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 antitumor antibiotic, named auromomycin, was isolated from the culture broth of Streptomyces macromomyceticus, a macromomycin-producing strain. The antibiotic was recovered from the culture filtrate by salting out with ammonium sulfate and further purified by successive application of ion-exchange chromatography on Amberlite IRA-93 (Cl form) and DEAE-Sephadex (OH form), Gel filtration on Sephadex G-50 and hydrophobic chromatography on Octyl-Sepharose CL-4B. The antibiotic is an acidic polypeptide with a molecular weitht of 12,500 and an isoelectric point of pH 5.4 and consists of 16 different amino acids. It has characteristic absorption maxima at 273 nm and 357 nm in the ultraviolet spectrum and two minima at 280 nm and 350 nm in the optical rotatory dispersion spectrum. Auromomycin exhibits antibacterial activity not only against Gram-positive bacteria, but also Gram-negative bacteria. Antitumor activities of auromomycin were revealed against EHRLICH ascites carcinoma, ascites sarcoma 180, L1210 leukemia and LEWIS lung carcinoma. Auromomycin was found to be converted into macromomycin by adsorption chromatography on Amberlite XAD.
 ...
PMID:Studies on auromomycin. 46 20

The production of immunoreactive somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) by the established cell line derived from a human lung carcinoma CALU-6 has been evidenced in the serum-free medium in increasing concentrations as a function of the incubation time. Gel filtration in acid conditions of cell-conditioned medium collected after 72 h showed peaks of immunoreactive Sm-C/IGF-I in the elution volume corresponding to the molecular weight of the synthetic Sm-C/IGF-I, and in the high molecular weight region, where specific binding sites for Sm-C/IGF-I could be also demonstrated. These results indicate that this established cell line produces high amounts of immunoreactive Sm-C/IGF-I and of Sm-C/IGF-I carrier protein. The pooled fractions corresponding to the molecular weight of synthetic Sm-C/IGF-I showed a competitive binding curve parallel to the standard in the Sm-C/IGF-I RIA system, and a mitogenic activity on cells from the same line similar to the one observed using two different pure Sm-C/IGF-I preparations, obtained by chemical synthesis or by DNA recombinant technology. When a monoclonal antibody (sm-1.2) raised against Sm-C/IGF-I was added into the medium, the mitogenic effect observed by both synthetic and cell-derived Sm-C/IGF-I peptide was completely abolished; the monoclonal antibody also partially inhibited the effect of 10% fetal calf serum and the thymidine incorporation observed in serum-free medium without growth factors. In serum-free medium the monoclonal antibody produced a 45% reduction of cells in S phase by thymidine labeling index without modification of the growth fraction as determined by primer-dependent alpha-DNA polymerase labeling index. In conclusion it seems that Sm-C/IGF-I has a critical role in the autocrine stimulation of the replication of this cell line.
 ...
PMID:Evidence for autocrine mitogenic stimulation by somatomedin-C/insulin-like growth factor I on an established human lung cancer cell line. 337 14

Polypeptide transforming growth factors: TGF alpha and TGF beta were isolated and separated from acidic ethanol extracts of mouse C-243 tumors. The purification of the acid-soluble extract was achieved by Bio-Gel P-60 filtration chromatography, followed by CM-Sepharose CL-6B ion exchange, Bio-Gel P-10 filtration, and dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). At the Bio-Gel P-10 purification step, TGF alpha was separated from TGF beta. TGF alpha stimulated mouse Balb/c-3T3, rat NRK-49F and human A549 cells to form colonies in soft agar, and competed with 125I-labeled epidermal growth factor (EGF) for binding to human placenta membrane receptors. Over 40,000-fold SDS-PAGE-purified TGF beta had an Mr of 25,000. Unlike TGF alpha, TGF beta stimulated the clonal growth of NRK fibroblasts only in the presence of the suboptimal amounts of EGF (0.5 ng/ml). TGF beta significantly inhibited the anchorage-independent growth of malignant human lung carcinoma A549 cells, and in the radioreceptor assay with 125I-EGF it had no affinity to EGF receptors.
 ...
PMID:Separation of transforming growth factors TGF alpha and TGF beta during chromatographic purification of extracts from mouse C-234 tumors. 350 41

