UMLS:C0242379 - FACTA Search

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Query: UMLS:C0242379 (lung cancer)
71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dihydropyridine, dexniguldipine hydrochloride (B859-35), has shown therapeutic activity in experimentally induced neuroendocrine hamster lung tumors and demonstrated antiproliferative effects in a mammary cancer cell line via inhibition of Ca2+ calmodulin. Studies in NIH 3T3 fibroblasts have provided evidence that dexniguldipine may also inhibit protein kinase C (PKC). In this study, we have tested the hypothesis that dexniguldipine may inhibit the proliferation of lung cancer cells in response to autocrine or exogenous activation of PKC. Using a panel of human lung cancer cell lines, we show that dexniguldipine is a potent inhibitor of mitogenic signal transduction pathways dependent on PKC activation in several small-cell and non-small-cell lung cancer cell lines while it failed to inhibit cyclic-AMP-dependent cell proliferation.
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PMID:Inhibition of protein-kinase-C--dependent cell proliferation of human lung cancer cell lines by the dihydropyridine dexniguldipine. 813 60

Small-cell lung carcinoma cells express different plasma membrane nicotinic acetylcholine receptor subtypes. We have now found that interacting with these receptors (-)-nicotine induces a dose-dependent and stereoselective release of [3H]serotonin which is dependent on external calcium and blocked by the specific ganglionic nicotinic antagonist mecamylamine. With the same potency (-)-nicotine stimulates tumor cell proliferation, an effect also blocked by mecamylamine. Serotonin itself stimulates cell proliferation in a dose-dependent manner, an effect blocked by the selective serotonergic receptor antagonists methiotepine and metergoline. These data suggest that nicotine might affect proliferation of small-cell lung carcinoma cells by inducing the release of hormones (such as serotonin) with autocrine capabilities and place both the nicotinic and the serotonergic receptors at key positions in the biological and, possibly, pharmacological approach to this human lung cancer.
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PMID:Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma. 822 98

Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent medical treatments are needed since malignant hypercalcemia progresses very rapidly. The intravenous administration of sufficient quantities of isotonic saline sometimes with loop diuretic agents is the first and fundamental step in the management of malignant hypercalcemia. As hormonal therapeutic agents for malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual candidates. Calcitonin exerts calcium-lowering effects both through its direct inhibitory effect on osteoclastic bone resorption and prevention of calcium reabsorption from renal tubulus. Among the anticalcemic agents available, calcitonin has the most rapid onset of action; the hypocalcemic effects appear within a few hours after administration. But continued usage diminishes its effect which is called the "escape phenomenon". The usual dosage of calcitonin is 80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for malignant hypercalcemia, even in the case of solid cancer such as lung cancer, though the mechanism is not clear. In lymphocytic proliferative disorders, a direct inhibitory effect on the proliferation of malignant cells accounts for the calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used for initial several days and glucocorticoid (30-40 mg/day) is continued along with calcitonin from the beginning of the treatment. Most effective and safe hypocalcemic agents for malignant hypercalcemia are the newly developed bisphosphonate compounds, which are not yet available in Japan. These agents interact chemically with hydroxyapatite on the bone surface and prevent osteoclastic function and activity. According to the data of our own investigation, pamidronate, one of the relatively new generation of bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia due to various kinds of malignancy by one intravenous administration (30-60 mg) without any adverse effect. In near future, the combination of calcitonin and bisphosphonates will also be the most effective medical management for malignant hypercalcemia in Japan.
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PMID:[Medical treatment of malignant hypercalcemia]. 825 44

This study updates a 1982 report on mortality at two German chromate-producing factories. The main objective of the study was to establish whether the change-over to a production process using lime-free conversion of chromite ore, thus eliminating the formation of calcium chromate, had resulted in a distinct reduction in bronchial carcinoma mortality among workers exposed for the first time after the change-over (completed in 1958 in Leverkusen and 1964 in Uerdingen). A total of 1417 workers with at least 1 year of exposure were enrolled in the study. The observation period ended on 31 December 1988. The expected number of deaths was calculated using population statistics for North Rhine-Westphalia. The risk was determined in the form of a standardised mortality ratio (SMR), i.e. the ratio of observed deaths to expected deaths. In the group of 739 workers exposed before the process change-over was completed, 432 died during the observation period, 66 of them from bronchial carcinoma. This significant excess produced an SMR of 2.27 (95% confidence interval: 1.78-2.85). Where the cause of death was unknown, cases were allocated to a cause of death on the basis of the percentage occurrence of various causes of death in the specific subcohort. The cohort of 678 workers first exposed after the process modification had been completed had a slightly increased SMR for lung cancer of 1.26 (95% confidence interval: 0.58-2.38) based on nine cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification. 828 15

