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Author Alexandre Evrard

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Model-based Quantification of Impact of Genetic Polymorphisms and Co-Medications on Pharmacokinetics of Tamoxifen and Six Metabolites in Breast Cancer.

Alicja Puszkiel, Cécile Arellano, Christelle Vachoux, Alexandre Evrard, Valérie Le Morvan, Jean-Christophe Boyer, Jacques Robert, Caroline Delmas, Florence Dalenc, Marc Debled, Laurence Venat-Bouvet, William Jacot, Nadine Dohollou, Chantal Bernard-Marty, Hortense Laharie-Mineur, Thomas Filleron, Henri Roché, Etienne Chatelut, Fabienne Thomas, Melanie White-Koning,

Variations in clinical response to tamoxifen (TAM) may be related to polymorphic cytochromes P450 (CYPs) involved in forming its active metabolite endoxifen (ENDO). We developed a population pharmacokinetic (popPK) model for tamoxifen and six metabolites to determine clinically relevant factors of ENDO exposure. Concentration-time data for TAM and six metabolites ... Read more >>

Clin Pharmacol Ther (Clinical pharmacology and therapeutics)
[2020, :]

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The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor.

Nicolas Creusot, Matthieu Gassiot, Elina Alaterre, Barbara Chiavarina, Marina Grimaldi, Abdelhay Boulahtouf, Lucia Toporova, Sabine Gerbal-Chaloin, Martine Daujat-Chavanieu, Alice Matheux, Roger Rahmani, Céline Gongora, Alexandre Evrard, Philippe Pourquier, Patrick Balaguer,

The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and ... Read more >>

Cells (Cells)
[2020, 9(7):]

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Liquid chromatography-tandem mass spectrometric assay for the quantification of CDK4/6 inhibitors in human plasma in a clinical context of drug-drug interaction.

Fanny Leenhardt, Matthieu Gracia, Catherine Perrin, Claudia Muracciole-Bich, Bénédicte Marion, Celine Roques, Marie Alexandre, Nelly Firmin, Stephane Pouderoux, Litaty Mbatchi, Celine Gongora, William Jacot, Alexandre Evrard,

The CDK4/6 inhibitors palbociclib and ribociclib are kinase inhibitors used in association with hormonal therapy for the management of patients with metastatic breast cancer. Like most kinase inhibitors, therapeutic drug monitoring may be used for personalize their dosage. To this aim, we developed and validated a sensitive and specific HPLC-MS/MS ... Read more >>

J Pharm Biomed Anal (Journal of pharmaceutical and biomedical analysis)
[2020, 188:113438]

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Pharmacogenetics and pharmacokinetics modeling of unexpected and extremely severe toxicities after sorafenib intake.

Hai le Ba, Litaty Mbatchi, Florence Gattacceca, Alexandre Evrard, Bruno Lacarelle, Benoit Blanchet, Joseph Ciccolini, Sébastien Salas,

A 53-year-old woman with papillary thyroid cancer treated with 800 mg sorafenib therapy rapidly experienced grade 3 toxicities. Dosing was reduced in a step-wise manner with several treatment discontinuations down to 200 mg every 2 days but severe toxicities continued. Plasma drug monitoring showed high exposure, even at low dose. Dosing was ... Read more >>

Pharmacogenomics (Pharmacogenomics)
[2020, 21(3):173-179]

Cited: 1 time

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Persistent response to vemurafenib in metastatic ameloblastoma with BRAF mutation: a case report.

Morgane Broudic-Guibert, Jean-Yves Blay, Léa Vazquez, Alexandre Evrard, Marie Karanian, Sophie Taïeb, Natalie Hoog-Labouret, Céline Mahier Ait Oukhatar, Rania Boustany-Grenier, Antoine Arnaud,

BACKGROUND:Ameloblastomas are uncommon locally aggressive tumors of odontogenic epithelium that rarely metastasize. Currently, there is no standard of care for the metastatic forms. Several studies have shown that ameloblastomas frequently have a BRAF mutation. CASE PRESENTATION:We report a case of a 33-year-old Caucasian woman with ameloblastoma diagnosed 30 years ago who ... Read more >>

J Med Case Rep (Journal of medical case reports)
[2019, 13(1):245]

Cited: 1 time

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Probing Quantum Criticality and Symmetry Breaking at the Microscopic Level.

