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)

The cytochrome P450, epoxide hydrolase, and glutathione S-transferase enzyme families play an important part in the metabolism of many carcinogens and anti-cancer drugs. The expression of two forms of cytochrome P450 (P450 1A and P450 3A), epoxide hydrolase and of the alpha, mu, and pi forms of glutathione S-transferase in normal colon, colonic adenomas, and adenocarcinoma of the colon were studied by immunohistochemistry. This allowed the precise cellular site and distribution of each enzyme to be determined. Expression of all the xenobiotic metabolising enzymes studied was almost wholly confined to the epithelial cells, whether in normal, adenoma or carcinoma samples, except that cytochrome P450 3A was also identified in mast cells and glutathione S-transferase pi was also present in chronic inflammatory cells. Cytochrome P450 was present in only a small proportion of normal colon samples, whereas epoxide hydrolase and glutathione S-transferase mu were identified in about half, and glutathione S-transferase alpha and pi in most normal samples. By contrast all the enzyme forms studied were expressed in virtually all adenomas and in over half the carcinomas. These results suggest that cytochrome P450 1A and cytochrome P450 3A are more specific markers of colonic neoplasia than epoxide hydrolase or glutathione S-transferases alpha, mu, and pi.
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PMID:Xenobiotic metabolising enzyme expression in colonic neoplasia. 840 61

Glutathione content, enzyme activity and isoenzyme composition of glutathione S-transferases were assayed in normal and Barrett's esophageal epithelium of ten patients with Barrett's esophagus. In addition, gastric and duodenal specimens from the same patients were also investigated. Glutathione content, glutathione S-transferase enzyme activity as well as glutathione S-transferase pi content were all significantly lower in Barrett's epithelium as compared to normal esophageal mucosa. In contrast, glutathione S-transferase class alpha enzymes are markedly expressed in Barrett's epithelium, whereas only low amounts are present in normal esophageal epithelium. Glutathione and glutathione S-transferase composition in Barrett's epithelium show striking similarities with gastric epithelium, whereas duodenal epithelium is provided with considerable higher amounts of glutathione and glutathione S-transferases, except for levels of glutathione S-transferase class pi, which are lower. A significant negative correlation exists between glutathione S-transferase enzyme activity in the mucosa along the gastrointestinal tract, and the tumour incidence. Since glutathione and glutathione S-transferase are correlated with protection against cellular or cytogenetic damage, the low content of glutathione and glutathione S-transferases in the Barrett's esophagus may be a factor of relevance for the increased tumour risk in this tissue.
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PMID:Glutathione and glutathione S-transferases in Barrett's epithelium. 851 26

Recent studies have suggested that glutathione S-transferase pi (GST-pi) may play a role in determining tumor sensitivities to cytotoxic drugs. In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers. Modestly increased resistance of the GST-pi transfectants preferentially to sublethal damage caused by ionizing radiation as well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were virtually unaltered. These results suggest that GST-pi may not play a major role in chemo- and radioresistance of lung cancers, although it could afford selective and limited protection against ADM- and ionizing radiation-induced damage.
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PMID:Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase pi gene. 855 60

To study the genetic changes that generate resistance to oxidants in mammalian cells, we isolated cell lines that are resistant to the naphthoquinone, menadione, from a Chinese hamster ovary cell line (CHO-K1). Corss-resistance to other oxidants (H2O2 and sodium arsenite) was observed. The IC50 of menadione (measured using a clonogenic assay) was 7.8-fold greater for one menadione-resistant cell line (MRc40) than for CHO-K1. Acquisition of resistance was associated with elevations of 2- and 3.2-fold in the low molecular weight thiols, glutathione and cysteine, respectively. Further, characterization demonstrated significant changes in the expression of enzymes associated with the oxidative stress response and with protection against oxidizing agents. The expressions of glutathione S-transferase pi (GST pi), glutathione peroxidase (GPX) and heme oxygenase mRNAs were all increased. Accompanying these changes the enzyme activity of GST pi, GPX and gamma-glutamyl transpeptidase (gamma-GT) were also elevated. Interestingly, in a revertant cell line heme oxygenase overexpression approached wild-type levels. Intriguingly, similar changes in gene expression seen in the menadione-resistant cells were also observed in wild-type cells following transient oxidative stress, indicating that the observed changes in the resistant line may be due to the immortalization of a normally transient adaptive stress response.
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PMID:Relationship between the adaptive response to oxidants and stable menadione-resistance in Chinese hamster ovary cell lines. 862 73

In 33 patients with primary ovarian cancer who had not received any chemotherapy before surgery, expression of glutathione S-transferase pi (GST-pi) was studied immunohistochemically in relation to the response to chemotherapy with CDDP, and furthermore it was examined whether numerical aberration of chromosome 11 was available as a prognostic indicator. The obtained results were as follows: 1. Of 33 ovarian cancer tissue samples, 19 (57.6%) showed positive staining and 14 (42.4%) negative staining for GST-pi. 2. The 5 year survival rate of the patients with GST-pi positive tumors was significantly lower than that of those with GST-pi negative tumors (p < 0.01). 3. The frequency of detection of cells showing numerical aberration of chromosome 11 in tissues was significantly higher in ovarian cancers than in benign ovarian tumors and normal ovaries. 4. The 5 year survival rate of the patients with ovarian cancer in which the cells showing numerical aberration of chromosome 11 at 20% or more was significantly lower than that of those in which such cells were under 20% (p < 0.02). These results show that expression of GST-pi and numerical aberration of chromosome 11 in the tissues of human ovarian cancers are useful as prognostic indicators.
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PMID:[Expression of glutathione S-transferase pi and numerical aberration of chromosome 11 in human ovarian cancer as a prognostic indicator]. 871 47

