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6 results on '"Secq, Véronique"'

1. Gene expression profiling of patient‐derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts

Author

Bian, Benjamin, Bigonnet, Martin, Gayet, Odile, Loncle, Céline, Maignan, Aurélie, Gilabert, Marine, Moutardier, Vincent, Garcia, Stéphane, Turrini, Olivier, Delpero, Jean-Robert, Giovannini, Marc, Grandval, Philippe, Gasmi, Mohamed, Ouaissi, Mehdi, Secq, Véronique, Poizat, Flora, Nicolle, Rémy, Blum, Yuna, Marisa, Laetitia, Rubis, Marion, Raoul, Jean-Luc, Bradner, James, Qi, Jun, Lomberk, Gwen, Urrutia, Raul, Saúl, Andres, Dusetti, Nelson, Iovanna, Juan, Bidaut, Ghislain, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Hôpital Nord [CHU - APHM], Department of Surgical Oncology, Université de la Méditerranée - Aix-Marseille 2, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Curie [Paris], (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dana-Farber Cancer Institute [Boston], Laboratory of Epigenetics and Chromatin Dynamics, Mayo Clinic, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Curie, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), and Centre de Recherche Saint-Antoine (CR Saint-Antoine)

Subjects
Adult, Male, Cell Survival, JQ1, [SDV]Life Sciences [q-bio], Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chromatin, Epigenetics, Genomics & Functional Genomics, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, transcriptomic signature, pancreatic adenocarcinoma, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, bromodomains, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Precision Medicine, Cells, Cultured, Research Articles, Aged, Cancer, Aged, 80 and over, Gene Expression Profiling, Azepines, Middle Aged, Triazoles, Chromatin, Pancreatic Neoplasms, [SDV] Life Sciences [q-bio], c-MYC, c‐MYC, Genomics and Functional Genomics, Heterografts, Female, Epigenetics, Research Article
Abstract

International audience; c-MYC controls more than 15% of genes responsible for proliferation , differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient-derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC-high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state, and a shorter survival time compared to the MYC-low subgroup. To define classifier expression signature, we selected a group of 10 MYC target transcripts which expression is increased in the MYC-high group and six transcripts increased in the MYC-low group. We validated the ability of these markers panel to identify MYC-high patient-derived xenografts from both: discovery and validation cohorts as well as primary cell cultures from the same patients. We then showed that cells from MYC-high patients are more sensitive to JQ1 treatment compared to MYC-low cells, in monolayer, 3D cultured spheroids and in vivo xenografted tumors, due to cell cycle arrest followed by apoptosis. Therefore, these results provide new markers and potentially novel therapeutic modalities for distinct subgroups of pancreatic tumors and may find application to the future management of these patients within the setting of individualized medicine clinics.

Published
2017

2. PAP/HIP protein is an obesogenic factor

Author

Secq, Véronique, Mallmann, Cecilia, Gironella, Meritxell, López, Belén, Closa, Daniel, García, Stéphane, Christa, Laurence, Montalto, Giuseppe, Dusetti, Nelson, Iovanna, Juan Lucio, Secq, V, Mallmann, C, Gironella, M, Lopez, B, Closa, D, Garcia, S, Christa, L, Montalto, G, Dusetti, N, and Iovanna, JL

Subjects
Transgenic mice, PAP/HIP, Severe obesity
Abstract

In this article we report the obesogenic role of the acute phase protein PAP/HIP. We found that the transgenic TgPAP/HIP mice develop spontaneous obesity under standard nutritional conditions, with high levels of glucose, leptin, and LDL and low levels of triglycerides and HDL in blood. Accordingly, PAP/HIP-deficient mice are skinny under standard nutritional conditions. We also found that expression of PAP/HIP is induced in intestinal epithelial cells in response to gavage with olive oil and this induction is AG490 sensitive. We demonstrated that incubation of 3T3-L1 preadipocytes with a low concentration as 1ng/ml of recombinant PAP/HIP results in accelerated BrdU incorporation in vitro. PAP/HIP-dependent adipocytes growth is sensitive to the MEK inhibitor U0126. Finally, patients with severe obesity present higher blood levels of PAP/HIP than non-obese control individuals. Altogether our data suggest that PAP/HIP could be a mediator of fat tissue development, released by the intestine and induced by the presence of food into the gut. © 2013 Wiley Periodicals, Inc., Funded by: INSERM.

