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

Molecular weight of human hepatocellular carcinoma (HCC)-associated antigen-HL2 antigen was detected to be about 50,000 dalton by SDS-PAGE and Western blot. One hundred and twenty-seven paraffin sections of cancers and pathological liver tissue were tests by ABC immunohistochemical staining. MAb HL2 reacted with 62.7% HCC and also with 8 of the 10 stomach carcinomas but only with a few other digestive system carcinomas (pancreas carcinoma, rectum carcinoma and duodenum carcinoma) and hepatitis. MAb HL2 was negative in hepatocirrhosis and other tumors (vesica carcinoma, skin carcinoma, breast carcinoma, neurogliocytoma and carcinoma of the lung). The results suggest that MAb HL2 has values in diagnosis of HCC and differential diagnosis between HCC and other tumours. HL2 antigen might be a new tumor-associated antigen (TAA). Further study of HL2 antigen will significantly show the actions of TAA in the occurrence and development of tumor.
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PMID:[Immunohistochemical observation of anti-human hepatocellular carcinoma monoclonal antibody HL2 in cancers]. 807 Jul 68

A Lewis lung carcinoma-derived low metastatic clone, P29, with a capacity to induce a fibrotic stromal response of host tissue, exhibits tumorigenesis depending on an interstitial matrix formed by the induced stromal cells. Using this clone, in the present study we isolated and characterized a membrane-intercalated proteoglycan that mediates interaction between the tumor cells and interstitial matrix. The tumor cells were cultured in the presence of [3H]glucosamine and [35S]sulfate or [35S]methionine, and hydrophobic proteoglycans were isolated by chromatography on DEAE-Sephacel and then Octyl-Sepharose CL-4B. Proteoglycans with high affinity to the octylresidue were obtained from the cell layer but not to any significant extent from the medium. By CsCl density gradient centrifugation, they were separated into bottom, middle, and top subfractions, which were shown to consist of homogeneous species with estimated M(r) values of 270,000 (named CPGIIIB), 200,000 (CPGIIIM), and 195,000 (CPGIIIT), respectively, by gel filtration on Sepharose CL-4B. These proteoglycans were intercalated into phosphatidylcholine liposomes, suggesting that they are all membrane-intercalated proteoglycans. Analyses of their glycosaminoglycans with chondroitinase ABC and heparitinase I plus II demonstrated that they all contain heparan sulfate as a major glycosaminoglycan (58-85%) and chondroitin 4-sulfate as a minor one (15-42%). Of these three proteoglycans, only CPGIIIB proteoglycan bound specifically to fibronectin-Sepharose 4B under physiological conditions. Molecular analyses of this proteoglycan by Sepharose CL-4B or SDS-PAGE before and after treatments with glycosaminoglycan degradation enzymes or trifluoromethanesulfonic acid demonstrated that CPGIIIB proteoglycan is a hybrid proteoglycan having heparan sulfate and chondroitin 4-sulfate chains on the same core protein with an M(r) of 40,000. Affinity chromatographies of the CPGIIIB proteoglycan on fibronectin-Sepharose 4B after treatments with these enzymes demonstrated that it bound to fibronectin via its heparan sulfate chains. On the basis of the above results, we propose that the CPGIIIB proteoglycan mediates the interaction between the tumor cells and interstitial matrix.
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PMID:Membrane-intercalated proteoglycan of a stroma-inducing clone from Lewis lung carcinoma binds to fibronectin via its heparan sulfate chains. 813 44

