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)

This paper describes the cellular and tissue distribution of P-glycoprotein (P-GP) (mdr1 gene product), the role of P-GP in vivo and immunodiagnosis of multi-drug-resistant cancers. We mainly used MRK 16 monoclonal antibody (MAb) reactive with P-GP. P-GP was found to be expressed very strongly in the adrenal cortex of adults and strongly in the renal tubules of the kidney, capillary blood vessels of the brain, and also in placenta. Interestingly, P-GP was not distributed in fetal and neonatal adrenals, and thus may be closely related to adrenal maturation. A high level of P-GP expression was also seen in all cases of functional hormone-producing adrenal tumor, one case of insulinoma, two cases of untreated colonic cancer, one case each of untreated lung cancer, gastric cancer and breast cancer, six cases of renal cell carcinoma and 17 cases of bladder cancer. Using flow cytometry and immunocytochemistry, we investigated the reactivity of MRK 16 MAb with peripheral human mononuclear cells (mainly blastic cells and lymphocytes) from 31 patients with leukemia or malignant lymphoma. Reactivity with MRK 16 MAb was observed in five cases. Some cases reflected the prior administration of adriamycin, vincristine and VP-16, which are known to induce P-GP expression. P-GP-MRK 16-protein A-Sepharose complex derived from human adrenal possessed marked ATPase activity. These data suggest that P-GP may play a physiological role in the human adrenal. Finally, diagnostic criteria of multi-drug-resistant cancers are presented.
 ...
PMID:Expression and functions of P-glycoprotein (mdr1 gene product) in normal and malignant tissues. 197 61

In 55 inoperable patients with lung cancer the use of tinidizole and metronidazole with X-ray therapy intensified the immunoregulative disbalance, increased the quantity of circulative immune complexes and reduced the Na+K+-ATPase activity of erythrocyte membranes in contrast to the data obtained from patients receiving only X-ray therapy. Thus the data obtained may be the basis for the use of the correcting therapy in inoperable patients with lung cancer.
 ...
PMID:[Effect of electron-acceptor compounds on the immunoregulatory mechanisms and ATPase activity of the erythrocyte membranes from patients with inoperable lung cancer]. 296 3

The activity of erythrocyte membrane Ca2+, Mg2+-ATPase (EC 3.6.1.3) was studied in 22 patients suffering from lung cancer. The enzyme activity was found to increase. The observed changes indicate significant disturbances in the mechanisms of ion transport in organs and tissues during tumour growth.
 ...
PMID:[Ca2+, Mg2+-ATPase activity of the erythrocyte membrane in patients with lung cancer]. 614 25

Normal human bronchial epithelial (NHBE) cells are the putative progenitor cells of all types of lung cancer. NHBE cells immortalized by SV40 T-antigen retain many characteristics of the primary cells and are a useful model for investigating the role of oncogenes, tumor suppressor genes, and certain chemical carcinogens in the molecular pathogenesis of lung cancer. In this study, SV40 T-antigen-positive cells (BEAS-2B) were characterized for their metabolic functions and were shown to continue to express epoxide hydrolase, glutathione S-transferase pi, glutathione peroxidase, and catalase. To increase their metabolic activity towards human procarcinogens, human cytochrome P450 1A2 (CYP1A2) was stably expressed by introducing CYP1A2 cDNA into BEAS-2B cells either by infection with a high-titer recombinant retrovirus (pXT-1A2) or by transfection with a CYP1A2 expression vector (pCMV1A2), which produced the cell lines B-1A2 and B-CMV1A2, respectively. Cell lines established with either expression system expressed enzymatically active CYP1A2 protein and were 50- to 400-fold more sensitive to the cytotoxic effect of the carcinogen aflatoxin B1 (AFB1) than the corresponding control cell lines. The cytotoxic effects of AFB1 were paralleled by increased metabolism of AFB1 and enhanced formation of the AFB1-N7 guanine adduct in B-CMV1A2 cells. Cytotoxicity and adduct formation correlated with a significantly higher protein expression of CYP1A2 by the cytomegalovirus promoter-driven plasmid. Since this human epithelial cell line is the precursor cell type of lung cancer, has normal phase II enzymes, and exhibits highly reproducible expression of phase I enzymes, this in vitro model should aid in the evaluation of putative human carcinogens and anticarcinogens.
 ...
PMID:Activation of promutagens in a human bronchial epithelial cell line stably expressing human cytochrome P450 1A2. 791 94

