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1.
Public Health Genomics ; 14(2): 96-103, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20395653

RESUMEN

Biobanks have recently gained great significance for research and personalised medicine, being recognised as a crucial infrastructure. At the same time, the widely varied practices in biobanking may also pose a barrier to cross-border research and collaboration by limiting access to samples and data. Nevertheless, the extent of the actual activities and the impact of the level of networking and harmonisation have not been fully assessed. To address these issues and to obtain missing knowledge on the extent of biobanking in Europe, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre, in collaboration with the European Science and Technology Observatory (ESTO), conducted a survey among European biobanks. In total, 126 biobanks from 23 countries responded to the survey. Most of them are small or medium-sized public collections set up either for population-based or disease-specific research purposes. The survey indicated a limited networking among the infrastructures. The large majority of them are stand-alone collections and only about half indicated to have a policy for cross-border sharing of samples. Yet, scientific collaborations based on the use of each biobank appear to be prominent. Significant variability was found in terms of consent requirements and related procedures as well as for privacy and data protection issues among the biobanks surveyed. To help promote networking of biobanks and thus maximise public health benefits, at least some degree of harmonisation should be achieved.


Asunto(s)
Bancos de Muestras Biológicas/organización & administración , Europa (Continente) , Unión Europea , Humanos , Cooperación Internacional , Medicina de Precisión , Salud Pública , Manejo de Especímenes , Encuestas y Cuestionarios
2.
Public Health Genomics ; 12(3): 134-41, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19204415

RESUMEN

This paper reviews the current situation in the field of pharmacogenetics/pharmacogenomics (PGx) in Europe. High expectations surrounding the clinical application of PGx remain largely unmet, as only a limited number of such applications have actually reached the market and clinical practice. Thus, the potential impact of PGx-based diagnostics on healthcare and its socio-economic implications are still unclear. With the aim of shedding some light on these uncertainties, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre (JRC) has conducted a review of the 'state of the art' and a further analysis on the use of pharmacogenetics diagnostics for preventing toxic drug reactions and improving drug efficacy in Europe. The paper presents highlights from the JRC-IPTS studies and discusses possibilities for improving translation of PGx research in Europe by comparing some experiences in the USA. We also illustrate the related barriers for the clinical uptake of PGx in Europe with specific case-studies. Most of the barriers identified extend beyond the European context. This reflects the global problems of scarcity of data demonstrating proven clinical validity or utility and favorable cost-effectiveness studies to support the clinical application of PGx diagnostic tests in the clinical setting. Another key barrier is the lack of incentives for the private sector to invest in the development and licensing of PGx diagnostic tests for improving the safety and efficacy of out-of-patent drugs. It therefore seems that one key aspect where policy can affect the clinical uptake of PGx is via sustaining large-scale industry-academia collaborations for developing and proving the utility of PGx diagnostics.


Asunto(s)
Farmacogenética/tendencias , Drogas en Investigación , Europa (Continente) , Regulación Gubernamental , Humanos , Proyectos de Investigación
3.
J Biol Chem ; 276(42): 38715-20, 2001 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-11514574

RESUMEN

The class II transactivator (CIITA) is a transcriptional co-activator regulating the constitutive and interferon-gamma-inducible expression of class II major histocompatibility complex (MHC) and related genes. Promoter remodeling occurs following CIITA induction, suggesting the involvement of chromatin remodeling factors. Transcription of numerous genes requires the histone acetyltransferase (HAT) activities of CREB-binding protein (CBP), p300, and/or p300/CBP-associated factor (pCAF). These co-activators cooperate with CIITA and are hypothesized to promote class II major histocompatibility complex transcription through their HAT activity. To directly test this, we used HAT-defective CBP and pCAF. We demonstrate that cooperation between CIITA and CBP is independent of CBP HAT activity. Further, although pCAF enhances CIITA-mediated transcription, pCAF HAT domain dependence appears contingent upon the concentration of available CIITA. When HAT-defective CBP and pCAF are both present, cooperativity with CIITA is maintained. Consistent with a recent report, we show that nuclear localization of CIITA is enhanced by lysine 144, an in vitro target of pCAF-mediated HAT. Yet we find that neither mutation of lysine 144 nor deletion of residues 132-209 affects transcriptional cooperation with CBP or pCAF. Thus, acetylation of this residue may not be the primary mechanism for pCAF/CBP cooperation with CIITA. In conclusion, the HAT activities of the co-activators are not necessary for cooperation with CIITA.


Asunto(s)
Acetiltransferasas/química , Proteínas Nucleares/química , Proteínas de Saccharomyces cerevisiae , Transactivadores/química , Transcripción Genética , Activación Transcripcional , Secuencia de Aminoácidos , Animales , Células COS , Proteína de Unión a CREB , Línea Celular , Núcleo Celular/metabolismo , Relación Dosis-Respuesta a Droga , Eliminación de Gen , Histona Acetiltransferasas , Lisina/química , Microscopía Fluorescente , Datos de Secuencia Molecular , Mutación , Plásmidos/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Transfección
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