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• keyword#1
Alain Puisieux, Roxane M Pommier, Agnès Tissier, Anne-Pierre Morel
Aberrant cell proliferation induced by activated oncogenes triggers oxidative stress and uncontrolled DNA replication, promoting genomic instability. We recently reported that human mammary stem cells exhibit the unique capacity to withstand an oncogenic activation by dint of an anti-oxidant program driven by the ZEB1 transcription factor. This pre-emptive program prevents the onset of chromosomal instability, leading to the development of tumors with unique pathological features.
2017: Molecular & Cellular Oncology
#2
Jean-Philippe Foy, Louis Bazire, Sandra Ortiz-Cuaran, Sophie Deneuve, Janice Kielbassa, Emilie Thomas, Alain Viari, Alain Puisieux, Patrick Goudot, Chloé Bertolus, Nicolas Foray, Youlia Kirova, Pierre Verrelle, Pierre Saintigny
BACKGROUND: Radiotherapy for head and neck squamous cell carcinomas (HNSCC) is associated with a substantial morbidity and inconsistent efficacy. Human papillomavirus (HPV)-positive status is recognized as a marker of increased radiosensitivity. Our goal was to identify molecular markers associated with benefit to radiotherapy in patients with HPV-negative disease. METHODS: Gene expression profiles from public repositories were downloaded for data mining. Training sets included 421 HPV-negative HNSCC tumors from The Cancer Genome Atlas (TCGA) and 32 HNSCC cell lines with available radiosensitivity data (GSE79368)...
September 1, 2017: BMC Medicine
#3
Charlotte Bouard, Raphael Terreux, Agnès Tissier, Laurent Jacqueroud, Arnaud Vigneron, Stéphane Ansieau, Alain Puisieux, Léa Payen
BACKGROUND: The bHLH transcription factor TWIST1 plays a key role in the embryonic development and in tumorigenesis. Some loss-of-function mutations of the TWIST1 gene have been shown to cause an autosomal dominant craniosynostosis, known as the Saethre-Chotzen syndrome (SCS). Although the functional impacts of many TWIST1 mutations have been experimentally reported, little is known on the molecular mechanisms underlying their loss-of-function. In a previous study, we highlighted the predictive value of in silico molecular dynamics (MD) simulations in deciphering the molecular function of TWIST1 residues...
May 18, 2017: BMC Structural Biology
#4
Anne-Pierre Morel, Christophe Ginestier, Roxane M Pommier, Olivier Cabaud, Emmanuelle Ruiz, Julien Wicinski, Mojgan Devouassoux-Shisheboran, Valérie Combaret, Pascal Finetti, Christelle Chassot, Christiane Pinatel, Frédérique Fauvet, Pierre Saintigny, Emilie Thomas, Caroline Moyret-Lalle, Joël Lachuer, Emmanuelle Despras, Jean-Luc Jauffret, François Bertucci, Jérôme Guitton, Anne Wierinckx, Qing Wang, Nina Radosevic-Robin, Frédérique Penault-Llorca, David G Cox, Frédéric Hollande, Stéphane Ansieau, Julie Caramel, Daniel Birnbaum, Arnaud M Vigneron, Agnès Tissier, Emmanuelle Charafe-Jauffret, Alain Puisieux
Chromosomal instability (CIN), a feature of most adult neoplasms from their early stages onward, is a driver of tumorigenesis. However, several malignancy subtypes, including some triple-negative breast cancers, display a paucity of genomic aberrations, thus suggesting that tumor development may occur in the absence of CIN. Here we show that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy...
May 2017: Nature Medicine
#5
Jean-Baptiste Beuscart, Michael Genin, Corrine Dupont, David Verloop, Alain Duhamel, Marguerite-Marie Defebvre, François Puisieux
Background: potentially inappropriate medication (PIM) prescribing is common in older people and leads to adverse events and hospital admissions. Objective: to determine whether prevalence of PIM prescribing varies according to healthcare supply and socioeconomic status. Methods: all prescriptions dispensed at community pharmacies for patients aged 75 and older between 1 January and 31 March 2012 were retrieved from French Health Insurance Information System of the Nord-Pas-de-Calais Region for patients affiliated to the Social Security scheme...
