Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with chronic renal failure (CRF) who undergo hemodialysis experience accelerated atherosclerosis and premature death. While the cause of uremic atherogenesis is unknown, we reported that uremic levels of oxalate, an excretory metabolite, severely inhibit proliferation and migration of human endothelial cells (EC) without affecting other cell types. Since the physical, cellular and molecular events of endothelial injury are clearly established as key factors in the development of plaque, and since inhibition of proliferation and migration would enhance endothelial injury, we have proposed that oxalate is an atherogenic toxin of uremia. In the current study, we used in situ cell counting and total DNA measurement to show that the inhibitory effect of oxalate on proliferation is exclusive to endothelial cells among human cell lines tested (endothelial cells, fibroblasts, aortic smooth muscle cells (SMC), glioblastoma and embryonic kidney cells). Using the fluorescent calcium indicators fura-2 and fluo-3, we correlated the inhibition of proliferation with a prolonged elevation in intracellular free calcium levels. We also demonstrated that all cells tested internalize 14C-oxalic acid. We conclude that plasma oxalate exerts its atherogenic effects by elevating intracellular calcium exclusively in endothelial cells and preventing re-endothelialization.
 ...
PMID:Oxalic acid alters intracellular calcium in endothelial cells. 1506 9

An 83-year-old man with chronic renal failure was referred to our hospital because of subacute progressive right hemiparesis. A brain MRI showed high-intensity lesions in bilateral middle cerebellar peduncles and white matter of the left frontal lobe on T2-weighted images. The lesions increased gradually, so we suspected a brain tumor because 1H-MRS images showed elevated Cho and decreased NAA, and also pathologic findings of the brain biopsy suggested glioblastoma. However, JC virus (JCV) in cerebrospinal fluid was revealed highly positive by PCR. So we reconsidered pathologically and finally found bizarre astrocytes which were infected with JCV in immunohistochemical studies and we diagnosed progressive multifocal leukoencephalopathy at last. Then we medicated with mefloquine and mirtazapine, and the JCV in cerebrospinal fluid disappeared, without new MRI lesions. This is a rare case in respect of the background of the patient and the clinical course.
 ...
PMID:A case of progressive multifocal leukoencephalopathy with chronic renal failure, whose JC virus in cerebrospinal fluid disappeared after mefloquine-mirtazapine dual therapy. 2764 58

Erythropoietin (EPO) is an erythropoiesis stimulating growth factor and hormone. EPO has been widely used in the treatment of chronic renal failure, cancer, and chemotherapy-related anemia for three decades. However, many clinical trials showed that EPO treatment may be associated with tumorigenesis and cancer progression. EPO is able to cross blood-brain barriers, and this may lead to an increased possibility of central nervous system tumors such as glioblastoma. Indeed, EPO promotes glioblastoma growth and invasion in animal studies. Additionally, EPO increases glioblastoma cell survival, proliferation, migration, invasion, and chemoresistancy in vitro. However, the exact mechanisms of cancer progression induced by EPO treatment are not fully understood. Posttranscriptional gene regulation through microRNAs may contribute to EPO's cellular and biological effects in tumor progression. Here, we aimed to study whether tumor suppressive microRNA, miR-451, counteracts the positive effects of EPO on U87 human glioblastoma cell line. Migration and invasion were evaluated by scratch assay and transwell invasion assay, respectively. We found that EPO decreased basal miR-451 expression and increased cell proliferation, migration, invasion, and cisplatin chemoresistancy in vitro. miR-451 overexpression by transfection of its mimic significantly reversed these effects. Furthermore, ectopic expression of miR-451 inhibited expression of its own target genes, such as metalloproteinases-2 and -9, which are stimulated by EPO treatment and involved in carcinogenesis processes, especially invasion. These findings suggest that miR-451 mimic delivery may be useful as adjuvant therapy in addition to chemotherapy and anemia treatment by EPO and should be tested in experimental glioblastoma models.
 ...
PMID:Erythropoietin Promotes Glioblastoma via miR-451 Suppression. 2862 21