The DNA fragmentation, a parameter of apoptosis, in non-small (NSCLC) and small (SCLC) cell lung cancer cell lines (N231 and PC-9) was evaluated. The DNA fragmentation in SCLC lines, but not in NSCLC lines, was observed in overgrown cells without exposure to anticancer drugs. In etoposide (VP-16)-treated N231 but not PC-9 cells, DNA fragmentation continued to increase up to 42 h, and the increase was dependent on the concentration of VP-16. The endonuclease activity of VP-16-treated N231, but not PC-9, cells required both Ca2+ and Mg2+ for full activity. It was elevated in a time- and concentration-dependent manner. As this activity was not affected by addition of cycloheximide, the activation of the endonuclease activity without protein synthesis may be involved in VP-16-induced cytotoxicity in N231.
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PMID:Apoptosis induced by etoposide in small-cell lung cancer cell lines. 830 12

The regulation of expression of parathyroid hormone-related protein (PTHRP) mRNA by protein kinase C and cyclic-AMP-dependent pathways was studied in a human lung cancer cell line (BEN). PTHRP mRNA was increased by agents which activate protein kinase C, but not by those which activate cyclic-AMP-dependent pathways. Activators of both second messenger pathways stimulated a dose-dependent increase in the accumulation of PTHRP in conditioned medium assayed using sensitive region-specific immunoassays for PTHRP1-34 and 1-86. Calcitonin had a dose-dependent effect on the accumulation of PTHRP in culture medium which may be mediated via cyclic AMP. Varying the calcium concentration from 0-2.5 mM had no effect on peptide secretion over 20 h, while short-term incubation (30 min) with ionomycin (2.5-75 micrograms/ml) significantly increased PTHRP immunoreactivity in the medium.
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PMID:Expression and secretion of parathyroid hormone-related protein by a human cancer cell line. 831 63

In the past decade, over 1000 continuous human cell lines have been established from lung cancer biopsy specimens. Numerous growth factors and receptors have been identified in the small cell lung cancer (SCLC) cell lines. SCLC is a neuroendocrine tumor which contains numerous peptides, including bombesin/gastrin releasing peptide (BN/GRP), and receptors. High levels of GRP mRNA and immunoreactivity are present in SCLC cells. The secretion rate of GRP from SCLC cells is increased by vasoactive intestinal peptide (VIP), which elevates the intracellular cAMP. GRP binds to cell surface receptors, elevates cytosolic calcium and stimulates the growth of SCLC cells. Additional SCLC growth factors include insulin-like growth factor I (IGF-I) and transferrin. IGF-I mRNA and protein is present in SCLC. IGF-I binds with high affinity to SCLC cells and stimulates tyrosine kinase activity and growth. Transferrin is also present in SCLC cells. Transferrin binds with high affinity to SCLC cells and stimulates iron transport and growth. Synthetic peptide antagonists and monoclonal antibodies have been identified which disrupt autocrine growth pathways and inhibit SCLC growth.
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PMID:Growth factor and peptide receptors in small cell lung cancer. 838 84

Lambert-Eaton myasthenic syndrome (LEMS) is one of the neurologic paraneoplastic syndromes often found in patients with lung cancer. It is characterized by a generalized deficit of neurotransmitter release. Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS. LEMS is an autoimmune disease, and autoantibodies that interfere with neurotransmitter release by binding to presynaptic voltage-operated calcium channels (VOCCs) have been found in sera of patients with LEMS. Both human neuronal and SCLC cell lines express omega-conotoxin-sensitive VOCCs, and autoantibodies from patients affected by LEMS can precipitate these channels. We have now screened a large population of patients and control subjects in order to define the specificity and sensitivity of the anti-VOCC antibody assay. We have tested sera from 52 patients with LEMS with and without SCLC; 32 sera from patients with SCLC without LEMS, 31 from patients with non-SCLC, 34 from patients with inflammatory lung diseases, 17 from patients with other neurologic disorders, and 48 from healthy control subjects. We have found that a positive result with this radioimmunoassay is highly specific for LEMS, with or without SCLC, when the antibody titer is higher than 14.21 pM. Anti-VOCC antibodies have also been found in about 40% of patients with SCLC without LEMS, but they were absent in all the other populations tested. We can conclude that this serologic assay is a very useful aid in the diagnosis of LEMS, and it might be useful also for the early diagnosis of SCLC.
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PMID:Calcium channel autoantibodies in myasthenic syndrome and small cell lung cancer. 838 55

