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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this report we describe the isolation and characterization of a neutral metalloproteinase, from human small cell lung cancer cells, which degrades a wide range of connective tissue proteins. Treatment of tumor cytosol by ammonium sulphate precipitation followed by zinc chelated column chromatography, anion exchange chromatography, and gel filtration chromatography yielded a single enzymatically active protein, which on SDS-PAGE appeared as a diffuse band of 65,000-70,000 daltons. The tumor metalloproteinase, which was inhibited by metal chelators and serum, was able to digest gelatin, type I collagen, type IV collagen, laminin, and fibronectin. We propose that the capacity of this proteinase to degrade both components of blood vessel basement membranes and other connective tissue matrices facilitates the dissemination of human lung cancer cells during the multistep process of metastasis.
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PMID:Characterization of a connective tissue degrading metalloproteinase from human small cell lung cancer cells. 283 54

A 41-year-old man with acromegaly was suffering from chronic, progressive backache and aware of reduction in his body height. Endocrine studies revealed increased glucose non-suppressible serum growth hormone (GH) and serum prolactin (PRL). Pituitary microadenoma was detected by a computerized axial tomogram and subsequently resected by trans-sphenoidal adenomectomy. The tumor proved to be a mixed GH- and PRL-secreting adenoma by electron microscopy and immunoperoxidase staining. Concurrent investigation of backache and reduced height disclosed markedly reduced radiodensity of the spinal bones, bilateral nephrocalcinosis, and hypercalciuria, which were ascribed to renal tubular acidosis (RTA) demonstrated by reduced urinary excretion of acids and insufficient reduction of urinary pH following oral administration of ammonium chloride. From the analogy to certain endocrinopathies, it appears likely that enhanced calcium metabolism and resultant hypercalciuria due to excess GH and PRL have led to the development of RTA, which further enhanced calciuria. Such enhanced calcium metabolism and consequent hypercalicuria conceivably led to accelerated demineralization of the spine and resulted in the reduced height of this patient in his early forties.
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PMID:A case of active acromegaly with reduced height and type 1 renal tubular acidosis. 289 4

The data relating to plasma steroid binding and transport (usually measured with dehydrotestosterone) are controversial. The plasma E2 binding of 79 breast carcinoma patients, 19 premenopausal and 60 postmenopausal, were compared to 46 controls, 21 premenopausal and 25 postmenopausal. In this study the authors removed the endogenous steroids with charcoal, incubated the plasma with 17-beta-E2 in non-saturation conditions, and used ammonium sulfate to precipitate the complex. The authors chose 17-beta-E2 as ligand because the plasma steroid binding system has not been shown to be homogeneous and because this binding function may vary independently for the different steroids. In these patients, the E2 binding was significantly (P less than 0.01) increased (85 +/- 11 pg/ml and 73 +/- 13 pg/ml in premenopausal and postmenopausal) compared to the normal controls (59 +/- 7 pg/ml and 58 +/- 5 pg/ml in premenopausal and postmenopausal women. It is still unclear whether this is a primary increase of the binding capacity or a reaction of the host for sequestering excess circulating E2. However, the small percentage of false-positives and false-negatives suggests that E2 binding could be used as a tumor marker in breast carcinoma.
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PMID:Breast carcinoma and plasma 17-beta-estradiol binding. 291 Apr 36

A hybridoma cell line that secretes monoclonal antibody, MAb-ER-Br-1-15-4-18 is established. The MAb is highly specific for estrogen receptor (ER) from human breast tumor cells. In order to raise the antibody, the ER was first isolated from human breast tumor. Mice were immunized with the partially purified ER and the fusion of the spleen cells from the mouse, showing the highest serum titer, with the cells of the NS-1 mouse myeloma line, produced hybrid cells which continuously secreted antibodies specific for ER. Three of the hybridoma cultures which tested strongly positive were cloned using limiting dilution method and one of the cell lines was selected for further study. The recovery of the MAb from the cell culture was done by ammonium sulfate precipitation followed by dialysis and then hydroxylapatite liquid chromatography using linear gradients. The purity of the antibody was checked by polyacrylamide gel electrophoresis. The MAb was isotyped and found to be IgG1. When checked against other antigens the MAb showed a minimal cross-reactivity to ER from rabbit uterus and none to ovalbumin or rat liver ferritin. Further experiments showed that the MAb recognized the ER bound to the hormone and ER in the nucleus of breast tumor cells.
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PMID:Production and characterization of a monoclonal antibody to partially purified estrogen receptor from human breast tumor. 292 8

