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 effect of pyran copolymer, injected into mice bearing the M109 Madison lung carcinoma, on serum concentrations of lysozyme, beta-glucuronidase, and N-acetyl-beta, D-glucosaminidase was studied and compared with that of other immunoadjuvants. Increases in lysozyme levels ranging from 50 to 100% were observed after injection of pyran, BCG and Bru-Pel; increases in the levels of the other enzymes were less consistent. Other immunoadjuvants were less effective in raising serum concentrations of lysosomal enzymes. The findings were correlated with the results of previous studies on macrophage activation and antineoplastic action produced by these immunoadjuvants and suggest that serum levels of lysozyme can serve as indices of these effects.
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PMID:Effect of macrophage activation by immunoadjuvants on serum levels of lysosomal hydrolases in mice. 55 9

Lactic dehydrogenase (LDH) isoenzymes were measured in the cerebrospinal fluid (CSF) patients suffering a variety of cancer-related neurologic problems. LDH-5 isoenzyme as a percentage of total LDH activity was abnormally elevated (above 10 to 15%) in leptomeningeal infiltration by carcinoma (breast carcinoma, lung carcinoma, and malignant melanoma) but not in other types of CNS metastases. Abnormal LDH isoenzyme patterns were also seen with CSF infections in which a granulocytic pleocytosis was present. In the absence of infection, an elevated LDH isoenzyme 5:1 ratio suggested leptomeningeal tumor and, when used with other CSF markers (beta-glucuronidase and CEA), LDH, isoenzymes aid in early detection of this metastatic neoplastic process. They may also help to differentiate leptomeningeal tumor from other chronic meningitides. Measurement of CSF markers also aids in assessing the effectiveness of treatment since marker levels often vary with the clinical course.
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PMID:Lactic dehydrogenase isoenzymes in the cerebrospinal fluid of patients with systemic cancer. 726 Aug 57

ADEPT (antibody-directed enzyme prodrug therapy) is a novel therapeutic approach that targets an enzyme into tumors to convert a relatively nontoxic prodrug into an active cytotoxic agent. This method has a number of advantages, including the reduction of systemic toxicity, but to date it has not realized its full potential. A critical component of ADEPT is the choice of the monoclonal antibody (MAb) to target the enzyme into the tumor mass. Prior studies have utilized MAbs directed against tumor cell surface antigens which are oftentimes labile and heterogeneous in nature and do not provide an ideal site for the enzyme. As an alternative approach, we now describe the use of Tumor Necrosis Therapy (TNT) MAbs to deliver the enzyme to necrotic regions of tumors in order to enhance the effectiveness of ADEPT. Biodistribution and autoradiographic studies performed using TNT MAbs have shown that localization of these antibodies occurs in degenerating cells and necrotic regions of tumors and that binding is retained within the tumor mass for extended periods of time. Since necrotic regions are often located in the center of tumors, are universal in nature, and constitute between 30 and 80% of the tumor mass, TNT MAbs may be ideal targeting agents for ADEPT. To test this hypothesis, fusion proteins consisting of single chain Fv (scFv), Fab, or F(ab')2 fragments of chTNT-3 and the human beta-glucuronidase (betaG) enzyme were constructed for ADEPT. Each of these reagents was tested to assess specificity and avidity of antigen binding as compared to the parental antibody. In addition, studies were performed to demonstrate enzymatic function of the fusion proteins and retention of catalytic activity in circulating blood, specific tissues, and tumor after in vivo administration. Pharmacokinetic and biodistribution studies of radiolabeled fusion proteins were conducted over time to evaluate the characteristics of the fusion proteins. Finally, one of the constructs (chTNT-3 Fab/betaG) was used in a pilot treatment study with a glucuronide prodrug of doxorubicin to demonstrate the anti-tumor activity of ADEPT using the chemoresistant MAD109 murine lung carcinoma tumor model transplanted into BALB/c mice. The results of these experiments show that all three constructs retained their antigen binding capability and demonstrated active enzymatic function against substrate in vitro. Moreover, after in vivo administration, the betaG enzyme was shown to localize to tumor and remain active for up to 9 days demonstrating a key characteristic of TNT targeting. Pharmacokinetic and biodistribution studies confirmed specific localization of the fusion proteins and rapid clearance from blood and normal tissues over time. Finally, therapeutic studies using only two doses of fusion protein followed by prodrug administration demonstrated active cytotoxicity against established tumors without systemic toxicity. These preliminary studies show that the use of TNT MAbs to target the enzyme to the tumor may be a significant advance in ADEPT and that further studies are warranted to test this novel therapeutic approach in the treatment of solid tumors.
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PMID:Chimeric TNT-3/human beta-glucuronidase fusion proteins for antibody-directed enzyme prodrug therapy (ADEPT). 1295 21

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.
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PMID:Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II). 1872 Jan 91

Some new complexes of tolfenamic acid (=2-[(2-methyl-3-chlorophenyl)amino]benzoic acid; Htolf) with potentially interesting biological activities are described. The complexes [Mn(tolf)(2)(H(2)O)(2)], [Co(tolf)(2)(H(2)O)(2)], [Ni(tolf(2)(H(2)O)(2)], [Cu(tolf)(2)(H(2)O)](2), and [Zn(tolf)(2)(H(2)O)] were prepared by the reaction of tolfenamic acid, a potent anti-inflammatory drug, with metal salts. The radical-scavenging activities of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay. Their ability to inhibit soybean lipoxygenase, beta-glucuronidase, and trypsin-induced proteolysis was studied. Their inhibitory effects on rat paw edema induced by carrageenin was studied and compared with those of tolfenamic acid. The complex [Zn(tolf)(2)(H(2)O)] exhibited the strongest in vivo inhibitory effect at 0.1 mm/kg Body Weight (BW; 93.0+/-0.9%), superior than the inhibition induced by tolfenamic acid at the same molar dose (76.0+/-0.9%). Tolfenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), and A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The complexes [Mn(tolf)(2)(H(2)O)(2)] and [Cu(tolf)(2)(H(2)O)](2) have shown selectivity against T24 cell line. The IC(50) values of these two complexes against T24 cancer cell lines are in a micromolar range similar or better to that of the antitumor drug cisplatin.
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PMID:Anti-inflammatory, antiproliferative, and radical-scavenging activities of tolfenamic acid and its metal complexes. 1955 37