19 results on '"Helena Polena"'
Search Results
2. Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker.
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Isabelle Vilgrain, Adama Sidibé, Helena Polena, Francine Cand, Tiphaine Mannic, Mélanie Arboleas, Sandra Boccard, Antoine Baudet, Danielle Gulino-Debrac, Laurence Bouillet, Jean-Louis Quesada, Christophe Mendoza, Jean-François Lebas, Laurent Pelletier, and François Berger
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Medicine ,Science - Abstract
Vessel abnormalities are among the most important features in malignant glioma. Vascular endothelial (VE)-cadherin is of major importance for vascular integrity. Upon cytokine challenge, VE-cadherin structural modifications have been described including tyrosine phosphorylation and cleavage. The goal of this study was to examine whether these events occurred in human glioma vessels. We demonstrated that VE-cadherin is highly expressed in human glioma tissue and tyrosine phosphorylated at site Y(685), a site previously found phosphorylated upon VEGF challenge, via Src activation. In vitro experiments showed that VEGF-induced VE-cadherin phosphorylation, preceded the cleavage of its extracellular adhesive domain (sVE, 90 kDa). Interestingly, metalloproteases (MMPs) secreted by glioma cell lines were responsible for sVE release. Because VEGF and MMPs are important components of tumor microenvironment, we hypothesized that VE-cadherin proteolysis might occur in human brain tumors. Analysis of glioma patient sera prior treatment confirmed the presence of sVE in bloodstream. Furthermore, sVE levels studied in a cohort of 53 glioma patients were significantly predictive of the overall survival at three years (HR 0.13 [0.04; 0.40] p ≤ 0.001), irrespective to histopathological grade of tumors. Altogether, these results suggest that VE-cadherin structural modifications should be examined as candidate biomarkers of tumor vessel abnormalities, with promising applications in oncology.
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- 2013
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3. ESDR141 - Focus on triggering factors in sensitive skin: two biomarkers in a new heat-cold stress in vivo model
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Michèle Sayag, Sandra Trompezinski, Elise Abric, Nathalie Ardiet, Marlène Chavagnac, Félix Giraud, Arnaud Fontbonne, and Helena Polena
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- 2022
4. Improvement of Quality of Life in Dialysis and Diabetic Patients by Skin Dryness and Pruritus Management with an Ecobiological Dermo-Cosmetic Product
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Helena Polena, Marlène Chavagnac-Bonneville, and Michèle Sayag
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Clinical, Cosmetic and Investigational Dermatology ,Dermatology - Abstract
Helena Polena,1 Marlène Chavagnac-Bonneville,1,2 Michèle Sayag1 1NAOS Group, Research and Development Department, Aix-en-Provence, France; 2NAOS Institute of Life Science, Aix-en-Provence, FranceCorrespondence: Helena Polena, NAOS Group, 355 rue Pierre Simon Laplace, Cedex 03, Aix-en-Provence, 13593, France, Tel +33 4 72 11 37 19, Fax +33 4 78 53 82 54, Email helena.polena@naos.comPurpose: Xerosis and pruritus are common chronic dermatological disorders among dialysis and diabetic patients that are frequently underdiagnosed or neglected, which can impact the quality of life of these patients. This study aimed to evaluate the efficacy and safety of a specific dermo-cosmetic product in the treatment of dry skin and pruritus associated with dialysis and diabetes.Patients and Methods: Twenty-nine dialysis patients (mean age 62 years) and 40 diabetic patients (mean age 57 years, 88% type 2) were included in two different single-center open-label uncontrolled clinical trials. All patients presented skin dryness according to the Scaling Roughness Redness and Cracks (SRRC) scale, and pruritus and/or insomnia. They applied the dermo-cosmetic product Medi-Secure Atoderm Xereane (NAOS, Laboratoire Bioderma) once or twice a day. The clinical efficacy (SRRC, pruritus, and insomnia), the skin-related quality of life (Dermatological Life Quality Index, DLQI), and the subjective efficacy were assessed at the inclusion visit and after 28 days of product application, as well as the safety.Results: After 28 days of application, the product significantly reduced the SRRC global score of 83% (0.9± 0.8 vs 5.1± 