Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A collagenase was purified from homogenates of V2 ascites-cell carcinoma growing in rabbit muscle. (NH4)2SO4 precipitation, ion-exchange and gel-filtration chromatography, and affinity chromatography (by using the CB7 CNBr) cleavage fragment of alpha 1(I) collagen linked to agarose) gave a 268000-fold purification and a sevenfold increase in total enzyme units recovered. The specific activity, defined as mumol of collagen in solution cleaved/h per mg of enzyme at 35 degrees C, WAS 1.74.2. The collagenase had a broad pH optimum from pH7.0 to 9.5, and a mol.wt. of between 33000 and 35000. It was inhibited by dithiothreitol, L-cysteine, D-penicillamine, EDTA and 1,10-phenanthroline, and by both rabbit and human serum. 3. Removal of cations by a chelating resin (Chelex 100) produced as inactive enzyme that could be reactiviated by the addition of Ca2+ ions at concentrations as low as 1muM. Other bivalent cations were not effective. 4. The purified collagenase cleaved peptides alpha2 and alpha1-CB7 (denatured polypeptides of collagen) at 37 degrees C at one site only. [alpha1 (I)]2alpha2 and [alpha1(III)]3 collagens in solution were cleaved at the same site approximately five times more rapidly than [alpha1 (II)]3. 5. An inhibitor of the enzyme in the tumour extracts, which was dissociable from the enzyme at the (NH4) 2SO4 precipitation step of purification, had a mol. wt. of between 40000 and 50000 but was distinct from the alpha1 trypsin inhibitor. 6. Studies with zonal density-gradient centrifugation suggested that the enzyme was bound to fibrillar substrate (collagen) extracellularly, but that it was not associated with enzymes originating in cell mitochondria, microsomal preparations or lysosomes.
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PMID:Purification and characterization of a collagenase extracted from rabbit tumours. 0 61

1. The immunological cross-reactivity between rabbit collagenases from a variety of normal and pathological sources was examined. The specific antibody raised against collagenase secreted from normal rabbit synovial fibroblasts gave reactions of complete identity with collagenases secreted from fibroblasts derived from rabbit skin, and from synovium from experimentally arthritic rabbits. 2. The rabbit fibroblast collagenase was immunologically identical with collagenases obtained from the organ culture medium of normal rabbit skin, synovium, ear fibrocartilage and subchondral bone. 3. Collagenases from the culture media of normal rabbit synovium and from hyperplastic synovium of rabbits made experimentally arthritic were identical. 4. The collagenase secreted from rabbit fibroblasts gave a reaction completely identical with that of a collagenase extracted directly from a rabbit carcinoma. 5. IgG (immunoglobulin G) from a specific antiserum to rabbit fibroblast collagenase was a potent inhibitor of the collagenases obtained from the culture media of the various rabbit cells and tissues. 6. Collagenases from human synovium and from mouse macrophages and bone were neither precipitated nor inhibited by antibodies to rabbit collagenase. 7. No immunoreactive material was found in lysates of rabbit polymorphonuclear leucocyte granules with the specific antisera to rabbit fibroblast collagenase. No evidence for inactive forms of rabbit collagenase in lysates of the rabbit synovial fibroblasts could be found, either by double immunodiffusion against the specific collagenase, or by displacement of active enzyme from inhibition by the IgG.
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PMID:Rabbit collagenase. Immunological identity of the enzymes released from cells and tissues in normal and pathological conditions. 5 76

Benign and malignant prostatic tissue was removed in surgery and partitioned for (a) ultrastructural study, (b) tissue culture, and (c) (c) immunochemical study. Fourteen malignant and 18 benign prostatic cancer specimens were examined by transmission electron microscopy (TEM) for the presence of viruses or virus-like particles. Viruses could not be identified with assurity in thin sections. Acinar cells of normal, benign prostatic hypertrophy (BPH), and neoplastic prostate tissue were examined in the scanning electron microscope and TEM and found to be extremely heterogenous in their surface morphologies. Three major types of surface morphologies were present: microvillous, ruffled, and bare. All three types of cells were present in normal, BPH, and neoplastic acini. A collagenase procedure was utilized to remove the stromal cells from glandular structures prior to in vitro cultivation. Partially purified extracts from 71 human urothelial tumors and 75 human urothelial nontumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of one of the structural components of type-C ribonucleic acid viruses, the p30 core protein. The urothelial tumors tested included 42 BPH specimens and 18 prostatic carcinoma specimens. Thirty-eight percent of the prostatic carcinoma tissues and 48% of the BPH tissues demonstrated the presence of a protein antigenically similar to the p30 core protein of an oncogenic RNA virus.
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PMID:Morphologic and immunologic studies of human prostatic carcinoma. 6 19