July 1, 2017: Age and Ageing
#6
Pietro Fici, Giulia Gallerani, Anne-Pierre Morel, Laura Mercatali, Toni Ibrahim, Emanuela Scarpi, Dino Amadori, Alain Puisieux, Michel Rigaud, Francesco Fabbri
Epithelial-to-mesenchymal transition (EMT) has been shown to be associated with tumor progression and metastasis. During this process in breast cancer, a crucial role is played by alternative splicing systems. To identify a new early prognostic marker of metastasis, we evaluated EMT-related gene expression in breast cell lines, and in primary tumor tissue from 31 patients with early breast cancer, focusing our attention on EMT-related splicing factors ESRP1, ESRP2 and RBFOX2. Results showed that the expression patterns of these genes were indicative of the onset of EMT in in-vitro models, but not in tissue samples...
January 10, 2017: Oncotarget
#7
REVIEW
Pierre Saintigny, Jean-Philippe Foy, Anthony Ferrari, Philippe Cassier, Alain Viari, Alain Puisieux
Since the first draft of the human genome sequence published in 2001, the cost of sequencing has dramatically decreased. The development of new technologies such as next generation sequencing led to a comprehensive characterization of a large number of tumors of various types as well as to significant advances in precision medicine. Despite the valuable information this technological revolution has allowed to produce, the vast amount of data generated resulted in the emergence of new challenges for the biomedical community, such as data storage, processing and mining...
March 2017: Bulletin du Cancer
#8
REVIEW
Caroline Moyret-Lalle, Roxane Pommier, Charlotte Bouard, Ebticem Nouri, Geoffrey Richard, Alain Puisieux
Metastatic dissemination consists of a sequence of events resulting in the invasion by cancer cells of tissues located away from the primary tumour. This process is highly inefficient, since each event represents an obstacle that only a limited number of cells can overcome. However, two biological phenomena intrinsically linked with tumour development facilitate the dissemination of cancer cells throughout the body and promote the formation of metastases, namely the genetic diversity of cancer cells within a given tumour, which arises from their genetic instability and from successive clonal expansions, and cellular plasticity conveyed to the cells by micro-environmental signals...
August 2016: Médecine Sciences: M/S
#9
Geoffrey Richard, Stéphane Dalle, Marie-Ambre Monet, Maud Ligier, Amélie Boespflug, Roxane M Pommier, Arnaud de la Fouchardière, Marie Perier-Muzet, Lauriane Depaepe, Romain Barnault, Garance Tondeur, Stéphane Ansieau, Emilie Thomas, Corine Bertolotto, Robert Ballotti, Samia Mourah, Maxime Battistella, Céleste Lebbé, Luc Thomas, Alain Puisieux, Julie Caramel
Targeted therapies with MAPK inhibitors (MAPKi) are faced with severe problems of resistance in BRAF-mutant melanoma. In parallel to the acquisition of genetic mutations, melanoma cells may also adapt to the drugs through phenotype switching. The ZEB1 transcription factor, a known inducer of EMT and invasiveness, is now considered as a genuine oncogenic factor required for tumor initiation, cancer cell plasticity, and drug resistance in carcinomas. Here, we show that high levels of ZEB1 expression are associated with inherent resistance to MAPKi in BRAF(V)(600)-mutated cell lines and tumors...
October 2016: EMBO Molecular Medicine
#10
Mathieu Chicard, Sandrine Boyault, Leo Colmet Daage, Wilfrid Richer, David Gentien, Gaelle Pierron, Eve Lapouble, Angela Bellini, Nathalie Clement, Isabelle Iacono, Stéphanie Bréjon, Marjorie Carrere, Cécile Reyes, Toby Hocking, Virginie Bernard, Michel Peuchmaur, Nadège Corradini, Cécile Faure-Conter, Carole Coze, Dominique Plantaz, Anne Sophie Defachelles, Estelle Thebaud, Marion Gambart, Frédéric Millot, Dominique Valteau-Couanet, Jean Michon, Alain Puisieux, Olivier Delattre, Valérie Combaret, Gudrun Schleiermacher
PURPOSE: The tumor genomic copy number profile is of prognostic significance in neuroblastoma patients. We have studied the genomic copy number profile of cell-free DNA (cfDNA) and compared this with primary tumor arrayCGH (aCGH) at diagnosis. EXPERIMENTAL DESIGN: In 70 patients, cfDNA genomic copy number profiling was performed using the OncoScan platform. The profiles were classified according to the overall pattern, including numerical chromosome alterations (NCA), segmental chromosome alterations (SCA), and MYCN amplification (MNA)...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
#11
Laurent Jacqueroud, Charlotte Bouard, Geoffrey Richard, Léa Payen, Mojgan Devouassoux-Shisheboran, Douglas B Spicer, Julie Caramel, Guillaume Collin, Alain Puisieux, Agnès Tissier, Stéphane Ansieau
The TWIST1 embryonic transcription factor displays biphasic functions during the course of carcinogenesis. It facilitates the escape of cells from oncogene-induced fail-safe programs (senescence, apoptosis) and their consequent neoplastic transformation. Additionally, it promotes the epithelial-to-mesenchymal transition and the initiation of the metastatic spread of cancer cells. Interestingly, cancer cells recurrently remain dependent on TWIST1 for their survival and/or proliferation, making TWIST1 their Achilles' heel...
