Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione peroxidase (GSH-Px), glutathione S-transferase (GSH-Tr) and glutathione reductase (GSSG-Rx) activities have been determined in normal and neoplastic human breast tissues. Large interindividual variations in the activities of all enzymes tested were found in both tumor and non-tumor specimens. In general a significant increase in the activities of the 3 enzymes was found in tumors, whereas in fibroadenoma they were as high as in healthy tissues. When a comparison was made between normal and neoplastic tissues of the same individual, GSH-Tr and GSSG-Rx activities were found to be higher in 15 and 11 cases, respectively, out of 17. GSG-Px activity was higher in all cases. From measurement of GSG-Px activity with both H202 and cumene hydroperoxide, it was deduced that human breast contains only the selenium-dependent form.
 ...
PMID:Glutathione peroxidase, glutathione S-transferase and glutathione reductase activities in normal and neoplastic human breast tissue. 299 88

In an attempt to characterize metabolism enzymes of the estrogen-induced kidney tumor in male Syrian hamsters, the activities of enzymes involved in drug and glutathione metabolism were determined in tumor tissue. Kidney tumors were induced in male Syrian hamsters by treatment with estradiol for 8 months. Cytochrome P-450 and cytochrome b5 concentrations in tumors were below detectable levels. However, when cytochrome P-450-mediated oxidation was analyzed by product formation assays, the oxidation of E-diethylstilbestrol to diethylstilbestrol-4',4"-quinone by tumor microsomes was 10-20% of the rate found in control microsomes. In kidney tissue surrounding estrogen-induced tumors, cytochrome P-450 and b5 contents were 50-60% less than those in untreated kidney. Activities of reducing enzymes of drug metabolism (cytochrome P-450, cytochrome b5 and NADH:cytochrome c reductases), glutathione metabolism enzymes (glutathione peroxidase, glutathione transferase, glutathione reductase, and gamma-glutamyl transpeptidase), and free radical scavenging enzymes (superoxide dismutase, catalase, and quinone reductase) in tumor were significantly lower than in untreated kidney tissue. The activities of these enzymes in renal tumor surrounding tissue were between those observed in tumor and control kidney. Glucose-6-phosphate dehydrogenase activity was increased by 50% in surrounding tissue and 430% in tumor compared to values in untreated controls. The decreased enzyme activity levels in hormone-exposed tissue surrounding tumors likely represented an adaptation of this tissue to the neoplastic environment induced by chronic estrogen treatment.
 ...
PMID:Characterization of drug metabolism enzymes in estrogen-induced kidney tumors in male Syrian hamsters. 304 47

The in vivo effects of hyperoxia were studied in lung colonies formed by B16-F10 melanoma cells in C57BL/6 mice. Several antioxidant defenses were found to change with in vivo exposure: glutathione reductase and glucose-6-phosphate dehydrogenase activities decreased as compared with levels in the cultured cells, glutathione peroxidase activity dramatically increased, and Mn-superoxide dismutase activity and levels of total glutathione were similar in vivo and in vitro. Exposure of tumor-bearing animals to 70%, O2 for 3 weeks did not alter the antioxidant defenses measured in the tumors. One hundred percent O2 exposure did not affect either initial arrest or subsequent retention of radiolabeled B16-F10 cells in the lung. Likewise, hyperoxia did not appear to alter cell division in B16-F10 cells growing in the lung. These results are consistent with our previous studies indicating that the B16-F10 cell line is resistant to levels of O2 in vivo that adversely affect other tumor cell lines.
 ...
PMID:Effects of hyperoxia on B16-F10 cells in vivo. 318 29

