Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the relationship among different biologic markers of breast cancer has been shown to be important in predicting cancer behavior, expression of these markers can be an attribute of the population under study. Breast cancer is the most common malignancy among Egyptian women. We have studied a number of prognostic tumor markers in infiltrating ductal carcinoma in a group of Egyptian women and have correlated our results with traditional histologic parameters of behavior such as tumor nuclear grade and lymph node status. Seventy-five cases of infiltrating ductal breast cancer were evaluated from pathology archives. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for PCNA, p53, c-erB-2, metallothionein, cathepsin-D, and GST-pi using specific antibodies and a standard avidin-biotin method. Most high-grade tumors were associated with higher PCNA expression and p53 abnormality. There was a significant difference between node-negative and node-positive tumors with regard to their metallothionein content; other markers, however, did not differ significantly between node-negative and node-positive tumors. PCNA expression, metallothionein expression, and p53 mutation appear to be markers of aggressive tumor behavior in Egyptian women with breast cancer.
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PMID:Immunohistochemical markers of tumor prognosis in breast cancer in Egypt. 916 36

One of the earliest responses of cells upon exposure to DNA-damaging agents is the induction of c-fos. To elucidate the biological role of Fos expression, we analyzed cells deficient in c-Fos upon treatment with different DNA-damaging agents, including carcinogens and antineoplastic drugs. We show that cells lacking c-Fos are hypersensitive with regard to reproductive cell death, apoptosis, and chromosomal breakage after treatment with agents inducing methylation lesions, bulky adducts, or crosslinks in DNA. They were not significantly hypersensitive to ionizing radiation. The activities of various repair enzymes and glutathione S-transferase and the level of proliferating cell nuclear antigen were not altered in c-fos-/- fibroblasts. Furthermore, the cells were able to remove the main methylation lesions from DNA. c-Fos-deficient cells exhibited a more severe mutagen-induced block to DNA replication and were compromised in the abolition of replication blockage. The data provide compelling evidence that c-Fos/activator protein-1 plays a decisive and general role in cellular defense against genotoxic agents, which require DNA replication to induce chromosomal instability. They are consistent with the hypothesis that impaired recovery from DNA replication inhibition upon mutagen exposure is causally involved in c-fos-/- hypersensitivity.
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PMID:A general role for c-Fos in cellular protection against DNA-damaging carcinogens and cytostatic drugs. 920 83

A cDNA encoding the proliferating cell nuclear antigen (PCNA) from Brassica napus (oilseed rape) was shown to complement the lethal deletion mutation in the PCNA gene (delta POL30) of Saccharomyces cerevisiae. We provide unequivocal evidence that the B. napus PCNA can perform all the essential functions of the yeast PCNA in DNA replication, although some species-specific differences may exist. In addition, the B. napus PCNA expressed as a fusion polypeptide with glutathione S-transferase (GST) was shown to stimulate the activity and processivity of two delta-like DNA polymerases from wheat in vitro. These experiments provide direct biochemical evidence that the B. napus PCNA may function as an auxiliary factor in plant cell DNA replication.
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PMID:Molecular genetic and biochemical analysis of Brassica napus proliferating cell nuclear antigen function. 924 51

S-Methylcysteine (SMC) occurs in a variety of plants, including Allium sativum, Phaseolus vulgaris, and Cruciferae. In this study, we synthesized five organosulfur compounds (OSCs), SMC and four analogs, and examined their modifying effects on diethylnitrosamine-induced neoplasia of the liver in male F344 rats, using the medium-term bioassay system of Ito (Ito test) based on the two-step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular focl. All OSCs examined had a tendency to decrease the number of GST-P-positive foci when given in the promotion stage of the Ito test, and in particular SMC and cysteine exerted significant inhibitory effects. When given during the initiation stage, these two OSCs also significantly inhibited focus formation. Regarding the mechanism underlying the inhibitory effects of SMC and cysteine, measurement of ornithine decarboxylase in SMC- and cysteine-treated liver tissues after partial hepatectomy (PH) revealed a significantly reduced activity, and the proportion of hepatocytes positive for proliferating cell nuclear antigen was significantly decreased by SMC or cysteine administration. Moreover, examination of the expression of the early response proto-oncogenes, c-fos, c-jun, and c-myc, after PH demonstrated down-regulated induction of c-jun mRNA transcripts by SMC, sustained for an eight-hour period. Our results support the view that SMC and cysteine are chemopreventive agents for rat hepatocarcinogenesis and that their intake may be importance for cancer prevention.
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PMID:S-methylcysteine and cysteine are inhibitors of induction of glutathione S-transferase placental form-positive foci during initiation and promotion phases of rat hepatocarcinogenesis. 924 99

