27 results on '"Bietrix F"'
Search Results
2. Bridging the translational innovation gap through good biomarker practice
- Author
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Gool, A.J. van, Bietrix, F., Caldenhoven, E., Zatloukal, K., Scherer, A., Litton, J.E., Meijer, G., Blomberg, N., Smith, A., Mons, B., Heringa, J., Koot, W.J., Smit, M.J., Hajduch, M., Rijnders, T., Ussi, A., Gool, A.J. van, Bietrix, F., Caldenhoven, E., Zatloukal, K., Scherer, A., Litton, J.E., Meijer, G., Blomberg, N., Smith, A., Mons, B., Heringa, J., Koot, W.J., Smit, M.J., Hajduch, M., Rijnders, T., and Ussi, A.
- Abstract
Item does not contain fulltext
- Published
- 2017
3. Glycosphingolipids and insulin resistance
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Aerts, J. M., Boot, R. G., van Eijk, M., Groener, J., Bijl, N., Lombardo, E., Bietrix, F. M., Dekker, N. [=Nick], Groen, A. K., Ottenhoff, R., van Roomen, C., Aten, J., Serlie, M., Langeveld, M., Wennekes, T., Overkleeft, H. S., Cowart, A., Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, Amsterdam institute for Infection and Immunity, Other departments, Vascular Medicine, Pathology, and Endocrinology
- Published
- 2010
4. Etude de l’absorption intestinale de lipides dans un modèle murin surexprimant au niveau intestinal le Scavenger Receptor Class B type I : SR-BI
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Bietrix, F, Yan, D, Nauze, M, Rolland, C, Schaak, S, Martin, Pascal G.P., Pineau, Thierry, Barbaras, R, Perret, B, Tercet, F, Collet, Xavier, Inconnu, Unité de recherche Pharmacologie-Toxicologie (UPT), Institut National de la Recherche Agronomique (INRA), Département Santé Animale (DEPT SA), and ProdInra, Migration
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2004
5. Abstract: P158 INHIBITION OF GLYCOSPHINGOLIPID SYNTHESIS STRONGLY REDUCES ATHEROSCLEROSIS DEVELOPMENT IN APOE*3 LEIDEN MICE
- Author
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Bietrix, F, primary, Lombardo, E, additional, van Roomen, C, additional, Ottenhoff, R, additional, Groen, A, additional, and Aerts, J, additional
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- 2009
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6. Mo-W11:6 Accelerated lipid absorption in mice overexpressing intestinal SR-BI
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Bietrix, F., primary, Daogang, Y., additional, Nauze, M., additional, Rolland, C., additional, Coméra, C., additional, Barbaras, R., additional, Groen, A.K., additional, Perret, B., additional, Tercé, F., additional, and Collet, X., additional
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- 2006
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7. Étude de l’absorption intestinale du cholestérol sur des souris surexprimant SR-BI au niveau intestinal
- Author
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Bietrix, F., primary, Daogang, Y., additional, Ferrand, C., additional, Rolland, C., additional, Nauze, M., additional, Barbaras, R., additional, Tercé, F., additional, Perret, B., additional, and Collet, X., additional
- Published
- 2004
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8. Enhancement of ultrasound images by multiscale analysis.
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Bietrix, F., Lovstrom, B., and Salomonsson, G.
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- 1992
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9. Glycosphingolipids and atherosclerosis
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Lombardo, Elisa, Aerts, Johannes M.F.G., Groen, A.K., Bietrix, F.M.D.F., Faculteit der Geneeskunde, Aerts, Johannes M. F. G., Groen, Bert K., Bietrix, F. M. D. F., and Medical Biochemistry
