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)

Oxygen radicals induce cytotoxicity via a variety of mechanisms, including DNA damage, lipid peroxidation and protein oxidation. Here, we explore the use of a polyethylene glycol (PEG)-stabilised enzyme capable of producing reactive oxygen species (ROS), glucose oxidase (GO), for the purpose of harnessing the cytotoxic potential of ROS for treating solid tumours. PEG-GO (200 U), administered by two intratumoral injections 3 h apart, produced a significant growth delay in subcutaneous rat 9L gliomas as compared with control animals receiving heat-denatured PEG-GO. Rats were protected from systemic toxicity by subsequent i.v. administration of PEG-superoxide dismutase (PEG-SOD) and PEG-catalase. In vivo tumour metabolic changes, monitored using 31P magnetic resonance spectroscopy (31P-MRS) 6 h following initial administration of PEG-GO, revealed a 96 +/- 2% reduction in the ATP/Pi ratio and a 0.72 +/- 0.10 unit decline in intracellular pH. A 3-fold sensitisation of 9L glioma cells in vitro to hydrogen peroxide could be achieved by a 24 h preincubation with buthionine sulphoximine (BSO). This study suggests that oxidation therapy, the use of an intratumoral ROS-generating enzyme system for the treatment of solid tumours, is a promising area which warrants further exploration.
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PMID:Oxidation therapy: the use of a reactive oxygen species-generating enzyme system for tumour treatment. 798 Oct 65

The 5'-flanking region of the human neurotrophin-3 (NT-3) gene was isolated from a human placental genomic library using the oligonucleotide corresponding to the 5'-noncoding region of the NT-3 cDNA as a probe. A 3.8 kbp genomic fragment containing the 5'-flanking region, the first exon and a portion of the first intron was isolated and sequenced. The transcriptional initiation site, identified by S1 nuclease mapping, was located 27 bp downstream from the TATA-like sequence. Several plasmids, in which the NT-3 promoter regions were fused to the chloramphenicol acetyltransferase (CAT) gene, were constructed. Transient expression in human glioma Hs683 cells demonstrated that a fragment of about 0.1 kbp from the transcriptional initiation site was sufficient for promoter activity. While, in human plasma cell leukemia ARH77 cells, in which NT-3 mRNA was not detected, the region upstream from -65 functioned to silence CAT activity. It is suggested that this region contains the transcriptional regulatory element for the specific expression of the NT-3 gene.
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PMID:Identification of the functional regulatory region of the neurotrophin-3 gene promoter. 838 96

A 3-year-old boy presented with an unusual consciousness disturbance accompanied by involuntary movement disorder after radical surgical removal of a huge hypothalamic glioma. Postoperative computed tomography and magnetic resonance imaging revealed a lesion in the bilateral basal ganglia. Marked neurological improvement was obtained by treatment with dopamine agonists, suggesting that the disruption of the dopaminergic pathway via the hypothalamus was the cause of these neurological symptoms.
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PMID:Akinetic mutism and involuntary movements following radical resection of hypothalamic glioma--case report. 874 74

Expression of the lactate dehydrogenase A subunit (LDH-A) gene can be controlled by transcriptional as well as posttranscriptional mechanisms. In rat C6 glioma cells, LDH-A mRNA is stabilized by activation and synergistic interaction of protein kinases A and C. In the present study, we aimed to identify the sequence domain which determines and regulates mRNA stability/instability by protein kinase A and focused our attention on the 3'-untranslated region (3'-UTR) of LDH-A mRNA. We have constructed various chimeric globin/lactate dehydrogenase (ldh) genes linked to the c-fos promoter and stably transfected them into rat C6 glioma cells. After their transfection, we determined the half-life of transcribed chimeric globin/ldh mRNAs. The results showed that at least three sequence domains within the LDH-A 3'-UTR consisting of nucleotides 1286-1351, 1453-1471, and 1471-1502 are responsible for the relatively rapid rate of LDH-A mRNA turnover in the cytoplasm. Whereas chimeric globin/ldh mRNAs containing the base sequences 1286-1351 and 1453-1471 were not stabilized by (Sp)-cAMPS, an activator of protein kinase A, instability caused by the 1471-1502 domain was significantly reversed. Additional deletion and mutational analyses demonstrated that the 3'-UTR fragment consisting of the 22 bases 1478-1499 is a critical determinant for the (Sp)-cAMPS-mediated LDH-A mRNA stabilizing activity. Because of its functional characteristics, we named the 22-base region "cAMP-stabilizing region."
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PMID:Protein kinase A-regulated instability site in the 3'-untranslated region of lactate dehydrogenase-A subunit mRNA. 973 91

Tumor cells become sensitive to the inert prodrug cyclophosphamide (CPA) after transfer of the gene encoding cytochrome P450 2B1. This enzyme activates CPA into 4-hydroxycyclophosphamide, which ultimately degrades into acrolein and phosphoramide mustard, the anticancer and DNA-alkylating metabolite. It is imperative that any prodrug-activating gene therapy strategy against cancer possess the capacity to affect the proliferation of tumor cells even when they do not express the transgene (bystander effect), because current methodologies cannot achieve gene transduction in all tumor cells. Prodrug-activating gene therapy schemes described to date exhibit a bystander effect that is not mediated by conditioned medium in culture and may depend on cell contact. In contrast, we find that CPA-sensitized, P450-expressing C6 glioma cells (C6-P450) transfer cytotoxicity to nonexpressing cells by releasing diffusible metabolites through the medium. A 3-h exposure to the prodrug is necessary and sufficient to achieve killing of the transfected cells, and medium conditioned by these cells can kill untransfected cells with similar potency. This bystander effect occurs in the presence of CPA even when only 10% of cells in culture express the P450 2B1 gene, and it is not reproduced by cells that have been irradiated. In an animal model of intracerebral brain tumors, expression of the P450 2B1 gene within the neoplastic cells enhanced significantly the antitumor effect of CPA, even when it was administered systemically. This study shows that CPA/P450 2B1 gene therapy represents a novel tumor-killing strategy that displays an expanded range of cytotoxic action both spatially and temporally within tumor cells and significantly potentiates the anticancer action of CPA when administered i.v.
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PMID:Diffusible cytotoxic metabolites contribute to the in vitro bystander effect associated with the cyclophosphamide/cytochrome P450 2B1 cancer gene therapy paradigm. 981 9

