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)

GST and CYP2E1 genes are involved in metabolism of several compounds (e.g., solvents) that may play a role in brain cancer etiology. We evaluated associations between polymorphisms in these genes and adult brain tumor incidence. Cases were 782 patients with brain tumors diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples that had been collected from 1277 subjects (80% of all subjects; 604 controls; 422 gliomas, 172 meningiomas, and 79 acoustic neuromas), and genotyping was successfully conducted for GSTM1 null, GSTT1 null, GSTP I105V, GSTP A114V, CYP2E1 RsaI, and CYP2E1 Ins96. The GSTP1 105 Val/Val genotype was associated with increased glioma incidence [odds ratio (OR), 1.8; 95% confidence limits (CLs), 1.2, 2.7], with the estimated effect following a trend of increasing magnitude by number of variant alleles (Ile/Ile: OR, 1.0; Ile/Val: OR, 1.3; Val/Val: OR, 2.1). The CYP2E1 RsaI variant was weakly associated with glioma (OR, 1.4; 95% CL, 0.9, 2.4) and acoustic neuroma (OR, 2.3; 95% CL, 1.0, 5.3), with some indication of stronger associations among younger subjects. Estimated effects of the gene variants differed by glioma subtype. There was evidence of supermultiplicativity of the joint effect of GSTP1 I105V and CYP2E1 RsaI variants on both glioma and acoustic neuroma, even following adjustment of estimates toward a common prior distribution using hierarchical regression models. Previously reported associations between the GSTT1 null genotype and overall glioma incidence were not replicated, but an association with meningioma was observed (OR, 1.5; 95% CL, 1.0, 2.3). These findings may provide clues to both genetic and environmental determinants of brain tumors.
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PMID:Genetic polymorphisms in GSTM1, -P1, -T1, and CYP2E1 and the risk of adult brain tumors. 1254 Apr 98

Malignant gliomas are extremely aggressive cancers currently lacking effective treatment modalities. Gene therapy represents a promising approach for this disease. A requisite component for improving gene-based therapies of brain cancer includes tumor suppressor genes that exhibit cancer constrained inhibitory activity. Subtraction hybridization identified melanoma differentiation associated gene-7 (mda-7) as a gene associated with melanoma cell growth, differentiation and progression. Ectopic expression of mda-7 by means of a replication-incompetent adenovirus (Ad), Ad.mda-7, induces growth suppression and apoptosis selectively in diverse human cancers, without producing any apparent harmful effect in normal cells. We presently demonstrate that Ad.mda-7 induces growth inhibition and apoptosis in malignant human gliomas expressing both mutant and wild-type p53, and these effects correlate with an elevation in expression of members of the growth arrest and DNA damage (GADD) gene family. In contrast, infection with a recombinant Ad expressing wild-type p53, Ad.wtp53, specifically affects mutant p53 expressing gliomas. When tested in early passage normal and immortal human fetal astrocytes, growth inhibition resulting from infection with Ad.mda-7 or Ad.wtp53 is significantly less than in malignant gliomas and no toxicity is evident in these normal cells. Moreover, infection of gliomas with Ad.mda-7 or treatment with purified GST-MDA-7 protein sensitizes both wild-type and mutant p53 expressing tumor cells to the growth inhibitory and antisurvival effects of ionizing radiation, and this response correlates with increased expression of specific members of the GADD gene family. Since heterogeneity in p53 expression is common in evolving gliomas, the present findings suggest that Ad.mda-7 may, in many instances, prove more beneficial for the gene-based therapy of malignant gliomas than administration of wild-type p53.
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PMID:Melanoma differentiation associated gene-7, mda-7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant gliomas in a p53-independent manner. 1260 43