Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015674 (chronic fatigue syndrome)
 2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Crow-Fukase syndrome is diagnosed based on the presence of chronic sensori-motor polyneuropathy along with other characteristic generalized symptoms denoted by the acronym of POEMS which stands for polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. In this syndrome, the serum levels of the vascular endothelial growth factor (VEGF) are abnormally elevated, and this is a predictive factor for its diagnosis. Although the causes of CFS/POEMS remain unknown, VEGF is evidently correlated with its pathogenesis. Human glioblastoma cells are known to express VEGF. In models of CFS/POEMS, mice that are peritoneally transplanted with human glioblastomas exhibit high serum levels of VEGF, prominent edema with increased circulation volume, and pathological findings in the liver, spleen, and kidney. VEGF that is highly concentrated in platelets may be released in massive amounts due to coagulation in the peripheral tissue and may thus exert its maximal physiological effects and produce the abovementioned diffuse pathological findings. The correlation between polyneuropathy and elevated VEGF remains unclear. However, VEGF may affect the blood-nerve barrier by increased microvascular hyperpermeability, upregulated cytokines such as matrix metalloproteases may induce blood-nerve barrier breakdown and demyelination of the peripheral nerve. Furthermore, microangiopathy due to proliferative endothelial cells and hypercoagulated occlusion also affect axonal damage. Novel strategies that have recently been proposed for the management of this disease include high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (PBSCT) and molecular-targeted therapy against plasma cells and VEGF. Notably, PBSCT exerts a dramatic effect on polyneuropathy; such an effect has rarely been achieved by the previously described modalities of low-dose melphallan and steroid therapy. PBSCT is observed to induce a rapid and persistent decrease in the serum VEGF levels. In conclusion, VEGF is not only the primary molecule involved in the pathogenesis of CSF, but also an important marker for both the diagnosis and treatment of this disease.
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PMID:[Crow-Fukase syndrome and VEGF]. 1856 56

Patients with chronic hepatitis C virus (HCV) infection show an increased incidence of nervous system disorders such as chronic fatigue syndrome, depression and cognitive dysfunction. It is unclear whether this is because of HCV replication in the brain and in peripheral neuronal cells or to more indirect effects of HCV infection on the central or peripheral nervous system. The aim of this study was to investigate whether cells originating from these tissues are permissive for HCV cell entry, RNA replication and virus assembly. Among eight cell lines analysed, the human peripheral neuroblastoma cell line SKNMC expressed all HCV entry factors and was efficiently infected with HCV pseudoparticles (HCVpp) independent of the HCV genotype. All remaining cell types including human neuroblastoma and glioblastoma cell lines and microglial cells lacked expression of at least one host factor essential for HCV entry. When transfected with HCV luciferase reporter virus RNA, inoculated with HCV reporter viruses or challenged with high-titre cell culture-derived HCV, none of these cells supported detectable HCV RNA replication. Thus, in conclusion, this comprehensive screening did not reveal evidence directly strengthening the notion that HCV enters and replicates in the central nervous system. However, productive viral entry into the peripheral neuroblastoma cell line SKNMC indicates that HCV may penetrate into certain nonhepatic cell types which may serve as viral reservoirs and could modulate viral pathogenesis.
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PMID:Hepatitis C virus enters human peripheral neuroblastoma cells - evidence for extra-hepatic cells sustaining hepatitis C virus penetration. 2057 78

(1) Background: The phase 2 Regorafenib in Relapsed Glioblastoma (REGOMA) trial indicated a survival benefit for patients with first recurrence of a glioblastoma when treated with the multikinase inhibitor regorafenib (REG) instead of lomustine. The aim of this retrospective study was to investigate REG penetration to cerebrospinal fluid (CSF), treatment efficacy, and effects on magnetic resonance imaging (MRI) in patients with recurrent high-grade gliomas. (2) Methods: Patients were characterized by histology, adverse events, steroid treatment, overall survival (OS), and MRI growth pattern. REG and its two active metabolites were quantified by liquid chromatography/tandem mass spectrometry in patients' serum and CSF. (3) Results: 21 patients mainly with IDH-wildtype glioblastomas who had been treated with REG were retrospectively identified. Thirteen CFS samples collected from 3 patients of the cohort were available for pharmacokinetic testing. CSF levels of REG and its metabolites were significantly lower than in serum. Follow-up MRI was available in 19 patients and showed progressive disease (PD) in all but 2 patients. Two distinct MRI patterns were identified: 7 patients showed classic PD with progression of contrast enhancing lesions, whereas 11 patients showed a T2-dominant MRI pattern characterized by a marked reduction of contrast enhancement. Median OS was significantly better in patients with a T2-dominant growth pattern (10 vs. 27 weeks respectively, p = 0.003). Diffusion restrictions were observed in 13 patients. (4) Conclusion: REG and its metabolites were detectable in CSF. A distinct MRI pattern that might be associated with an improved OS was observed in half of the patient cohort. Treatment response in the total cohort was poor.
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PMID:Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients. 3176 26