Mice were given i.v. injections of various tumor cell lines and, beginning 24 h later exposed for 3 weeks to 70% oxygen. Hyperoxia reduced the number of lung colonies derived from MT-7 cells (originally a mammary carcinoma) and of the lung-tumor derived cell lines 498 and Line-1 early passage. Lung colonies derived from Line-1 late passage, lines M109, B16-F10 and Lewis lung carcinoma were oxygen resistant. Lung metastases following i.m. injection of MT-7 cells were oxygen-sensitive and metastases derived from B16-F10 cells or Lewis lung carcinoma were oxygen resistant. Pre-exposure of mice for 48 h to 100% oxygen enhanced colony formation for all cell lines examined whereas exposure to 100% oxygen after i.v. injection only curtailed the growth of the cell lines previously shown to be sensitive to 70% oxygen. There was no correlation between oxygen sensitivity or resistance and the levels of total glutathione or activities of superoxide dismutase (SOD), glutathione reductase or peroxidase or glucose 6-phosphate dehydrogenase in the cell lines. However, upon injection in mice a resistant cell line increased its anti-oxidant defense mechanisms while growing in vivo whereas a sensitive cell line failed to show such adaptation.
 ...
PMID:Effects of hyperoxia on growth of experimental lung metastasis. 334 81

In the present studies we have compared the levels of glutathione (GSH) and GSH-related enzymes in lung tumors and corresponding normal tissues obtained from the same individuals. We have also immunologically quantitated the relative amounts of glutathione S-transferase pi (or GST-P) type antigen in tumors and adjacent normal tissues from five patients. GST activities towards 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid were found to be elevated in tumors from two out of five patients (patients #1 and 4), whereas the activity towards these substrates was markedly suppressed in the tumor tissue from one of the patients (#5). Immunotitration and Western blot studies using antibodies raised against pi-type GST isoenzymes of human lung and placenta indicated induction of GST pi-type isoenzyme in tumors from patients #1 and 4 and suppression of this isoenzyme in tumor from patient #5. The tumors from patients #2 and 3 did not show any increase in GST activity or GST pi-type antigen. Except for the tumor from patient #5, the GSH content was higher in the tumors from other patients. GSH reductase activity was found to be elevated in tumors of all the patients examined in this study. These results indicate that GSH and GSH related enzymes are differentially altered in lung tumors and GSH levels and GST pi- or GST-P-type isoenzyme(s) are not uniformly elevated in all tumors.
 ...
PMID:Glutathione S-transferase isoenzymes in human lung tumors. 340 73

The development of new nitrosoureas is described using selected examples. Results obtained with water-soluble analogs and with compounds linked to biomolecules as for instance amino acids, oligopeptides and steroids, are presented. The pronounced antineoplastic effect of some water-soluble analogs is paralleled by an increased rate of DNA-interstrand cross-links and by an increased suppression of hematopoietic stem cells. The suppression of bone marrow stem cells is followed by their rapid regeneration. Water-soluble nitrosoureas induce significant less inhibition of glutathione reductase as compared with established compounds. With regard to long-term toxicity and carcinogenicity water-soluble are superior to established compounds as for instance BCNU. Linking of the nitrosourea moiety to amino acids and oligopeptides led to some analogs with outstanding therapeutic ratio. Out of a group of steroid-linked nitrosoureas, CNC-L-alanine-estradiol-17-ester (CNC-ala-17-E2) is chosen to demonstrate the possibility of reducing bone marrow toxicity despite unchanged or increased therapeutic activity by attachment of the nitrosourea moiety to a steroid. Results of a comparative interspecies in vitro evaluation of CNC-ala-17-E2 in transplanted MXT mammary carcinoma of the mouse, MNU-induced autochthonous rat mammary carcinoma and primary human mammary carcinomas are presented and the question is discussed to what extent in vitro activity of such receptor agents using the tumor stem cell assay reflects their in vivo activity.
 ...
PMID:[Chemotherapeutic characterization of new nitrosourea compounds]. 341 33

From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.
 ...
PMID:Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines. 361 36

