Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mucolytic agent, methyl cysteine HC1 (Cytoclair), has been used to obtain a centrifuged cell deposit for the detection of malignant cells in sputum. In 178 sputum samples from 52 patients with primary lung cancer there was a slightly higher rate of detection with the mucolytic method than with the routine method: 54 positives from 27 patients compared with 48 positives from 24 patients. Morphological studies using the mucolytic agent indicated that a millipore filter with fixation of cells in suspension produces a satisfactory cell preparation and is valuable in certain problem cases.
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PMID:Use of a mucolytic agent (Cytoclair) in the preparation of cell material for the detection of malignant cells in sputum. 67 Apr 14

The three ras genes code for proteins with a putative role in cellular signal transduction. They belong to a larger family of small guanosine-triphosphate (GTP)-binding proteins. The ras proteins acquire transforming activity when amino acids are substituted at one of a few specific sites, as a result of a point mutation in the gene. In about one third of adenocarcinomas of the lung, a K-ras mutation is present in codon 12 of the gene. Patients with early stages of K-ras mutation-positive tumors have a very unfavorable prognosis, even if apparently radical resection of the tumor has taken place. K-ras mutations are very rare among nonsmokers, and it is reasonable to assume that carcinogens in tobacco smoke directly cause the mutation. The types of ras mutations found in lung cancer are different from those in gastrointestinal malignancies. Colon cancer is mainly associated with mutations leading to substitution of the normal glycine at amino acid position 12 of K-ras by either valine or aspartic acid, and mutations in N-ras are not exceptional. In contrast, the predominant mutation in lung cancer leads to substitution of cysteine in codon 12. Several other members of the ras gene superfamily are also expressed in human lung cancer, but a possible relationship with lung tumorigenesis remains to be established.
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PMID:The ras gene family in human non-small-cell lung cancer. 132 34

The combined effect of Vit. A and E, selenium, cysteine and BHA on 3MC-induced lung cancer in Wistar rats was investigated. The supplementation of these compounds at their safe doses reduced the incidence of lung cancer from 47.2% to 31.6% (P less than 0.05). The total superoxide dismutase (SOD) and Mn-SOD activities in the lung cancer tissue were much lower than those in the normal tissue (P less than 0.001). It is possible that in the early stage of carcinogenesis, this change occurs only in the limited focus and does not affect the enzyme level as a whole, so SOD assay of peripheral blood can not reflect the carcinogenesis status in the lung.
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PMID:[Inhibitory effect of micronutrients and BHA on lung cancer induced in rats]. 207 36

We have previously identified a small-cell lung cancer cell line (NCI-H209) that expresses an aberrant, underphosphorylated form of the retinoblastoma protein RB1. Molecular analysis of RB1 mRNA from this cell line revealed a single point mutation within exon 21 that resulted in a nonconservative amino acid substitution (cysteine to phenylalanine) at codon 706. Stable expression of this mutant RB1 cDNA in a human cell line lacking endogenous RB1 demonstrated that this amino acid change was sufficient to inhibit phosphorylation. In addition, this cysteine-to-phenylalanine substitution also resulted in loss of RB1 binding to the simian virus 40 large tumor and adenovirus E1A transforming proteins. These results confirm the importance of exon 21 coding sequences and suggest that the cysteine residue at codon 706 may play a role in achieving a specific protein conformation essential for protein-protein interactions.
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PMID:A single amino acid substitution results in a retinoblastoma protein defective in phosphorylation and oncoprotein binding. 216 63

