Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of neurotensin on pancreatic carcinogenesis induced by azaserine was investigated in Wistar rats. Rats were given weekly injections of 10 mg/kg body weight of azaserine for 25 weeks and 200 micrograms/kg body weight of neurotensin in depot form every other day for 62 weeks. Carcinogen-induced pancreatic lesions were examined by histochemical techniques, and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histological analysis showed that prolonged administration of neurotensin significantly reduced the volume (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the ultimate development of pancreatic cancer. Histologically, pancreatic adenocarcinomas occurred at a significantly lower rate in rats treated with neurotensin than in untreated rats. Administration of neurotensin also significantly decreased the labelling indices of carcinogen-induced pancreatic lesions, but not of the surrounding acinar cells. These findings indicate that neurotensin inhibits pancreatic carcinogenesis, and that this may be related to the reduction of ATPase-positive lesions and to the inhibition of cell proliferation in neoplastic lesions of the pancreas.
Int J Cancer 1991 Feb 01
PMID:Inhibition by neurotensin of azaserine-induced carcinogenesis in rat pancreas. 199 48

The H2-antagonist loxtidine and the H+/K(+)-ATPase inhibitor omeprazole inhibit gastric acid secretion and both have been associated with the appearance of gastric tumours in rat cancer studies. Loxtidine is not genotoxic in a range of in vitro and in vivo assays. As false negative results can occur if the organotropic nature of the drug is not considered, both drugs were evaluated using an assay which estimates the uptake of tritiated thymidine by cells of the gastric mucosa (the target tissue) in comparison with the positive control, N-methyl-N-nitro-nitrosoguanidine (MNNG), which others have shown to induce genetic damage in the stomach mucosa of rats. Such uptake may be, in part, indicative of unscheduled DNA synthesis (UDS) resultant from genotoxic damage. Serum gastrin levels were also determined at various times after either loxtidine or omeprazole treatment. Increased uptake of tritiated thymidine was only obtained after omeprazole or MNNG treatment, when this was estimated scintillometrically. The nature of the formulation of omeprazole was critical. The uptake of tritiated thymidine was greatest when omeprazole was administered in vehicle which had been buffered to pH 9. These effects were unlikely to be due to the trophic effects of gastrin since serum gastrin levels were similar after either loxtidine or omeprazole treatment. Autoradiographic analysis of stomach sections was also carried out and revealed a 2- to 3-fold increase in the number of labelled cells within the fundic mucosa as compared to the control values after treatment with MNNG or Losec (enteric coated granules of omeprazole).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Uptake of tritiated thymidine by cells of the rat gastric mucosa after exposure to loxtidine or omeprazole. 203 67

The purpose of this study was to determine if the dietary antioxidant selenium could inhibit hepatocarcinogenesis induced by peroxisome proliferators, which are hypothesized to induce tumors by increased production of hydrogen peroxide or other reactive oxygen species. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (0.04, 0.2, or 1.0 ppm) of selenium for 6 or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci at 21 months were lower in rats fed higher levels of selenium (no foci or tumors were seen at 6 mo). Indices of oxidative damage in the liver (thiobarbituric acid reactants, conjugated dienes, and lipid-soluble fluorescence products), however, were not decreased in rats fed the high-selenium diet. Therefore, selenium was protective against ciprofibrate-induced hepatocarcinogenesis, but not by reducing the degree of oxidative damage. The liver selenium and glutathione concentrations, and liver selenium-dependent glutathione peroxidase activity, increased as dietary selenium increased. Therefore, inhibition of carcinogenesis by selenium was correlated with increased levels of glutathione and glutathione peroxidase, but these did not inhibit the indices of oxidative damage. Peroxisomal beta-oxidation also increased with the dietary selenium content; it therefore does not appear to be a factor in the inhibition of hepatocarcinogenesis in rats fed higher levels of selenium.
Nutr Cancer 1990
PMID:Effect of dietary selenium on the induction of altered hepatic foci and hepatic tumors by the peroxisome proliferator ciprofibrate. 208 22

The interaction of the antiestrogen tamoxifen (Tx) with calmodulin (CaM) was investigated by cross-linking between the protein and [3H] tamoxifen aziridine. We observed that CaM binds Tx in a Ca2(+)-dependent manner and that two components are involved in the binding, with apparent dissociation constants (Kd) of about 6 nM and 9 microM. The high affinity binding site has a maximal capacity of 25 pmol/mg protein, whereas the low affinity binding site has a Bmax value of 120 nmol/mg protein. The stimulatory effect of Ca2+ is maximal at the pCa value of 5, and it is noncompetitively inhibited by Mg2+. In the micromolar range, the cation-dependent interaction of Tx with CaM exhibits positive cooperativity (nH = 1.4) and it is specific in the sense that it is inhibited by unlabeled Tx and by the CaM antagonist trifluoperazine. In contrast, no specificity was observed for the Tx binding, which is cation independent. Tx in the nanomolar range forms complexes with CaM which can be visualized by fluorography after electrophoretic separation in a polyacrylamide gel. Furthermore, CaM antagonism of Tx was observed with respect to inhibition of the CaM effect on the RBC membrane (Ca2(+) + Mg2+)-ATPase. The results indicate that Tx may alter Ca2(+)-dependent processes by interacting directly with CaM.
Cancer Res 1990 May 01
PMID:Ca2(+)-dependent binding of tamoxifen to calmodulin isolated from bovine brain. 213 60