1.2) and 66% (1.4± 1.2 vs 4.2± 0.5), pruritus intensity of 76% (1.1± 1.3 vs 4.6± 2.1) and 78% (0.9± 1.7 vs 4.2± 2.6), and insomnia intensity of 61% (0.9± 1.3 vs 2.4± 2.3) and 82% (0.9± 1.7 vs 4.8± 2.7) in dialysis and diabetic patients, respectively. Furthermore, the product’s application led to an improvement of the skin-related quality of life of 50% (5.4 vs 2.7; p< 0.0001) in dialysis patients and 71% (6.6 vs 1.9; p< 0.0001) in diabetic patients at D28. In addition, the product was greatly appreciated by all patients for its soothing, comforting, repairing, nourishing, and hydrating effects and was very well tolerated by the entire panels.Conclusion: This specific dermo-cosmetic product significantly reduces skin dryness, pruritus, and insomnia in dialysis and diabetic patients, thereby greatly improves their skin-related quality of life. By managing and avoiding bothersome symptoms associated with their disease or treatment, this ecobiological dermo-cosmetic can prevent serious complications that constitute a substantial burden on their daily life.Keywords: xerosis, itch, uremic, diabetes mellitus, insomnia, emollient
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- 2022
5. Burden of Sensitive Skin (BoSS) Questionnaire and Current Perception Threshold: Use as Diagnostic Tools for Sensitive Skin Syndrome
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Laurent Misery, Marlène Chavagnac-Bonneville, Michèle Sayag, and Helena Polena
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medicine.medical_specialty ,Skin type ,neurometer ,media_common.quotation_subject ,Sensation ,diagnostic ,Dermatology ,Diagnostic tools ,smoking ,Sensitive skin ,burden ,Perception ,Surveys and Questionnaires ,medicine ,Humans ,media_common ,Skin ,integumentary system ,business.industry ,General Medicine ,Syndrome ,Phototype ,sensory perception ,Boss ,sensitive skin ,RL1-803 ,Smoking status ,Female ,business - Abstract
The assessment of sensitive skin syndrome, characterized by subjective unpleasant sensations, remains a challenge, since there is no international consensus on the best diagnostic tools. This study evaluated the combination of the Burden of Sensitive Skin (BoSS) questionnaire and the current perception threshold as diagnostic tools for sensitive skin syndrome, and the relationship between BoSS and the subjects’ smoking status, phototype and skin type. A total of 100 women completed the BoSS questionnaire, and current perception threshold was measured on the face. The BoSS score was significantly higher in the self-reported sensitive skin group compared with the non-sensitive skin group (25.61 vs 14.05; p
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- 2021
6. Soluble vascular endothelial (VE) cadherin and autoantibodies to VE-cadherin in rheumatoid arthritis patients treated with etanercept or adalimumab
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Xavier Le-Loët, Christopher Banse, Estelle Houivet, Christian Marcelli, Barry Stidder, Helena Polena, Isabelle Vilgrain, Olivier Vittecoq, Peggy Philippe, Patrice Fardellone, Thierry Lequerré, Abir Khalil-Mgharbel, CHU Rouen, Normandie Université (NU), Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service de rhumatologie, CHU Amiens-Picardie, Service de Rhumatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,0301 basic medicine ,Systemic disease ,Soluble VE cadherin ,Severity of Illness Index ,Gastroenterology ,Etanercept ,Arthritis, Rheumatoid ,Cohort Studies ,0302 clinical medicine ,Longitudinal Studies ,Prospective Studies ,skin and connective tissue diseases ,Middle Aged ,Cadherins ,Treatment Outcome ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Rheumatoid arthritis ,Biomarker (medicine) ,Female ,France ,medicine.drug ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,Anti-vascular endothelial-cadherin antibody ,Risk Assessment ,03 medical and health sciences ,Rheumatology ,Antigens, CD ,Internal medicine ,medicine ,Adalimumab ,Humans ,Rheumatoid factor ,Aged ,Autoantibodies ,030203 arthritis & rheumatology ,business.industry ,Autoantibody ,medicine.disease ,030104 developmental biology ,Solubility ,Immunology ,Methotrexate ,business ,Biomarkers ,Follow-Up Studies - Abstract
Objectives The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. Methods This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. Results Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. Conclusions sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.
