Service de Biologie Cellulaire

Paris, France

Service de Biologie Cellulaire

Paris, France
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Lamy P.-J.,Institute Medical dAnalyse Genomique | Allory Y.,Service de Pathologie | Gauchez A.-S.,Grenoble University Hospital Center | Asselain B.,University Paris - Sud | And 15 more authors.
European Urology Focus | Year: 2017

Context: Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. Objective: This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). Evidence acquisition: All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. Evidence synthesis: The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Conclusions: Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. Patient summary: We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the prognostic parameters currently used by clinicians. Accurate prognosis of localized prostate cancer is crucial for selection of the best strategy among the different clinical options available for initial management of this disease. This review gives a comprehensive overview of the prognostic validity and clinical utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, and Decipher). According to the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the prognostic parameters currently used by clinicians. However, owing to the increasing contribution of magnetic resonance imaging to prostate cancer diagnosis and management, the place of these biomarkers should be reconsidered in association with this imaging technique. © 2017 European Association of Urology.


Verger E.,Service de Biologie Cellulaire | Cassinat B.,Service de Biologie Cellulaire | Chauveau A.,Brest University Hospital Center | Chauveau A.,University of Western Brittany | And 14 more authors.
Blood | Year: 2015

Myeloproliferative neoplasmsare clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis.Few therapeutic options are available, among which interferon α (IFNα)presents interesting properties like the ability to induce hematologic responses (HRs) andmolecular responses (MRS) inpatients with JAK2 mutation.We reportonthe response to IFNatherapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years).HRwas achievedin all patients.MedianCALRmutant allelicburden (%CALR) significantly decreased from 41% at base line to 26%after treatment, and 2patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, withonlyminorornoMRS in this subsetofpatients.Analysisof theevolutionof the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNa induces high rates of HRs and MRS in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy. © 2015 by The American Society of Hematology.


PubMed | Brest University Hospital Center, Institute Of Cancerologie Du Gard, University of Angers, Service de Biologie Cellulaire and 5 more.
Type: Journal Article | Journal: Blood | Year: 2015

Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon (IFN) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFN therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFN in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFN induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy.


Ianotto J.-C.,Institute Of Cancero Hematologie | Boyer-Perrard F.,Angers University Hospital Center | Gyan E.,CNRS Genetics, Immunotherapy, Chemistry & Cancer Laboratory | Laribi K.,Service dhematologie | And 16 more authors.
British Journal of Haematology | Year: 2013

Myeloproliferative neoplasm-related myelofibrosis is associated with cytopenic or proliferative phases, splenomegaly and constitutional symptoms. Few effective treatments are available and small series suggested that interferon could be an option for myelofibrosis therapy. We performed a retrospective study of pegylated-interferon α-2a (Peg-IFNα-2a) therapy in myelofibrosis. Sixty-two patients treated with Peg-IFNα-2a at 17 French and Belgian centres were included. Responses were determined based on the criteria established by the International Working Group for Myelofibrosis Research and Treatment. Mean follow-up was 26 months. Sixteen of 25 anaemic patients (64%) (eight concomitantly receiving recombinant erythropoietin) achieved a complete response and transfusion-independence was obtained in 5/13 patients (38·5%). Constitutional symptoms resolved in 82% of patients. All five leucopenic patients normalized their leucocyte counts, whereas a normal platelet count was obtained in 5/8 thrombocytopenic patients. Splenomegaly was reduced in 46·5% of patients, and complete resolution of thrombocytosis and leucocytosis were observed in 82·8% and 68·8% of patients, respectively. Side effects (mostly haematological) were mainly of grade 1-2. The only factor independently associated with treatment failure was a spleen enlargement of more than 6 cm below the costal margin. In conclusion, Peg-IFNα-2a induced high response rates with acceptable toxicity in a large proportion of patients with primary and secondary myelofibrosis, especially in early phases. © 2013 John Wiley & Sons Ltd.


