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

ADAMTS13 specifically cleaves unusually large von Willebrand factor (VWF) multimers, which induce platelet thrombi formation under high shear stress. The determination of plasma levels of ADAMTS13 activity is prerequisite for a differential diagnosis of thrombotic microangiopathies (TMAs). Here, we describe a unique and highly sensitive enzyme immunoassay of ADAMTS13 activity for routine laboratory use. ADAMTS13 hydrolyses the peptide bond between Y1605 and M1606 of VWF. In this enzyme immunoassay, a recombinant fusion protein (GST-VWF73-His) is used as a substrate. We have produced a panel of mouse monoclonal antibodies (anti-N10 mAb) that specifically recognizes the peptide containing Y1605 which is the C-terminal edge residue newly generated by the enzymatic cleavage. Using horseradish peroxidase-conjugated anti N10 mAb, a standard enzyme activity assay was established by ELISA. This assay was highly sensitive, and the detection limit was 0.5% of the normal. Further, an inhibitor of ADAMTS13 was measured to a level of 0.1 Bethesda U/ml. The activity measured by our novel assay and by the classic VWF multimer assay showed high correlation. We have also established ADAMST13 antigen ELISA assay using two clones of anti-ADAMST13 monoclonal antibody. The plasma antigen level of ADAMTS13 has generally good correlate to the plasma activity, but the several samples from acquired TTP patients with below 3% activity showed apparently high antigen level from 5 to 30%. Here, we have established a convenient and highly sensitive enzyme immunoassay for ADAMTS13 activity. This assay will be introduced for routine laboratory work in transfusion medicine.
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PMID:[Development of a novel ADAMTS13 activity assay for diagnosis of TMA and criteria for judgment of platelet transfusion]. 1731 94

Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer. We attempted to determine whether single nucleotide polymorphisms in ERCC1, GST, TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Total genomic DNA was extracted from the whole blood of patients. The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1, GST, TS and UGT1A1. The response rate of FOLFOX (N=75) was 24%. Grade 3-4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16%, respectively. TTP and OS of first-line administration of FOLFOX (N=35) were 3.1 months (95% CI, 0.1-6.1 months) and 13.9 months (95% CI, 12.2-15.6 months), respectively. Only the GSTM1 positive genotype exhibited a significantly better time to progression (P=0.023). However, significant genotypic variation of TS, GST and ERCC1, which was assumed to affect the activity of oxaliplatin, was not observed to affect RR, toxicity and overall survival. The response rate of FOLFIRI (N=74) was 23%. Grade 3-4 neutropenia and diarrhea were observed in 55.4 and 9.5% of cases, respectively. TTP and OS of first-line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5-6.4 months) and 19.0 months (95% CI, 8.5-29.5 months). The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia. However, significant genotypic variation of UGT1A1, which was assumed to affect irinotecan toxicity, was not observed to affect RR, toxicity or survival. In this study, the GSTM1 positive genotype evidenced a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX. The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade >or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI.
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PMID:Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI. 1951 14