Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new mouse monoclonal antibody 9A3 (IgGl,K) raised against human poorly differentiated gastric adenocarcinoma cell line TMK-1 was produced. Immunohistochemically, 9A3 antibody reacted strongly with gastric carcinoma, colon carcinoma, pancreas carcinoma, lung carcinoma, breast carcinoma and cervical carcinoma of the uterus. This antibody did not react with various normal tissues from the whole body with the exception of neutrophils and macrophages. In fetal tissues, 9A3 antibody reacted with esophageal mucosa and colon epithelium, but did not react with purified carcinoembryonic antigen (CEA). The molecular weight of the antigen extracted with NP-40 from TMK-1 cells was estimated to be about 46,000 daltons by SDS-PAGE. The 9A3 antigen was also detected in conditioned tissue culture medium of the TMK-1 cell line and sera of gastric cancer patients and tumor imaging could be performed in xenotransplantable human gastric carcinoma in nude mice. In summary, 9A3 antibody may serve as a new marker for detection of cancer by immunohistochemical, cytological techniques and serologically in the sera of cancer patients.
 ...
PMID:[Monoclonal antibody 9A3 raised against a human poorly differentiated gastric adenocarcinoma cell line]. 372 60

We have investigated whether urokinase-type plasminogen activator (u-PA) is present in the mouse in vivo as the proenzyme or as the active enzyme. u-PA in extracts of various murine tissues was of a one-polypeptide chain form with an electrophoretic mobility indistinguishable from purified proenzyme (pro-u-PA), as demonstrated by SDS-polyacrylamide gel electrophoresis under reducing conditions followed by immunoblotting. No 2-chain u-PA was detected in any of the extracts (detection limit 10% of that of one-chain u-PA). In bladder urine more than half of the u-PA was of the one-chain form. Together with previous immunocytochemical studies of the normal murine tissues and studies of the Lewis lung carcinoma, the present results indicate that in these tissues the one-chain proenzyme is the predominant form of u-PA in intracellular stores and for the first time demonstrates that at least in some cases the one-chain form constitutes a sizeable fraction of the u-AP in extracellular fluids in the intact organism.
 ...
PMID:Proenzyme to urokinase-type plasminogen activator in the mouse in vivo. 388 75

The free chromophores isolated from the antitumor protein antibiotics, auromomycin (AUR) and macromomycin (MCR), were rapidly inactivated by incubation in serum-containing medium at 37 degrees C in the dark with respect to cytocidal activity to human lung carcinoma A549 cells. Under the same conditions, the intact antibiotics, their pronase-hydrolysates and reconstituents from the chromophores and apo-proteins were stable. Intact and reconstituted AUR and MCR were more resistant to pronase digestion than the apo-proteins. The analyses of the pronase-hydrolysates of AUR and MCR by SDS-polyacrylamide gel electrophoresis and ultrafiltration showed that the antibiotics (13 kilodaltons (kDa] were degraded to produce peptide fragments (1-3 kDa) in which most cytotoxicity of the pronase-hydrolysates resided. The pronase-hydrolysates exhibited a differential cytocidal activity to normal diploid fibroblasts (WI38), their SV40-transformants (VA13) and carcinoma cells (A549) of human lung origin as was observed for the intact antibiotics. These results indicate that specific interaction between the chromophores and the pronase-resistant peptide segments (1-3 kDa) of the protein moiety stabilizes the cytocidal activity of the chromophores and also protects the peptide segments from pronase digestion.
 ...
PMID:Role of pronase-resistant peptide segments of the antitumor protein antibiotics, auromomycin and macromomycin, in stabilizing cytocidal activity of the chromophore moieties to carcinoma cells. 630 61

A new macromolecular peptide antibiotic, named AN-1, was isolated from the culture broth of Streptomyces albus AJ9003. From 18 liters of culture broth (110 units/ml activity) a 300 mg sample of AN-1 was obtained with a specific activity of 1,160 units/mg was obtained. AN-1 is a basic polypeptide with a molecular weight of 12,000, isoelectric point of pH 8.3, and gives a single band on SDS polyacrylamide gel electrophoresis. It is soluble in water but insoluble in ethanol, butanol and acetone. It was stable at pH 6 approximately 9 but very unstable at pH 2. The UV absorption spectrum shows a maximum at 280 nm. AN-1 had no antibacterial activity against the Gram-positive and Gram-negative bacteria tested, but shows strong inhibitory activity toward Escherichia coli MP2, a macromolecule permeable mutant. In addition to being highly mutagenic, AN-1 inhibits the in vitro cell growth of L1210 (ED50 0.41 micrograms/ml). However, AN-1 had no antitumor activity against mouse leukemia L1210 or Lewis lung carcinoma in mouse.
 ...
PMID:The fermentation, isolation and characterization of a macromolecular peptide antibiotic: AN-1. 636 71

The invasively growing and metastasizing Lewis lung carcinoma consistently contained urokinase-type plasminogen activator (u-PA) enzyme activity. When investigated immunocytochemically with antibodies against u-PA, different parts of individual tumors showed a pronounced heterogeneity in staining intensity. Strong staining was found in areas with invasive growth and degradation of surrounding normal tissue, while other areas were completely devoid of staining. Immunoreactivity occurred both with a perinuclear cytoplasmic localization in tumor cells and associated with apparently extracellular material. SDS PAGE of tumor extracts, under both reducing and nonreducing conditions, followed by immunoblotting, showed only one immunocytochemically stainable band with an electrophoretic mobility corresponding to that of purified proenzyme to u-PA, while no two-chain u-PA was detected. This indicates that the major part of the activator in Lewis lung carcinoma is present as one-chain pro-u-PA.
 ...
PMID:Immunocytochemical localization of urokinase-type plasminogen activator in Lewis lung carcinoma. 637 27

Monoclonal antibodies were produced by immunizing BALB/c mice with a human lung squamous carcinoma line (UCLA-SO-P3) or with freshly obtained lung carcinoma cells and by fusing the immunized splenocytes to mouse myeloma S194. Six monoclonal antibodies were selected after testing the reactivity to a panel of human tumors and non-tumors by an indirect 125I-protein A binding assay, a complement dependent microcytotoxicity assay or an immunofluorescence assay. As a result, four types of antigens were identified. MoAb 169D4 is of IgM class and reacted only to P3 lung carcinoma and to one of the colon carcinomas. This antibody actually possessed the A1 Lewis d specificity. MoAb 172D5 reacted to 8 out of 11 carcinomas but did not react to other types of tumor or lymphoid cells while detecting a carcinoma-associated antigen. MoAb 170C5, 754A3 and 806B4 reacted to carcinomas and embryonic cells, but detected antigenic determinants other than the carcinoembryonic antigen. By means of a protein antigen analysis using immunoprecipitation and SDS-polyacrylamide gel electrophoresis, MoAb 170C5, 754A3 and 806B4 detected molecular weights of 130,000, 55,000, and 135,000, respectively. MoAb 169F3 reacted to all the tested carcinomas, sarcomas, and melanomas, and some of the leukemias. This antibody also reacted to human peripheral monocytes and platelets and was shown to detect an antigen widely distributed among tumors and parts of normal cells.
 ...
PMID:Analysis of cell surface antigens expressed on a human lung carcinoma by monoclonal antibodies. 662 11

Receptors for peanut agglutinin (PNA) were isolated from Lewis lung carcinoma cells (3LL) by detergent solubilization and affinity chromatography on PNA-agarose. The isolated receptors showed heterogeneous yet distinct molecular species when they were analyzed by SDS gel electrophoresis. In vivo inoculation of the isolated receptors could induce potent cytotoxic effector cells against 3LL cells, which were detected by Winn's tumor neutralization assay. The PNA receptors were also effective in preventing the settlement of the intravenously injected 3LL tumors in the lung. These findings suggest that PNA receptors can be used for immunological therapy of certain cancers.
 ...
PMID:Isolation of tumor associated antigens from Lewis lung carcinoma by affinity chromatography on peanut agglutinin-agarose. 671 70

An antigenic activity in pleural effusions of patients with squamous-cell carcinoma of the lung has been prepared in highly purified form by a 5-step fractionation scheme. The purified substance, designated LuCA (lung cancer antigen), was assessed during the course of the fractionation procedure by a radioimmunometric assay carried out with specific soluble reagents. Sensitive saturation-binding assays showed no or only weak uptake of the 125I-labelled antigen preparation by a panel of antisera specific for known bronchogenic tumour markers, and for normal human serum proteins. The preparation appeared to contain lung-tumour-associated antigens, one of them probably distinct for squamous-cell carcinomas. The antigen fraction consists of acid-soluble glycoproteins, and was demonstrated by SDS-polyacrylamide gel electrophoresis as a single band in the mol. wt region of 43,000. The gel-filtration elution volume appeared to indicate the occurrence of the antigenic activity in multiples of this smaller unit. Pilot radioimmunoassays performed with LuCA and an absorbed specific antiserum suggest the possible suitability of the marker preparation for screening lung-cancer patients.
 ...
PMID:An improved antigenic marker of human lung carcinomas and its use in radioimmunoassays. 722 79