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- 2017
7. 16382 Efficacy and tolerance assessment of a dermocosmetic balm in Mexican pediatric subjects with mild to moderate atopic dermatitis through reflectance confocal microscopy
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Adriana Valencia Herrera, Helena Polena, Mirna E. Toledo-Bahena, Clariza Infante, Rodrigo Roldán-Marín, García-Hernandez Alejandra, Gustavo Segura-Moreno, Marysol Macedo Pérez, Ethel Pinto, Elizabeth Ortíz Moreno, Ethel Pinto Carrillo, and Michele Sayag
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Reflectance confocal microscopy ,medicine.medical_specialty ,business.industry ,medicine ,Dermatology ,Atopic dermatitis ,medicine.disease ,business - Published
- 2020
8. A Biomimetic Lipid Membrane Device Reveals the Interaction of Cancer Biomarkers with Human Serum Lipidic Moieties
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Abir Khalil-Mgharbel, Paul K. Dembélé, Isabelle Vilgrain, Jean-Pierre Alcaraz, Md. Mehadi Hasan Sohag, Donald K. Martin, Helena Polena, Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), and Alcaraz, Jean-Pierre
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0301 basic medicine ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Lipoproteins ,[SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics ,[SDV]Life Sciences [q-bio] ,Population ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Antigens, CD ,Biomimetic Materials ,Biomarkers, Tumor ,medicine ,Humans ,Immunoprecipitation ,Nanotechnology ,[SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics ,education ,Lipid bilayer ,ComputingMilieux_MISCELLANEOUS ,education.field_of_study ,Apolipoprotein A-I ,biology ,Chemistry ,Cancer ,General Medicine ,Models, Theoretical ,Cadherins ,medicine.disease ,Kidney Neoplasms ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,3. Good health ,[SDV] Life Sciences [q-bio] ,Cholesterol ,HEK293 Cells ,030104 developmental biology ,Biochemistry ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Biomarker (medicine) ,lipids (amino acids, peptides, and proteins) ,Apolipoprotein A1 ,Cancer biomarkers ,Ultracentrifuge ,Biotechnology ,Lipoprotein - Abstract
A major problem for the detection of cancer biomarkers in plasma or serum is that common clinical practice does not require the patient to be in a fasting state. Considering that lipoproteins are the main population affected by food intake, the authors hypothesized that biomarkers could be embedded in lipid particles and thereby opens a new avenue for detection. Using the recently published biomarker, soluble VE-cadherin (sVE), the authors tested our hypothesis using techniques of biophysics, biochemistry and the tools of nanobiotechnology on serum samples from kidney cancer patients (n = 106). Optical density as well as contact angle measurements of serum revealed heterogeneity in the particle content of the serum samples. Isolation of the lipidic moieties by ultracentrifugation showed that sVE was detected in this compartment. Further, isolation of lipoprotein subclasses by precipitation with sodium phosphotungstate and MgCl2 , showed that HDL carried the majority of sVE. Immunoprecipitation of sVE confirmed that it was associated with Apolipoprotein A1, a major compound of HDL. Using a biomimetic lipid bilayer membrane coupled with impedance spectroscopy the authors quantified, in real-time, that the sVE adsorbed to the lipid bilayer membrane without altering its structure. Taken together, these results show for the first time a direct interaction of a cancer biomarker with lipids. The authors anticipate these results to prompt fasting for future blood tests for large-scale studies in the biomarkers research field.
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- 2018
9. The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma
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Helena Polena, Ellen Blanc, Abir Khalil-Mgharbel, Delphine Borchiellini, Gilles Pagès, Jean-Marc Ferrero, Maeva Dufies, Isabelle Vilgrain, Céline Ferlay-Segura, Aude Salomon, Alban Deroux, Odile Filhol, Adama Sidibé, Jean-Louis Quesada, Sylvie Negrier, Julie Creuzet, Bernard Escudier, Caroline Roelants, Claude Cochet, Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Grenoble Alpes - Institut d'Administration des Entreprises (UGA IAE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Invasion mechanisms in angiogenesis and cancer (IMAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Grenoble Alpes - UFR Médecine (UGA UFRM), CIC - Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Délégation à la Recherche Clinique et à l'Innovation [Lyon] (DRCI), UNICANCER - Centre Léon Bérard Lyon (Rhône)-Centre de Lutte Contre le Cancer de Lyon et Rhône-Alpes, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Lyon, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Angiogenèse hormono-regulée et angiogenèse tumorale (LAPV), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transduction du signal : signalisation calcium, phosphorylation et inflammation, Centre Léon Bérard [Lyon], Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Centre Léon Bérard [Lyon]-UNICANCER - Centre Léon Bérard Lyon (Rhône), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
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0301 basic medicine ,Cancer Research ,Bevacizumab ,Endothelium ,medicine.drug_class ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Tyrosine-kinase inhibitor ,Biomarkers, Pharmacological ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Human Umbilical Vein Endothelial Cells ,Sunitinib ,Humans ,Molecular Targeted Therapy ,Neoplasm Metastasis ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Carcinoma, Renal Cell ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,Retrospective Studies ,Clinical Trials as Topic ,business.industry ,medicine.disease ,Cadherins ,Metastatic breast cancer ,Kidney Neoplasms ,3. Good health ,Endothelial stem cell ,030104 developmental biology ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Endothelium, Vascular ,VE-cadherin ,business ,Kidney cancer ,medicine.drug - Abstract
Background Vascular endothelial (VE)-cadherin is an endothelial cell-specific protein responsible for endothelium integrity. Its adhesive properties are regulated by post-translational processing, such as tyrosine phosphorylation at site Y685 in its cytoplasmic domain, and cleavage of its extracellular domain (sVE). In hormone-refractory metastatic breast cancer, we recently demonstrated that sVE levels correlate to poor survival. In the present study, we determine whether kidney cancer therapies had an effect on VE-cadherin structural modifications and their clinical interest to monitor patient outcome. Methods The effects of kidney cancer biotherapies were tested on an endothelial monolayer model mimicking the endothelium lining blood vessels and on a homotypic and heterotypic 3D cell model mimicking tumour growth. sVE was quantified by ELISA in renal cell carcinoma patients initiating sunitinib (48 patients) or bevacizumab (83 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials). Results Human VE-cadherin is a direct target for sunitinib which inhibits its VEGF-induced phosphorylation and cleavage on endothelial monolayer and endothelial cell migration in the 3D model. The tumour cell environment modulates VE-cadherin functions through MMPs and VEGF. We demonstrate the presence of soluble VE-cadherin in the sera of mRCC patients (n = 131) which level at baseline, is higher than in a healthy donor group (n = 96). Analysis of sVE level after 4 weeks of treatment showed that a decrease in sVE level discriminates the responders vs. non-responders to sunitinib, but not bevacizumab. Conclusions These data highlight the interest for the sVE bioassay in future follow-up of cancer patients treated with targeted therapies such as tyrosine-kinase inhibitors.
