Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A fusion protein consisting of the humanised Fab fragment of the anti CEA MAb BW 431 and the human beta-glucuronidase was expressed in BHK cells. Functional testing revealed that the specificity and avidity of the humanised V region was similar to the original murine MAb BW 431. Furthermore, the enzymatic activity, pH sensitivity and stability of the human beta-glucuronidase in the fusion protein was comparable to the activity of recombinant human beta-glucuronidase. Using anti-idiotype affinity chromatography, two molecules of a molecular weight of 125 kDa or 250 kDa could be visualized under nonreducing conditions in SDS-PAGE. Reducing conditions revealed a 25 kDa light and 100 kDa heavy chain. Due to its suitable biological characteristics this fusion protein might be an appropriate molecule allowing a site specific antibody directed enzyme prodrug therapy (ADEPT) in vivo.
Br J Cancer 1992 Feb
PMID:Molecular and functional characterisation of a fusion protein suited for tumour specific prodrug activation. 173 23

In patients with precancerous states and cancer of the uterine cervix prior to and after radiotherapy exhibit the decreased activity of neutrophil beta-glucuronidase. Moreover, patients treated by radiotherapy before the age 6 to 9 years demonstrate deficiency of N-acetyl-beta-glucuronidase in the above cells. The main finding in lymphocytes of the patients studied was in the appearance by diffusion of the above enzymes and of acid phosphatase in the cytoplasm, reflecting their release from lysosomes and immunological mobilization of these cells. The authors discuss the possible role of neutrophil enzymatic deficiency in lowering the antitumor cytotoxic effect of these cells.
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PMID:The intracellular enzymatic response of neutrophils and lymphocytes in patients with precancerous states and cancer of the uterine cervix. 175 56

Long-chain fatty acids inhibit glucuronidation of benzo(a)pyrene phenols in perfused liver; therefore, this study was designed to investigate interactions of fatty acids with beta-glucuronidase, glucuronosyl transferase, and energy supply. In beta-glucuronidase-deficient C3H/He mice, infusion of oleate (250 microM) increased the release of free benzo(a)pyrene phenols from 14 to 33 nmol/g/h and decreased release of glucuronides into the perfusate from 25 to 17 nmol/g/h. Rates of accumulation of glucuronides in the liver were also diminished from 11 to 4 nmol/g/h after infusion of oleate (250 microM). Fatty acids did not affect the release of benzo(a)pyrene metabolites into bile, and the ratio of free phenol to glucuronide production was increased from 0.57 to 1.30. A similar trend was observed in livers from DBA/2 mice that have beta-glucuronidase. Rates of hydrolysis of benzo(a)pyrene-O-glucuronide were not altered in isolated microsomes by addition of oleoyl coenzyme A (CoA) or octanoyl CoA (10- approximately 100 microM). Thus, we conclude that fatty acids do not alter glucuronidation by acting on beta-glucuronidase. The concentration of cofactors (UDP-glucuronic acid, UDP-glucose, and adenine nucleotides) involved in hepatic conjugation was not altered by infusion of concentrations of oleate (300 microM) that inhibited glucuronidation in perfused livers. When oleate concentrations were increased to 600 microM, UDP-glucuronic acid and UDP-glucose decreased 44 and 49%, respectively, and the ATP:ADP ratio declined concomitantly. Oleoyl CoA inhibited UDP-glucuronosyl transferase noncompetitively (half-maximal inhibition, 10 microM) in microsomes with 3-hydroxy-benzo(a)pyrene or p-nitrophenol as substrate. In contrast, octanoyl CoA was a very poor inhibitor of transferase activity. Inhibition of the transferase by oleoyl CoA was increased markedly by treatment with detergents (Triton X-100), i.e., half-inhibition of glucuronosyl transferase was obtained with about 2 microM oleoyl CoA. Inhibition of UDP-glucuronosyl transferase by oleoyl CoA was also increased in a dose-dependent manner by albumin, possibly due to increasing access of the CoA derivative to the enzyme. Collectively, these data indicate that fatty acids diminish glucuronidation via the formation of acyl CoA compounds that inhibit UDP-glucuronosyl transferase noncompetitively.
Cancer Res 1991 Sep 01
PMID:Inhibition of glucuronidation of benzo(a)pyrene phenols by long-chain fatty acids. 190 48