4-methoxy-beta-naphthylamide and 7-amino-4-methyl coumarin, derivatives of Z-Ala-Arg-Arg, Leu- and Gly-Phe-beta-naphthylamides were used as substrates in estimation of peptide hydrolases activity in blood serum of patients with malignant tumors and glomerulonephritis in order to ascertain their efficiency for diagnostic purposes in clinic. Each of the fluorogenic substrates studied was hydrolyzed by various peptide hydrolases from blood serum both under normal and pathological conditions: metallopeptidases, cysteine- and serine-dependent peptide hydrolases. The rate of Z-Ala-Arg-Arg-MNA hydrolysis was decreased in lung, kidney and ileum cancer as well as in glomerulonephritis as compared with normal state. The "alkaline-resistant" cysteine-dependent cathepsin B-like proteinase, hydrolyzing this peptide, was not detected in blood serum neither in normal state nor in these diseases studied. Leu-NA and Gly-Phe-NA were hydrolyzed most effectively in blood serum of patients with lung cancer and glomerulonephritis as compared with normal state; cysteine-dependent peptide hydrolases were most markedly activated. Alterations in the enzymatic activity, detected in blood serum, did not exhibit any specificity for definite diseases, they were observed both in malignant and inflammatory impairments. The data obtained suggest that the fluorogenic substrates studied could not be suitable for clinico-diagnostic purposes.
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PMID:[The use of various fluorogenic substrates for determining peptide hydrolase activity of the blood serum]. 266 94

U-1810, a human large-cell lung cancer line, was found to express a PDGF-like growth factor. 35S-cysteine labelling and immunoprecipitation revealed the synthesis and secretion of a 31-kDa PDGF-like protein. Serum-free conditioned medium contained PDGF-receptor-competing and mitogenic activity when tested on human fibroblasts. Whereas the receptor-competing activity was fully neutralized by anti-PDGF antibodies, the mitogenic activity was only partially affected. We therefore probed U-1810 mRNA with a panel of growth-factor DNA clones. We found expression of the genes for PDGF A- and B-chains, TGF-alpha, TGF-beta and IGF-II but not EGF or IGF-I. U-1810 cells lacked specific binding sites for PDGF but showed specific binding of EGF and expressed EGF-receptor transcripts. Thus, U-1810 is an example of a human tumor cell line that expresses multiple growth factor genes; in the intact tumor the corresponding growth factors may operate in autocrine stimulation of the tumor cells as well as in paracrine growth reactions (i.e. stroma recruitment).
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PMID:Expression of multiple growth factors in a human lung cancer cell line. 303 Sep 41

Human lung tumors PR310 and PR371 maintained in nude mice contain activated c-K-ras oncogenes detectable by the ability of their DNAs to induce the morphological transformation of NIH 3T3 mouse fibroblasts. Using phage libraries constructed with DNA from NIH 3T3 mouse fibroblast transformants, we have isolated human sequences that span greater than 40 kilobase pairs of the c-K-ras oncogene. Based on the conservation of these human sequences in mouse fibroblast transformants, we conclude that the transforming ability of the oncogene activated in these tumors resides within a 43- to 46-kilobase-pair DNA region. No clear differences were observed between the structures of the PR310 and PR371 cloned oncogene sequences. Nucleotide sequence analysis in concert with DNA transfection experiments suggests that the PR371 oncogene has been activated by a single base change in the first exon, which results in the substitution of cysteine for glycine in position 12 of the predicted amino acid sequence. The genetic alteration responsible for the transforming activity of the PR310 oncogene, however, does not reside in the first exon. These results indicate that the activation of the c-K-ras oncogene in human lung cancer can occur by different mutational events.
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PMID:Isolation of transforming sequences of two human lung carcinomas: structural and functional analysis of the activated c-K-ras oncogenes. 632 Jan 74

