Association of secondary glioblastoma and pituitary adenoma : case report

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

IDH1 Mutations in Diffusely Infiltrating Astrocytomas Grade Specificity, Association With Protein Expression, and Clinical Relevance

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 83.3%] secondary, and 1/42 2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < .001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM.

Targeting EGFR Induced Oxidative Stress by PARP1 Inhibition in Glioblastoma Therapy

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis [1,2], EGFR targeted therapies have achieved limited clinical efficacy [3]. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction [4,5]. A directed RNAi screen revealed that glioblastoma cells overexpressing EGFRvIII [6], an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII overexpression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyperactivation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

The use of online counselling within an Australian secondary school setting: a practitioner’s viewpoint

This paper proposes that the provision of online counselling services for young people accessed through their local school website has the potential to assist students with mental health issues as well as increasing their help seeking behaviours. It stems from the work of the authors who trialled an online counselling service within one Australian secondary school. In Australia, online counselling with the adult population is now an accepted part of the provision of mental health services. Online provision of mental health information for young people is also well accepted. However, online counselling for young people is provided by only a few community organisations such as Kids Help Line within Australia. School based counselling services which are integral to most secondary schools in Australia, seem slow to provide this service in spite of initial interest and enthusiasm by individual school counsellors. This discussion is the product of reflection on the potential benefits of this trial with a consideration of relevant research of the issues raised. It highlights the need for further research into the use of computer mediated communication in the provision of counselling within a school setting.

Secondary teachers’ conceptions of teaching and learning

This paper presents a phenomenographic analysis of the conceptions of teaching and learning held by a sample of 16 secondary school teachers in two Australian schools. It provides descriptions of four categories, derived from pooled data, of the ways in which these teachers thought about teaching and about learning, their teaching strategies, and their focus on student or content. The categories for teaching and learning are described with each teacher allocated to the category most typical of their conceptions of teaching and of learning. The lack of congruence, in some cases, between the conceptions of teaching and of learning held by these teachers is discussed.