Epidermal growth factor receptor: Structure-function informing the design of anticancer therapeutics.

Research on the epidermal growth factor (EGF) family and the family of receptors (EGFR) has progressed rapidly in recent times. New crystal structures of the ectodomains with different ligands, the activation of the kinase domain through oligomerisation and the use of fluorescence techniques have revealed profound conformational changes on ligand binding. The control of cell signaling from the EGFR-family is complex, with heterodimerisation, ligand affinity and signaling cross-talk influencing cellular outcomes. Analysis of tissue homeostasis indicates that the control of pro-ligand processing is likely to be as important as receptor activation events. Several members of the EGFR-family are overexpressed and/or mutated in cancer cells. The perturbation of EGFR-family signaling drives the malignant phenotype of many cancers and both inhibitors and antagonists of signaling from these receptors have already produced therapeutic benefits for patients. The design of affibodies, antibodies, small molecule inhibitors and even immunotherapeutic drugs targeting the EGFR-family has yielded promising new approaches to improving outcomes for cancer patients. In this review, we describe recent discoveries which have increased our understanding of the structure and dynamics of signaling from the EGFR-family, the roles of ligand processing and receptor cross-talk. We discuss the relevance of these studies to the development of strategies for designing more effective targeted treatments for cancer patients.

An unusual case of spinal cord compression from concomitant spinal epidural lipomatosis and Hodgkin's lymphoma.

Spinal epidural lipomatosis (SEL) results from an abnormal accumulation of unencapsulated fat within the epidural space and is a rare cause of spinal cord compression, which needs to be considered with a high index of suspicion. It most commonly occurs secondary to chronic corticosteroid use and endocrinopathies. Idiopathic cases are highly associated with obesity. We report an unusual case of idiopathic thoracic SEL in a 69-year-old male, with an adjacent infiltrative Hodgkin's lymphoma and associated vertebral crush fracture, which resulted in ataxia and sensory loss. Magnetic resonance imaging scans displayed extensive SEL and an infiltrative disease process causing thoracic cord compression. Surgical decompression confirmed the presence of extensive epidural lipomatosis and Hodgkin's lymphoma and subsequently led to improvement in neurological symptoms. To our knowledge, this is the first reported case of concomitant SEL with an adjacent Hodgkin's lymphoma resulting in cord compression.

The effect of formal training on the clinical utility of transcranial Doppler ultrasound monitoring in patients with aneurysmal subarachnoid haemorrhage.

We have previously shown that the clinical utility of transcranial Doppler (TCD) ultrasound monitoring for vasospasm in patients with aneurysmal subarachnoid haemorrhage, as performed by untrained operators in a busy neurosurgical unit, is questionable, despite the recommendations for its use in the literature. We determined if formal training improved the utility of TCD. Twelve untrained operators and one trained operator performed a total of 206 TCD examinations. There was poor agreement of results between trained and untrained operators. For the left middle cerebral artery (MCA), right MCA, left anterior cerebral artery (ACA) and right ACA, the blood flow velocities (BFV) recorded by the trained operator were greater than those recorded by the untrained operators by a mean (95% confidence interval) of 27.7 (25.0-30.4), 24.3 (21.4-27.1), 28.2 (25.6-30.9) and 28.1 (24.9-31.1) cm/s, respectively (p<0.001 for all vessels). Greater sensitivity was observed in TCD measurements from the trained operator (100%) compared to untrained operators (40%). To improve the utility of TCD, operators should be provided with training or a professional sonographer employed.

Gliomatosis cerebri in a patient with Ollier disease.

Gliomatosis cerebri (GC) is an uncommon brain tumour defined as a diffuse neoplastic glial cell infiltration of the brain, involving more than two cerebral lobes and, occasionally, the infratentorial structures or the spinal cord. GC of the oligodendroglial phenotype is extremely rare, especially in the paediatric setting. We describe an unusual case of oligodendroglial GC diagnosed in a 16-year-old boy with Ollier disease. To our knowledge this is the first case of GC reported in a child with Ollier disease.

Metastatic olfactory neuroblastoma invading a radiation-induced meningioma.

Olfactory neuroblastomas are malignant, neuroectodermal nasal tumours. We describe a 62-year-old patient with a recurrent olfactory neuroblastoma invading a radiation-induced meningioma. Given the temporal and spatial relationship between the primary lesion and the described recurrence, this was due to metastatic rather than direct contiguous spread, fulfilling all the criteria for true tumour-to-tumour metastasis. To our knowledge, this is the first description of an olfactory neuroblastoma metastasising to a meningioma.