Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transplantable pregnancy-dependent mouse mammary tumor line TPDMT-4 behaves like a preneoplastic lesion in virgin mice when implanted with tissue pieces. This study was conducted to elucidate whether enzymatic cell dissociation enhances the tumorigenic potential as in hyperplastic mammary nodules. When tissue pieces were implanted in virgin mice, there was an increase in tumor incidence from 0% at generation 14 (F14) to 40% at 38 (F38) during the 6-month observation; early (F8), middle (F16-18) and late (F39-40) transplant generation (ETG, MTG and LTG respectively) tumors were dissociated with collagenase and hyaluronidase. DDD strain females receiving an injection of 10(5) dissociated cells into the fat pad were observed as virgin or ovariectomized. ETG cells formed palpable tumors in 18 (43%) and 21 (50%) of 28 virgins at latent periods of 133 +/- 11 (mean +/- SE) and 142 +/- 10 days for 6 and 8 months respectively. MTG and LTG cells did so in 24 (60%) of 40 and 25 (89%) of 28 virgins at 77 +/- 5 and 68 +/- 5 days respectively for 6 months. In ovariectomized mice, however, no palpable tumors developed from any of these cells. Most ETG and MTG cell-derived tumors repeated palpable growth and total regression one or more times, and subsequently disappeared or grew slowly, whereas almost all LTG tumors grew progressively from the onset. MTG cells infiltrated into the fat pad more extensively than ETG and LTG cells: MTG cells occupied almost the whole fat pad at 6 weeks, whereas the outgrowths of the other cells were confined to one-eight of the fat pad. Southern blot analyses demonstrated the absence of certain extra MMTV DNA fragments in MTG tumors, although the distinct behaviors of MTG cells could not be ascribed to it alone. The results suggest that enzymatic cell dissociation may enhance tumorigenesis by hormone-dependent mammary tumor cells at lower hormone levels.
Carcinogenesis 1988 Jun
PMID:Enhancement of tumorigenic potential in virgin mice of a pregnancy-dependent mouse mammary tumor (TPDMT-4) by enzymatic cell dissociation. 283 7

Hepatocytes were prepared from rainbow trout by perfusion in situ with collagenase and hyaluronidase. Preparations normally showed high initial viability (95 +/- 5% dye exclusion, 92 +/- 5% lactate dehydrogenase retention) and gradually decreased in viability and glutathione concentration over 5 hours. Cellular metabolism of aflatoxin B1 (AFB1), a potent hepatocarcinogen, was characterized by an investigation of the following parameters: kinetics of AFB1 metabolism and DNA adduct formation, dose response, viabilities of detoxication and activation pathways with time, influence of organic solvents, and effect of variation in cell concentration. The AFB1 metabolites and DNA adducts were resolved and quantitated by high-performance liquid chromatography. From these results a standardized assay procedure was derived which we used to examine AFB1 metabolism and DNA adduct formation in hepatocytes from fish fed dietary substances known to alter the carcinogenic response to this mycotoxin. Dietary beta-naphthoflavone, which strongly inhibits AFB1 carcinogenesis in rainbow trout, dramatically and reproducibly altered AFB1 binding and metabolism in isolated hepatocytes. Overall rate of AFB1 metabolism and rates of detoxication reactions increased, whereas DNA binding decreased. Dietary cyclopropenoid fatty acids, powerful synergists and promoters of AFB1 carcinogenesis in trout, also repressed AFB1-DNA binding. Both dietary factors appeared to depress initial DNA damage by AFB1 but operated through different metabolic pathways to do so.
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PMID:Dietary modification of aflatoxin B1 carcinogenesis: mechanism studies with isolated hepatocytes from rainbow trout. 643 Dec 90