Human osteosarcoma and mammary carcinoma cells were cultured separately in a medium supplemented with fetal calf serum, until they were confluent. The medium was then replaced by serum-free medium supplemented with heparin. Both cell cultures secreted collagenase, and this activity was inhibited by a cartilage-derived protein of low molecular weight. Since cartilage is rarely invaded by neoplasms, the presence of this inhibitor may play an important role in the regulation of tumor invasion.
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PMID:Tumor cell collagenase and its inhibition by a cartilage-derived protease inhibitor. 19 81

Serum-free media of minced tissue cultures of VX-2 rabbit carcinoma contained a specific collagenolytic activity capable of releasing soluble radioactive peptides from [14C]-labeled collagen fibrils. It was also capable of reducing the viscosity of acid-soluble collagen solutions by cleaving the tropocollagen (TC) molecules primarily at one site to TCA (75%) and TCB (25%) fragments. Three chromatographic fractions were separated by gel filtration: F1, (MW 85-110,000) present in larger amounts in early cultures of younger tumor tissue; F2, (MW-35-40,000) the major component with maximum production in the day 3 media of younger and advanced tumor tissues; F3, (MW 18-22,000) the minor component. Early cultures of younger tumor tissue contained a latent collagenase and were subject to trypsin activation suggesting the presence of inactive enzyme precursors or an enzyme-inhibitor complex.
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PMID:Changes in the collagenolytic activity released by primary VX-2 carcinoma cultures as a function of tumor growth. 19 82

By means of a biological assay for the enzyme collagenase the activity of this protease was examined in 12 invasive adenocarcinomas of the colon. In spite of considerable quantitative differences collagenolytic activity in the dimensions of 10(-3) units/mm theta tissue could be revealed in all cases. EDTA inhibited the reaction by 19%, normal human serum by 23% in the average, whereas 1,10-0-phenanthroline, D-penicillamine as well as the cytostatic 5-fluorouracil resulted in nearly total inhibition. It can be suggested that the activity of the colonic carcinoma is not derived from granulocytes, serum, or normal mucosa, but from the tumor itself. Contrasting to the limited inhibition by normal serum inhibitors, the enzyme is nearly fully inhibited by 5-fluorouracil.
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PMID:[5-fluorouracil inhibits the collagenolytic activity of invasive colonic adenocarcinomas in vitro]. 21 50

Tissues from seventy-one patients were obtained within one-half hour of biopsy, mastectomy, or reduction mammoplasty and processed for scanning electron microscopy (SEM). Epithelial structures were detected by supravital staining with methylene blue and isolated by microdissection. Mammary lobules and ductules required bacterial collagenase digestion to remove the covering stroma for optimal visualization. Major histopathological categories were compared and correlated with the characteristics observed with methylene blue supravital staining and light microscopy and/or transmission electron microscopy as a function of surface features revealed by SEM. Mammary ducts can be readily distinguished from ductules and lobules by their characteristic surface epithelium. Duct epithelium undergoes a variety of changes in fibrocystic disease (FCD) and in carcinoma. Both apocrine and merocrine secretory activity was observed in the surface epithelium. Proliferation of both epithelial and stromal elements was observed in benign fibroadenomata. Intraductal carcinomas were distinguished by their relative lack of surface microvilli. SEM offers a practical tool in the potential identification of premalignant cells of the human breast epithelium.
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PMID:Diseases of the human breast: selective isolation and exposure of epithelia and their correlative surface features and histopathology. 23 May 74