Ninety-five specimens from patients with endometrial carcinoma (82 of endometrial type, 6 of adenoacanthoma, 4 of adenosquamous carcinoma, 3 of atypical endometrial hyperplasia) and 13 with ovarian endometrioid carcinoma were stained immunohistochemically with a rabbit polyclonal antibody prepared against the placental form of the enzyme glutathione S-transferase pi (GST-pi). Histological studies showed that the degree of staining decreased as the tumor lost its differentiation in endometrial carcinoma, but the degree of staining was independent of the differentiation in the case of ovarian endometrioid carcinoma. A comparison between the grade of staining of GST-pi in 82 cases of the endometrial type of endometrial carcinoma and 13 cases of ovarian endometrioid carcinoma revealed a stronger stain for the endometrial carcinoma than for ovarian endometrioid carcinoma (p < 0.01, Mann-Whitney's U test). Therefore, the GST-pi value for endometrial carcinoma was different from that for endometrioid carcinoma. In general, as compared with ovarian endometrioid carcinoma, endometrial carcinoma is considered to be resistant to chemotherapeutic agents. In conclusion, these results suggest that there is an apparent correlation between the GST-pi value and chemoresistance of the tumor.
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PMID:[An immunohistological study on expression of glutathione S-transferase pi (form) in human endometrial carcinoma]. 871 49

Tamoxifen as sole initial therapy is gaining importance in the management of post-menopausal breast cancer patients. Age oestrogen (ER) and progesterone (PR) receptor status are accurately considered to select patients for hormonal treatment. However, additional markers are needed. By immunohistochemistry (IHC), we studied tumour expression of ER, PR, pS2, c-erbB-2 and glutathione S-transferase pi (GST pi) on initial core biopsies of 208 post-menopausal patients with a non-metastatic invasive ductal carcinoma, treated by neoadjuvant tamoxifen therapy. A good response to tamoxifen was defined as tumoral regression > or = 50% (110 patients). Relationship between response and age, tumour size, T, N, histological grade, ER and PR contents evaluated by radioimmunoassay, ER, PR, pS2, c-erbB-2 and GST pi expression evaluated by IHC were studied. Univariate and multivariate analysis showed that tumoral regression was linked only to pS2 (P = 0.004) and ER (P = 0.018) IHC expression. According to the immunohistochemical profile, three groups could be defined: pS2- and ER-positive tumours, pS2- or ER-positive tumours and pS2- and ER-negative tumours with response rates of 60%, 45% and 8% respectively. Although prospective studies are needed to confirm these results, we conclude that pS2 and ER immunohistochemical status are useful tools for predicting tumour regression with neoadjuvant tamoxifen in post-menopausal breast carcinoma patients.
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PMID:pS2 protein: a marker improving prediction of response to neoadjuvant tamoxifen in post-menopausal breast cancer patients. 885 85

In order to explore the protective function of human glutathione S-transferase pi (GST-pi) in vitro and in vivo, transfected NIH 3T3 clones were examined in cytotoxicity assays using the carcinogen (+/-)anti-benzo(a)pyrene 7,8-diol-9,10-epoxide (BPDE) or inoculated into nude mice and treated with the carcinogen benzo(a)pyrene (BP) to induce tumor formation. The human GST-pi cDNA under the control of the murine alpha 2(I)collagen promoter was transfected into NIH 3T3 cells and G418 resistant clones were analyzed by Southern, northern, western, and two-dimensional analysis. Clone A2 stably expressed human GST-pi and has 2.5-fold greater activity toward the substrate 1-chloro-2,4-dinitrobenzene and a 1.7-fold increase in LD50 for BPDE in vitro when compared to control-transfected clone G3. This increase in protection, however, did not prevent the formation of BP-induced tumors in vivo.
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PMID:Overexpression of human glutathione S-transferase pi protects NIH 3T3 cells against (+/-)anti BPDE cytotoxicity but not tumor formation. 886 91

Human glutathione S-transferase pi has been known to be a good marker for several tumor types because of the high frequency with which it is overexpressed. In order to determine whether GST pi is useful as an indicator for head and neck cancers, expression of GST pi was investigated by Northern analysis. Overexpression of mRNA was detected in 9 of 36 primary head and neck squamous cell carcinomas. To examine the relationship between overexpression and amplification of GST pi gene, Southern analysis was performed on all samples. Only 3 of the 36 tumors showed amplification GST pi genes, indicating that gene amplification may not play a key role in GST pi mRNA overexpression in these cancers.
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PMID:Overexpression of glutathione S-transferase pi messenger RNA and its relationship to gene amplification in head and neck squamous cell carcinoma. 906 50

Over-expression of glutathione S-transferase pi (GST-pi) class isozyme is often associated with malignant transformation and/or drug resistance. To determine whether GST-pi is implicated in betel and tobacco related oral carcinogenesis and/or drug resistance, its expression was studied in oral untreated primary squamous cell carcinomas (SCCs), recurrent tumours and matched normal oral tissues by immunohistochemical and immunoblotting techniques. The GST-pi expression in primary tumours predominantly varied from mild to moderate levels and no significant difference in its expression was observed in the matched normal tissue surrounding these lesions. Mild to moderate levels of GST-pi expression in the oral mucosa of consumers of betel and tobacco observed in the matched normal tissues may support the physiological role of this detoxification enzyme in the metabolism of xenobiotics and elimination of toxic constituents of tobacco. The hallmark of the study is the significant increase in GST-pi expression in recurrent oral SCCs, compared to the matched normal tissues, as well as primary oral tumours, suggesting its potential role as an indicator of prolonged exposure to carcinogens, or prognosis of the disease.
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PMID:Glutathione S-transferase pi expression in matched human normal and malignant oral mucosa. 923 Nov 63


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