Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used two kinds of vectors to express a cDNA of human tissue plasminogen activator (t-PA) in mammalian cells. In one case, cDNAs inserted into vectors based on bovine papilloma virus were introduced into cultured murine cells and cell lines were established that efficiently and continuously secrete enzymatically active t-PA into the medium. Second, the t-PA gene was used to replace the sequences of the simian virus (SV40) genome that code for the viral coat proteins. Virus stocks were generated and used to infect a stable line of cultured simian cells. During the resulting lytic infection, expression of the t-PA gene is governed by the potent SV40 late promoter and enzymatically active t-PA accumulates rapidly in the medium. We have used these two vector systems to analyze the biosynthesis and transport of recombinant t-PA and to compare its properties with those of "natural" t-PA secreted by the Bowes line of human melanoma cells. t-PA secreted from all three sources is identical in specific activity (approximately 20,000 units/mg) despite differences in patterns of terminal glycosylation. Furthermore, non-glycosylated t-PA synthesized in the presence of tunicamycin was secreted efficiently and was indistinguishable in specific activity from glycosylated t-PAs.
Mol Biol Med 1986 Dec
PMID:Expression of human tissue-type plasminogen activator from lytic viral vectors and in established cell lines. 303 88

Homologous human macrophage hybridoma cell lines were obtained by somatic cell fusion between peripheral blood monocyte-derived macrophages and a subclone of the myelomonocytic cell line, U937-F9. The hybridoma cell lines grown in vitro for more than a year were confirmed by manifestations of phagocytosis, adherence, nonspecific esterase, acid phosphatase, chromosome numbers and other cell surface antigens. Cell surface antigens on hybridomas were detected by flow cytometry analysis with monoclonal antibodies. With interclonal differences, a typical phenotype of hybridoma cells was CDw14+, OKM5+, Mac-1+ (equivalent to OKM1 and Mol), OKT9+, HLA-DR- and CD20+. After stimulation with lipopolysaccharide and calcium ionophore A23187, culture supernatants of clones c18A and c29A showed cytotoxic activity against human melanoma A375 Met-Mix and other cell lines which were resistant to the tumor necrosis factor, lymphotoxin and interleukin 1. This cytotoxic factor was found to be distinct from the tumor necrosis factor, lymphotoxin and interleukin 1 using the anti-tumor necrosis factor, anti-lymphotoxin and anti-interleukin 1 antisera.
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PMID:Homologous human macrophage hybridomas that produce a novel cytotoxic factor in their culture supernatants. 328 4

Transfection of a functional major histocompatibility complex class I gene into certain tumor cells, induced by oncogenic viruses or chemical carcinogens, can effectively abrogate their tumorigenic activity. Since experimentally induced tumors possess strong tumor-specific transplantation antigens, expression of cell surface class I antigens may present the tumor cells to appropriate immune effector cells. Most spontaneously arising tumors do not possess tumor-specific transplantation antigens, and their tumorigenicity may not be affected by the expression of a transfected class I gene. We demonstrate that the poorly immunogenic B16-BL6 melanoma can be rendered nontumorigenic in syngeneic mice by the expression of the class I H-2K antigen but not the class II I-A antigen. Furthermore, the poorly tumorigenic, class I-expressing B16-BL6-transfected cells can effectively immunize syngeneic C57BL/6 mice against the highly tumorigenic, class I-deficient B16-BL6 parental cells. Our success in experimentally manipulating the tumorigenicity of a spontaneously derived neoplasm offers hope for a potential modality for the effective treatment of human cancer.
Mol Cell Biol 1988 Apr
PMID:Rejection of B16 melanoma induced by expression of a transfected major histocompatibility complex class I gene. 338 Jan 2

Tumor cells produce a variety of hormones and growth factors that are associated with modulation of the growth pattern of malignant cells. Hs294T human malignant melanoma cells produce a monolayer mitogen, melanoma growth stimulatory activity (MGSA), that stimulates the growth of Hs294T cultures in serum-free medium. MGSA has been purified to homogeneity from conditioned medium of Hs294T human malignant melanoma cells using acetic acid extraction of the crude conditioned medium followed by three chromatographic processes, including gel-filtration, heparin-Sepharose, and reverse-phase HPLC. MGSA was eluted from the heparin-Sepharose resin with 0.1-0.3 M NaCl. The binding affinity is similar to that of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) but much less than many endothelial cell-derived growth factors which require significantly higher salt concentrations for elution. These procedures resulted in a final yield of purified MGSA that was significantly greater than yields obtained using previously reported procedures. The homogeneous 16,000 and 13,000 molecular weight moieties obtained by means of these procedures exhibited similar bioactivities (stimulating a 2- to 3-fold increase in Hs294T cell growth) over a 0.06-6 ng concentration range. This bioactivity was progressively inactivated during storage at -80 degrees C. These results indicate that the combination of heparin-Sepharose chromatography and reverse phase-HPLC provides a more efficient means of purification of MGSA.
Mol Cell Endocrinol 1988 May
PMID:High yield purification of melanoma growth stimulatory activity. 339 57

