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Dales J.-P.,Plateforme Transcriptome | Beaufils N.,Biochemistry and Molecular Biology | Silvy M.,Etablissement francais du sang Alpes Mediterranee | Picard C.,Etablissement francais du sang Alpes Mediterranee | And 5 more authors.
BMC Medicine | Year: 2010

Background: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known.Methods: Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1α and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1α splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival.Results: HIF-1α isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1αTAG) and HIF-1α736mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1αTAGmRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1αTAG(P = 0.048), and total HIF-1α (P = 0.048) mRNA levels. HIF-1αTAGmRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1αTAGmRNA levels correlated with shortened metastasis free survival (P = 0.01).Conclusions: Our results show for the first time that mRNA expression of a HIF-1αTAGsplice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45. © 2010 Dales et al; licensee BioMed Central Ltd.

Bagnis C.,Etablissement francais du sang Alpes Mediterranee | Bagnis C.,Aix - Marseille University
Blood Reviews | Year: 2015

In the field of transfusion, controlling expression of blood group system antigens on the surface of RBCs has been envisioned as a major research objective for five decades. With the advent of gene transfer techniques in the 1980s, genetic manipulation acquired the tools and know-how necessary to propose this goal along with other strategies. Besides the use of gene transfer to study blood group antigens and to develop tools for transfusion purposes, since the beginning of the new millennium, technological advances in combination with the recognition of the clinical potential of gene transfer have led the transfusion domain into development of cell therapy approaches for therapeutic purposes based on genetic manipulation. © 2014 Published by Elsevier Ltd.

The Marseille public hospital system (APHM) has expressed its willingness to pool its services of immunohematology and delivery of labile blood products with those of the French blood institute Alps Mediterranean division (EFS AM). An agreement setting out the terms of this partnership was signed between the two parties. The users of the APHM and EFS AM blood watch wished to preserve the channels of distribution. Implementation of this reorganization has focused on ensuring transfusional safety, reinforcing harmonization of APHM practices, and finding ways to reduce costs. Despite joint information campaigns (to medical and paramedical personnel) carried out by the APHM and EFS AM blood watch, problems have arisen during start-up and adjustments have been necessary on both sides. The success of this project hinges on the involvement of the EFS AM in our transfusional practices, deployment of a system for diffusion of information, and consolidation of physical and human resources at the level of the APHM blood watch. © 2009 Elsevier Masson SAS. All rights reserved.

Elkaim E.,Aix - Marseille University | Picard C.,Etablissement francais du sang Alpes Mediterranee | Picard C.,Aix - Marseille University | Galambrun C.,Aix - Marseille University | And 7 more authors.
British Journal of Haematology | Year: 2014

This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0·001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15-30 post-transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT. © 2014 John Wiley & Sons Ltd.

Duboz P.,French National Center for Scientific Research | Lazaygues C.,Etablissement francais du sang Alpes Mediterranee | Boetsch G.,Cheikh Anta Diop University | Chiaroni J.,Etablissement francais du sang Alpes Mediterranee
Transfusion Clinique et Biologique | Year: 2012

Aim: Blood donor retention represents a fundamental objective in public health. Comparison between the sociodemographic characteristics and motivational factors between lapsed and regular donors is then required. The objectives of this analysis were: (1) to compare the sociodemographic characteristics of lapsed donors and current donors; (2) to compare the motivations to donate blood expressed by lapsed and current donors. Patients and methods: Data from a 2008 survey, representative of the population by crossed quotas method, of 1400 individuals questioned by phone were used to reach these objectives. Chi 2 tests and binary logistic regressions were used. Results: Results show that socio-occupational categories and motivational factors are different between lapsed and regular donors. Workers, senior management and higher intellectual professions are more often lapsed than regular donors. Concerning motivations, results show that lapsed donors more frequently mention the first experience with blood donation (with colleagues, friends, and parents) than regular donors, for whom altruistic and community motivations are more frequently cited. Conclusion: Workers, senior management and higher intellectual professions should be targeted uppermost, in order to convert them in regular donors. Finally, concerning motivations, the social pressure applied to lapsed donors for their first blood donation appears crucial, whereas regular donors have internalized their motives, more often altruistic and community motivations. © 2011 Elsevier Masson SAS.

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