The murine monoclonal antibody (MAb) RS7-3G11 is an IgG1 with pancarcinoma reactivity, which has been raised against human squamous-cell carcinoma of the lung. Immunoperoxidase staining of frozen tissue sections demonstrated that the antigen defined by RS7-3G11 is present in tumors of the lung, stomach, bladder, breast, ovary, uterus and prostate. The rate and extent of internalization of RS7-3G11 into Calu-3, an adenocarcinoma of the lung cell line, was investigated using unconjugated MAb, followed by fluorescence labelling, and by binding 125I-RS7-3G11 followed by acid removal of surface-bound antibody. Rapid internalization of MAb RS7-3G11 into target cells was observed. Antibody internalization was noted at 30 min, and by 2 hr virtually all MAb RS7-3G11 was internal. Although MAb RS7-3G11 was raised against non-small-cell carcinoma of the lung, ME-180, a cervical-carcinoma cell line, expresses higher quantities of the antigen than the lung-carcinoma cell lines. Due to the higher antigen density in ME-180 cells, this line was used for immunoprecipitation studies and antigen purification. Immunoprecipitation studies using the ME-180 cervical-carcinoma cell line metabolically labeled with [3H]leucine or [3H]glucosamine demonstrated that the antigen defined by RS7-3G11 is a glycoprotein of M(r) 46 kDa. Deglycosylation by treatment with endoglycosidase-F resulted in a protein with a M(r) of 35 kDa. RS7-3G11-antigen was purified from ME-180 tissue-culture cells using affinity-column chromatography. By SDS-PAGE it was seen that the antigen was highly purified. The major band appeared at M(r) of 45 to 48 kDa. This result is in agreement with the immunoprecipitation studies. The broad band observed in the SDS-PAGE is typical of many glycoproteins, and suggests heterogeneity of glycosylation. Chemical and enzymatic treatments of the antigen, followed by Western blot analyses, suggest that the RS7-3G11 antigenic determinant is composed of a conformation-dependent peptide.
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PMID:Specificity and properties of MAb RS7-3G11 and the antigen defined by this pancarcinoma monoclonal antibody. 825 31

Many previous studies have demonstrated that antisense oligodeoxynucleotides (ODNs) bind to surface proteins in a manner compatible with receptor-mediated endocytosis and, unless specifically modified, are internalized into endosomes with little access to the cytoplasmic structures or to the nucleus. Reports vary as to the specific proteins involved in the mechanism, and this study examines the conditions of binding, some proteins that might contribute to the process, and whether changes in binding patterns occur during differentiation. Native gel electrophoresis was used to optimize the surface binding of a phosphorothioate end-capped 16-mer to T15 mouse fibroblast cells, and comparisons are made with some human epithelial tumor cell lines. Binding to individual proteins was visualized using SDS-PAGE and autoradiography. Binding at 4 degrees C was almost exclusively to a 46 kDa protein and decreased in the presence of an excess of unlabeled ODN and heparin but not ATP. Increasing the temperature of ODN binding from 4 degrees C to 37 degrees C for 10 minutes changed the binding pattern observed. ODN binding to the total cytoplasmic and membrane proteins immobilized on a membrane showed a greater number of binding proteins, the most prominent being one of 30 kDa. Examination of the effects of serum on binding were made using the human lung carcinoma cell line COR-L23, which can be grown in serum-free conditions. Serum starvation led to an increased total binding seen on native gels coinciding with increased binding to a 46 kDa protein. Demonstration that changes in binding proteins occur when cells differentiate was made using the premacrophage cell line THP-1. Differentiation of these cells increased the total ODN binding and appeared to initiate the synthesis of some new binding proteins, although binding to a 46 kDa protein was reduced.
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PMID:Interaction of oligodeoxynucleotides with mammalian cells. 891 3

p21waf1/cip1 mRNA and protein accumulate in intact cells exposed to oxidizing agents through a p53-independent, MAPK-dependent mechanism. Treatment with oxidizing agents also yields a second form of this protein (FM p21), characterized by a faster migration on SDS-PAGE. This phenomenon depends on the modification of intracellular redox conditions induced by diethylmaleate, a glutathione-depleting agent, being prevented by the pretreatment with the glutathione precursor N-acetylcysteine. The appearance of this FM p21 form is very early, being observed 5 min after exposure to diethylmaleate, long before the already observed accumulation of p21 induced by oxidative stress. Furthermore, experiments with dominant negative mutants of MEK demonstrate that, in contrast with that observed for the oxidative stress-induced accumulation of p21 mRNA and protein, the appearance of FM p21 form is not dependent from the activation of the MAPK pathway. It was previously observed (Tchou et al, 1996) that in some lung carcinoma cells long exposure to high doses of phorbol esters also induces the appearance of a faster-migrating p21 electrophoretic band and it was suggested that this could result from a different phosphorylation or from a proteolytic processing at the C-terminus of the protein. The latter is not the case for the diethylmaleate-induced FM p21 whose C-terminus is intact, as demonstrated by the expression of a C-terminus tagged p21 cDNA. On the contrary, the observed migration shift seems to be dependent on the hypophosphorylation of the protein; in fact, a pretreatment of cells with okadaic acid, an inhibitor of (serine/threonine) phosphatases, inhibits the oxidation-dependent appearance of the FM p21 and the block of protein synthesis, caused by cycloeximide, does not affect the appearance of FM p21, that thus could derive from the dephosphorylation of preexisting protein.
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PMID:A new p21waf1/cip1 isoform is an early event of cell response to oxidative stress. 984 80