Lung cancer is the leading cause of malignancy-related mortality in the U.S. and is predicted to increase over the remainder of this decade. Despite attempts to advance early diagnosis and use combination therapies, the clinical response of this cancer yields an overall 5-year survival rate of less than 15%. Clearly, new strategies for therapy are indicated. Although carcinogenesis is complex, tumor growth beyond 1-2 mm3 is dependent on angiogenesis. One of the potential mechanisms that allows for tumorigenesis is dysregulation of the balance of angiogenic and angiostatic factors that favors net neovascularization within the primary tumor. Numerous studies have investigated the role of a variety of molecules in the regulation of angiogenesis. Recently, interleukin-8 (IL-8), a member of the C-X-C chemokine family, has been found to be an angiogenic factor. In contrast, platelet factor 4 (PF4), another C-X-C chemokine, has been shown to have angiostatic properties. It is interesting that the major structural difference between IL-8 and PF4 is the presence of the NH2-terminal ELR (Glu-Leu-Arg) motif that precedes the first cysteine amino acid residue of IL-8 and is important in ligand/receptor interactions. We hypothesize that angiogenesis associated with tumorigenesis is dependent on members of the C-X-C chemokine family acting as either angiogenic or angiostatic factors. This paradigm predicts that the biological balance in the expression of these C-X-C chemokines dictates whether the neoplasm grows and develops metastatic potential or regresses. In this review we discuss our recent laboratory findings that support this contention and suggest that further elucidation of the biology of C-X-C chemokines in the context of neovascularization of nonsmall cell lung cancer will permit novel targeted therapy aimed specifically at attenuating tumor growth and metastasis.
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PMID:Role of C-X-C chemokines as regulators of angiogenesis in lung cancer. 753 29

The cysteine proteases cathepsin B and cathepsin L are very likely involved in invasive processes of normal and malignant cells, they become relevant for a number of diseases and are possibly prognostic markers for the outcome of human lung cancer. Therefore, we have determined activities of these related enzymes in cells and in cell extracts of human lung carcinoma cell lines of different cathepsin composition by flow cytometry and by spectrophotometry, respectively. To this end we applied the synthetic dipeptidyl substrates benzoxycarbonyl-arginyl-arginine- and benzoxycarbonyl-phenyl-arginine- coupled to 4-methoxy-beta-naphthylamide, aminomethyl-coumarine or rhodamine R110. The apparent enzymatic activities were differentially defined by protease inhibitors, particularly E-64 and CA-074. Independent of the dipeptidyl-composition more than 99 per cent of the apparent activity was due to cathepsin B when 4-methoxy-beta-naphthylamide or aminomethylcoumarine were the leaving groups. The 4-methoxy-beta-naphthylamide precipitate used for detection of cell associated activities revealed a wide spectrum of excitation to fluorescence thwarting the application of other possible fluorescent tags. Therefore, its application is restricted to uniparametric fluorescence investigations. Both dipeptidylgroups coupled to rhodamine R110 were promiscuous: only 25 to 30% of the apparent activity were due to cathepsin B; the predominant activity came from cathepsin L, irrespective whether intracellular or activities of cellular extracts were analyzed. However, rhodamine R110-coupled substrates open the way for multiparametric fluorescent analysis of cathepsins B and L containing cells if appropriate inhibitors for specification of the enzymatic activities are additionally applied. In very contrast to 4-methoxy-beta-naphthylamide, which causes irreparable damage to the cells, the rhodamine substrates permit studies with living cells and live cell sorting.
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PMID:Quantification of intracellular cathepsin activities in human lung tumor cell lines by flow cytometry. 757 37

Lung cancer arises as a focal transformation of chronically injured epithelium with cigarette smoke as one of its well recognized causes. Apart from oxidants, cigarette smoke contains several precarcinogens, and it is surprising that not every heavy smoker becomes a victim of malignant disease. This points to the interindividual variability in susceptibility to carcinogens and there are several lines of evidence that metabolic factors are involved in such variability. Metabolism of carcinogens and also the subsequent multisteps of carcinogenesis are affected by host factors and governed by the balance between opposite forces, such as metabolic activation and detoxification, formation, and scavenging of radicals and DNA damage and repair. This implies that carcinogenic compounds can initiate tumor growth only in amounts saturating detoxification mechanisms. In this context it is well known that glutathione plays a crucial role in the detoxification of xenobiotics. N-acetylcysteine (NAC), an aminothiol and precursor of intracellular cysteine and glutathione, has been shown not only to be an efficient antidote in acetaminophen poisoning but also to possess important chemopreventive properties. In this article, sites and mechanisms of the therapeutic action of NAC are reviewed with special reference to its chemopreventive characteristics.
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PMID:N-acetylcysteine for lung cancer prevention. 775 Mar 44


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