Exposure of target cells to a bolus of H2O2 induced cell lysis after a latent period of several hours, which was prevented only when the H2O2 was removed within the first 30 min of injury by addition of catalase. This indicated that early metabolic events take place that are important in the fate of the cell exposed to oxidants. In this study, we described two early and independent events of H2O2-induced injury in P388D1 macrophagelike tumor cells: activation of the glutathione cycle and depletion of cellular NAD. Glutathione cycle and hexose monophosphate shunt (HMPS) were activated within seconds after the addition of H2O2. High HMPS activity maintained glutathione that was largely reduced. However, when HMPS activity was inhibited--by glucose depletion or by incubation at 4 degrees C--glutathione remained in the oxidized state. Total pyridine nucleotide levels were diminished when cells were exposed to H2O2, and the breakdown product, nicotinamide, was recovered in the extracellular medium. Intracellular NAD levels fell by 80% within 20 min of exposure of cells to H2O2. The loss of NADP(H) and stimulation of the HMPS could be prevented when the glutathione cycle was inhibited by either blocking glutathione synthesis with buthionine sulfoximine (BSO) or by inhibiting glutathione reductase with (1,3-bis) 2 chlorethyl-1-nitrosourea. The loss of NAD developed independently of glutathione cycle and HMPS activity, as it also occurred in BSO-treated cells.
 ...
PMID:Glutathione cycle activity and pyridine nucleotide levels in oxidant-induced injury of cells. 384 Jan 76

Studies were carried out on microsomes isolated from the highly differentiated (slow-growing) Morris hepatoma 9618A, on microsomes and plasma membranes from the poorly differentiated (fast-growing) Morris hepatoma 3924A, and rat liver used as control. The lipid composition (phospholipid and cholesterol content, degree of fatty acid unsaturation) and peroxidation of such membranes has been correlated with the order and fluidity of the membrane bilayer. The results indicate that substrate availability is the rate-limiting step in microsomal and plasma membrane lipid peroxidation of hepatoma 3924A. From diphenylhexatriene fluorescence depolarization measurements it appears that the changes in lipid composition cause an increase in the order of the lipid bilayer on going from the control to hepatoma 9618A and 3924A microsomes, while fluidity is virtually unchanged. Conversely, for similar chemical changes, in plasma membranes from hepatoma 3924A the order is nearly the same and there is a decrease in fluidity. The changes in the above parameters of tumor membranes might be partly related to the loss of protective enzymes against oxygen radicals. This is supported by the observation that inhibition of liver superoxide dismutase and glutathione reductase, by treatment of rats with diethyldithiocarbamate and chloroethyl nitrosourea, respectively, renders the microsomal membranes more resistant to lipid peroxidation in vitro.
 ...
PMID:Lipid composition, physical state, and lipid peroxidation of tumor membranes. 609 10

Human lung cancers of distinct histology exhibit different responses to radiation therapy in vivo. For examination of the basis of this phenomenon, the radiation survival curves and levels of relevant enzymes were determined in 16 lung cancer cell lines derived from tumors of different histology. These included lines from 5 adenocarcinomas, 7 small cell tumors, 3 variant small cell tumors, and 1 large cell tumor. These findings were compared to those obtained with the use of a normal skin fibroblast cell line. Whether cloned in liquid culture or soft agarose, cell lines had similar radiation survival curves. These curves were consistent with the apparent in vivo radiation responsiveness of the tumors. Although considerable heterogeneity in radiation survival curves was observed among the cell lines, cells from large cell lines and small variant lines had pronounced shoulders and extrapolation numbers (n) from 5.6 to 14. In contrast, cells from small cell lines and adenocarcinoma cell lines were more "sensitive" (-n values of 1-3.3). In these cell lines, levels of DNA polymerase beta, glutathione (GSH), GSH transferase, GSH reductase (NAD(P)H), gamma-glutamyltransferase did not correlate with radiation parameters of sensitivity. DNA polymerase beta and GSH levels were, however, higher than those in a line of normal skin fibroblasts. These cell lines may be useful in identifying the basis of the variable responsiveness of human lung cancer cells to ionizing radiation.
 ...
PMID:Heterogeneity in the radiation survival curves and biochemical properties of human lung cancer cell lines. 614 44


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