A method for improved refolding and purification of recombinant human interferon-alpha (rh-IFN-alpha) from inclusion bodies is described. The optimal conditions of refolding were obtained by the addition of 0.5 M l-arginine to the refolding buffer. The rh-IFN-alpha was purified to near homogeneity utilizing a single-step chromatography on a mimetic dye-ligand matrix. Improved refolding, coupled to a single-column affinity purification strategy, resulted in a 10-fold increase in the yield of rh-IFN-alpha. This single-step purification protocol yielded approximately 50 mg of purified rh-IFN-alpha from 1 liter of shake flask culture. The rh-IFN-alpha prepared by this protocol was found to be essentially monomeric based on HPLC gel filtration and nonreducing SDS-PAGE. It had a specific activity of approximately 2.8 x 10(8) IU/mg, measured as inhibition of cytopathic effect of encephalomyocarditis virus on A549 human lung carcinoma cells.
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PMID:Affinity purification of recombinant interferon-alpha on a mimetic ligand adsorbent. 1004 81

Gastrin-releasing peptide (GRP), a member of the bombesin family of peptides, has been shown to have mitogenic activity in small cell lung carcinoma (SCLC), and to be produced by SCLC in an autocrine fashion. In this report, we demonstrate that both GRP and another member of the bombesin family of peptides, neuromedin B (NMB), are also autocrine growth factors for non-small cell lung carcinoma (NSCLC). Using the reverse transcription-polymerase chain reaction (RT-PCR), we have detected mRNA for the neuromedin B receptor (NMBR) in all 14 of the NSCLC cell lines examined. GRP receptor (GRPR) mRNA was also expressed in the majority of NSCLC cell lines (nine of 14). By immunoblotting using SDS-PAGE gradient gels fixed in trichloroacetic acid, GRP and NMB were found in fractions of culture medium that had been purified by high pressure liquid chromatography (HPLC) from NSCLC cell lines. NMB was detected in the conditioned medium of seven of nine cell lines and GRP in seven of nine cell lines; both peptides were produced in six cell lines. In four of the cell lines where both peptides were produced, the relative amount of NMB secreted into the medium was 7-15 times that of GRP; in the other two cases, the relative amounts of GRP and NMB were equivalent. Cultured human bronchial epithelial (HBE) cells expressed the GRPR and NMBR but did not produce either peptide. A subline of A549 cells that was adapted to grow in serum-free and growth factor-free conditions, termed A549-R(0), secreted both bombesin-like peptides (BLPs) into the culture medium. Using either a colony-forming assay or a BrDU incorporation assay, both NMB and GRP were found to be mitogens for three NSCLC cell lines that express mRNA for BLP receptors and secrete BLPs, regardless of which peptide and/or receptor subtype was detected. The monoclonal antibody 2A11, which preferentially recognizes GRP, was able to block the in vitro proliferative response to GRP in the BrDU incorporation assay, and partially blocked the response to NMB. The 2A11 antibody could only partially block the in vivo growth of cell lines that showed proliferative responses to BLPs. 2A11 antibody was more effective against the 239T cell line, which secreted a low amount of GRP into the medium (0.6 nM), compared to the 201T cell line, which secreted a higher amount of both GRP and NMB (4.2 nM and 36.6 nM, respectively). These results suggest that both NMB and GRP are autocrine growth factors for NSCLC, but that the production of NMB and expression of the NMBR may be more prominent than the production of GRP and expression of the GRP receptor. If BLP ligand-receptor systems are to be targeted therapeutically in NSCLC, it will be necessary to inhibit both NMB and GRP.
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PMID:Evidence for autocrine actions of neuromedin B and gastrin-releasing peptide in non-small cell lung cancer. 1054 85

