The pleiotropic cytokine interleukin-6 (IL-6) contributes to malignant progression and apoptosis resistance of various cancer types. Although IL-6 is elevated in malignant gliomas, and glioma cells respond to IL-6, its functional role in gliomagenesis is unclear. We have investigated this role of IL-6 in a mouse model of spontaneous astrocytoma by crossbreeding glial fibrillary acidic protein (GFAP)-viral src oncogene transgenic mice with IL-6-deficient mice. We show here that ablation of IL-6 prevents tumour formation in these predisposed animals, but did not affect preneoplastic astrogliosis. Moreover, we demonstrate phosphorylation and nuclear translocation of the transcription factor signal transducer and activator of transcription (STAT)3, a prerequisite for IL-6 signalling, in 51 human gliomas WHO grade II-IV and all experimental mouse tumours investigated. Together with the observation that STAT3 activation increases with malignancy, these findings indicate an important role for IL-6 in the development and malignant progression of astrocytomas.
Matrix metalloproteinases (MMPs) are a gene family of neutral proteases involved in normal and pathological processes in the central nervous system (CNS). Normally released into the extracellular space, MMPs break down the extracellular matrix (ECM) to allow cell growth and to facilitate remodeling. Proteolysis becomes pathological when the normal balance between the proteases and their inhibitors, tissue inhibitors to metalloproteinases (TIMPs), is lost. Cancer cells secrete neutral proteases to facilitate spread through the ECM. MMPs increase capillary permeability, and they have been implicated in demyelination. Neurological diseases, such as brain tumors, multiple sclerosis, Guillain-Barré, ischemia, Alzheimer's disease, and infections, lead to an increase in the matrix-degrading proteases. Two classes of neutral proteases have been extensively studied, namely the MMPs and the plasminogen activators (PAs), which act in concert to attack the ECM. After proteolytic injury occurs, the process of ECM remodeling begins, which can lead to fibrosis of blood vessels and gliosis. TIMPs are increased after the acute injury and may add to the fibrotic buildup of ECM components. Thus, an imbalance in proteolytic activity either during the acute injury or in recovery may aggravate the underlying disease process. Agents that affect the proteolytic process at any of the regulating sites are potentially useful in therapy.
The incidence of aSDH associated with SAH is low. Most of the patients with aSDH due to a ruptured aneurysm present in exceptionally poor neurological condition. Nevertheless, rapid surgical treatment of the hematoma and aneurysm obliteration can lead to a favorable outcome. Routine CTA should be performed in all patients presenting with an aSDH associated with SAH and no clear history of trauma.
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