Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
ISSN: 0305-1048

hal-01146849
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146849
DOI : 10.1093/nar/gkv350
PUBMED : 25897122

Éditeur(s) : HAL CCSD
Résumé : International audience
INTRODUCTION: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by imaging features consisting of the association of centrilobular and/or paraseptal emphysema and pulmonary fibrosis. Virtually all patients are smokers and thus at high risk of developing lung cancer. METHODS: This retrospective multicentre study was conducted by the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). RESULTS: A total of 47 patients presenting with lung cancer and CPFE syndrome were identified. All patients were smokers, with a mean of 47 pack-years. A pathological diagnosis of lung cancer was obtained for 38 (81%) patients. Histological type was squamous cell carcinoma in 17 (36%) patients, adenocarcinoma in 14 (30%), non-small-cell lung cancer not otherwise specified in three (6%), small-cell lung cancer in three (6%), and sarcomatoid carcinoma in one (2%). Overall, 20 of the 47 patients could not receive standard-of-care treatment for lung cancer, as per international recommendations or guidelines; this limitation was considered to be directly related to the CPFE syndrome in eight (40%) cases. CONCLUSION: Lung cancer in patients with CPFE syndrome represents a specific entity with a poor prognosis, that further represents the most characteristic and severe model of tobacco-related disease.
Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer

hal-01063912
https://hal.archives-ouvertes.fr/hal-01063912
DOI : 10.1097/JTO.0000000000000209
PUBMED : 25157769

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: Until recently, synonymous mutations (which do not change amino acids) have been much neglected. Some evidence suggests that this kind of mutations could affect mRNA secondary structure or stability, translation kinetics and protein structure. To explore deeper the role of synonymous mutations, we studied their consequence on the functional activity of the estrogen receptor alpha (ERα). The ERα is a ligand-inducible transcription factor that orchestrates pleiotropic cellular effects, at both genomic and non-genomic levels in response to estrogens. In this work we analyzed in transient transfection experiments, the activity of ERα carrying the synonymous mutation Ala87, a polymorphism involving about 5-10% of the population. In comparison to the wild type receptor, our results show that ERαA87 mutation reduces the transactivation efficiency of ERα on an ERE reporter gene while its expression level remains similar. This mutation enhances 4-OHT-induced transactivation of ERα on an AP1 reporter gene. Finally, the mutation affects the subcellular localization of ERα in a cell type specific manner. It enhances the cytoplasmic location of ERα without significant changes in non-genomic effects of E2. The functional alteration of the ERαA87 determined in this work highlights the relevance of synonymous mutations for biomedical and pharmacological points of view.
Journal of steroid biochemistry and molecular biology

inserm-01015532
http://www.hal.inserm.fr/inserm-01015532
DOI : 10.1016/j.jsbmb.2014.02.016
PUBMED : 24607813

Éditeur(s) : HAL CCSD
Résumé : National audience
Objectifs La recherche d’anticorps anti-aspergillaires est une analyse essentielle au diagnostic des formes chroniques d’aspergilloses. De nombreuses techniques sont disponibles, commerciales ou non, regroupées par la nomenclature française en méthodes de dépistage et de confirmation. La SFMM a mené en janvier–février 2015 une étude de type « avis d’expert » sur les performances de ces techniques et leur stratégie de mise en œuvre. Méthodes Quarante experts ont été sollicités pour répondre à un questionnaire en ligne comprenant 37 questions. Les réponses, obligatoires pour tous les items, devaient être cotées de 1 à 9 selon l’accord total (9) ou le désaccord total (1) de l’expert. L’analyse a été faite sur la valeur de la cote médiane et les coefficients de variation (écart-type/moyenne) pour juger de la variabilité des réponses. Résultats Trente-six questionnaires ont été complétés. Les CV des réponses allaient de 10 % à 75 %, seuls 38 % d’entre eux étant supérieurs à 50 %. La distinction entre méthode de dépistage et méthode de confirmation est globalement jugée comme pertinente (médiane = 7) mais un positionnement clair des techniques en dépistage ou confirmation n’est obtenu avec un CV inférieur à 30 % que pour l’Elisa en dépistage et l’immunoélectrophorèse et le western blot en confirmation. La pratique d’une technique de confirmation est essentiellement recommandée en cas de positivité de la méthode de dépistage (médiane = 9 ; CV = 14 %), en fonction du contexte clinique (8 ; 31 %) ou lors d’un suivi (8 ; 33 %). En cas de discordance entre méthode de dépistage et de confirmation, les experts recommandent une interprétation directe des résultats en donnant priorité aux résultats de la méthode de confirmation (en fonction du dossier du patient) (8 ; 28 %). Conclusion Cette enquête montre l’absence de consensus sur la stratégie de détection des anticorps anti-aspergillaires et doit inciter les mycologues français à harmoniser au mieux leurs pratiques, afin de répondre à la demande des cliniciens
Congrès de la SFMM
Talence-Bordeaux, France