- Published
- 2013
10. Recommendations for robust and reproducible preclinical research in personalised medicine.
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Fosse V, Oldoni E, Bietrix F, Budillon A, Daskalopoulos EP, Fratelli M, Gerlach B, Groenen PMA, Hölter SM, Menon JML, Mobasheri A, Osborne N, Ritskes-Hoitinga M, Ryll B, Schmitt E, Ussi A, Andreu AL, and McCormack E
- Subjects
- Humans, Precision Medicine
- Abstract
Background: Personalised medicine is a medical model that aims to provide tailor-made prevention and treatment strategies for defined groups of individuals. The concept brings new challenges to the translational step, both in clinical relevance and validity of models. We have developed a set of recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine., Methods: These recommendations have been developed following four main steps: (1) a scoping review of the literature with a gap analysis, (2) working sessions with a wide range of experts in the field, (3) a consensus workshop, and (4) preparation of the final set of recommendations., Results: Despite the progress in developing innovative and complex preclinical model systems, to date there are fundamental deficits in translational methods that prevent the further development of personalised medicine. The literature review highlighted five main gaps, relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. We identified five points of focus for the recommendations, based on the consensus reached during the consultation meetings: (1) clinically relevant translational research, (2) robust model development, (3) transparency and education, (4) revised regulation, and (5) interaction with clinical research and patient engagement. Here, we present a set of 15 recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine., Conclusions: Appropriate preclinical models should be an integral contributor to interventional clinical trial success rates, and predictive translational models are a fundamental requirement to realise the dream of personalised medicine. The implementation of these guidelines is ambitious, and it is only through the active involvement of all relevant stakeholders in this field that we will be able to make an impact and effectuate a change which will facilitate improved translation of personalised medicine in the future., (© 2023. The Author(s).)
- Published
- 2023
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11. An iterative and interdisciplinary categorisation process towards FAIRer digital resources for sensitive life-sciences data.
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David R, Ohmann C, Boiten JW, Abadía MC, Bietrix F, Canham S, Chiusano ML, Dastrù W, Laroquette A, Longo D, Mayrhofer MT, Panagiotopoulou M, Richard AS, Goryanin S, and Verde PE
- Subjects
- Pilot Projects, Software, Biological Science Disciplines
- Abstract
For life science infrastructures, sensitive data generate an additional layer of complexity. Cross-domain categorisation and discovery of digital resources related to sensitive data presents major interoperability challenges. To support this FAIRification process, a toolbox demonstrator aiming at support for discovery of digital objects related to sensitive data (e.g., regulations, guidelines, best practice, tools) has been developed. The toolbox is based upon a categorisation system developed and harmonised across a cluster of 6 life science research infrastructures. Three different versions were built, tested by subsequent pilot studies, finally leading to a system with 7 main categories (sensitive data type, resource type, research field, data type, stage in data sharing life cycle, geographical scope, specific topics). 109 resources attached with the tags in pilot study 3 were used as the initial content for the toolbox demonstrator, a software tool allowing searching of digital objects linked to sensitive data with filtering based upon the categorisation system. Important next steps are a broad evaluation of the usability and user-friendliness of the toolbox, extension to more resources, broader adoption by different life-science communities, and a long-term vision for maintenance and sustainability., (© 2022. The Author(s).)
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- 2022
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12. Tackling the translational challenges of multi-omics research in the realm of European personalised medicine: A workshop report.
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Oldoni E, Saunders G, Bietrix F, Garcia Bermejo ML, Niehues A, 't Hoen PAC, Nordlund J, Hajduch M, Scherer A, Kivinen K, Pitkänen E, Mäkela TP, Gut I, Scollen S, Kozera Ł, Esteller M, Shi L, Ussi A, Andreu AL, and van Gool AJ
- Abstract
Personalised medicine (PM) presents a great opportunity to improve the future of individualised healthcare. Recent advances in -omics technologies have led to unprecedented efforts characterising the biology and molecular mechanisms that underlie the development and progression of a wide array of complex human diseases, supporting further development of PM. This article reflects the outcome of the 2021 EATRIS-Plus Multi-omics Stakeholder Group workshop organised to 1) outline a global overview of common promises and challenges that key European stakeholders are facing in the field of multi-omics research, 2) assess the potential of new technologies, such as artificial intelligence (AI), and 3) establish an initial dialogue between key initiatives in this space. Our focus is on the alignment of agendas of European initiatives in multi-omics research and the centrality of patients in designing solutions that have the potential to advance PM in long-term healthcare strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oldoni, Saunders, Bietrix, Garcia Bermejo, Niehues, ’t Hoen, Nordlund, Hajduch, Scherer, Kivinen, Pitkänen, Mäkela, Gut, Scollen, Kozera, Esteller, Shi, Ussi, Andreu and van Gool.)
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- 2022
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13. Evaluating Translational Methods for Personalized Medicine-A Scoping Review.