Although the mechanisms responsible for alveolar liquid clearance have been studied in several species, there has not been any information regarding the effect of ion transport agonists or antagonists on alveolar liquid clearance in the human lung. Therefore, we studied alveolar liquid clearance in the recently resected human lung from patients who underwent surgery for lung cancer. A test solution of 40 ml of isosmolar albumin solution was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air spaces very slowly, the concentration of alveolar protein over 4 h was used to quantify alveolar liquid clearance. Basal alveolar liquid clearance was 12 +/- 2% over 4 h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, and ouabain (10(-3) M), an inhibitor of Na,K-ATPase activity, reduced alveolar liquid clearance by 40 and 49%, respectively (p < 0.005). Terbutaline (10(-3) or 10(-4) M) doubled alveolar liquid clearance to 28 +/- 9% over 4 h (p < 0.05). Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in alveolar liquid clearance. In conclusion, (1) alveolar liquid clearance in the human lung can be markedly reduced by inhibition of apical sodium channel uptake or Na,K-ATPase activity, and (2) beta-adrenergic stimulation markedly increases the rate of alveolar liquid clearance in the resected human lung without pulmonary perfusion.
 ...
PMID:Alveolar fluid clearance in the resected human lung. 804 6

Little information is available regarding the effect of ion transport agonists and antagonists on ion transport in the human lung. Therefore, we studied ion transport in lungs resected from patients with lung cancer. A test solution of 45 ml of isosmotic albumin was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air space very slowly, the concentration of alveolar protein over 4 h was used to quantify the volume of alveolar fluid. Ion transport was measured from the changes in ion concentrations and the volume of alveolar fluid. In the basal condition, the net efflux of Na+ and Cl- were 4.66 +/- 0.83 mEq/l/h and 3.52 +/- 0.84 mEq/l/h, respectively. In contrast, the net influx of K+ was 0.44 +/- 0.07 mEq/l/h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, ouabain (10(-3) M), an inhibitor of Na(+)-K+ ATPase, and hypothermia (8 degrees C) reduced the efflux of Na+ and Cl-. Ouabain and hypothermia increased the net influx of K+. Terbutaline (10(-3) or 10(-4) M) increased the efflux of Na+ and Cl-, but did not affect the influx of K+. Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in the transport of Na+ and Cl-. Alveolar fluid clearance was closely correlated with Na+ transport and with Cl- transport. However, the values of Na+ transport were greater than those of Cl- transport. These data suggest that Na+ transport is accompanied by Cl- transport and fluid movement out of the alveolar space in resected human lungs.
 ...
PMID:[Transport of ions across alveolar epithelial cells in resected human lungs]. 853 92

We examined the effect of selective thromboxane A2 (TXA2) receptor antagonists, calcium 5(Z)-1R, 2S, 3S, 4S-7-[3-phenylsulphonylaminobicyclo [2.2.1] hept-2-yl]-5-heptonoate hydrate (S-1452) and +/- -7-(3,5,6,-trimethyl-1,4-benzoquinon-2-yl)-7-phenylhaptanoic acid (AA-2414), on sensitivity to cis-diamminedichloroplatinum (II) (CDDP) in non-small-cell lung cancer cell lines. IC50 values to CDDP using MTT assay were decreased 2.1- and 4.6-fold respectively by treatment with 250 or 500 microM S-1452, for a 2 h simultaneous drug exposure, and those of PC-9/CDDP, a CDDP-resistant cell line, were decreased 3.1- and 6.1-fold. Sensitivity to carboplatin was also enhanced by the treatment with S-1452. IC50 values to CDDP and carboplatin were decreased by treatment with AA-2414 in a dose-dependent manner. Isobologram analysis showed that the combination of CDDP with S-1452 or AA-2414 produced supra-additive or additive effects in each cell line. Neither glutathione content nor glutathione S-transferase activity was changed in either cell line by treatment with 500 microM S-1452. Accumulation of platinum into PC-9 and PC-9/CDDP was increased by the treatment in a dose-dependent manner. Na+, K+-ATPase activity of PC-9 and PC-9/CDDP was enhanced by the treatment of S-1452 in a dose-dependent manner. These data show that the TXA2 receptor antagonists may enhance the sensitivity of non-small-cell lung cancer cell lines to platinum agents. Increase in Na+, K+-ATPase activity induced by S-1452 may be the mechanism of its sensitising effect through increase in platinum accumulation.
 ...
PMID:Modulation of sensitivity to cis-diamminedichloroplatinum (II) by thromboxane A2 receptor antagonists in non-small-cell lung cancer cell lines. 893 34

