Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colon tumors induced with azoxymethane in male Fischer rats were cytochemically analyzed for beta-glucuronidase using naphthol AS-B1 glucuronide (6-bromo-2-hydroxy-3-naphthoyl-O-anisidine) as a substrate and hexazonium pararosanin as a diazo reagent. This method effectively localizes the bulk of beta-glucuronidase in the surface epithelium, the lamina propria and in the endothelial cells of the lymphoid sinuses and postcapillary venules. Polypoid lesions, adenocarcinomas and mucinous adenocarcinomas show no difference in the amount or in the localization of beta-glucuronidase; however, mucinous adenocarcinomas show a slight increase in the amount of beta-glucuronidase. The few tumors that did metastasize to lymph nodes did not show any difference in their enzyme patterns. Intestinal crypts that show a change in size and shape have a definite increase in beta-glucuronidase activity. An increase in the activity of this enzyme can also be seen in well defined neoplasms as opposed to normal areas of the colon.
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PMID:The cytochemical demonstration of beta-glucuronidase in colon neoplasms of rats exposed to azoxymethane. 62 76

A spontaneous, hypomelanotic variant (MI) of the highly melanotic transplantable hamster melanoma of Bomirski (Ma) is the subject of this report. Tyrosinase activity is 2-3 times higher, but melanin content significantly lower than in the parental Ma melanotic melanoma. Acid phosphatase activity is similar in both, but beta-glucuronidase and aryl-sulfatase A are 2-3 times higher in the hypomelanotic variant. Transplanted MI melanomas grow more slowly than the parental tumor, but metastasize with similar incidence and localization. Hypomelanotic variant melanoma cells, even those in grossly nonnecrotic parts of the transplants, show signs of low viability like swelling of the cytoplasm or cellular condensation, and disintegration. Autophagic vacuoles are numerous. They appear to be formed by enclosure of a portion of cytoplasm by cisternae of smooth endoplasmic reticulum or trans-Golgi network. These limiting cisternae contain tyrosinase as evidenced by deposition of electron dense reaction product on incubation with tyrosine or DOPA. Other sites of ultrastructural tyrosinase reaction are melanosomes and the smooth-surfaced cisternae and vesicles of the trans-Golgi network. We postulate the low cell viability, associated with autophagosome formation, is the cause for the growth retardation of the MI variant, and that the lower melanin content of these tyrosinase-rich cells is due to sequestration of a substantial portion of newly synthesized enzyme into autophagic vacuoles before it has the chance of being incorporated into melanosomes.
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PMID:Pathology and ultrastructural characteristics of a hypomelanotic variant of transplantable hamster melanoma with elevated tyrosinase activity. 311 4

We have assessed the diagnostic value of the determination of cerebrospinal fluid lactate dehydrogenase, carcinoembryonic antigen, beta 2-microglobulin, beta-glucuronidase and total protein, using linear discriminant analysis, in detecting central nervous system metastases from extracranial malignancies. We conclude that, using these tests, it is impossible to differentiate between control individuals and patients with brain or epidural metastases. Leptomeningeal dissemination from either solid tumours or non-Hodgkin lymphoma could be differentiated from control individuals and patients with brain or epidural metastases. In this differentiation it is essential that bacterial, fungal or tuberculous meningitis be excluded from the differential diagnosis by other diagnostic procedures. The combination of beta-glucuronidase and beta 2-microglobulin provides almost the same diagnostic information as the combination of all parameters.
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PMID:Tumour markers in the cerebrospinal fluid of patients with central nervous system metastases from extracranial malignancies. 340 30

Glycosidases have been demonstrated to be elevated in the interstitial fluid of tumors, sera of animals and patients with tumors, and in some tumor tissue as compared to normal adjacent tissue. Elevations of serum beta-N-acetylglucosaminidase and beta-glucuronidase most commonly have been found to occur and these enzymes have been shown to be secreted into the extracellular medium by many different tumor cell types in vitro. The mechanism of cellular release of these hydrolytic enzymes probably involves tumor lysosomal exocytosis. Increased tumor glycosidase levels may promote increased tumor cell shedding from primary tumors, local invasion and perhaps be responsible directly, or indirectly for structural changes in tumor cell surface glycoconjugates. These cell surface changes could facilitate tumor cell thrombus formation, secondary site implantation and attachment in the microcirculation to endothelial cells and/or subendothelial basement membrane components. Other studies have demonstrated a correlation between metastatic cell potential and increased endoglycosidase and polysaccharide lyase activity. Generally, metastatic tumor cell variants have been found to be more invasive and capable of degrading proteoglycan basement membrane components, in part due to these increased levels of degradative enzymes. Hence, it is of considerable interest to develop inhibitors against these enzymes. Initial studies with glucuronidase inhibitors in the therapy of bladder tumors have been promising and with the advent of better agents and the use of appropriate in vitro metastatic models it may be possible to design and develop agents which interfere in various metastatic events and limit tumor progression.
Cancer Metastasis Rev 1985
PMID:Glycosidases in cancer and invasion. 388 85

beta-Glucuronidase activities were determined in cerebrospinal fluid from 249 patients suffering from various neurological diseases. Reference values were established as 9-27 mU/l. Marked elevations of cerebrospinal beta-glucuronidase activities were observed in patients with bacterial and carcinomatous meningitis. Slight elevations of cerebrospinal beta-glucuronidase activities were observed in epidural and parenchymal metastases from solid tumours. Comparison was made with the determination of total protein, glucose and lactate dehydrogenase in cerebrospinal fluid. Cerebrospinal beta-glucuronidase activity appeared the most useful test in monitoring patients at risk in developing meningeal metastases from solid primary tumours.
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PMID:Cerebrospinal fluid beta-glucuronidase activities in patients with central nervous system metastases. 398 58

A case of adenocarcinoma of Bartholin's glands in a middle aged female is presented. This well known, but rather uncommon malignancy is reported since it shows an unusual structure consisting of a combination of two different histological entities, namely an adeno-cystic component and adenopapillary component. An interval of 21 years elapsed between the appearance of the primary lesion and the recurrence which showed extensive haematogenous and lymphogenous metastases and proved fatal within two years of the recurrence. The study includes an enzyme histochemical evaluation and a fine needle cytological examination. The former revealed a high degree of activity of the NADP+ regenerating enzymes of the pentose shunt as well as a definite, but variable, activity of many lysosomal enzymes, mainly non specific esterases, acid phosphatase, aryl sulphatase and beta-glucuronidase. In contrast to other adenocarcinomas arising in the female genital tract, especially those of endometrium and ovary, the tumour cells showed only a slight activity of alkaline phosphatase, As is the case in many other adenocarcinomas, the activity of lactate dehydrogenase was strongly evident.
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PMID:Histochemical and cytochemical studies of metastasizing carcinoma of Bartholin's gland. 645 95

beta-Glucuronidase and carcinoembryonic antigen (CEA) were measured in the cerebrospinal fluid of patients with cancer. Both substances were found to reliably detect the presence of leptomeningeal infiltration by carcinoma. Neither substance was reliable in the detection of leptomeningeal infiltration by lymphoma or of metastases to the brain parenchyma or spinal epidural space. beta-Glucuronidase was moderately elevated in chronic infectious meningitis, whereas CEA was not. Both markers approached control levels with favorable treatment of the leptomeningeal metastases, reflecting the effectiveness of treatment. Both beta-glucuronidase and CEA hold promise as indicators of early metastatic involvement of the leptomeninges by carcinoma.
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PMID:Cerebrospinal fluid biochemical markers of central nervous system metastases. 721 47

Most cancer cells differ from normal cells in that they show higher beta-glucuronidase activity and lower pH of their cytoplasm. Anti-cancer drugs can be designed which take advantage of these gradients to deliver maximal toxicity to tumors and minimal toxicity to normal tissue. Many design criteria are suggested here, the most basic of which is the use of the glucuronide structure, in which glucuronic acid acts as a protective carrier of a toxic fragment which becomes active when split off by the beta-glucuronidase at the tumor site. The high beta-glucuronidase activity in cancer cells is also discussed here as a possible explanation for some of the pathognomonic features of a malignant growth: the automatic proliferation of tumor tissue, the invasion of tumors into adjacent tissue, the metastases to remote sites, and the weak response of the immune system.
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PMID:A minimal toxicity approach to cancer therapy: possible role of beta-glucuronidase. 738 90

Animal models of osteosarcoma with spontaneous pulmonary metastasis which retain metastatic capacity and osteoid formation after serial passages have been reported infrequently. In this communication we describe some biological features of a transplantable osteosarcoma, Os515, induced by BK-virus in Syrian golden hamsters. The subcutaneously transplanted tumours in 2-week-old animals grew progressively until death, with a mean survival time of 32 days. Distant metastases occurred only in the lungs in all animals. The histological appearance was osteosarcoma of osteoblastic type. Enzyme-histochemical staining showed alkaline phosphatase activity in many cells and beta-glucuronidase activity in few cells. Tumours transplanted intramuscularly in the hind limbs were amputated radically at 5 or 11 days. A small number of animals died from lung metastases without local relapse during the observation period of 140 days after grafting. All the control hamsters bearing unamputated tumours died much earlier. Necropsy revealed large metastatic nodules in the lungs of limb-amputated animals and small diffuse nodules in the lungs of untreated control animals. The development of lung metastases was monitored by soft X-ray without sacrificing the animals. This model will be useful in studies of mechanisms of metastasis and for the experimental treatment of osteosarcoma.
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PMID:An experimental transplantable osteosarcoma with spontaneous pulmonary metastasis in hamsters. 814 74