Normal C57BL/6 mouse spleen cells cultured for five days in the presence of fetal calf serum (FCS-induced suppressor generation culture) were shown, in mixing experiments, to suppress the primary humoral response of freshly explanted C57BL/6 spleen cells against sheep erythrocytes (SRBC). This suppressor cell generation was largely dependent on the FCS concentration in the suppressor generation culture. Ten or 5% FCS effectively supported the generation of suppressor cells, but 1% FCS only marginally supported it. When mouse serum (MS) from normal C57BL/6 mice was added to the suppressor generation culture, it inhibited the generation of the suppressor cells. Sera from allogeneic mice and athymic nude mice were also effective. The effect of MS was resistant to heat treatment (56 degrees C, 30 min). The inhibitory activity of MS was not dialyzable, and concentrated into the fraction which was not precipitated by 50% saturation of ammonium sulfate and which was eluted at a concentration of about 0.2 M NaCl from a DEAE-Sephadex A-50 column. The active fraction of MS also effectively inhibited the growth of Ehrlich tumor cells in culture. Further, MS also inhibited the generation of Con A-induced suppressor cells. The inhibition by MS of FCS-induced suppressor generation was eliminated by an interleukin 2-containing preparation.
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PMID:Inhibition of suppressor cell generation by mouse serum in culture. 293 49

A human T-T hybridoma clone with helper cell phenotype was established from fusions between a HPRT- variant of the human T-cell lymphoma Molt4, and PPD-activated normal human T-lymphocytes. The hybrid clone (MP-6) was characterized with regard to expression of markers and lymphokine secretion. The T-T hybridoma was positive for Leu 3a, and thus of T-helper cell lineage. The transferrin receptor (T-9) and the interleukin 2 (IL-2) receptor (Tac) were also expressed as judged by immunofluorescence analysis using monoclonal antibodies. The hybridoma produces B-cell stimulatory factor (BSF) with proliferation and maturation activities, growth inhibitory factor (GIF), leukocyte migration inhibitory factor (LIF) constitutively under serum free conditions, but no detectable interferons (IFN-alpha, IFN-beta, IFN-delta), nor interleukin 2 (IL-2). Weak interleukin 1 (IL-1)-like activity was found. The B-cell stimulatory factor (BSF) induced solid phase-anti-mu triggered resting B-cells obtained from human spleen, tonsil or peripheral blood to proliferate and to secrete IgM and IgG. Without anti-mu triggering the BSF had no proliferation inducing effect. The BSF was characterized and partially purified using ammonium sulphate precipitation, Blue-Sepharose, HPLC hydrophobic interaction and HPLC gel filtration chromatography. The BSF was heat labile at 56 degrees C and was present in two forms, one with high and one with intermediate hydrophobicity. The more hydrophobic form of BSF has a molecular weight of 12K-14K. Kinetic studies of the lymphokine secretion revealed that BSF was produced in detectable amounts in low density (0, 2 X 10(6) cells/ml) 18-24 h cultures. In 48 h to 72 h cultures there was a significant influence of growth inhibitory activities (GIF) produced. GIF, with an apparent MW of 90K could be absorbed out on certain tumor cell lines or on Blue-Sepharose. Further absorption analysis of BSF activities show that anti-mu triggered B-cells but neither resting B-cells nor T-cells could absorb BSF activity.
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PMID:A T-helper cell x Molt4 human hybridoma constitutively producing B-cell stimulatory and inhibitory factors. 294 47

A series of potential prodrug 5-halouridine 3',5'-cyclic monophosphates (5-X-cUMPs, X = F, Cl, Br, I, 1-4) has been prepared and tested for antitumor activity against murine leukemia L1210/0 and human lymphoblast Raji/0 cells and their deoxythymidine kinase deficient (TK-) counterparts, as well as for antiviral activity in primary rabbit kidney cells infected with herpes simplex virus type 1 or 2, vaccinia virus, or vesicular stomatitis virus. The 5-halopyrimidine bases, nucleosides (5-X-U), and 5'-monophosphates (5-X-UMP) were tested for comparison. 5-F-cUMP (1) showed reasonably potent inhibition of tumor cell proliferation (ID50 = 0.33-1.6 micrograms/mL), while the remaining diesters displayed ID50's ranging from 210 to greater than 1000 micrograms/mL. 5-F-cUMP was 70- to 300-fold less active than 5-F-dU in the same systems. With TK- L1210 cells, 5-F-cUMP was as potent as with the normal (L1210/0) line but was about fourfold less active with TK- Raji cells compared to Raji/0 cells. The 5-X-cUMPs showed little potency as antivirals. A single-crystal X-ray analysis of the ammonium salt of 5-I-cUMP confirmed its structure and showed the conformation of the phosphate ring to be the expected chair. The ribose pucker is near 3(4)T, and the torsion angle about the beta-glycosidic N(1)-C(1') bond is in the syn range (-84.8 degrees).
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PMID:Synthesis, structure, and antitumor and antiviral activities of a series of 5-halouridine cyclic 3',5'-monophosphates. 300 59

