Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Literatures showed that cyclic AMP of cultured neoplastic cells of any kind was very low in concentration and also the effect of cyclic AMP and its derivatives on the malignant cells, especially on the malignant glioma, was already reported in vivo or in vitro from several neurosurgical units. The intrinsic content of cyclic AMP of the human cerebrum and the human brain tumors was first reported by authors in 1971. In this presentation the authors intended to confirm that the lower concentration of the cyclic AMP the more histologically malignant cerebral neoplasm, as well as in the cerebrospinal fluid, was observed. Concentration of cyclic AMP in the subcortical white matter, glioma, meningioma and medullobalstoma was much lower than in the gray matter tissue, however, it was not clear that the difference of the cyclic AMP concentration be possibly related to the malignancy of the human brain tumor. Furthermore, the cyclic AMP content of the cerebrospinal fluid of the patients with various brain tumor was not clearly different. The activity of adenyl cyclase was reported the highest in the synaptosome-containing fraction of the rat brain homogenate and this fact was significantly consistent with the finding that the highest concentration of the cyclic AMP was found in the human grey matter tissue. With the human brain gray matter authors determined successfully the activity of the human cerebral phosphodiesterase, which was probably localized in the post-synaptic membrane and was 158 nmole/mg protein/min. Its apparent Km was 0.9 x 10(-4) M. The results reported above have suggested the important participation of the cyclic AMP to cerebral synaptic transmission of nerve impulses, which was studied by light and electron-microscopic autoradiography utilizing the pulse labeling method with 3H-adenine. According to our study the majority of the adenyl cyclase of the human cerebrum was located synaptic structure and the finding obtained was quite compatible, as the first morphological study, with previously reported biochemical analyses. It was indicated that the cyclic AMP in the human brain was concerned to the cerebral synaptic transmission of nerve impulses and this should be very interesting and important to the clinical application for recovering cerebral function of neurosurgical patients.
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PMID:[Studies on cyclic 3', 5'-AMP system in human brain and its clinical application in Neurosurgical practice (author's transl)]. 17 18

Calmodulin (CaM), a calcium-binding protein, is present in human tumor tissues and in meningioma. Following a purification procedure using DEAE-cellulose and the polymeric resin 3520, the CaM content of tumor extracts was assayed using CaM-deficient phosphodiesterase (PDE). In the presence of low amounts of the extracts, a concentration dependent stimulation of PDE was observed. However, further addition of higher concentrations of the extract produced a marked inhibition of the CaM stimulation of PDE in 13 of 15 specimens. A wide range (2.44-51.31 units/1 mg tumor [wet weight]) of inhibitor concentration was noted. However, no detectable inhibitory activity of this magnitude was observed in normal human meningeal extracts. The final extracts showed no calcineurin-phosphatase activity in the presence of Ni++, a known activator of this phosphatase. SDS-polyacrylamide gel (10%) electrophoresis of the extracts revealed the typical calmodulin band at 17 kDa plus two additional bands with apparent molecular masses of 21 and 36 kDa respectively. These bands were not seen using normal meningeal extracts.
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PMID:Evidence for a calmodulin inhibitory substance(s) isolated from human meningiomas. 830 44

Meningiomas are the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although meningiomas are stratified according to their histology and clinical behavior, the underlying molecular genetics predicting aggressiveness are not thoroughly understood. We performed whole transcript expression profiling in 10 grade I and four grade II meningiomas, three of which invaded the brain. Microarray expression analysis identified deleted in colorectal cancer (DCC) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into DCC low expression (3 grade I and 3 grade II tumors), DCC medium expression (2 grade I and 1 grade II tumors), and DCC high expression (5 grade I tumors) groups. Comparison between the DCC low expression and DCC high expression groups resulted in 416 DEGs (p-value<0.05; fold change>2). The most significantly downregulated genes in the DCC low expression group comprised DCC, phosphodiesterase 1C (PDE1C), calmodulin-dependent 70kDa olfactomedin 2 (OLFM2), glutathione S-transferase mu 5 (GSTM5), phosphotyrosine interaction domain containing 1 (PID1), sema domain, transmembrane domain (TM) and cytoplasmic domain, (semaphorin) 6D (SEMA6D), and indolethylamine N-methyltransferase (INMT). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (C5orf63), homeodomain interacting protein kinase 2 (HIPK2), and basic helix-loop-helix family, member e40 (BHLHE40). Biofunctional analysis identified as predicted top upstream regulators beta-estradiol, TGFB1, Tgf beta complex, LY294002, and dexamethasone and as predicted top regulator effectors NFkB, PIK3R1, and CREBBP. The microarray expression data served also for a comparison between meningiomas from female and male patients and for a comparison between brain invasive and non-invasive meningiomas resulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, DCC may constitute a valid biomarker to identify those benign meningiomas at risk for progression.
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PMID:Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression. 2709 27