In the 1960s, a close relationship between heavy exposures to crocidolite asbestos and mesothelioma was established. The debate on the diagnosis of mesothelioma became complicated because of the possibility of litigation. Well differentiated mesothelioma cells are mucicarmine negative but alcian blue and periodic acid-Schiff (PAS) positive, which are removed by hyaluronidase and diastase digestion. By electron microscopy (EM), they show bush-like elongated, slender, and branching microvilli. By immunohistochemistry they express both keratin and vimentin but not carcinoembryonic antigenicity (CEA), B72.3, Ber-EP4, and Leu-M1. In poorly differentiated mesotheliomas, chromosomal and molecular biological alterations are common and complex but these alterations also overlap with that of poorly differentiated tumours of the lung and other organs. A poorly differentiated pleural tumour is most likely metastatic and needs good team work to locate the primary site. The diagnosis of a mesothelioma and asbestosis should be established separately. Future studies will be focused less on the phenotypic differences but more on the broad molecular and multi-phasic mechanisms of carcinogenesis, irrespective of the aetiological agents, in poorly differentiated tumours.
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PMID:Pleural mesothelioma: an approach to diagnostic problems. 944 Nov 14

Apigenin is a plant flavonoid that is thought to play a role in the prevention of carcinogenesis. However, its mechanism of action has not yet been elucidated. Because of the importance of angiogenesis in tumor growth, we investigated the effect of apigenin on endothelial and smooth-muscle cells in an in vitro model. Apigenin markedly inhibited the proliferation, and, to a lesser degree, the migration of endothelial cells, and capillary formation in vitro, independently of its inhibition of hyaluronidase activity. In contrast, it strongly stimulated vascular smooth-muscle-cell proliferation. The molecular mechanisms of apigenin activity were analyzed in these 2 types of cells. Our results show that apigenin inhibits endothelial-cell proliferation by blocking the cells in the G(2)/M phase as a result of the accumulation of the hyperphosphorylated form of the retinoblastoma protein. Apigenin stimulation of smooth-muscle cells was attributed to the reduced expression of 2 cyclin-dependent kinase inhibitors, p21 and p27, which negatively regulate the G(1)-phase cyclin-dependent kinase.
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PMID:Apigenin inhibits endothelial-cell proliferation in G(2)/M phase whereas it stimulates smooth-muscle cells by inhibiting P21 and P27 expression. 1069 50

Hyaluronidase and hyaluronic acid, two substances thought to be strongly implicated in carcinogenesis, were assessed in the plasma of 35 patients with newly documented monoclonal gammapathy and in 25 control patients. A significant increase was found in plasma hyaluronidase activity in the patients with monoclonal gammapathy. A statistically significant positive correlation was found between hyaluronidase activity and monoclonal immunoglobulin levels in plasma. An increase in serum hyaluronidase activities may be a response to the deleterious effect of hyaluronic acid in cell migration and tumor progression. Further studies are needed to assess the value of hyaluronidase activity as a marker of tumor progression.
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PMID:Hyaluronidase activity in serum of patients with monoclonal gammapathy. 1102 Apr 70

It has been reported that two inducible prostaglandin synthetic enzymes, cylooxygenase-2 (COX-2) and microsomal PGE synthase, are over-expressed in non-small cell lung cancer (NSCLC). Using quantitative reverse transcription-polymerase chain reaction, we analyzed RNA levels of the key prostaglandin catabolic enzyme, NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH), in 19 pairs of NSCLC tumors and adjacent non-malignant tissue from the same patient. We found that 100% of tumor-tissue pairs showed at least a 2-fold decrease and 61% showed a 10-fold decrease. This suggests that the increased expression of COX-2 and PGE synthase in tumors may work in concert with the decreased expression of 15-PGDH to amplify an increase in tissue levels of proliferative PGE2. To further explore if 15-PGDH is related to tumorigenesis, athymic nude mice were injected with control A549 cells or cells transiently over-expressing wild-type or mutant 15-PGDH (Y151F). It was found that mice injected with control A549 cells or with cells expressing mutant enzyme produced tumors normally. However, mice injected with A549 cells expressing wild-type 15-PGDH had a significant decrease in tumor growth. Examining the effects of 15-PGDH expression on cellular changes in A549 cells, we found that over-expression of 15-PGDH induced apoptosis of A549 cells as evidenced by fragmentation of DNA, activation of pro-caspase 3, cleavage of poly(ADP-ribose) polymerase and decreased expression of Bcl-2. We also found that the expression of 15-PGDH was negatively related to that of pro-adhesive and invasive CD44. Furthermore, the expression of 15-PGDH was found to be stimulated by hyaluronidase. These results suggest that 15-PGDH may decrease the level of proliferative PGE2, induce apoptosis and function like a tumor suppressor.
Carcinogenesis 2005 Jan
PMID:NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. 1535 36