A novel inhibitor of angiogenesis named SCAIF80 (shark cartilage-derived angiogenesis inhibitory factor) from shark cartilage has been isolated and characterized. SDS-PAGE analysis followed by silver staining revealed a single band with molecular weight (M(r)) of 80 kD. To determine whether this protein was capable of inhibiting angiogensis, it was assayed in endothelial cell (EC) proliferation and migration assay. The results showed that SCAIF80 significantly suppressed EC proliferation and migration in a dose-dependent manner. In the chick chorioallantoic membrane (CAM) assay, SCAIF80 also showed a potent inhibitory activity on angiogenesis in vivo. In animal tests, the growth of tumor was potently suppressed by SCAIF80 therapy. Lewis lung carcinoma was inhibited by 93.83 % at a dose of 5 mg/(kg.d). These findings suggest that shark cartilage may produce a novel protein with anti-angiogenic and anti-tumor activity.
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PMID:SCAIF80, a Novel Inhibitor of Angiogenesis, and Its Effect on Tumor Growth. 1205 97

Glycosaminoglycans (GAGs) are complex polysaccharides that participate in the regulation of physiological processes through the interactions with a wide variety of proteins. Acharan sulfate (AS), isolated from the giant African snail Achatina fulica, primarily consists of the repeating disaccharide structure alpha-D-N-acetylglucosaminyl (1-->4) 2-sulfoiduronic acid. Exogenous AS was injected subcutaneously near the tumor tissue in C57BL/6 mice that had been implanted with Lewis lung carcinoma cells (LLCs). The location of AS in the tumor was assessed by staining of sectioned tissues with alcian blue and periodic acid-Schiff (PAS) reagent. In vitro assays indicated binding of cells to 50 microg/ml AS (or heparin) after a 5-h incubation. Immunofluorescence assays, using anti-AS antibody, detected AS at the cell surface. The outer-surface of LLCs were next biotinylated to identify the AS-binding proteins. Biotinylated cells were lysed, and the lysates were fractionated on the AS affinity column using a stepwise salt gradient (0, 0.1, 0.3, 0.5, 0.7, 1.0, and 2.0 M). The fractions were analyzed by SDS-PAGE with silver staining and western blotting. We focused on the proteins with high affinity for AS (eluting at 1 M NaCl) and detected only two bands by western blotting. ESI Q-TOF MS analysis of one of these bands, molecular weight approximately 110 kDa, showed it to be nucleolin. A phosphorylated form of nucleolin on the surface of cells acts as a cell surface receptor for a variety of ligands, including growth factors (i.e., basic fibroblast growth factor) and chemokines (i.e., midkine). These results show that nucleolin is one of several AS-binding proteins and suggest that AS might demonstrate its tumor growth inhibitory activity by binding the nucleolin receptor protein on the surface of cancer cells.
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PMID:Nucleolin: acharan sulfate-binding protein on the surface of cancer cells. 1532 57

Stem bromelain (EC 3.4.22.32) is a major cysteine proteinase, isolated from pineapple ( Ananas comosus) stem. Its main medicinal use is recognized as digestive, in vaccine formulation, antitumoral and skin debrider for the treatment of burns. To verify the identity of the principle in stem fractions responsible for the antitumoral effect, we isolated bromelain to probe its pharmacological effects. The isolated bromelain was obtained from stems of adult pineapple plants by buffered aqueous extraction and cationic chromatography. The homogeneity of bromelain was confirmed by reverse phase HPLC, SDS-PAGE and N-terminal sequencing. The in vivo antitumoral/antileukemic activity was evaluated using the following panel of tumor lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascitic tumor (EAT), Lewis lung carcinoma (LLC), MB-F10 melanoma and ADC-755 mammary adenocarcinoma. Intraperitoneal administration of bromelain (1, 12.5, 25 mg/kg), began 24 h after tumor cell inoculation in experiments in which 5-fluorouracil (5-FU, 20 mg/kg) was used as positive control. The antitumoral activity was assessed by the survival increase (% survival index) following various treatments. With the exception of MB-F10 melanoma, all other tumor-bearing animals had a significantly increased survival index after bromelain treatment. The largest increase ( approximately 318 %) was attained in mice bearing EAT ascites and receiving 12.5 mg/kg of bromelain. This antitumoral effect was superior to that of 5-FU, whose survival index was approximately 263 %, relative to the untreated control. Bromelain significantly reduced the number of lung metastasis induced by LLC transplantation, as observed with 5-FU. The antitumoral activity of bromelain against S-37 and EAT, which are tumor models sensitive to immune system mediators, and the unchanged tumor progression in the metastatic model suggests that the antimetastatic action results from a mechanism independent of the primary antitumoral effect.
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PMID:In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. 1789 36


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