Published
2014

3. Regional molecular genetics centers in thoracic oncology: what and who should be tested?

Author

Barlési, Fabrice, Tomasini, Pascale, Fina, Frédéric, Secq, Véronique, Greillier, Laurent, Nanni-Metellus, Isabelle, Garcia, Stéphane, Ouafik, L'Houcine, Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], service hospitalier d'anatomie et cytologie pathologique humaine, APHM, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Ouafik, L'Houcine, Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)

Subjects
personalized therapy, lung cancer, french NCI, [SDV.CAN] Life Sciences [q-bio]/Cancer, molecular profiling, bioguided treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, molecular genetics center
Abstract

International audience; Management of NSCLC patients is more and more individualized especially on the base of bioguided treatments. In order to guarantee an access for all the patients too this type of strategy, the French NCI supports since 2006 a nationwide network of 28 regional genetics center. The financial support is based on public funds. The French NCI recommends today the assessment of seven biomarkers for all stage IV non squamous NSCLC patients. Due to financial and technical reasons, this recommendation must be followed. However, the molecular profiling of lung cancer patients would ideally be extended across all stages and all histological types of the disease in order to improve our knowledge in this field and provides the patient with an opportunity to access a bioguided treatment as frequently as possible.

Published
2013

4. Single-domain antibodies: a versatile and rich source of binders for breast cancer diagnostic approaches

Author

Even-Desrumeaux, Klervi, Fourquet, Patrick, Secq, Véronique, Baty, Daniel, Chames, Patrick, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and This work was supported by the ANR (Agence Nationale de Recherche) program 'Nanosciences and Nanotechnologies' under the grant ANR-07-PNANO-051-01 and by the ARC (Association pour la Recherche contre le Cancer).

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Single domain antibodies, cancer, diagnostic, biomarkers, beads array, [INFO.INFO-BT]Computer Science [cs]/Biotechnology
Abstract

International audience; Noninvasive early detection of breast cancer through the use of biomarkers is urgently needed since the risk of recurrence, morbidity, and mortality is closely related to disease stage at the time of primary surgery. A crucial issue in this approach is the availability of relevant markers and corresponding monoclonal antibodies suitable for the development of effective immunodiagnostic modalities. The identification of such markers from human pathological lesions and the isolation of specific antibodies using conventional approaches remain major challenges. Camelids produce functional antibodies devoid of light chains in which the single N-terminal domain of the heavy chain is fully capable of antigen binding. When produced as an independent domain, these so-called single-domain antibody fragments (sdAbs) or nanobodies have several advantages for biotechnological applications owing to their unique properties of size (13 kDa), stability, solubility, and expression yield. In this work, we have generated phage display libraries from animals immunized with breast cancer biopsies. These libraries were used to isolate sdAbs against known and relevant antigens such as HER2, or several cancer-specific sdAbs against unknown targets. We describe the identification of one these targets, cytokeratin 19, using affinity purification in combination with mass spectrometry. Some of these sdAbs were used in several straightforward diagnostic applications such as immunohistochemical analysis of tumor samples, multiplexed cytometric bead array analysis of crude samples, or an immune enrichment procedure of rare cells. Here, we demonstrate that phage display-based selection of single-domain antibodies is an efficient and high-throughput compatible approach to generate binders with excellent characteristics for the fast development of diagnostic and prognostic modalities.

Published
2012

5. Single-domain antibodies: a versatile and rich source of binders for breast cancer diagnostic approaches

Author

Even-Desrumeaux, Klervi, Fourquet, Patrick, Secq, Véronique, Baty, Daniel, Chames, Patrick, Chames, Patrick, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and This work was supported by the ANR (Agence Nationale de Recherche) program 'Nanosciences and Nanotechnologies' under the grant ANR-07-PNANO-051-01 and by the ARC (Association pour la Recherche contre le Cancer).