Vasiliy Makhalov, Tanish Satoor, Alexandre Evrard, Thomas Chalopin, Raphael Lopes, Sylvain Nascimbene,

We report on an experimental study of the Lipkin-Meshkov-Glick model of quantum spins interacting at infinite range in a transverse magnetic field, which exhibits a ferromagnetic phase transition in the thermodynamic limit. We use dysprosium atoms of electronic spin J=8, subjected to a quadratic Zeeman light shift, to simulate 2J=16 ... Read more >>

Phys Rev Lett (Physical review letters)
[2019, 123(12):120601]

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Enhanced Magnetic Sensitivity with Non-Gaussian Quantum Fluctuations.

Alexandre Evrard, Vasiliy Makhalov, Thomas Chalopin, Leonid A Sidorenkov, Jean Dalibard, Raphael Lopes, Sylvain Nascimbene,

The precision of a quantum sensor can overcome its classical counterpart when its constituents are entangled. In Gaussian squeezed states, quantum correlations lead to a reduction of the quantum projection noise below the shot noise limit. However, the most sensitive states involve complex non-Gaussian quantum fluctuations, making the required measurement ... Read more >>

Phys. Rev. Lett. (Physical review letters)
[2019, 122(17):173601]

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Toxicity and pharmacokinetic profile of SGM-101, a fluorescent anti-CEA chimeric antibody for fluorescence imaging of tumors in patients.

Bérénice Framery, Marian Gutowski, Karen Dumas, Alexandre Evrard, Nathalie Muller, Vincent Dubois, Jérôme Quinonero, François Scherninski, André Pèlegrin, Françoise Cailler,

The real-time improvement of the intraoperative discrimination between different tissue types (particularly between tumor and adjacent normal tissue) using intraoperative imaging represents a considerable advance for oncology surgeons. However, the development of imaging agents is much slower than that of drug therapies, although surgery represents one of the few curative ... Read more >>

(Toxicology reports)
[2019, 6:409-415]

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Factors Affecting Tamoxifen Metabolism in Patients With Breast Cancer: Preliminary Results of the French PHACS Study.

Alicja Puszkiel, Cécile Arellano, Christelle Vachoux, Alexandre Evrard, Valérie Le Morvan, Jean-Christophe Boyer, Jacques Robert, Caroline Delmas, Florence Dalenc, Marc Debled, Laurence Venat-Bouvet, William Jacot, Etienne Suc, Isabelle Sillet-Bach, Thomas Filleron, Henri Roché, Etienne Chatelut, Melanie White-Koning, Fabienne Thomas,

In addition to the effect of cytochrome P450 (CYP) 2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy and toxicity). This analysis focused on the pharmacokinetic (PK)-pharmacogenetic evaluation of tamoxifen in 730 patients with adjuvant breast cancer included in ... Read more >>

Clin. Pharmacol. Ther. (Clinical pharmacology and therapeutics)
[2019, 106(3):585-595]

Cited: 1 time

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[5-fluorouracil therapeutic drug monitoring: Update and recommendations of the STP-PT group of the SFPT and the GPCO-Unicancer].

Florian Lemaitre, Françoise Goirand, Manon Launay, Etienne Chatelut, Jean-Christophe Boyer, Alexandre Evrard, Marie-Noelle Paludetto, Romain Guilhaumou, Joseph Ciccolini, Antonin Schmitt,

Despite being 60-years old now, 5-FU remains the backbone of numerous regimen to treat a variety of solid tumors such as breast, head-and-neck and digestive cancers either in neo-adjuvant, adjuvant or metastatic settings. Standard 5-FU usually claims 15-40% of severe toxicities and up to 1% of toxic-death. Numerous studies show ... Read more >>

Bull Cancer (Bulletin du cancer)
[2018, 105(9):790-803]

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[Dihydropyrimidine déhydrogenase (DPD) deficiency screening and securing of fluoropyrimidine-based chemotherapies: Update and recommendations of the French GPCO-Unicancer and RNPGx networks].

Marie-Anne Loriot, Joseph Ciccolini, Fabienne Thomas, Chantal Barin-Le-Guellec, Bernard Royer, Gérard Milano, Nicolas Picard, Laurent Becquemont, Céline Verstuyft, Céline Narjoz, Antonin Schmitt, Christine Bobin-Dubigeon, Alexandre Harle, Angelo Paci, Vianney Poinsignon, Sylvie Quaranta, Alexandre Evrard, Benjamin Hennart, Franck Broly, Xavier Fonrose, Claire Lafay-Chebassier, Anne-Sophie Wozny, Fadil Masskouri, Jean-Christophe Boyer, Marie-Christine Etienne-Grimaldi,

Fluoropyrimidines (FU) are still the most prescribed anticancer drugs for the treatment of solid cancers. However, fluoropyrimidines cause severe toxicities in 10 to 40% of patients and toxic deaths in 0.2 to 0.8% of patients, resulting in a real public health problem. The main origin of FU-related toxicities is a ... Read more >>

Bull Cancer (Bulletin du cancer)
[2018, 105(4):397-407]

Cited: 7 times

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Genetic variations of the xenoreceptors NR1I2 and NR1I3 and their effect on drug disposition and response variability.

