Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to the fibrous mineral erionite is known to induce mesothelioma in man and laboratory animals. Previous studies demonstrated the presence of a trypsin-like protease associated with tumour cells. This protease could be demonstrated by the use of fluorescent probes which located cells possessing this enzyme. We have employed this fluorescent probe technique to follow the early events in the lungs of rats exposed to erionite. The evidence presented shows that the mesothelial cells initially lack this enzyme but the enzyme can be detected within hours of exposure of the rat to erionite. The number of mesothelial cells possessing the enzyme steadily increased after a single exposure to the mineral until the animal finally died with a massive pleural tumour. This is the first study of such fluorescent probes in the early stages of tumour induction.
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PMID:A study of guanidinobenzoatase during development of mesothelioma induced in the rat by fibrous erionite. 285 10

Intermediate-sized filaments have been noted in epithelioid sarcoma by previous investigators, two of whom have reported that the filaments represent vimentin. We utilized polyclonal antibodies directed against keratin and immunoperoxidase techniques (PAP) to stain 32 of the more than 300 cases accumulated at the AFIP . All of our material was formalin-fixed, paraffin-embedded. Seventy-five percent of our cases (24/32) showed positive immunoreactivity, a feature that may be of diagnostic help in distinguishing epithelioid sarcoma from modular fasciitis, benign and malignant fibrous histiocytoma, malignant melanoma, and necrotizing granuloma. In these cases, the reaction was enhanced using predigestion with trypsin. The immunoreactivity varied from tumor to tumor, perhaps due to formalin fixation. Since synovial sarcoma and mesothelioma may also be cytokeratin-positive, our findings indicate that keratin immunoreactivity is not confined to epithelial tumors and may also occur in neoplasms traditionally regarded as mesenchymal.
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PMID:Keratin in epithelioid sarcoma. An immunohistochemical study. 620 17

Hyaluronan-binding sites were demonstrated on the cell surface of three malignant mesothelioma cell lines derived from human tumors using either [3H]hyaluronan or fluorescein-tagged hyaluronan. No hyaluronan-binding activity was observed on normal human mesothelial cells. The absence of hyaluronan receptors on normal human mesothelial cells was not due to a down-regulation by endogenously synthesized hyaluronan, since no binding sites appeared when the cells were cultured under conditions known to suppress hyaluronan synthesis (in starvation medium containing either hydrocortisone or n-butyrate) or to degrade endogenously synthesized hyaluronan (in the presence of Streptomyces or testicular hyaluronidase). The binding of [3H]hyaluronan on mesothelioma cells could be partially inhibited by prior incubation of the cells with trypsin, indicating that the hyaluronan-binding site is a protein. The binding sites on human malignant mesothelioma cells were shown to be saturable with about 54,000 hyaluronan molecules (M(r) 1.4 x 10(6)) bound per cell with a Kd of 0.3 x 10(-9) M. The binding was specific for hyaluronan inasmuch as a number of other macromolecules gave negligible inhibition of the binding. High molecular weight preparations of hyaluronan inhibited the binding more effectively than low molecular weight preparations; hyaluronan oligosaccharides down to a length of six monosaccharide units showed competing activity. The hyaluronan receptor appeared to be related to CD44 (a cell surface glycoprotein previously suggested to function as a hyaluronan receptor) since Hermes-1 monoclonal antibodies which inhibit the binding of hyaluronan to CD44 blocked a major part of the binding of hyaluronan to the mesothelioma cells. However, there was no strict correlation between the hyaluronan-binding activity on the mesothelioma cell lines tested and the levels of CD44 molecules on their cell surface, suggesting that only a subfraction of the CD44 molecules bound hyaluronan or that other hyaluronan-binding proteins also exist on those cells. The presence of hyaluronan receptors on mesothelioma cells, but not on their normal counterparts, may be of importance for the migration of the transformed cells in hyaluronan-enriched matrices and for their ability to form metastases.
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PMID:Hyaluronan receptors are expressed on human malignant mesothelioma cells but not on normal mesothelial cells. 751 23

A human malignant pleural mesothelioma cell line (STAV) was studied with respect to production of the extracellular matrix components laminin, type IV collagen, and fibronectin, and interactions with these proteins in vitro. We also analyzed STAV cell serum-free conditioned medium with respect to the possible presence of "autocrine motility factor-like" substance. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of biosynthetically labeled STAV serum-free conditioned medium showed that STAV cells released several proteins into the medium, including components with molecular weights of 850,000, 540,000 and 440,000. Using Western blotting we identified these proteins as laminin, type IV collagen, and fibronectin, respectively. By immunocytochemistry laminin, type IV collagen, and fibronectin were detected as a matrix surrounding the cells. Plastic culture dishes coated with microgram quantities of laminin, type IV collagen, and fibronectin induced attachment and spreading of STAV cells. Laminin, type IV collagen, and fibronectin stimulated directional (chemotactic) migration of STAV cells in Boyden chambers fitted with 8 microns filters. The same cells also migrated to insoluble step gradients of filter-bound extracellular matrix components (haptotaxis). When STAV serum-free conditioned medium was separated by using fast protein liquid chromatography Superose 6 gel filtration, two motility-inducing protein peaks were detected. The first peak contained proteins with molecular weight > 220,000 that had both chemotactic and haptotactic properties, while the second peak contained material with apparent molecular weights of approximately 67,000 that had chemotactic and chemokinetic (random motility) but not haptotactic properties. Analysis of the M(r) 67,000 material indicated that it was a heat-sensitive and trypsin-digestible protein. The production of both soluble and insoluble extracellular matrix components by human mesothelioma cells and the motile response to these molecules as well as the production of a M(r) 67,000 autocrine motility factor-like substance may be important for the highly invasive motile behavior of this tumor.
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PMID:Chemotaxis and haptotaxis of human malignant mesothelioma cells: effects of fibronectin, laminin, type IV collagen, and an autocrine motility factor-like substance. 836 33

The hyaluronan production by three human malignant mesothelioma cell lines and nine primary human mesothelial cell types was determined. The mesothelioma cell lines produced only minute amounts of hyaluronan (less than 0.1 microgram/10(6) cells/48 h) whereas mesothelial cells synthesized large quantities of hyaluronan (10-72 micrograms/10(6) cells/48 h). Conditioned media from the mesothelioma cell lines were investigated for their ability to stimulate hyaluronan production by fibroblasts and mesothelial cells in vitro, and in all cases stimulatory effects were found. The factor(s) in the conditioned medium of the mesothelioma cell line Mero-25 that were responsible for hyaluronan stimulation were heat stable and partially trypsin resistant. The stimulatory activity was partially inhibited by an antiserum against platelet-derived growth factor and basic fibroblast growth factor. Our data suggest that the increased hyaluronan synthesis seen in patients with mesothelioma is due to the release of factors from mesothelioma cells that stimulate other cells to produce hyaluronan.
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PMID:Human mesothelioma cells produce factors that stimulate the production of hyaluronan by mesothelial cells and fibroblasts. 841 31

We report a woman with ascites, hydrothorax, pancreatic tumor, left cystic ovarian tumor, and an elevated serum cancer antigen 125 level. Exploratory laparotomy was performed to determine peritoneal disseminated carcinoma of unknown origin. Immunohistochemical analysis demonstrated positive staining for carcinoembryonic antigen, trypsin, and progesterone receptor and nonspecific or negative reaction for calretinin, estrogen receptor, amylase, lipase, Wilms tumor gene 1 protein, and inhibin or chromogranin A. These results together with the morphology of tubular structure suggested the pathological diagnosis of adenocarcinoma with pancreatic characteristics and contradicted ovarian cancer or mesothelioma. Immunohistochemistry is an adjunct tool to differentiate the primary site of carcinomatous peritonitis.
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PMID:Immunohistochemistry for the differentiation of peritoneal disseminated carcinoma of unknown origin. 1520 56

The purpose of this study was to investigate immunological effector cells and angiogenesis in malignant pleural mesothelioma (MPM) patients, who underwent multimodality treatments. Clinical and pathological characteristics of 57 patients, with International Mesothelioma Interest Group stage II-III MPM, who underwent two different multimodality treatments (with and without immunotherapy) between 1999 and 2008 were analyzed. CD8+, CD4+ and Foxp3+ tumor-infiltrating lymphocytes, tryptase and chymase mast cells (MCs), CD34, number of microvessels and vascular endothelial growth factor were determined by immunohistochemistry. The histology was 51 epitheliomorf and 6 biphasic. The stage was III in 41 cases and II in 16 cases. With an average follow-up of 69 months (range 9-115) 14 patients are still alive and the overall median actuarial survival is 21.4 months. Tryptase MCs, CD8+ and Foxp3+ lymphocytes had significantly increased in the interleukin 2 (IL-2) treated group. Moreover, the number of microvessels was significantly lower in IL-2 treated patients. This study indicates that immunotherapy leads to an increase in cytotoxic CD8+ lymphocytes and tryptase MCs and to a decrease of the tumoral neoangiogenesis. Changes in MPM microenvironment induced by immunotherapy may play a major role in the local control of this disease and need further investigations.
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PMID:Multimodality treatment of malignant pleural mesothelioma with or without immunotherapy: does it change anything? 2005 97

Angiogenesis plays a crucial role in progression of pleural malignant mesothelioma. A significantly increased incidence of pleural mesothelioma has been attributed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. In this study, we have investigated the expression of CD68-positive macrophages, tryptase-positive mast cells and CD31 positive areas, as expression of microvascular density, in lung tissue of sheeps exposed to fluoro-edenite fibers vs controls, by immunohistochemical, morphometric and Western blot analysis. The result have evidenced a significant increase in the expression of CD68-positive macrophages, tryptase-positive mast cells as well as a significant increase in microvascular density evaluated as CD31 positive areas in lung tissue of of sheeps exposed to fluoro-edenite fibers vs controls. These data confirmed the important role played by tumor microenvironment components, including macrophages and mast cells, in favour of angiogenesis in pleural mesothelioma induced by fluoro-edenite exposure.
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PMID:Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers. 2734 91