Journal articles

The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in the environment from increased industrial and domestic use. The extent to which such compounds contribute to cellular toxicity is unclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins and the metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown.

p73 belongs to a family of transcription factors, including p53 and p63, that mediate response to DNA damage and cellular stress by inducing DNA repair, cell cycle arrest, and apoptosis. TP73 gene contains two promotors and several splice variants resulting in up to 24 possible permutations of p73 proteins which underlies the complexity of the family and its regulatory mechanisms. p73 variants lacking the N-terminal, denoted as DeltaTAp73, are not transcriptionally competent and they act in a dominant negative fashion over TAp73.

The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. CD4+ T cells comprise a large proportion of the inflammatory cells that invade the synovial tissue and may therefore be a cell type of pathogenic importance.

Understanding therapeutic mechanisms of drug anticancer cytotoxicity represents a key challenge in preclinical testing. Here we have performed a meta-analysis of publicly available tumor cell line growth inhibition assays (~ 70 assays from 6 independent experimental groups covering ~ 500 000 molecules) with the primary goal of understanding molecular therapeutic mechanisms of cancer cytotoxicity. To implement this we have collected currently available information on protein targets for molecules that were tested in the assays.

B-cell lymphomas are a heterogeneous group of diseases that can arise at different stages of B-cell development, often as a result of errors in the cells' unique ontogeny. Common oncogenic features are often observed, including chromosomal rearrangements, somatic mutations and transcriptional change. Disruption of translation regulation is also frequently implicated in both B-cell lymphoma development and progression.

Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking.

Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma.

The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes.

The use of existing drugs for new therapeutic applications, commonly referred to as drug repositioning, is a way for fast and cost-efficient drug discovery. Drug repositioning in oncology is commonly initiated by in vitro experimental evidence that a drug exhibits anticancer cytotoxicity. Any independent verification that the observed effects in vitro may be valid in a clinical setting, and that the drug could potentially affect patient survival in vivo is of paramount importance.

We describe here two systems for encoding foreign amino acid sequences in the exposed N-terminal segment of the major coat protein of bacteriophage fd. Small peptides can be encoded directly; larger peptides are encoded in hybrid bacteriophage particles, in which the capsid is formed from a mixture of wild-type and modified coat proteins. In both cases, the peptides are present in multiple copies per phage particle.