May 2016: Neoplasia: An International Journal for Oncology Research
#12
Charlotte Bouard, Raphael Terreux, Mylène Honorat, Brigitte Manship, Stéphane Ansieau, Arnaud M Vigneron, Alain Puisieux, Léa Payen
The TWIST1 bHLH transcription factor controls embryonic development and cancer processes. Although molecular and genetic analyses have provided a wealth of data on the role of bHLH transcription factors, very little is known on the molecular mechanisms underlying their binding affinity to the E-box sequence of the promoter. Here, we used an in silico model of the TWIST1/E12 (TE) heterocomplex and performed molecular dynamics (MD) simulations of its binding to specific (TE-box) and modified E-box sequences. We focused on (i) active E-box and inactive E-box sequences, on (ii) modified active E-box sequences, as well as on (iii) two box sequences with modified adjacent bases the AT- and TA-boxes...
June 20, 2016: Nucleic Acids Research
#13
Adeline Granzotto, Mohamed Amine Benadjaoud, Guillaume Vogin, Clément Devic, Mélanie L Ferlazzo, Larry Bodgi, Sandrine Pereira, Laurène Sonzogni, Fabien Forcheron, Muriel Viau, Aurélie Etaix, Karim Malek, Laurence Mengue-Bindjeme, Clémence Escoffier, Isabelle Rouvet, Marie-Thérèse Zabot, Aurélie Joubert, Anne Vincent, Nicole Dalla Venezia, Michel Bourguignon, Edme-Philippe Canat, Anne d'Hombres, Estelle Thébaud, Daniel Orbach, Dominique Stoppa-Lyonnet, Abderraouf Radji, Eric Doré, Yoann Pointreau, Céline Bourgier, Pierre Leblond, Anne-Sophie Defachelles, Cyril Lervat, Stéphanie Guey, Loic Feuvret, Françoise Gilsoul, Claire Berger, Coralie Moncharmont, Guy de Laroche, Marie-Virginie Moreau-Claeys, Nicole Chavaudra, Patrick Combemale, Marie-Claude Biston, Claude Malet, Isabelle Martel-Lafay, Cécile Laude, Ngoc-Hanh Hau-Desbat, Amira Ziouéche, Ronan Tanguy, Marie-Pierre Sunyach, Séverine Racadot, Pascal Pommier, Line Claude, Frédéric Baleydier, Bertrand Fleury, Renaud de Crevoisier, Jean-Marc Simon, Pierre Verrelle, Didier Peiffert, Yazid Belkacemi, Jean Bourhis, Eric Lartigau, Christian Carrie, Florent De Vathaire, François Eschwege, Alain Puisieux, Jean-Léon Lagrange, Jacques Balosso, Nicolas Foray
PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases...
March 1, 2016: International Journal of Radiation Oncology, Biology, Physics
#14
Roxane M Pommier, Johann Gout, David F Vincent, Lindsay B Alcaraz, Nicolas Chuvin, Vanessa Arfi, Sylvie Martel, Bastien Kaniewski, Guillaume Devailly, Geneviève Fourel, Pascal Bernard, Caroline Moyret-Lalle, Stéphane Ansieau, Alain Puisieux, Ulrich Valcourt, Stéphanie Sentis, Laurent Bartholin
The transcription accessory factor TIF1γ/TRIM33/RFG7/PTC7/Ectodermin functions as a tumor suppressor that promotes development and cellular differentiation. However, its precise function in cancer has been elusive. In the present study, we report that TIF1γ inactivation causes cells to accumulate chromosomal defects, a hallmark of cancer, due to attenuations in the spindle assembly checkpoint and the post-mitotic checkpoint. TIF1γ deficiency also caused a loss of contact growth inhibition and increased anchorage-independent growth in vitro and in vivo...
