative du caractère EBV positif, et décrit pour la première fois la variation dans le temps de son influence pronostique.Peripheral T-cell lymphomas form an heterogeneous group of tumors, among which the most frequent histological subtype is the one designed as " peripheral T-cell lymphoma, not otherwise specified ". Some of these cases have been associated with the Epstein-Barr virus (EBV). We used EBER in-situ hybridization to assess the association to EBV in a population of 110 patients presenting with " T-cell lymphoma, not otherwise specified ". The incidence of such an association was 41%. We did confirm the poor prognosis associated with EBV positivity. We also did describe for the first time the time-dependant variation of the prognostic influence of EBV positivity.ST QUENTIN EN YVELINES-BU (782972101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Risques compétitifs de survenue d'évènements après autogreffe de lymphomes agressifs

L'autogreffe est devenue fondamentale dans le traitement des lymphomes non hodgkiniens (LNH) agressifs de mauvais pronostic ou en rechute. Le toxicité tardive de ce traitement (3 mois après l'autogreffe) doit être prise en compte, de même que le risque de cancers secondaires. Parmi les malades atteints de lymphomes autogreffés dans le service d'onco-hématologie entre 1993 et 2001, 158 correspondent à des LNH agressifs. Au diagnostic, 116 patients avaient un stade disséminé, l'ECOG était de 1-2 chez 135, les LDH étaient élevées chez 90, l'IPI à 2-3 ans chez 39 ; 115 avaient 0 ou 1 site extranodal envahi et 31 un envahissement médullaire. Le nombre médian de poussées avant l'autogreffe était de 1 (1-4) et 90 patients ont été greffés en consolidation en première ligne thérapeutique. Une RP chez 35,8 étant réfractaires. Une irradiation localisée après la greffe a été réalisée chez 31 patients. Avec un suivi médian de 3 ans, la survie globale et la survie sans rechute sont respectivement de 65+/-9% ET 55+/-8%. 8 seconds cancers ont été diagnostiqués. La toxicité tardive non tumorale affecte 43 patients. 33 pts ont eu une toxicité majeure dont aucun n'est décédé. 9 pts ont présenté une cardiotoxicité dont 3 ont necessité un traitement. L'analyse univariée met en évidence une association entre le nombre de régimes de chimiothérapie reçus ainsi que la réalisation d'une TBI et la survenue d'une toxicité tardive, entre le nombre de poussées et la survenue de seconds cancers. En analyse univariée tenant compte des risques compétitifs, l'âge est associé significativement à la rechute et à la survenue d'un second cancer, le nombre de poussées à la survenue d'une toxicité tardive non tumorale. L'autogreffe est un traitement efficace et peu toxique.PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF