Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronidase has gained increasing interest as an adjuvant in local and systemic cancer therapy, despite the incomplete knowledge of its physiological function. To this end, direct intratumoral injection of bovine testicular hyaluronidase (500, 1600 or 7500 U in 50 microl phosphate-buffered saline (PBS)) was performed in orthotopic (o.t.) osteosarcoma xenografts grown in the hind leg of nude mice. Control tumours received 50 microl PBS alone or supplemented with 10% bovine serum albumin (BSA). Central tumour interstitial fluid pressure (IFP) and mean arterial blood pressure (MABP) were measured using the wick-in-needle technique and after cannulation of the carotid artery, respectively. IFP was 32 +/- 8 mmHg (n = 44, mean +/- SD) in untreated tumours and there was a significant correlation between tumour IFP and volume (P < 0.01). The hyaluronidase injection reduced IFP to 63-84% after 1 h compared with controls (P < 0.05) and in a non-linear concentration-dependent manner. MABP was not affected significantly. In conclusion, an intratumoral hyaluronidase injection might reduce IFP temporally in solid osteosarcoma xenografts.
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PMID:Hyaluronidase reduces the interstitial fluid pressure in solid tumours in a non-linear concentration-dependent manner. 983 21

Results regarding hyaluronidase activity in tumor extracts or cell lines are subject to variations according to the method used for the assay and, sometimes, within an assay. Hyaluronidase was assayed at pH 3.8 in the culture medium of the human cancer-derived cell lines SA87 and H460M by several techniques: HPLC, Reissig technique, ELSA technique, and zymographic analysis. The optimal pH was between 3.3 and 4 in solutions at constant 150 mM sodium concentration. The enzyme was reversibly inhibited by sodium concentration over 200 mM. The activity of purified hyaluronidase increased in the presence of low concentrations of the specific HA-binding glycoprotein hyaluronectin, or of bovine serum albumin or immunoglobulins, or of human albumin, transferrin, or hemoglobin, showing that proteins cooperate in enzyme activity. The ELSA technique showed that optimal pH was slightly lower in the presence of HN than that with BSA. The optimal BSA concentration was determined with the ELSA technique at 0.1 g/liter, and excess of either protein inhibited hyaluronidase. When measured with the Reissig technique, the activity of purified enzyme in the presence of 0.1 g/liter BSA was up to fourfold that without BSA. The cooperative effect of BSA was visualized by zymography. We conclude that the total protein content of hyaluronidase solutions must be considered to correctly interpret quantitation of the enzyme in sera or tissue extracts because protein concentrations above 200 microg/liter lead to underestimation of the enzyme.
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PMID:Activation and inhibition of human cancer cell hyaluronidase by proteins. 1003 58

The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigated expression of the hyaluronic acid receptor CD44 protein in five human (T98G, A172, U87MG, 86HG39, 85HG66) and two rat (C6, 9L) glioma cell lines. Influence of anti-CD44 antibody and hyaluronidase-preincubation on the HA-binding was determined using HA/BSA (bovine serum albumin)-coated culture plates. While all gliomas were highly positive for CD44 with no differences in the number of positive staining cells, median fluorescence intensity decreased as follows: C6>T98G>9L>85HG66> 86HG39>A172>U87MG. Using HA/BSA coated culture plates the relative levels of specific adhesion to HA were determined as T98G>A172>9L>86HG39>U87MG> 85HG66. C6 cells failed to bind HA specifically. Incubation with anti-human-CD44 MAb significantly decreased HA-adhesion of T98G, A172, 85HG66 and U87MG human glioma cells. However the binding capacity was completely blocked only in 85HG66 cells. The three other cell lines kept a specific HA-adhesion after saturation of the receptor. Hyaluronidase pretreatment markedly enhanced HA-adhesion of C6 and 9L rat glioma cells. These results suggest that (i) HA-adhesion of malignant glioma cells is mainly, but not only, mediated by CD44, (ii) expression of CD44 does not correspond with adhesion capacity and (iii) cell-bound glycosaminoglycans may influence glioma cell adhesion to extracellular HA.
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PMID:CD44 expression and hyaluronic acid binding of malignant glioma cells. 1039 Jan 50

We investigated the mechanism of adhesion of highly malignant ascites hepatoma AH66F cells to mesothelial cells. The adhesion rate of AH66F cells to mesentery-derived mesothelial cells (M-cells) was about 46% at 37 degrees C, but it decreased to about 27% at 4 degrees C. The adhesion rate of AH66F cells was about 25% in the presence of leukocyte function-associated antigen 1 (LFA-1) mAb at both 4 C and 37 C. When M-cells were treated with hyaluronidase, the AH66F/M-cell adhesion was decreased to half at 37 degrees C and had nearly disappeared at 4 degrees C. The residual adhesion of AH66F cells to M-cells treated with hyaluronidase almost disappeared in the presence of LFA-1 mAb. AH66F cells strongly adhered to a hyaluronate (HA)-coated plate, but not to a bovine serum albumin-coated plate. AH66F cells expressed a CD44 molecule (a HA receptor) in the plasma membrane, with a molecular size of about 85 to 90 kDa, corresponding to the CD44H isoform. These results indicated that the adhesion of AH66F cells to mesothelial cells is composed of pathways of CD44/HA and LFA-1/ICAM-1.
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PMID:Adhesive interaction of highly malignant hepatoma AH66F cells with mesothelial cells. 1044 75

Elevated interstitial fluid pressure (IFP) in solid tumors may reduce the effect of systemically administered anticancer drugs. Modulation of the tumor extracellular matrix might reduce the elevated IFP. To study the influence of the microenvironment, the IFP was measured in human osteosarcoma xenografts grown both subcutaneously and orthotopically. The IFP response was recorded in xenografts grown at both sites after direct intratumoral injection of bovine testicular hyaluronidase (500 or 1600 units in 50 microliters saline). Control tumors received 50 microliters saline alone or 10% bovine serum albumin in saline. IFP was measured centrally in the tumors using the wick-in-needle technique, and mean arterial blood pressure was monitored after carotid cannulation. Tumor tissue sections were stained with hyaluronectin and analyzed for hyaluronan content using confocal laser scanning fluorescence microscopy. The baseline IFP was significantly higher in orthotopic (30 +/- 9 mmHg, n = 30) compared with subcutaneous tumors (17 +/- 6 mmHg, n = 11) of comparable sizes (p < 0.001). Injection of hyaluronidase reduced the IFP in both tumor models to 61-81% compared with controls 1 h after injection (p < 0.05), without affecting the mean arterial blood pressure significantly. The hyaluronan staining intensity increased in subcutaneous tumor sections, but remained unchanged in orthotopic tumor sections 1 h after injection of 1600 units of hyaluronidase. The IFP was restored within 48 h after hyaluronidase injection. Interestingly, IFP increased with tumor volume in orthotopic tumors, but not in subcutaneous tumors. In conclusion, intratumoral hyaluronidase injection reduces the IFP transiently in solid osteosarcoma xenografts. Furthermore, this study emphasizes that physiological parameters might differ significantly between human osteosarcoma xenografts grown subcutaneously versus orthotopically in nude mice.
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PMID:Interstitial fluid pressure in human osteosarcoma xenografts: significance of implantation site and the response to intratumoral injection of hyaluronidase. 1113 54

Four hundred and fifteen actinomycete strains were screened for hyaluronidase activity in two plate assays media. In the first one, using hyaluronic acid as substrate and bovine serum albumin (BSA) to help precipitation of the nondegraded substrate, only strain 594 and hyaluronidase control were positive. In the second assay, plates with hyaluronic acid, but not BSA, gave the same results. For plates containing only BSA, proteinase activity was detected in strain 594. When hyaluronic acid was treated with pronase, the only clear zones, in the second assay without BSA, were those around hyaluronidase controls. Protease activity, commonly found in actinomycetes, was detected only in strain 594, among the 415 studied, when tested in hyaluronidase assay using hyaluronate plus BSA. This may be due to the composition of the growth medium, since media with different composition gave different results for protease activity in each of the 15 strains analyzed. These data suggest that proteases can affect an accurate detection of hyaluronidase in media containing proteins, not only from hyaluronate preparations, but also from other medium ingredients. Thus, for a correct interpretation of the method, they must be excluded. Commercial Hyaluronidase used as controls must be also tested for the presence of protease contamination.
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PMID:Proteases from actinomycetes interfere in solid media plate assays of hyaluronidase activity. 1134 78

Quantitative determination of newly reported enzymes activity in the crude skin toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase, lesser activities of phospholipase A2, lactate dehydrogenase (LDH), cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich carcinoma-bearing mice demonstrated by an increase in the mean survival time (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the relative weights of heart and liver after three weeks, while modulating the elevation in the relative spleen weight throughout the treatment periods (three, six, and nine weeks). The levels of serum triglyceride, total cholesterol, and liver total lipids were normalized after three weeks, whereas the serum albumin and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and creatine kinase (CK) activities were significantly modulated throughout the treatment periods. Histological examinations of the tumor and liver tissues of treated tumor-bearing animals were carried out. Tumor tissues showed many cytolytic and cytopathic changes after treatment, while liver tissues showed moderate dysplastic changes after six weeks of treatment, which became more marked after nine weeks.
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PMID:Biological activities of the crude skin toxin of the Suez Gulf oriental catfish (Plotosus lineatus) and its antitumor effect in vivo (mice). 1250 71

Matrices made of glyceryl trimyristate as a bioerodible and biocompatible material were manufactured by compression in dimensions that would still allow an application via injection. Pyranine, as a low molecular hydrophilic compound with a low detection limit, and tetramethylrhodamine labeled bovine serum albumin (TAMRA-BSA), as a high molecular weight (66 kDa) protein compound, served as model drugs for release investigations. In vitro studies with pyranine revealed that release depends substantially on the gelatin content of the matrices, which proved to be a useful tool as a release modifier. The duration of the drug release period can be adjusted to a desired time interval ranging from days to weeks by choosing the right gelatin content. Moreover, results illustrated the importance of the molecular weight and the nature of the compound to be incorporated into such matrices, since investigations with TAMRA-BSA showed a more pronounced burst release and altered release profiles and periods. Experiments with hyaluronidase, which served as a model enzyme to assess the problem of protein integrity in such matrices, suggested that proteins may display sufficient stability during the manufacturing procedure of the cylinders or while in contact with the triglyceride matrices. In addition to in vitro investigations, a study in mice revealed that after 15 days of subcutaneous implantation the matrices showed a good in vivo stability. The main conclusion that could be drawn from these results was that triglycerides are a promising alternative to biodegradable polymers for the development of parenteral release systems for protein and peptide drugs.
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PMID:Monolithic triglyceride matrices: a controlled-release system for proteins. 1266 99

In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties. Abbreviations. compound K:20- O-beta- D-glucopyranosyl-20( S)-protopanaxadiol DNP:dinitrophenol DSCG:disodium cromoglycate DPPC:dipalmitoylphosphatidylcholine DPPH:1,1-diphenyl-2-picrylhydrazyl HSA:human serum albumin IC 50 :50% inhibitory concentration EC 50 :50% effective concentration XOD:xanthine oxidase ICR:Institute of Cancer Research PBS:phosphate buffered saline PCA:passive cutaneous anaphylaxis RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia SD:Sprague-Dawley
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PMID:Antiallergic activity of ginseng and its ginsenosides. 1286 69

This study was aimed to explore a simple and applicable method of separating mature sperms from human testicular tissue for intracytoplasmic sperm injection and embryo transfer. The suspension of human testicular tissue was cultured in 10% human serum albumin and human tubule fluid with different concentrations (0 u/ml; 50 u/ml; 100 u/ml; 150 u/ml; 200 u/ml) of hyaluronidase for 24 h, and then the Percoll gradient centrifugation was processed to separate the sperms; meanwhile the sperms were counted and graded according to their motility. The difference in quality and quantity among the groups and the difference between the groups and the zero-hour culturing group were detected. It was shown that the four hyaluronidase-treated groups contained large quantity and high quality of sperms as compared with the two contrast groups (P<0.01). The groups in the solution of 50 u/ml, 100 u/ml and 150 u/ml concentrations of hyaluronidase had almost the same amount of sperms that displayed higher motility as compared against the sperms in the group treated with 200 u/ml concentration of hyaluronidase (P<0.01). There was no difference between the two contrast groups (P>0.05), or among the groups treated with 50 u/ml, 100 u/ml, and 150 u/ml of hyaluronidase concentration (P>0.05). This method of adopting hyaluronidase with Percoll gradient centrifugation in the process for separating mature sperms from human testicular tissue is applicable. It can increase the quantity and quality of sperms separated from testicular tissue suspensions when adequate concentrations of hyaluronidase is used.
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PMID:[Primary study on the method for separating mature sperms from human testicular tissue]. 1588 57


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