A human lung tumor-associated protein has been purified from an extract of a human small cell carcinoma of the lung and shown by Ouchterlony double diffusion analysis to be antigenically identical to a component which was previously demonstrated in 84 of 98 lung tumor extracts of all histological types but absent from extracts of normal adult and fetal lung, other normal tissues, and tumors of other organs. These studies utilized xenoantisera raised against a pool of lung tumor extracts which were exhaustively adsorbed with normal serum and tissue extracts. A radial immunodiffusion assay developed for the antigen permitted its quantitation throughout the course of isolation. Purification was accomplished by ion-exchange chromatography, gel filtration, and affinity immunoadsorption. By ion-exchange chromatography, the proteins appeared to be quite heterogeneous, with immunological reactivity detected in three different peaks. However, all the active components were immunologically identical. Gel filtration of the major antigenic component from diethylaminoethyl cellulose similarly demonstrated a further fractionation into several active, immunologically identical forms. These results suggest a charge-size isomeric relationship among the various forms, all of which possess a common and identical antigenic site. The major component was isolated throughout the purification scheme. The final product represented 9% of the input activity, produced a single, although broad, protein-staining region on 7% polyacrylamide gels which was coincident with antigenic activity, and exhibited immunological identity with the antigen in the crude extract as well as with that in an extract from another lung tumor.
 ...
PMID:Identification and purification of a human lung tumor-associated antigen from a primary lung tumor. 617 16

High intracellular levels of BN-like peptides are present in tumors and cell lines of small cell carcinoma of the lung (SCCL) as well as the putative precursor cells of this tumor, the pulmonary endocrine cell. In cell line NCI-H209 the density of bombesin-like peptides was 8.9 +/- 1.1 pmol/mg total protein. Gel filtration chromatography of an extract of these cells revealed one major peak of immunoreactivity which coeluted with synthetic bombesin (1620 daltons). Also, high pressure liquid chromatography revealed one major peak of immunoreactivity was present which eluted before synthetic peptide. Therefore, SCCL bombesin-like peptides may be of similar size but are more hydrophilic than synthetic peptide. Cells maintained in culture continuously release bombesin-like peptides into the growth medium. Also, high concentrations of K+ stimulated the secretion of immunoreactive bombesin from cell lines in a Ca++-dependent manner. These SCCL bombesin-like peptides may function as important regulatory agents in the malignant lung.
 ...
PMID:Bombesin-like peptides in small cell lung cancer: biochemical characterization and secretion from a cell line. 629 91

A study was made of immunoreactive calcitonin (iCT) secretion by continuous cultures of small cell carcinoma of the lung (SCCL). Using an antiserum region specific for the midportion of the molecule, 9/12 cultures were found to secrete iCT. Gel filtration studies were performed on both supernatant fluid (SF) and cell pellet (CP) extract from a culture secreting high levels of iCT. Multiple iCT fractions were found in the SF with the major fraction being of high molecular weight (MW). In contrast, the CP had apparently monomeric CT as its principal iCT fraction. These studies demonstrate frequent iCT secretion by SCCL cultures and significant disparities between the iCT moieties found extra- and intracellularly.
 ...
PMID:Calcitonin secretion by continuous cultures of small cell carcinoma of the lung: incidence and immunoheterogeneity studies. 629 19