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- 2018
10. Mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination
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Jean-Louis Herrmann, Cécile Lecointe, Mattia Pelizzola, Soa Fy Andriamandimby, Frédéric Boudou, Paola Ricciardi-Castagnoli, Niaina Rakotosamimanana, Patricia Charles, Helena Polena, Ludovic Tailleux, Sylvain Tilleul, Nicolas Dubois-Colas, Voahangy Rasolofo, Vaomalala Raharimanga, Brigitte Gicquel, Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Unité d'Epidémiologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Unité des Mycobactéries [Antananarivo, Madagascar] (IPM), This research project was co-financed by Institut Pasteur and the European Commission, as part of the 6th Framework Programme, contract numbers LSH-2003-2.3.0-1 and LSHP-CT-2003-503367, the 7th Framework Programme, grant number HEALTH-F3-2009-241745., European Project: 241745,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,NEWTBVAC(2010), Tailleux, Ludovic, and Discovery and preclinical development of new generation tuberculosis vaccines - NEWTBVAC - - EC:FP7:HEALTH2010-01-01 - 2014-02-28 - 241745 - VALID
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0301 basic medicine ,MESH: Mycobacterium tuberculosis ,Angiogenesis ,Mice, SCID ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Neovascularization ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH: Up-Regulation ,MESH: Animals ,Angiogenic Proteins ,MESH: Mice, SCID ,Pathogen ,Lung ,Cells, Cultured ,Multidisciplinary ,Neovascularization, Pathologic ,3. Good health ,Up-Regulation ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Female ,medicine.symptom ,MESH: Cells, Cultured ,Tuberculosis ,MESH: Angiogenic Proteins ,Biology ,Article ,Mycobacterium tuberculosis ,03 medical and health sciences ,In vivo ,medicine ,Animals ,Humans ,MESH: Lung ,Progenitor cell ,Tuberculosis, Pulmonary ,[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity ,MESH: Tuberculosis, Pulmonary ,MESH: Humans ,MESH: Transcriptome ,MESH: Host-Pathogen Interactions ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,Immunology ,Cancer research ,Bone marrow ,Transcriptome ,MESH: Neovascularization, Pathologic ,MESH: Female - Abstract
The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly understood. Herein, we used a transcriptomic approach to investigate the host cell gene expression profile in M. tuberculosis–infected human macrophages (ΜΦ). We identified 33 genes, encoding proteins involved in angiogenesis, for which the expression was significantly modified during infection, and we show that the potent angiogenic factor VEGF is secreted by M. tuberculosis-infected ΜΦ, in an RD1-dependent manner. In vivo these factors promote the formation of blood vessels in murine models of the disease. Inhibiting angiogenesis, via VEGF inactivation, abolished mycobacterial spread from the infection site. In accordance with our in vitro and in vivo results, we show that the level of VEGF in TB patients is elevated and that endothelial progenitor cells are mobilized from the bone marrow. These results strongly strengthen the most recent data suggesting that mycobacteria take advantage of the formation of new blood vessels to disseminate.