Intracranial metastasis without pulmonary involvement of Wilms' tumor is very rare, and most previously reported metastatic sites have been in the cerebral parenchyma. We experienced a rare case of metastasis of Wilms' tumor in the tectal plate without pulmonary involvement. A 3-month-old boy was admitted to our hospital due to hydrocephalus. After insertion of a ventriculoperitoneal shunt, there were no neurological deficits. Five months after the operation, a mass 5 cm in diameter extending from the tectal plate into the third ventricle was found. A mass 10 cm in diameter within the retroperitoneal space, which occupied the right kidney, was also found. Both tumors were resected and diagnosed histologically as Wilms' tumor. Despite every effort including chemotherapy and radiotherapy, the patient died at 14 months old. The majority of children with hydrocephalus showing thickening of the tectal plate would most likely have tectal glioma; however, this unusual case report reminds us that metastasis of Wilms' tumor can occur in the tectal plate causing hydrocephalus.
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PMID:Intracranial metastasis of Wilms' tumor involving the tectal plate without pulmonary involvement. Case report. 1049 60

We report a case of optic glioma with bilateral optic atrophy. A 3-year-old girl presented with vomiting and left hemiparesis. She had hypothalamic dysfunction, right ptosis, right monocular nystagmus, left facial palsy, left hemiparesis, and left pes adductus. Neuroimaging studies showed obstructive hydrocephalus with a large suprasellar calcified tumor with a ring-like enhancement mimicking craniopharyngioma. Visual-evoked potentials showed delayed latency of N75 in the right occipital lead. The tumor, a pilocytic astrocytoma in the right optic tract and chiasma, was partially removed via a right frontotemporal craniotomy. The right optic nerve had shrunk to half the normal diameter and became twisted downwardly. Intracranial pressure (ICP) increased to 40 cm H2O. The fundus had bilateral optic atrophy without disc swelling. To our knowledge, this is the first report of a lamina/dot sign of the optic disc in a small child with a brain tumor and a normal neuroretinal fiber layer. These ocular findings may result from possible interruption of the axonal flow caused by the tumor and not increased ICP.
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PMID:Optic glioma with characteristic bilateral optic atrophy in a 3-year-old girl. 1070 32

The strong tendency of malignant glioma cells to invade locally into surrounding normal brain precludes effective surgical resection, reduces the efficacy of radiotherapy, and is associated with increased resistance to chemotherapy regimens. We report that the N-terminal FERM domain of Pyk2 regulates its promigratory function. A 3-dimensional model of the Pyk2 FERM domain was generated and mutagenesis studies identified residues essential for Pyk2 promigratory function. Model-based targeted mutations within the FERM domain decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate glioma cell migration but did not significantly alter the intracellular distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments containing analogous mutations exhibited reduced capacity to inhibit glioma cell migration and Pyk2 phosphorylation relative to expression of an autonomous wild type FERM domain fragment. These results indicate that the FERM domain plays an important role in regulating the functional competency of Pyk2 as a promigratory factor in glioma.
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PMID:Critical role of the FERM domain in Pyk2 stimulated glioma cell migration. 1696 67

Acute hyponatremia, following neurosurgery, results from inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW). CSW is due to abnormally high atrial or brain natriuretic peptides (ANP, BNP), which block all stimulators of zona glomerulosa steroidogenesis, resulting in mineralocorticoid deficiency. A 3 year-old girl presented CSW at day 4, after resection of craniopharyngioma and hypophysectomy. Hyponatremia, hyperkalemia and high natriuresis occurred on day 8, with low renin and aldosterone and elevated BNP 120.3 ng/ml (undetectable before surgery). Fludrocortisone 100 microg/day controlled natriuresis and restored electrolytes within 24 hours. A 5 year-old boy presented CSW at day 6 after partial resection of optic glioma. Fludocortisone 100 microg/day restored electrolytes within 8 hours. ANP was elevated, 60.6 ng/l, aldosterone and renin were low. Fludrocortisone supplementation should be considered in CSW, as excessive natriuresis is controlled, and electrolytes are easily restored, avoiding life-threatening complications of this complex disorder.
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PMID:Mineralocorticoid deficiency in post-operative cerebral salt wasting. 1805 34

A 3-step glioblastoma-tropic delivery and therapy method using nanoparticle programmed self-destructive neural stem cells (NSCs) is demonstrated in vivo: 1) FDA-approved NSCs for clinical trials are loaded with pH-sensitive MSN-Dox; 2) the nanoparticle conjugates provide a delayed drug-releasing mechanism and allow for NSC migration towards a distant tumor site; 3) NSCs eventually undergo cell death and release impregnated MSN-Dox, which subsequently induces toxicity towards surrounding glioma cells.
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PMID:Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy. 2387 26


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