1. Human small-cell lung cancer (SCLC) cells are believed to express the antigens responsible for the production of pathological antibodies in the Lambert-Eaton syndrome (LES), a Ca2+ channel disorder in which quantal transmitter release from the motor nerve terminal is impaired. Whole-cell patch-clamp techniques were used to study the voltage-dependent Ca2+ channels expressed by H146 SCLC cells and the effects of LES antibodies on these channels. The types of Ca2+ channels were determined using biophysical properties and pharmacological sensitivity to several antagonists. 2. Whole-cell Ca2+ currents (ICa) in SCLC cells are sensitive to the dihydropyridine (DHP) nicardipine, omega-conotoxin GVIA (omega-CgTX GVIA) and omega-agatoxin IVA (omega-AgTX IVA). Nicardipine at 100 nM and 10 microM reduced ICa by 35 and 45% (n = 38 cells), respectively, while omega-CgTX GVIA (1 microM) inhibited ICa by 32% (n = 31). Application of omega-AgTX IVA at 50 and 100 nM to the cancer cells decreased ICa by 41 and 42%, respectively (n = 22). 3. Measurement of cell membrane capacitance (Cm) revealed that Ca(2+)-dependent exocytosis underlies the secretory activity of SCLC cells. Exocytosis, when induced by step depolarizing pulses and measured by increases in Cm, was markedly inhibited by nicardipine (10 microM) and omega-AgTX IVA (100 nM). In contrast, omega-CgTX GVIA (1 microM) was not as effective in altering increases in Cm. 4. From negative (-80 mV) and depolarized (-40 mV) holding potentials, both peak and plateau ICa were inhibited by the presence of LES antibodies (1 mg ml-1 IgG). LES serum also reduced depolarization-induced increases in Cm by 48% (n = 15). 5. To determine whether the LES antibodies are downregulating a specific type(s) of Ca2+ channel, nicardipine (10 microM), omega-CgTX GVIA (1 microM) or omega-AgTX IVA (100 nM) was applied to tumour cells that had been previously exposed to LES serum for 24 h. The most pronounced change was that omega-AgTX IVA was 38-84% less effective at reducing ICa after the IgG treatment. The effectiveness of nicardipine was diminished by 18% after incubation with the LES antibodies, whereas the omega-CgTX GVIA was seen to be more effective. These results suggest that LES IgG downregulates P-type Ca2+ channels and, possibly, to a lesser extent L-type channels. 6. In view of recent evidence that P-type Ca2+ channels mediate cholinergic transmitter release at the mammalian neuromuscular junction (NMJ), the expression of P-type Ca2+ channels in the SCLC cells and the reactivity of LES IgG with these channels support the hypothesis that P-type Ca2+ channels in these cancer cells may trigger the autoantibody production in this disorder. The antibodies so produced are implicated in the functional impairment of the Ca2+ channels characteristic of LES.
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PMID:Inhibition of calcium currents and exocytosis by Lambert-Eaton syndrome antibodies in human lung cancer cells. 856 72

Neutral endopeptidase (NEP; CALLA, CD10, EC 3.4.24.11) is a cell surface endopeptidase that hydrolyses bioactive peptides, including the bombesin-like peptides, as well as other neuropeptides. Bombesin-like peptides and other neuropeptides are autocrine growth factors for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Low expression of NEP has been reported in SCLC and NSCLC cell lines. NEP inhibition has been shown to increase proliferation in one cell line. To date, NEP expression has not been quantitatively evaluated in normal adult lung, SCLC or NSCLC tumors, paired uninvolved lung from the same patient, or in other pulmonary neoplasms such as mesotheliomas and carcinoids. We examined the expression of NEP in these tissues and human cell lines using immunohistochemistry, flow cytometry, enzyme activity, ELISA, Western blot, and reverse transcription (RT)-PCR. Uninvolved lung tissue from different individuals displayed considerable variation in NEP activity and protein. By immunohistochemistry, NEP expression was detectable in alveolar and airway epithelium, fibroblasts of normal lung, and in mesotheliomas, whereas it was undetectable in most SCLC, adenocarcinoma, squamous cell carcinoma, and carcinoid tumors of the lung. NEP activity and protein levels were lower in all SCLC and adenocarcinoma tumors when compared to adjacent uninvolved lung, often at levels consistent with expression derived from contaminating stroma. NEP expression and activity were reduced or undetectable in most SCLC and lung adenocarcinoma cell lines. NEP mRNA by RT-PCR was not expressed or was in low abundance in the majority of lung cancer cell lines. The majority of lung tumors did not express NEP by RT-PCR as compared with normal adjacent lung. In addition, recombinant NEP abolished, whereas an NEP inhibitor potentiated, the calcium flux generated by neuropeptides in some lung cancer cell lines, demonstrating potential physiological significance for low NEP expression. NEP, therefore, is a signal transduction and possibly a growth modulator for both SCLC and NSCLC, emphasizing the role of neuropeptides in the pathogenesis of the major histological forms of lung cancer.
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PMID:Neutral endopeptidase: variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux. 863 Oct 21

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