Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association between multiple sclerosis and tumours of the central nervous system is unusual. The authors analyzed the clinico-pathological elements of the correlation. The pertinent literature on this subject is critically reviewed. Ten cases of patients with an history of multiple sclerosis for more than 15 years and a clinical and radiological evidence of brain tumour were submitted to surgery in order to remove the lesion and/or to chemo- and radiotherapy. The various aspects of the association were studied in detail. A patient with multiple sclerosis, particularly with atypical symptoms, should be evaluated by an annual MRI investigation with intravenous paramagnetic contrast medium. The diagnostic work-up should be: clinical and radiological assessment; MRI in the event of atypical symptoms; Sstereotactic or neuronavigation-aided biopsy in any suspected lesions. Patients with multiple sclerosis and glioma present survival times identical to those observed in patients not suffering from multiple sclerosis. The coexistence of multiple sclerosis and brain tumours does not seem to influence the clinical evolution of either of these pathologies. We believe that it is important to achieve an early diagnosis of brain tumour in such patients with a clinical and neuroradiological follow up, so that they can be treated promptly.
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PMID:Multiple sclerosis and gliomas. Clinical remarks on 10 cases and critical review of the literature. 1555 83

Clinical diffusion magnetic resonance (MR) imaging in humans started in the last decade with the demonstration of the capabilities of this technique of depicting the anatomy of the white matter fibre tracts in the brain. Two main approaches in terms of reconstruction and evaluation of the images obtained with application of diffusion sensitising gradients to an echo planar imaging sequence are possible. The first approach consists of reconstruction of images in which the effect of white matter anisotropy is averaged -- known as the isotropic or diffusion weighted images, which are usually evaluated subjectively for possible areas of increased or decreased signal, reflecting restricted and facilitated diffusion, respectively. The second approach implies reconstruction of image maps of the apparent diffusion coefficient (ADC), in which the T2 weighting of the echo planar diffusion sequence is cancelled out, and their objective, i.e. numerical, evaluation with regions of interest or histogram analysis. This second approach enables a quantitative and reproducible assessment of the diffusion changes not only in areas exhibiting signal abnormality in conventional MR images but also in areas of normal signal. A further level of image post-processing requires the acquisition of images after application of sensitising gradients along at least 6 different spatial orientations and consists of computation of the diffusion tensor and reconstruction of maps of the mean diffusivity (D) and of the white matter anisotropic properties, usually in terms of fractional anisotropy (FA). Diffusion-weighted imaging is complementary to conventional MR imaging in the evaluation of the acute ischaemic stroke. The combination of diffusion and perfusion MR imaging has the potential of providing all the information necessary for the diagnosis and management of the individual patient with acute ischaemic stroke. Diffusion-weighted MR, in particular quantitative evaluation based on the diffusion tensor, has a fundamental role in the assessment of brain maturation and of white matter diseases in the fetus, in the neonate and in the child. Diffusion MR imaging enables a better characterisation of the lesions demonstrated by conventional MR imaging, for instance in the hypoxic-ischaemic encephalopathy, in infections and in the inherited metabolic diseases, and is particularly important for the longitudinal evaluation of these conditions. Diffusion-weighted MR imaging has an established role in the differential diagnosis between brain abscess and cystic tumour and between epidermoid tumour and arachnoid cyst. On the other hand, the results obtained with diffusion MR in the characterisation of type and extension of glioma do not yet allow decision making in the individual patient. Diffusion is one of the most relevant MR techniques to have contributed to a better understanding of the pathophysiological mechanisms of multiple sclerosis (MS). In fact, it improves the specificity of MR in characterising the different pathological substrata underlying the rather uniform lesion appearance on the conventional images and enables detection of damage in the normal-appearing white and grey matter. In MS patients the ADC or D values in the normal-appearing white matter are increased as compared to control values, albeit to a lesser degree than in the lesions demonstrated by T2-weighted images. In addition, the D of the normal appearing grey matter is increased in MS patients and this change correlates with the cognitive deficit of these patients. Histogram analysis in MS patients shows that the peak of the brain D is decreased and right-shifted, reflecting an increase of its value, and the two features correlate with the patient's clinical disability. Ageing is associated to a mild but significant increase of the brain ADC or D which is predominantly due to changes in the white matter. Region of interest and histogram studies have demonstrated that D or ADC are increased in either the areas of leukoaraiosis or the normal-appearing white matter in patients with inherited cerebral autosomal dominant arteriopathy with subcortical infarcts and stroke or sporadic ischaemic leukoencephalopathy. Diffusion changes might be a more sensitive marker for progression of the disease than conventional imaging findings. In neurodegenerative diseases of the central nervous system such as Alzheimer's disease, Huntington's disease, hereditary ataxias and motor neuron disease, quantitative diffusion MR demonstrates the cortical and subcortical grey matter damage, which is reflected in a regional increase of D or ADC, but also reveals the concomitant white matter changes that are associated with an increase in D or ADC and decrease in FA. In all these diseases the diffusion changes are correlated to the clinical deficit and are potentially useful for early diagnosis and longitudinal evaluation, especially in the context of pharmacological trials.
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PMID:Diffusion-weighted MR of the brain: methodology and clinical application. 1577 87