hal-01198639
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01198639
DOI : 10.1016/j.mycmed.2015.06.012

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: While it is known that cancer risk is related to area-level socioeconomic status, the extent to which these inequalities are explained by contextual effects is poorly documented especially for head and neck cancer. Methods: A case-control study, ICARE, included 2415 head and neck cancer cases and 3555 controls recruited between 2001 and 2007 from 10 French regions retrieved from a general cancer registry. Individual socioeconomic status was assessed using marital status, highest educational level and occupational social class. Area-level socioeconomic status was assessed using the French version of the European Deprivation Index (EDI). The relationship between both individual and area-based socioeconomic level and the risk of head and neck cancer was assessed by multilevel analyses. Results: A higher risk for head and neck cancer was found in divorced compared with married individuals (OR = 2.14, 95% CI = 1.78-2.57), for individuals with a basic school-leaving qualification compared with those with higher education (OR = 4.55 95% CI = 3.72-5.57), for manual workers compared with managers (OR = 4.91, 95% CI = 3.92-6.15) and for individuals living in the most deprived areas compared with those living in the most affluent ones (OR = 1.98, 95% CI = 1.64-2.41). The influence of area-level socioeconomic status measured by EDI remained after controlling for individual socioeconomic characteristics (OR = 1.51; 95% confidence interval: 1.23-1.85, p-value = 0.0003). Conclusions: The role of individual socioeconomic status in the risk of head and neck cancer is undeniable, although contextual effects of deprived areas also increase the susceptibility of individuals developing the disease. (C) 2017 Elsevier Ltd. All rights reserved.
ISSN: 1368-8375

hal-01578588
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578588
DOI : 10.1016/j.oraloncology.2017.06.014
PUBMED : 28688682

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
PURPOSE: Multiple myeloma, a hematological malignancy generally affecting elderly people, was diagnosed at the beginning of the pregnancy of a 33-year-old woman. We carried out a literature review in order to evaluate the consequences of this cancer on pregnancy and of pregnancy on multiple myeloma, as to determine the specific follow-up required. METHODS: A systematic search for articles of interest published between 1949 and 16 November 2010 was performed in MEDLINE, SCOPUS and EMBASE, using the words "multiple myeloma" and "pregnancy". We identified 398 publications of potential interest, 20 of which were selected and included in the analysis. RESULTS: The selected articles included 26 cases. No specific risk factors were identified in pregnant women. The most common presentations were bone pain and/or anemia, as in the general population. Pregnancy seemed to have no effect on multiple myeloma progression. Most pregnancies went to term, with only two medical terminations and six cesareans performed before term, due to the severity of the cancer. No effect of the cancer or its treatment by chemotherapy during pregnancy was found in the children. CONCLUSION: Pregnancy does not seem to be contraindicated in women with multiple myeloma. Nevertheless, the management of pregnant patients with multiple myeloma is a diagnostic, therapeutic and social challenge, requiring a multidisciplinary approach and regular follow-up. Decisions should be taken based on the severity of the disease, its prognosis and maternal choice.
ISSN: 0932-0067

hal-00682571
https://hal.archives-ouvertes.fr/hal-00682571
DOI : 10.1007/s00404-011-1985-8
PUBMED : 21786002

Éditeur(s) : HAL CCSD Springer Verlag (Germany) Springer Verlag
Résumé : International audience
ISSN: 1292-3818

hal-01118280
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118280
DOI : 10.1007/s10269-011-1983-2