A human epithelial cell line, WISH, and a mouse cell line, LB6-uPAR, transfected with the human urokinase receptor (uPAR), both expressed high affinity uPAR but undetectable levels of urokinase (uPA). In two independent assays, binding of exogenous pro-uPA produced an up to threefold enhancement of migration. The migration was time and concentration dependent and did not involve extracellular proteolysis. This biologic response suggested that uPAR can trigger an intracellular signal. Since this receptor is a glycosyl-phosphatidylinositol-linked protein, we postulated that it must do so by interacting with other proteins, among which, by analogy to other systems, would be a kinase. To test this hypothesis, we carried out a solid phase capture of uPAR from WISH cell lysates using either antibodies against uPAR or pro-uPA adsorbed to plastic wells, followed by in vitro phosphorylation of the immobilized proteins. SDS-PAGE and autoradiography revealed two phosphorylated protein bands of 47 and 55 kD. Both proteins were phosphorylated on serine residues. Partial sequence of the two proteins showed a 100% homology to cytokeratin 18 (CK18) and 8 (CK8), respectively. A similar pattern of phosphorylation was obtained with lysates from A459 cells, a lung carcinoma, but not HL60, LB6-uPAR or HEp3 cell lysates, suggesting that the identified multiprotein uPAR-complex may be specific for simple epithelia. Moreover, immunocapture with antibody to another glycosyl-phosphatidylinositol-linked protein, CD55, which is highly expressed in WISH cells, was ineffective. The kinase was tentatively identified as protein kinase C, because it was inhibited by an analogue of staurosporine more specific for PKC and not by a PKA or tyrosine kinase inhibitors. The kinase was tentatively identified as PKC epsilon because of its resistance to PMA down-modulation, independence of Ca2+ for activity, and reaction with a specific anti-PKC epsilon antibody in Western blots. Cell fractionation into cytosolic and particulate fractions revealed that all four proteins, the kinase, uPAR, CK18, and CK8, were present in the particulate fraction. In vivo, CK8, and to a lesser degree CK18, were found to be phosphorylated on serine residues. Occupation of uPAR elicited a time-dependent increase in the phosphorylation intensity of CK8, a cell shape change and a redistribution of the cytokeratin filaments. These results strongly suggest that uPAR serves not only as an anchor for uPA but participates in a signal transduction pathway resulting in a pronounced biological response.
 ...
PMID:Induction of cell migration by pro-urokinase binding to its receptor: possible mechanism for signal transduction in human epithelial cells. 751 43

A highly purified urinary trypsin inhibitor (UTI) inhibits not only tumor cell invasion in an in vitro assay but also production of experimental and spontaneous lung metastasis in an in vivo mouse model. UTI is present both in the lysate of tumor cells (human choriocarcinoma SMT-cc1 cells, human promyeloid leukemia U937 cells, and murine Lewis lung carcinoma 3LL cells) and human neutrophils. In each medium from tumor cells, most of the cell-associated UTI is on the cell surface. Cell-binding experiments employing cell enzyme-linked immunosorbent assay and flow cytometry indicated that tumor cells (SMT-cc1 and 3LL cells) have specific binding sites for UTI on their cell surface. UTI binds rapidly and with relatively high affinity to SMT-cc1 and 3LL cells. UTI is bound to a specific surface receptor that is incompletely saturated. U937 cells and neutrophils did not show any specific binding to UTI, since UTI receptors on the cell surface of U937 cells and neutrophils were completely saturated with endogenous UTI. UTI forms yielded cross-linked 150- and 80-kDa ligand receptor complexes with cultured SMT-cc1 cells, suggesting molecular masses of 110 and 40 kDa for the UTI receptors. Purification of the two UTI receptor proteins by ligand affinity chromatography (ligand-blotting analysis) yielded two bands when analyzed by SDS-polyacrylamide gel electrophoresis, corresponding in electrophoretic mobility to those calculated by cross-linking analysis. The results reported here showing that some tumor cells carry UTI receptors are in line with a possible role of surface-bound UTI in modulating plasmin activity to the close environment of the cell surface and in processes like prevention of tumor cell invasion and metastasis.
 ...
PMID:Characterization of the cellular binding site for the urinary trypsin inhibitor. 805 Nov 63


<< Previous 1 2 3 4 Next >>