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

An evaluation of the 5'-nucleotide phosphodiesterase isozyme V (5'-NPD-V) test for liver metastases in gastrointestinal (GI) cancer patients was undertaken with a coded serum panel provided by NCI Mayo Clinic. Upon decoding, 28 of 30 patients (93%) with known liver metastases and 11 or 32 patients (36%) with no known liver metastases were positive. In 20 patients with various benign GI diseases, there were 6 (30%) positive for 5'-NPD-V. 2 of these positive patients with benign GI diseases had identifiable liver disorders. Statistical analysis of the data supports 5'-NPD-V can discriminate between GI cancer patients with and without liver metastases and patients with benign GI diseases.
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PMID:Detection of liver metastases with 5'-nucleotide phosphodiesterase isozyme-V in gastrointestinal cancer patients. 625 58

A novel structural analogue of cyclic AMP has been synthesized. This compound has been found to activate protein kinase from skeletal muscle (Ka 5.0 microM). It is virtually resistant to degradation by beef heart cAMP phosphodiesterase. It is an inhibitor of this enzyme with an [I]50 of 47.0 microM. The proliferation of cancer cells (HT-29) is inhibited by this compound. It represents the first example of a 2',3'-cyclic nucleotide with marked biological activity.
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PMID:Methyl 5'-(6-aminopurin-9-yl)-5'-deoxy-beta-D-ribofuranoside 2',3'-cyclic monophosphate: a novel, biologically active, structural analogue of cyclic AMP. 625 19

The effect of the alkylating agent 2,3,5-tris(ethyleneimino)benzoquinone (Trenimon) on the uptake of 2-aminoisobutyric acid, 1-aminocyclopentane-1-carboxylic acid (cycloleucine), 3-O-methyl-D-glucose, and 86Rb was studied. All transport studies were performed at nonsaturating conditions where the specific transport system was rate limiting for the uptake. The activities of all systems are reduced after treatment with the alkylating agent. The impairment of the plasma membrane is expressed 30 sec after exposure to the drug, as measured by the 86Rb uptake, and lasts for at least 12 hr according to the reduced 3-O-methyl-D-glucose uptake. Inhibition of protein synthesis by cycloheximide for 2 hr does not affect the uptake of 86Rb. The short interval which is necessary before an inhibition of 86Rb uptake can be registered and the resistance of the 86Rb transport system to an inhibition of protein synthesis are considered as indicative for a direct alkylation of a membrane constituent. Treatment with the alkylating agent increases the cyclic adenosine 3':5'-monophosphate of the cells. This effect is not due to an effect on adenylate cyclase or the membrane-bound cyclic adenosine 3':5'-monophosphate phosphodiesterase. In view of the known correlations between plasma membrane functions and the regulation of cell division, it is proposed that the growth inhibition by Trenimon of Ehrlich ascites tumor cells may be caused by its interaction with the plasma membrane.
Cancer Res 1981 Jan
PMID:Interaction of the alkylating antitumor agent 2,3,5-tris(ethyleneimino)benzoquinone with the plasma membrane of Ehrlich ascites tumor cells. 625 62

When applied to mouse skin in vivo, both the strong tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 nmol) and the divalent cation ionophore A 23187 (200 nmol) caused the same responses, i.e., skin inflammation and prostaglandin E2-mediated epidermal hyperplasia. In both cases, these events were accompanied by certain biochemical reactions in the epidermis such as an increase in the biosynthesis of and sensitivity to prostaglandin E2, increase in ornithine decarboxylase and phosphodiesterase activities, and refractoriness of cyclic adenosine 3':5'-monophosphate production to beta-adrenergic stimulation. In contrast to A 23187, TPA did not induce degranulation of mast cells; whereas, in contrast with TPA, A 23187 did not show tumor-promoting activity. These results indicate that the observed biological effects of TPA are no indication of tumor-promoting ability and that, on the other hand, the mitogenic effects of A 23187 are possibly not due to its properties as a calcium ionophore.
Cancer Res 1981 Feb
PMID:Prostaglandin E-mediated mitogenic stimulation of mouse epidermis in vivo by divalent cation ionophore A 23187 and by tumor promoter 12-O-tetradecanoylphorbol-13-acetate. 625 72

In this study, adenylate cyclase, phosphodiesterase and cyclic adenosine 3',5'-monophosphate (cAMP) levels were measured in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors with different growth characteristics in both intact and ovariectomized rats. Tumors were classified as growing, stable, or regressing over a 10-14-day period before excision. Regressing or static tumors had a higher cAMP concentration relative to tumors that were growing actively. This was due to high adenylate cyclase activity and low phosphodiesterase (both high and low Km) activities. Although estrogen deprivation resulted in a much greater rate of tumor regression than would occur spontaneously under normal conditions, the levels of adenylate cyclase, phosphodiesterases and cAMP were the same in tumors obtained from either intact or ovariectomized rats, when comparisons were made within the same category of tumor. These observations suggest that cAMP metabolism is independent of estrogen, since it is related to enhancement or retardation of growth rather than to the presence of absence of estrogen.
Cancer Lett 1980 Jan
PMID:Regulation of cyclic adenosine 3',5'-monophosphate in relation to growth of dimethylbenz[a]anthracene-induced mammary tumors in rats. 626 41