Although experimental studies indicate that overexpression of metallothionein (MT), glutathione-S-transferase-pi (GST-pi), or P-glycoprotein (P-GP) is related to the drug resistance of cancer cells, the clinical significance of the overexpression remains to be elucidated. The expressions of MT, GST-pi, and P-GP wre evaluated immunohistochemically in 74 specimens of gastric adenocarcinoma in T1-3N1-2 stages which were resected with curative intent. Fluorinated pyrimidines, mitomycin C, and Adriamycin were prescribed in 73, 54, and 2 patients, respectively. The staining characteristics were investigated in relation to the clinical results. The cell-proliferative activity was studied with anti-proliferating cell nuclear antigen antibody. Expressions of GST-pi and P-GP correlated with the staining intensity of normal mucosa. Five-year disease-free survival rates (DFSRs) of GST-pi-negative and GST-pi-positive groups were 75.0 and 49.0%. The 5-year DFSRs of P-GP-negative and P-GP-positive groups were 68.2 and 38.6%. Concurrent expression among the three proteins was associated with the survival: 5-year DFSR of no- or one-protein-positive group was 75.0%, while those of 2- and 3-protein-positive groups were 56.0 and 38.9%, respectively. Tumors concurrently expressing 2 or 3 proteins have a high proliferative activity. Expressions of MT, GST-pi, and P-GP by the tumor are associated with a poorer prognosis of the patients.
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PMID:Prognostic significance of the expressions of metallothionein, glutathione-S-transferase-pi, and P-glycoprotein in curatively resected gastric cancer. 926 Jun 1

Studies of multiple markers in tumors are required for adequate biological characterization. We have characterized the expression of multiple proteins in human ovarian tumors using the technique of 2-dimensional gel electrophoresis (2-DE/PDQUEST). Tumor cells were prepared from the tissue of 22 ovarian tumors. Large variations were observed between tumors in the expression of various polypeptides, indicating heterogeneity in gene expression. An increase in the spot density of 2 cell-cycle-related proteins, PCNA and OP18/stathmin, was observed in carcinomas. Borderline tumors expressed low levels of these proteins. Significant increases in the levels of nm23, GST-pi, elongation factor 2 and triose phosphate isomerase were recorded in ovarian carcinomas. Furthermore, decreases in the levels of tropomyosin-2 and lamin C were observed in malignant as compared with benign tumors. The pattern of expression of 9 protein markers was examined in individual tumors. All malignant tumors showed simultaneous alterations in the expression of 5 or more of these proteins, whereas no benign tumor showed alterations in the expression of more than 3 polypeptides. Borderline tumors showed alterations in 0 to 6 markers. We conclude that the simultaneous analysis of multiple polypeptides, which can be achieved by 2-DE, is useful for characterization of gene expression and diagnostic studies in ovarian tumors.
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PMID:Phenotypic analysis of ovarian carcinoma: polypeptide expression in benign, borderline and malignant tumors. 939 45

Choline deficiency (CD) was previously shown to trigger apoptosis in rat hepatocytes in culture and in vivo. In the present study we investigated the effects of short-term withdrawal of choline from the diet on the expression of putative preneoplastic foci in OXYS rats, an inbred strain with an inherited overproduction of free radicals. Animals were fed a defined, choline-sufficient (CS, control) or choline-deficient (CD) diet for 6 weeks. Eosinophilic, glutathione S-transferase (pi class) (+) preneoplastic foci were found in histologic sections of control OXYS rat liver. CD caused a 60% decrease in the number of eosinophilic foci per liver section (27.0+/-6.1 vs. 10.6+/-4.6 foci/section) compared to CS controls. Apoptotic bodies were detected in 0.18+/-0.03% of hepatocytes in CD livers compared to 0.05+/-0.009% of hepatocytes in controls. Cells which exhibited an apoptotic morphology in hematoxylin and eosin-stained sections were TUNEL-positive, confirming the induction of apoptosis. Also in CD animals compared to controls, there was an increased expression of p27Kip1 protein, and a reduction in PCNA nuclear labeling and the number of mitotic figures, consistent with an inhibition of cell proliferation in the livers of CD animals. This study shows that the liver of OXYS rats with an inherited overgeneration of free radicals retains sensitivity to CD, and that this p53-independent trigger of apoptosis can decrease the number of eosinophilic foci in the livers of these animals.
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PMID:Choline deficiency induces apoptosis and decreases the number of eosinophilic preneoplastic foci in the liver of OXYS rats. 964 30