Subjects
[INFO.INFO-BT] Computer Science [cs]/Biotechnology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Single domain antibodies, cancer, diagnostic, biomarkers, beads array, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology
Abstract

International audience; Noninvasive early detection of breast cancer through the use of biomarkers is urgently needed since the risk of recurrence, morbidity, and mortality is closely related to disease stage at the time of primary surgery. A crucial issue in this approach is the availability of relevant markers and corresponding monoclonal antibodies suitable for the development of effective immunodiagnostic modalities. The identification of such markers from human pathological lesions and the isolation of specific antibodies using conventional approaches remain major challenges. Camelids produce functional antibodies devoid of light chains in which the single N-terminal domain of the heavy chain is fully capable of antigen binding. When produced as an independent domain, these so-called single-domain antibody fragments (sdAbs) or nanobodies have several advantages for biotechnological applications owing to their unique properties of size (13 kDa), stability, solubility, and expression yield. In this work, we have generated phage display libraries from animals immunized with breast cancer biopsies. These libraries were used to isolate sdAbs against known and relevant antigens such as HER2, or several cancer-specific sdAbs against unknown targets. We describe the identification of one these targets, cytokeratin 19, using affinity purification in combination with mass spectrometry. Some of these sdAbs were used in several straightforward diagnostic applications such as immunohistochemical analysis of tumor samples, multiplexed cytometric bead array analysis of crude samples, or an immune enrichment procedure of rare cells. Here, we demonstrate that phage display-based selection of single-domain antibodies is an efficient and high-throughput compatible approach to generate binders with excellent characteristics for the fast development of diagnostic and prognostic modalities.

Published
2012

6. BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)

Author

Juan-Luis Blazquez, Salem Chouaib, Jean-Charles Dagorn, Juan L. Iovanna, Anne-Sophie Chretien, Giuseppe Montalto, Véronique Secq, Audrey Benyamine, Meritxell Gironella, Elena Vila-Navarro, Mauro Modesti, Nelson Dusetti, Céline Castanier, Etienne Foucher, Celine Loncle, Daniel Olive, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), École supérieure du professorat et de l'éducation - Aix Marseille (ESPE AMU), Aix Marseille Université (AMU), Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Gastrointestinal and Pancreatic oncology, Laboratoire d'Immunologie des Tumeurs, Université de la Méditerranée - Aix-Marseille 2-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Modesti, Mauro, Centre Alexis Vautrin (CAV), Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du stress pancréatique, Institut National de la Santé et de la Recherche Médicale (INSERM), Benyamine, Audrey, Loncle, Céline, Foucher, Etienne, Blazquez, Juan-Lui, Castanier, Céline, Chrétien, Anne-Sophie, Secq, Véronique, Chouaib, Salem, Gironella, Meritxell, Vila-Navarro, Elena, Montalto, Giuseppe, Dagorn, Jean-Charle, Dusetti, Nelson, Iovanna, Juan, Olive, Daniel, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)

Subjects
0301 basic medicine, Oncology, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Pancreatic ductal adenocarcinoma, endocrine system diseases, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, btn3a, pancreatic ductal adenocarcinoma, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, medicine, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, business.industry, cd277, Aggressive cancer, Cancer, Prognosis Marker, Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, butyrophilin 3 a, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, immunotherapy, business, lcsh:RC581-607, Research Article
Abstract

Vγ9Vδ2 T cells are anti-tumor immune effectors of growing interest in cancer including Pancreatic Ductal Adenocarcinoma (PDAC), an especially aggressive cancer characterized by a hypoxic and nutrient-starved immunosuppressive microenvironment. Since Butyrophilin 3 A (BTN3A) isoforms are critical activating molecules of Vγ9Vδ2 T cells, we set out to study BTN3A expression under both basal and stress conditions in PDAC primary tumors, and in novel patient-derived xenograft and PDAC-derived cell lines. BTN3A2 was shown to be the most abundant isoform in PDAC and was stress-regulated. Vγ9Vδ2 T cells cytolytic functions against PDAC required BTN3A and this activity was strongly enhanced by the agonist anti-BTN3A 20.1 mAb even under conditions of hypoxia. In PDAC primary tumors, we established that BTN3A expression and high plasma levels of soluble BTN3A were strongly associated with a decreased survival. These findings may have important implications in the design of new immunotherapeutic strategies that target BTN3A for treating PDAC.

Published
2017

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