The purpose of this study has been to compare collagen-gelatin degrading enzymes isolated from cancer cell organelles and cytosol to the metalloproteinases released by cancer cells. To this end, metastatic mouse melanoma cell organelles were isolated by sucrose density gradient centrifugation and metalloproteinases were assayed using native and denatured [methyl-3H]collagen substrates. Solubilized proteinases were purified by ammonium sulfate precipitation, anion exchange, concanavalin A affinity and gel-filtration column chromatographic procedures and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The conclusions were as follows: malignant melanoma cells have a metalloproteinase (Mr = 59,000) which is shed from cells into conditioned medium as a component of intact membrane vesicles rather than as a soluble enzyme; storage of tumor-conditioned medium leads to the generation of autoactivated soluble metalloproteinases of lower molecular weight; purification of these metalloproteinase species yielded variant collagenases that have considerable gelatinolytic activity and a cleavage preference site for the Gly-Ile bond in a collagen-like synthetic octapeptide substrate which is typical for collagenase-type metalloproteinases. It is proposed that localization of potent proteinases to the surface of cancer cells facilitates the local breakdown of connective tissues during the invasive process.
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PMID:Metastatic mouse melanoma cells release collagen-gelatin degrading metalloproteinases as components of shed membrane vesicles. 303 Apr 44

A monoclonal antibody to a cell surface glycoprotein on human colorectal carcinomas was raised using the undifferentiated colon carcinoma cell line MIP 101 as the immunogen. This antibody, ND4, is an IgG2a which does not cross-react with carcinoembryonic antigen (CEA), non-specific cross-reacting antigen, or blood group substances A, B, and H. Immunoprecipitation using lysates of cells grown in [35S]methionine or [3H]glucosamine and lysates of cells surface labeled with 125I showed binding to a cell surface glycoprotein with a molecular weight of approximately 160,000. Indirect immunofluorescence showed binding to the cell surface of 14 of 15 human colorectal carcinoma cell lines including six of six that do not secrete CEA. Two of seven human noncolorectal carcinoma lines and one of six nonhuman cell lines also bound antibody. Immunoperoxidase staining of formalin-fixed tissues showed prominent antibody binding with 19 of 33 (58%) human colorectal carcinomas, including five of six poorly differentiated tumors, five of 43 (12%) normal colonic mucosal biopsies, and one of 17 (6%) normal noncolonic tissues. One of 11 (9%) noncolonic tumors, a gastric adenocarcinoma, stained with ND4. Preliminary data obtained by a nonquantitative nitrocellulose dot-immunoassay have tentatively identified this glycoprotein in the serum of 15 of 37 (41%) patients with colorectal cancer. Three of the 15 patients had early stage disease and normal CEA levels (less than 2.5 ng/ml). Three patients had circulating antigen detectable preoperatively but not after tumor resection. Only one of 11 (9%) sera samples from normal subjects was positive. The characteristics of ND4 suggest that it may be of value in monitoring patients with colorectal carcinomas who do not have plasma CEA elevations. It may also be of value in the differential diagnosis of metastatic, poorly differentiated adenocarcinomas of unknown primary origin.
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PMID:A cell surface glycoprotein expressed by colorectal carcinomas including poorly differentiated, noncarcinoembryonic antigen-producing colorectal tumors. 305 11

Using immunocytochemical methods, we localized several glycoproteins of the extracellular matrix to leptomeningeal cells and meningiomas in vitro. Three cell lines derived from normal human leptomeninges and seven from meningiomas were studied by indirect immunofluorescence to evaluate the cellular production of fibronectin, laminin, collagen type IV, and procollagen type III. All leptomeningeal cell lines stained intensely and uniformly for all matrix proteins; all meningioma cell cultures stained uniformly, but the intensity of staining varied considerably. After removal of the cells in culture adherent to glass with 25 mM ammonium hydroxide, indirect immunofluorescence demonstrated an exuberant residual extracellular residue enriched with fibronectin, laminin, collagen type IV, and procollagen type III. Electron microscopic examination of all leptomeningeal and meningioma cultures revealed desmosomes and dense tonofilament formation; in addition, granular, filamentous basement membrane-like material was abundant in the extracellular spaces of all cultures. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the cell layer of two leptomeningeal and four meningioma cultures showed production of interstitial collagen types I and III; diethylaminoethyl (DEAE)-cellulose chromatography of the medium demonstrated preferential production of procollagen type I. Our findings show conclusively that normal arachnoid cells in vitro synthesize several of the collagen subtypes and may be responsible for the "fibrous response" of the leptomeninges to trauma, infection, or infiltration by tumor. The similarities between leptomeningeal cells and meningiomas demonstrated by electron microscopy and by indirect immunofluorescence support the notion that meningiomas are derived from arachnoid cells. The localization of various mesenchymal glycoproteins within the intra- and extracellular spaces and the ubiquity of specialized intercellular junctions suggest that leptomeningeal cells in culture have the potential to behave like both stromal and epithelial cells.
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PMID:An ultrastructural and immunocytochemical analysis of leptomeningeal and meningioma cultures. 308 53


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