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Fosse V, Oldoni E, Gerardi C, Banzi R, Fratelli M, Bietrix F, Ussi A, Andreu AL, McCormack E, and The Permit Group
- Abstract
The introduction of personalized medicine, through the increasing multi-omics characterization of disease, brings new challenges to disease modeling. The scope of this review was a broad evaluation of the relevance, validity, and predictive value of the current preclinical methodologies applied in stratified medicine approaches. Two case models were chosen: oncology and brain disorders. We conducted a scoping review, following the Joanna Briggs Institute guidelines, and searched PubMed, EMBASE, and relevant databases for reports describing preclinical models applied in personalized medicine approaches. A total of 1292 and 1516 records were identified from the oncology and brain disorders search, respectively. Quantitative and qualitative synthesis was performed on a final total of 63 oncology and 94 brain disorder studies. The complexity of personalized approaches highlights the need for more sophisticated biological systems to assess the integrated mechanisms of response. Despite the progress in developing innovative and complex preclinical model systems, the currently available methods need to be further developed and validated before their potential in personalized medicine endeavors can be realized. More importantly, we identified underlying gaps in preclinical research relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. To achieve a broad implementation of predictive translational models in personalized medicine, these fundamental deficits must be addressed.
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- 2022
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14. A call to action for translational sciences in COVID-19 and future pandemics.
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Wan KK, Davis D, Lee TN, Ford-Scheimer SL, Andreu AL, Bietrix F, Bryans J, Castro MT, Chiba N, Faupel-Badger JM, Haynes B, Hirasawa R, Morel CM, Souza TML, Morrow D, Munro T, Newman S, Ussi AE, Zorzal PB, Hall MD, Lo DC, and Cutillo CM
- Subjects
- Communication Barriers, Drug Development, Forecasting, Global Health standards, Global Health trends, Humans, International Cooperation, Public Health, SARS-CoV-2, COVID-19 epidemiology, COVID-19 prevention & control, Civil Defense organization & administration, Civil Defense trends, Communicable Disease Control methods, Communicable Disease Control organization & administration, Communicable Disease Control trends, Translational Research, Biomedical methods, Translational Research, Biomedical standards, Translational Research, Biomedical trends
- Published
- 2022
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15. Minimal information for chemosensitivity assays (MICHA): a next-generation pipeline to enable the FAIRification of drug screening experiments.
- Author
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Tanoli Z, Aldahdooh J, Alam F, Wang Y, Seemab U, Fratelli M, Pavlis P, Hajduch M, Bietrix F, Gribbon P, Zaliani A, Hall MD, Shen M, Brimacombe K, Kulesskiy E, Saarela J, Wennerberg K, Vähä-Koskela M, and Tang J
- Abstract
Chemosensitivity assays are commonly used for preclinical drug discovery and clinical trial optimization. However, data from independent assays are often discordant, largely attributed to uncharacterized variation in the experimental materials and protocols. We report here the launching of Minimal Information for Chemosensitivity Assays (MICHA), accessed via https://micha-protocol.org. Distinguished from existing efforts that are often lacking support from data integration tools, MICHA can automatically extract publicly available information to facilitate the assay annotation including: 1) compounds, 2) samples, 3) reagents and 4) data processing methods. For example, MICHA provides an integrative web server and database to obtain compound annotation including chemical structures, targets and disease indications. In addition, the annotation of cell line samples, assay protocols and literature references can be greatly eased by retrieving manually curated catalogues. Once the annotation is complete, MICHA can export a report that conforms to the FAIR principle (Findable, Accessible, Interoperable and Reusable) of drug screening studies. To consolidate the utility of MICHA, we provide FAIRified protocols from five major cancer drug screening studies as well as six recently conducted COVID-19 studies. With the MICHA web server and database, we envisage a wider adoption of a community-driven effort to improve the open access of drug sensitivity assays., (© The Author(s) 2021. Published by Oxford University Press.)
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- 2022
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16. Minimal information for Chemosensitivity assays (MICHA): A next-generation pipeline to enable the FAIRification of drug screening experiments.
