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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven small cell lung carcinoma cell lines of human origin were exposed to different colony stimulating factors (CSFs) to study whether CSFs could enhance the spontaneous cell proliferation and modify the action of cytotoxic drugs. In ten cell lines no suppressive or stimulative effect was observed when measured in a [3H]thymidine assay and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. However, one cell line (GLC-20) could be stimulated by interleukin 3 (IL-3) when measured with a proliferative as well as a clonogenic assay. This enhancing effect was cell concentration dependent in the [3H]thymidine assay. Additional CSFs such as granulocyte-macrophage-CSF, granulocyte-CSF, IL-4, IL-6, insulin, or bombesin could not further augment the IL-3 supported proliferation. In addition, IL-3 binding studies demonstrated the presence of IL-3 receptors on the GLC-20 cells. Two types of receptors were demonstrated by Scatchard analysis: high affinity receptors (59 +/- 4 sites/cell) with a dissociation constant (Kd) of 31 +/- 9 pmol/liter; and low affinity receptors (1915 +/- 91 sites/cell) with a Kd of 2.0 +/- 0.8 nmol/liter. Finally, it was shown that the toxic effects of adriamycin and cisplatin on the proliferation of the GLC-20 cell line could partially be abrogated in the presence of IL-3. These data indicate that in some cases CSFs can modulate the proliferation of small cell lung carcinoma cell lines and interfere with the effects of chemotherapeutic drugs.
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PMID:The effects of five hematopoietic growth factors on human small cell lung carcinoma cell lines: interleukin 3 enhances the proliferation in one of the eleven cell lines. 170 41

The alkyllysophospholipid, racemic-l-O-octadecyl-2-O-methylglycero-3- phosphocholine (ET-18-OCH3) was previously shown to inhibit invasion of malignant cells into precultured heart fragments (PHF) in vitro. In particular, pretreatment of PHF with 10 micrograms ET-18-OCH3 for 48 h was sufficient to induce in the host tissue resistance towards invasion by mouse MO4 cells. Resistance was obvious when MO4 cells were confronted either immediately (the pretreatment experiment) or after withdrawal of the drug 7 days prior to confrontation (the reversibility experiment). In the present study, the survival of PHF cells in the pretreatment and reversibility experiments was similar to that of untreated PHF cells as determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) test and by the PHF explantation test. The effective anti-invasive concentration was 6 micrograms/ml in the pretreatment experiment while 3 micrograms/ml was sufficient to inhibit invasion in the reversibility experiment. Induction of resistance towards invasion in pretreated PHF was shown to occur not only with MO4 cells but also with mouse LLC-H61 Lewis lung carcinoma and mouse BW-O-Li1 T-lymphoma cells. The increase in molecular weight of N-linked cell surface glycosylpeptides (N-GP) of PHF was apparent in the pretreatment experiment and was enhanced in the reversibility experiment. This effect was completely abolished in cells obtained from pretreated PHF which were converted into a cell suspension and further cultured as a monolayer on tissue culture plastic without drug for 7 days. The results reported here provide additional evidence for the causal involvement of N-GP of the PHF host tissue in the anti-invasive activity of ET-18-OCH3 in vitro.
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PMID:Role of the host tissue in the anti-invasive activity of the alkyllysophospholipid, ET-18-OCH3, in vitro. 175 86

The possible role of cyclic AMP (cAMP) in the regulation of the vasopressin (VP) gene was tested in two cellular expression systems: one cell line with endogenous VP expression and the other which was transiently with a VP promoter-luciferase fusion gene. 8,Bromo-cAMP stimulated the VP mRNA content about 4-fold in the human VP-expressing small cell lung carcinoma cell line GLC-8. The luciferase activity in P19 embryonal carcinoma cells which were transiently transfected with -174 to +44 of the 5'-flanking region of the human VP gene linked to the firefly luciferase gene, was stimulated about 2-fold by the cAMP analogue. The results indicate that cAMP plays a role in the upregulation of the VP gene and hence point to several putative nucleotide motives in the promoter functionally conferring this response.
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PMID:Vasopressin gene expression is stimulated by cyclic AMP in homologous and heterologous expression systems. 217 21

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
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PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71