A 48-year-old woman with a history of viral influenza infection was admitted with rapidly progressive numbness and weakness of the right extremities. On admission, general physical examination revealed no abnormality. Cerebrospinal fluid analysis showed no abnormal findings. Brain computed tomography and magnetic resonance imaging showed an open ring-like enhanced lesion in the white matter of the right parietal lobe with massive perifocal edema. Cerebral angiography showed no tumor staining and thallium-201 single photon emission computed tomography showed no abnormal uptake. The preoperative diagnosis was malignant glioma and partial resection was performed. Histological examination showed perivascular accumulation of small lymphocytes and a large number of macrophages with reactive astrocytes. Phagocytosis of myelin was observed in the macrophages and nuclear fragmentation in the reactive astrocytes. The histological diagnosis was acute inflammatory demyelinating disease. After therapy with methylprednisolone, her neurological symptoms improved gradually and no relapse occurred during 18 months of follow up. Tumor-like masses of demyelination may occupy an intermediate position between acute multiple sclerosis and postinfectious encephalitis. Open ring sign may be a pathognomonic feature of these lesions.
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PMID:Monofocal acute inflammatory demyelination manifesting as open ring sign. Case report. 1686 30

Oxidative mechanisms of injury are involved in many neurodegenerative diseases such as stroke, ischemia-reperfusion injury and multiple sclerosis. G protein-coupled receptor kinase 2 (GRK2) plays a key role in G protein-coupled receptor (GPCR) signaling modulation, and its expression levels are decreased after brain hypoxia/ischemia and reperfusion as well as in several inflammatory conditions. We report here that hydrogen peroxide downregulates GRK2 expression in C6 rat glioma cells. The hydrogen peroxide-induced decrease in GRK2 is prevented by a calpain protease inhibitor, but does not involve increased GRK2 degradation or changes in GRK2 mRNA level. Instead we show that hydrogen peroxide treatment impairs GRK2 translation in a process that requires Cdk1 activation and involves the mTOR pathway. This novel mechanism for the control of GRK2 expression in glial cells upon oxidative stress challenge may contribute to the modulation of GPCR signaling in different pathological conditions.
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PMID:Hydrogen peroxide impairs GRK2 translation via a calpain-dependent and cdk1-mediated pathway. 1696 27

DJ-1 plays an important role in oxidative stress, and is involved in various neurodegenerative diseases. Accumulating evidence suggests a central role for oxidative stress in multiple sclerosis (MS). The aim of this study was to examine whether changes occur in DJ-1 expression in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and protein expression levels in EAE and a correlation between disease severity and increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells. Immunocytochemical staining demonstrated that DJ-1 is present both in the cytoplasm and the nuclei of these cells. This is the first report of modulation of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar results were observed in glioma cells exposed to ROS. In view of the accumulating evidence on the central role of oxidative stress in MS, and the importance of DJ-1 in oxidative stress management by the CNS, we believe that DJ-1 will be found to have a central role in MS.
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PMID:Experimental encephalomyelitis induces changes in DJ-1: implications for oxidative stress in multiple sclerosis. 1703 44

The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined two anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimise the presence of blood borne macrophages within tumour tissue. The two lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [(11)C](R)-PK11195 and the corresponding tumour tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterised for molecules involved in antigen presentation and cytotoxic activity. As comparison, PBR was investigated in three brains with multiple sclerosis (MS) and three with Parkinson's disease (PD). The expression profile of four anaplastic astrocytomas was also exploited and results were compared to the profile of eleven samples of normal temporal lobe and nine cases of PD. PET studies showed that [(11)C](R)-PK11195 binding was markedly lower in tumours than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. PBR and cytotoxic molecules were highly represented in MS and PD. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumours.
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PMID:The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas. 1752 Jan 79

Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action of many of these cells are unknown and this raises the concern of unpredictable results in the future. Nevertheless there is considerable optimism that immune suppression and anti-inflammatory properties of mesenchymal stem cells will be of benefit for many conditions such as graft versus host disease, solid organ transplants and pulmonary fibrosis. Where bone marrow and mesenchymal stem cells are being studied for heart disease, stroke and other neurodegenerative disorders, again progress is mixed and mostly without significant benefit. However, correction of multiple sclerosis, at least in the short term is encouraging. Clinical trials on the use of embryonic stem cell derivatives for spinal injury and macular degeneration are beginning and a raft of other clinical trials can be expected soon, for example, the use of neural stem cells for killing inoperable glioma and embryonic stem cells for regenerating beta islet cells for diabetes. The change in attitude to embryonic stem cell research with the incoming Obama administration heralds a new co-operative environment for study and evaluation of stem cell therapies. The Californian stem cell initiative (California Institute for Regenerative Medicine) has engendered global collaboration for this new medicine that will now also be supported by the US Federal Government. The active participation of governments, academia, biotechnology, pharmaceutical companies, and private investment is a powerful consortium for advances in health.
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PMID:New perspectives in human stem cell therapeutic research. 1951 78

The epidermal growth factor receptor (EGFR) family (also known as the ErbB protein family) is comprised of four structurally-related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease. In contrast, excessive ErbB signaling is associated with the development of a wide variety of solid tumors. ErbB-1 and -2 are found in many human cancers and their excessive signaling may be critical factors in the development and malignancy of solid tumors. Several molecular strategies have been developed recently to modulate either EGFR or the downstream signal beyond the cell surface receptor. In the present study, we used human EGFR-overexpressing glioma xenograft cells 4910 and 5310 and targeted MMP-2 expression using an adenoviral RNAi construct. We observed that the RNAi-mediated downregulation of MMP-2 causes the upregulation of ErbB-2 in certain EGFR-overexpressing glioma xenograft cells both in vitro and in vivo. Targeted MMP-2 downregulation was observed in a dose-dependent manner with no apparent off-target effects in these xenograft cells. We also noted that the overexpression of ErbB-2 induced by MMP-2 downregulation is consistent with p50-mediated cell death in 5310 cells but not in 4910 cells. In addition, APAF-1 expression levels increased in correlation with increased ErbB-2 expression after MMP-2 downregulation in vitro and in vivo. Our results suggest that MMP-2 may play a role in a hitherto unknown signaling pathway mediated via ErbB-2 in certain cancer cell types.
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PMID:MMP-2 downregulation mediates differential regulation of cell death via ErbB-2 in glioma xenografts. 1957 38

Rapid advances in the field of nanotechnology promise revolutionary improvements in the diagnosis and therapy of neuroinflammatory disorders. An array of iron oxide nano- and microparticle agents have been developed for in vivo molecular magnetic resonance imaging (mMRI) of cerebrovascular endothelial targets, such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and the glycoprotein receptor GP IIb/IIIa expressed on activated platelets. Molecular markers of glioma cells, such as matrix metalloproteinase-2 (MMP-2), and markers for brain tumor angiogenesis, such as alpha (v) beta (3) integrin (alpha(v)beta(3)), have also been successfully targeted using nanoparticle imaging probes. This chapter provides an overview of targeted, iron oxide nano- and microparticles that have been applied for in vivo mMRI of the brain in experimental models of multiple sclerosis (MS), brain ischemia, cerebral malaria (CM), brain cancer, and Alzheimer's disease. The potential of targeted nanoparticle agents for application in clinical imaging is also discussed, including multimodal and therapeutic approaches.
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PMID:Chapter 4 - Applications of nanotechnology in molecular imaging of the brain. 2030 29

Increasing pieces of evidence indicate that the chemokine system influences several aspects of brain physiology and pathology. A deregulated chemokine expression pattern is observed during neurological diseases, including multiple sclerosis and brain tumor. Gliomas are the most common primary tumors affecting human central nervous system (CNS). Chemokines expressed by stromal cells or endogenously produced by glioma cells may influence tumor cell migration, invasion, proliferation, angiogenesis and immune cell infiltration in the tumor mass. Herein we focus on chemokines and chemokine receptors expressed by glioma cells and their role in the regulation of glioma cell functional behaviour, including its ability to attract immune cells.
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PMID:Chemokines and glioma: invasion and more. 2065 28


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