Evidence for gene dosage effect for beta-glucuronidase (GUSB) and phosphoserine phosphatase (PSP), whose genes are mapped on chromosome 7, was searched in a group of 13 patients with myeloproliferative disorders and acquired monosomy 7. The monosomy 7 was the sole anomaly in nine patients and was associated with other chromosome changes in four. A group of 19 patients with similar diseases but with normal karyotype or with anomalies not involving chromosome 7 served as control. beta-galactosidase and arylsulphatase A, whose genes are not on chromosome 7, were tested as control enzymes. We obtained evidence for a gene dosage effect for GUSB, but not for PSP. When all cases with monosomy 7 were compared with controls, no dosage effect was observed for PSP, but when this group was split into two, according to the presence of anomalies additional to the monosomy 7, the values of activity in the group with additional anomalies were significantly lower than in the controls. Thus, in the case of PSP, the loss of one allele is not followed immediately by reduction in activity, and this could be due to the specific importance of PSP in nucleic acid metabolism. We postulate that some regulatory mechanisms are able to keep normal levels of PSP even in the presence of only one allele, and that they are overwhelmed only when additional chromosome changes are present. These changes tend to involve chromosomes carrying genes for enzymes involved in a metabolic pathway closely related to PSP functions, and only then is a gene dosage effect for PSP detectable.
Genes Chromosomes Cancer 1990 Jan
PMID:Gene dosage effect in acquired monosomy 7: distinct behaviour of beta-glucuronidase and phosphoserine phosphatase. 196 82

The results of cerebrospinal fluid (CSF) biochemical markers were compared with conventional CSF cytology in patients treated for leptomeningeal metastases from extra cranial malignancies. For lumbar CSF, before treatment, no statistically significant difference of the probabilities of being positive was found between CSF cytology and a classification by linear discriminant analysis, based on patient's age, of beta-glucuronidase and beta 2-microglobulin. During treatment, classification by linear discriminant analysis was found more often positive than cytology. Possible mechanisms for this difference are discussed. For ventricular CSF a correlation was found between CSF cytology and beta-glucuronidase for solid tumours, and between CSF cytology and beta 2-microglobulin for haematological malignancies. Reference values for ventricular protein, CEA beta-glucuronidase and beta 2-microglobulin were obtained for cytological negative samples.
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PMID:Cerebrospinal fluid tumour markers in patients treated for meningeal malignancy. 201 36

GR63178A is the second pentacyclic pyrroloquinone to enter clinical trials as an anticancer drug. We developed a reversed-phase, gradient-elution high-performance liquid chromatography (HPLC) method along with a Bond Elut C2 mini-column sample-preparation technique for the analysis of GR63178A, its 9-hydroxy-metabolite GR54374X and internal standard GR70440A in human plasma and urine. The limit of detection is 2 ng/ml for both GR63178A and GR54374X. Analysis of GR63178A is complicated by its light instability, whereby a number of chromatographically distinct, stable degradation products can form. These can be practically eliminated if clinical specimens are frozen immediately and all subsequent sample preparation is performed in a darkroom. Using this methodology, a total of six metabolites (including GR54374X) were detected in human plasma and urine specimens. The five new metabolites were characterised according to polarity (HPLC retention time), UV-visible absorption maxima and the effect of incubation with beta-glucuronidase and aryl-sulphatase. Application of this methodology to the analysis of GR63178A will aid in the development of this novel synthetic anticancer drug.
Cancer Chemother Pharmacol 1991
PMID:Chromatographic characterisation of six human metabolites of the new anticancer drug GR63178A. 204 30