Cisplatin is the most active anticancer agent for lung cancer. It has been reported that intracellular accumulation of cisplatin is important in determining resistance to cisplatin, which may be modulated by Na+, K(+)-ATPase activity. On the other hand, it is well-known that sorbitol, a metabolite of glucose mediated by aldose reductase, reduces Na+, K(+)-ATPase in diabetic neuropathy. In this study, the effect of exogenous sorbitol on Na+, K(+)-ATPase activity and sensitivity to cisplatin was evaluated using human non-small-cell lung cancer (NSCLC) cell lines. In the NSCLC cell lines, EBC-1, PC-3, and RERF-LC-MS the cytotoxicities of cisplatin were impaired by exposure to sorbitol in these cell lines. Na+, K(+)-ATPase was inactivated and intracellular accumulation of cisplatin was decreased by the exposure. These results suggest that accumulation of sorbitol may induce resistance to cisplatin in NSCLC cells, and diabetes poorly controlled may be one of the determinants of the antitumor effect of cisplatin in NSCLC.
 ...
PMID:Exposure to sorbitol induces resistance to cisplatin in human non-small-cell lung cancer cell lines. 941 70

Thallium-201 single-photon emission computerized tomography (SPECT) was used to clarify the relationship between 201Tl uptake and the response in chemotherapy to platinum compounds in 21 patients with small-cell lung cancer. 201Tl-SPECT scans were obtained twice: at 15 min (early scan) and 120 min (delayed scan) after an intravenous injection of 111 MBq (3 mCi) of thallium-201 chloride. We obtained the uptake ratio from each scan and calculated the retention index:uptake ratio = region of interest uptake/contralateral normal lung uptake; retention index = (delayed ratio - early ratio)/early ratio. After 201Tl scintigraphy, 12 patients received chemotherapy consisting of platinum compounds and nine were treated with chemoradiation. Among patients receiving only chemotherapy, the retention index correlated with the responses to chemotherapy. In an in vitro study, ouabain, an inhibitor of the Na,K-ATPase pump, reduced sensitivity to cisplatin and inhibited intracellular thallium uptake in the small-cell lung cancer cell line. These studies suggest that 201Tl-SPECT is a useful indicator of response to chemotherapy with platinum compounds in small-cell lung cancer, and that Na,K-ATPase is commonly involved in transporting both thallium and platinum compounds into cancer cells.
 ...
PMID:Predicting chemotherapeutic response to small-cell lung cancer of platinum compounds by thallium-201 single-photon emission computerized tomography. 957 47

cis-Diamminedichloroplatinum(II) (CDDP) is a key anticancer agent. It has been reported that intracellular accumulation of CDDP is an important step as a determinant for resistance to CDDP, which may be modulated by Na+, K(+)-ATPase activity. In this study, the significance of membrane Na+, K(+)-ATPase activity and the role of thromboxane (TX) receptors were evaluated using human lung cancer cell lines. In the non-small-cell lung cancer (NSCLC) cell line, EBC-1, sensitivity to CDDP was improved by treatment with two different selective thromboxane receptor antagonists, calcium 5(z)-[1R,2S,3S,4S-7-[3-phenylsulfonylaminobicyclo [2.2.1]hept-2-yl]-5-heptenoate hydrate (S-1452), and (3R)-3-(4-fluorophenyl sulfonamido)-1,2,3,4-tetrahydro-9-carbazolepropanoic acid (BAYu3405). Na+, K(+)-ATPase was activated and intracellular accumulation of CDDP increased with treatment in EBC-1. In the small-cell lung cancer (SCLC) cell lines, SBC-1, sensitivity to CDDP and Na+, K(+)-ATPase activity did not change significantly, and intracellular accumulation of CDDP was not modulated. These results suggest the importance of the TX receptors as determinants of the sensitivity to CDDP in NSCLC cell lines. However, Na+, K(+)-ATPase activity and the role of TX receptors may not be so significant in the resistance mechanisms to CDDP in SCLC cell lines. In EBC-1 cells, the specific binding of S-145 was evident, but not in SBC-1 cells. The difference in TX receptors in NSCLC and SCLC cell lines may be one of the reasons for the variety of the antitumor effects of CDDP in chemotherapy for lung cancer.
 ...
PMID:Role of thromboxane receptor on the intracellular accumulation of cis-diamminedichloroplatinum(II) in non-small-cell but not in small-cell lung cancer cell lines. 961 69


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