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)

Altered expression of the glutathione S-transferases (GSTs) has been implicated in the progression to tumour after exposure to carcinogens, and GST Pi has been suggested as a possible marker of preneoplasia in the cervix. We have studied expression of the GST isoenzymes in normal cervix, non-dysplastic cervical condylomata, cervical intraepithelial neoplasia (CIN), and invasive squamous carcinoma of the cervix using immunocytochemistry. An increase in GST Pi in CIN as compared with normal cervix was paralleled by a reduction in the expression of microsomal GST. Similar changes were seen in cervical condylomata and immature squamous metaplasia, and thus neither isoenzyme is a marker of dysplasia. Microsomal GST was expressed in only 66 per cent of cases and in 22 per cent showed strong expression in vascular endothelium. These findings are of particular interest in view of the association between cervical carcinoma and cigarette smoking. Differences between individuals in the ability to detoxify environmental carcinogens may influence the likelihood of progression from benign proliferation to invasive malignancy.
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PMID:Glutathione S-transferase detoxication enzymes in cervical neoplasia. 229 Jan 15

Expression of the human placental form of glutathione S-transferase (GST-pi) in dysplasia (53 cases), carcinoma in situ (10 cases), and invasive carcinoma (46 cases) of human uterine cervix was investigated immunohistochemically with specific anti-GST-pi rabbit antibody. While normal squamous epithelium was largely negative, the binding of antibody was appreciable in mild and moderate dysplasias, especially in the cytoplasm of cells demonstrating koilocytotic atypia. In severe dysplasia, the nuclei as well as the cytoplasm were strongly stained in all cell layers except for the superficial layer, and in carcinoma in situ both of them were also strongly stained in all cell layers. In invasive carcinoma, over 90% of cases exhibited strong cytoplasmic staining and in over 70% the nuclei were positive. GST activity towards 1-chloro-2,4-dinitrobenzene and GST-pi protein content were significantly increased in all of 4 squamous cell carcinomas examined as compared to values for normal cervical epithelia. Two-dimensional gel electrophoresis followed by immunoblotting using the GST-pi antibody demonstrated that, of many cytoplasmic proteins, only the GST-pi subunit was specifically bound. These results indicate that GST-pi is a potentially useful immunohistochemical marker for (pre)neoplasia of human uterine cervix. In addition, it was demonstrated that the cells in severe dysplasia, carcinoma in situ, and invasive carcinoma expressing GST-pi were often characterized by staining with a monoclonal antibody to the v-H-ras gene product.
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PMID:Immunohistochemical detection of the placental form of glutathione S-transferase in dysplastic and neoplastic human uterine cervix lesions. 349 81

The expression and localization of glutathione S-transferase (GST) isoenzymes in the epithelium of normal oral mucosa (n = 9), overlying reactive fibrous hyperplasia (n = 9), and of potentially malignant [leukoplakia (n = 25), submucous fibrosis (n = 12), verrucous hyperplasia (n = 16)] and malignant [squamous cell carcinoma (n = 36), verrucous carcinoma (n = 13)] oral lesions were examined immunohistochemically using polyclonal antibodies raised against GST isoenzymes (alpha, mu and pi) with the standard avidin-biotin-peroxidase complex (ABC) method. GST alpha, mu and pi were almost completely absent in the epithelium of normal oral mucosa and overlying benign fibrous tissues. GST alpha staining was cytoplasmic and focally positive, while GST mu staining was similar to but weaker than that seen for GST alpha. GST pi showed both cytoplasmic and nuclear staining and was expressed in 60% of leukoplakias with mild dysplasia (n = 15), 80% of leukoplakias with moderate to severe dysplasia (n = 10). 75% of submucous fibrosis samples (n = 12), 75% of verrucous hyperplasias (n = 16), 77% of verrucous carcinomas (n = 13), 81% of well-differentiated squamous cell carcinomas (n = 26) and 70% of moderate- to poorly-differentiated squamous cell carcinomas (n = 10). In addition, GST pi expression was independent of the state of differentiation of oral cancers. Since GST pi was significantly over-expressed in the oral premalignant and malignant lesions, the kinetics of GST pi-positive cells and the value of GST pi as a tumor marker in oral carcinogenesis need further investigation.
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PMID:Immunohistochemical demonstration of epithelial glutathione S-transferase isoenzymes in normal, benign, premalignant and malignant human oral mucosa. 747 69