A number of nucleoside and nucleotide derivatives of 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin, 1) were prepared and tested for their antiviral and cytostatic activity in cell culture. Treatment of 1 with benzyl bromide gave 4-O-benzylpyrazofurin (4). Methylation of 4 with CH2N2 and subsequent removal of the benzyl group by catalytic hydrogenation provided 1-methylpyrazofurin (8). Direct methylation of 1 with CH3I furnished 4-O-methylpyrazofurin (6). Dehydration of the pentaacetylpyrazofurin (9) with phosgene furnished 4-acetoxy-3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1-acetylpyrazol e-5-carbonitrile (10). A similar dehydration of the precursor tetraacetyl derivative of 4 gave the corresponding carbonitrile, which on deprotection and subsequent treatment with hydroxylamine furnished 4- (benzyloxy)-3-beta-D-ribofuranosylpyrazole-5-carboxamidoxime (13). Treatment of the tetraacetyl derivative of 4 with Lawesson's reagent and subsequent deacetylation furnished a mixture of 4- (benzyloxy)-3-beta-D-ribofuranosylpyrazole-5-thiocarboxamide (15) and the corresponding nitrile derivative (16). Phosphorylation of unprotected 4 with POCl3 and subsequent debenzylation of the intermediate 17 gave pyrazofurin 5'-phosphate (18), which provided the first chemical synthesis of 18. Similar phosphorylation of 4 with POCl3 and quenching the reaction mixture with either EtOH or MeOH, followed by debenzylation, furnished the 5'-O-(ethyl phosphate) (19b) and 5'-O-(dimethyl phosphate) (20b) derivatives of pyrazofurin. DCC-mediated cyclization of 17, followed by debenzylation, gave pyrazofurin 3',5'-(cyclic)phosphate (21b). The NAD analogue 23b was also prepared by the treatment of 17 with an activated form of AMP in the presence of AgNO3. The structural assignment of 7,8, and 20a were made by single-crystal X-ray analysis, and along with pyrazofurin, their intramolecular hydrogen bond characteristics have been studied. All of these compounds were tested in Vero cell cultures against a spectrum of viruses. Compounds 18 and 23b were active at concentrations very similar to pyrazofurin but are less toxic to the cells than pyrazofurin. Compounds 19b, 20b, and the 3',5'-(cyclic)phosphate 21b are less active than 1. Compounds 18, 19b, 20b, and 23b also exhibited significant inhibitory effects on the growth of L1210 and P388 leukemias and Lewis lung carcinoma cells in vitro, whereas B16 melanoma cells were less sensitive to growth inhibition by these compounds. Pyrazofurin derivatives modified at the 1-, 4-, or 5-position showed neither antiviral nor cytostatic activity in cell culture.
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PMID:Synthesis and biological activity of certain nucleoside and nucleotide derivatives of pyrazofurin. 395 Sep 8

Some 150 tumor specimens from 49 patients with non-small-cell carcinoma of the lung (23 epidermoid, 14 adenocarcinoma, 12 large-cell carcinoma) and three with nonneoplastic lung disease were analysed for cellular DNA content by flow cytometry. Monodispersed cells were stained with ethidium bromide and mithramycin. Normal specimens and samples from patients with nonneoplastic disease constantly yielded a single cell population with diploid DNA content. Twenty of 23 epidermoid carcinomas exhibited one or more than one aneuploid subpopulation. Ten of 12 large-cell carcinomas were characterized by one aneuploid clone and 2/12 by two aneuploid clones. Adenocarcinoma exhibited multiclonal cell subpopulations (one to five aneuploid clones). Further information has been obtained on the differential presence of clones in various tumor areas and in infiltrated lymph nodes. These tumors appear characterized by a remarkable degree of cellular heterogeneity. The cytometric ploidy level(s) and the cell population multiclonal structure yield, in comparison with, and in addition to, pathology, indications of possible clinical interest. A correlation between the clonal DNA content and a prognostic parameter such as the tumor mass doubling time has been demonstrated.
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PMID:Non-small-cell lung carcinoma: tumor characterization on the basis of flow cytometrically determined cellular heterogeneity. 631 7

Various kinds of water-soluble quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines were synthesized in a search for compounds with potent antitumor activity and low toxicity. Some compounds exhibited more potent antitumor activities than elliptinium (1) and SUN 4599 (3). In particular, 2-(3'-methoxy-2'-oxopropanoxy)-9- hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium bromide (4d) showed potent antitumor activities against P388 leukemia, colon 26, and Lewis lung carcinoma.
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PMID:Synthesis and antitumor activity of quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines. 902 75