October 15, 2015: Cancer Research
#15
REVIEW
Jean-Yves Blay, Olivier Tredan, Isabelle Ray-Coquard, Michel Rivoire, Patrick Mehlen, Alain Puisieux, Thomas Bachelot
Cancers can now be classified by multidimensional criteria including tumour site, histology, primary - "driver" - molecular alterations, secondary molecular alterations, characteristics of the immune stroma, and genetic profile of the patient. The development of tools for the characterisation of the cancers, as well as novel molecular and immune therapeutics are evolving at an unprecedented pace. In 2012, a list of future challenges was identified at the occasion of the European Organisation for Research and Treatment of Cancer (EORTC) 50(th) anniversary...
June 2015: Bulletin du Cancer
#16
Guillaume Devailly, Mélodie Grandin, Laury Perriaud, Pauline Mathot, Jean-Guy Delcros, Yannick Bidet, Anne-Pierre Morel, Jean-Yves Bignon, Alain Puisieux, Patrick Mehlen, Robert Dante
DNA methylation is thought to induce transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators unable to bind their target sites when methylated, and the recruitment of transcriptional repressors with specific affinity for methylated DNA. The Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. Here, we present MBD2 ChIPseq data obtained from the endogenous MBD2 in an isogenic cellular model of oncogenic transformation of human mammary cells...
July 13, 2015: Nucleic Acids Research
#17
David G Cox, Alain Puisieux
No abstract text is available yet for this article.
March 2015: Mutagenesis
#18
Philippe Télouk, Alain Puisieux, Toshiyuki Fujii, Vincent Balter, Victor P Bondanese, Anne-Pierre Morel, Gilles Clapisson, Aline Lamboux, Francis Albarede
The isotope effect describes mass-dependent variations of natural isotope abundances for a particular element. In this pilot study, we measured the (65)Cu/(63)Cu ratios in the serums of 20 breast and 8 colorectal cancer patients, which correspond to, respectively, 90 and 49 samples taken at different times with molecular biomarker documentation. Copper isotope compositions were determined by multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). When compared with the literature data from a control group of 50 healthy blood donors, abundances of Cu isotopes predict mortality in the colorectal cancer group with a probability p = 0...
February 2015: Metallomics: Integrated Biometal Science
#19
Abdelkader Selmi, Maud de Saint-Jean, Anne-Catherine Jallas, Elisabeth Garin, Michael D Hogarty, Jean Bénard, Alain Puisieux, Aurélien Marabelle, Sandrine Valsesia-Wittmann
In neuroblastoma, MYCN amplification is associated with a worse prognosis and is a criterion used in the clinic to provide intensive treatments to children even with localized disease. In correlation with MYCN amplification, upregulation of TWIST1, a transcription factor playing a crucial role in inhibition of apoptosis and differentiation, was previously reported. Clinical data set analysis of MYCN, MYC and TWIST1 expression permits us to confirm that TWIST1 expression is upregulated in MYCN amplified neuroblastoma but also in a subset of neuroblastoma harboring high expression of MYCN or MYC without gene amplification...
February 1, 2015: Cancer Letters
#20
Léa Payen, Mylène Honorat, Jérôme Guitton, Charlotte Gauthier, Charlotte Bouard, Florine Lecerf-Schmidt, Basile Peres, Raphaël Terreux, Héloïse Gervot, Catherine Rioufol, Ahcène Boumendjel, Alain Puisieux, Attilio Di Pietro
ABCG2 is responsible for the multidrug resistance (MDR) phenotype, and strongly modulates cancer outcomes. Its high expression at a number of physiological barriers, including blood-brain and intestinal barriers, impacts on drug pharmacokinetics parameters. We characterized MBL-II-141, a specific and potent ABCG2 inhibitor. Combination of 10 mg/kg MBL-II-141 with the anticancer agent CPT-11 completely blocked the growth of 90% freshly implanted ABCG2-positive tumors. Moreover, the same combination slowed the growth of already established tumors...
December 15, 2014: Oncotarget
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