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- 2016
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11. Soluble VE-cadherin in metastatic breast cancer: an independent prognostic factor for both progression-free survival and overall survival
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Helena Polena, Thomas Bachelot, Olivier Tredan, Isabelle Vilgrain, François-Clément Bidard, Jean-Yves Pierga, Camille Schiffler, Abir Khalil-Mgharbel, Etienne Brain, Sylvie Chabaud, Pauline Rochefort, Centre Léon Bérard [Lyon], Service d'Oncologie Médicale, Institut Curie [Paris], Institut Curie - Saint Cloud (ICSC), Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Saint-Cloud], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,Prognostic variable ,medicine.medical_specialty ,Colorectal cancer ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Breast Neoplasms ,survival ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication ,Antigens, CD ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Progression-free survival ,Neoplasm Metastasis ,skin and connective tissue diseases ,Lung cancer ,prognostic factor ,Molecular Diagnostics ,Survival analysis ,Aged ,Aged, 80 and over ,business.industry ,soluble VE-cadherin ,Middle Aged ,medicine.disease ,Cadherins ,Prognosis ,Metastatic breast cancer ,Survival Analysis ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,metastatic breast cancer ,business ,Liver cancer - Abstract
Background: Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC. Methods: Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study. Serum concentrations of VE-cadherin were measured at inclusion for 141 patients and 6 weeks after the beginning of chemotherapy, using a sandwich enzyme immunoassay. Results: The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free (PFS) and overall survival (OS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level was an independent adverse prognostic variable for PFS (median PFS 9.7 (IC95: 8; 11.9) vs 5.8 (IC95: 4.1; 8) months P=0.0008) and OS (median OS 34 (IC95: 26.6; 47.1) vs 14.8 (IC95: 9.3; 21.4) months P=0.0007). Moreover, VE-cadherin decrease during chemotherapy was also associated with good prognosis. Conclusions: Serum VE-cadherin levels correlate to poorer survival in patients with hormone-refractory MBC. As sVE-cadherin reflects tumour angiogenesis, this could have therapeutic implications for antiangiogenic treatment.
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- 2016
12. UGT1A1, UGT1A6 and UGT1A7 Genetic Analysis
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Maria J. Brilhante, Helena Polena, Rita Cabral, Claudia C. Branco, Luisa Mota-Vieira, Francesc Sigalat, Paula Pacheco, and Cristina Ballart
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Linkage disequilibrium ,Glucuronosyltransferase ,Genotype ,Population ,Antineoplastic Agents ,Biology ,Pharmacology ,Irinotecan ,digestive system ,Genetic analysis ,Linkage Disequilibrium ,Gene Frequency ,Genetics ,Humans ,Allele ,education ,Gene ,Alleles ,education.field_of_study ,Polymorphism, Genetic ,Haplotype ,General Medicine ,Haplotypes ,Pharmacogenetics ,biology.protein ,Molecular Medicine ,Camptothecin - Abstract
Background: Glucuronidation reactions, catalyzed by uridine-diphosphate glucuronosyltransferase (UGT) enzymes, constitute a detoxification process that adds glucuronic acid to endogenous and exogenous compounds, aiding their excretion. UGT1A proteins have been implicated as risk factors for both the development of cancer and adverse drug effects. Methods: Here, we assess the genome of 469 individuals from Sao Miguel Island (Azores, Portugal) in order to determine the frequencies of polymorphisms and haplotypes in UGT1A1, UGT1A6, and UGT1A7, the co-occurrence of reduced enzyme activity UGT1A variants related to irinotecan toxicity, and to calculate the extent of linkage disequilibrium (LD) in the genomic region encompassing these genes. Results: Allelic analysis disclosed the presence of rare alleles — UGT1A1*36 and UGT1A1*37 — only found in individuals of African descent, and UGT1A 7*4. These alleles confirm our previous results on the Sao Miguel Island genetic background. We identified five different genotypes in UGT1A1 and UGT1A6 and nine in UGT1A7. Haplotype analysis showed that three haplotypes constituted approximately 80% of the allelic variants. Interestingly, haplotype 3 (UGT1A1*28- UGT1A6*2- UGT1A7*3), with a frequency of 0.235, gathers the three alleles encoding the low-function UGT isoforms. Additionally, LD indicates a strong interaction between functional polymorphisms related to the alteration of the UGT enzyme activity. Conclusions: In summary, the results demonstrate a high variability of alleles and haplotypes, which have important roles in modifying expression and activity of UGTs. The data presented here could improve the understanding of the predisposition to cancers and susceptibility to the adverse effects of irinotecan in the Sao Miguel Island population.