When cultured in-vitro, originating from different breast cancer patients, tumor cells, identified histologically as carcinoma cells, varied in their proliferation patterns and cell morphology. If exposed for brief periods to vibrio cholera neuraminidaes (VCN), the amount of sialic acid released from the cells varied from one culture to another and increased with higher enzyme concentrations. If exposed to trypsin, the amount of released proteins varied also from one culture to another. Significant difference was observed between the effect of VCN or collagenase on normal and neoplastic cell cultures. Whether human or murine cell cultures, the cell-free media harvested from cultures of neoplastic cells containing high concentrations of collagenolytic-caseinolytic-fibrinolytic and esterolytic activities. Two effects of concanavalin A (Con A) have been distinguished on thymidine incorporation, the first is a decrease in the maximal thymidine uptake, whereas the second is a shift to the maximum thymidine uptake to higher Con A concentrations. At low concentrations, alpha-1-antitrypsin (AAT) had no effect, but at high concentrations it inhibited 3H-thymidine uptake. At low concentrations human profibrinolysin inhibited and at higher concentration sit enhanced uptake of the labeled precursor. Therefore, the collagen olytic caseinolytic-fibrinolytic enzyme is a pacemaker for proliferation of human mammary carcinoma cells.
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PMID:Human mammary carcinoma cells. The enzyme pacemaker profibrinolysin. 31 26

Our investigation of normal, hyperplastic, and neoplastic prostatic tissue during the past 2 1/2 years has produced several findings which have been published or accepted for publication. (a) Cells from hamster prostates with intense histochemically demonstrable acid phosphatase activity (HDAP) after fixation with formaldehyde which we believe to be epithelial cells can be obtained in 97.2% +/- 0.8% purity by velocity sedimentation in a previously described isokinetic density gradient; (b) similarly, cells with HDAP, many of which contain lipofuscin granules, can be obtained as 81.0% +/- 12.2% of nucleated cells from hyperplastic human prostates and as 86.4% +/- 9.4% of nucleated cells from human prostatic carcinomas; (c) more cells were obtained from human hyperplastic prostates and prostates with prostatic carcinoma per gram of tissue with the aid of Pronase than were obtained with trypsin, collagenase, or mechanical methods; (d) more cells per gram of tissue were obtained from surgically removed prostates than from prostates obtained at even very rapid autopsies, and a much larger proportion of the cells from surgically removed prostates were viable as assessed both by dye exclusion and by plating efficiency; (e) none of several substrates and inhibitors which we tested were highly specific for acid phosphatase from purified prostatic epithelial cells compared with several other kinds of purified human cells; and (f) purified hamster prostatic epithelial cells incorporate large amounts of tritiated thymidine in 72-hour cultures.
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PMID:Separation and characterization of epithelial cells from prostates and prostatic carcinomas: a review. 87 27

The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) on matrix metalloproteinases (MMP) and metalloproteinase inhibitors was studied in a variety of human cell lines. Expression of the mammalian collagenase (MMP-1), 72-kD gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), 92-kD gelatinase/type IV collagenase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was assessed by zymography and Northern blot analysis. MMP-2 and TIMP-2 activities were refractory to TPA, IL-1 and TNF-alpha treatment in most of the cell lines. In contrast, MMP-3, MMP-9 and TIMP-1 activities were markedly stimulated by TPA in most of the tumor cell lines and human umbilical vein endothelial cells (HUVEC), whereas the fibroblast lines were minimally stimulated or unresponsive to TPA. The MMP-3, MMP-9 and TIMP-1 stimulation in response to IL-1 and TNF-alpha treatment was detected in some of the tumor cell lines and HUVEC. The increase in activity was less marked than in TPA. A breast carcinoma cell line, MDA-MB-231, which did not express MMP-2, had high expression of MMP-3 and MMP-9 which were unaffected by TPA and cytokine treatment. Northern blot analysis of MMP and TIMP mRNA expression reflected the zymogram findings for most of the cell lines. TPA-mediated stimulation of MMP-1 was similar to that of MMP-3 and MMP-9. Exceptions were the fibroblast cell lines which showed either a much more marked mRNA response of MMP-9 to TPA than observed at protein level, or a high constitutive MMP-9 mRNA when MMP-9 activity was not detectable by zymography. TPA-mediated stimulation of MMP-9 and TIMP-1 activity was blocked by staurosporine, an inhibitor of protein kinase C (PKC). A non-PKC-activating phorbol ester, 4 alpha-phorbol-12,13-didecanoate, did not stimulate MMP-9 and TIMP-1 activity. TPA treatment caused the increased expression of c-fos containing AP-1-specific binding activity in selected tumor cell lines. This activity was maximal at 6 h. An association was observed between AP-1 binding activity and increased expression of MMP-1, MMP-3 and MMP-9, which possess TPA-responsive elements (TRE). TPA-sensitive MMPs and TIMP-1 were variably stimulated by biologically relevant cytokines, such as IL-1 and TNF-alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of phorbol ester and cytokines on matrix metalloproteinase and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines. 128 26


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