Fumonisin B1 (FB1), a mycotoxin produced by a common corn contaminant Fusarium moniliforme and a hepatocarcinogen in rats, has been previously suggested to act as a poor initiator, but a better promoter of gamma-glutamyltranspeptidase (GGT)-positive rat liver preneoplastic lesions. Using glutathione S-transferase-placental form (GSTP) as a more sensitive marker of initiation, we have further evaluated the initiating capacity of various doses of purified FB1 administered (a) intraperitoneally (i.p.) to male Sprague-Dawley (SD) rats for 4 days and (b) orally (PO) to male and female SD rats for 11 days. Compared to their respective controls, significant increases in GSTP-positive hepatocytes were observed in male rats administered FB1 i.p. at 10 mg/kg body weight/day for 4 days, as well as in male and female rats treated with 35 and 75 mg/kg body weight/day FB1 p.o. for 11 days. The percentage section area of liver occupied by GSTP-positive mini-foci comprising of three to 12 cells was increased significantly in male rats given 10 mg/kg FB1 i.p., or in p.o.-treated males and females with 75 mg/kg FB1. Both i.p. and p.o. FB1 treatments resulted in dose-related enhanced hepatocyte proliferation as measured by proliferating cell nuclear antigen (PCNA) labeling with significant increases in the number of PCNA-positive nuclei at the same i.p. and p.o. dose levels where the number of GSTP-positive cells were elevated. In all studies, enhanced PCNA and GSTP expression occurred at FB1 doses which, based on serum biochemical and histopathological data previously reported from our laboratory, were shown to be hepatotoxic. Therefore, our data suggest that in a manner similar to known genotoxic carcinogens, FB1 has the capacity to initiate GSTP-positive hepatocytes with their subsequent development into GSTP mini-foci at exposure levels that induce enhanced hepatocyte proliferation in response to liver toxicity. In SD rats, this occurs as early as within 4 days of i.p. treatment or 11 days of p.o. treatment.
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PMID:Glutathione S-transferase-placental form expression and proliferation of hepatocytes in fumonisin B1-treated male and female Sprague-Dawley rats. 965 90

A two stage carcinogenesis promotion test using phenobarbital (PB) as a positive control was performed on mesalazine in rats (F344,male). Pathological and immunohistological examinations were performed to examine the cell damage and proliferation in the liver and kidneys. As the initiation treatment, groups 1,2,3 and 5 were administered 300 mg/kg diethylnitrosamine (DEN)dissolved in 0.9% physiological saline, and group 4 was administered 5 ml/kg 0.9% physiological saline once intraperitoneally. Then group 1 was orally administered a water solution (5 ml/kg) containing 0.5% CMC-Na, and groups 2,3 and 4 similar water solution but containing 150, 300 and 300 mg/kg mesalazine, respectively. Group 5 was administered 0.05% PB mixed in feed from weeks 2 to 8. Partial (2/3) hepatectomy was performed in all 5 groups at week 3 after DEN administration. NO clear differences between the groups were observed in general conditions, body weight or amount of food consumption. The number or area-size of hepatic GST-P positive altered cell foci revealed no significant differences between groups 1,2 and 3, but a significant increase in number and area-size was observed in group 5. No GST-P positive cell foci were detected in group 4. The number of altered cell foci (H.E. staining) in the DENgroups administered mesalazine was the same as that in group 1. Thus, mesalazine did not promote hepatocarcinogenesis in the present experimental system. Statistically insignificant appearances of basophilic and acidophilic changes were observed in the renal tubular epithelium and mineral deposits in the renal papillary region and cortical margin region. The PCNA labeling rate was significantly lower in group 4, corresponding with the histological finding showing no proliferation of the renal tubular epithelium. Judging from the above test results, mesalazine was likely to show neither a promotion effect on the initiation induced by DEN nor cell proliferative activity on the kidneys by administration for this experimental period.
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PMID:[Effects of mesalazine on liver carcinogenesis in medium-term bioassay using rats]. 976 Apr 11

Mammalian E2F transcription factors comprise a family of proteins encoded by distinct genes which function in the form of heterodimers with DP proteins. In Drosophila melanogaster, only a single E2F-related transcription factor, dE2F, has been reported. We have now identified and characterized a cDNA encoding another E2F family member in Drosophila, termed dE2F2. The predicted amino acid sequence shares 38.8% identity with dE2F, including the QKRRIYDITNVLEGI motif which is highly conserved in mammalian E2F family members and dE2F. The 18 amino acids, located in the carboxy-terminal region of the mammalian E2F family, sufficient for binding to pRb are also conserved in dE2F2. Band mobility shift analyses with glutathione S-transferase fusion proteins revealed dE2F2 binding to E2F-recognition sites to be dependent on the presence of dDP protein, in apparent contrast to dE2F. Furthermore, cotransfection experiments in Kc cells demonstrated dE2F2 repression of the PCNA gene promoter activity, while dE2F caused activation, the target site for the repression being identical to the dE2F-recognition site.
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PMID:dE2F2, a novel E2F-family transcription factor in Drosophila melanogaster. 979 88


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