Litaty Céphanoée Mbatchi, Jean-Paul Brouillet, Alexandre Evrard,

NR1I2 (PXR) and NR1I3 (CAR) are nuclear receptors that are classified as xenoreceptors. Upon activation by various xenobiotics, including marketed drugs, they regulate the transcription level of major drug-metabolizing enzymes and transporters and facilitate the elimination of xenobiotics from the body. The modulation of the activity of these two xenoreceptors ... Read more >>

Pharmacogenomics (Pharmacogenomics)
[2018, 19(1):61-77]

Cited: 3 times

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Heritability of the resistance to pepper huasteco yellow vein virus in wild genotypes of Capsicum annuum

JesúsEnrique Retes-Manjarrez, Sergio Hernández-Verdugo, Alexandre Evrard, José Antonio Garzón-Tiznado,

Pepper huasteco yellow vein virus (PHYVV) is the main virus of pepper crop in Mexico. No resistant cultivars are available and resistance breeding is hampered by the lack of knowledge of heritability (h ²) of PHYVV resistance. This is a continuation of previous studies and the objectives were to analyze ... Read more >>

(Euphytica: Netherlands journal of plant breeding)
[2017, 213(12):275]

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An automated quantitative image analysis tool for the identification of microtubule patterns in plants.

Christine Faulkner, Ji Zhou, Alexandre Evrard, Gildas Bourdais, Dan MacLean, Heidrun Häweker, Peter Eckes, Silke Robatzek,

High throughput confocal imaging poses challenges in the computational image analysis of complex subcellular structures such as the microtubule cytoskeleton. Here, we developed CellArchitect, an automated image analysis tool that quantifies changes to subcellular patterns illustrated by microtubule markers in plants. We screened microtubule-targeted herbicides and demonstrate that high throughput ... Read more >>

Traffic (Traffic (Copenhagen, Denmark))
[2017, 18(10):683-693]

Cited: 2 times

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Association of NR1I2, CYP3A5 and ABCB1 genetic polymorphisms with variability of temsirolimus pharmacokinetics and toxicity in patients with metastatic bladder cancer.

Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede,

Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has ... Read more >>

Cancer Chemother. Pharmacol. (Cancer chemotherapy and pharmacology)
[2017, 80(3):653-659]

Cited: 4 times

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Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: The multiparametric approach is not convincing.

Marie-Christine Etienne-Grimaldi, Chantal Barin Le Guellec, Jean-Christophe Boyer, Etienne Chatelut, Alexandre Evrard, Marie-Anne Loriot, Angelo Paci, Bernard Royer, Fabienne Thomas, Joseph Ciccolini,

Semin. Oncol. (Seminars in oncology)
[2017, 44(2):159-160]

Cited: 0 times

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New advances in DPYD genotype and risk of severe toxicity under capecitabine.

Marie-Christine Etienne-Grimaldi, Jean-Christophe Boyer, Christophe Beroud, Litaty Mbatchi, André van Kuilenburg, Christine Bobin-Dubigeon, Fabienne Thomas, Etienne Chatelut, Jean-Louis Merlin, Frédéric Pinguet, Christophe Ferrand, Judith Meijer, Alexandre Evrard, Laurence Llorca, Gilles Romieu, Philippe Follana, Thomas Bachelot, Loic Chaigneau, Xavier Pivot, Véronique Dieras, Rémy Largillier, Mireille Mousseau, Anthony Goncalves, Henri Roché, Jacques Bonneterre, Véronique Servent, Nadine Dohollou, Yann Château, Emmanuel Chamorey, Jean-Pierre Desvignes, David Salgado, Jean-Marc Ferrero, Gérard Milano,

Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequencing and to examine relationships between DPYD variants ... Read more >>

PLoS One (PloS one)
[2017, 12(5):e0175998]

Cited: 10 times

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Cancer genomics guide clinical practice in personalized medicine.

Jacqueline Lehmann-Che, Brigitte Poirot, Jean-Christophe Boyer, Alexandre Evrard,

Targeted therapies have revolutionized the treatment of many cancers. Widely developed over the last decade, this new concept of precision medicine relies on the use of genomic technologies to analyze tumor samples in order to identify actionable targets and biomarkers of resistance. The goal is to optimize treatment by identifying ... Read more >>

Therapie (Therapie)
[2017, 72(4):439-451]

Cited: 2 times

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La génétique somatique des tumeurs solides, un incontournable à l’ère de la médecine de précision.