In order to study the process by which human melanoma cells achieve invasion of basement membranes, a modification of the Membrane Invasion Culture System was developed to allow the in vitro collection of human melanoma cell populations that had invaded acellular human amniotic membranes. A significant increase in the number of double-minute chromosomes (DMs) was observed in metaphase nuclei of A375P human melanoma cells which had passed through two amniotic membranes (A375P-2) over that of control cells. Eighteen percent of the first monolayer of A375P-2 cells contained 1-89 DMs/cell, whereas 3-8.3% of the control A375P cells contained 1-10 DMs/cell. There was a rapid loss of DMs in A375P-2 cells as a function of passage number. After 25 days in tissue culture, the incidence of DMs had essentially dropped below the control range. These data indicate that an unstable gene amplification event may be part of the process by which melanoma cells execute invasion through basement membranes.
Somat Cell Mol Genet 1988 Jan
PMID:Cytogenetic evidence of gene amplification as a mechanism for tumor cell invasion. 342 21

The human malignant melanoma cell line NK14 contains a novel transforming gene which was identified using DNA transfection into NIH3T3 cells (1). This gene has been assigned to chromosome 19p13.2-q13.2 using human-mouse and human-hamster somatic cell hybrids.
Somat Cell Mol Genet 1986 Nov
PMID:Chromosomal assignment of c-MEL, a human transforming oncogene, to chromosome 19 (p13.2-q13.2). 346 61

Somatic cell hybrids formed by crossing PG19 mouse melanoma cells with mouse embryo fibroblasts have a reduced ability to proliferate in growth factor-unsupplemented serum-free medium relative to the parental melanoma cells. The suppression of growth of the hybrid cells in serum-free medium is attributable to a strict requirement of these cells for polypeptide growth factors (insulin plus platelet-derived growth factor, fibroblast growth factor, or epidermal growth factor). In contrast, the parental melanoma cells are able to grow without exogenously added growth factors. Fifteen hybrids derived from crosses between mouse L cells and normal human skin fibroblasts also have been tested for ability to grow in growth factor-unsupplemented serum-free medium. Depending on which human chromosomes are retained, growth of these hybrids in serum-free medium is also suppressed relative to growth of the L cell parent. There appear to be several genes on different chromosomes that are involved in suppression of serum-free growth of the fibroblast x L cell hybrids. One weak suppressor gene appears to be on the human X chromosome.
Somat Cell Mol Genet 1987 Nov
PMID:Growth suppression of hybrids between transformed cells and normal fibroblasts in serum-free medium: correlation with retention of human chromosomes. 347 14

Finely divided, insoluble inulin (gamma polymorph), given intraperitoneally (i.p.) to C57BL mice 1-3 days after i.p. B16 melanoma cells, very significantly increased their mean survival time (MST) in low doses (less than or equal to 40 and less than or equal to 100 micrograms/mouse in 50 and 80% of tests, respectively). The gamma inulin was pure and free of endotoxin and soluble inulin, and was developed as a potent reagent specific for activating the alternative pathway of complement (APC). Its antitumour action paralleled its in vitro APC activation, namely, both activities were sharply dose-dependent up to a threshold dose above which they were dose-independent; dissolved inulin was inactive in vitro and in vivo, decreased the MST of the mice and in a mixture antagonized the in vitro and in vivo activities of gamma inulin; the more soluble (alpha) polymorphs were active in proportion to their gamma content but the effects were blocked at higher doses presumably by dissolved inulin. In addition, depletion of host APC with cobra venom factor or inulin before giving B16 cells increased their malignancy and abrogated the subsequent antitumour action of gamma inulin. The minimum i.p. dose of gamma inulin found to activate serum APC in vivo was 50 micrograms (2.5 mg/kg), i.e. close to the minimum antitumour dose. These close correlations and the specificity of the reagent indicate that activation in vivo of the APC (cellular or humoral) is an important first contact in stimulating host antitumour defences in this mouse model.
Mol Immunol 1986 Aug
PMID:The anti-melanoma activity of inulin in mice. 354 Jun 19

Twenty-two sugars and related compounds, nine neoglycoproteins, dopamine, four polyamines and oligomers of glucosamine were examined for their effect on the cytoadherence of Plasmodium falciparum-infected erythrocytes to melanoma cells. Inhibition of cytoadherence was high in the presence of the amino-sugars, glucosamine, galactosamine and mannosamine, and dopamine, and significant, although lower, in the presence of the polyamines, spermine, spermidine and putrescine. N-acetylated amino-sugars and the other compounds were not significant inhibitors of cytoadherence.
Mol Biochem Parasitol 1987 Feb
PMID:Amino-sugars inhibit the in vitro cytoadherence of Plasmodium falciparum-infected erythrocytes to melanoma cells. 355 37

The ability of lonidamine [1-(2,4)-dichlorobenzyl-1H-indazol-3-carboxylic acid], to induce a stress response in human and murine cultured melanoma cells has been demonstrated. In the M14 and M10 human melanoma cell lines, lonidamine enhances the synthesis of a unique set of proteins, characterized by SDS-PAGE by an Mr of about 72 kDa. In the B16 murine melanoma cell line, exposure to lonidamine increases the synthetic rate of two polypeptides of mol mass 86 and 72 kDa, respectively. Lonidamine is a drug which specifically acts on mitochondria. Therefore the observation that it can also promote a stress response indicates that the mitochondria might be one of the primary cellular targets and postulates a causal relationship between an impairment of the energy supply and induction of stress protein synthesis.
Exp Mol Pathol 1986 Apr
PMID:Induction of stress proteins by lonidamine in human and murine melanoma cells. 369 38


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