- Author
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Tanoli Z, Aldahdooh J, Alam F, Wang Y, Seemab U, Fratelli M, Pavlis P, Hajduch M, Bietrix F, Gribbon P, Zaliani A, Hall MD, Shen M, Brimacombe K, Kulesskiy E, Saarela J, Wennerberg K, Vähä-Koskela M, and Tang J
- Abstract
Chemosensitivity assays are commonly used for preclinical drug discovery and clinical trial optimization. However, data from independent assays are often discordant, largely attributed to uncharacterized variation in the experimental materials and protocols. We report here the launching of MICHA (Minimal Information for Chemosensitivity Assays), accessed via https://micha-protocol.org. Distinguished from existing efforts that are often lacking support from data integration tools, MICHA can automatically extract publicly available information to facilitate the assay annotation including: 1) compounds, 2) samples, 3) reagents, and 4) data processing methods. For example, MICHA provides an integrative web server and database to obtain compound annotation including chemical structures, targets, and disease indications. In addition, the annotation of cell line samples, assay protocols and literature references can be greatly eased by retrieving manually curated catalogues. Once the annotation is complete, MICHA can export a report that conforms to the FAIR principle (Findable, Accessible, Interoperable and Reusable) of drug screening studies. To consolidate the utility of MICHA, we provide FAIRified protocols from five major cancer drug screening studies, as well as six recently conducted COVID-19 studies. With the MICHA webserver and database, we envisage a wider adoption of a community-driven effort to improve the open access of drug sensitivity assays.
- Published
- 2021
- Full Text
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17. Biomarker Research and Development for Coronavirus Disease 2019 (COVID-19): European Medical Research Infrastructures Call for Global Coordination.
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Oldoni E, van Gool A, García Bermejo L, Scherer A, Mayrhofer MT, Florindi F, Demotes J, Kubiak C, Fauvel AC, Bietrix F, Ussi A, and Andreu AL
- Subjects
- Biological Specimen Banks, Biomarkers, COVID-19 Testing, Humans, Pandemics, SARS-CoV-2, Biomedical Research, COVID-19
- Abstract
An effective response to the coronavirus disease 2019 (COVID-19) pandemic requires a better understanding of the biology of the infection and the identification of validated biomarker profiles that would increase the availability, accuracy, and speed of COVID-19 testing. Here, we describe the strategic objectives and action lines of the European Alliance of Medical Research Infrastructures (AMRI), established to improve the research process and tackle challenges related to diagnostic tests and biomarker development. Recommendations include: the creation of a European taskforce for validation of novel diagnostic products, the definition and promotion of criteria for COVID-19 samples biobanking, the identification and validation of biomarkers as clinical endpoints for clinical trials, and the definition of immune biomarker signatures at different stages of the disease. An effective management of the COVID-19 pandemic is possible only if there is a high level of knowledge and coordination between the public and private sectors within a robust quality framework., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
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18. The Fundamental Characteristics of a Translational Scientist.
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Gilliland CT, White J, Gee B, Kreeftmeijer-Vegter R, Bietrix F, Ussi AE, Hajduch M, Kocis P, Chiba N, Hirasawa R, Suematsu M, Bryans J, Newman S, Hall MD, and Austin CP
- Abstract
Translational science is defined as the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Further development of the field is advanced by describing the key desirable characteristics of individuals who seek to uncover these principles to increase the efficiency and efficacy of translation. The members of Translation Together, a newly launched international collaborative effort to advance translational innovation, present here a consensus representation of the fundamental characteristics of a translational scientist. We invite all stakeholders to contribute in the ongoing efforts to develop the field and educate the next generation of translational scientists., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)
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- 2019
- Full Text
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19. Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE): A vision for the vaccines of tomorrow.
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Medaglini D, De Azero MR, Leroy O, Bietrix F, and Denoel P
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- Biomedical Research economics, Europe, Humans, International Cooperation, Investments, Biomedical Research organization & administration, Vaccines
- Abstract
A clear vision for vaccines research and development (R&D) is needed if Europe is to continue to lead the discovery of next generation vaccines. Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE) is a collaboration between leading vaccine experts to develop a roadmap setting out how Europe can best invest in the science and technology essential for vaccines innovation. This FP7 project, started in December 2013, brought together more than 130 key public and private stakeholders from academia, public health institutes, regulators, industry and small and medium-sized enterprises to determine and prioritise the gaps and challenges to be addressed to bolster innovation in vaccines and vaccination in Europe. The IPROVE consultation process was structured around seven themes: vaccine R&D, manufacturing and quality control, infrastructure, therapeutic vaccines, needs of small and medium-sized enterprises, vaccines acceptance and training needs. More than 80 recommendations were made by the consultation groups, mainly focused on the need for a multidisciplinary research approach to stimulate innovation, accelerated translation of scientific knowledge into technological innovation, and fostering of real collaboration within the European vaccine ecosystem. The consultation also reinforced the fact that vaccines are only as good as their vaccine implementation programmes, and that more must be done to understand and address vaccination hesitancy of both the general public and healthcare professionals. Bringing together a wide range of stakeholders to work on the IPROVE roadmap has increased mutual understanding of their different perspectives, needs and priorities. IPROVE is a first attempt to develop such a comprehensive view of the vaccine sector. This prioritisation effort, aims to help policy-makers and funders identify those vaccine-related areas and technologies where key investment is needed for short and medium-long term success., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2018
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20. Bridging the translational innovation gap through good biomarker practice.
