Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

Synthèse de fluoroalcènes et disaccharides comme peptidomimétiques visant l'interaction PKC -RACK

The protein kinase C family has been implicated in the transduction of a large variety of cellular signals between the receptor and the intracellular machinery that will be responsible for the desired action. This has led to a considerable interest in the inhibition of PKC, in particular in the inhibition of single isoforms of PKC. A novel approach consists of targeting the localization of PKC on the cytoplasmic membrane, rather than the enzyme itself, by inhibiting the interaction of PKC with its receptor, RACK-2. The objective of this work is the design and synthesis of fluoroalkene and disaccharide-based peptidomimetics of the octapeptide EAVSLKPT, an inhibitor of the PKC -RACK interaction reported by Mochly Rosen et al. The fluoroalkene peptidomimetics were synthesized by a route inspired by Waelchli s synthesis of unfunctionalized peptidomimetics of the parathyroïd hormone. The second family of peptidomimetics was designed based on a disaccharide scaffold. This skeleton offers a semi-rigid backbone with several well defined conformations around the aglyconic bond, ten functionaliseable positions, and a sufficient size to mimic a relatively linear peptide chain. Pharmacophore modeling and conformational analysis allowed us to identify a particular saccharide, a D-glucose b(1-3) L-Glucose substituted at the 4 position with a tetrahydropyran and the 3 position with a carboxy-bearing chain, which matched the peptide pharmacophores in a favorable solution conformationLa famille des protéines kinase C est impliquée dans de la transduction d un grand nombre de signaux cellulaires entre le récepteur et l appareillage intracellulaire qui effectuera la fonction désirée. Son inhibition fait l étude de nombreuses recherches, notamment dans la recherche d inhibiteurs visant une seule des isozymes de la PKC. Une nouvelle stratégie consiste à viser non pas l inhibition de l enzyme elle-même, mais plutôt d empêcher sa localisation sur la membrane cytoplasmique par l inhibition de l interaction avec son récepteur, RACK-2. L objectif de cette thèse est la synthèse de fluoroalcènes et de disaccharides comme peptidomimétiques de l octapeptide EAVSLKPT, un inhibiteur de l interaction de PKC -RACK décrit par Mochly-Rosen et al., afin de mieux comprendre le rôle de cette interaction dans la transduction du signal. La synthèse de peptidomimétiques fluoroalcènes portant des chaînes latérales fonctionnalisées est inspirée de la voie développée par Waelchli pour la préparation de dipeptides non fonctionnalisés, comme analogues de l hormone parathyroïde. Une deuxième famille de peptidomimetiques a été conçue sur la base de disaccharides. Ce squelette confère à la molécule une semi-rigidité, car en effet, la liaison aglyconique offre différentes orientations bien définies de la molécule dans l espace. Les dix positions fonctionnalisables permettent l accès à un grand nombre de molécules, tandis que sa taille permet de mimer une molécule qui est assez étendue dans l espace. La modélisation et l analyse conformationnelle ont permis de trouver une molécule qui se juxtapose au modèle pharmacophore: un D-Glucose-b(1-3)-L-Glucose substitué en position 4 par un tétrahydropyrane et en position 3 par une chaîne portant un acide carboxyliqueLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Bases de chronobiologie (vers une stratégie chronothérapeutique)

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

From generic to task-oriented speech recognition : French experience in the NESPOLE! European project

This paper presents CLIPS laboratory activities in speech recognition related to language model adaptation and acoustic model adaptation in the NESPOLE! European project. ASR system needed to be adapted in two ways. The language model had to deal with task specific vocabulary and the acoustic model had to be robust to VoIP (Voice over IP) speech. It was shown that Internet, as a very large source of text, can be a very interesting database for spoken language modelling adaptation. The influence of different VoIP codecs on the performance of our speech recognition engine was investigated and a new strategy was proposed to cope with degradation due to low bitrate coding. The acoustic models of the speech recognition system were trained with transcoded speech. Results have shown that this strategy allows to recover acceptable performance for the NESPOLE! project context. 1

Démarche de prévention dans le secteur médico-social : MESOCAP

International audienc

Investigation of aromatic hydrocarbon inclusion into cyclodextrins by Raman spectroscopy and thermal analysis

Among various cavitand molecules, cyclodextrins are extensively studied due to their ability to form host-guest complexes with small hydrophobic molecules. Aiming to explore cyclodextrin implementation on the scopes related to the environmental pollution monitoring or remediation, extensive studies for understanding the cyclodextrin-based host-guest complex formation with selected targeted substances are conducted. In this context, two polycyclic aromatic hydrocarbons, naphthalene and fluoranthene as well as toluene as a member of volatile organic compounds, were studied regarding their ability to encapsulate into cyclodextrin cavities. Synthesised complexes were examined by thermogravimetric analysis combined with Raman spectroscopy. The obtained results demonstrated that the size between targeted molecules and the cyclodextrin cavities strongly correlates with its ability to engage in complexation. Thus, this latter parameter plays an important role in the inclusion complex formation as well as in the strength of the interaction between the molecules

ISOLD: A New Highly Sensitive Interleukin Score for Intraocular Lymphoma Diagnosis

International audienc

Inhibition of Hedgehog signaling for the treatment of lymphoma and CLL: a phase II study from the LYSA

International audienceno abstrac