We describe immunohistochemical studies of the expression of alpha and pi class glutathione S-transferases (GSTs) in normal fetal kidneys. These define, in greater detail, changes in expression of alpha isoforms in the proximal tubule. At about 36 weeks of gestation expression of alpha isoforms was down-regulated in the distal tubules and collecting ducts while pi was expressed throughout the nephron. Tubular expression of alpha isoforms was restricted to the part adjacent to the glomerulus; cells farthest from the glomerulus were negative. After 40 weeks of gestation, alpha isoforms were expressed along the entire proximal tubule, while pi was restricted to the distal tubule and collecting ducts. GST expression was also studied in multicystic renal dysplasia, autosomal recessive polycystic kidney disease, and autosomal dominant polycystic kidney disease to determine whether the patterns of expression of alpha and pi isoforms allow identification of the origin of the cysts that characterize these diseases. Cysts were lined by epithelia that were strongly positive for alpha and pi isoforms. The epithelia of noncystic nephrons in renal cystic dysplasia demonstrated delayed maturity, suggesting that GST expression was dependent on the stage of development and not length of gestation.
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PMID:Immunocytochemical studies of the distribution of alpha and pi isoforms of glutathione S-transferase in cystic renal diseases. 806 5

This study investigated the immunohistochemical expression of human placental glutathione S-transferase (GST-pi) in the epithelium of oral premalignant and malignant lesions. Epithelial lining of normal oral mucosa, hyperplastic lesions and oral epithelium exhibiting mild dysplasia showed weak to moderate GST-pi staining. Moderate epithelial dysplasia revealed an increased antibody content while severe dysplasia, carcinoma-in-situ (CIS) and squamous cell carcinoma (SCC) demonstrated markedly increased antibody binding. The GST-pi staining was evident mainly in the cytoplasm. Severe dysplasia, CIS and SCC were also characterized by areas of cells with intensive nuclear GST-pi staining. These findings support the hypothesis that GST-pi plays a role in human oral carcinogenesis and may be used as a tumor marker for human oral premalignant and malignant lesions.
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PMID:Increase in placental glutathione S-transferase in human oral epithelial dysplastic lesions and squamous cell carcinomas. 816 57

Glutathione-S-transferase pi (GST pi) is a multifunctional protein that acts as an enzyme, involved in the detoxification of drugs and carcinogens. It has been implicated both in drug resistance and malignant transformation of epithelium. Using an indirect immunohistochemical technique, we have evaluated cytoplasmic and nuclear staining in normal urothelium, 23 superficial bladder tumours and 26 invasive tumours. All 26 invasive tumours had been treated with platinum-based chemotherapy. Cytoplasmic staining was seen in normal urothelium and all bladder tumours. Nuclear staining was seen in 1 superficial tumour and in 13 invasive tumours. There was no association between nuclear staining and response to chemotherapy. Nuclear staining was seen in 1 area of dysplasia and in 2 of 3 areas of carcinoma in situ. GST pi expression is not a predictor of response to chemotherapy. Increased intra-nuclear expression of GST pi may be associated with progression of transitional cell carcinoma of the bladder.
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PMID:Glutathione-S-transferase pi expression in transitional cell carcinoma of the bladder. 828 6

The glutathione S-transferase (GST) pi has been studied in association with the mechanisms of multidrug resistance and as a marker for malignant tumors. In this study, specimens from 92 cases of cervical neoplasms and 10 cases of normal squamous epithelium adhering to myoma were stained immunohistochemically with a rabbit polyclonal antibody to GST-pi. In 6 cases of normal squamous epithelium, the intermediate layer was positively stained with the GST-pi antibody. In all 20 cases of dysplasia, the cells with koilocytotic atypia were stained positively. In all 10 cases of carcinoma in situ and all 16 cases of stage Ia squamous cell carcinoma, various intensities of GST-pi staining were demonstrated. Forty-six specimens of stage Ib or more squamous cell carcinoma were positive for GST-pi binding except only one case. In general, squamous cell carcinoma of the uterine cervix is resistant to chemotherapeutic agents. GST-pi is most frequently stained in cervical squamous cell carcinoma as compared with ovarian or endometrial carcinoma. In conclusion, these results suggest that GST-pi may be a marker for cervical squamous cell carcinoma.
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PMID:[An immunohistological study on expression of glutathione S-transferase pi (form) in dysplastic and neoplastic human uterine cervix lesions]. 875 94