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- 2009
13. Soluble vascular endothelial-cadherin and auto-antibodies to human vascular endothelial-cadherin in human diseases: Two new biomarkers of endothelial dysfunction
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Helena Polena, Isabelle Vilgrain, Sophie Blaise, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hypoxie et physiopathologies cardiovasculaire et respiratoire, and Institut National de la Santé et de la Recherche Médicale (INSERM)
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Pathology ,medicine.medical_specialty ,Molecular Sequence Data ,Inflammation ,autoimmune disease ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,endothelial dysfunction ,Autoimmune Diseases ,Adherens junction ,Capillary Permeability ,sepsis ,Antigens, CD ,Predictive Value of Tests ,Medicine ,Animals ,Humans ,cancer ,Amino Acid Sequence ,Vascular Diseases ,Endothelial dysfunction ,[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology ,Autoantibodies ,business.industry ,Autoantibody ,biomarkers ,medicine.disease ,Cadherins ,Prognosis ,Transmembrane protein ,3. Good health ,Vascular endothelial growth factor B ,Vascular endothelial growth factor A ,Vascular endothelial growth factor C ,inflammation ,Cancer research ,Endothelium, Vascular ,medicine.symptom ,atherosclerosis ,Cardiology and Cardiovascular Medicine ,business - Abstract
International audience; Vascular endothelial-cadherin is the most important transmembrane component of endothelial adherens junctions, exclusively expressed by endothelial cells in all types of vessels. Targeting either the extracellular domain or the cytoplasmic tail deleteriously affects the junctional strength and leads to vascular permeability. Recently, cytokine-induced phosphorylation of the vascular endothelial-cadherin cytoplasmic domain was reported to trigger cleavage of its extracellular domain, producing the soluble form of the protein - soluble vascular endothelial-cadherin. Hence, the presence of soluble vascular endothelial-cadherin or auto-antibodies to human vascular endothelial-cadherin in human serum could signalize the presence of vascular abnormalities. This systematic review covers many human studies reporting increased levels of soluble vascular endothelial-cadherin, as well as auto-antibodies to human vascular endothelial-cadherin, which could be promising biomarkers of endothelial dysfunction in a large panel of diseases.
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- 2015
14. Dynamic phosphorylation of VE-cadherin Y685 throughout mouse estrous cycle in ovary and uterus
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Soumalamaya Bama, Isabelle Vilgrain, Adama Sidibé, Laurence Bouillet, Helena Polena, Tiphaine Mannic, Nicolas Chaumontel, Philippe Huber, Danielle Gulino-Debrac, Jeremy Razanajatovo, Irene Marechal, Université Grenoble Alpes - Institut d'Administration des Entreprises (UGA IAE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie vasculaire : interactions cellulaires, signalisation et vieillissement, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)
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Time Factors ,Gonadotropins, Equine ,Physiology ,Angiogenesis ,[SDV]Life Sciences [q-bio] ,Chorionic Gonadotropin ,chemistry.chemical_compound ,0302 clinical medicine ,Phosphorylation ,reproductive and urinary physiology ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,Cadherins ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,Vascular endothelial growth factor ,src-Family Kinases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Cardiology and Cardiovascular Medicine ,Tyrosine kinase ,hormones, hormone substitutes, and hormone antagonists ,Proto-oncogene tyrosine-protein kinase Src ,endocrine system ,medicine.medical_specialty ,Estrous Cycle ,Ovary ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Vascular Remodeling ,Biology ,03 medical and health sciences ,Antigens, CD ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,030304 developmental biology ,Estrous cycle ,urogenital system ,Uterus ,Tyrosine phosphorylation ,Mice, Inbred C57BL ,Endocrinology ,chemistry ,Tyrosine ,Reports - Abstract
We previously reported that vascular endothelial growth factor induced vascular endothelial (VE)-cadherin tyrosine phosphorylation at Y685 in a Src-dependent manner in vitro. Here, we studied the occurrence of Y685 phosphorylation in vivo in the female reproductive tract because it is a unique model of physiological vascular remodeling dependent on vascular endothelial growth factor. We first developed and characterized an anti-phospho-specific antibody against the site Y685 of VE-cadherin to monitor VE-cadherin phosphorylation along the four phases of mouse estrous cycle, termed proestrus, estrus, metestrus, and diestrus. A dynamic profile of tyrosine phosphorylated proteins was observed in both uterus and ovary throughout mouse estrous cycle, including kinase Src, which was found highly active at the estrus phase. The extent of tyrosine phosphorylated VE-cadherin was low at proestrus but strongly increased at estrus and returned to baseline at metestrus and diestrus, suggesting a potent hormonal regulation of this specific process. Indeed, C57Bl/6 female mice treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin confirmed a significant increase in phosphoY685-VE-cadherin compared with that in untreated mice. These results demonstrate that VE-cadherin tyrosine phosphorylation at Y685 is a physiological and hormonally regulated process in female reproductive organs. In addition, this process was concomitant with the early steps of vascular remodeling taking place at estrus stage, suggesting that phosphoY685-VE-cadherin is a biomarker of endothelial cell activation in vivo.