Transcriptional regulation of human UGT1A6, a UDP glucuronosyltransferase isoform conjugating a wide variety of planar phenols, has been studied using transfection experiments with plasmids containing its 3-kb 5' upstream region and chloramphenicol acetyltransferase as reporter gene. Previously, two modes of expression of the isoform have been described: in colon carcinoma Caco-2 cells UGT1A6 was found to be TCDD-inducible, whereas in lung carcinoma A549 cells it was constitutively expressed. Therefore functional analysis of UGT1A6 regulation was carried out using these two cell lines. In the upstream region of human UGT1A6 one xenobiotic-responsive element (XRE) was found between-1498 and -1502 bp. In Caco-2 cells the reporter gene activity of the entire plasmid and of deletion mutants containing the XRE were TCDD-inducible, in contrast to experiments with a deletion mutant which did not contain the XRE. TCDD induction was marginal in transfection studies with A549 cells. Gel mobility shift analysis indicated that the aryl hydrocarbon receptor and its partner Arnt bind to the XRE. Furthermore, primer extension studies suggest cell-specific use of multiple TATA boxes. Hence, regulation of human UGT1A6 appears to be cell-specific including both constitutive and aryl hydrocarbon receptor-controlled expression.
 ...
PMID:Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6. 946 22

The small cell lung carcinoma (SCLC) cell line DMS-79 has been used as a model for studying the molecular mechanism underlying the ectopic ACTH syndrome. We previously showed that two domains of the human Proopiomelanocortin (POMC) gene promoter were specifically active in DMS-79 cells. The present study focuses on the more distal one, Domain IV (-376/-417). DNaseI footprinting experiments identified a single binding site for DMS-79 cell proteins in this domain. Gel-shift and sequence analysis indicated that E2F proteins might bind this site. Indeed, proteins from DMS-79 cells which bind this site (i) have in vitro DNA binding properties indistinguishable from those of E2F proteins (ii) form, like E2F proteins, multiprotein complexes which can be dissociated by sodium deoxycholate and (iii) are recognized by antibodies directed against E2F proteins. Further, we show that the rat POMC distal promoter domain contains a homologous sequence which constitutes a natural mutant of the human POMC E2F binding site, since it does not bind E2F. We show by transient transfection that this natural mutant, in the context of the rat POMC promoter, is not active in DMS-79 cells by contrast to the human POMC E2F binding site. We conclude that E2F binding is required for the activity of Domain IV in DMS-79 cells and contributes to the expression of the POMC gene in SCLC. Further studies are required to elucidate the role of E2F factors in POMC gene transcription in SCLC cells, but our results have identified mechanisms different from those in pituitary corticotroph cells that are used by these SCLC tumor cells.
 ...
PMID:Analysis of the human proopiomelanocortin gene promoter in a small cell lung carcinoma cell line reveals an unusual role for E2F transcription factors. 1035 6

