Liquid chromatography tandem mass spectrometry method for the quantitative analysis of ceritinib in human plasma and its application to pharmacokinetic studies.

Ceritinib is a highly selective inhibitor of an important cancer target, anaplastic lymphoma kinase (ALK). Because it is an investigational compound, there is a need to develop a robust and reliable analytical method for its quantitative determination in human plasma. Here, we report the validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the rapid quantification of ceritinib in human plasma.

Design and pre-clinical profiling of a Plasmodium falciparum MSP-3 derived component for a multi-valent virosomal malaria vaccine.

Background: Clinical profiling of two components for a synthetic peptide-based virosomal malaria vaccine has yielded promising results, encouraging the search for additional components for inclusion in a final multi-valent vaccine formulation. This report describes the immunological characterization of linear and cyclized synthetic peptides comprising amino acids 211-237 of Plasmodium falciparum merozoite surface protein (MSP-3).

Methods: These peptides were coupled to phosphatidylethanolamine (PE); the conjugates were intercalated into immunopotentiating reconstituted influenza virosomes (IRIVs) and then used for immunizations in mice to evaluate their capacity to elicit P.

Preclinical profiling of the immunogenicity of a two-component subunit malaria vaccine candidate based on virosome technology.

Presentation of synthetic peptides on immunopotentiating reconstituted influenza virosomes is a promising technology for subunit vaccine development. An optimized virosomally delivered peptide representing 5 NPNA repeats of P. falciparum circumsporozoite protein is highly immunogenic in mice.

Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial.

Background: Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune responses to both the pre-erythrocytic and blood stages of the P. falciparum life cycle.

Synthesis, solution structure and immune recognition of an epidermal growth factor-like domain from Plasmodium falciparum merozoite surface protein-1.

The Plasmodium falciparum merozoite surface protein-1 19 kDa fragment (MSP-1(19)) comprises two closely packed EGF-like domains (EGF=epidermal growth factor), each stabilized by three disulfide bonds. The native conformation of this protein is important for eliciting P. falciparum growth inhibitory antibodies.

Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1.

Mutations in the parkin gene are linked to autosomal-recessive juvenile parkinsonism (AR-JP). Parkin functions as a ubiquitin protein ligase in the degradation of several proteins, including the neuron-specific septin CDCrel-1. AR-JP-associated parkin mutations inhibit ubiquitination and degradation of CDCrel-1 and other parkin target proteins.

Induction of parasite growth-inhibitory antibodies by a virosomal formulation of a peptidomimetic of loop I from domain III of Plasmodium falciparum apical membrane antigen 1.

Apical membrane antigen 1 (AMA-1) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. Its ectodomain can be divided into three subdomains, each with disulfide bond-stabilized structures. Since the majority of antibodies raised against the ectodomain appear to recognize strain-specific epitopes in domain I, we attempted to develop a vaccine formulation which directs the immune response to a region that contains more conserved epitopes.

Identification of nuclear proteins that interact differentially with Plasmodium falciparum var gene promoters.

The Plasmodium falciparum virulence factor PfEMP1 is responsible for both antigenic variation and cytoadherence of infected erythrocytes in malaria. Approximately 50 var genes per parasite genome code for this highly polymorphic surface protein. We showed recently that chromosome-central and subtelomeric var genes are controlled by different promoters.