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- 2014
15. [Endothelial junctions: exploiting their instability in the development of biomarkers for vascular remodelling]
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Tiphaine Mannic, Helena Polena, Laurence Bouillet, Isabelle Vilgrain, Barry Stidder, Olivier Vittecoq, Adama Sidibé, Alban Deroux, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Biologie-Informatique-Mathématique (LBIM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Genève (UNIGE), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Biologie, Informatique et Mathématiques, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université de Genève = University of Geneva (UNIGE)
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Synaptic vesicle exocytosis ,Chemistry ,[SDV]Life Sciences [q-bio] ,Lipid bilayer fusion ,Secretion ,General Medicine ,Vacuole ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Molecular biology ,General Biochemistry, Genetics and Molecular Biology ,Exocytosis ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
10. Ammar MR, Kassas N, Chasserot-Golaz S, et al. Lipids in regulated exocytosis: what are they doing? Front Endocrinol (Lausanne) 2013 ; 4 : 125. 4. Peters C, Bayer MJ, Buhler S, et al. Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion. Nature 2001 ; 409 : 581-8. 5. Strasser B, Iwaszkiewicz J, Michielin O, Mayer A. The V-ATPase proteolipid cylinder promotes the lipidmixing stage of SNARE-dependent fusion of yeast vacuoles. EMBO J 2011 ; 30 : 4126-41. 6. Hiesinger PR, Fayyazuddin A, Mehta SQ, et al. The v-ATPase V(0) subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell 2005 ; 121 : 607-20. 7. Liegeois S, Benedetto A, Garnier JM, et al. The V0-ATPase mediates apical secretion of exosomes REFERENCES
- Published
- 2014
16. Exploring the role of circulating VE-cadherin (VE-C) in metastatic colorectal adenocarcinoma (mCA) patients (pts) treated by bevacizumab (Bev)
- Author
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Pierre Guibert, Ellen Blanc, Christelle De La Fouchardiere, Isabelle Vilgrain, Matthieu Sarabi, Françoise Desseigne, Olfa Derbel-Miled, Pascal Artru, Sylvie Chabaud, Nadia Oussaid, Helena Polena, Centre Léon Bérard [Lyon], Délégation à la Recherche Clinique et à l'Innovation [Lyon] (DRCI), UNICANCER - Centre Léon Bérard Lyon (Rhône)-Centre de Lutte Contre le Cancer de Lyon et Rhône-Alpes, IRAMAT-Centre de recherche en physique appliquée à l’archéologie (IRAMAT-CRP2A), Institut de Recherches sur les Archéomatériaux (IRAMAT), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Montaigne-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Montaigne-Université de Technologie de Belfort-Montbeliard (UTBM), Laboratoire de développement et vieillissement de l'endothélium, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Clinique Saint Jean, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon]-UNICANCER - Centre Léon Bérard Lyon (Rhône), and Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)
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Cancer Research ,Pathology ,medicine.medical_specialty ,Bevacizumab ,Endothelium ,business.industry ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Tumor response ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,cardiovascular system ,medicine ,Cancer research ,Colorectal adenocarcinoma ,VE-cadherin ,business ,ComputingMilieux_MISCELLANEOUS ,030215 immunology ,medicine.drug ,Predictive biomarker - Abstract
e14614^ Background: No predictive biomarker of tumor response or resistance to Bev has been identified in mCA. VE-C is an endothelium-specific adhesion molecule of vital importance for endothelium ...
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- 2014
17. Soluble Vascular Endothelial (VE)-Cadherin: Toward a Marker of Endothelial Dysfunction
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Adama Sidibé, Laurence Bouillet, Helena Polena, Isabelle Vilgrain, Tiphaine Mannic, and Barry Stidder
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Endothelium ,Cadherin ,Kinase ,business.industry ,medicine.disease ,Adherens junction ,Endothelial stem cell ,medicine.anatomical_structure ,Cancer research ,medicine ,VE-cadherin ,Endothelial dysfunction ,Signal transduction ,business - Abstract
Endothelial dysfunction is a hallmark for vascular diseases. It is often seen in patients with coronary artery disease, diabetes, hypertension, rheumatoid arthritis, systemic vasculitis, and cancer. Identification of serologic markers that are associated with disease activity to diagnose or predict relapse is a challenging task. At the cellular level, endothelial dysfunction is the result of activation of several signaling pathways due to increased levels of cytokines associated with the disease. Endothelium integrity is dependent upon the adhesive function of the major molecule located at endothelial adherens junctions called vascular endothelial (VE)-cadherin. As in the case of other members of the cadherin family, VE-cadherin is able to mediate homotypic types of endothelial cellular interactions in a Ca2+-dependent manner and to link the underlying cytoskeleton. In conditions mimicking endothelial cell activation, the junctional complexes are subjected to posttranslational modifications such as phosphorylations or proteolysis reactions mediated by kinases and proteases, respectively, which are supposed to weaken the junctional strength. This chapter summarizes recent studies on VE-cadherin structural modifications in endothelial biology having potential applications in disease management and patient care.