- Author
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van Gool AJ, Bietrix F, Caldenhoven E, Zatloukal K, Scherer A, Litton JE, Meijer G, Blomberg N, Smith A, Mons B, Heringa J, Koot WJ, Smit MJ, Hajduch M, Rijnders T, and Ussi A
- Subjects
- Humans, Molecular Targeted Therapy methods, Molecular Targeted Therapy trends, Translational Research, Biomedical, Biomarkers, Drug Discovery methods, Drug Discovery trends, Inventions
- Published
- 2017
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21. Assessing opportunities for coordinated R&D in early cancer detection and management in Europe.
- Author
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Ussi AE, Rebolj M, Thorat MA, Bietrix F, Fauvel AC, Hajdúch M, Hill C, Walker I, van Engeland M, Cuzick J, and Meijer G
- Subjects
- Europe epidemiology, Humans, Neoplasms epidemiology, Early Detection of Cancer, Neoplasms diagnosis, Research
- Published
- 2017
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22. Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015.
- Author
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Williams DJ, Archer R, Archibald P, Bantounas I, Baptista R, Barker R, Barry J, Bietrix F, Blair N, Braybrook J, Campbell J, Canham M, Chandra A, Foldes G, Gilmanshin R, Girard M, Gorjup E, Hewitt Z, Hourd P, Hyllner J, Jesson H, Kee J, Kerby J, Kotsopoulou N, Kowalski S, Leidel C, Marshall D, Masi L, McCall M, McCann C, Medcalf N, Moore H, Ozawa H, Pan D, Parmar M, Plant AL, Reinwald Y, Sebastian S, Stacey G, Thomas RJ, Thomas D, Thurman-Newell J, Turner M, Vitillo L, Wall I, Wilson A, Wolfrum J, Yang Y, and Zimmerman H
- Subjects
- Biotechnology methods, Biotechnology trends, Humans, Manufacturing and Industrial Facilities, United Kingdom, Pluripotent Stem Cells transplantation, Regenerative Medicine legislation & jurisprudence, Regenerative Medicine methods, Regenerative Medicine trends
- Abstract
This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates.
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- 2016
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23. Putting translational science on to a global stage.
- Author
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Gilliland CT, Zuk D, Kocis P, Johnson M, Hay S, Hajduch M, Bietrix F, Aversa G, Austin CP, and Ussi AE
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- Biomedical Research organization & administration, Global Health trends, Humans, Organizational Innovation, International Cooperation, Inventions, Technology Transfer, Therapies, Investigational, Translational Research, Biomedical organization & administration, Translational Research, Biomedical trends
- Abstract
Global collaboration in translational science promises to accelerate the discovery, development and dissemination of new medical interventions. Here, we introduce a new international collaboration of translational science organizations and highlight our initial strategy to reduce or remove bottlenecks in translation.
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- 2016
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24. Correction of liver steatosis by a hydrophobic iminosugar modulating glycosphingolipids metabolism.