Experimental examination of normal human mammary epithelial cell (HMEC) behavior, and how normal cells acquire abnormal properties, can be facilitated by in vitro culture systems that more accurately model in vivo biology. The use of human derived material for studying cellular differentiation, aging, senescence, and immortalization is particularly advantageous given the many significant molecular differences in these properties between human and commonly utilized rodent cells. Mammary cells present a convenient model system because large quantities of normal and abnormal tissues are available due to the frequency of reduction mammoplasty and mastectomy surgeries. The mammary gland consists of a complex admixture of many distinct cell types, e.g., epithelial, adipose, mesenchymal, endothelial. The epithelial cells are responsible for the differentiated mammary function of lactation, and are also the origin of the vast majority of human breast cancers. We have developed methods to process mammary gland surgical discard tissues into pure epithelial components as well as mesenchymal cells. The processed material can be stored frozen indefinitely, or initiated into primary culture. Surgical discard material is transported to the laboratory and manually dissected to enrich for epithelial containing tissue. Subsequent digestion of the dissected tissue using collagenase and hyaluronidase strips stromal material from the epithelia at the basement membrane. The resulting small pieces of the epithelial tree (organoids) can be separated from the digested stroma by sequential filtration on membranes of fixed pore size. Depending upon pore size, fractions can be obtained consisting of larger ductal/alveolar pieces, smaller alveolar clusters, or stromal cells. We have observed superior growth when cultures are initiated as organoids rather than as dissociated single cells. Placement of organoids in culture using low-stress inducing media supports long-term growth of normal HMEC with markers of multiple lineage types (myoepithelial, luminal, progenitor). Sufficient numbers of cells can be obtained from one individual's tissue to allow extensive experimental examination using standardized cell batches, as well as interrogation using high throughput modalities. Cultured HMEC have been employed in a wide variety of studies examining the normal processes governing growth, differentiation, aging, and senescence, and how these normal processes are altered during immortal and malignant transformation. The effects of growth in the presence of extracellular matrix material, other cell types, and/or 3D culture can be compared with growth on plastic. Cultured HMEC, starting with normal cells, provide an experimentally tractable system to examine factors that may propel or prevent human aging and carcinogenesis.
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PMID:Processing of human reduction mammoplasty and mastectomy tissues for cell culture. 2332 88

Hyaluronic acid is an evolutionarily ancient molecule commonly found in vertebrate tissues and capsules of some bacteria. Here we review modern data regarding structure, properties, and biological functions of hyaluronic acid in mammals and Streptococcus spp. bacteria. Various aspects of biogenesis and degradation of hyaluronic acid are discussed, biosynthesis and degradation metabolic pathways for glycosaminoglycan together with involved enzymes are described, and vertebrate and bacterial hyaluronan synthase genes are characterized. Special attention is given to the mechanisms underlying the biological action of hyaluronic acid as well as the interaction between polysaccharide and various proteins. In addition, all known signaling pathways involving hyaluronic acid are outlined. Impaired hyaluronic acid metabolism, changes in biopolymer molecular weight, hyaluronidase activity, and enzyme isoforms often accompany carcinogenesis. The interaction between cells and hyaluronic acid from extracellular matrix that may be important during malignant change is discussed. An expected role for high molecular weight hyaluronic acid in resistance of naked mole rat to oncologic diseases and the protective role of hyaluronic acid in bacteria are discussed.
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PMID:Hyaluronic Acid--an "Old" Molecule with "New" Functions: Biosynthesis and Depolymerization of Hyaluronic Acid in Bacteria and Vertebrate Tissues Including during Carcinogenesis. 2655 63