Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach.

BACKGROUND: Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. MATERIALS AND METHODS: We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM. RESULTS: We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM. CONCLUSIONS: Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.

Selective antimicrobial activity of maggots against pathogenic bacteria.

Maggot therapy, also known as biosurgery, is an ancient method for the healing of chronic infected wounds. Although clinicians have reported on the beneficial activities of the Lucilia sericata larvae that have been used for healing chronic wounds, the selectivity of this therapy against the different pathogenic micro-organisms that are found in chronic wounds has never been analysed. In the present study, we have investigated the in vitro activities of larval excreta/secreta both against selected bacterial strains that frequently occur in chronically infected wounds, and against bacteria isolated directly from the larvae and their excreta/secreta. Additionally, the antibacterial activities were investigated in in vivo studies, by comparing bacterial diversity in wounds before and after the application of L. sericata larvae. In conclusion, larval therapy is highly recommended, particularly for the treatment of wounds infected with Gram-positive bacteria, like Staphylococcus aureus, but less so for wounds infected with Gram-negative bacteria, especially Proteus spp. and Pseudomonas spp. strains. Bacteria from the genus Vagococcus were resistant to the maggot excreta/secreta.

Electronic lab notebooks: can they replace paper?

Despite the increasingly digital nature of society there are some areas of research that remain firmly rooted in the past; in this case the laboratory notebook, the last remaining paper component of an experiment. Countless electronic laboratory notebooks (ELNs) have been created in an attempt to digitise record keeping processes in the lab, but none of them have become a 'key player' in the ELN market, due to the many adoption barriers that have been identified in previous research and further explored in the user studies presented here. The main issues identified are the cost of the current available ELNs, their ease of use (or lack of it) and their accessibility issues across different devices and operating systems. Evidence suggests that whilst scientists willingly make use of generic notebooking software, spreadsheets and other general office and scientific tools to aid their work, current ELNs are lacking in the required functionality to meet the needs of the researchers. In this paper we present our extensive research and user study results to propose an ELN built upon a pre-existing cloud notebook platform that makes use of accessible popular scientific software and semantic web technologies to help overcome the identified barriers to adoption.

Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with a Prognostic Impact on Survival and Those of Viral Origin.

BACKGROUND: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis in spite of a plethora of established diagnostic and prognostic biomarkers and treatment modalities. Therefore, the current goal is the detection of novel biomarkers, possibly detectable in the blood of GBM patients that may enable an early diagnosis and are potential therapeutic targets, leading to more efficient interventions. EXPERIMENTAL PROCEDURES: MicroRNA profiling of 734 human and human-associated viral miRNAs was performed on blood plasma samples from 16 healthy individuals and 16 patients with GBM, using the nCounter miRNA Expression Assay Kits. RESULTS: We identified 19 miRNAs with significantly different plasma levels in GBM patients, compared to the healthy individuals group with the difference limited by a factor of 2. Additionally, 11 viral miRNAs were found differentially expressed in plasma of GBM patients and 24 miRNA levels significantly correlated with the patients' survival. Moreover, the overlap between the group of candidate miRNAs for diagnostic biomarkers and the group of miRNAs associated with survival, consisted of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa miR 592 and hsa miR 514a 3p have not been previously described in GBM and represent novel candidates for selective biomarkers. The possible signalling, induced by the revealed miRNAs is discussed, including those of viral origin, and in particular those related to the impaired immune response in the progression of GBM. CONCLUSION: The GBM burden is reflected in the alteration of the plasma miRNAs pattern, including viral miRNAs, representing the potential for future clinical application. Therefore proposed biomarker candidate miRNAs should be validated in a larger study of an independent cohort of patients.

A "crossomics" study analysing variability of different components in peripheral blood of healthy caucasoid individuals.

BACKGROUND: Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable. METHODOLOGY/PRINCIPAL FINDINGS: To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics" analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4+T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset. CONCLUSIONS/SIGNIFICANCE: Our study shows that the intra-individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective.