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.

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.

Intervenção psicoeducacional em cuidador de criança com câncer: relato de caso / Psychoeducational intervention for caregiver of a child with cancer: a case report

Estudos em psico-oncologia pediátrica sobre programas de intervenções podem contribuir na adesão e prevenção de efeitos tardios do tratamento. O objetivo do presente estudo foi avaliar o impacto de um programa psicoeducacional sobre práticas parentais em um cuidador de criança com câncer, e as dificuldades relatadas pelo cuidador em relação aos problemas de comportamento da criança, pré e pós-intervenção. Método: Foi avaliada a mãe de uma criança com câncer de cinco anos, com diagnóstico de osteossarcoma e queixa de comportamentos agressivos. Os instrumentos utilizados foram: ficha de identificação, entrevista semi-estruturada, Inventário de Estilo Parental (Parental Bonding Instrument) e Inventário de Comportamentos da Infância e da Adolescência (CBCL). A participante respondeu aos inventários e entrevistas em quatro momentos: na fase pré-intervenção, pós-intervenção e em dois seguimentos. Foram realizadas quatro sessões do programa educacional, que seguiu o modelo cognitivo-comportamental. Resultados: foram identificadas práticas do estilo parental indulgente na avaliação pré-intervenção. A intervenção educacional diminuiu os comportamentos de superproteção e manteve os altos escores de carinho, apresentando mudança na forma de lidar com a criança, com práticas parentais do estilo autoritativo ou participativo. A criança apresentou escore clínico para comportamentos agressivos, reduzindo pós-intervenção, e escore não clínico nos seguimentos. Conclusão: Programas educativos como este podem ser incluídos no tratamento global da criança pelo psicólogo que integra equipes interdisciplinares de oncopediatria.

Studies on Pediatric Psychooncology related to intervention programs can contribute in the adhesion andprevention of late effects of the treatment. Objective: The present study evaluated the impact of a psychoeducacional program on parental practices of a caregiver of a child with cancer, and the difficulties reported by the caregiver regarding the child´s behavior problems pre and post-intervention. Methods: Amother of a 5-year-old child with cancer, osteosarcoma diagnosis and complaints of aggressive behaviorwas evaluated. Identification card, semi-directed interview, Inventory of parental style (Parental BondingInstrument) and Inventory of the childhood and adolescence behavior (CBCL) were used. This participant answered to the inventories and interviews in four moments: in the pre-intervention phase, post-interventionand into two segments. Four sessions of the education program were accomplished, following the cognitive-behavioral model. Results: The results identified practices of the indulgent parental style in the pre-interventionevaluation. The educational intervention reduced the excessive protection behaviors and maintained the high scores of affection, presenting change in the manner of dealing with the child, with parental practicesof authoritative or participative style. Conclusion: The child has presented clinical score for aggressive behavior, reducing post-intervention, and non clinical score in the follow-up. Educational programs similar to this one can be included in the child’s global treatment by the psychologist who is part of the interdisciplinary teams of Oncopediatrics.