- Author
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Lombardo E, van Roomen CP, van Puijvelde GH, Ottenhoff R, van Eijk M, Aten J, Kuiper J, Overkleeft HS, Groen AK, Verhoeven AJ, Aerts JM, and Bietrix F
- Subjects
- 1-Deoxynojirimycin analogs & derivatives, 1-Deoxynojirimycin chemistry, 1-Deoxynojirimycin pharmacology, Actins genetics, Actins metabolism, Adamantane analogs & derivatives, Adamantane chemistry, Adamantane pharmacology, Animals, Apolipoprotein E3 genetics, Apolipoprotein E3 metabolism, Cell Membrane chemistry, Cell Membrane drug effects, Cell Membrane metabolism, Diet, High-Fat adverse effects, Dose-Response Relationship, Drug, Fatty Acids metabolism, Fatty Liver etiology, Fatty Liver genetics, Female, Gene Expression drug effects, Glycosphingolipids metabolism, Humans, Hydrophobic and Hydrophilic Interactions, Imino Sugars chemistry, Immunohistochemistry, Insulin blood, Lipid Metabolism drug effects, Liver metabolism, Liver pathology, Mice, Mice, Knockout, Mice, Transgenic, Muscle, Smooth chemistry, Oxidation-Reduction drug effects, Receptors, LDL deficiency, Receptors, LDL genetics, Fatty Liver prevention & control, Glycosphingolipids antagonists & inhibitors, Imino Sugars pharmacology, Liver drug effects
- Abstract
The iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynoijirimycin (AMP-DNM), an inhibitor of glycosphingolipid (GSL) biosynthesis is known to ameliorate diabetes, insulin sensitivity and to prevent liver steatosis in ob/ob mice. Thus far the effect of GSL synthesis inhibition on pre-existing NASH has not yet been assessed. To investigate it, LDLR(-/-) mice were kept on a western-type diet for 12 weeks to induce NASH. Next, the diet was continued for 6 weeks in presence or not of AMP-DNM in the diet. AMP-DNM treated mice showed less liver steatosis, inflammation and fibrosis. Induction of fatty acid beta-oxydation was observed, as well as a reduction of plasma lipids. Our study demonstrates that AMP-DNM treatment is able to significantly correct pre-existing NASH, suggesting that inhibiting GSL synthesis may represent a novel strategy for the treatment of this pathology.
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- 2012
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25. Inhibition of glycosphingolipid synthesis induces a profound reduction of plasma cholesterol and inhibits atherosclerosis development in APOE*3 Leiden and low-density lipoprotein receptor-/- mice.
- Author
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Bietrix F, Lombardo E, van Roomen CP, Ottenhoff R, Vos M, Rensen PC, Verhoeven AJ, Aerts JM, and Groen AK
- Subjects
- 1-Deoxynojirimycin pharmacology, Adamantane pharmacology, Animals, Atherosclerosis genetics, Atherosclerosis metabolism, Bile metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Down-Regulation, Feces chemistry, Female, Glucosyltransferases metabolism, Hyperlipidemias genetics, Hyperlipidemias metabolism, Hyperlipidemias prevention & control, Kinetics, Liver drug effects, Liver metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Mutation, Receptors, LDL genetics, 1-Deoxynojirimycin analogs & derivatives, Adamantane analogs & derivatives, Apolipoproteins E genetics, Atherosclerosis prevention & control, Cholesterol blood, Enzyme Inhibitors pharmacology, Glucosyltransferases antagonists & inhibitors, Glycosphingolipids biosynthesis, Receptors, LDL deficiency
- Abstract
Objective: The iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynoijirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase catalyzing glycosphingolipid (GSL) biosynthesis, ameliorates diabetes and reduces liver steatosis in ob/ob mice. Because an accumulation of sphingolipids, including sphingomyelin and GSLs, has been reported in atherosclerotic lesions in animal models and in humans, the objective of this study was to determine whether AMP-DNM also exerts beneficial effects on the development of atherosclerosis., Methods and Results: APOE*3 Leiden mice, maintained on a high-cholesterol diet, were treated for up to 18 weeks with AMP-DNM. The iminosugar prevented hyperlipidemia, generated a less atherogenic lipid profile, and induced a dramatic reduction in the development of atherosclerotic lesions. At the highest dose, no lesions were detectable. The effect of AMP-DNM was associated with a decrease in liver cholesterol, an increase in bile secretion, and enhanced excretion of cholesterol in the feces. Similar effects of AMP-DNM were observed in mice deficient for the low-density lipoprotein receptor., Conclusion: By lowering plasma cholesterol, the iminosugar AMP-DNM dramatically reduces the development of atherosclerosis in APOE*3 Leiden and low-density lipoprotein receptor -/- mice. Thus, targeting GSL synthesis may be a new treatment modality to prevent cardiovascular disease.
- Published
- 2010
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26. Accelerated lipid absorption in mice overexpressing intestinal SR-BI.
