Center for Biologics Evaluation and Research

About: Center for Biologics Evaluation and Research is a facility organization based out in Silver Spring, Maryland, United States. It is known for research contribution in the topics: Virus & Vaccination. The organization has 3024 authors who have published 4648 publications receiving 228078 citations. The organization is also known as: CBER.

Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival.

Abstract: Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains ∼60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children9s Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) IV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser473 (overall survival P

A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain.

Abstract: The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-specific cDNA libraries for genes containing the fork head box sequence that encodes a DNA-binding domain similar to that of the Drosophila homeotic gene fork head and rat hepatocyte nuclear factor HFNSp. These genes were subsequently tested for expression in the organizer region of blastula/gast rula-stage embryos as well as inducibility by activin. Our effort resulted in the isolation of a gene, XFKHl, that is primarily expressed in the dorsal blastopore lip of early gastrulae and is inducible by activin. At later stages it is expressed in the notochord and neural floor plate. Because of its spatial and temporal expression pattern, as well as its inducibility by activin, this gene is a good candidate to have a regulatory function in the initial processes of axis formation in Xenopus laevis embryos.

Mycobacterium tuberculosis Triggers Host Type I IFN Signaling To Regulate IL-1β Production in Human Macrophages

Abstract: Mycobacterium tuberculosis is a virulent intracellular pathogen that survives in macrophages even in the presence of an intact adaptive immune response. Type I IFNs have been shown to exacerbate tuberculosis in mice and to be associated with disease progression in infected humans. Nevertheless, the mechanisms by which type I IFNs regulate the host response to M. tuberculosis infection are poorly understood. In this study, we show that M. tuberculosis induces an IFN-related gene expression signature in infected primary human macrophages, which is dependent on host type I IFN signaling as well as the mycobacterial virulence factor, region of difference-1. We further demonstrate that type I IFNs selectively limit the production of IL-1b, a critical mediator of immunity to M. tuberculosis. This regulation occurs at the level of IL1B mRNA expression, rather than caspase-1 activation or autocrine IL-1 amplification and appears to be preferentially used by virulent mycobacteria since avirulent M. bovis

Medical applications of microarray technologies: a regulatory science perspective

Abstract: The potential medical applications of microarrays have generated much excitement, and some skepticism, within the biomedical community. Some researchers have suggested that within the decade microarrays will be routinely used in the selection, assessment, and quality control of the best drugs for pharmaceutical development, as well as for disease diagnosis and for monitoring desired and adverse outcomes of therapeutic interventions. Realizing this potential will be a challenge for the whole scientific community, as breakthroughs that show great promise at the bench often fail to meet the requirements of clinicians and regulatory scientists. The development of a cooperative framework among regulators, product sponsors, and technology experts will be essential for realizing the revolutionary promise that microarrays hold for drug development, regulatory science, medical practice and public health.