Guinde J.,Service dOncologie Thoracique | Laroumagne S.,Service dOncologie Thoracique | Kaspi E.,Service de Biologie Cellulaire | Kaspi E.,Aix - Marseille University | And 5 more authors.
Revue des Maladies Respiratoires | Year: 2015

The diagnosis of malignant pleural mesothelioma relies mostly on the pathological examination of pleural samples, validated by a panel of experts and generally obtained during medical or surgical thoracoscopy performed for the management of an exudative pleural effusion. In the absence of pleural effusion (dry-type mesothelioma), the diagnostic approach depends on the features of the lesions (pleural thickness, nodules and/or masses) and their pleural location. Ultrasound and CT-guided needle aspiration represent recognized alternative diagnostic techniques in these situations. We present the case of a patient, presenting a dry-type mesothelioma, whose diagnosis was obtained by endobronchial ultrasound (EBUS)-guided needle aspiration of a pleural mediastinal mass and confirmed by a CT-guided needle aspiration of another pleural mass in close contact with the chest wall. The samples have been compared and show quantitative and qualitative similarities. EBUS represents a minimally invasive alternative diagnostic technique for dry-type mesothelioma, showing thickness of the mediastinal pleura in contact with a central airway or when thoracoscopy, which remains the "gold standard" diagnostic approach, is not feasible. © 2015 SPLF.


Six E.,French Institute of Health and Medical Research | Six E.,University of Paris Pantheon Sorbonne | Lagresle-Peyrou C.,French Institute of Health and Medical Research | Lagresle-Peyrou C.,University of Paris Pantheon Sorbonne | And 26 more authors.
Cell Death and Disease | Year: 2015

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation. © 2015 Macmillan Publishers Limited.


Zassadowski F.,Service de Biologie Cellulaire | Zassadowski F.,French Institute of Health and Medical Research | Pokorna K.,French Institute of Health and Medical Research | Ferre N.,French Institute of Health and Medical Research | And 14 more authors.
Leukemia | Year: 2015

We recently identified that the MEK/ERK1/2 pathway synergized with retinoic acid (RA) to restore both transcriptional activity and RA-induced differentiation in RA-resistant acute promyelocytic leukemia (APL) cells. To target the MEK/ERK pathway, we identified glycogen synthase kinase-3β (GSK-3β) inhibitors including lithium chloride (LiCl) as activators of this pathway in APL cells. Using NB4 (RA-sensitive) and UF-1 (RA-resistant) APL cell lines, we observed that LiCl as well as synthetic GSK-3β inhibitors decreased proliferation, induced apoptosis and restored, in RA-resistant cells, the expression of RA target genes and the RA-induced differentiation. Inhibition of the MEK/ERK1/2 pathway abolished these effects. These results were corroborated in primary APL patient cells and translated in vivo using an APL preclinical mouse model in which LiCl given alone was as efficient as RA in increasing survival of leukemic mice compared with untreated mice. When LiCl was combined with RA, we observed a significant survival advantage compared with mice treated by RA alone. In this work, we demonstrate that LiCl, a well-tolerated agent in humans, has antileukemic activity in APL and that it has the potential to restore RA-induced transcriptional activation and differentiation in RA-resistant APL cells in an MEK/ERK-dependent manner. © 2015 Macmillan Publishers Limited.


Hamy A.-S.,Center des Maladies du Sein | Porcher R.,Center dEpidemiologie Clinique | Porcher R.,Paris West University Nanterre La Défense | Cuvier C.,Center des Maladies du Sein | And 12 more authors.
Reproductive BioMedicine Online | Year: 2014

Anti-Müllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 months of amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context. © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.


PubMed | University of Paris 13, Service de Biologie Cellulaire, French Institute of Health and Medical Research, Center des Maladies du Sein and Laboratoire des Urgences et Gardes
Type: Journal Article | Journal: Reproductive biomedicine online | Year: 2014

Anti-Mllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 monthsof amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context.

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