- Author
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Bietrix F, Yan D, Nauze M, Rolland C, Bertrand-Michel J, Coméra C, Schaak S, Barbaras R, Groen AK, Perret B, Tercé F, and Collet X
- Subjects
- Absorption, Animals, Apolipoproteins chemistry, Bile Acids and Salts metabolism, Cell Membrane metabolism, Cholesterol chemistry, Cholesterol metabolism, Chylomicrons chemistry, DNA, Complementary metabolism, Homeostasis, Immunohistochemistry, Intestines chemistry, Lipoproteins chemistry, Liver metabolism, Mice, Mice, Transgenic, Promoter Regions, Genetic, Receptors, Lipoprotein metabolism, Receptors, Scavenger chemistry, Tissue Distribution, Triglycerides metabolism, Triolein chemistry, Intestinal Mucosa metabolism, Lipids chemistry, Scavenger Receptors, Class B metabolism
- Abstract
Dietary cholesterol absorption contributes to a large part of the circulating cholesterol. However, the mechanism of sterol intestinal uptake is not clearly elucidated. Scavenger receptor class B type I (SR-BI), major component in the control of cholesterol homeostasis, is expressed in the intestine, but its role in this organ remains unclear. We have generated transgenic mice overexpressing SR-BI primarily in the intestine by using the mouse SR-BI gene under the control of intestinal specific "apoC-III enhancer coupled with apoA-IV promoter." We found SR-BI overexpression with respect to the natural protein along the intestine and at the top of the villosities. After a meal containing [(14)C]cholesterol and [(3)H]triolein, SR-BI transgenic mice presented a rise in intestinal absorption of both lipids that was not due to a defect in chylomicron clearance nor to a change in the bile flow or the bile acid content. Nevertheless, SR-BI transgenic mice showed a decrease of total cholesterol but an increase of triglyceride content in plasma without any change in the high density lipoprotein apoA-I level. Thus, we described for the first time a functional role in vivo for SR-BI in cholesterol but also in triglyceride intestinal absorption.
- Published
- 2006
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27. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte.
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Reboul E, Klein A, Bietrix F, Gleize B, Malezet-Desmoulins C, Schneider M, Margotat A, Lagrost L, Collet X, and Borel P
- Subjects
- Absorption, Animals, Binding, Competitive, Biological Transport, CD36 Antigens metabolism, Caco-2 Cells, Cell Differentiation, Cholesterol metabolism, Dose-Response Relationship, Drug, Epithelial Cells metabolism, Humans, Intestinal Mucosa metabolism, Lipids chemistry, Mice, Mice, Transgenic, Micelles, RNA, Messenger metabolism, Temperature, Time Factors, Tocopherols metabolism, alpha-Tocopherol metabolism, gamma-Tocopherol metabolism, CD36 Antigens physiology, Enterocytes metabolism, Vitamin E metabolism
- Abstract
Although cellular uptake of vitamin E was initially described as a passive process, recent studies in the liver and brain have shown that SR-BI (scavenger receptor class B type I) is involved in this phenomenon. As SR-BI is expressed at high levels in the intestine, the present study addressed the involvement of SR-BI in vitamin E trafficking across enterocytes. Apical uptake and efflux of the main dietary forms of vitamin E were examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium. (R,R,R)-gamma-tocopherol bioavailability was compared between wild-type mice and mice overexpressing SR-BI in the intestine. The effect of vitamin E on enterocyte SR-BI mRNA levels was measured by real-time quantitative reverse transcription-PCR. Concentration-dependent curves for vitamin E uptake were similar for (R,R,R)-alpha-, (R,R,R)-gamma-, and dl-alpha-tocopherol. (R,R,R)-alpha-tocopherol transport was dependent on incubation temperature, with a 60% reduction in absorption at 4 degrees C compared with 37 degrees C (p < 0.05). Vitamin E flux in enterocytes was directed from the apical to the basal side, with a relative 10-fold reduction in the transfer process when measured in the opposite direction (p < 0.05). Co-incubation with cholesterol, gamma-tocopherol, or lutein significantly impaired alpha-tocopherol absorption. Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 80% of vitamin E uptake and up to 30% of apical vitamin E efflux (p < 0.05), and similar results were obtained for (R,R,R)-gamma-tocopherol. SR-BI mRNA levels were not significantly modified after a 24-h incubation of Caco-2 cells with vitamin E. Finally, (R,R,R)-gamma-tocopherol bioavailability was 2.7-fold higher in mice overexpressing SR-BI than in wild-type mice (p < 0.05). The present data show for the first time that vitamin E intestinal absorption is, at least in part, mediated by SR-BI.
- Published
- 2006
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