The results of determination of the serum 5'-NPDase isozymes in 95 cases of primary liver carcinoma and other kinds of disease are presented. The 5'-NPDase-V was positive in 83.2% of primary liver cancer cases. This test might be a useful supplement to AFP determination, especially in AFP-negative liver cancer patients. In most patients who had undergone successful liver resection for primary carcinoma, the test became negative. A positive 5'NPDase-V test in patients with cancer elsewhere in the body may suggest liver metastasis. In addition, this test may be of some help in the differentiation of primary liver cancer from other kinds of liver disease. The problem of "false-positive" results of this test is discussed.
Int J Cancer 1980 Jul 15
PMID:The significance of 5'-nucleotide phosphodiesterase isozymes in the diagnosis of liver carcinoma. 626 4

We have been studying the regulation of growth by cyclic adenosine 3':5'-monophosphate (cyclic AMP) and other factors in untransformed (K16) and chemically transformed (W8) rat liver epithelial cells. Initially, we found that 8-bromocyclic adenosine 3':5'-monophosphate was a more potent inhibitor of cell replication in K16 than in W8 cells. In addition, the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX) caused marked growth inhibition in K16 but not in W8 cells. Through the use of cholera toxin (CT) with or without MIX, we elevated intracellular cyclic AMP levels in a quantifiable fashion. With CT alone or combined with MIX, we observed a dose-dependent morphological change in W8 cells, which consisted of extensive "process" formation. K16 morphology was not altered at any concentration of CT +/- MIX tested. K16 cell growth was only marginally inhibited by CT alone, but markedly inhibited by CT plus MIX. W8 cell growth was moderately inhibited by CT alone or combined with MIX. Analysis of cyclic AMP levels revealed that, at all concentrations of CT +/- MIX and at all time periods tested, W8 cells produced significantly more cyclic AMP than K16 cells. It appears that morphological changes and growth inhibition are not necessarily linked and that MIX may inhibit K16 cell replication by means other than its ability to increase intracellular cyclic AMP levels.
Cancer Res 1981 Oct
PMID:Differential sensitivity of normal and chemically transformed epithelial cells to cholera toxin. 626 34

Individual human infiltrating ductal carcinomas and fibroadenomas were sectioned frozen to yield an alternating sequence of stained and lyophilized material. Stained preparations were used as references permitting microdissection of regions of tumor involvement in the corresponding dried sections. Tissues quantities of 5 to 25 micrograms dry weight were incubated under mineral oil in reaction volumes of 5 microliters and analyzed for cyclic adenosine 3':5'-monophosphate phosphodiesterase (PDE). The observed affinity constants for the 27,000 x g soluble PDE from benign tumors were 4.7 and 49.9 microM, while those for malignant tumors were 6.3 and 28.5 microM. The soluble enzyme of both tumor types eluted in three peaks on DEAE-Sephacel microcolumns. Both tumor types possessed a PDE activator eluting at 350 mM NaCl, although endogenous PDE activities were unaffected by additions of either this activator or 200 microM ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid. Individual microsections of benign tumors contained total PDE levels 2-fold higher than those of malignant tumors. Homogenates prepared from pooled microsections of the same tumors possessed only one-half of the total activity. Differential losses of enzyme in various preparation schemes as well as the use of tumor samples differing in cell density were suggested to account for some of the apparently conflicting literature values for breast tumor PDE.
Cancer Res 1982 May
PMID:Implementation of micromethods to resolve problems of human breast tumor heterogeneity in analysis of cyclic 3':5'-nucleotide phosphodiesterase. 627 80

The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic glucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1 greater than PGE1 greater than PGB1 greater than PGF2 alpha. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virus-stimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormone-like substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.
J Cancer Res Clin Oncol 1982
PMID:Role of natural prostaglandins in the control of murine mammary tumor virus expression. 628 Dec 84

5'-nucleotide phosphodiesterase isozyme-V (5'-NPD-V) was evaluated in 85 biopsy proven breast cancer patients as a potential marker for early liver metastasis. It correctly predicts liver metastasis in 6/7 (85.7%) patients with abnormal radiologic liver scan and 2/2 other patients with palpable liver. Serum glutamic-oxaloacetic transaminase (SGOT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total bilirubin (B) were also determined in 79 of these patients as routine liver function tests (LFT). Forty-one out of 79 from this group had all four markers all within normal limits. Yet of the 41 patients, 12 patients were found positive for 5'-NPD-V. Of these 12, one was found to have liver metastasis at surgery and one had abnormal liver scan. Five other patients had liver dysfunction and one had been diagnosed as an alcoholic. Four others had no evidence of either liver problems or liver metastasis, but follow-up data were lacking. This retrospective study, therefore suggests that there is a definite advantage to include the 5'-NPD-V in the liver profile studies for breast cancer patients, although a positive 5'-NPD-V may only indicate liver repair or liver regeneration. Long-term prospective studies of these tests with breast cancer patients should be worthwhile. No relation was found between 5'-NPV-V and axillary lymph node involvement or the estrogen receptor status of the excised tumor. Thus there is no evidence currently that the appearance of the 5'-NPD-V in serum is related to lymph node metastases or hormonal control.
Cancer 1982 Jul 15
PMID:Evaluation of 5'-nucleotide phosphodiesterase isozyme-V as a predictor for liver metastasis in breast cancer patients. 628 35


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