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

The cancer chemotherapeutic efficacy of 3,4-dihydroxybenzylamine (DHBA), a dopamine analog with reduced neurotoxic effects, was evaluated in strain A mice bearing transplantable Ehrlich's ascites carcinoma. The analog was administered intraperitoneally on day 1 post-transplantation at dose schedules of 50, 100 and 200 mg/kg/day for 7 consecutive days. The results demonstrated a significant inhibition of tumor growth and prolongation of the survival time of EAC tumor bearing mice following DHBA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with the stimulated activity of the lysosomal enzyme beta-glucuronidase in the DHBA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. Tumor inhibition was accompanied by marked improvements in hemoglobin concentration. RBC count and bone marrow cellularity. The results demonstrated that DHBA did not adversely affect hematological profile of the host while it inhibited the growth of Ehrlich's ascites carcinoma.
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PMID:Tumor inhibition and hematological improvements by dopamine analog 3,4-dihydroxybenzylamine in mice bearing transplantable carcinoma. 223

Little is known of the pharmacology of rhodamine 123 (RH-123), an agent reported to have carcinoma-selective experimental antitumor activity. Accordingly, using a high-performance liquid chromatographic assay system with fluorescence detection, we examined the plasma decay and the biliary and urinary elimination of parent drug and metabolites in female Sprague-Dawley rats receiving RH-123 at an intravenous dose (5 mg/kg) equivalent to the therapeutic dose used in murine tumor models. Following drug administration to unconscious animals, plasma levels of drug-associated fluorescence fell in a triphasic manner (t1/2 alpha, 15 min; t1/2 beta, 1 h; t1/2 gamma, 4.7 h). In plasma, unchanged drug predominated but lower levels of the deacylated metabolite rhodamine 110 (RH-110) and two unknowns were also detectable throughout the study. Drug fluorescence was recovered extensively in both urine and bile. In unconscious animals with ureteral cannulae, urinary excretion (11.4% of the dose in 6 h) occurred predominantly as unchanged RH-123 (97% of the total), with low levels of RH-110 (2.4%) and two unknowns (less than 0.6% combined) also being present. Similarly dosed conscious animals (without surgical intervention) housed in metabolic cages showed a comparable pattern of urinary excretion, with 11.9% of the drug dose being recovered in 6 h and 21.9%, by 48 h. Biliary drug elimination accounted for 8% of the delivered dose in 6 h in unconscious animals and for 11% by 36 h in conscious animals fitted with biliary cannulae. In contrast to urinary excretion, in which unchanged drug predominated, only 50% of the fluorescence recovered in bile was attributable to RH-123. The remainder was due to a number of products that were detectable throughout the study. Of these, one present at significant levels was identified as a glucuronide conjugate of RH-123, based on the liberation of parent drug when the purified metabolite was incubated with beta-glucuronidase or hydrolyzed with 1 N hydrochloric acid. Further studies with a radiolabeled form of RH-123 are necessary to establish the identity of the remaining unknowns disclosed in this work.
Cancer Chemother Pharmacol 1990
PMID:Metabolism and elimination of rhodamine 123 in the rat. 226 56

Dietary glucarate has previously been shown to inhibit chemical carcinogen-induced rat mammary tumorigenesis. It is demonstrated in this paper that in the mammary gland of the female Sprague-Dawley rat, feeding glucarate at a dose of 70 mmol/kg AIN76A diet for 2 weeks beginning at 35 days of age, markedly reduces [3H]thymidine labeling. Specific histochemical staining for beta-glucuronidase is used to show that the glucarate diet fed to rats for 2-4 weeks inhibits beta-glucuronidase activity in the mammary gland and has a marked antiproliferative effect on mammary epithelium. Glucarate may inhibit rat mammary carcinogenesis, in part, by changing the proliferative status of the target organ.
Cancer Lett 1990 Jan
PMID:Antiproliferative effect of dietary glucarate on the Sprague-Dawley rat mammary gland. 230 96