The effect of tetragastrin on pancreatic tumors induced by azaserine was investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight of azaserine and 1 mg/kg body weight of tetragastrin as a suspension in olive oil every other day. Carcinogen-induced pancreatic lesions were examined by histochemical techniques, and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histological analysis showed that prolonged administration of tetragastrin had little or no influence on the number and size of the carcinogen-induced pancreatic lesions, although it caused significantly increased cell proliferation, indicated by a greater labelling index of the pancreatic acinar cells.
Int J Cancer 1990 Sep 15
PMID:Effect of tetragastrin on azaserine-induced carcinogenesis in rat pancreas. 214 63

The effect of each of twelve mammalian lignan derivatives on the growth of human mammary tumor ZR-75-1 cells was examined. At a concentration less than 10 micrograms/ml, tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol(hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC50) of 2.1 micrograms/ml. Hattalin inhibited membrane Na+, K(+)-ATPase of canine kidney cortex. It also inhibited the ATPase of the plasma membrane fraction from both cultured cells and a section of human breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane ATPase from either ZR-75-1 cells or breast carcinoma tissue was inhibited by 2.0 mM of ouabain, suggesting that the target ATPase of hattalin was other than ouabain-sensitive ATPase. The relative incorporation of [3H]thymidine per 1 x 10(5) cells into the acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 micrograms/ml of hattalin, while a marked decrease resulted from 1-10 micrograms/ml of 5-fluorouracil (5-FU). These results suggest that the suppressive effect of hattalin on tumor cell growth may not occur through inhibition of DNA synthesis but rather partly by inhibition of the plasma membrane ATPase other than Na+ and K(+)-dependent ones.
Cancer Invest 1990
PMID:Antiproliferative activity of mammalian lignan derivatives against the human breast carcinoma cell line, ZR-75-1. 214 33

Presence of chlorpromazine, a non-active-site inhibitor of Na(+)-K(+)-ATPase catalytic activity, in a reaction system exposed to 9.14 GHz CW radiation, resulted in approximately 23% inhibition. This effect was temperature-independent within the normal range for this protein. A low-level microwave field also inhibited the enzyme catalytic rate. Loci of chlorpromazine inhibition and of low-level microwave inhibition appear to be distinct and non-interactive under the conditions of this study. Use of enzyme reaction systems as models for microwave causation of leukemia and the possible involvement of pharmacological agents, such as ouabain and chlorpromazine, in this process has been considered.
Cancer Biochem Biophys 1990 Nov
PMID:Microwave effect upon chlorpromazine-inhibited kidney ATPase. 215 Apr 98

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediate-cell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) and gamma-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplastic transformation of the hepatocytes.
J Cancer Res Clin Oncol 1990
PMID:Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. 215 41

Some 3,3-dimethyltriazenes were shown to be capable of selective antimetastatic activity, i. e. preventing metastatic spreading of experimental tumors without affecting primary tumor or apparent metastases. The mechanism of antimetastatic effect of 3,3-dimethyltriazenes is discussed. The drugs represent a new promising pharmacological class of agents used for postsurgical adjuvant treatment of cancer. The effect of diazo derivatives produced in the course of disintegration of aromatic and heterocyclic 3,3-dimethyltriazenes on the in vitro activity of Ca-ATPase of the sarcoplasmic reticulum should be evaluated as a test-system for selecting new antimetastatic agents with cryptodiazonic properties.
 ...
PMID:[Rational approaches to selective synthesis of antimetastatic agents]. 215 97

The effects and modes of action of certain antineoplastic phospholipid analogues (racemic 1-O-octadecyl-2-O-methyl glycero-3-phosphocholine, BM 41.440, JH-1, CV-3988, and HePC) on (sodium plus potassium)-activated adenosine triphosphatase (Na,K-ATPase) and sodium pump activities were investigated. Inhibition of Na,K-ATPase in purified rat brain synaptosomal membranes by these lipids, in contrast to ouabain, was subject to membrane surface dilution and unaffected by whether the reaction was started with KCl, NaCl, or ATP. Kinetic analysis indicated that the analogues, again dissimilar to ouabain, were likely to interact directly or indirectly with sodium-binding sites of Na,K-ATPase located at the intracellular surface of the plasma membrane, a conclusion also supported by studies using the inside-out vesicles of human erythrocyte membranes. The studies also showed that ouabain (but not the lipids) increased the affinity constant of Na,K-ATPase for K+, whereas the lipids (but not ouabain) increased that for Na+. The lipids also inhibited 86Rb uptake by intact human leukemia HL60 cells at potencies quite comparable to those seen for inhibition of purified protein kinase C or Na,K-ATPase. It is suggested that Na,K-ATPase (sodium pump) might represent a hitherto unrecognized site of action for the lipid analogues, and that the antineoplastic effects of the agents might be due to, in part, inhibition of both protein kinase C and Na,K-ATPase and perhaps other membrane-associated enzymes.
Cancer Res 1990 May 15
PMID:Inhibition of protein kinase C, (sodium plus potassium)-activated adenosine triphosphatase, and sodium pump by synthetic phospholipid analogues. 215 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>