The human GSTP1 gene is frequently over-expressed in many human cancers and the expression increases with tumor progression and is associated with a more aggressive biology, poor patient survival, and resistance to therapy. The molecular regulation of the human GSTP1 gene during malignancy is, however, still not well understood. Recently, we reported the presence of a cAMP response element (CRE) in the 5'-region of the human GSTP1 gene, raising the possibility that the cAMP signaling pathway, frequently aberrant in human cancers, may play an important role in the transcriptional activation of the GSTP1 gene in human tumors. In this study, we report that the GSTP1 gene is an early cAMP response gene. Treatment of cells of the human lung carcinoma cell line, Calu-6, with 25 microM forskolin to activate the cAMP pathway resulted in a rapid and significant (sevenfold after 30 min) increase in GSTP1 gene transcripts, which peaked at 12-fold after 4 h. The forskolin-activated GSTP1 transcription in Calu-6 cells was suppressed dose-dependently by a 2-h pre-treatment with 0.1, 1.0, and 10 microM of the adenylate cyclase inhibitor, 2', 5'-dideoxyadenosine. Western blot analysis showed a rapid, fivefold increase, in GSTP1 protein levels after treatment with 25 microM forskolin, with a peak at 2 h post-treatment. The levels of phosphorylated CRE (Ser133) binding protein-1 (CREB-1) increased rapidly, sevenfold at 30 min, and reached 10-fold at 4 h following forskolin treatment. Intracellular cAMP levels also increased rapidly reaching 12-fold at 30 min. Gel mobility shift and supershift assays and DNase/footprinting analyses demonstrated that CREB-1 bZIP and CREB-containing nuclear extracts recognized the GSTP1 CRE with high affinity and specificity. Binding of CREB-1 bZIP to the GSTP1 CRE was abolished when the GSTP1 CRE sequence 5'-CGTCA-3', was mutated at the core nucleotides. Finally, transfection studies using luciferase plasmid constructs showed the GSTP1 CRE to be required for the cAMP-activated gene expression. Together, these findings describe a novel cAMP- and CREB-1-mediated mechanism of transcriptional regulation of the GSTP1 gene and suggest that this may be an important mechanism underlying the increased GSTP1 expression observed in tumors with an aberrant cAMP signaling pathway and in normal cells under conditions of stress, associated with increased intracellular cAMP.
 ...
PMID:Cyclic AMP mediated GSTP1 gene activation in tumor cells involves the interaction of activated CREB-1 with the GSTP1 CRE: a novel mechanism of cellular GSTP1 gene regulation. 1221 Jul 27

Tumor cell expression of COX-2 has been implicated in the progression of murine and human lung cancer. Inhibition of COX-2 by nonsteroidal antiinflammatory drugs reduces the risk of cancer development in humans and suppresses tumor growth in animal models. However, the underlying mechanisms for this beneficial effect are not fully understood. Here we explore the potential link between the anticancer effects of COX-2 inhibitors and the expression of the integrin alpha5beta1. Expression of this integrin in carcinoma cells is associated with invasiveness and malignant progression. This, together with our studies showing that fibronectin, the ligand of alpha5beta1, stimulates the growth of human lung carcinoma cells, and that this effect is mediated through alpha5beta1-dependent signals, has prompted us to examine the effects of COX-2 inhibitors on alpha5beta1 expression in human non small cell lung carcinoma (NSCLC) cells. We found that the selective COX-2 inhibitors NS398 and Nimesulide decreased mRNA expression and protein production of the integrin alpha5 subunit. This effect was associated with inhibition of NSCLC cell adhesion to fibronectin. The COX-2 inhibitors triggered the phosphorylation of extracellular signal-regulated kinase (Erk) in a time-dependent manner, and the inhibitor of Mek-1/Erk PD98095 prevented their inhibitory effects on integrin alpha5 expression. Transient transfection assays showed that the COX-2 inhibitors affected integrin alpha5 gene transcription by acting between -92 to -41 bp of the human integrin alpha5 gene promoter. Gel mobility shift assays showed that the COX-2 inhibitors increased Sp1 DNA binding, but decreased that of AP-1. These effects were accompanied by an increase in Sp1 protein and a decrease in c-Jun protein expression, as well as inhibition of SAPK/JNK phosphorylation. The Sp1 inhibitor, Mithramycin A, also blocked the inhibitory effect of the COX-2 inhibitors on alpha5 expression and promoter activity. Overall, these findings suggest that COX-2 inhibitors suppress alpha5beta1 integrin expression in NSCLC through effects on integrin alpha5 gene transcription mediated by Erk activation, increased Sp1, decreased AP-1 DNA binding and inactivation of SAPK/JNK signals. Our observations unveil a new mechanism of action against NSCLC for COX-2 inhibitors that relates to regulation of integrin alpha5 gene expression and, consequently, recognition of extracellular matrices (i.e., fibronectin) by tumor cells. (c) 2005 Wiley-Liss, Inc.
 ...
PMID:COX-2 inhibitors suppress integrin alpha5 expression in human lung carcinoma cells through activation of Erk: involvement of Sp1 and AP-1 sites. 2625 13


1 2 Next >>