The effects of dietary calcium, magnesium, and butterfat on intestinal function and flora in rats initiated with 1,2-dimethylhydrazine (DMH) were studied. Male weanling rats were assigned to six isocaloric diets that varied in their levels of calcium and magnesium (0.25% Ca with 0.05% Mg, 1.0% Ca with 0.05% Mg, or 0.625% Ca with 0.50% Mg) and butterfat (5% or 20%). One-half of the rats in each treatment were injected subcutaneously with DMH weekly for four weeks. This short-term exposure to DMH increased colonic ornithine decarboxylase (ODC) activity and the mass of cecal contents. Ingestion of the high levels of either calcium or magnesium depressed colonic ODC activity and depressed apparent absorption of organic matter, calcium, magnesium, and phosphorus. Ingestion of excess magnesium increased the mass of the cecal contents by twofold, caused hypertrophy of cecal walls, and increased the total amount of protein and total nitroreductase and beta-glucuronidase activity in the ceca of rats. Ingestion of supplemental calcium had less dramatic effects and increased the mass of cecal contents by only 28% and decreased the total amount of protein in the ceca. On the basis of their different effects on cecal microflora, magnesium appears to have less potential than does calcium as a protective agent against colon cancer.
Nutr Cancer 1990
PMID:Changes in intestinal function of rats initiated with DMH and fed varying levels of butterfat, calcium, and magnesium. 230 74

Comparative intestinal nitroreductase, azo reductase, beta-glucuronidase, dechlorinase and dehydrochlorinase activities in young male Fischer 344 rats and young male CD-1 mice were measured in vitro while the comparative biotransformation of 2,6-dinitrotoluene to mutagenic metabolites was determined in vivo. The mice, which exhibit a high spontaneous incidence of hepatomas, had markedly greater nitroreductase activity and metabolized significantly more 2,6-dinitrotoluene to mutagenic metabolites than did Fischer 344 rats, which show a low incidence of liver tumors. Results of this study indicate that species differences in the incidence of hepatomas may be influenced by microbial flora and/or the biotransformation of xenobiotics in the G.I. tract.
Cancer Lett 1990 Jun 30
PMID:Comparative gastrointestinal enzyme activity and activation of the promutagen 2,6-dinitrotoluene in male CD-1 mice and male Fischer 344 rats. 235 14

The activity of acid phosphatase, beta-glucuronidase and N-acetyl-beta-glucosaminidase was assessed using semiquantitative cytochemical methods in peripheral blood lymphocytes of 45 untreated patients with gastric cancer and 80 healthy subjects. In cancer patients the study demonstrated a statistically significant decrease in the number of lymphocytes with granular reaction for acid phosphatase and N-acetyl-beta-glucosaminidase, as well as an increase in the number of lymphocytes showing a granular-diffuse reaction for the above enzymes and a diffuse reaction for all the studied lysosomal enzymes. Possible mechanisms of the observed changes are discussed.
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PMID:Lysosomal enzymes in peripheral blood lymphocytes of patients with gastric cancer. 243 66

Beta-glucuronidase activity was extracted from prostatic carcinomas and hyperplastic prostates. It was 3.6-fold higher (P less than 0.0001) in prostatic carcinoma than in prostatic hyperplasia. Analysis for isoenzymes of prostatic beta-glucuronidase by disc-gel electrophoresis in nondenaturing polyacrylamide gels demonstrated only one form of the enzyme. Histochemically, enzymatic activity was observed almost entirely in epithelial cells in both prostatic carcinoma and benign prostatic hyperplasia.
Cancer 1989 Aug 15
PMID:Beta-glucuronidase activity in prostatic carcinoma and benign prostatic hyperplasia. 247 70