Immunocytochemical expression of the pi class glutathione S-transferase (GST) was investigated in preneoplastic and neoplastic lingual lesions in a 4-nitro-quinoline 1-oxide (4NQO)-induced rat genetic model [Wistar/Furth rats (WF) and Dark-Agouti rats (DA)] and in human surgical material [fibrous polyp, mild to moderate dysplasia, severe dysplasia, carcinoma in situ (CIS), squamous cell carcinoma (SCC)]. Two polyclonal antibodies raised against rat (GST-P) and human (GST-pi) antigens were used. In the rat model, DA and WF rats showed contrasting susceptibility to 4NQO, DA rats having a much higher tumour incidence and a significantly shorter survival time than WF rats. While the established lingual SCC in DA and WF rats all expressed GST-P, the number of GST-P+ foci in the preneoplastic lingual epithelium was significantly higher in DA (14.5 +/- 6.5) than in WF rats (5.5 +/- 2.6; P < 0.0001). In contrast, GST-pi epithelial staining in human specimens was more variable and the results overlapped in different groups. More frequent nuclear and/or basal cell staining was detected in severe dysplasia, CIS and SCC than in benign and mild to moderate dysplastic lesions. Although the pi class GST may be a useful marker for rat lingual carcinogenesis, its value in clinical applications is unclear. GST-pi staining patterns and their distribution may be helpful in identifying high-risk lingual lesions in humans.
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PMID:Glutathione S-transferase pi-class as a tumour marker in lingual preneoplastic and neoplastic lesions of rats and humans. 924 31

Prostate secretory protein (PSP94, 94 amino acids) is one of the most abundant proteins secreted from the prostate. Its biological role is unknown and still controversial, although it is assumed to have the potential to be a biomarker and a suppressor of prostate cancer. In order to establish an animal model to further elucidate its biological role, we expressed the mature form of rat PSP94 in Escherichia coli, using a glutathione S-transferase (GST) fusion expression vector; we generated a polyclonal rabbit antibody against the recombinant protein. The antibody specifically recognized recombinant rat PSP94 and cross-reacted only very weakly with its human homologue. Using the characterized anti-rat PSP94 antibody, we found that PSP94 was located primarily in rat prostate. Furthermore, PSP94 is present at different levels in different lobes of rat prostate, with significant levels detectable only in the lateral lobe (LP). In addition, the most abundant PSP94 expression was found in the prostate lobe secretions, and PSP94 levels in LP secretions were at least seven times higher than in secretions from the dorsal prostate (DP). The rat ventral prostate (VP) and other regions of the male accessory glands were found to be almost completely devoid of PSP94. Since most rat prostate dysplasia induced by steroid hormone treatment occurs only in dorsolateral prostate, prostate tissue-specific expression and the expression of PSP94 in dorsolateral, but not other, lobes of the prostate suggest a potential role in prostate targeting and prostate cancer development.
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PMID:Differential expression of PSP94 in rat prostate lobes as demonstrated by an antibody against recombinant GST-PSP94. 1041 42

The expression of Fhit (fragile histidine triad) protein in oral squamous cell carcinoma (OSCC) and adjacent oral epithelium was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded blocks of 32 cases of OSCC. Rabbit polyclonal anti-GST-Fhit antiserum at 1:600 was used, after antigen enhancement in a microwave pressure cooker, in a saturated lead thiocyanate solution. This antiserum has been shown specifically to detect human Fhit by immunohistochemistry at dilutions up to 1:10,000. The Fhit protein expression was evaluated using both the intensity and extent of staining. Normal stratified squamous epithelium showed strong positivity, especially in the stratum spinosum and areas of keratinisation. Basal and parabasal cells were negative or expressed low levels of Fhit relative to the squamous epithelium. Mild and moderate epithelial dysplasia showed Fhit expression in the superficial layers, while Fhit expression was absent from severely dysplastic lesions. A reduction or loss of Fhit expression was found in 21 (66%) of the OSCC. The alterations in Fhit protein expression in OSCC, and not in normal tissues, are consistent with the proposal that Fhit inactivation plays a role in oral carcinogenesis.
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PMID:Immunohistochemical evaluation of Fhit protein expression in oral squamous cell carcinomas. 1055 39


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