- Published
- 2014
18. Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker
- Author
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Tiphaine Mannic, Francine Cand, Laurent Pelletier, Mélanie Arboleas, Jean-Louis Quesada, Jean-Francois LeBas, Christophe Mendoza, Laurence Bouillet, Isabelle Vilgrain, Danielle Gulino-Debrac, François Berger, Sandra Boccard, Adama Sidibé, Helena Polena, and Antoine Baudet
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Endothelium ,lcsh:Medicine ,chemistry.chemical_compound ,Young Adult ,Antigens, CD ,Glioma ,medicine ,Biomarkers, Tumor ,Human Umbilical Vein Endothelial Cells ,Tumor Microenvironment ,Humans ,Phosphorylation ,lcsh:Science ,Aged ,Tumor microenvironment ,Multidisciplinary ,Chemistry ,Cadherin ,Brain Neoplasms ,lcsh:R ,Endothelial Cells ,Tyrosine phosphorylation ,Middle Aged ,medicine.disease ,Cadherins ,medicine.anatomical_structure ,Female ,lcsh:Q ,Endothelium, Vascular ,VE-cadherin ,Proto-oncogene tyrosine-protein kinase Src ,Research Article - Abstract
Vessel abnormalities are among the most important features in malignant glioma. Vascular endothelial (VE)-cadherin is of major importance for vascular integrity. Upon cytokine challenge, VE-cadherin structural modifications have been described including tyrosine phosphorylation and cleavage. The goal of this study was to examine whether these events occurred in human glioma vessels. We demonstrated that VE-cadherin is highly expressed in human glioma tissue and tyrosine phosphorylated at site Y(685), a site previously found phosphorylated upon VEGF challenge, via Src activation. In vitro experiments showed that VEGF-induced VE-cadherin phosphorylation, preceded the cleavage of its extracellular adhesive domain (sVE, 90 kDa). Interestingly, metalloproteases (MMPs) secreted by glioma cell lines were responsible for sVE release. Because VEGF and MMPs are important components of tumor microenvironment, we hypothesized that VE-cadherin proteolysis might occur in human brain tumors. Analysis of glioma patient sera prior treatment confirmed the presence of sVE in bloodstream. Furthermore, sVE levels studied in a cohort of 53 glioma patients were significantly predictive of the overall survival at three years (HR 0.13 [0.04; 0.40] p ≤ 0.001), irrespective to histopathological grade of tumors. Altogether, these results suggest that VE-cadherin structural modifications should be examined as candidate biomarkers of tumor vessel abnormalities, with promising applications in oncology.
- Published
- 2013
19. AB0248 Clinical Significance of Soluble Vascular Endothelial-Cadherin and Anti-Vascular Endothelial-Cadherin Antibody in Rheumatoid Arthritis Treated with Etanercept or Adalimumab
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P. Fardellone, Barry Stidder, Isabelle Vilgrain, E. Houivet, Helena Polena, Christian Marcelli, Thierry Lequerré, Peggy Philippe, A. Khallil-Mgharbel, Olivier Vittecoq, X. Le Loët, and C. Banse
- Subjects
medicine.medical_specialty ,Systemic disease ,medicine.diagnostic_test ,business.industry ,Immunology ,Autoantibody ,medicine.disease ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Etanercept ,Rheumatology ,Internal medicine ,Erythrocyte sedimentation rate ,Rheumatoid arthritis ,medicine ,Adalimumab ,Immunology and Allergy ,Biomarker (medicine) ,Methotrexate ,business ,medicine.drug - Abstract
Background The extra cellular domain of vascular endothelial-cadherin (sVE) increases in rheumatoid arthritis (RA) through TNF induction. Objectives The aim of our study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibody (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate, in terms of disease activity, prediction of structural prognosis and response to treatment. Methods This was an 18-month prospective multicenter study in which patients had active RA, refractory to conventional Disease-Modifying Antirheumatic Drug (DMARD) requiring TNF antagonist. Fluctuations of sVE rates and AAVE titers were measured respectively by dot blot and ELISA at different time points over the follow-up period. Their relationship with parameters reflecting articular or systemic disease activity, progression of structural damage defined by ultrasonography (US) erosions, and response or remission to treatment based on EULAR criteria was analyzed. Results Forty-eight patients received TNF blocking agents, i.e, etanercept (n=18) and adalimumab (n=30). Variation of sVE rates significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52 (r=0.4869, p=0.0008; r=0.3909, p=0.0087; r=0.3148, p=0.0450 and r=0.5477, p=0.0014 respectively). There was a significant decrease in sVE levels in the group with a decrease in CRP levels compared to the group with unmodified CRP (initial CRP ≤10 mg/l or initial CRP>10 mg/l with a variation of less than 50%). AAVE titers correlated with Erythrocyte Sedimentation Rate (ESR) (r=0.381, p=0.0128), CRP (r=-0.3361, p=0.0317), number of swollen joints (r=0.3102, p=0.0456) and total power doppler score (r=0.3841, p=0.0132). At baseline, AAVE was correlated with rheumatoid factors and a to lesser degree anti-CCP (respectively r=0.5801, p Conclusions sVE seems to be a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA and had stable titers under TNF blocking agents. Disclosure of Interest None declared
- Published
- 2015
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