Jacqueline Lehmann-Che, Brigitte Poirot, Jean Christophe Boyer, Alexandre Evrard,

Therapie (Therapie)
[2017, 72(2):217-230]

Cited: 0 times

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Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients.

Litaty Céphanoée Mbatchi, Jacques Robert, Marc Ychou, Jean-Christophe Boyer, Maguy Del Rio, Matthieu Gassiot, Fabienne Thomas, Nicole Tubiana, Alexandre Evrard,

Nuclear receptors PXR (pregnane X receptor, NR1I2) and CAR (constitutive androstane receptor, NR1I3) are key regulators of irinotecan metabolism, and ligand-dependent modulation of their activity leads to significant drug-drug interactions. Because genetic polymorphisms can also affect the activity of these xenobiotic-sensing receptors, we hypothesized that they could contribute to the ... Read more >>

Clin Pharmacokinet (Clinical pharmacokinetics)
[2016, 55(9):1145-1157]

Cited: 7 times

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Cell re-entry assays do not support models of pathogen- independent translocation of AvrM and AVR3a effectors into plant cells

Benjamin Petre, Michaela Kopischke, Alexandre Evrard, Silke Robatzek, Sophien Kamoun,

The cell re-entry assay is widely used to evaluate pathogen effector protein uptake into plant cells. The assay is based on the premise that effector proteins secreted out of a leaf cell would translocate back into the cytosol of the same cell via a yet unknown host-derived uptake mechanism. Here, ... Read more >>

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Avr4 promotes Cf-4 receptor-like protein association with the BAK1/SERK3 receptor-like kinase to initiate receptor endocytosis and plant immunity.

Jelle Postma, Thomas W H Liebrand, Guozhi Bi, Alexandre Evrard, Ruby R Bye, Malick Mbengue, Hannah Kuhn, Matthieu H A J Joosten, Silke Robatzek,

The first layer of plant immunity is activated by cell surface receptor-like kinases (RLKs) and proteins (RLPs) that detect infectious pathogens. Constitutive interaction with the SUPPRESSOR OF BIR1 (SOBIR1) RLK contributes to RLP stability and kinase activity. As RLK activation requires transphosphorylation with a second associated RLK, it remains elusive ... Read more >>

New Phytol (The New phytologist)
[2016, 210(2):627-642]

Cited: 46 times

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Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis.

Claire Roger, Bastian Nucci, Benjamin Louart, Arnaud Friggeri, Haroun Knani, Alexandre Evrard, Jean-Philippe Lavigne, Bernard Allaouchiche, Jean-Yves Lefrant, Jason A Roberts, Laurent Muller,

Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis.Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an ... Read more >>

J. Antimicrob. Chemother. (The Journal of antimicrobial chemotherapy)
[2016, 71(1):208-212]

Cited: 21 times

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Polymorphisms in SLCO1B3 and NR1I2 as genetic determinants of hematotoxicity of carboplatin and paclitaxel combination.

Litaty Céphanoée Mbatchi, Antonin Schmitt, Fabienne Thomas, Yoann Cazaubon, Jacques Robert, Serge Lumbroso, Jean-Paul Brouillet, Philippe Pourquier, Etienne Chatelut, Jean-Christophe Boyer, Alexandre Evrard,

The goal of our study was to assess the impact of patients' genetic background on their sensitivity to carboplatin/paclitaxel hematotoxicity.Parameters describing sensitivity to neutropenia and to thrombocytopenia of 201 patients were extracted from a previous pharmacokinetic/pharmacodynamics analysis, in order to assess their association with 52 candidates SNPs in 18 genes.Carriers ... Read more >>

Pharmacogenomics (Pharmacogenomics)
[2015, 16(13):1439-1450]

Cited: 8 times

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The Cf-4 receptor-like protein associates with the BAK1 receptor-like kinase to initiate receptor endocytosis and plant immunity

Jelle Postma, Thomas Liebrand, Guozhi Bi, Alexandre Evrard, Ruby Bye, Malick Mbengue, Matthieu Joosten, Silke Robatzek,

The first layer of plant immunity is activated by cell surface receptor-like kinases (RLKs) and proteins (RLPs) that detect infectious pathogens. Constitutive interaction with the RLK SUPPRESSOR OF BIR1 (SOBIR1) contributes to RLP stability and kinase activity. As RLK activation requires transphosphorylation with a second associated RLK, it remains elusive ... Read more >>

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Cited: 2 times

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