Three 13C-labeled 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]-ethyl)amino-9,10- anthracenedione dihydrochloride (mitoxantrone) isotopomers were synthesized to prove the proposed chemical structures of human urinary metabolites by means of nuclear magnetic resonance spectroscopy. After application of labeled mitoxantrone to an anesthetized pig, urine was collected by way of a vesicourethral catheter. The urinary metabolites were isolated by liquid chromatography using a new procedure developed for extraction of mitoxantrone metabolites. Structural elucidation by nuclear magnetic resonance spectroscopy and tandem mass spectrometry confirmed the proposed mono- and dicarboxylic acid structures of the metabolites. High-performance liquid chromatography of native pig urine showed an additional metabolite detected by its UV-visible absorption. The new metabolite was identified as a glucuronic acid conjugate of mitoxantrone by means of nuclear magnetic resonance spectroscopy and tandem mass spectrometry. Incubation with beta-glucuronidase under high-performance liquid chromatography control revealed mitoxantrone as the sole product. Quantitative high-performance liquid chromatography analyses showed that the new urinary metabolite represents the main biotransformational pathway of mitoxantrone in pigs, indicating significant interspecies variation in mitoxantrone biotransformation. Expressed in equivalents of mitoxantrone, the new metabolite amounts to 25% and 31%, respectively, of urinary excreted drug-related material. Extraction of patient urine using the same procedure led to the isolation of pure metabolite B. Tandem mass spectrometric data delivered definitive evidence for the structure of metabolite B as monocarboxylic acid of mitoxantrone.
Cancer Res 1991 Jul 01
PMID:Isolation and structure elucidation of urinary metabolites of mitoxantrone. 205 83

This investigation studied the effects of a shift from a mixed diet to a lactovegetarian diet on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lactovegetarian diet, there was a significant decrease in beta-glucuronidase, beta-glucosidase, and sulphatase activities per gram feces wet weight (p less than 0.05, less than 0.05, and less than 0.001, respectively). In contrast, glucuronide and glucoside hydrolysis remained unchanged per gram dry weight, although sulphatase activity was still significantly lowered when expressed this way (p less than 0.01). However, the fecal excretion increased significantly (p less than 0.05). Part of the explanation for the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content. The higher water content was probably due to a higher fiber intake (p less than 0.001). Thus, the results in this paper indicate that a change from a mixed diet to a lactovegetarian diet leads to a decrease in certain enzyme activities proposed to be risk factors for colon cancer.
Nutr Cancer 1990
PMID:Shift from a mixed diet to a lactovegetarian diet: influence on some cancer-associated intestinal bacterial enzyme activities. 212 19

There is now growing evidence from animal models for the possible control of different stages of the carcinogenic process by the beta-glucuronidase inhibitor D-glucaro-1,4-lactone and its precursors such as D-glucaric acid salts, D-glucarates. D-Glucaric acid is a natural, non-toxic compound produced in small amounts by mammals, including humans. It was recently found in some vegetables and fruits. D-Glucaro-1,4-lactone and D-glucarate exhibit potent antiproliferative properties in vivo. Some human subpopulations could have reduced risk of cancer development by ingesting food rich in D-glucaric acid or self-medication with D-glucarates alone or in combination with other chemopreventive agents.
Cancer Lett 1990 Oct 08
PMID:Potential use of D-glucaric acid derivatives in cancer prevention. 220 84

The XAD-2 resin concentration/elution system for concentration of mutagens contained in urines was optimized for cancer patients who had been administered such antineoplastic agents as adriamycin (ADR; doxorubicin), cyclophosphamide (CP), methotrexate, vincristine, and 5-fluorouracil. In the reverse mutation assay, Salmonella typhimurium strains TA1535 and TA98 differentiated between CP (with S9 fraction) and ADR (without S9), respectively. No dose-response for CP was observed. There was a dose-response to ADR by TM677 in the presence of S9 using a forward mutation assay. However, while the reverse mutation assays successfully detected ADR and CP administration in the presence of each other in terms of urine mutagenicity, the forward mutation assay did not, since unidentified CP metabolites were also detected in the latter. None of these systems detected mutagenic urines from tobacco smokers, although reaction of these urines with beta-glucuronidase allowed this type of source to be detected also.
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PMID:Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide. 220 75


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