7-Hydroxystaurosporine (UCN-01), a protein kinase inhibitor in clinical development, demonstrates potent antineoplastic activity. To determine whether specific genetic abnormalities would modulate the response to UCN-01, a model of human non-small cell lung carcinoma (NSCLC) cell lines with differential abnormalities of p16CDKN2, RB, and p53 was used for these studies. Cell growth was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and cell cycling was studied using flow cytometric analysis of DNA content. Changes in protein levels and phosphorylation were assessed by Western blotting. In cell lines expressing wild-type RB (A549 and Calul), UCN-01 treatment resulted in dose-dependent growth inhibition, arrest of cells in G1, and a reduction of cells in S phase. p16CDKN2-null cells showed similar growth inhibition to normal fetal lung fibroblasts. UCN-01-induced growth arrest was accompanied by induction of p21CDKN1 and a shift of Rb to the hypophosphorylated state in both p53 wild-type and mutant cell lines. In contrast, UCN-01 treatment of the RB-null cell line H596 resulted in less growth inhibition. To test the role of RB in response to UCN-01, effects of treatment were examined in two human isogenic models of RB expression: the bladder cancer cell line 5637 (RB-null) and the prostate cancer cell line DU-145 (RB-mutant). In the Rb-expressing 5637 subline (RB5), UCN-01 treatment resulted in Rb hypophosphorylation and an accumulation in G1 in contrast to the parent line. Similarly, the wild-type Rb-expressing DU-145 sublines (DU1.1 and B5) showed increased G1 arrest compared with the parent cells. We conclude that UCN-01-induced G1 arrest can occur in cells null for p53 and p16CDKN2, and that RB status influences the ability of UCN-01 to induce a G1 arrest. These data suggest that the molecular profile of cell cycle regulating genes in individual tumors may predict responsiveness and provide insight into optimal therapeutic application of this new antineoplastic agent.
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PMID:RB status as a determinant of response to UCN-01 in non-small cell lung carcinoma. 1049 38

A type IV collagen-binding protein of 41 kDa was isolated from the mushroom Hypsizigus marmoreus and the protein was designated as HM41. The Western blotting analysis with anti-HM41 antibodies demonstrated that HM41 was unrelated to HM23, which had been shown to have an affinity for type IV collagen. The microsequence analysis of the membrane-blotted peptides generated by fragmentation with cyanogen bromide showed no homologous proteins reported. HM41 had cell adhesion-promoting activity for murine Lewis lung carcinoma LL2 cells and human fibrosarcoma HT1080 cells. These results indicate that HM41 is a hitherto undescribed fungus protein that can interact both with animal extracellular matrix protein type IV collagen and with animal tumor cells.
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PMID:Isolation of a 41-kDa protein with cell adhesion activity for animal tumor cells from the mushroom Hypsizigus marmoreus by affinity chromatography with type IV collagen immobilized on agarose. 1083 Apr 92

In the human lung carcinoma cell line A549, Taxol (20 nM) causes a decreased electrophoretic mobility of the 66-kDa Shc isoform (p66shc), beginning 4 h after drug exposure, and reaching a maximum at 9-18 h. No shift was observed for the 52- and 46-kDa isoforms of Shc. The electrophoretic mobility shift of p66shc caused by Taxol is not the result of tyrosine phosphorylation, and there is no indication of a Shc/Grb2 complex in Taxol-treated A549 cells. This modification is blocked by the serine/threonine protein phosphatase 2A. In vivo 32P-labeling and subsequent phosphoamino acid analysis of p66shc indicated that both the original and the shifted p66shc were predominantly serine phosphorylated. Cyanogen bromide digestion of p66shc produced a phosphorylated fragment with an apparent molecular weight of approximately 7.9 kDa from the untreated cells and two phosphorylated fragments, of approximately 7.9 and approximately 9.6 kDa, from the Taxol-treated cells. The domain of Taxol-induced serine phosphorylation is thought to be in the cyanogen bromide fragment containing residues 2-65. The Taxol-induced electrophoretic mobility shift of p66shc was inhibited by the protein synthesis inhibitor, cycloheximide, but not by the mitogen-activated and extracellular signal-regulated protein kinase kinase (MEK) inhibitor, PD98059. This mobility shift did not occur in Taxol-resistant A549-T12 cells treated with 20 nM Taxol. In addition to Taxol, other microtubule-interacting drugs caused a decreased electrophoretic mobility of p66shc. This Taxol-mediated serine phosphorylation seen in p66shc may result from a MEK-independent signaling pathway that is activated in cells that have a prolonged or abnormal mitotic phase of the cell cycle and may play a role in signaling events that lead to cell death.
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PMID:Taxol mediates serine phosphorylation of the 66-kDa Shc isoform. 1101 45


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