Random bred Syrian hamsters given s.c. injections of SV40 small t deletion mutants dl883, dl884, and dl890 rapidly develop reticulum cell sarcomas in the abdominal cavity in addition to slowly developing s.c. fibrosarcomas at the site of virus inoculation. Injection of wild type SV40 s.c. induces only fibrosarcomas at the site of inoculation. In an attempt to understand why mutations in the SV40 small t gene should lead to this difference in tumor-inducing capacity in hamsters, we studied cells from 12 abdominal reticulum cell sarcomas which were induced by the s.c. injection of SV40 mutants. Morphological and functional analyses indicate that these tumor cells are derived from MAC-2+ macrophages. They are highly granulated, vacuolated, and multinucleated, and they generally adhere to glass and plastic. In addition, they (a) phagocytose latex beads; (b) express high levels of class II major histocompatibility complex antigens; (c) contain beta-glucuronidase, acid phosphatase, and fluoride-inhibited nonspecific esterase; (d) contain lysozyme and fibronectin; and (e) express cell surface MAC-2 antigens. Thus, the small t deletions in the SV40 genome appear to permit the virus to transform cells that are distant from the site of virus inoculation; at this distant site, the cells transformed are of a specific lineage, MAC-2+ peritoneal macrophages. This specific tropism may reflect a unique characteristic of MAC-2+ cells or their precursors that renders these cells susceptible to SV40 mutants which are otherwise restricted in the range of cells that they can transform.
Cancer Res 1989 Mar 15
PMID:Characterization of hamster tumors induced by simian virus 40 small t deletion mutants as true histiocytic lymphomas. 253 29

In 234 patients with various malignant diseases including cancer of the larynx, cancer of the lung, cancer of the stomach, cancer of large intestine as well as patients with Hodgkin's disease, plasma cell myeloma and precancerous states of the larynx, the count of peripheral blood lymphocytes showing intact beta-glucuronidase-positive lysosomes was determined using a semiquantitative histochemical method. All the patients studied, except patient with cancer of the lung, showed a tendency toward a low count of such cells significant in patients with precancerous states of the larynx, cancer of larynx, cancer of the larynx after radiotherapy and Hodgkin's disease and nonsignificant in cancer of the stomach, cancer of the large intestine and plasma cell myeloma. In patients with cancer of the lung the count of lymphocytes with intact beta-glucuronidase-positive lysosomes was significantly increased as compared with that in healthy subjects. The possible relationship between the low immune response in the patients and the functional state of the lymphocyte lysosomal system is discussed.
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PMID:Beta-glucuronidase-positive lymphocyte population with intact enzyme-positive lysosomes in patients with malignancies. 261 75

1. The interactions of B16-F1 and B16-F10 tumors with their surrounding tissues in terms of enzyme activities such as cathepsin B, hemoglobin(Hb)-hydrolase, acid phosphatase, beta-glucuronidase and plasminogen activator were investigated when said tumors proliferated locally and at secondary sites throughout the host's circulatory system. 2. In the case of B16-F1 and B16-F10 tumor cells proliferating under the skin, statistical differences were not detected between the enzyme activities of the skin surrounding the tumors and control skin, nor between B16-F1 and B16-F10 tumors, except for beta-glucuronidase. 3. In the case of B16-F1 and B16-F10 tumor cells metastasizing to lung, statistical differences were detected between numerous enzyme activities of the lung tissues surrounding the tumors and control lung tissue, and also between B16-F1 and B16-F10 tumors. 4. The activities of cathepsin B and acid phosphatase of lung tissue surrounding B16-F1 tumor were lower than those of the control lung. 5. beta-Glucuronidase activity of lung tissue surrounding B16-F10 tumor was higher than that of the control lung. 6. The activities of cathepsin B, Hb-hydrolase and beta-glucuronidase of the B16-F10 tumor were higher than those of the B16-F1 tumor. 7. Results indicate that metastasized B16 melanoma tumor cells interact with surrounding lung tissues, and that cathepsin B, Hb-hydrolase and beta-glucuronidase might play important roles in the metastasis of the malignant tumor.
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PMID:Interaction of tumor and surrounding tissue of mice inoculated B16 melanoma variants in terms of enzyme activity. 266 66


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